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Special Report II: Tackling Burnout
Last month, we introduced the epidemic of burnout and the adverse consequences for both our vascular surgery patients and ourselves. Today we will outline a framework for addressing these issues. The foundation of this framework is informed by the social and neurosciences.
From the perspective of the social scientist: Christina Maslach, the originator of the widely used Maslach Burnout Inventory, theorized that burnout arises from a chronic mismatch between people and their work setting in some or all of the following domains: Workload (too much, wrong kind); control (lack of autonomy, or insufficient control over resources); reward (insufficient financial or social rewards commensurate with achievements); community (loss of positive connection with others); fairness (lack of perceived fairness, inequity of work, pay, or promotion); and values (conflict of personal and organizational values). The reality of practicing medicine in today’s business milieu – of achieving service efficiencies by meeting performance targets – brings many of these mismatches into sharp focus.
From the perspective of the neuroscientist: Recent advances, including functional MRI, have demonstrated that the human brain is hard wired for compassion. Compassion is the deep feeling that arises when confronted with another’s suffering, coupled with a strong desire to alleviate that suffering. There are at least two neural pathways: one activated during empathy, having us experience another’s pain; and the other activated during compassion, resulting in our sense of reward. Thus, burnout is thought to occur when you know what your patient needs but you are unable to deliver it. Compassionate medical care is purposeful work, which promotes a sense of reward and mitigates burnout.
Because burnout affects all caregivers (anyone who touches the patient), a successful program addressing workforce well-being must be comprehensive and organization wide, similar to successful patient safety, CPI [continuous process improvement] and LEAN [Six Sigma] initiatives.
There are no shortcuts. Creating a culture of compassionate, collaborative care requires an understanding of the interrelationships between the individual provider, the unit or team, and organizational leadership.
1) The individual provider: There is evidence to support the use of programs that build personal resilience. A recently published meta-analysis by West and colleagues concluded that while no specific physician burnout intervention has been shown to be better than other types of interventions, mindfulness, stress management, and small-group discussions can be effective approaches to reducing burnout scores. Strategies to build individual resilience, such as mindfulness and meditation, are easy to teach but place the burden for success on the individual. No amount of resilience can withstand an unsupportive or toxic workplace environment, so both individual and organizational strategies in combination are necessary.
2) The unit or team: Scheduling time for open and honest discussion of social and emotional issues that arise in caring for patients helps nourish caregiver to caregiver compassion. The Schwartz Center for Compassionate Healthcare is a national nonprofit leading the movement to bring compassion to every patient-caregiver interaction. More than 425 health care organization are Schwartz Center members and conduct Schwartz Rounds™ to bring doctors, nurses, and other caregivers together to discuss the human side of health care. (www.theschwartzcenter.org). Team member to team member support is essential for navigating the stressors of practice. With having lunch in front of your computer being the norm, and the disappearance of traditional spaces for colleagues to connect (for example, nurses’ lounge, physician dining rooms), the opportunity for caregivers to have a safe place to escape, a place to have their own humanity reaffirmed, a place to offer support to their peers, has been eliminated.
3) Organizational Leadership: Making compassion a core value, articulating it, and establishing metrics whereby it can be measured, is a good start. The barriers to a culture of compassion are related to our systems of care. There are burgeoning administrative and documentation tasks to be performed, and productivity expectations that turn our clinics and hospitals into assembly lines. No, we cannot expect the EMR [electronic medical records] to be eliminated, but workforce well-being cannot be sustainable in the context of inadequate resources. A culture of compassionate collaborative care requires programs and policies that are implemented by the organization itself. Examples of organization-wide initiatives that support workforce well-being and provider engagement include: screening for caregiver burnout, establishing policies for managing adverse events with an eye toward the second victim, and most importantly, supporting systems that preserve work control autonomy of physicians and nurses in clinical settings. The business sector has long recognized that workplace stress is a function of how demanding a person’s job is and how much control that person has over his or her responsibilities. The business community has also recognized that the experience of the worker (provider) drives the experience of the customer (patient). In a study of hospital compassionate practices and HCAHPS [the Hospital Consumer Assessment of Healthcare Providers and Systems], McClelland and Vogus reported that how well a hospital compassionately supports it employees and rewards compassionate acts is significantly and positively is associated with that hospital’s ratings and likelihood of patients recommending it.
How does the Society of Vascular Surgery, or any professional medical/nursing society for that matter, fit into this model?
We propose that the SVS find ways to empower their members to be agents for culture change within their own health care organizations. How might this be done:
- Teach organizational leadership skills, starting with the SVS Board of Directors, the presidential line, and the chairs of committees. Offer leadership courses at the Annual Meeting.
- Develop a community of caregivers committed to creating a compassionate collaborative culture. The SVS is a founding member of the Schwartz Center Healthcare Society Leadership Council, and you, as members of the SVS benefit from reduced registration at the Annual Compassion in Action Healthcare Conference, June 24-27, 2017 in Boston. (http://compassioninactionconference.org) This conference is designed to be highly experiential, using a hands-on “how to do it” model.
- The SVS should make improving the overall wellness of its members a specific goal and find specific metrics to monitor our progress towards this goal. Members can be provided with the tools to identify, monitor, and measure burnout and compassion. Each committee and council of the SVS can reexamine their objectives through the lens of reducing burnout and improving the wellness of vascular surgeons.
- Provide members with evidence-based programs that build personal resilience. This will not be a successful initiative unless our surgeons recognize and acknowledge the symptoms of burnout, and are willing to admit vulnerability. Without doing so, it is difficult to reach out for help.
- Redesign postgraduate resident and fellowship education. Standardizing clinical care may reduce variation and promote efficiency. However, when processes such as time-limited appointment scheduling, EMR templates, and protocols that drive physician-patient interactions are embedded in Resident and Fellowship education, the result may well be inflexibility in practice, reduced face time with patients, and interactions that lack compassion; all leading to burnout. Graduate Medical Education leaders must develop programs that support the learner’s ability to connect with patients and families, cultivate and role-model skills and behaviors that strengthen compassionate interactions, and strive to develop clinical practice models that increase Resident and Fellow work control autonomy.
The SVS should work proactively to optimize workload, fairness, and reward on a larger scale for its members as it relates to the EMR, reimbursement, and systems coverage. While we may be relatively small in size, as leaders, we are perfectly poised to address these larger, global issues. Perhaps working within the current system (i.e., PAC and APM task force) and considering innovative solutions at a national leadership scale, the SVS can direct real change!
Changing culture is not easy, nor quick, nor does it have an easy-to-follow blueprint. The first step is recognizing the need. The second is taking a leadership role. The third is thinking deeply about implementation.
*The authors extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, MD, scholar in residence, Schwartz Center for Compassionate Care, Boston and clinical professor of orthopedics at Seattle Children’s Hospital.
REFERENCES
1. J Managerial Psychol. (2007) 22:309-28
2. Annu Rev Neurosci. (2012) 35:1-23
3. Medicine. (2016) 44:583-5
4. J Health Organization Manag. (2015) 29:973-87
5. De Zulueta P Developing compassionate leadership in health care: an integrative review. J Healthcare Leadership. (2016) 8:1-10
6. Dolan ED, Morh D, Lempa M et al. Using a single item to measure burnout in primary care staff: A psychometry evaluation. J Gen Intern Med. (2015) 30:582-7
7. Karasek RA Job demands, job decision latitude, and mental strain: implications for job design. Administrative Sciences Quarterly (1979) 24: 285-308
8. Lee VS, Miller T, Daniels C, et al. Creating the exceptional patient experience in one academic health system. Acad Med. (2016) 91:338-44
9. Linzer M, Levine R, Meltzer D, et al. 10 bold steps to prevent burnout in general internal medicine. J Gen Intern Med. (2013) 29:18-20
10. Lown BA, Manning CF The Schwartz Center Rounds: Evaluation of an interdisciplinary approach to enhancing patient-centered communication, teamwork, and provider support. Acad Med. (2010) 85:1073-81
11. Lown BA, Muncer SJ, Chadwick R Can compassionate healthcare be measured? The Schwartz Center Compassionate Care Scale. Patient Education and Counseling (2015) 98:1005-10
12. Lown BA, McIntosh S, Gaines ME, et. al. Integrating compassionate collaborative care (“the Triple C”) into health professional education to advance the triple aim of health care. Acad Med (2016) 91:1-7
13. Lown BA A social neuroscience-informed model for teaching and practicing compassion in health care. Medical Education (2016) 50: 332-342
14. Maslach C, Schaufeli WG, Leiter MP Job burnout. Annu Rev Psychol (2001) 52:397-422
15. McClelland LE, Vogus TJ Compassion practices and HCAHPS: Does rewarding and supporting workplace compassion influence patient perceptions? HSR: Health Serv Res. (2014) 49:1670-83
16. Shanafelt TD, Noseworthy JH Executive leadership and physician well-being: Nine organizational strategies to promote engagement and reduce burnout. Mayo Clin Proc. (2016) 6:1-18
17. Shanafelt TD, Dyrbye LN, West CP Addressing physician burnout: the way forward. JAMA (2017) 317:901-2
18. Singer T, Klimecki OM Empathy and compassion Curr Biol. (2014) 24: R875-8
19. West CP, Dyrbye LN, Satele DV et. al. Concurrent validity of single-item measures of emotional exhaustion and depersonalization in burnout assessment. J Gen Intern Med. (2012) 27:1445-52
20. West CP, Dyrbye LN, Erwin PJ, et al. Interventions to address and reduce physician burnout: a systematic review and meta-analysis. Lancet. (2016) 388:2272-81
21. Wuest TK, Goldberg MJ, Kelly JD Clinical faceoff: Physician burnout-Fact, fantasy, or the fourth component of the triple aim? Clin Orthop Relat Res. (2016) doi: 10.1007/5-11999-016-5193-5
Last month, we introduced the epidemic of burnout and the adverse consequences for both our vascular surgery patients and ourselves. Today we will outline a framework for addressing these issues. The foundation of this framework is informed by the social and neurosciences.
From the perspective of the social scientist: Christina Maslach, the originator of the widely used Maslach Burnout Inventory, theorized that burnout arises from a chronic mismatch between people and their work setting in some or all of the following domains: Workload (too much, wrong kind); control (lack of autonomy, or insufficient control over resources); reward (insufficient financial or social rewards commensurate with achievements); community (loss of positive connection with others); fairness (lack of perceived fairness, inequity of work, pay, or promotion); and values (conflict of personal and organizational values). The reality of practicing medicine in today’s business milieu – of achieving service efficiencies by meeting performance targets – brings many of these mismatches into sharp focus.
From the perspective of the neuroscientist: Recent advances, including functional MRI, have demonstrated that the human brain is hard wired for compassion. Compassion is the deep feeling that arises when confronted with another’s suffering, coupled with a strong desire to alleviate that suffering. There are at least two neural pathways: one activated during empathy, having us experience another’s pain; and the other activated during compassion, resulting in our sense of reward. Thus, burnout is thought to occur when you know what your patient needs but you are unable to deliver it. Compassionate medical care is purposeful work, which promotes a sense of reward and mitigates burnout.
Because burnout affects all caregivers (anyone who touches the patient), a successful program addressing workforce well-being must be comprehensive and organization wide, similar to successful patient safety, CPI [continuous process improvement] and LEAN [Six Sigma] initiatives.
There are no shortcuts. Creating a culture of compassionate, collaborative care requires an understanding of the interrelationships between the individual provider, the unit or team, and organizational leadership.
1) The individual provider: There is evidence to support the use of programs that build personal resilience. A recently published meta-analysis by West and colleagues concluded that while no specific physician burnout intervention has been shown to be better than other types of interventions, mindfulness, stress management, and small-group discussions can be effective approaches to reducing burnout scores. Strategies to build individual resilience, such as mindfulness and meditation, are easy to teach but place the burden for success on the individual. No amount of resilience can withstand an unsupportive or toxic workplace environment, so both individual and organizational strategies in combination are necessary.
2) The unit or team: Scheduling time for open and honest discussion of social and emotional issues that arise in caring for patients helps nourish caregiver to caregiver compassion. The Schwartz Center for Compassionate Healthcare is a national nonprofit leading the movement to bring compassion to every patient-caregiver interaction. More than 425 health care organization are Schwartz Center members and conduct Schwartz Rounds™ to bring doctors, nurses, and other caregivers together to discuss the human side of health care. (www.theschwartzcenter.org). Team member to team member support is essential for navigating the stressors of practice. With having lunch in front of your computer being the norm, and the disappearance of traditional spaces for colleagues to connect (for example, nurses’ lounge, physician dining rooms), the opportunity for caregivers to have a safe place to escape, a place to have their own humanity reaffirmed, a place to offer support to their peers, has been eliminated.
3) Organizational Leadership: Making compassion a core value, articulating it, and establishing metrics whereby it can be measured, is a good start. The barriers to a culture of compassion are related to our systems of care. There are burgeoning administrative and documentation tasks to be performed, and productivity expectations that turn our clinics and hospitals into assembly lines. No, we cannot expect the EMR [electronic medical records] to be eliminated, but workforce well-being cannot be sustainable in the context of inadequate resources. A culture of compassionate collaborative care requires programs and policies that are implemented by the organization itself. Examples of organization-wide initiatives that support workforce well-being and provider engagement include: screening for caregiver burnout, establishing policies for managing adverse events with an eye toward the second victim, and most importantly, supporting systems that preserve work control autonomy of physicians and nurses in clinical settings. The business sector has long recognized that workplace stress is a function of how demanding a person’s job is and how much control that person has over his or her responsibilities. The business community has also recognized that the experience of the worker (provider) drives the experience of the customer (patient). In a study of hospital compassionate practices and HCAHPS [the Hospital Consumer Assessment of Healthcare Providers and Systems], McClelland and Vogus reported that how well a hospital compassionately supports it employees and rewards compassionate acts is significantly and positively is associated with that hospital’s ratings and likelihood of patients recommending it.
How does the Society of Vascular Surgery, or any professional medical/nursing society for that matter, fit into this model?
We propose that the SVS find ways to empower their members to be agents for culture change within their own health care organizations. How might this be done:
- Teach organizational leadership skills, starting with the SVS Board of Directors, the presidential line, and the chairs of committees. Offer leadership courses at the Annual Meeting.
- Develop a community of caregivers committed to creating a compassionate collaborative culture. The SVS is a founding member of the Schwartz Center Healthcare Society Leadership Council, and you, as members of the SVS benefit from reduced registration at the Annual Compassion in Action Healthcare Conference, June 24-27, 2017 in Boston. (http://compassioninactionconference.org) This conference is designed to be highly experiential, using a hands-on “how to do it” model.
- The SVS should make improving the overall wellness of its members a specific goal and find specific metrics to monitor our progress towards this goal. Members can be provided with the tools to identify, monitor, and measure burnout and compassion. Each committee and council of the SVS can reexamine their objectives through the lens of reducing burnout and improving the wellness of vascular surgeons.
- Provide members with evidence-based programs that build personal resilience. This will not be a successful initiative unless our surgeons recognize and acknowledge the symptoms of burnout, and are willing to admit vulnerability. Without doing so, it is difficult to reach out for help.
- Redesign postgraduate resident and fellowship education. Standardizing clinical care may reduce variation and promote efficiency. However, when processes such as time-limited appointment scheduling, EMR templates, and protocols that drive physician-patient interactions are embedded in Resident and Fellowship education, the result may well be inflexibility in practice, reduced face time with patients, and interactions that lack compassion; all leading to burnout. Graduate Medical Education leaders must develop programs that support the learner’s ability to connect with patients and families, cultivate and role-model skills and behaviors that strengthen compassionate interactions, and strive to develop clinical practice models that increase Resident and Fellow work control autonomy.
The SVS should work proactively to optimize workload, fairness, and reward on a larger scale for its members as it relates to the EMR, reimbursement, and systems coverage. While we may be relatively small in size, as leaders, we are perfectly poised to address these larger, global issues. Perhaps working within the current system (i.e., PAC and APM task force) and considering innovative solutions at a national leadership scale, the SVS can direct real change!
Changing culture is not easy, nor quick, nor does it have an easy-to-follow blueprint. The first step is recognizing the need. The second is taking a leadership role. The third is thinking deeply about implementation.
*The authors extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, MD, scholar in residence, Schwartz Center for Compassionate Care, Boston and clinical professor of orthopedics at Seattle Children’s Hospital.
REFERENCES
1. J Managerial Psychol. (2007) 22:309-28
2. Annu Rev Neurosci. (2012) 35:1-23
3. Medicine. (2016) 44:583-5
4. J Health Organization Manag. (2015) 29:973-87
5. De Zulueta P Developing compassionate leadership in health care: an integrative review. J Healthcare Leadership. (2016) 8:1-10
6. Dolan ED, Morh D, Lempa M et al. Using a single item to measure burnout in primary care staff: A psychometry evaluation. J Gen Intern Med. (2015) 30:582-7
7. Karasek RA Job demands, job decision latitude, and mental strain: implications for job design. Administrative Sciences Quarterly (1979) 24: 285-308
8. Lee VS, Miller T, Daniels C, et al. Creating the exceptional patient experience in one academic health system. Acad Med. (2016) 91:338-44
9. Linzer M, Levine R, Meltzer D, et al. 10 bold steps to prevent burnout in general internal medicine. J Gen Intern Med. (2013) 29:18-20
10. Lown BA, Manning CF The Schwartz Center Rounds: Evaluation of an interdisciplinary approach to enhancing patient-centered communication, teamwork, and provider support. Acad Med. (2010) 85:1073-81
11. Lown BA, Muncer SJ, Chadwick R Can compassionate healthcare be measured? The Schwartz Center Compassionate Care Scale. Patient Education and Counseling (2015) 98:1005-10
12. Lown BA, McIntosh S, Gaines ME, et. al. Integrating compassionate collaborative care (“the Triple C”) into health professional education to advance the triple aim of health care. Acad Med (2016) 91:1-7
13. Lown BA A social neuroscience-informed model for teaching and practicing compassion in health care. Medical Education (2016) 50: 332-342
14. Maslach C, Schaufeli WG, Leiter MP Job burnout. Annu Rev Psychol (2001) 52:397-422
15. McClelland LE, Vogus TJ Compassion practices and HCAHPS: Does rewarding and supporting workplace compassion influence patient perceptions? HSR: Health Serv Res. (2014) 49:1670-83
16. Shanafelt TD, Noseworthy JH Executive leadership and physician well-being: Nine organizational strategies to promote engagement and reduce burnout. Mayo Clin Proc. (2016) 6:1-18
17. Shanafelt TD, Dyrbye LN, West CP Addressing physician burnout: the way forward. JAMA (2017) 317:901-2
18. Singer T, Klimecki OM Empathy and compassion Curr Biol. (2014) 24: R875-8
19. West CP, Dyrbye LN, Satele DV et. al. Concurrent validity of single-item measures of emotional exhaustion and depersonalization in burnout assessment. J Gen Intern Med. (2012) 27:1445-52
20. West CP, Dyrbye LN, Erwin PJ, et al. Interventions to address and reduce physician burnout: a systematic review and meta-analysis. Lancet. (2016) 388:2272-81
21. Wuest TK, Goldberg MJ, Kelly JD Clinical faceoff: Physician burnout-Fact, fantasy, or the fourth component of the triple aim? Clin Orthop Relat Res. (2016) doi: 10.1007/5-11999-016-5193-5
Last month, we introduced the epidemic of burnout and the adverse consequences for both our vascular surgery patients and ourselves. Today we will outline a framework for addressing these issues. The foundation of this framework is informed by the social and neurosciences.
From the perspective of the social scientist: Christina Maslach, the originator of the widely used Maslach Burnout Inventory, theorized that burnout arises from a chronic mismatch between people and their work setting in some or all of the following domains: Workload (too much, wrong kind); control (lack of autonomy, or insufficient control over resources); reward (insufficient financial or social rewards commensurate with achievements); community (loss of positive connection with others); fairness (lack of perceived fairness, inequity of work, pay, or promotion); and values (conflict of personal and organizational values). The reality of practicing medicine in today’s business milieu – of achieving service efficiencies by meeting performance targets – brings many of these mismatches into sharp focus.
From the perspective of the neuroscientist: Recent advances, including functional MRI, have demonstrated that the human brain is hard wired for compassion. Compassion is the deep feeling that arises when confronted with another’s suffering, coupled with a strong desire to alleviate that suffering. There are at least two neural pathways: one activated during empathy, having us experience another’s pain; and the other activated during compassion, resulting in our sense of reward. Thus, burnout is thought to occur when you know what your patient needs but you are unable to deliver it. Compassionate medical care is purposeful work, which promotes a sense of reward and mitigates burnout.
Because burnout affects all caregivers (anyone who touches the patient), a successful program addressing workforce well-being must be comprehensive and organization wide, similar to successful patient safety, CPI [continuous process improvement] and LEAN [Six Sigma] initiatives.
There are no shortcuts. Creating a culture of compassionate, collaborative care requires an understanding of the interrelationships between the individual provider, the unit or team, and organizational leadership.
1) The individual provider: There is evidence to support the use of programs that build personal resilience. A recently published meta-analysis by West and colleagues concluded that while no specific physician burnout intervention has been shown to be better than other types of interventions, mindfulness, stress management, and small-group discussions can be effective approaches to reducing burnout scores. Strategies to build individual resilience, such as mindfulness and meditation, are easy to teach but place the burden for success on the individual. No amount of resilience can withstand an unsupportive or toxic workplace environment, so both individual and organizational strategies in combination are necessary.
2) The unit or team: Scheduling time for open and honest discussion of social and emotional issues that arise in caring for patients helps nourish caregiver to caregiver compassion. The Schwartz Center for Compassionate Healthcare is a national nonprofit leading the movement to bring compassion to every patient-caregiver interaction. More than 425 health care organization are Schwartz Center members and conduct Schwartz Rounds™ to bring doctors, nurses, and other caregivers together to discuss the human side of health care. (www.theschwartzcenter.org). Team member to team member support is essential for navigating the stressors of practice. With having lunch in front of your computer being the norm, and the disappearance of traditional spaces for colleagues to connect (for example, nurses’ lounge, physician dining rooms), the opportunity for caregivers to have a safe place to escape, a place to have their own humanity reaffirmed, a place to offer support to their peers, has been eliminated.
3) Organizational Leadership: Making compassion a core value, articulating it, and establishing metrics whereby it can be measured, is a good start. The barriers to a culture of compassion are related to our systems of care. There are burgeoning administrative and documentation tasks to be performed, and productivity expectations that turn our clinics and hospitals into assembly lines. No, we cannot expect the EMR [electronic medical records] to be eliminated, but workforce well-being cannot be sustainable in the context of inadequate resources. A culture of compassionate collaborative care requires programs and policies that are implemented by the organization itself. Examples of organization-wide initiatives that support workforce well-being and provider engagement include: screening for caregiver burnout, establishing policies for managing adverse events with an eye toward the second victim, and most importantly, supporting systems that preserve work control autonomy of physicians and nurses in clinical settings. The business sector has long recognized that workplace stress is a function of how demanding a person’s job is and how much control that person has over his or her responsibilities. The business community has also recognized that the experience of the worker (provider) drives the experience of the customer (patient). In a study of hospital compassionate practices and HCAHPS [the Hospital Consumer Assessment of Healthcare Providers and Systems], McClelland and Vogus reported that how well a hospital compassionately supports it employees and rewards compassionate acts is significantly and positively is associated with that hospital’s ratings and likelihood of patients recommending it.
How does the Society of Vascular Surgery, or any professional medical/nursing society for that matter, fit into this model?
We propose that the SVS find ways to empower their members to be agents for culture change within their own health care organizations. How might this be done:
- Teach organizational leadership skills, starting with the SVS Board of Directors, the presidential line, and the chairs of committees. Offer leadership courses at the Annual Meeting.
- Develop a community of caregivers committed to creating a compassionate collaborative culture. The SVS is a founding member of the Schwartz Center Healthcare Society Leadership Council, and you, as members of the SVS benefit from reduced registration at the Annual Compassion in Action Healthcare Conference, June 24-27, 2017 in Boston. (http://compassioninactionconference.org) This conference is designed to be highly experiential, using a hands-on “how to do it” model.
- The SVS should make improving the overall wellness of its members a specific goal and find specific metrics to monitor our progress towards this goal. Members can be provided with the tools to identify, monitor, and measure burnout and compassion. Each committee and council of the SVS can reexamine their objectives through the lens of reducing burnout and improving the wellness of vascular surgeons.
- Provide members with evidence-based programs that build personal resilience. This will not be a successful initiative unless our surgeons recognize and acknowledge the symptoms of burnout, and are willing to admit vulnerability. Without doing so, it is difficult to reach out for help.
- Redesign postgraduate resident and fellowship education. Standardizing clinical care may reduce variation and promote efficiency. However, when processes such as time-limited appointment scheduling, EMR templates, and protocols that drive physician-patient interactions are embedded in Resident and Fellowship education, the result may well be inflexibility in practice, reduced face time with patients, and interactions that lack compassion; all leading to burnout. Graduate Medical Education leaders must develop programs that support the learner’s ability to connect with patients and families, cultivate and role-model skills and behaviors that strengthen compassionate interactions, and strive to develop clinical practice models that increase Resident and Fellow work control autonomy.
The SVS should work proactively to optimize workload, fairness, and reward on a larger scale for its members as it relates to the EMR, reimbursement, and systems coverage. While we may be relatively small in size, as leaders, we are perfectly poised to address these larger, global issues. Perhaps working within the current system (i.e., PAC and APM task force) and considering innovative solutions at a national leadership scale, the SVS can direct real change!
Changing culture is not easy, nor quick, nor does it have an easy-to-follow blueprint. The first step is recognizing the need. The second is taking a leadership role. The third is thinking deeply about implementation.
*The authors extend their thanks and appreciation for the guidance, resources and support of Michael Goldberg, MD, scholar in residence, Schwartz Center for Compassionate Care, Boston and clinical professor of orthopedics at Seattle Children’s Hospital.
REFERENCES
1. J Managerial Psychol. (2007) 22:309-28
2. Annu Rev Neurosci. (2012) 35:1-23
3. Medicine. (2016) 44:583-5
4. J Health Organization Manag. (2015) 29:973-87
5. De Zulueta P Developing compassionate leadership in health care: an integrative review. J Healthcare Leadership. (2016) 8:1-10
6. Dolan ED, Morh D, Lempa M et al. Using a single item to measure burnout in primary care staff: A psychometry evaluation. J Gen Intern Med. (2015) 30:582-7
7. Karasek RA Job demands, job decision latitude, and mental strain: implications for job design. Administrative Sciences Quarterly (1979) 24: 285-308
8. Lee VS, Miller T, Daniels C, et al. Creating the exceptional patient experience in one academic health system. Acad Med. (2016) 91:338-44
9. Linzer M, Levine R, Meltzer D, et al. 10 bold steps to prevent burnout in general internal medicine. J Gen Intern Med. (2013) 29:18-20
10. Lown BA, Manning CF The Schwartz Center Rounds: Evaluation of an interdisciplinary approach to enhancing patient-centered communication, teamwork, and provider support. Acad Med. (2010) 85:1073-81
11. Lown BA, Muncer SJ, Chadwick R Can compassionate healthcare be measured? The Schwartz Center Compassionate Care Scale. Patient Education and Counseling (2015) 98:1005-10
12. Lown BA, McIntosh S, Gaines ME, et. al. Integrating compassionate collaborative care (“the Triple C”) into health professional education to advance the triple aim of health care. Acad Med (2016) 91:1-7
13. Lown BA A social neuroscience-informed model for teaching and practicing compassion in health care. Medical Education (2016) 50: 332-342
14. Maslach C, Schaufeli WG, Leiter MP Job burnout. Annu Rev Psychol (2001) 52:397-422
15. McClelland LE, Vogus TJ Compassion practices and HCAHPS: Does rewarding and supporting workplace compassion influence patient perceptions? HSR: Health Serv Res. (2014) 49:1670-83
16. Shanafelt TD, Noseworthy JH Executive leadership and physician well-being: Nine organizational strategies to promote engagement and reduce burnout. Mayo Clin Proc. (2016) 6:1-18
17. Shanafelt TD, Dyrbye LN, West CP Addressing physician burnout: the way forward. JAMA (2017) 317:901-2
18. Singer T, Klimecki OM Empathy and compassion Curr Biol. (2014) 24: R875-8
19. West CP, Dyrbye LN, Satele DV et. al. Concurrent validity of single-item measures of emotional exhaustion and depersonalization in burnout assessment. J Gen Intern Med. (2012) 27:1445-52
20. West CP, Dyrbye LN, Erwin PJ, et al. Interventions to address and reduce physician burnout: a systematic review and meta-analysis. Lancet. (2016) 388:2272-81
21. Wuest TK, Goldberg MJ, Kelly JD Clinical faceoff: Physician burnout-Fact, fantasy, or the fourth component of the triple aim? Clin Orthop Relat Res. (2016) doi: 10.1007/5-11999-016-5193-5
Migraine Treatment Outcomes
Outcomes of Acute and Preventive Migraine Therapy Based on Patient Sex
I previously have addressed myths about migraine as they pertain to men and women. When I found an interesting study recently published in Cephalalgia investigating the effectiveness of calcitonin gene-related peptide receptor (CGRP-R) antagonists (gepants) for acute care and prevention of episodic migraine and CGRP monoclonal antibodies for preventive treatment of episodic and chronic migraine in men and women, I thought I would discuss it here.
The study’s aim was to discern if patient sex contributed to outcomes in each specific treatment arm. Female sex hormones have been recognized as factors in promoting migraine, and women show increased severity, persistence, and comorbidity in migraine profiles, and increased prevalence of migraine relative to men.
Gepants used for acute therapy (ubrogepant, rimegepant, zavegepant) and preventive therapy (atogepant, rimegepant) were studied in this trial. Erenumab, fremanezumab, galcanezumab, and eptinezumab are monoclonal antibodies that either sit on the CGRP receptor (erenumab) or inactivate the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) and are used for migraine prevention. CGRP-based therapies are not effective in all patients and understanding which patient groups respond preferentially could reduce trial and error in treatment selection. The effectiveness of treatments targeting CGRP or the CGRP receptor may not be uniform in men and women, highlighting the need for further research and understanding of CGRP neurobiology in both sexes.
Key findings:
- In the trial by Porreca et al: In women, the 3 gepants approved by the FDA for the acute care of migraine (ubrogepant, rimegepant, zavegepant) produced a statistically significant drug effect for the 2-hour pain freedom (2h-PF) endpoint, with an average drug effect of 9.5% (CI: 7.4 to 11.6) and an average number needed to treat (NNT) of 11.
- Men did not show statistically significant effects with the acute use of gepants. The average drug effect was 2.8%, and the average NNT was 36.
- For both men and women, CGRP-targeting therapies for prevention of migraine (the 4 monoclonal antibodies) were equally effective; however, possible sex differences remain uncertain and need further study.
- In patients with chronic migraine, CGRP/CGRP-R antibodies were similarly effective in both men and women.
- For the 2-hour freedom from most bothersome symptom (2h-MBS) endpoint when gepants were given acutely, the effects were much better in women than men, with an average drug effect of 10.2% and an average NNT of 10.
- In men, these medications produced observed treatment effects on 2h-MBS with an average drug effect of 3.2% and an average NNT of 32.
- In men, 5 out of 12 estimates favored placebo over the active treatment, suggesting a treatment with little to no effect.
- The pooled treatment effects for women were 3 times as large, at 9.2% and 10.2%, respectively.
- The placebo response rates for 2 of the 3 ubrogepant studies and one of 2 zavegepant studies were higher in men than in women.
The study concludes that, while small molecule CGRP-R antagonists are dramatically effective for acute therapy of migraine in women, available data do not demonstrate effectiveness in men. The treatment effect was found to always favor active treatment numerically for both men and women for prevention of episodic and chronic migraine. The data highlight possible differential effects of CGRP-targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. The study also emphasizes the need to understand which patient groups preferentially respond to CGRP-based therapies to reduce trial and error in treatment. Note that rimegepant data on prevention were not available for analysis at the time of the writing.
It would be interesting to perform a meta-analysis of multiple well-done, large, real-world studies to see if the same differences and similarities are found in men versus women for acute care of migraine and prevention of episodic and chronic migraine. I suspect that we would find that acute care results favor women but that some men do well.
The Effectiveness of Prednisolone for Treating Medication Overuse Headache
I often discuss medication overuse headache (MOH), as it is difficult to diagnose and treat, so I wanted to comment on another pertinent study. It is a post hoc analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE). The RELEASE trial is an ongoing, multicenter, observational, cohort study of MOH that has been conducted in Korea since April 2020. Findings were recently published in Headache by Lee et al.
MOH is a secondary headache disorder that develops in patients with a preexisting primary headache when they overuse acute care headache medications of any type except gepants. This includes prescription medications such as triptans, ergots, butalbital-containing medications; opioids; aspirin; acetaminophen; any type of combination medication often containing caffeine; or a combination of medications. This condition significantly impacts patients’ quality of life and productivity, usually increasing the frequency of headaches per month and leading to higher healthcare-related costs.
Treating MOH is challenging due to the lack of high-quality drug trials specifically designed for MOH and doctor inexperience. Current evidence is based largely on subgroup analyses of drug trials for the treatment of chronic migraine that contain these patient types.
Withdrawal of acute care headache medications that are being overused has traditionally been considered an important aspect of MOH treatment, although this may be changing. Withdrawal symptoms, such as increased intensity of headache pain, frequency of headaches, and other symptoms like agitation and sleep disturbance, can prevent patients from discontinuing overused medications. Systemic corticosteroids are widely used to reduce these withdrawal headaches, but clinical trials are sparse and have failed to meet proper endpoints. Despite this, corticosteroids have shown potential benefits, such as decreasing withdrawal headaches, reducing the use of rescue medications, and lowering headache intensity at certain time points after treatment.
Given these findings, this published study hypothesized that prednisolone may play a role in converting MOH to non-MOH at 3 months after treatment. The objective was to evaluate the outcome of prednisolone therapy in reversing medication overuse at 3 months posttreatment in patients with MOH using prospective multicenter registry data. Prednisolone was prescribed to 59 out of 309 patients (19.1%) enrolled during this observational study period, with doses ranging from 10 to 40 mg/day for 5-14 days. Of these patients, 228 (73.8%) completed the 3-month follow-up period.
Key findings:
- The MOH reversal rates at 3 months postbaseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the no prednisolone group (p = 0.034).
- The steroid effect remained significant (adjusted odds ratio, 2.78; 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of combined preventive medications.
The study had several strengths, including the multicenter collection of data, prospective follow-ups, and comprehensiveness of data acquisition. However, it also had significant limitations, such as the noninterventional, observational nature of the study, potential bias in steroid prescription (every doctor prescribed what they wanted), and heterogeneity in the patient population. Also, there were a variety of treatments, and they were not standardized. Further external validation may be necessary before generalizing the study results.
Despite these limitations, the results do suggest that prednisolone may be one part of a valid treatment option for patients with MOH. I suspect, if the proper studies are done, we will see that using a good preventive medication, with few adverse events, and with careful education of the patient, formal detoxification will not be necessary when treating many patients with MOH. This has been my experience with MOH treatment utilizing the newer anti-CGRP preventive medications, including the older monoclonal antibodies and the newer gepants.
Outcomes of Acute and Preventive Migraine Therapy Based on Patient Sex
I previously have addressed myths about migraine as they pertain to men and women. When I found an interesting study recently published in Cephalalgia investigating the effectiveness of calcitonin gene-related peptide receptor (CGRP-R) antagonists (gepants) for acute care and prevention of episodic migraine and CGRP monoclonal antibodies for preventive treatment of episodic and chronic migraine in men and women, I thought I would discuss it here.
The study’s aim was to discern if patient sex contributed to outcomes in each specific treatment arm. Female sex hormones have been recognized as factors in promoting migraine, and women show increased severity, persistence, and comorbidity in migraine profiles, and increased prevalence of migraine relative to men.
Gepants used for acute therapy (ubrogepant, rimegepant, zavegepant) and preventive therapy (atogepant, rimegepant) were studied in this trial. Erenumab, fremanezumab, galcanezumab, and eptinezumab are monoclonal antibodies that either sit on the CGRP receptor (erenumab) or inactivate the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) and are used for migraine prevention. CGRP-based therapies are not effective in all patients and understanding which patient groups respond preferentially could reduce trial and error in treatment selection. The effectiveness of treatments targeting CGRP or the CGRP receptor may not be uniform in men and women, highlighting the need for further research and understanding of CGRP neurobiology in both sexes.
Key findings:
- In the trial by Porreca et al: In women, the 3 gepants approved by the FDA for the acute care of migraine (ubrogepant, rimegepant, zavegepant) produced a statistically significant drug effect for the 2-hour pain freedom (2h-PF) endpoint, with an average drug effect of 9.5% (CI: 7.4 to 11.6) and an average number needed to treat (NNT) of 11.
- Men did not show statistically significant effects with the acute use of gepants. The average drug effect was 2.8%, and the average NNT was 36.
- For both men and women, CGRP-targeting therapies for prevention of migraine (the 4 monoclonal antibodies) were equally effective; however, possible sex differences remain uncertain and need further study.
- In patients with chronic migraine, CGRP/CGRP-R antibodies were similarly effective in both men and women.
- For the 2-hour freedom from most bothersome symptom (2h-MBS) endpoint when gepants were given acutely, the effects were much better in women than men, with an average drug effect of 10.2% and an average NNT of 10.
- In men, these medications produced observed treatment effects on 2h-MBS with an average drug effect of 3.2% and an average NNT of 32.
- In men, 5 out of 12 estimates favored placebo over the active treatment, suggesting a treatment with little to no effect.
- The pooled treatment effects for women were 3 times as large, at 9.2% and 10.2%, respectively.
- The placebo response rates for 2 of the 3 ubrogepant studies and one of 2 zavegepant studies were higher in men than in women.
The study concludes that, while small molecule CGRP-R antagonists are dramatically effective for acute therapy of migraine in women, available data do not demonstrate effectiveness in men. The treatment effect was found to always favor active treatment numerically for both men and women for prevention of episodic and chronic migraine. The data highlight possible differential effects of CGRP-targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. The study also emphasizes the need to understand which patient groups preferentially respond to CGRP-based therapies to reduce trial and error in treatment. Note that rimegepant data on prevention were not available for analysis at the time of the writing.
It would be interesting to perform a meta-analysis of multiple well-done, large, real-world studies to see if the same differences and similarities are found in men versus women for acute care of migraine and prevention of episodic and chronic migraine. I suspect that we would find that acute care results favor women but that some men do well.
The Effectiveness of Prednisolone for Treating Medication Overuse Headache
I often discuss medication overuse headache (MOH), as it is difficult to diagnose and treat, so I wanted to comment on another pertinent study. It is a post hoc analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE). The RELEASE trial is an ongoing, multicenter, observational, cohort study of MOH that has been conducted in Korea since April 2020. Findings were recently published in Headache by Lee et al.
MOH is a secondary headache disorder that develops in patients with a preexisting primary headache when they overuse acute care headache medications of any type except gepants. This includes prescription medications such as triptans, ergots, butalbital-containing medications; opioids; aspirin; acetaminophen; any type of combination medication often containing caffeine; or a combination of medications. This condition significantly impacts patients’ quality of life and productivity, usually increasing the frequency of headaches per month and leading to higher healthcare-related costs.
Treating MOH is challenging due to the lack of high-quality drug trials specifically designed for MOH and doctor inexperience. Current evidence is based largely on subgroup analyses of drug trials for the treatment of chronic migraine that contain these patient types.
Withdrawal of acute care headache medications that are being overused has traditionally been considered an important aspect of MOH treatment, although this may be changing. Withdrawal symptoms, such as increased intensity of headache pain, frequency of headaches, and other symptoms like agitation and sleep disturbance, can prevent patients from discontinuing overused medications. Systemic corticosteroids are widely used to reduce these withdrawal headaches, but clinical trials are sparse and have failed to meet proper endpoints. Despite this, corticosteroids have shown potential benefits, such as decreasing withdrawal headaches, reducing the use of rescue medications, and lowering headache intensity at certain time points after treatment.
Given these findings, this published study hypothesized that prednisolone may play a role in converting MOH to non-MOH at 3 months after treatment. The objective was to evaluate the outcome of prednisolone therapy in reversing medication overuse at 3 months posttreatment in patients with MOH using prospective multicenter registry data. Prednisolone was prescribed to 59 out of 309 patients (19.1%) enrolled during this observational study period, with doses ranging from 10 to 40 mg/day for 5-14 days. Of these patients, 228 (73.8%) completed the 3-month follow-up period.
Key findings:
- The MOH reversal rates at 3 months postbaseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the no prednisolone group (p = 0.034).
- The steroid effect remained significant (adjusted odds ratio, 2.78; 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of combined preventive medications.
The study had several strengths, including the multicenter collection of data, prospective follow-ups, and comprehensiveness of data acquisition. However, it also had significant limitations, such as the noninterventional, observational nature of the study, potential bias in steroid prescription (every doctor prescribed what they wanted), and heterogeneity in the patient population. Also, there were a variety of treatments, and they were not standardized. Further external validation may be necessary before generalizing the study results.
Despite these limitations, the results do suggest that prednisolone may be one part of a valid treatment option for patients with MOH. I suspect, if the proper studies are done, we will see that using a good preventive medication, with few adverse events, and with careful education of the patient, formal detoxification will not be necessary when treating many patients with MOH. This has been my experience with MOH treatment utilizing the newer anti-CGRP preventive medications, including the older monoclonal antibodies and the newer gepants.
Outcomes of Acute and Preventive Migraine Therapy Based on Patient Sex
I previously have addressed myths about migraine as they pertain to men and women. When I found an interesting study recently published in Cephalalgia investigating the effectiveness of calcitonin gene-related peptide receptor (CGRP-R) antagonists (gepants) for acute care and prevention of episodic migraine and CGRP monoclonal antibodies for preventive treatment of episodic and chronic migraine in men and women, I thought I would discuss it here.
The study’s aim was to discern if patient sex contributed to outcomes in each specific treatment arm. Female sex hormones have been recognized as factors in promoting migraine, and women show increased severity, persistence, and comorbidity in migraine profiles, and increased prevalence of migraine relative to men.
Gepants used for acute therapy (ubrogepant, rimegepant, zavegepant) and preventive therapy (atogepant, rimegepant) were studied in this trial. Erenumab, fremanezumab, galcanezumab, and eptinezumab are monoclonal antibodies that either sit on the CGRP receptor (erenumab) or inactivate the CGRP ligand (fremanezumab, galcanezumab, and eptinezumab) and are used for migraine prevention. CGRP-based therapies are not effective in all patients and understanding which patient groups respond preferentially could reduce trial and error in treatment selection. The effectiveness of treatments targeting CGRP or the CGRP receptor may not be uniform in men and women, highlighting the need for further research and understanding of CGRP neurobiology in both sexes.
Key findings:
- In the trial by Porreca et al: In women, the 3 gepants approved by the FDA for the acute care of migraine (ubrogepant, rimegepant, zavegepant) produced a statistically significant drug effect for the 2-hour pain freedom (2h-PF) endpoint, with an average drug effect of 9.5% (CI: 7.4 to 11.6) and an average number needed to treat (NNT) of 11.
- Men did not show statistically significant effects with the acute use of gepants. The average drug effect was 2.8%, and the average NNT was 36.
- For both men and women, CGRP-targeting therapies for prevention of migraine (the 4 monoclonal antibodies) were equally effective; however, possible sex differences remain uncertain and need further study.
- In patients with chronic migraine, CGRP/CGRP-R antibodies were similarly effective in both men and women.
- For the 2-hour freedom from most bothersome symptom (2h-MBS) endpoint when gepants were given acutely, the effects were much better in women than men, with an average drug effect of 10.2% and an average NNT of 10.
- In men, these medications produced observed treatment effects on 2h-MBS with an average drug effect of 3.2% and an average NNT of 32.
- In men, 5 out of 12 estimates favored placebo over the active treatment, suggesting a treatment with little to no effect.
- The pooled treatment effects for women were 3 times as large, at 9.2% and 10.2%, respectively.
- The placebo response rates for 2 of the 3 ubrogepant studies and one of 2 zavegepant studies were higher in men than in women.
The study concludes that, while small molecule CGRP-R antagonists are dramatically effective for acute therapy of migraine in women, available data do not demonstrate effectiveness in men. The treatment effect was found to always favor active treatment numerically for both men and women for prevention of episodic and chronic migraine. The data highlight possible differential effects of CGRP-targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women. The study also emphasizes the need to understand which patient groups preferentially respond to CGRP-based therapies to reduce trial and error in treatment. Note that rimegepant data on prevention were not available for analysis at the time of the writing.
It would be interesting to perform a meta-analysis of multiple well-done, large, real-world studies to see if the same differences and similarities are found in men versus women for acute care of migraine and prevention of episodic and chronic migraine. I suspect that we would find that acute care results favor women but that some men do well.
The Effectiveness of Prednisolone for Treating Medication Overuse Headache
I often discuss medication overuse headache (MOH), as it is difficult to diagnose and treat, so I wanted to comment on another pertinent study. It is a post hoc analysis of the Registry for Load and Management of Medication Overuse Headache (RELEASE). The RELEASE trial is an ongoing, multicenter, observational, cohort study of MOH that has been conducted in Korea since April 2020. Findings were recently published in Headache by Lee et al.
MOH is a secondary headache disorder that develops in patients with a preexisting primary headache when they overuse acute care headache medications of any type except gepants. This includes prescription medications such as triptans, ergots, butalbital-containing medications; opioids; aspirin; acetaminophen; any type of combination medication often containing caffeine; or a combination of medications. This condition significantly impacts patients’ quality of life and productivity, usually increasing the frequency of headaches per month and leading to higher healthcare-related costs.
Treating MOH is challenging due to the lack of high-quality drug trials specifically designed for MOH and doctor inexperience. Current evidence is based largely on subgroup analyses of drug trials for the treatment of chronic migraine that contain these patient types.
Withdrawal of acute care headache medications that are being overused has traditionally been considered an important aspect of MOH treatment, although this may be changing. Withdrawal symptoms, such as increased intensity of headache pain, frequency of headaches, and other symptoms like agitation and sleep disturbance, can prevent patients from discontinuing overused medications. Systemic corticosteroids are widely used to reduce these withdrawal headaches, but clinical trials are sparse and have failed to meet proper endpoints. Despite this, corticosteroids have shown potential benefits, such as decreasing withdrawal headaches, reducing the use of rescue medications, and lowering headache intensity at certain time points after treatment.
Given these findings, this published study hypothesized that prednisolone may play a role in converting MOH to non-MOH at 3 months after treatment. The objective was to evaluate the outcome of prednisolone therapy in reversing medication overuse at 3 months posttreatment in patients with MOH using prospective multicenter registry data. Prednisolone was prescribed to 59 out of 309 patients (19.1%) enrolled during this observational study period, with doses ranging from 10 to 40 mg/day for 5-14 days. Of these patients, 228 (73.8%) completed the 3-month follow-up period.
Key findings:
- The MOH reversal rates at 3 months postbaseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the no prednisolone group (p = 0.034).
- The steroid effect remained significant (adjusted odds ratio, 2.78; 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of combined preventive medications.
The study had several strengths, including the multicenter collection of data, prospective follow-ups, and comprehensiveness of data acquisition. However, it also had significant limitations, such as the noninterventional, observational nature of the study, potential bias in steroid prescription (every doctor prescribed what they wanted), and heterogeneity in the patient population. Also, there were a variety of treatments, and they were not standardized. Further external validation may be necessary before generalizing the study results.
Despite these limitations, the results do suggest that prednisolone may be one part of a valid treatment option for patients with MOH. I suspect, if the proper studies are done, we will see that using a good preventive medication, with few adverse events, and with careful education of the patient, formal detoxification will not be necessary when treating many patients with MOH. This has been my experience with MOH treatment utilizing the newer anti-CGRP preventive medications, including the older monoclonal antibodies and the newer gepants.
Tender Dermal Nodule on the Temple
The Diagnosis: Lymphoepithelioma-like Carcinoma
Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.1 Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).1 The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.2 These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.3 The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.2
The usual treatment of LELC is wide local excision or Mohs micrographic surgery.1 Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.3 Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.1
Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.4 Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.4 The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.4
Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.6 Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.7 Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.6 Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.8
Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.9 Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.3
Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.10 Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.11 The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).12 The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.11 An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.12
- Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
- Fisher JC, White RM, Hurd DS. Lymphoepithelioma-like carcinoma of the skin: a case of one patient presenting with two primary cutaneous neoplasms. J Am Osteopath Coll Dermatol. 2015;33:40-41.
- Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
- Yu R, Salama S, Alowami S. Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall. Rare Tumors. 2014;6:5358.
- Monteagudo C, Fúnez R, Sánchez-Sendra B, et al. Cutaneous lymphadenoma is a distinct trichoblastoma-like lymphoepithelial tumor with diffuse androgen receptor immunoreactivity, Notch1 ligand in Reed-Sternberg-like Cells, and common EGFR somatic mutations. Am J Surg Pathol. 2021;45:1382-1390.
- Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017;11:16-22.
- Almomani MH, Zulfiqar H, Nagalli S. Nasopharyngeal carcinoma (NPC, lymphoepithelioma). StatPearls Publishing; 2022.
- Lassen CB, Lock-Andersen J. Lymphoepithelioma-like carcinoma of the skin: a case with perineural invasion. Plast Reconstr Surg Glob Open. 2014;2:E252.
- Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants. Adv Anat Pathol. 2017;24:171-194.
- Pileri A, Facchetti F, Rütten A, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100-109.
- Ryu HJ, Kim SI, Jang HO, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides [published October 15, 2021]. Cells. 2021;10:2758. doi:10.3390/cells10102758
- Lehmer LM, Amber KT, de Feraudy SM. Syringotropic mycosis fungoides: a rare form of cutaneous T-cell lymphoma enabling a histopathologic “sigh of relief.” Am J Dermatopathol. 2017;39:920-923.
The Diagnosis: Lymphoepithelioma-like Carcinoma
Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.1 Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).1 The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.2 These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.3 The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.2
The usual treatment of LELC is wide local excision or Mohs micrographic surgery.1 Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.3 Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.1
Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.4 Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.4 The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.4
Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.6 Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.7 Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.6 Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.8
Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.9 Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.3
Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.10 Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.11 The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).12 The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.11 An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.12
The Diagnosis: Lymphoepithelioma-like Carcinoma
Lymphoepithelioma-like carcinoma (LELC) is a rare, poorly differentiated, primary cutaneous neoplasm that occurs on sun-exposed skin, particularly on the head and neck of elderly individuals. It often manifests as an asymptomatic, slow-growing, flesh-colored or erythematous dermal nodule, though ulceration and tenderness have been reported.1 Histopathologically, these neoplasms often are poorly circumscribed and can infiltrate surrounding subcutaneous and soft tissue. As a biphasic tumor, LELC is characterized by islands, nests, or trabeculae of epithelioid cells within the mid dermis surrounded by a dense lymphocytic infiltrate with plasma cells (Figure 1).1 The epithelial component rarely communicates with the overlying epidermis and is composed of atypical polygonal cells with eosinophilic cytoplasm, vesicular nuclei, prominent nucleoli, and frequent mitosis.2 These epithelial nests can be highlighted by pancytokeratin AE1/AE3 or other epithelial differentiation markers (eg, CAM 5.2, CK5/6, epithelial membrane antigen, high-molecular-weight cytokeratin), while the surrounding lymphocytic infiltrate consists of an admixture of T cells and B cells. Lymphoepithelioma-like carcinomas also can demonstrate sebaceous, eccrine, or follicular differentiations.3 The epithelial nests of LELC also are positive for p63 and epithelial membrane antigen.2
The usual treatment of LELC is wide local excision or Mohs micrographic surgery.1 Despite the poorly differentiated morphology of the tumor, LELC has a generally good prognosis with low metastatic potential and few reports of local recurrence after incomplete excision.3 Patients who are not candidates for surgery as well as recalcitrant cases are managed with radiotherapy.1
Cutaneous lymphadenoma (CL) is a benign adnexal neoplasm that manifests as a small, solitary, fleshcolored nodule usually in the head and neck region.4 Histologically, CL consists of well-circumscribed epithelial nests within the dermis that are peripherally outlined by palisading basaloid cells and filled with clear to eosinophilic epithelioid cells (Figure 2).5 The fibrotic tumor stroma often is infiltrated by numerous intralobular dendritic cells and lymphocytes that occasionally can be arranged in germinal center–like nodules.4 The lymphoepithelial nature of CL can be challenging to distinguish morphologically from LELC, and immunohistochemistry stains may be required. In CL, both the basaloid and epithelioid cells stain positive for pancytokeratin AE1/ AE3, but the peripheral palisaded basaloid cells also stain positive for BerEP4. Additionally, the fibrotic stroma can be highlighted by CD34 and the intralobular dendritic cells by S-100.4
Nasopharyngeal carcinoma (NPC), formerly known as lymphoepithelioma, refers to carcinoma arising within the epithelium of the nasopharynx.6 Endemic to China, NPC manifests as an enlarging nasopharyngeal mass, causing clinical symptoms such as nasal obstruction and epistaxis.7 Histologically, nonkeratinizing NPC exhibits a biphasic morphology consisting of epithelioid neoplastic cells and background lymphocytic infiltrates (Figure 3). The epithelial component consists of round to oval neoplastic cells with amphophilic to eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli.6 Nasopharyngeal carcinoma is associated strongly with the Epstein-Barr virus while LELC is not; thus, Epstein- Barr encoding region in situ hybridization can reliably distinguish these entities. Metastatic NPC is rare but has been reported; therefore, it is highly recommended to perform an otolaryngologic examination in addition to testing for Epstein-Barr virus reactivity as part of a complete evaluation.8
Cutaneous squamous cell carcinoma (SCC) is a common epidermal malignancy with multiple subtypes and variable morphology. The clinical presentation of SCC is similar to LELC—an enlarging hyperkeratotic papule or nodule on sun-exposed skin that often is ulcerated and tender.9 Histologically, poorly differentiated nonkeratinizing SCC can form nests and trabeculae of epithelioid cells that are stained by epithelial differentiation markers, resembling the epithelioid nests of LELC. Distinguishing between LELC and poorly differentiated SCC with robust inflammatory infiltrate can be challenging (Figure 4). In fact, some experts support LELC as an SCC variant rather than a separate entity.9 However, in contrast to LELC, the dermal nests of SCC usually maintain an epidermal connection and often are associated with an overlying area of SCC in situ or welldifferentiated SCC.3
Mycosis fungoides (MF) is a primary cutaneous T-cell lymphoma. It is the most common type of cutaneous lymphoma, accounting for almost 50% of all reported cases.10 Classic MF has an indolent course and progresses through several clinical stages. Patches and plaques characterize early stages; lymphadenopathy indicates progression to later stages in which erythroderma may develop with coalescence of patches, plaques, and tumors; and MF present in blood or lymph nodes characterizes the late stage. Each stage of MF is different histologically—from a superficial lichenoid infiltrate with exocytosis of malignant T cells in the patch stage, to more robust epidermotropism and dermal infiltrate in the plaque stage, and finally a dense dermal infiltrate in the late stage.11 The rare syringotropic variant of MF clinically manifests as solitary or multiple erythematous lesions, often with overlying alopecia. Syringotropic MF uniquely exhibits folliculotropism and syringotropism along with syringometaplasia on histologic evaluation (Figure 5).12 The syringometaplasia can be difficult to distinguish from the epithelial nests of LELC, particularly with the lymphocytic background. Immunohistochemical panels for T-cell markers can highlight aberrant T cells in syringotropic MF through their usual loss of CD5 and CD7, in comparison to normal T cells in LELC.11 An elevated CD4:CD8 ratio of 4:1 and molecular analysis for T-cell receptor gene clonal rearrangements also can support the diagnosis of MF.12
- Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
- Fisher JC, White RM, Hurd DS. Lymphoepithelioma-like carcinoma of the skin: a case of one patient presenting with two primary cutaneous neoplasms. J Am Osteopath Coll Dermatol. 2015;33:40-41.
- Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
- Yu R, Salama S, Alowami S. Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall. Rare Tumors. 2014;6:5358.
- Monteagudo C, Fúnez R, Sánchez-Sendra B, et al. Cutaneous lymphadenoma is a distinct trichoblastoma-like lymphoepithelial tumor with diffuse androgen receptor immunoreactivity, Notch1 ligand in Reed-Sternberg-like Cells, and common EGFR somatic mutations. Am J Surg Pathol. 2021;45:1382-1390.
- Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017;11:16-22.
- Almomani MH, Zulfiqar H, Nagalli S. Nasopharyngeal carcinoma (NPC, lymphoepithelioma). StatPearls Publishing; 2022.
- Lassen CB, Lock-Andersen J. Lymphoepithelioma-like carcinoma of the skin: a case with perineural invasion. Plast Reconstr Surg Glob Open. 2014;2:E252.
- Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants. Adv Anat Pathol. 2017;24:171-194.
- Pileri A, Facchetti F, Rütten A, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100-109.
- Ryu HJ, Kim SI, Jang HO, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides [published October 15, 2021]. Cells. 2021;10:2758. doi:10.3390/cells10102758
- Lehmer LM, Amber KT, de Feraudy SM. Syringotropic mycosis fungoides: a rare form of cutaneous T-cell lymphoma enabling a histopathologic “sigh of relief.” Am J Dermatopathol. 2017;39:920-923.
- Morteza Abedi S, Salama S, Alowami S. Lymphoepithelioma-like carcinoma of the skin: case report and approach to surgical pathology sign out. Rare Tumors. 2013;5:E47.
- Fisher JC, White RM, Hurd DS. Lymphoepithelioma-like carcinoma of the skin: a case of one patient presenting with two primary cutaneous neoplasms. J Am Osteopath Coll Dermatol. 2015;33:40-41.
- Welch PQ, Williams SB, Foss RD, et al. Lymphoepithelioma-like carcinoma of head and neck skin: a systematic analysis of 11 cases and review of literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:78-86.
- Yu R, Salama S, Alowami S. Cutaneous lymphadenoma: a rare case and brief review of a diagnostic pitfall. Rare Tumors. 2014;6:5358.
- Monteagudo C, Fúnez R, Sánchez-Sendra B, et al. Cutaneous lymphadenoma is a distinct trichoblastoma-like lymphoepithelial tumor with diffuse androgen receptor immunoreactivity, Notch1 ligand in Reed-Sternberg-like Cells, and common EGFR somatic mutations. Am J Surg Pathol. 2021;45:1382-1390.
- Stelow EB, Wenig BM. Update from the 4th edition of the World Health Organization classification of head and neck tumours: nasopharynx. Head Neck Pathol. 2017;11:16-22.
- Almomani MH, Zulfiqar H, Nagalli S. Nasopharyngeal carcinoma (NPC, lymphoepithelioma). StatPearls Publishing; 2022.
- Lassen CB, Lock-Andersen J. Lymphoepithelioma-like carcinoma of the skin: a case with perineural invasion. Plast Reconstr Surg Glob Open. 2014;2:E252.
- Motaparthi K, Kapil JP, Velazquez EF. Cutaneous squamous cell carcinoma: review of the eighth edition of the American Joint Committee on Cancer Staging Guidelines, Prognostic Factors, and Histopathologic Variants. Adv Anat Pathol. 2017;24:171-194.
- Pileri A, Facchetti F, Rütten A, et al. Syringotropic mycosis fungoides: a rare variant of the disease with peculiar clinicopathologic features. Am J Surg Pathol. 2011;35:100-109.
- Ryu HJ, Kim SI, Jang HO, et al. Evaluation of the International Society for Cutaneous Lymphoma Algorithm for the Diagnosis of Early Mycosis Fungoides [published October 15, 2021]. Cells. 2021;10:2758. doi:10.3390/cells10102758
- Lehmer LM, Amber KT, de Feraudy SM. Syringotropic mycosis fungoides: a rare form of cutaneous T-cell lymphoma enabling a histopathologic “sigh of relief.” Am J Dermatopathol. 2017;39:920-923.
A 77-year-old man presented with a 1.2-cm dermal nodule on the left temple of 1 year’s duration. The lesion had become tender and darker in color. An excision was performed and submitted for histologic examination. Additional immunohistochemistry staining for Epstein-Barr virus was negative.
E-Consults in Dermatology: A Retrospective Analysis
Dermatologic conditions affect approximately one-third of individuals in the United States.1,2 Nearly 1 in 4 physician office visits in the United States are for skin conditions, and less than one-third of these visits are with dermatologists. Although many of these patients may prefer to see a dermatologist for their concerns, they may not be able to access specialist care.3 The limited supply and urban-focused distribution of dermatologists along with reduced acceptance of state-funded insurance plans and long appointment wait times all pose considerable challenges to individuals seeking dermatologic care.2 Electronic consultations (e-consults) have emerged as a promising solution to overcoming these barriers while providing high-quality dermatologic care to a large diverse patient population.2,4 Although e-consults can be of service to all dermatology patients, this modality may be especially beneficial to underserved populations, such as the uninsured and Medicaid patients—groups that historically have experienced limited access to dermatology care due to the low reimbursement rates and high administrative burdens accompanying care delivery.4 This limited access leads to inequity in care, as timely access to dermatology is associated with improved diagnostic accuracy and disease outcomes.3 E-consult implementation can facilitate timely access for these underserved populations and bypass additional barriers to care such as lack of transportation or time off work. Prior e-consult studies have demonstrated relatively high numbers of Medicaid patients utilizing e-consult services.3,5
Although in-person visits remain the gold standard for diagnosis and treatment of dermatologic conditions, e-consults placed by primary care providers (PCPs) can improve access and help triage patients who require in-person dermatology visits.6 In this study, we conducted a retrospective chart review to characterize the e-consults requested of the dermatology department at a large tertiary care medical center in Winston-Salem, North Carolina.
Methods
The electronic health record (EHR) of Atrium Health Wake Forest Baptist (Winston-Salem, North Carolina) was screened for eligible patients from January 1, 2020, to May 31, 2021. Patients—both adult (aged ≥18 years) and pediatric (aged <18 years)—were included if they underwent a dermatology e-consult within this time frame. Provider notes in the medical records were reviewed to determine the nature of the lesion, how long the dermatologist took to complete the e-consult, whether an in-person appointment was recommended, and whether the patient was seen by dermatology within 90 days of the e-consult. Institutional review board approval was obtained.
For each e-consult, the PCP obtained clinical photographs of the lesion in question either through the EHR mobile application or by having patients upload their own photographs directly to their medical records. The referring PCP then completed a brief template regarding the patient’s clinical question and medical history and then sent the completed information to the consulting dermatologist’s EHR inbox. From there, the dermatologist could view the clinical question, documented photographs, and patient medical record to create a brief consult note with recommendations. The note was then sent back via EHR to the PCP to follow up with the patient. Patients were not charged for the e-consult.
Results
Two hundred fifty-four dermatology e-consults were requested by providers at the study center (eTable), which included 252 unique patients (2 patients had 2 separate e-consults regarding different clinical questions). The median time for completion of the e-consult—from submission of the PCP’s e-consult request to dermatologist completion—was 0.37 days. Fifty-six patients (22.0%) were recommended for an in-person appointment (Figure), 33 (58.9%) of whom ultimately scheduled the in-person appointment, and the median length of time between the completion of the e-consult and the in-person appointment was 16.5 days. The remaining 198 patients (78.0%) were not triaged to receive an in-person appointment following the e-consult,but 2 patients (8.7%) were ultimately seen in-person anyway via other referral pathways, with a median length of 33 days between e-consult completion and the in-person appointment. One hundred seventy-six patients (69.8%) avoided an in-person dermatology visit, although 38 (21.6%) of those patients were fewer than 90 days out from their e-consults at the time of data collection. The 254 e-consults included patients from 50 different zip codes, 49 (98.0%) of which were in North Carolina.
Comment
An e-consult is an asynchronous telehealth modality through which PCPs can request specialty evaluation to provide diagnostic and therapeutic guidance, facilitate PCP-specialist coordination of care, and increase access to specialty care with reduced wait times.7,8 Increased care access is especially important, as specialty referral can decrease overall health care expenditure; however, the demand for specialists often exceeds the availability.8 Our e-consult program drastically reduced the time from patients’ initial presentation at their PCP’s office to dermatologist recommendations for treatment or need for in-person dermatology follow-up.
In our analysis, patients were of different racial, ethnic, and socioeconomic backgrounds and lived across a variety of zip codes, predominantly in central and western North Carolina. Almost three-quarters of the patients resided in zip codes where the average income was less than the North Carolina median household income ($66,196).9 Additionally, 82 patients (32.3%) were uninsured or on Medicaid (eTable). These economically disadvantaged patient populations historically have had limited access to dermatologic care.4 One study showed that privately insured individuals were accepted as new patients by dermatologists 91% of the time compared to a 29.8% acceptance rate for publicly insured individuals.10 Uninsured and Medicaid patients also have to wait 34% longer for an appointment compared to individuals with Medicare or private insurance.2 Considering these patients may already be at an economic disadvantage when it comes to seeing and paying for dermatologic services, e-consults may reduce patient travel and appointment expenses while increasing access to specialty care. Based on a 2020 study, each e-consult generates an estimated savings of $80 out-of-pocket per patient per avoided in-person visit.11
In our study, the most common condition for an e-consult in both adult and pediatric patients was rash, which is consistent with prior e-consult studies.5,11 We found that most e-consult patients were not recommended for an in-person dermatology visit, and for those who were recommended to have an in-person visit, the wait time was reduced (Figure). These results corroborate that e-consults may be used as an important triage tool for determining whether a specialist appointment is indicated as well as a public health tool, as timely evaluation is associated with better dermatologic health care outcomes.3 However, the number of patients who did not present for an in-person appointment in our study may be overestimated, as 38 patients’ (21.6%) e-consults were conducted fewer than 90 days before our data collection. Although none of these patients had been seen in person, it is possible they requested an in-person visit after their medical records were reviewed for this study. Additionally, it is possible patients sought care from outside providers not documented in the EHR.
With regard to the payment model for the e-consult program, Atrium Health Wake Forest Baptist initially piloted the e-consult system through a partnership with the American Academy of Medical Colleges’ Project CORE: Coordinating Optimal Referral Experiences (https://www.aamc.org/what-we-do/mission-areas/health-care/project-core). Grant funding through Project CORE allowed both the referring PCP and the specialist completing the e-consult to each receive approximately 0.5 relative value units in payment for each consult completed. Based on early adoption successes, the institution has created additional internal funding to support the continued expansion of the e-consult system and is incentivized to continue funding, as proper utilization of e-consults improves patient access to timely specialist care, avoids no-shows or last-minute cancellations for specialist appointments, and decreases back-door access to specialist care through the emergency department and urgent care facilities.5 Although 0.5 relative value units is not equivalent compensation to an in-person office visit, our study showed that e-consults can be completed much more quickly and efficiently and do not utilize nursing staff or other office resources.
Conclusion
E-consults are an effective telehealth modality that can increase patients’ access to dermatologic specialty care.
Acknowledgments—The authors thank the Wake Forest University School of Medicine Department of Medical Education and Department of Dermatology (Winston-Salem, North Carolina) for their contributions to this research study as well as the Wake Forest Clinical and Translational Science Institute (Winston-Salem, North Carolina) for their help extracting EHR data.
- Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527-1534.
- Naka F, Lu J, Porto A, et al. Impact of dermatology econsults on access to care and skin cancer screening in underserved populations: a model for teledermatology services in community health centers. J Am Acad Dermatol. 2018;78:293-302.
- Mulcahy A, Mehrotra A, Edison K, et al. Variation in dermatologist visits by sociodemographic characteristics. J Am Acad Dermatol. 2017;76:918-924.
- Yang X, Barbieri JS, Kovarik CL. Cost analysis of a store-and-forward teledermatology consult system in Philadelphia. J Am Acad Dermatol. 2019;81:758-764.
- Wang RF, Trinidad J, Lawrence J, et al. Improved patient access and outcomes with the integration of an econsult program (teledermatology) within a large academic medical center. J Am Acad Dermatol. 2020;83:1633-1638.
- Lee KJ, Finnane A, Soyer HP. Recent trends in teledermatology and teledermoscopy. Dermatol Pract Concept. 2018;8:214-223.
- Parikh PJ, Mowrey C, Gallimore J, et al. Evaluating e-consultation implementations based on use and time-line across various specialties. Int J Med Inform. 2017;108:42-48.
- Wasfy JH, Rao SK, Kalwani N, et al. Longer-term impact of cardiology e-consults. Am Heart J. 2016;173:86-93.
- United States Census Bureau. QuickFacts: North Carolina; United States. Accessed February 26, 2024. https://www.census.gov/quickfacts/fact/table/NC,US/PST045222
- Alghothani L, Jacks SK, Vander Horst A, et al. Disparities in access to dermatologic care according to insurance type. Arch Dermatol. 2012;148:956-957.
- Seiger K, Hawryluk EB, Kroshinsky D, et al. Pediatric dermatology econsults: reduced wait times and dermatology office visits. Pediatr Dermatol. 2020;37:804-810.
Dermatologic conditions affect approximately one-third of individuals in the United States.1,2 Nearly 1 in 4 physician office visits in the United States are for skin conditions, and less than one-third of these visits are with dermatologists. Although many of these patients may prefer to see a dermatologist for their concerns, they may not be able to access specialist care.3 The limited supply and urban-focused distribution of dermatologists along with reduced acceptance of state-funded insurance plans and long appointment wait times all pose considerable challenges to individuals seeking dermatologic care.2 Electronic consultations (e-consults) have emerged as a promising solution to overcoming these barriers while providing high-quality dermatologic care to a large diverse patient population.2,4 Although e-consults can be of service to all dermatology patients, this modality may be especially beneficial to underserved populations, such as the uninsured and Medicaid patients—groups that historically have experienced limited access to dermatology care due to the low reimbursement rates and high administrative burdens accompanying care delivery.4 This limited access leads to inequity in care, as timely access to dermatology is associated with improved diagnostic accuracy and disease outcomes.3 E-consult implementation can facilitate timely access for these underserved populations and bypass additional barriers to care such as lack of transportation or time off work. Prior e-consult studies have demonstrated relatively high numbers of Medicaid patients utilizing e-consult services.3,5
Although in-person visits remain the gold standard for diagnosis and treatment of dermatologic conditions, e-consults placed by primary care providers (PCPs) can improve access and help triage patients who require in-person dermatology visits.6 In this study, we conducted a retrospective chart review to characterize the e-consults requested of the dermatology department at a large tertiary care medical center in Winston-Salem, North Carolina.
Methods
The electronic health record (EHR) of Atrium Health Wake Forest Baptist (Winston-Salem, North Carolina) was screened for eligible patients from January 1, 2020, to May 31, 2021. Patients—both adult (aged ≥18 years) and pediatric (aged <18 years)—were included if they underwent a dermatology e-consult within this time frame. Provider notes in the medical records were reviewed to determine the nature of the lesion, how long the dermatologist took to complete the e-consult, whether an in-person appointment was recommended, and whether the patient was seen by dermatology within 90 days of the e-consult. Institutional review board approval was obtained.
For each e-consult, the PCP obtained clinical photographs of the lesion in question either through the EHR mobile application or by having patients upload their own photographs directly to their medical records. The referring PCP then completed a brief template regarding the patient’s clinical question and medical history and then sent the completed information to the consulting dermatologist’s EHR inbox. From there, the dermatologist could view the clinical question, documented photographs, and patient medical record to create a brief consult note with recommendations. The note was then sent back via EHR to the PCP to follow up with the patient. Patients were not charged for the e-consult.
Results
Two hundred fifty-four dermatology e-consults were requested by providers at the study center (eTable), which included 252 unique patients (2 patients had 2 separate e-consults regarding different clinical questions). The median time for completion of the e-consult—from submission of the PCP’s e-consult request to dermatologist completion—was 0.37 days. Fifty-six patients (22.0%) were recommended for an in-person appointment (Figure), 33 (58.9%) of whom ultimately scheduled the in-person appointment, and the median length of time between the completion of the e-consult and the in-person appointment was 16.5 days. The remaining 198 patients (78.0%) were not triaged to receive an in-person appointment following the e-consult,but 2 patients (8.7%) were ultimately seen in-person anyway via other referral pathways, with a median length of 33 days between e-consult completion and the in-person appointment. One hundred seventy-six patients (69.8%) avoided an in-person dermatology visit, although 38 (21.6%) of those patients were fewer than 90 days out from their e-consults at the time of data collection. The 254 e-consults included patients from 50 different zip codes, 49 (98.0%) of which were in North Carolina.
Comment
An e-consult is an asynchronous telehealth modality through which PCPs can request specialty evaluation to provide diagnostic and therapeutic guidance, facilitate PCP-specialist coordination of care, and increase access to specialty care with reduced wait times.7,8 Increased care access is especially important, as specialty referral can decrease overall health care expenditure; however, the demand for specialists often exceeds the availability.8 Our e-consult program drastically reduced the time from patients’ initial presentation at their PCP’s office to dermatologist recommendations for treatment or need for in-person dermatology follow-up.
In our analysis, patients were of different racial, ethnic, and socioeconomic backgrounds and lived across a variety of zip codes, predominantly in central and western North Carolina. Almost three-quarters of the patients resided in zip codes where the average income was less than the North Carolina median household income ($66,196).9 Additionally, 82 patients (32.3%) were uninsured or on Medicaid (eTable). These economically disadvantaged patient populations historically have had limited access to dermatologic care.4 One study showed that privately insured individuals were accepted as new patients by dermatologists 91% of the time compared to a 29.8% acceptance rate for publicly insured individuals.10 Uninsured and Medicaid patients also have to wait 34% longer for an appointment compared to individuals with Medicare or private insurance.2 Considering these patients may already be at an economic disadvantage when it comes to seeing and paying for dermatologic services, e-consults may reduce patient travel and appointment expenses while increasing access to specialty care. Based on a 2020 study, each e-consult generates an estimated savings of $80 out-of-pocket per patient per avoided in-person visit.11
In our study, the most common condition for an e-consult in both adult and pediatric patients was rash, which is consistent with prior e-consult studies.5,11 We found that most e-consult patients were not recommended for an in-person dermatology visit, and for those who were recommended to have an in-person visit, the wait time was reduced (Figure). These results corroborate that e-consults may be used as an important triage tool for determining whether a specialist appointment is indicated as well as a public health tool, as timely evaluation is associated with better dermatologic health care outcomes.3 However, the number of patients who did not present for an in-person appointment in our study may be overestimated, as 38 patients’ (21.6%) e-consults were conducted fewer than 90 days before our data collection. Although none of these patients had been seen in person, it is possible they requested an in-person visit after their medical records were reviewed for this study. Additionally, it is possible patients sought care from outside providers not documented in the EHR.
With regard to the payment model for the e-consult program, Atrium Health Wake Forest Baptist initially piloted the e-consult system through a partnership with the American Academy of Medical Colleges’ Project CORE: Coordinating Optimal Referral Experiences (https://www.aamc.org/what-we-do/mission-areas/health-care/project-core). Grant funding through Project CORE allowed both the referring PCP and the specialist completing the e-consult to each receive approximately 0.5 relative value units in payment for each consult completed. Based on early adoption successes, the institution has created additional internal funding to support the continued expansion of the e-consult system and is incentivized to continue funding, as proper utilization of e-consults improves patient access to timely specialist care, avoids no-shows or last-minute cancellations for specialist appointments, and decreases back-door access to specialist care through the emergency department and urgent care facilities.5 Although 0.5 relative value units is not equivalent compensation to an in-person office visit, our study showed that e-consults can be completed much more quickly and efficiently and do not utilize nursing staff or other office resources.
Conclusion
E-consults are an effective telehealth modality that can increase patients’ access to dermatologic specialty care.
Acknowledgments—The authors thank the Wake Forest University School of Medicine Department of Medical Education and Department of Dermatology (Winston-Salem, North Carolina) for their contributions to this research study as well as the Wake Forest Clinical and Translational Science Institute (Winston-Salem, North Carolina) for their help extracting EHR data.
Dermatologic conditions affect approximately one-third of individuals in the United States.1,2 Nearly 1 in 4 physician office visits in the United States are for skin conditions, and less than one-third of these visits are with dermatologists. Although many of these patients may prefer to see a dermatologist for their concerns, they may not be able to access specialist care.3 The limited supply and urban-focused distribution of dermatologists along with reduced acceptance of state-funded insurance plans and long appointment wait times all pose considerable challenges to individuals seeking dermatologic care.2 Electronic consultations (e-consults) have emerged as a promising solution to overcoming these barriers while providing high-quality dermatologic care to a large diverse patient population.2,4 Although e-consults can be of service to all dermatology patients, this modality may be especially beneficial to underserved populations, such as the uninsured and Medicaid patients—groups that historically have experienced limited access to dermatology care due to the low reimbursement rates and high administrative burdens accompanying care delivery.4 This limited access leads to inequity in care, as timely access to dermatology is associated with improved diagnostic accuracy and disease outcomes.3 E-consult implementation can facilitate timely access for these underserved populations and bypass additional barriers to care such as lack of transportation or time off work. Prior e-consult studies have demonstrated relatively high numbers of Medicaid patients utilizing e-consult services.3,5
Although in-person visits remain the gold standard for diagnosis and treatment of dermatologic conditions, e-consults placed by primary care providers (PCPs) can improve access and help triage patients who require in-person dermatology visits.6 In this study, we conducted a retrospective chart review to characterize the e-consults requested of the dermatology department at a large tertiary care medical center in Winston-Salem, North Carolina.
Methods
The electronic health record (EHR) of Atrium Health Wake Forest Baptist (Winston-Salem, North Carolina) was screened for eligible patients from January 1, 2020, to May 31, 2021. Patients—both adult (aged ≥18 years) and pediatric (aged <18 years)—were included if they underwent a dermatology e-consult within this time frame. Provider notes in the medical records were reviewed to determine the nature of the lesion, how long the dermatologist took to complete the e-consult, whether an in-person appointment was recommended, and whether the patient was seen by dermatology within 90 days of the e-consult. Institutional review board approval was obtained.
For each e-consult, the PCP obtained clinical photographs of the lesion in question either through the EHR mobile application or by having patients upload their own photographs directly to their medical records. The referring PCP then completed a brief template regarding the patient’s clinical question and medical history and then sent the completed information to the consulting dermatologist’s EHR inbox. From there, the dermatologist could view the clinical question, documented photographs, and patient medical record to create a brief consult note with recommendations. The note was then sent back via EHR to the PCP to follow up with the patient. Patients were not charged for the e-consult.
Results
Two hundred fifty-four dermatology e-consults were requested by providers at the study center (eTable), which included 252 unique patients (2 patients had 2 separate e-consults regarding different clinical questions). The median time for completion of the e-consult—from submission of the PCP’s e-consult request to dermatologist completion—was 0.37 days. Fifty-six patients (22.0%) were recommended for an in-person appointment (Figure), 33 (58.9%) of whom ultimately scheduled the in-person appointment, and the median length of time between the completion of the e-consult and the in-person appointment was 16.5 days. The remaining 198 patients (78.0%) were not triaged to receive an in-person appointment following the e-consult,but 2 patients (8.7%) were ultimately seen in-person anyway via other referral pathways, with a median length of 33 days between e-consult completion and the in-person appointment. One hundred seventy-six patients (69.8%) avoided an in-person dermatology visit, although 38 (21.6%) of those patients were fewer than 90 days out from their e-consults at the time of data collection. The 254 e-consults included patients from 50 different zip codes, 49 (98.0%) of which were in North Carolina.
Comment
An e-consult is an asynchronous telehealth modality through which PCPs can request specialty evaluation to provide diagnostic and therapeutic guidance, facilitate PCP-specialist coordination of care, and increase access to specialty care with reduced wait times.7,8 Increased care access is especially important, as specialty referral can decrease overall health care expenditure; however, the demand for specialists often exceeds the availability.8 Our e-consult program drastically reduced the time from patients’ initial presentation at their PCP’s office to dermatologist recommendations for treatment or need for in-person dermatology follow-up.
In our analysis, patients were of different racial, ethnic, and socioeconomic backgrounds and lived across a variety of zip codes, predominantly in central and western North Carolina. Almost three-quarters of the patients resided in zip codes where the average income was less than the North Carolina median household income ($66,196).9 Additionally, 82 patients (32.3%) were uninsured or on Medicaid (eTable). These economically disadvantaged patient populations historically have had limited access to dermatologic care.4 One study showed that privately insured individuals were accepted as new patients by dermatologists 91% of the time compared to a 29.8% acceptance rate for publicly insured individuals.10 Uninsured and Medicaid patients also have to wait 34% longer for an appointment compared to individuals with Medicare or private insurance.2 Considering these patients may already be at an economic disadvantage when it comes to seeing and paying for dermatologic services, e-consults may reduce patient travel and appointment expenses while increasing access to specialty care. Based on a 2020 study, each e-consult generates an estimated savings of $80 out-of-pocket per patient per avoided in-person visit.11
In our study, the most common condition for an e-consult in both adult and pediatric patients was rash, which is consistent with prior e-consult studies.5,11 We found that most e-consult patients were not recommended for an in-person dermatology visit, and for those who were recommended to have an in-person visit, the wait time was reduced (Figure). These results corroborate that e-consults may be used as an important triage tool for determining whether a specialist appointment is indicated as well as a public health tool, as timely evaluation is associated with better dermatologic health care outcomes.3 However, the number of patients who did not present for an in-person appointment in our study may be overestimated, as 38 patients’ (21.6%) e-consults were conducted fewer than 90 days before our data collection. Although none of these patients had been seen in person, it is possible they requested an in-person visit after their medical records were reviewed for this study. Additionally, it is possible patients sought care from outside providers not documented in the EHR.
With regard to the payment model for the e-consult program, Atrium Health Wake Forest Baptist initially piloted the e-consult system through a partnership with the American Academy of Medical Colleges’ Project CORE: Coordinating Optimal Referral Experiences (https://www.aamc.org/what-we-do/mission-areas/health-care/project-core). Grant funding through Project CORE allowed both the referring PCP and the specialist completing the e-consult to each receive approximately 0.5 relative value units in payment for each consult completed. Based on early adoption successes, the institution has created additional internal funding to support the continued expansion of the e-consult system and is incentivized to continue funding, as proper utilization of e-consults improves patient access to timely specialist care, avoids no-shows or last-minute cancellations for specialist appointments, and decreases back-door access to specialist care through the emergency department and urgent care facilities.5 Although 0.5 relative value units is not equivalent compensation to an in-person office visit, our study showed that e-consults can be completed much more quickly and efficiently and do not utilize nursing staff or other office resources.
Conclusion
E-consults are an effective telehealth modality that can increase patients’ access to dermatologic specialty care.
Acknowledgments—The authors thank the Wake Forest University School of Medicine Department of Medical Education and Department of Dermatology (Winston-Salem, North Carolina) for their contributions to this research study as well as the Wake Forest Clinical and Translational Science Institute (Winston-Salem, North Carolina) for their help extracting EHR data.
- Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527-1534.
- Naka F, Lu J, Porto A, et al. Impact of dermatology econsults on access to care and skin cancer screening in underserved populations: a model for teledermatology services in community health centers. J Am Acad Dermatol. 2018;78:293-302.
- Mulcahy A, Mehrotra A, Edison K, et al. Variation in dermatologist visits by sociodemographic characteristics. J Am Acad Dermatol. 2017;76:918-924.
- Yang X, Barbieri JS, Kovarik CL. Cost analysis of a store-and-forward teledermatology consult system in Philadelphia. J Am Acad Dermatol. 2019;81:758-764.
- Wang RF, Trinidad J, Lawrence J, et al. Improved patient access and outcomes with the integration of an econsult program (teledermatology) within a large academic medical center. J Am Acad Dermatol. 2020;83:1633-1638.
- Lee KJ, Finnane A, Soyer HP. Recent trends in teledermatology and teledermoscopy. Dermatol Pract Concept. 2018;8:214-223.
- Parikh PJ, Mowrey C, Gallimore J, et al. Evaluating e-consultation implementations based on use and time-line across various specialties. Int J Med Inform. 2017;108:42-48.
- Wasfy JH, Rao SK, Kalwani N, et al. Longer-term impact of cardiology e-consults. Am Heart J. 2016;173:86-93.
- United States Census Bureau. QuickFacts: North Carolina; United States. Accessed February 26, 2024. https://www.census.gov/quickfacts/fact/table/NC,US/PST045222
- Alghothani L, Jacks SK, Vander Horst A, et al. Disparities in access to dermatologic care according to insurance type. Arch Dermatol. 2012;148:956-957.
- Seiger K, Hawryluk EB, Kroshinsky D, et al. Pediatric dermatology econsults: reduced wait times and dermatology office visits. Pediatr Dermatol. 2020;37:804-810.
- Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. J Invest Dermatol. 2014;134:1527-1534.
- Naka F, Lu J, Porto A, et al. Impact of dermatology econsults on access to care and skin cancer screening in underserved populations: a model for teledermatology services in community health centers. J Am Acad Dermatol. 2018;78:293-302.
- Mulcahy A, Mehrotra A, Edison K, et al. Variation in dermatologist visits by sociodemographic characteristics. J Am Acad Dermatol. 2017;76:918-924.
- Yang X, Barbieri JS, Kovarik CL. Cost analysis of a store-and-forward teledermatology consult system in Philadelphia. J Am Acad Dermatol. 2019;81:758-764.
- Wang RF, Trinidad J, Lawrence J, et al. Improved patient access and outcomes with the integration of an econsult program (teledermatology) within a large academic medical center. J Am Acad Dermatol. 2020;83:1633-1638.
- Lee KJ, Finnane A, Soyer HP. Recent trends in teledermatology and teledermoscopy. Dermatol Pract Concept. 2018;8:214-223.
- Parikh PJ, Mowrey C, Gallimore J, et al. Evaluating e-consultation implementations based on use and time-line across various specialties. Int J Med Inform. 2017;108:42-48.
- Wasfy JH, Rao SK, Kalwani N, et al. Longer-term impact of cardiology e-consults. Am Heart J. 2016;173:86-93.
- United States Census Bureau. QuickFacts: North Carolina; United States. Accessed February 26, 2024. https://www.census.gov/quickfacts/fact/table/NC,US/PST045222
- Alghothani L, Jacks SK, Vander Horst A, et al. Disparities in access to dermatologic care according to insurance type. Arch Dermatol. 2012;148:956-957.
- Seiger K, Hawryluk EB, Kroshinsky D, et al. Pediatric dermatology econsults: reduced wait times and dermatology office visits. Pediatr Dermatol. 2020;37:804-810.
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>Salisbury</fileName> <TBEID>0C02F328.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02F328</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname>Salisbury</storyname> <articleType>1</articleType> <TBLocation>Copyfitting-CT</TBLocation> <QCDate/> <firstPublished>20240305T083011</firstPublished> <LastPublished>20240305T083011</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20240305T083010</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline>Katherine R. Salisbury, BS; Caroline L. Porter, MD</byline> <bylineText>Katherine R. Salisbury, BS; Caroline L. Porter, MD; Ailia K. Ali, MD; Lindsay C. Strowd, MD</bylineText> <bylineFull>Katherine R. Salisbury, BS; Caroline L. Porter, MD</bylineFull> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange>107-109,E3</pageRange> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>Dermatologic conditions affect approximately one-third of individuals in the United States.1,2 Nearly 1 in 4 physician office visits in the United States are fo</metaDescription> <articlePDF>300453</articlePDF> <teaserImage/> <title>E-Consults in Dermatology: A Retrospective Analysis</title> <deck/> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2024</pubPubdateYear> <pubPubdateMonth>March</pubPubdateMonth> <pubPubdateDay/> <pubVolume>113</pubVolume> <pubNumber>3</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>2159</CMSID> </CMSIDs> <keywords> <keyword>practice management</keyword> </keywords> <seeAlsos/> <publications_g> <publicationData> <publicationCode>CT</publicationCode> <pubIssueName>March 2024</pubIssueName> <pubArticleType>Departments | 2159</pubArticleType> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Cutis</journalTitle> <journalFullTitle>Cutis</journalFullTitle> <copyrightStatement>Copyright 2015 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">12</term> </publications> <sections> <term canonical="true">50892</term> </sections> <topics> <term canonical="true">278</term> </topics> <links> <link> <itemClass qcode="ninat:composite"/> <altRep contenttype="application/pdf">images/180026dd.pdf</altRep> <description role="drol:caption"/> <description role="drol:credit"/> </link> </links> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>E-Consults in Dermatology: A Retrospective Analysis</title> <deck/> </itemMeta> <itemContent> <p class="abstract">Dermatology electronic consultations (e-consults) placed by primary care providers (PCPs) can increase access to specialty care while reducing wait times and providing accurate clinical outcomes. These e-consults also may reduce barriers for underserved patients who historically have limited access to dermatologic care. Our retrospective chart review examines patient outcomes from a dermatology e-consult program at a tertiary care medical center. E-consults effectively increased access to dermatology care while shortening wait times and reducing health care expenditures.</p> <p> <em><em>Cutis. </em>2024;113:107-109, E3.</em> </p> <p>Dermatologic conditions affect approximately one-third of individuals in the United States.<sup>1,2</sup> Nearly 1 in 4 physician office visits in the United States are for skin conditions, and less than one-third of these visits are with dermatologists. Although many of these patients may prefer to see a dermatologist for their concerns, they may not be able to access specialist care.<sup>3</sup> The limited supply and urban-focused distribution of dermatologists along with reduced acceptance of state-funded insurance plans and long appointment wait times all pose considerable challenges to individuals seeking dermatologic care.<sup>2</sup> Electronic consultations (e-consults) have emerged as a promising solution to overcoming these barriers while providing high-quality dermatologic care to a large diverse patient population.<sup>2,4</sup> Although e-consults can be of service to all dermatology patients, this modality may be especially beneficial to underserved populations, such as the uninsured and Medicaid patients—groups that historically have experienced limited access to dermatology care due to the low reimbursement rates and high administrative burdens accompanying care delivery.<sup>4</sup> This limited access leads to inequity in care, as timely access to dermatology is associated with improved diagnostic accuracy and disease outcomes.<sup>3</sup> E-consult implementation can facilitate timely access for these underserved populations and bypass additional barriers to care such as lack of transportation or time off work. Prior e-consult studies have demonstrated relatively high numbers of Medicaid patients utilizing e-consult services.<sup>3,5</sup> </p> <p>Although in-person visits remain the gold standard for diagnosis and treatment of dermatologic conditions, e-consults placed by primary care providers (PCPs) can improve access and help triage patients who require in-person dermatology visits.<sup>6</sup> In this study, we conducted a retrospective chart review to characterize the e-consults requested of the dermatology department at a large tertiary care medical center in Winston-Salem, North Carolina.</p> <h3>Methods</h3> <p>The electronic health record (EHR) of Atrium Health Wake Forest Baptist (Winston-Salem, North Carolina) was screened for eligible patients from January 1, 2020, to May 31, 2021. Patients—both adult (aged ≥18 years) and pediatric (aged <span class="body"><</span>18 years)—were included if they underwent a dermatology e-consult within this time frame. Provider notes in the medical records were reviewed to determine the nature of the lesion, how long the dermatologist took to complete the e-consult, whether an in-person appointment was recommended, and whether the patient was seen by dermatology within 90 days of the e-consult. Institutional review board approval was obtained.</p> <p>For each e-consult, the PCP obtained clinical photographs of the lesion in question either through the EHR mobile application or by having patients upload their own photographs directly to their medical records. The referring PCP then completed a brief template regarding the patient’s clinical question and medical history and then sent the completed information to the consulting dermatologist’s EHR inbox. From there, the dermatologist could view the clinical question, documented photographs, and patient medical record to create a brief consult note with recommendations. The note was then sent back via EHR to the PCP to follow up with the patient. Patients were not charged for the e-consult.</p> <h3>Results</h3> <p>Two hundred fifty-four dermatology e-consults were requested by providers at the study center (eTable), which included 252 unique patients (2 patients had 2 separate e-consults regarding different clinical questions). The median time for completion of the e-consult—from submission of the PCP’s e-consult request to dermatologist completion—was 0.37 days. Fifty-six patients (22.0%) were recommended for an in-person appointment (Figure), 33 (58.9%) of whom ultimately scheduled the in-person appointment, and the median length of time between the completion of the e-consult and the in-person appointment was 16.5 days. The remaining 198 patients (78.0%) were not triaged to receive an in-person appointment following the e-consult,but 2 patients (8.7%) were ultimately seen in-person anyway via other referral pathways, with a median length of 33 days between e-consult completion and the in-person appointment. One hundred seventy-six patients (69.8%) avoided an in-person dermatology visit, although 38 (21.6%) of those patients were fewer than 90 days out from their e-consults at the time of data collection. The 254 e-consults included patients from 50 different zip codes, 49 (98.0%) of which were in North Carolina. </p> <h3>Comment</h3> <p>An e-consult is an asynchronous telehealth modality through which PCPs can request specialty evaluation to provide diagnostic and therapeutic guidance, facilitate PCP-specialist coordination of care, and increase access to specialty care with reduced wait times.<sup>7,8</sup> Increased care access is especially important, as specialty referral can decrease overall health care expenditure; however, the demand for specialists often exceeds the availability.<sup>8</sup> Our e-consult program drastically reduced the time from patients’ initial presentation at their PCP’s office to dermatologist recommendations for treatment or need for in-person dermatology follow-up.</p> <p>In our analysis, patients were of different racial, ethnic, and socioeconomic backgrounds and lived across a variety of zip codes, predominantly in central and western North Carolina. Almost three-quarters of the patients resided in zip codes where the average income was less than the North Carolina median household income ($66,196).<sup>9</sup> Additionally, 82 patients (32.3%) were uninsured or on Medicaid (eTable). These economically disadvantaged patient populations historically have had limited access to dermatologic care.<sup>4</sup> One study showed that privately insured individuals were accepted as new patients by dermatologists 91% of the time compared to a 29.8% acceptance rate for publicly insured individuals.<sup>10</sup> Uninsured and Medicaid patients also have to wait 34% longer for an appointment compared to individuals with Medicare or private insurance.<sup>2</sup> Considering these patients may already be at an economic disadvantage when it comes to seeing and paying for dermatologic services, e-consults may reduce patient travel and appointment expenses while increasing access to specialty care. Based on a 2020 study, each e-consult generates an estimated savings of $80 out-of-pocket per patient per avoided in-person visit.<sup>11</sup><br/><br/>In our study, the most common condition for an e-consult in both adult and pediatric patients was rash, which is consistent with prior e-consult studies.<sup>5,11</sup> We found that most e-consult patients were not recommended for an in-person dermatology visit, and for those who were recommended to have an in-person visit, the wait time was reduced (Figure). These results corroborate that e-consults may be used as an important triage tool for determining whether a specialist appointment is indicated as well as a public health tool, as timely evaluation is associated with better dermatologic health care outcomes.<sup>3</sup> However, the number of patients who did not present for an in-person appointment in our study may be overestimated, as 38 patients’ (21.6%) e-consults were conducted fewer than 90 days before our data collection. Although none of these patients had been seen in person, it is possible they requested an in-person visit after their medical records were reviewed for this study. Additionally, it is possible patients sought care from outside providers not documented in the EHR.<br/><br/>With regard to the payment model for the e-consult program, Atrium Health Wake Forest Baptist initially piloted the e-consult system through a partnership with the American Academy of Medical Colleges’ Project CORE: Coordinating Optimal Referral Experiences (https://www.aamc.org/what-we-do/mission-areas/health-care/project-core). Grant funding through Project CORE allowed both the referring PCP and the specialist completing the e-consult to each receive approximately 0.5 relative value units in payment for each consult completed. Based on early adoption successes, the institution has created additional internal funding to support the continued expansion of the e-consult system and is incentivized to continue funding, as proper utilization of e-consults improves patient access to timely specialist care, avoids no-shows or last-minute cancellations for specialist appointments, and decreases back-door access to specialist care through the emergency department and urgent care facilities.<sup>5</sup> Although 0.5 relative value units is not equivalent compensation to an in-person office visit, our study showed that e-consults can be completed much more quickly and efficiently and do not utilize nursing staff or other office resources.</p> <h3>Conclusion</h3> <p>E-consults are an effective telehealth modality that can increase patients’ access to dermatologic specialty care. <hl name="5"/>Patients who typically are underrepresented in dermatology practices especially may benefit from increased accessibility, and all patients requiring in-person visits may benefit from reduced appointment wait times. The savings generated by in-person appointment avoidance reduce overall health care expenditure as well as the burden of individual expenses. The short turnaround time for e-consults also allows PCPs to better manage dermatologic issues in a timely manner. Integrating and expanding e-consult programs into everyday practice would extend specialty care to broader populations and help reduce barriers to access to dermatologic care.<br/><br/><i><br/><br/>Acknowledgments—</i>The authors thank the Wake Forest University School of Medicine Department of Medical Education and Department of Dermatology (Winston-Salem, North Carolina) for their contributions to this research study as well as the Wake Forest Clinical and Translational Science Institute (Winston-Salem, North Carolina) for their help extracting EHR data.</p> <h2>References</h2> <p class="reference"> 1. Hay RJ, Johns NE, Williams HC, et al. The global burden of skin disease in 2010: an analysis of the prevalence and impact of skin conditions. <em>J Invest Dermatol.</em> 2014;134:1527-1534.<br/><br/> 2. Naka F, Lu J, Porto A, et al. Impact of dermatology econsults on access to care and skin cancer screening in underserved populations: a model for teledermatology services in community health centers. <em>J Am Acad Dermatol.</em> 2018;78:293-302.<br/><br/> 3. Mulcahy A, Mehrotra A, Edison K, et al. Variation in dermatologist visits by sociodemographic characteristics. <em>J Am Acad Dermatol.</em> 2017;76:918-924.<br/><br/> 4. Yang X, Barbieri JS, Kovarik CL. Cost analysis of a store-and-forward teledermatology consult system in Philadelphia. <em>J Am Acad Dermatol. </em>2019;81:758-764.<br/><br/> 5. Wang RF, Trinidad J, Lawrence J, et al. Improved patient access and outcomes with the integration of an econsult program (teledermatology) within a large academic medical center. <em>J Am Acad Dermatol. </em>2020;83:1633-1638.<br/><br/> 6. Lee KJ, Finnane A, Soyer HP. Recent trends in teledermatology and teledermoscopy. <em>Dermatol Pract Concept.</em> 2018;8:214-223.<br/><br/> 7. Parikh PJ, Mowrey C, Gallimore J, et al. Evaluating e-consultation implementations based on use and time-line across various specialties. <em>Int J Med Inform.</em> 2017;108:42-48.<br/><br/> 8. Wasfy JH, Rao SK, Kalwani N, et al. Longer-term impact of cardiology e-consults. <em>Am Heart J.</em> 2016;173:86-93.<br/><br/> 9. United States Census Bureau. QuickFacts: North Carolina; United States. Accessed February 26, 2024. https://www.census.gov/quickfacts/fact/table/NC,US/PST045222<br/><br/>10. Alghothani L, Jacks SK, Vander Horst A, et al. Disparities in access to dermatologic care according to insurance type. <em>Arch Dermatol. </em>2012;148:956-957.<br/><br/>11. Seiger K, Hawryluk EB, Kroshinsky D, et al. Pediatric dermatology econsults: reduced wait times and dermatology office visits. <em>Pediatr Dermatol.</em> 2020;37:804-810.</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>bio</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="disclosure">From the <hl name="17866"/>Center for Dermatology Research, Department of Dermatology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.</p> <p class="disclosure">Katherine R. Salisbury and Drs. Porter and Ali report no conflict of interest. <hl name="17867"/>Dr. Strowd has received grants or support from AbbVie, Galderma, Pfizer, and Sanofi-Regeneron.<br/><br/>The eTable is available in the Appendix online at www.mdedge.com/dermatology. <br/><br/>Correspondence: Katherine R. Salisbury, BS, Department of Dermatology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157-1071 (ksalisbu@wakehealth.edu).<br/><br/>doi:10.12788/cutis.0975</p> </itemContent> </newsItem> <newsItem> <itemMeta> <itemRole>in</itemRole> <itemClass>text</itemClass> <title/> <deck/> </itemMeta> <itemContent> <p class="insidehead">Practice <strong>Points</strong></p> <ul class="insidebody"> <li>Most electronic consult patients may be able to avoid in-person dermatology appointments.</li> <li>E-consults can increase patient access to dermatologic specialty care.</li> </ul> </itemContent> </newsItem> </itemSet></root>
Practice Points
- Most electronic consult patients may be able to avoid in-person dermatology appointments.
- E-consults can increase patient access to dermatologic specialty care.
Commentary: PPI Dosing, Biomarkers, and Eating Behaviors in Patients With EoE, March 2024
This study provides compelling evidence that a twice-daily dosing regimen of moderate-dose proton pump inhibitors (PPIs) is superior to a once-daily regimen for inducing histologic remission in eosinophilic esophagitis (EoE). This finding suggests a significant paradigm shift in EoE management, challenging the current standard treatment guideline that recommends a PPI trial of 20-40 mg twice daily. The limited data on various dosing regimens for EoE treatment underscores the importance of this research. Dr Muftah and colleagues from Brigham and Women's Hospital have conducted a novel retrospective cohort study to address the question: Does a twice-daily PPI dose induce a higher remission rate in EoE than a once-daily regimen does regardless of the total daily dose?
The study enrolled adult patients with newly-diagnosed treatment-naive EoE at a tertiary care center, dividing participants into four groups on the basis of their treatment regimen: once-daily standard dose (20 mg omeprazole), once-daily moderate dose (40 mg), twice-daily moderate dose (20 mg), and twice-daily high dose (40 mg). Patients underwent endoscopy 8-12 weeks after initiating PPI treatment, with the primary outcome being the histologic response to PPI, defined as fewer than 15 eosinophils/high power field in repeat esophageal biopsies.
Out of 305 patients (54.6% men, mean age 44.7 ± 16.7 years), 42.3% achieved a histologic response to PPI treatment. Patients receiving the standard PPI dose (20 mg omeprazole once daily) vs those on twice-daily moderate and high doses showed significantly higher histologic response rates (52.8% vs 11.8%, P < .0001; and 54.3% vs 11.8%, P < .0001; respectively). Multivariable analysis revealed that twice-daily moderate and high doses were significantly more effective (adjusted odds ration [aOR] 6.75; CI 2.53-18.0, P = .0008; and aOR 12.8, CI 4.69-34.8, P < .001; respectively).
However, the study's retrospective design limits its ability to establish causality and may introduce selection bias. In addition, the lack of specified adjustments for PPI dosing based on diet and lifestyle factors across the cohort could influence treatment response and outcomes. Last, as a single-center study, the results may not generalize across diverse patient populations, particularly those with different demographics or disease severities.
This research heralds a shift toward a more effective treatment strategy in EoE management, suggesting that a twice-daily PPI regimen may be more beneficial than once-daily dosing is for inducing histologic remission, especially in patients inadequately responding to once-daily PPI treatment. It advocates for a personalized treatment approach, considering factors such as symptom severity, previous PPI response, and potential for adherence to a twice-daily regimen.
Distinguishing between inflammatory bowel disease (IBD)–induced eosinophilia and EoE poses a significant challenge for clinicians. Given that the incidence of EoE is 3-5 times higher in patients with IBD compared with the general population, there is a pressing need for new biomarkers to differentiate between these two conditions. In response to this need, Dr Butzke and colleagues at Nemours Children's Health in Wilmington, Delaware, conducted a retrospective study to evaluate the roles of Major Basic Protein (MBP) and interleukin (IL)-13 in distinguishing these diseases. The study included participants who underwent esophagogastroduodenoscopy with esophageal biopsies for IBD workup or suspicion of EoE. It comprised 27 patients with EoE-IBD, 39 with EoE, 29 with IBD eosinophilia, 30 with IBD only, and 30 control patients. The biopsies were stained with MBP and IL-13 antibodies, and the results (percent staining/total tissue area), demographic, and clinical findings were compared among the groups.
The study revealed that MBP staining levels among patients with EoE-IBD were 3.8 units, which is significantly lower than those in the EoE group at 52.8 units and higher than those with IBD eosinophilia at 0.2 units (P < .001). IL-13 expression was significantly higher only compared with the IBD and control groups and not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity, whereas IL-13 demonstrated 83% sensitivity and 90% specificity using a cutoff point from the cohort of patients without EoE-IBD. Based on the MBP cutoff point of 3.49 units that distinguished between EoE and non-EoE cases, 100% of patients with EoE were MBP-positive compared with 3% of patients with IBD-associated eosinophilia (P < .05).
To implement this new biomarker into clinical practice, guidelines for interpreting MBP staining results should be developed and established, including defining cutoff points for positive and negative results. However, this study faces several limitations, such as not evaluating the differences in MBP results based on EoE-IBD type and disease activity. The retrospective nature of the study and its small sample size limit its power. In addition, the study did not assess how different treatments and disease activity affect MBP levels nor did it address the lack of longitudinal evaluation in assessing MBP levels.
Despite these limitations, the study presents a compelling case for the use of MBP as a biomarker to distinguish true EoE from EoE-IBD. This differentiation is crucial because it can guide therapeutic approaches, influencing medication choices and dietary interventions. MBP shows promise as an excellent biomarker for distinguishing true EoE from eosinophilia caused by IBD. When combined with endoscopic and histologic changes, MBP can assist with the diagnosis of EoE in IBD patients, thereby reducing the possibility of misdiagnosis.
Being diagnosed with EoE poses a challenging and life-altering experience for patients and their families. They face numerous challenges, from undergoing diagnostic procedures and treatments to adapting daily diets. Limited information is available on the eating habits of patients diagnosed with EoE. In this study, Dr Kennedy and colleagues explored how a diagnosis of EoE affects eating behaviors among pediatric patients.
The researchers conducted a prospective study involving 27 patients diagnosed with EoE and compared their eating behaviors to those of 25 healthy control participants. The participants were evaluated on the basis of their responses to four food textures (puree, soft solid, chewable, and hard solid), focusing on the number of chews per bite, sips of fluid per food, and consumption time.
The study found that, on average, patients with EoE (63.5% boys, mean age 11 years) required more chews per bite across several food textures (soft solid P = .031; chewable P = .047; and hard solid P = .037) and demonstrated increased consumption time for soft solid (P = .002), chewable (P = .005), and hard solid foods (P = .034) compared to healthy controls. In addition, endoscopic reference scores positively correlated with consumption time (r = 0.53; P = .008) and the number of chews (r = 0.45; P = .027) for chewable foods as well as with the number of chews (r = 0.44; P = .043) for hard solid foods. Increased consumption time also correlated with increased eosinophil counts (r = 0.42; P = .050) and decreased esophageal distensibility (r = -0.82; P < .0001).
Though these findings open promising avenues for the noninvasive assessment and personalized management of EoE, further research with larger, longitudinal studies is essential to validate these behaviors as reliable clinical biomarkers. Increasing the sample size would enhance the study's power and broaden the generalizability of its findings to a wider pediatric EoE population. The study's cross-sectional nature limits the ability to assess how eating behaviors change over time with treatment or disease progression.
This study underscores the potential of eating behaviors as clinical markers for pediatric patients with EoE, enabling early identification through increased chewing and consumption times, especially with harder textures. Such markers could prompt diagnostic evaluations in settings where endoscopy and biopsy are gold standards for diagnosing EoE. Moreover, eating patterns could assist in monitoring disease activity and progression, offering a noninvasive means of assessing disease status and response to therapy, thus allowing for more frequent assessments of disease status without the need for invasive procedures. Understanding these behaviors allows healthcare providers to tailor dietary advice and interventions, potentially enhancing treatment compliance and improving the quality of life for pediatric patients with EoE.
This study provides compelling evidence that a twice-daily dosing regimen of moderate-dose proton pump inhibitors (PPIs) is superior to a once-daily regimen for inducing histologic remission in eosinophilic esophagitis (EoE). This finding suggests a significant paradigm shift in EoE management, challenging the current standard treatment guideline that recommends a PPI trial of 20-40 mg twice daily. The limited data on various dosing regimens for EoE treatment underscores the importance of this research. Dr Muftah and colleagues from Brigham and Women's Hospital have conducted a novel retrospective cohort study to address the question: Does a twice-daily PPI dose induce a higher remission rate in EoE than a once-daily regimen does regardless of the total daily dose?
The study enrolled adult patients with newly-diagnosed treatment-naive EoE at a tertiary care center, dividing participants into four groups on the basis of their treatment regimen: once-daily standard dose (20 mg omeprazole), once-daily moderate dose (40 mg), twice-daily moderate dose (20 mg), and twice-daily high dose (40 mg). Patients underwent endoscopy 8-12 weeks after initiating PPI treatment, with the primary outcome being the histologic response to PPI, defined as fewer than 15 eosinophils/high power field in repeat esophageal biopsies.
Out of 305 patients (54.6% men, mean age 44.7 ± 16.7 years), 42.3% achieved a histologic response to PPI treatment. Patients receiving the standard PPI dose (20 mg omeprazole once daily) vs those on twice-daily moderate and high doses showed significantly higher histologic response rates (52.8% vs 11.8%, P < .0001; and 54.3% vs 11.8%, P < .0001; respectively). Multivariable analysis revealed that twice-daily moderate and high doses were significantly more effective (adjusted odds ration [aOR] 6.75; CI 2.53-18.0, P = .0008; and aOR 12.8, CI 4.69-34.8, P < .001; respectively).
However, the study's retrospective design limits its ability to establish causality and may introduce selection bias. In addition, the lack of specified adjustments for PPI dosing based on diet and lifestyle factors across the cohort could influence treatment response and outcomes. Last, as a single-center study, the results may not generalize across diverse patient populations, particularly those with different demographics or disease severities.
This research heralds a shift toward a more effective treatment strategy in EoE management, suggesting that a twice-daily PPI regimen may be more beneficial than once-daily dosing is for inducing histologic remission, especially in patients inadequately responding to once-daily PPI treatment. It advocates for a personalized treatment approach, considering factors such as symptom severity, previous PPI response, and potential for adherence to a twice-daily regimen.
Distinguishing between inflammatory bowel disease (IBD)–induced eosinophilia and EoE poses a significant challenge for clinicians. Given that the incidence of EoE is 3-5 times higher in patients with IBD compared with the general population, there is a pressing need for new biomarkers to differentiate between these two conditions. In response to this need, Dr Butzke and colleagues at Nemours Children's Health in Wilmington, Delaware, conducted a retrospective study to evaluate the roles of Major Basic Protein (MBP) and interleukin (IL)-13 in distinguishing these diseases. The study included participants who underwent esophagogastroduodenoscopy with esophageal biopsies for IBD workup or suspicion of EoE. It comprised 27 patients with EoE-IBD, 39 with EoE, 29 with IBD eosinophilia, 30 with IBD only, and 30 control patients. The biopsies were stained with MBP and IL-13 antibodies, and the results (percent staining/total tissue area), demographic, and clinical findings were compared among the groups.
The study revealed that MBP staining levels among patients with EoE-IBD were 3.8 units, which is significantly lower than those in the EoE group at 52.8 units and higher than those with IBD eosinophilia at 0.2 units (P < .001). IL-13 expression was significantly higher only compared with the IBD and control groups and not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity, whereas IL-13 demonstrated 83% sensitivity and 90% specificity using a cutoff point from the cohort of patients without EoE-IBD. Based on the MBP cutoff point of 3.49 units that distinguished between EoE and non-EoE cases, 100% of patients with EoE were MBP-positive compared with 3% of patients with IBD-associated eosinophilia (P < .05).
To implement this new biomarker into clinical practice, guidelines for interpreting MBP staining results should be developed and established, including defining cutoff points for positive and negative results. However, this study faces several limitations, such as not evaluating the differences in MBP results based on EoE-IBD type and disease activity. The retrospective nature of the study and its small sample size limit its power. In addition, the study did not assess how different treatments and disease activity affect MBP levels nor did it address the lack of longitudinal evaluation in assessing MBP levels.
Despite these limitations, the study presents a compelling case for the use of MBP as a biomarker to distinguish true EoE from EoE-IBD. This differentiation is crucial because it can guide therapeutic approaches, influencing medication choices and dietary interventions. MBP shows promise as an excellent biomarker for distinguishing true EoE from eosinophilia caused by IBD. When combined with endoscopic and histologic changes, MBP can assist with the diagnosis of EoE in IBD patients, thereby reducing the possibility of misdiagnosis.
Being diagnosed with EoE poses a challenging and life-altering experience for patients and their families. They face numerous challenges, from undergoing diagnostic procedures and treatments to adapting daily diets. Limited information is available on the eating habits of patients diagnosed with EoE. In this study, Dr Kennedy and colleagues explored how a diagnosis of EoE affects eating behaviors among pediatric patients.
The researchers conducted a prospective study involving 27 patients diagnosed with EoE and compared their eating behaviors to those of 25 healthy control participants. The participants were evaluated on the basis of their responses to four food textures (puree, soft solid, chewable, and hard solid), focusing on the number of chews per bite, sips of fluid per food, and consumption time.
The study found that, on average, patients with EoE (63.5% boys, mean age 11 years) required more chews per bite across several food textures (soft solid P = .031; chewable P = .047; and hard solid P = .037) and demonstrated increased consumption time for soft solid (P = .002), chewable (P = .005), and hard solid foods (P = .034) compared to healthy controls. In addition, endoscopic reference scores positively correlated with consumption time (r = 0.53; P = .008) and the number of chews (r = 0.45; P = .027) for chewable foods as well as with the number of chews (r = 0.44; P = .043) for hard solid foods. Increased consumption time also correlated with increased eosinophil counts (r = 0.42; P = .050) and decreased esophageal distensibility (r = -0.82; P < .0001).
Though these findings open promising avenues for the noninvasive assessment and personalized management of EoE, further research with larger, longitudinal studies is essential to validate these behaviors as reliable clinical biomarkers. Increasing the sample size would enhance the study's power and broaden the generalizability of its findings to a wider pediatric EoE population. The study's cross-sectional nature limits the ability to assess how eating behaviors change over time with treatment or disease progression.
This study underscores the potential of eating behaviors as clinical markers for pediatric patients with EoE, enabling early identification through increased chewing and consumption times, especially with harder textures. Such markers could prompt diagnostic evaluations in settings where endoscopy and biopsy are gold standards for diagnosing EoE. Moreover, eating patterns could assist in monitoring disease activity and progression, offering a noninvasive means of assessing disease status and response to therapy, thus allowing for more frequent assessments of disease status without the need for invasive procedures. Understanding these behaviors allows healthcare providers to tailor dietary advice and interventions, potentially enhancing treatment compliance and improving the quality of life for pediatric patients with EoE.
This study provides compelling evidence that a twice-daily dosing regimen of moderate-dose proton pump inhibitors (PPIs) is superior to a once-daily regimen for inducing histologic remission in eosinophilic esophagitis (EoE). This finding suggests a significant paradigm shift in EoE management, challenging the current standard treatment guideline that recommends a PPI trial of 20-40 mg twice daily. The limited data on various dosing regimens for EoE treatment underscores the importance of this research. Dr Muftah and colleagues from Brigham and Women's Hospital have conducted a novel retrospective cohort study to address the question: Does a twice-daily PPI dose induce a higher remission rate in EoE than a once-daily regimen does regardless of the total daily dose?
The study enrolled adult patients with newly-diagnosed treatment-naive EoE at a tertiary care center, dividing participants into four groups on the basis of their treatment regimen: once-daily standard dose (20 mg omeprazole), once-daily moderate dose (40 mg), twice-daily moderate dose (20 mg), and twice-daily high dose (40 mg). Patients underwent endoscopy 8-12 weeks after initiating PPI treatment, with the primary outcome being the histologic response to PPI, defined as fewer than 15 eosinophils/high power field in repeat esophageal biopsies.
Out of 305 patients (54.6% men, mean age 44.7 ± 16.7 years), 42.3% achieved a histologic response to PPI treatment. Patients receiving the standard PPI dose (20 mg omeprazole once daily) vs those on twice-daily moderate and high doses showed significantly higher histologic response rates (52.8% vs 11.8%, P < .0001; and 54.3% vs 11.8%, P < .0001; respectively). Multivariable analysis revealed that twice-daily moderate and high doses were significantly more effective (adjusted odds ration [aOR] 6.75; CI 2.53-18.0, P = .0008; and aOR 12.8, CI 4.69-34.8, P < .001; respectively).
However, the study's retrospective design limits its ability to establish causality and may introduce selection bias. In addition, the lack of specified adjustments for PPI dosing based on diet and lifestyle factors across the cohort could influence treatment response and outcomes. Last, as a single-center study, the results may not generalize across diverse patient populations, particularly those with different demographics or disease severities.
This research heralds a shift toward a more effective treatment strategy in EoE management, suggesting that a twice-daily PPI regimen may be more beneficial than once-daily dosing is for inducing histologic remission, especially in patients inadequately responding to once-daily PPI treatment. It advocates for a personalized treatment approach, considering factors such as symptom severity, previous PPI response, and potential for adherence to a twice-daily regimen.
Distinguishing between inflammatory bowel disease (IBD)–induced eosinophilia and EoE poses a significant challenge for clinicians. Given that the incidence of EoE is 3-5 times higher in patients with IBD compared with the general population, there is a pressing need for new biomarkers to differentiate between these two conditions. In response to this need, Dr Butzke and colleagues at Nemours Children's Health in Wilmington, Delaware, conducted a retrospective study to evaluate the roles of Major Basic Protein (MBP) and interleukin (IL)-13 in distinguishing these diseases. The study included participants who underwent esophagogastroduodenoscopy with esophageal biopsies for IBD workup or suspicion of EoE. It comprised 27 patients with EoE-IBD, 39 with EoE, 29 with IBD eosinophilia, 30 with IBD only, and 30 control patients. The biopsies were stained with MBP and IL-13 antibodies, and the results (percent staining/total tissue area), demographic, and clinical findings were compared among the groups.
The study revealed that MBP staining levels among patients with EoE-IBD were 3.8 units, which is significantly lower than those in the EoE group at 52.8 units and higher than those with IBD eosinophilia at 0.2 units (P < .001). IL-13 expression was significantly higher only compared with the IBD and control groups and not with EoE-IBD or IBD eosinophilia. MBP predicted EoE with 100% sensitivity and 99% specificity, whereas IL-13 demonstrated 83% sensitivity and 90% specificity using a cutoff point from the cohort of patients without EoE-IBD. Based on the MBP cutoff point of 3.49 units that distinguished between EoE and non-EoE cases, 100% of patients with EoE were MBP-positive compared with 3% of patients with IBD-associated eosinophilia (P < .05).
To implement this new biomarker into clinical practice, guidelines for interpreting MBP staining results should be developed and established, including defining cutoff points for positive and negative results. However, this study faces several limitations, such as not evaluating the differences in MBP results based on EoE-IBD type and disease activity. The retrospective nature of the study and its small sample size limit its power. In addition, the study did not assess how different treatments and disease activity affect MBP levels nor did it address the lack of longitudinal evaluation in assessing MBP levels.
Despite these limitations, the study presents a compelling case for the use of MBP as a biomarker to distinguish true EoE from EoE-IBD. This differentiation is crucial because it can guide therapeutic approaches, influencing medication choices and dietary interventions. MBP shows promise as an excellent biomarker for distinguishing true EoE from eosinophilia caused by IBD. When combined with endoscopic and histologic changes, MBP can assist with the diagnosis of EoE in IBD patients, thereby reducing the possibility of misdiagnosis.
Being diagnosed with EoE poses a challenging and life-altering experience for patients and their families. They face numerous challenges, from undergoing diagnostic procedures and treatments to adapting daily diets. Limited information is available on the eating habits of patients diagnosed with EoE. In this study, Dr Kennedy and colleagues explored how a diagnosis of EoE affects eating behaviors among pediatric patients.
The researchers conducted a prospective study involving 27 patients diagnosed with EoE and compared their eating behaviors to those of 25 healthy control participants. The participants were evaluated on the basis of their responses to four food textures (puree, soft solid, chewable, and hard solid), focusing on the number of chews per bite, sips of fluid per food, and consumption time.
The study found that, on average, patients with EoE (63.5% boys, mean age 11 years) required more chews per bite across several food textures (soft solid P = .031; chewable P = .047; and hard solid P = .037) and demonstrated increased consumption time for soft solid (P = .002), chewable (P = .005), and hard solid foods (P = .034) compared to healthy controls. In addition, endoscopic reference scores positively correlated with consumption time (r = 0.53; P = .008) and the number of chews (r = 0.45; P = .027) for chewable foods as well as with the number of chews (r = 0.44; P = .043) for hard solid foods. Increased consumption time also correlated with increased eosinophil counts (r = 0.42; P = .050) and decreased esophageal distensibility (r = -0.82; P < .0001).
Though these findings open promising avenues for the noninvasive assessment and personalized management of EoE, further research with larger, longitudinal studies is essential to validate these behaviors as reliable clinical biomarkers. Increasing the sample size would enhance the study's power and broaden the generalizability of its findings to a wider pediatric EoE population. The study's cross-sectional nature limits the ability to assess how eating behaviors change over time with treatment or disease progression.
This study underscores the potential of eating behaviors as clinical markers for pediatric patients with EoE, enabling early identification through increased chewing and consumption times, especially with harder textures. Such markers could prompt diagnostic evaluations in settings where endoscopy and biopsy are gold standards for diagnosing EoE. Moreover, eating patterns could assist in monitoring disease activity and progression, offering a noninvasive means of assessing disease status and response to therapy, thus allowing for more frequent assessments of disease status without the need for invasive procedures. Understanding these behaviors allows healthcare providers to tailor dietary advice and interventions, potentially enhancing treatment compliance and improving the quality of life for pediatric patients with EoE.
Commentary: New Research on BC Chemotherapies, March 2024
The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.[5]
TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.
Additional References
- Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
- Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
- Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
- Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
- Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
- Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
- Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source
The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.[5]
TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.
Additional References
- Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
- Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
- Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
- Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
- Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
- Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
- Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source
The phase 3 KEYNOTE-355 trial established the role of chemotherapy in combination with pembrolizumab in the first-line setting for programmed death-ligand 1 (PD-L1)–positive advanced triple-negative breast cancer (TNBC). Patients unselected for PD-L1 status in this trial who received platinum- or taxane-based chemotherapy with placebo had a median progression-free survival of 5.6 months.[3] Strategies to improve upon efficacy and tolerability are desired in this space, and various trials have evaluated "switch maintenance" that involves receipt of an intensive induction regimen followed by a switch to an alternative/more tolerable regimen after response is achieved.[4] The phase II DORA trial randomized 45 patients with advanced TNBC and ongoing stable disease or complete or partial response from first- or second-line platinum-based chemotherapy to a maintenance regimen of olaparib (300 mg orally twice daily) with or without durvalumab (1500 mg on day 1 and every 4 weeks) (Tan et al). At a median follow-up of 9.8 months, median progression-free survival was 4.0 months (95% CI 2.6-6.1) with olaparib and 6.1 months (95% CI 3.7-10.1) with the combination; both were significantly longer than the historical control of continued platinum-based therapy (P = .0023 and P < .0001, respectively). Durable disease control appeared more pronounced in patients with complete or partial response to prior platinum therapy, and no new safety signals were observed. Future efforts to study this approach include the phase 2/3 KEYLYNK-009 trial, which is evaluating olaparib plus pembrolizumab maintenance therapy after first-line chemotherapy plus pembrolizumab for TNBC.[5]
TNBC is a heterogenous subtype, characterized by aggressive biology, and it benefits from chemotherapy and immunotherapy treatment approaches. Presently, the management of early-stage TNBC often involves neoadjuvant systemic therapy; however, a proportion of patients receive treatment in the postoperative setting, highlighting the relevance of time to initiation of adjuvant therapy as well.[6] Various prior studies have showed that delayed administration of adjuvant chemotherapy for EBC can lead to adverse survival outcomes. Furthermore, this effect is subtype-dependent, with more aggressive tumors (luminal B, triple-negative, human epidermal growth factor receptor 2 [HER2]-positive) exhibiting inferior outcomes with delayed chemotherapy.[7] A retrospective cohort study that included 245 patients with early TNBC who received adjuvant chemotherapy after surgery evaluated the impact of time to initiation of adjuvant therapy in this population (Hatzipanagiotou et al). Superior survival outcomes were observed for the group receiving systemic therapy 22-28 days after surgery (median overall survival 10.2 years) compared with those receiving adjuvant chemotherapy at later time points (29-35 days, 36-42 days, and >6 weeks after surgery; median overall survival 8.3 years, 7.8 years, and 6.9 years, respectively). Patients receiving chemotherapy 22-28 days after surgery had significantly better survival than those receiving chemotherapy 29-35 days (P = .043) and >6 weeks (P = 0.033) postoperatively. This study emphasizes the importance of timely administration of adjuvant chemotherapy for early TNBC, and efforts aimed to identify potential challenges and propose solutions to optimize outcomes in this space are valuable.
Additional References
- Gnant M, Frantal S, Pfeiler G, et al, for the Austrian Breast & Colorectal Cancer Study Group. Long-term outcomes of adjuvant denosumab in breast cancer. NEJM Evid. 2022;1:EVIDoa2200162. doi: 10.1056/EVIDoa2200162 Source
- Fassio A, Idolazzi L, Rossini M, et al. The obesity paradox and osteoporosis. Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity. 2018;23:293-30 doi: 10.1007/s40519-018-0505-2 Source
- Cortes J, Cescon DW, Rugo HS, et al, for the KEYNOTE-355 Investigators. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for previously untreated locally recurrent inoperable or metastatic triple-negative breast cancer (KEYNOTE-355): A randomised, placebo-controlled, double-blind, phase 3 clinical trial. Lancet. 2020;396:1817-1828. doi: 10.1016/S0140-6736(20)32531-9 Source
- Bachelot T, Filleron T, Bieche I, et al. Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: The randomized phase II SAFIR02-BREAST IMMUNO trial. Nat Med. 2021;27:250-255. doi: 10.1038/s41591-020-01189-2 Source
- Saji S, Cussac AL, Andre F, et al. 68TiP KEYLYNK-009: a phase II/III, open-label, randomized study of pembrolizumab (pembro) + olaparib (ola) vs pembro + chemotherapy after induction with first-line (1L) pembro + chemo in patients (pts) with locally recurrent inoperable or metastatic TNBC (abstract). Ann Oncol. 2020;31(Suppl 6):S1268. doi: 10.1016/j.annonc.2020.10.088 Source
- Ortmann O, Blohmer JU, Sibert NT, et al for 55 breast cancer centers certified by the German Cancer Society. Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: Analysis of individual data from 94,638 patients treated in 55 breast cancer centers. J Cancer Res Clin Oncol. 2023;149:1195-1209. doi: 10.1007/s00432-022-03938-x Source
- Yu KD, Fan L, Qiu LX, et al. Influence of delayed initiation of adjuvant chemotherapy on breast cancer survival is subtype-dependent. Oncotarget. 2017;8:46549-46556. doi: 10.18632/oncotarget.10551 Source
Commentary: Medication Timing and Other Dupilumab Concerns, March 2024
When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.
Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.
Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.
I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib.
When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.
Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.
Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.
I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib.
When skin diseases affect the palm or sole, they can have a disproportionately large negative effect on patients' lives. Hand and foot dermatitis can be disabling. Simpson and colleagues find that dupilumab is an effective treatment for AD of the hands and feet. Having safe and effective treatment for hand and foot dermatitis will be life-changing for many of our patients.
Patients often do very well with biologic treatment. When they do, they often wonder, Do I need to continue taking the medication? Lasheras-Pérez and colleagues found that the great majority of patients doing well taking dupilumab for AD could stretch out their dosing interval. I suspect a lot of our patients are doing this already. I used to worry that stretching out the dosing interval might lead to antidrug antibodies and loss of activity. Such loss of activity doesn't appear common. Because we also have multiple alternative treatments for severe AD, I think it may be quite reasonable for patients to try spreading out their doses after their disease has been well controlled for a good long time.
Superficial skin infections aren't rare in children, particularly children with AD. Paller and colleagues' study is informative about the safety of dupilumab in children. The drug, which blocks a pathway of the immune system, was associated with fewer infections. This is good news. The reduction in infections could be through restoring "immune balance" (whatever that means) or by improving skin barrier function. Perhaps the low rate of infection explains why dupilumab is not considered immunosuppressive.
I love studies of drug survival because I think that knowing the percentage of patients who stay with drug treatment is a good measure of overall safety and efficacy. Pezzolo and colleagues found — perhaps not surprisingly given the extraordinary efficacy of upadacitinib for AD — that almost no one discontinued the drug over 1.5 years due to lack of efficacy. There were patients who discontinued due to adverse events (and additional patients lost to follow-up who perhaps also discontinued the drug), but 80% of patients were still in the study at the end of 1.5 years. Three patients who weren't vaccinated for shingles developed shingles; encouraging patients to get the shingles vaccine may be a prudent measure when starting patients taking upadacitinib.
Commentary: Allergies, EDN, and the Psychosocial Burden of EoE, February 2024
A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.
Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.
The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.
This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.
This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.
Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.
Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.
EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.
Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.
EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.
EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.
The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.
In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).
The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).
Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.
This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.
Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.
Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.
A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.
Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.
The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.
This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.
This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.
Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.
Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.
EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.
Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.
EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.
EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.
The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.
In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).
The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).
Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.
This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.
Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.
Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.
A significant gap in our understanding of eosinophilic esophagitis (EoE) lies in how environmental factors, such as allergens or food, influence the response to proton pump inhibitor (PPI) therapy. While PPI achieve histologic remission in approximately 50% of patients, the response in the remaining 50% remains unclear. Addressing this, Muftah and colleagues conducted a study to evaluate the relationship between environmental and food allergies and PPI response in newly diagnosed EoE patients.
Between 2012 and 2016, adult patients newly diagnosed with EoE were tested for environmental and food allergies. Following diagnosis, patients participated in an 8-week trial of twice-daily PPI therapy. The treatment's effectiveness was assessed through repeated upper endoscopies with esophageal biopsies.
The study's primary outcome was the histologic remission of EoE, defined as a decrease in eosinophils to < 15 eosinophils/high-powered field (eos/hpf) in all esophageal biopsy samples during repeat endoscopy. Out of 61 patients, 21 achieved histologic remission, while 40 were classified as having PPI-nonresponding EoE. Among PPI-nonresponding EoE patients, positive food allergen testing was significantly more prevalent compared with PPI-responding EoE patients (82.5% vs 42.9%; P = .0003). Additionally, patients with >10 positive environmental allergen tests were significantly less likely to be PPI-responding EoE patients than those with <10 positive results (21% vs 53.9%; P = .03). A similar trend was observed in patients with >5 positive environmental allergens.
This study is not without limitations. It may exhibit a selection bias toward more severe cases and has a relatively small sample size, affecting its statistical power and generalizability.
This research supports the idea of more tailored management for EoE patients, focusing on their allergen profile, potentially leading to more effective treatment strategies and reducing unnecessary PPI trials. The statistically significant results pave the way for further research, providing an additional tool to predict PPI responsiveness and prevent delays in achieving remission.
Clinicians should consider patient characteristics, particularly positive food allergen tests, that might affect treatment response. More studies are needed, however, to understand the effect of environmental allergies on PPI response fully. A notable finding is that specific aeroallergens, such as oak, birch, Hormodendrum mold, dust mite (Dermatophagoides pteronyssinus), tree mix, and grass mix allergens, are associated with a lack of PPI response. This raises questions about whether exposure to these allergens during peak seasons could worsen PPI response in allergic EoE patients.
Key takeaways from this study include: (1) the importance of integrating allergen testing in EoE patients, especially those unresponsive to standard PPI therapy or suspected as having allergic phenotypes; (2) the need to monitor and adjust therapy based on clinical and histologic responses; and (3) the necessity of staying abreast of emerging research in this area.
EoE diagnosis presents unique challenges, particularly when patients exhibit exclusive distal esophageal eosinophilia or when discrepancies arise between endoscopic and histologic findings. Eosinophil-derived neurotoxin (EDN), a molecule previously studied for its role in monitoring allergy-mediated inflammatory diseases such as asthma and eczema, can shed light on these diagnostic difficulties.
Thomas and coworkers conducted a retrospective study in which they reviewed 231 pediatric patients, obtaining a minimum of four biopsies from at least two different levels of the esophagus. The study aimed to evaluate whether EDN concentrations, determined through esophageal epithelial brushing at the time of biopsy, could serve as an adjunctive diagnostic tool for EoE.
EDN levels proved sensitive (84.4%) and specific (94.6%) in evaluating active EoE when several measures of EoE were used in patients with active EoE compared with those with inactive EoE and the control group. Previous studies at the same institution had found EDN useful for differentiating EoE patients from non-EoE patients. Moreover, an EDN concentration > 10 μg/mL, when collected through esophageal epithelial brushing, was highly sensitive (97%) and specific (89%) for active EoE. This finding suggests the potential for using EDN as a biochemical marker, enhancing diagnostic accuracy and reducing the need for additional interventions in complex cases.
EDN as a biomarker could be invaluable for distinguishing difficult cases, such as those involving distal eosinophilia, active vs nonactive EoE, or non-EoE conditions, such as gastroesophageal reflux disease. Of note, lower EDN levels were observed in pediatric EoE patients who responded to PPI, suggesting EDN's potential utility in predicting PPI responsiveness. Incorporating the measurement of eosinophilic activity could add a new dimension to existing criteria, equipping clinicians with more precise diagnostic tools and reducing the reliance on multiple procedures. This approach would strengthen the correlation between symptomatic, endoscopic, and histologic data.
The study by Jensen and colleagues sheds light on a crucial aspect of EoE management: the psychosocial burden. A recent EoE diagnosis can be associated with increased symptom burden, somatization, and anxiety in patients and families, underscoring the need for a multidisciplinary approach to patient care that considers both physical and mental health. To date, numerous studies have focused on understanding the disease, its follow-up, and treatment. However, there has been limited exploration of the psychosocial burden and patient-associated factors in EoE.
In this context, this team aimed to enhance our understanding of the burden of EoE by evaluating psychosocial comorbidities, such as disordered sleep, anxiety, and somatization, in a pediatric population with EoE. The study included 87 patients of age 8-18 years who completed validated assessments during routine clinic visits, encompassing EoE symptoms (Pediatric Eosinophilic Esophagitis Symptom Scores, PEESSv2.0), quality of life (PedsQL-EoE), anxiety state and trait (State-Trait Anxiety Inventory for Children, STAI-C), somatization (Children's Somatic Symptoms Inventory-24, CSSI-24), and sleep-disordered breathing (University of Michigan Pediatric Sleep Questionnaire, PSQ).
The mean age of the participants was 12.8 years, highlighting the importance of addressing psychosocial distress in this age group, which undergoes crucial developmental stages. Most patients (82%, 71) had been diagnosed with EoE at least 12 months prior, and 60% (52) were treated with multiple approaches. Additionally, 34% (29) had undergone seven or more esophagogastroduodenoscopies, and nearly one third (33%, 27) had experienced a gastrointestinal-related emergency department visit. These factors potentially increase patient stress due to the continuous need for repeat procedures and hospital visits. An intriguing finding was that patients with shorter disease durations (6-12 months since diagnosis) experienced higher symptom burdens (P = .03). Patients with public insurance had less favorable scores for sleep-disordered breathing (P = .01).
Significantly, patients with neurodevelopmental comorbidities had higher scores for somatic symptoms, trait anxiety, and sleep-disordered breathing, and lower quality-of-life scores, compared with those without such comorbidities (P < .01 for all), suggesting that patients with neurodevelopmental issues might particularly benefit from tailored treatments addressing these aspects of the disease. Furthermore, patients with shorter disease durations since diagnosis exhibited higher somatic symptoms and trait anxiety (both P < .01). The study also revealed that patients with fewer esophagogastroduodenoscopies (1-3) had higher somatic symptom scores (P < .01), state anxiety (P = .02), and trait anxiety (P = .03). EoE-associated symptom burden was significantly correlated with increased somatic symptoms (0.34; 95% CI 0.23-0.45) and decreased quality of life (-0.42; 95% CI -0.59 to -0.25). Concerns about eating food and EoE-associated symptoms were both linked to the EoE-associated symptom burden.
This study has several limitations, including a relatively small sample size, which decreases the power and limits inferences for smaller groups within the sample. There was also an imbalance in gender distribution, with only 26% of patients being female, potentially limiting the generalizability of the findings. Moreover, the study included only EoE patients, lacking a control group for comparison to the general pediatric population.
Highlighting a significant aspect of pediatric EoE treatment, this study illuminates an area that might affect patients' long-term quality of life. It underscores the need for multidisciplinary care for EoE patients, where mental health professionals, such as psychologists or psychiatrists, can play a vital role in improving mental health through early identification and intervention for anxiety and somatization disorders. They can also provide education for patients and families on coping strategies. Peer support groups for children and adolescents could be another beneficial tool, allowing them to share experiences and reduce feelings of isolation.
Physicians who treat chronic diseases such as EoE should consider psychosocial factors, as they can affect both physical and mental quality of life. Using screening tools (such as PEESSv2.0, PedsQL-EoE, STAI-C, CSSI-24, or PSQ) during clinic visits can facilitate a more comprehensive evaluation.
Commentary: Risks for Eosinophilic Esophagitis: IBD, Eczema, Diet, and Acid Suppressants, January 2024
Although there exists a recognized association between IBD and secondary EoE diagnoses, studies focusing on the primary diagnosis of EoE alongside IBD have yielded conflicting results. Dr Amiko Uchida, from the University of Utah Department of Medicine, working with colleagues from the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden, led by Dr Jonas F. Ludvigsson, conducted a comprehensive study spanning 1990-2019 to explore the relationship between these two diseases.
Dr Uchida and colleagues assessed the association among Swedish patients diagnosed with biopsy-verified EoE (n = 1587) between 1990 and 2017. These patients were age- and sex-matched with up to five reference individuals from the general population (n = 7808). The primary focus was to discern the relationship between the primary diagnosis of EoE and the subsequent diagnosis of IBD.
The study's findings underscore the importance of heightened awareness among healthcare professionals regarding the potential association between EoE and the development of subsequent IBD. Collaborative efforts between physicians, gastroenterologists, and specialists in allergic diseases are crucial to ensure comprehensive care and timely identification of gastrointestinal complications in patients with EoE.
These results indicate a potential interplay between EoE and the pathogenesis of IBD, particularly Crohn's disease. In patients with EoE, careful consideration of gastrointestinal symptoms suggestive of IBD, such as abdominal pain, diarrhea, and rectal bleeding, is pivotal, necessitating further evaluation and appropriate monitoring for early detection and management of IBD.
Upon diagnosis, clinicians must develop a management plan for this chronic and critical disease. This study aids in planning future screenings for these patients, because one third of those diagnosed with EoE are at risk of developing IBD within a year. Therefore, primary physicians must remain vigilant for the development of gastrointestinal symptoms leading to a diagnosis of Crohn's disease or ulcerative colitis. Additionally, family awareness is crucial owing to observed associations between siblings, suggesting a potential role of genetics or early environmental factors in EoE development and future IBD diagnoses.
Further research is necessary to elucidate the shared pathophysiologic mechanisms connecting EoE and IBD. It is important to consider certain details, however; for instance, 31% of all subsequent IBD cases were diagnosed within the first year after an EoE diagnosis, potentially indicating a role of detection bias in these findings. Using a validated nationwide cohort and comparing study individuals with their siblings helped control for potential intrafamilial confounders as well as some environmental confounders, minimizing such biases as selection bias due to socioeconomic status. This strengthens the observed association in this study.
These insights into the increased risk for IBD, notably Crohn's disease, among patients with EoE underscore the need for thorough clinical evaluation and vigilant monitoring for gastrointestinal complications in this population.
A retrospective study conducted in pediatric patients presenting with an aerodigestive manifestation aimed to assess the factors associated with EoE and the diagnostic role of triple endoscopy. The results suggested a potential association between a family history of eczema and a diet lacking allergenic foods with a future diagnosis of EoE.
This study by Sheila Moran and colleagues, led by Dr Christina J. Yang from the Department of Otorhinolaryngology, Head and Neck Surgery at the Albert Einstein College of Medicine, Bronx, New York, aimed to identify preoperative risk factors linked to an EoE diagnosis in children undergoing triple endoscopy. They evaluated 119 pediatric patients aged 0-21 years who underwent triple endoscopy (including flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagoscopy with biopsy) at the Children's Hospital at Montefiore between January 1, 2015, and December 31, 2019.
The study underscored the significance of both genetic predisposition and dietary influences in EoE development. Understanding the interplay between familial atopic conditions and dietary choices among pediatric patients with aerodigestive dysfunction is crucial for early identification and implementing preventive strategies against EoE.
As clinicians, it's essential to consider rare diseases like EoE when patients present with mixed symptoms, including aerodigestive symptoms, a family history of eczema, and a history of environmental allergies, given the association between these conditions. The potential link between a family history of eczema and increased EoE risk suggests a shared genetic susceptibility among allergic conditions. Therefore, clinicians evaluating children with aerodigestive dysfunction, particularly those with a familial history of eczema, should maintain a high index of suspicion for EoE, prompting vigilant monitoring and appropriate diagnostic assessments.
When contemplating advanced procedures, such as triple endoscopy or biopsy sampling, considering the patient's previous medical history and the effect of dietary modifications, such as incorporating or excluding dairy from the diet, warrants further investigation in the context of EoE prevention. Clinicians should consider providing dietary counseling and personalized nutritional plans based on evidence-based approaches to potentially mitigate EoE risk in susceptible pediatric populations.
Additionally, it's crucial to consider EoE in minority racial groups and underserved communities and encourage the use of diagnostic tests, such as triple endoscopy, to facilitate early diagnosis. Healthcare providers should contemplate integrating family history assessments, particularly regarding eczema, into the evaluation of children with aerodigestive dysfunction. This information can assist in risk assessment and early identification of individuals at a higher risk of developing EoE, enabling prompt intervention and management.
The increasing incidence of EoE across different nations, including the United States, has underscored the need for a deeper understanding of its causes, early diagnosis, and treatment. A novel population-based study conducted in Denmark aimed to explore the relationship between maternal and infant use of antibiotics and acid suppressants in the development of EoE. The study yielded significant results based on a population of 392 cases. Dr Elizabeth T. Jensen, MPH, PhD, from the Department of Epidemiology & Prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, conducted a comprehensive study spanning the last 20 years to decipher potential causes contributing to the rising incidence of EoE.
Dr Jensen and her colleagues evaluated the association between maternal and infant use of antibiotics and acid suppressants in Denmark. They used pathology, prescription, birth, inpatient, and outpatient health registry data, ensuring complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. The research obtained a census of cases from a registered sample of approximately 1.4 million children, matching EoE cases to controls using a 1:10 ratio through incidence density sampling. A total of 392 patients with EoE and 3637 control patients were enrolled. The primary outcome of the study focused on the development of EoE, revealing a dose-response association between maternal and infant antibiotic and acid suppressant use and increased EoE risk.
This study demonstrated a robust correlation between the dosage of antibiotics and acid suppressants and the development of EoE in offspring during childhood. These findings hold significance because these medications represent some of the most common prescriptions in clinical practice. Pregnancy triggers significant physiologic changes in women, including increased hormonal effects and abdominal pressure on the lower esophageal sphincter, making pregnant individuals more prone to esophageal reflux and necessitating the use of gastric acid suppressants. As clinicians, it's crucial to consider lifestyle modifications and dietary adjustments before resorting to acid suppressants, reserving their use for only when absolutely necessary.
Postpregnancy, emphasizing exclusive breastfeeding for the first 6 months and proper feeding techniques can aid in reducing the likelihood of reflux disease in newborns. Acid suppressants have been linked to alterations in infant microbiome colonization, potentially increasing the susceptibility to immunoreactive diseases, such as asthma, atopic dermatitis, and allergic rhinitis. Given that exclusive breastfeeding in the initial 6 months has demonstrated preventive benefits against such diseases, primary physicians play a crucial role in advocating its importance. Although gastric acid suppressants and antibiotics are essential for managing various health conditions, including infections and gastroesophageal reflux disease (GERD), their potential impact on EoE development should not be overlooked.
Though this study had a relatively small sample size, the strong population registry of Denmark significantly reduced recall bias. However, cultural differences and over-the-counter access to drugs, such as acid suppressants, in other countries, including the United States, warrant further research to ascertain their effect on EoE development.
In light of these findings, clinicians should carefully weigh the risks and benefits of prescribing antibiotics and acid suppressants during pregnancy and infancy. Adherence to evidence-based guidelines and considering alternative treatment options, such as lifestyle modifications, should be prioritized. Prescribing antibiotics only when medically necessary and using nonpharmacologic strategies for managing GERD in infants should be considered to mitigate potential risks associated with these medications.
Although there exists a recognized association between IBD and secondary EoE diagnoses, studies focusing on the primary diagnosis of EoE alongside IBD have yielded conflicting results. Dr Amiko Uchida, from the University of Utah Department of Medicine, working with colleagues from the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden, led by Dr Jonas F. Ludvigsson, conducted a comprehensive study spanning 1990-2019 to explore the relationship between these two diseases.
Dr Uchida and colleagues assessed the association among Swedish patients diagnosed with biopsy-verified EoE (n = 1587) between 1990 and 2017. These patients were age- and sex-matched with up to five reference individuals from the general population (n = 7808). The primary focus was to discern the relationship between the primary diagnosis of EoE and the subsequent diagnosis of IBD.
The study's findings underscore the importance of heightened awareness among healthcare professionals regarding the potential association between EoE and the development of subsequent IBD. Collaborative efforts between physicians, gastroenterologists, and specialists in allergic diseases are crucial to ensure comprehensive care and timely identification of gastrointestinal complications in patients with EoE.
These results indicate a potential interplay between EoE and the pathogenesis of IBD, particularly Crohn's disease. In patients with EoE, careful consideration of gastrointestinal symptoms suggestive of IBD, such as abdominal pain, diarrhea, and rectal bleeding, is pivotal, necessitating further evaluation and appropriate monitoring for early detection and management of IBD.
Upon diagnosis, clinicians must develop a management plan for this chronic and critical disease. This study aids in planning future screenings for these patients, because one third of those diagnosed with EoE are at risk of developing IBD within a year. Therefore, primary physicians must remain vigilant for the development of gastrointestinal symptoms leading to a diagnosis of Crohn's disease or ulcerative colitis. Additionally, family awareness is crucial owing to observed associations between siblings, suggesting a potential role of genetics or early environmental factors in EoE development and future IBD diagnoses.
Further research is necessary to elucidate the shared pathophysiologic mechanisms connecting EoE and IBD. It is important to consider certain details, however; for instance, 31% of all subsequent IBD cases were diagnosed within the first year after an EoE diagnosis, potentially indicating a role of detection bias in these findings. Using a validated nationwide cohort and comparing study individuals with their siblings helped control for potential intrafamilial confounders as well as some environmental confounders, minimizing such biases as selection bias due to socioeconomic status. This strengthens the observed association in this study.
These insights into the increased risk for IBD, notably Crohn's disease, among patients with EoE underscore the need for thorough clinical evaluation and vigilant monitoring for gastrointestinal complications in this population.
A retrospective study conducted in pediatric patients presenting with an aerodigestive manifestation aimed to assess the factors associated with EoE and the diagnostic role of triple endoscopy. The results suggested a potential association between a family history of eczema and a diet lacking allergenic foods with a future diagnosis of EoE.
This study by Sheila Moran and colleagues, led by Dr Christina J. Yang from the Department of Otorhinolaryngology, Head and Neck Surgery at the Albert Einstein College of Medicine, Bronx, New York, aimed to identify preoperative risk factors linked to an EoE diagnosis in children undergoing triple endoscopy. They evaluated 119 pediatric patients aged 0-21 years who underwent triple endoscopy (including flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagoscopy with biopsy) at the Children's Hospital at Montefiore between January 1, 2015, and December 31, 2019.
The study underscored the significance of both genetic predisposition and dietary influences in EoE development. Understanding the interplay between familial atopic conditions and dietary choices among pediatric patients with aerodigestive dysfunction is crucial for early identification and implementing preventive strategies against EoE.
As clinicians, it's essential to consider rare diseases like EoE when patients present with mixed symptoms, including aerodigestive symptoms, a family history of eczema, and a history of environmental allergies, given the association between these conditions. The potential link between a family history of eczema and increased EoE risk suggests a shared genetic susceptibility among allergic conditions. Therefore, clinicians evaluating children with aerodigestive dysfunction, particularly those with a familial history of eczema, should maintain a high index of suspicion for EoE, prompting vigilant monitoring and appropriate diagnostic assessments.
When contemplating advanced procedures, such as triple endoscopy or biopsy sampling, considering the patient's previous medical history and the effect of dietary modifications, such as incorporating or excluding dairy from the diet, warrants further investigation in the context of EoE prevention. Clinicians should consider providing dietary counseling and personalized nutritional plans based on evidence-based approaches to potentially mitigate EoE risk in susceptible pediatric populations.
Additionally, it's crucial to consider EoE in minority racial groups and underserved communities and encourage the use of diagnostic tests, such as triple endoscopy, to facilitate early diagnosis. Healthcare providers should contemplate integrating family history assessments, particularly regarding eczema, into the evaluation of children with aerodigestive dysfunction. This information can assist in risk assessment and early identification of individuals at a higher risk of developing EoE, enabling prompt intervention and management.
The increasing incidence of EoE across different nations, including the United States, has underscored the need for a deeper understanding of its causes, early diagnosis, and treatment. A novel population-based study conducted in Denmark aimed to explore the relationship between maternal and infant use of antibiotics and acid suppressants in the development of EoE. The study yielded significant results based on a population of 392 cases. Dr Elizabeth T. Jensen, MPH, PhD, from the Department of Epidemiology & Prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, conducted a comprehensive study spanning the last 20 years to decipher potential causes contributing to the rising incidence of EoE.
Dr Jensen and her colleagues evaluated the association between maternal and infant use of antibiotics and acid suppressants in Denmark. They used pathology, prescription, birth, inpatient, and outpatient health registry data, ensuring complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. The research obtained a census of cases from a registered sample of approximately 1.4 million children, matching EoE cases to controls using a 1:10 ratio through incidence density sampling. A total of 392 patients with EoE and 3637 control patients were enrolled. The primary outcome of the study focused on the development of EoE, revealing a dose-response association between maternal and infant antibiotic and acid suppressant use and increased EoE risk.
This study demonstrated a robust correlation between the dosage of antibiotics and acid suppressants and the development of EoE in offspring during childhood. These findings hold significance because these medications represent some of the most common prescriptions in clinical practice. Pregnancy triggers significant physiologic changes in women, including increased hormonal effects and abdominal pressure on the lower esophageal sphincter, making pregnant individuals more prone to esophageal reflux and necessitating the use of gastric acid suppressants. As clinicians, it's crucial to consider lifestyle modifications and dietary adjustments before resorting to acid suppressants, reserving their use for only when absolutely necessary.
Postpregnancy, emphasizing exclusive breastfeeding for the first 6 months and proper feeding techniques can aid in reducing the likelihood of reflux disease in newborns. Acid suppressants have been linked to alterations in infant microbiome colonization, potentially increasing the susceptibility to immunoreactive diseases, such as asthma, atopic dermatitis, and allergic rhinitis. Given that exclusive breastfeeding in the initial 6 months has demonstrated preventive benefits against such diseases, primary physicians play a crucial role in advocating its importance. Although gastric acid suppressants and antibiotics are essential for managing various health conditions, including infections and gastroesophageal reflux disease (GERD), their potential impact on EoE development should not be overlooked.
Though this study had a relatively small sample size, the strong population registry of Denmark significantly reduced recall bias. However, cultural differences and over-the-counter access to drugs, such as acid suppressants, in other countries, including the United States, warrant further research to ascertain their effect on EoE development.
In light of these findings, clinicians should carefully weigh the risks and benefits of prescribing antibiotics and acid suppressants during pregnancy and infancy. Adherence to evidence-based guidelines and considering alternative treatment options, such as lifestyle modifications, should be prioritized. Prescribing antibiotics only when medically necessary and using nonpharmacologic strategies for managing GERD in infants should be considered to mitigate potential risks associated with these medications.
Although there exists a recognized association between IBD and secondary EoE diagnoses, studies focusing on the primary diagnosis of EoE alongside IBD have yielded conflicting results. Dr Amiko Uchida, from the University of Utah Department of Medicine, working with colleagues from the Department of Medical Epidemiology and Biostatistics at Karolinska Institutet in Stockholm, Sweden, led by Dr Jonas F. Ludvigsson, conducted a comprehensive study spanning 1990-2019 to explore the relationship between these two diseases.
Dr Uchida and colleagues assessed the association among Swedish patients diagnosed with biopsy-verified EoE (n = 1587) between 1990 and 2017. These patients were age- and sex-matched with up to five reference individuals from the general population (n = 7808). The primary focus was to discern the relationship between the primary diagnosis of EoE and the subsequent diagnosis of IBD.
The study's findings underscore the importance of heightened awareness among healthcare professionals regarding the potential association between EoE and the development of subsequent IBD. Collaborative efforts between physicians, gastroenterologists, and specialists in allergic diseases are crucial to ensure comprehensive care and timely identification of gastrointestinal complications in patients with EoE.
These results indicate a potential interplay between EoE and the pathogenesis of IBD, particularly Crohn's disease. In patients with EoE, careful consideration of gastrointestinal symptoms suggestive of IBD, such as abdominal pain, diarrhea, and rectal bleeding, is pivotal, necessitating further evaluation and appropriate monitoring for early detection and management of IBD.
Upon diagnosis, clinicians must develop a management plan for this chronic and critical disease. This study aids in planning future screenings for these patients, because one third of those diagnosed with EoE are at risk of developing IBD within a year. Therefore, primary physicians must remain vigilant for the development of gastrointestinal symptoms leading to a diagnosis of Crohn's disease or ulcerative colitis. Additionally, family awareness is crucial owing to observed associations between siblings, suggesting a potential role of genetics or early environmental factors in EoE development and future IBD diagnoses.
Further research is necessary to elucidate the shared pathophysiologic mechanisms connecting EoE and IBD. It is important to consider certain details, however; for instance, 31% of all subsequent IBD cases were diagnosed within the first year after an EoE diagnosis, potentially indicating a role of detection bias in these findings. Using a validated nationwide cohort and comparing study individuals with their siblings helped control for potential intrafamilial confounders as well as some environmental confounders, minimizing such biases as selection bias due to socioeconomic status. This strengthens the observed association in this study.
These insights into the increased risk for IBD, notably Crohn's disease, among patients with EoE underscore the need for thorough clinical evaluation and vigilant monitoring for gastrointestinal complications in this population.
A retrospective study conducted in pediatric patients presenting with an aerodigestive manifestation aimed to assess the factors associated with EoE and the diagnostic role of triple endoscopy. The results suggested a potential association between a family history of eczema and a diet lacking allergenic foods with a future diagnosis of EoE.
This study by Sheila Moran and colleagues, led by Dr Christina J. Yang from the Department of Otorhinolaryngology, Head and Neck Surgery at the Albert Einstein College of Medicine, Bronx, New York, aimed to identify preoperative risk factors linked to an EoE diagnosis in children undergoing triple endoscopy. They evaluated 119 pediatric patients aged 0-21 years who underwent triple endoscopy (including flexible bronchoscopy, rigid direct laryngoscopy and bronchoscopy, and esophagoscopy with biopsy) at the Children's Hospital at Montefiore between January 1, 2015, and December 31, 2019.
The study underscored the significance of both genetic predisposition and dietary influences in EoE development. Understanding the interplay between familial atopic conditions and dietary choices among pediatric patients with aerodigestive dysfunction is crucial for early identification and implementing preventive strategies against EoE.
As clinicians, it's essential to consider rare diseases like EoE when patients present with mixed symptoms, including aerodigestive symptoms, a family history of eczema, and a history of environmental allergies, given the association between these conditions. The potential link between a family history of eczema and increased EoE risk suggests a shared genetic susceptibility among allergic conditions. Therefore, clinicians evaluating children with aerodigestive dysfunction, particularly those with a familial history of eczema, should maintain a high index of suspicion for EoE, prompting vigilant monitoring and appropriate diagnostic assessments.
When contemplating advanced procedures, such as triple endoscopy or biopsy sampling, considering the patient's previous medical history and the effect of dietary modifications, such as incorporating or excluding dairy from the diet, warrants further investigation in the context of EoE prevention. Clinicians should consider providing dietary counseling and personalized nutritional plans based on evidence-based approaches to potentially mitigate EoE risk in susceptible pediatric populations.
Additionally, it's crucial to consider EoE in minority racial groups and underserved communities and encourage the use of diagnostic tests, such as triple endoscopy, to facilitate early diagnosis. Healthcare providers should contemplate integrating family history assessments, particularly regarding eczema, into the evaluation of children with aerodigestive dysfunction. This information can assist in risk assessment and early identification of individuals at a higher risk of developing EoE, enabling prompt intervention and management.
The increasing incidence of EoE across different nations, including the United States, has underscored the need for a deeper understanding of its causes, early diagnosis, and treatment. A novel population-based study conducted in Denmark aimed to explore the relationship between maternal and infant use of antibiotics and acid suppressants in the development of EoE. The study yielded significant results based on a population of 392 cases. Dr Elizabeth T. Jensen, MPH, PhD, from the Department of Epidemiology & Prevention at Wake Forest University School of Medicine, Winston-Salem, North Carolina, conducted a comprehensive study spanning the last 20 years to decipher potential causes contributing to the rising incidence of EoE.
Dr Jensen and her colleagues evaluated the association between maternal and infant use of antibiotics and acid suppressants in Denmark. They used pathology, prescription, birth, inpatient, and outpatient health registry data, ensuring complete ascertainment of all EoE cases among Danish residents born between 1997 and 2018. The research obtained a census of cases from a registered sample of approximately 1.4 million children, matching EoE cases to controls using a 1:10 ratio through incidence density sampling. A total of 392 patients with EoE and 3637 control patients were enrolled. The primary outcome of the study focused on the development of EoE, revealing a dose-response association between maternal and infant antibiotic and acid suppressant use and increased EoE risk.
This study demonstrated a robust correlation between the dosage of antibiotics and acid suppressants and the development of EoE in offspring during childhood. These findings hold significance because these medications represent some of the most common prescriptions in clinical practice. Pregnancy triggers significant physiologic changes in women, including increased hormonal effects and abdominal pressure on the lower esophageal sphincter, making pregnant individuals more prone to esophageal reflux and necessitating the use of gastric acid suppressants. As clinicians, it's crucial to consider lifestyle modifications and dietary adjustments before resorting to acid suppressants, reserving their use for only when absolutely necessary.
Postpregnancy, emphasizing exclusive breastfeeding for the first 6 months and proper feeding techniques can aid in reducing the likelihood of reflux disease in newborns. Acid suppressants have been linked to alterations in infant microbiome colonization, potentially increasing the susceptibility to immunoreactive diseases, such as asthma, atopic dermatitis, and allergic rhinitis. Given that exclusive breastfeeding in the initial 6 months has demonstrated preventive benefits against such diseases, primary physicians play a crucial role in advocating its importance. Although gastric acid suppressants and antibiotics are essential for managing various health conditions, including infections and gastroesophageal reflux disease (GERD), their potential impact on EoE development should not be overlooked.
Though this study had a relatively small sample size, the strong population registry of Denmark significantly reduced recall bias. However, cultural differences and over-the-counter access to drugs, such as acid suppressants, in other countries, including the United States, warrant further research to ascertain their effect on EoE development.
In light of these findings, clinicians should carefully weigh the risks and benefits of prescribing antibiotics and acid suppressants during pregnancy and infancy. Adherence to evidence-based guidelines and considering alternative treatment options, such as lifestyle modifications, should be prioritized. Prescribing antibiotics only when medically necessary and using nonpharmacologic strategies for managing GERD in infants should be considered to mitigate potential risks associated with these medications.
Coronary Artery Bypass Graft Saphenous Vein Harvest Site Hyperpigmentation
A 59-year-old man with a history of coronary artery bypass grafting (CABG), ischemic cardiomyopathy (ejection fraction, 15%-20%) with implantable cardioverter-defibrillator, recurrent paroxysmal ventricular tachycardia on amiodarone and mexiletine, and heart failure requiring left ventricular assist device (LVAD) placement presented for recurrent cellulitis and infection of the LVAD driveline exit site. He was initiated on minocycline 100 mg twice daily in combination with cefadroxil 500 mg twice daily. At his 8-week follow-up, the driveline site appeared improved with minimal erythema and no drainage. However, the patient developed a well-demarcated, linear, hyperpigmented patch along the length of the saphenous vein CABG harvest site and a few hyperpigmented macules medial to the harvest site (Figure).
Discussion
Hyperpigmentation presenting within scar tissue, as seen in this patient undergoing minocycline therapy, is a classic presentation of minocycline-induced hyperpigmentation (MIH) type I.
MIH is an uncommon, potentially cosmetically disfiguring adverse effect associated with systemic minocycline use. MIH can affect skin, teeth, nails, oral mucosa, sclera, and internal organs. The cumulative incidence of MIH in patients receiving minocycline over prolonged periods of time has been estimated from 2% to 15% in patients with acne and rosacea, to approximately 50% over 5 years in orthopedic patient populations.1-3 The risk for developing MIH increases with vitamin D deficiency, liver disease, concurrent use with other medications that can induce hyperpigmentation, and higher cumulative doses (> 70-100 g; more important for MIH types II and III).3,4
There are 3 distinct types of MIH. Type I MIH is characterized by blue-black macules and patches at sites of inflammation or prior scarring, most commonly described in facial acne scars.1,2,4 Type II is typified by blue-grey pigmentation on normal-appearing skin, most commonly on the shins, but also on sun-exposed sites.3 Biopsies of type I and II MIH demonstrate pigmented granules within macrophages or within the dermis.4,5 Both Perls iron stain and Fontana-Masson melanin stain are positive in type I and II MIH.5 Type III MIH presents as diffuse brownish hyperpigmentation on normal skin in chronically sun-exposed sites.3 Histopathology of type III MIH can be distinguished by increased melanin noted inside basal keratinocytes as well as dermal melanophages that stain positive for only Fontana-Masson.5 The current case exemplifies a unique presentation of type I MIH along the length of the saphenous vein CABG harvest site. The concomitant use of amiodarone with minocycline may have contributed to the presentation.
The differential diagnosis for MIH depends on the type of MIH. Blue-grey pigmentation within scars is fairly unique to minocycline but has been reported with other medications, including vandetanib.6 The differential diagnosis for diffuse blue-grey or brown hyperpigmentation in predominately sun-exposed sites is broader, including endocrine disorders (ie, Addison disease), heavy metal poisoning (ie, argyria), inherited conditions (ie, alkaptonuria, Wilson disease, and hemochromatosis), medication-induced hyperpigmentation (ie, antipsychotics, anticonvulsant, antimalarials, amiodarone, and cytotoxic drugs), as well as inflammatory dermatoses, such as erythema dyschromicum perstans.7
MIH typically fades over months to years following minocycline discontinuation, so prompt recognition and discontinuation is recommended. Unfortunately, some cases persist or only partially fade over time. While MIH is benign, it can be of aesthetic concern, cause anxiety, and impact patients’ quality of life.3,8 Persistent MIH is typically recalcitrant to topical hydroquinone.9 However, persistent MIH has been shown to improve with Q-switched, nanosecond lasers such as the 694 nm ruby, 755 nm alexandrite, and 1064 nm neodymium-doped yttrium aluminum garnet neodymium (Nd:YAG) lasers, as well as the 755 nm picosecond alexandrite laser.4,9,10
In our patient, minocycline therapy was discontinued and replaced with doxycycline 100 mg twice daily monotherapy. At a subsequent visit 12 weeks later, the hyperpigmentation remained unchanged.
Conclusions
Though uncommon, we hope to encourage clinician awareness of MIH through our case, as prompt diagnosis and the discontinuation of minocycline are preferred to improve patient outcomes.
1. Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol. 1996;134(4):693-695. doi:10.1111/j.1365-2133.1996.tb06972.x
2. Dwyer CM, Cuddihy AM, Kerr RE, Chapman RS, Allam BF. Skin pigmentation due to minocycline treatment of facial dermatoses. Br J Dermatol. 1993;129(2):158-162. doi:10.1111/j.1365-2133.1993.tb03519.x
3. Hanada Y, Berbari EF, Steckelberg JM. Minocycline-induced cutaneous hyperpigmentation in an orthopedic patient population. Open Forum Infect Dis. 2016;3(1):ofv107. doi:10.1093/ofid/ofv107
4. Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf. 1998;18(6):431-440. doi:10.2165/00002018-199818060-00004
5. Bowen AR, McCalmont TH. The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836-839. doi:10.1016/j.jaad.2007.04.028
6. Perlmutter JW, Cogan RC, Wiseman MC. Blue-grey hyperpigmentation in acne after vandetanib therapy and doxycycline use: a case report. SAGE Open Med Case Rep. 2022;10:2050313X221086316. doi:10.1177/2050313X221086316
7. Judson T, Mihara K. Minocycline-induced hyperpigmentation. J Gen Intern Med. 2017;32(1):133. doi:10.1007/s11606-016-3735-x
8. Li Y, Zhen X, Yao X, Lu J. Successful treatment of minocycline-induced facial hyperpigmentation with a combination of chemical peels and intense pulsed light. Clin Cosmet Investig Dermatol. 2023;16:253-256. doi:10.2147/CCID.S394754
9. Sasaki K, Ohshiro T, Ohshiro T, et al. Type 2 Minocycline-induced hyperpigmentation successfully treated with the novel 755 nm picosecond alexandrite laser – a case report. Laser Ther. 2017;26(2):137-144. doi:10.5978/islsm.17-CR-03
10. Nisar MS, Iyer K, Brodell RT, Lloyd JR, Shin TM, Ahmad A. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects. Clin Cosmet Investig Dermatol. 2013;6:159-162. doi:10.2147/CCID.S42166
A 59-year-old man with a history of coronary artery bypass grafting (CABG), ischemic cardiomyopathy (ejection fraction, 15%-20%) with implantable cardioverter-defibrillator, recurrent paroxysmal ventricular tachycardia on amiodarone and mexiletine, and heart failure requiring left ventricular assist device (LVAD) placement presented for recurrent cellulitis and infection of the LVAD driveline exit site. He was initiated on minocycline 100 mg twice daily in combination with cefadroxil 500 mg twice daily. At his 8-week follow-up, the driveline site appeared improved with minimal erythema and no drainage. However, the patient developed a well-demarcated, linear, hyperpigmented patch along the length of the saphenous vein CABG harvest site and a few hyperpigmented macules medial to the harvest site (Figure).
Discussion
Hyperpigmentation presenting within scar tissue, as seen in this patient undergoing minocycline therapy, is a classic presentation of minocycline-induced hyperpigmentation (MIH) type I.
MIH is an uncommon, potentially cosmetically disfiguring adverse effect associated with systemic minocycline use. MIH can affect skin, teeth, nails, oral mucosa, sclera, and internal organs. The cumulative incidence of MIH in patients receiving minocycline over prolonged periods of time has been estimated from 2% to 15% in patients with acne and rosacea, to approximately 50% over 5 years in orthopedic patient populations.1-3 The risk for developing MIH increases with vitamin D deficiency, liver disease, concurrent use with other medications that can induce hyperpigmentation, and higher cumulative doses (> 70-100 g; more important for MIH types II and III).3,4
There are 3 distinct types of MIH. Type I MIH is characterized by blue-black macules and patches at sites of inflammation or prior scarring, most commonly described in facial acne scars.1,2,4 Type II is typified by blue-grey pigmentation on normal-appearing skin, most commonly on the shins, but also on sun-exposed sites.3 Biopsies of type I and II MIH demonstrate pigmented granules within macrophages or within the dermis.4,5 Both Perls iron stain and Fontana-Masson melanin stain are positive in type I and II MIH.5 Type III MIH presents as diffuse brownish hyperpigmentation on normal skin in chronically sun-exposed sites.3 Histopathology of type III MIH can be distinguished by increased melanin noted inside basal keratinocytes as well as dermal melanophages that stain positive for only Fontana-Masson.5 The current case exemplifies a unique presentation of type I MIH along the length of the saphenous vein CABG harvest site. The concomitant use of amiodarone with minocycline may have contributed to the presentation.
The differential diagnosis for MIH depends on the type of MIH. Blue-grey pigmentation within scars is fairly unique to minocycline but has been reported with other medications, including vandetanib.6 The differential diagnosis for diffuse blue-grey or brown hyperpigmentation in predominately sun-exposed sites is broader, including endocrine disorders (ie, Addison disease), heavy metal poisoning (ie, argyria), inherited conditions (ie, alkaptonuria, Wilson disease, and hemochromatosis), medication-induced hyperpigmentation (ie, antipsychotics, anticonvulsant, antimalarials, amiodarone, and cytotoxic drugs), as well as inflammatory dermatoses, such as erythema dyschromicum perstans.7
MIH typically fades over months to years following minocycline discontinuation, so prompt recognition and discontinuation is recommended. Unfortunately, some cases persist or only partially fade over time. While MIH is benign, it can be of aesthetic concern, cause anxiety, and impact patients’ quality of life.3,8 Persistent MIH is typically recalcitrant to topical hydroquinone.9 However, persistent MIH has been shown to improve with Q-switched, nanosecond lasers such as the 694 nm ruby, 755 nm alexandrite, and 1064 nm neodymium-doped yttrium aluminum garnet neodymium (Nd:YAG) lasers, as well as the 755 nm picosecond alexandrite laser.4,9,10
In our patient, minocycline therapy was discontinued and replaced with doxycycline 100 mg twice daily monotherapy. At a subsequent visit 12 weeks later, the hyperpigmentation remained unchanged.
Conclusions
Though uncommon, we hope to encourage clinician awareness of MIH through our case, as prompt diagnosis and the discontinuation of minocycline are preferred to improve patient outcomes.
A 59-year-old man with a history of coronary artery bypass grafting (CABG), ischemic cardiomyopathy (ejection fraction, 15%-20%) with implantable cardioverter-defibrillator, recurrent paroxysmal ventricular tachycardia on amiodarone and mexiletine, and heart failure requiring left ventricular assist device (LVAD) placement presented for recurrent cellulitis and infection of the LVAD driveline exit site. He was initiated on minocycline 100 mg twice daily in combination with cefadroxil 500 mg twice daily. At his 8-week follow-up, the driveline site appeared improved with minimal erythema and no drainage. However, the patient developed a well-demarcated, linear, hyperpigmented patch along the length of the saphenous vein CABG harvest site and a few hyperpigmented macules medial to the harvest site (Figure).
Discussion
Hyperpigmentation presenting within scar tissue, as seen in this patient undergoing minocycline therapy, is a classic presentation of minocycline-induced hyperpigmentation (MIH) type I.
MIH is an uncommon, potentially cosmetically disfiguring adverse effect associated with systemic minocycline use. MIH can affect skin, teeth, nails, oral mucosa, sclera, and internal organs. The cumulative incidence of MIH in patients receiving minocycline over prolonged periods of time has been estimated from 2% to 15% in patients with acne and rosacea, to approximately 50% over 5 years in orthopedic patient populations.1-3 The risk for developing MIH increases with vitamin D deficiency, liver disease, concurrent use with other medications that can induce hyperpigmentation, and higher cumulative doses (> 70-100 g; more important for MIH types II and III).3,4
There are 3 distinct types of MIH. Type I MIH is characterized by blue-black macules and patches at sites of inflammation or prior scarring, most commonly described in facial acne scars.1,2,4 Type II is typified by blue-grey pigmentation on normal-appearing skin, most commonly on the shins, but also on sun-exposed sites.3 Biopsies of type I and II MIH demonstrate pigmented granules within macrophages or within the dermis.4,5 Both Perls iron stain and Fontana-Masson melanin stain are positive in type I and II MIH.5 Type III MIH presents as diffuse brownish hyperpigmentation on normal skin in chronically sun-exposed sites.3 Histopathology of type III MIH can be distinguished by increased melanin noted inside basal keratinocytes as well as dermal melanophages that stain positive for only Fontana-Masson.5 The current case exemplifies a unique presentation of type I MIH along the length of the saphenous vein CABG harvest site. The concomitant use of amiodarone with minocycline may have contributed to the presentation.
The differential diagnosis for MIH depends on the type of MIH. Blue-grey pigmentation within scars is fairly unique to minocycline but has been reported with other medications, including vandetanib.6 The differential diagnosis for diffuse blue-grey or brown hyperpigmentation in predominately sun-exposed sites is broader, including endocrine disorders (ie, Addison disease), heavy metal poisoning (ie, argyria), inherited conditions (ie, alkaptonuria, Wilson disease, and hemochromatosis), medication-induced hyperpigmentation (ie, antipsychotics, anticonvulsant, antimalarials, amiodarone, and cytotoxic drugs), as well as inflammatory dermatoses, such as erythema dyschromicum perstans.7
MIH typically fades over months to years following minocycline discontinuation, so prompt recognition and discontinuation is recommended. Unfortunately, some cases persist or only partially fade over time. While MIH is benign, it can be of aesthetic concern, cause anxiety, and impact patients’ quality of life.3,8 Persistent MIH is typically recalcitrant to topical hydroquinone.9 However, persistent MIH has been shown to improve with Q-switched, nanosecond lasers such as the 694 nm ruby, 755 nm alexandrite, and 1064 nm neodymium-doped yttrium aluminum garnet neodymium (Nd:YAG) lasers, as well as the 755 nm picosecond alexandrite laser.4,9,10
In our patient, minocycline therapy was discontinued and replaced with doxycycline 100 mg twice daily monotherapy. At a subsequent visit 12 weeks later, the hyperpigmentation remained unchanged.
Conclusions
Though uncommon, we hope to encourage clinician awareness of MIH through our case, as prompt diagnosis and the discontinuation of minocycline are preferred to improve patient outcomes.
1. Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol. 1996;134(4):693-695. doi:10.1111/j.1365-2133.1996.tb06972.x
2. Dwyer CM, Cuddihy AM, Kerr RE, Chapman RS, Allam BF. Skin pigmentation due to minocycline treatment of facial dermatoses. Br J Dermatol. 1993;129(2):158-162. doi:10.1111/j.1365-2133.1993.tb03519.x
3. Hanada Y, Berbari EF, Steckelberg JM. Minocycline-induced cutaneous hyperpigmentation in an orthopedic patient population. Open Forum Infect Dis. 2016;3(1):ofv107. doi:10.1093/ofid/ofv107
4. Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf. 1998;18(6):431-440. doi:10.2165/00002018-199818060-00004
5. Bowen AR, McCalmont TH. The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836-839. doi:10.1016/j.jaad.2007.04.028
6. Perlmutter JW, Cogan RC, Wiseman MC. Blue-grey hyperpigmentation in acne after vandetanib therapy and doxycycline use: a case report. SAGE Open Med Case Rep. 2022;10:2050313X221086316. doi:10.1177/2050313X221086316
7. Judson T, Mihara K. Minocycline-induced hyperpigmentation. J Gen Intern Med. 2017;32(1):133. doi:10.1007/s11606-016-3735-x
8. Li Y, Zhen X, Yao X, Lu J. Successful treatment of minocycline-induced facial hyperpigmentation with a combination of chemical peels and intense pulsed light. Clin Cosmet Investig Dermatol. 2023;16:253-256. doi:10.2147/CCID.S394754
9. Sasaki K, Ohshiro T, Ohshiro T, et al. Type 2 Minocycline-induced hyperpigmentation successfully treated with the novel 755 nm picosecond alexandrite laser – a case report. Laser Ther. 2017;26(2):137-144. doi:10.5978/islsm.17-CR-03
10. Nisar MS, Iyer K, Brodell RT, Lloyd JR, Shin TM, Ahmad A. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects. Clin Cosmet Investig Dermatol. 2013;6:159-162. doi:10.2147/CCID.S42166
1. Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. Br J Dermatol. 1996;134(4):693-695. doi:10.1111/j.1365-2133.1996.tb06972.x
2. Dwyer CM, Cuddihy AM, Kerr RE, Chapman RS, Allam BF. Skin pigmentation due to minocycline treatment of facial dermatoses. Br J Dermatol. 1993;129(2):158-162. doi:10.1111/j.1365-2133.1993.tb03519.x
3. Hanada Y, Berbari EF, Steckelberg JM. Minocycline-induced cutaneous hyperpigmentation in an orthopedic patient population. Open Forum Infect Dis. 2016;3(1):ofv107. doi:10.1093/ofid/ofv107
4. Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. Drug Saf. 1998;18(6):431-440. doi:10.2165/00002018-199818060-00004
5. Bowen AR, McCalmont TH. The histopathology of subcutaneous minocycline pigmentation. J Am Acad Dermatol. 2007;57(5):836-839. doi:10.1016/j.jaad.2007.04.028
6. Perlmutter JW, Cogan RC, Wiseman MC. Blue-grey hyperpigmentation in acne after vandetanib therapy and doxycycline use: a case report. SAGE Open Med Case Rep. 2022;10:2050313X221086316. doi:10.1177/2050313X221086316
7. Judson T, Mihara K. Minocycline-induced hyperpigmentation. J Gen Intern Med. 2017;32(1):133. doi:10.1007/s11606-016-3735-x
8. Li Y, Zhen X, Yao X, Lu J. Successful treatment of minocycline-induced facial hyperpigmentation with a combination of chemical peels and intense pulsed light. Clin Cosmet Investig Dermatol. 2023;16:253-256. doi:10.2147/CCID.S394754
9. Sasaki K, Ohshiro T, Ohshiro T, et al. Type 2 Minocycline-induced hyperpigmentation successfully treated with the novel 755 nm picosecond alexandrite laser – a case report. Laser Ther. 2017;26(2):137-144. doi:10.5978/islsm.17-CR-03
10. Nisar MS, Iyer K, Brodell RT, Lloyd JR, Shin TM, Ahmad A. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects. Clin Cosmet Investig Dermatol. 2013;6:159-162. doi:10.2147/CCID.S42166
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<root generator="drupal.xsl" gversion="1.7"> <header> <fileName>1223 FED CVD WYD CABG</fileName> <TBEID>0C02EB68.SIG</TBEID> <TBUniqueIdentifier>NJ_0C02EB68</TBUniqueIdentifier> <newsOrJournal>Journal</newsOrJournal> <publisherName>Frontline Medical Communications Inc.</publisherName> <storyname/> <articleType>1</articleType> <TBLocation>Copyfitting-FED</TBLocation> <QCDate/> <firstPublished>20231202T144414</firstPublished> <LastPublished>20231202T144414</LastPublished> <pubStatus qcode="stat:"/> <embargoDate/> <killDate/> <CMSDate>20231202T144414</CMSDate> <articleSource/> <facebookInfo/> <meetingNumber/> <byline/> <bylineText>Katelyn J. Rypkaa,b*; Sophie M. Cronka,c*; Travis Fulk, MDa,b; Anne-Marie Leuck, MDb,^; Noah Goldfarb, MDa,b,^ </bylineText> <bylineFull/> <bylineTitleText/> <USOrGlobal/> <wireDocType/> <newsDocType/> <journalDocType/> <linkLabel/> <pageRange/> <citation/> <quizID/> <indexIssueDate/> <itemClass qcode="ninat:text"/> <provider qcode="provider:"> <name/> <rightsInfo> <copyrightHolder> <name/> </copyrightHolder> <copyrightNotice/> </rightsInfo> </provider> <abstract/> <metaDescription>A 59-year-old man with a history of coronary artery bypass grafting (CABG), ischemic cardiomyopathy (ejection fraction, 15%-20%) with implantable cardioverter-d</metaDescription> <articlePDF/> <teaserImage/> <title>Coronary Artery Bypass Graft Saphenous Vein Harvest Site Hyperpigmentation</title> <deck/> <eyebrow>What’s Your Diagnosis?</eyebrow> <disclaimer/> <AuthorList/> <articleURL/> <doi/> <pubMedID/> <publishXMLStatus/> <publishXMLVersion>1</publishXMLVersion> <useEISSN>0</useEISSN> <urgency/> <pubPubdateYear>2023</pubPubdateYear> <pubPubdateMonth>December</pubPubdateMonth> <pubPubdateDay/> <pubVolume>40</pubVolume> <pubNumber>6</pubNumber> <wireChannels/> <primaryCMSID/> <CMSIDs> <CMSID>3639</CMSID> </CMSIDs> <keywords/> <seeAlsos/> <publications_g> <publicationData> <publicationCode>FED</publicationCode> <pubIssueName>December 2023</pubIssueName> <pubArticleType>Feature Articles | 3639</pubArticleType> <pubTopics/> <pubCategories/> <pubSections/> <journalTitle>Fed Pract</journalTitle> <journalFullTitle>Federal Practitioner</journalFullTitle> <copyrightStatement>Copyright 2017 Frontline Medical Communications Inc., Parsippany, NJ, USA. All rights reserved.</copyrightStatement> </publicationData> </publications_g> <publications> <term canonical="true">16</term> </publications> <sections> <term canonical="true">58390</term> </sections> <topics> <term canonical="true">194</term> </topics> <links/> </header> <itemSet> <newsItem> <itemMeta> <itemRole>Main</itemRole> <itemClass>text</itemClass> <title>Coronary Artery Bypass Graft Saphenous Vein Harvest Site Hyperpigmentation</title> <deck/> </itemMeta> <itemContent> <p>A 59-year-old man with a history of coronary artery bypass grafting (CABG), ischemic cardiomyopathy (ejection fraction, 15%-20%) with implantable cardioverter-defibrillator, recurrent paroxysmal ventricular tachycardia on amiodarone and mexiletine, and heart failure requiring left ventricular assist device (LVAD) placement presented for recurrent cellulitis and infection of the LVAD driveline exit site. He was initiated on minocycline 100 mg twice daily in combination with cefadroxil 500 mg twice daily. At his 8-week follow-up, the driveline site appeared improved with minimal erythema and no drainage. However, the patient developed a well-demarcated, linear, hyperpigmented patch along the length of the saphenous vein CABG harvest site and a few hyperpigmented macules medial to the harvest site (Figure). </p> <h2>Discussion</h2> <p>Hyperpigmentation presenting within scar tissue, as seen in this patient undergoing minocycline therapy, is a classic presentation of minocycline-induced hyperpigmentation (MIH) type I. </p> <p>MIH is an uncommon, potentially cosmetically disfiguring adverse effect associated with systemic minocycline use. MIH can affect skin, teeth, nails, oral mucosa, sclera, and internal organs. The cumulative incidence of MIH in patients receiving minocycline over prolonged periods of time has been estimated from 2% to 15% in patients with acne and rosacea, to approximately 50% over 5 years in orthopedic patient populations.<sup>1-3</sup> The risk for developing MIH increases with vitamin D deficiency, liver disease, concurrent use with other medications that can induce hyperpigmentation, and higher cumulative doses (> 70-100 g; more important for MIH types II and III).<sup>3,4</sup><b> <br/><br/></b>There are 3 distinct types of MIH. Type I MIH is characterized by blue-black macules and patches at sites of inflammation or prior scarring, most commonly described in facial acne scars.<sup>1,2,4</sup><b> </b>Type II is typified by blue-grey pigmentation on normal-appearing skin, most commonly on the shins, but also on sun-exposed sites.<sup>3</sup> Biopsies of type I and II MIH demonstrate pigmented granules within macrophages or within the dermis.<sup>4,5</sup> Both Perls iron stain and Fontana-Masson melanin stain are positive in type I and II MIH.<sup>5</sup> Type III MIH presents as diffuse brownish hyperpigmentation on normal skin in chronically sun-exposed sites.<sup>3</sup> Histopathology of type III MIH can be distinguished by increased melanin noted inside basal keratinocytes as well as dermal melanophages that stain positive for only Fontana-Masson.<sup>5</sup> The current case exemplifies a unique presentation of type I MIH along the length of the saphenous vein CABG harvest site. The concomitant use of amiodarone with minocycline may have contributed to the presentation.<br/><br/>The differential diagnosis for MIH depends on the type of MIH. Blue-grey pigmentation within scars is fairly unique to minocycline but has been reported with other medications, including vandetanib.<sup>6</sup> The differential diagnosis for diffuse blue-grey or brown hyperpigmentation in predominately sun-exposed sites is broader, including endocrine disorders (ie, Addison disease), heavy metal poisoning (ie, argyria), inherited conditions (ie, alkaptonuria, Wilson disease, and hemochromatosis), medication-induced hyperpigmentation (ie, antipsychotics, anticonvulsant, antimalarials, amiodarone, and cytotoxic drugs), as well as inflammatory dermatoses, such as erythema dyschromicum perstans.<sup>7<br/><br/></sup>MIH typically fades over months to years following minocycline discontinuation, so prompt recognition and discontinuation is recommended. Unfortunately, some cases persist or only partially fade over time. While MIH is benign, it can be of aesthetic concern, cause anxiety, and impact patients’ quality of life.<sup>3,8</sup> Persistent MIH is typically recalcitrant to topical hydroquinone.<sup>9</sup> However, persistent MIH has been shown to improve with Q-switched, nanosecond lasers such as the 694 nm ruby, 755 nm alexandrite, and 1064 nm neodymium-doped yttrium aluminum garnet neodymium (Nd:YAG) lasers, as well as the 755 nm picosecond alexandrite laser.<sup>4,9,10<br/><br/></sup>In our patient, minocycline therapy was discontinued and replaced with doxycycline 100 mg twice daily monotherapy. At a subsequent visit 12 weeks later, the hyperpigmentation remained unchanged. </p> <h2>Conclusions</h2> <p>Though uncommon, we hope to encourage clinician awareness of MIH through our case, as prompt diagnosis and the discontinuation of minocycline are preferred to improve patient outcomes.</p> <p class="isub">Author affiliations</p> <p> <em><sup>a</sup>Minneapolis Veterans Affairs Medical Center, Minnesota<br/><br/><sup>b</sup>University of Minnesota, Minneapolis<br/><br/><sup>c</sup>Texas Christian University, Fort Worth</em> </p> <p class="isub">Author disclosures</p> <p> <em>Dr. Goldfarb has participated in clinical trials with Abbvie, Pfizer, Chemocentrix, and DeepX Health, and has served on advisory boards and consulted for Novartis and Boehringer Ingelheim. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of any other companies or organizations. All other authors report no actual or potential conflicts of interest or outside sources of funding with regard to this article.</em> </p> <p class="isub">Disclaimer</p> <p> <em>The opinions expressed herein are those of the authors and do not necessarily reflect those of <i>Federal Practitioner</i>, Frontline Medical Communications Inc., the US Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.</em> </p> <p class="isub">Ethics and consent</p> <p> <em>The patient gave verbal and written consent for their photographs and medical information to be published in print and online with the understanding that this information may be publicly available.</em> </p> <h2>References</h2> <p class="reference"> 1. Goulden V, Glass D, Cunliffe WJ. Safety of long-term high-dose minocycline in the treatment of acne. <i>Br J Dermatol.</i> 1996;134(4):693-695. doi:10.1111/j.1365-2133.1996.tb06972.x<br/><br/> 2. Dwyer CM, Cuddihy AM, Kerr RE, Chapman RS, Allam BF. Skin pigmentation due to minocycline treatment of facial dermatoses. <i>Br J Dermatol</i>. 1993;129(2):158-162. doi:10.1111/j.1365-2133.1993.tb03519.x<br/><br/> 3. Hanada Y, Berbari EF, Steckelberg JM. Minocycline-induced cutaneous hyperpigmentation in an orthopedic patient population. <i>Open Forum Infect Dis</i>. 2016;3(1):ofv107. doi:10.1093/ofid/ofv107<br/><br/> 4. Eisen D, Hakim MD. Minocycline-induced pigmentation. Incidence, prevention and management. <i>Drug Saf.</i> 1998;18(6):431-440. doi:10.2165/00002018-199818060-00004<br/><br/> 5. Bowen AR, McCalmont TH. The histopathology of subcutaneous minocycline pigmentation. <i>J Am Acad Dermatol. </i>2007;57(5):836-839. doi:10.1016/j.jaad.2007.04.028<br/><br/> 6. Perlmutter JW, Cogan RC, Wiseman MC. Blue-grey hyperpigmentation in acne after vandetanib therapy and doxycycline use: a case report. <i>SAGE Open Med Case Rep</i>. 2022;10:2050313X221086316. doi:10.1177/2050313X221086316<br/><br/> 7. Judson T, Mihara K. Minocycline-induced hyperpigmentation. <i>J Gen Intern Med</i>. 2017;32(1):133. doi:10.1007/s11606-016-3735-x<br/><br/> 8. Li Y, Zhen X, Yao X, Lu J. Successful treatment of minocycline-induced facial hyperpigmentation with a combination of chemical peels and intense pulsed light. <i>Clin Cosmet Investig Dermatol</i>. 2023;16:253-256. doi:10.2147/CCID.S394754<br/><br/> 9. Sasaki K, Ohshiro T, Ohshiro T, et al. Type 2 Minocycline-induced hyperpigmentation successfully treated with the novel 755 nm picosecond alexandrite laser – a case report. <i>Laser Ther</i>. 2017;26(2):137-144. doi:10.5978/islsm.17-CR-03<br/><br/>10. Nisar MS, Iyer K, Brodell RT, Lloyd JR, Shin TM, Ahmad A. Minocycline-induced hyperpigmentation: comparison of 3 Q-switched lasers to reverse its effects. <i>Clin Cosmet Investig Dermatol</i>. 2013;6:159-162. doi:10.2147/CCID.S42166</p> </itemContent> </newsItem> </itemSet></root>