EXPERT COMMENTARY

Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.¹ Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.

Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.^2-6

_

Details of the study

This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.

Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).

The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.

Study strengths and weaknesses

This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.

However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.

In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,^4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.¹ Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.

Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.^2-6

_

Details of the study

This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.

Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).

The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.

Study strengths and weaknesses

This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.

However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.

In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,^4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

EXPERT COMMENTARY

Epidemiologic studies conducted in ovarian cancer suggest an association between chronic inflammation and incidence of disease.¹ Nonsteroidal anti-inflammatory drugs (NSAIDs) work to decrease inflammation through the inhibition of cyclo-oxygenase (COX). Therefore, anti-inflammatory agents such as NSAIDs have been proposed to play a role in the pathophysiology of ovarian cancer.

Previous studies of this association show conflicting data. The majority of these studies are retrospective, and those that are prospective do not include detailed data regarding dosing and frequency of ASA use.^2-6

_

Details of the study

This study by Barnard and colleagues is a prospective cohort study evaluating a total of 205,498 women from 1980–2015 from 2 separate cohorts (the Nurses’ Health Study and the Nurses’ Health Study II). The primary outcome was “to evaluate whether regular aspirin or nonaspirin NSAID use and patterns of use are associated with lower ovarian cancer risk.” Analgesic use and data regarding covariates were obtained via self-reported questionnaires. Ovarian cancer diagnosis was confirmed via medical records.

Results demonstrated that current low-dose aspirin use was associated with a decreased risk of ovarian cancer (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61–0.96). This significance was not maintained upon further controlling for inflammatory factors (hypertension, autoimmune disease, inflammatory diet scores, smoking, etc) (HR, 0.94; 95% CI, 0.69–1.26). Other significant findings included an increased risk of developing ovarian cancer with standard-dose ASA use of ≥5 years or standard-dose use at 6 to 9 tablets per week (HR, 1.77; 95% CI, 1.13–2.77 and HR, 2.00; 95% CI, 1.27–3.15, respectively). An increased risk of developing ovarian cancer also was found for >10-year use or use of >10 tablets per week of nonaspirin NSAIDs (HR, 2.00; 95% CI, 1.27–3.15 and HR, 1.35; 95% CI, 1.02–1.79, respectively).

The authors concluded that there was a slight inverse association for low-dose aspirin and ovarian cancer risk and that standard aspirin or NSAID use actually may be associated with an increased risk of ovarian cancer.

Study strengths and weaknesses

This study has many strengths. It was a large prospective cohort investigation with adequate power to detect clinically significant differences. The authors collected detailed exposure data, which was novel. They also considered a latency period prior to the diagnosis of ovarian cancer during which a patient may increase their analgesic use in order to treat pain caused by the impending cancer.

However, the conclusions of the authors seem to be overstated in the setting of the data. Specifically, the deduction regarding a decreased risk of ovarian cancer with low-dose aspirin use given the loss of the statistical significance when controlling for pertinent cofounders. Further, the study authors did not evaluate adverse effects associated with low-dose aspirin use, which would be clinically applicable when determining whether the results from this study should become formal recommendations. Lastly, other important clinical factors, such as the presence of genetic mutations or endometriosis, were not considered, and these considerations would greatly affect results.

In the setting of previous large prospective studies that suggest no association between ASA use and ovarian cancer risk,^4-6 data from this study are not compelling enough to recommend regular low-dose aspirin use to all women.

Share your thoughts! Send your Letter to the Editor to rbarbieri@mdedge.com. Please include your name and the city and state in which you practice.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

SAN ANTONIO – A phase 3 randomized controlled trial jointly conducted by GEICAM and CIBOMA is negative, showing that adding adjuvant capecitabine (Xeloda) to surgery and standard chemotherapy does not improve disease-free or overall survival in women with early-stage triple-negative breast cancer, reported lead investigator Miguel Martín, MD, PhD.

At the San Antonio Breast Cancer Symposium, he discussed the overall findings and intriguing subgroup results suggesting that there was a benefit in women with tumors having the nonbasal phenotype. Dr. Martín also detailed implications in the context of the CREATE-X trial findings and the era of personalized medicine, and outlined next avenues of research.

The trial was supported by Roche, which also provided capecitabine. Dr. Martín disclosed that he has received speakers honoraria from Pfizer and Lilly; honoraria for participation in advisory boards from AstraZeneca, Novartis, Roche-Genentech, Pfizer, GlaxoSmithKline, PharmaMar, Taiho Oncology, and Lilly; and research grants from Novartis and Roche.

ASHEVILLE, NC—Although neurologists tend to classify disorders as problems of either the CNS or the peripheral nervous system, patients with headache may have symptoms that indicate the involvement of both systems, according to an overview provided at the Eighth Annual Scientific Meeting of the Southern Headache Society. Research has revealed anatomic connections between extracranial and intracranial spaces that could contribute to the generation of headaches. Thus, the central and peripheral nervous systems “do not have to be two separate spaces and two separate pathologies,” said Pamela Blake, MD, Director of the Headache Center of Greater Heights in Houston.

Problems With Prevention and Acute Treatment

One patient presented to Dr. Blake with an eight-year history of throbbing headaches and constant pain and tightness in the neck and occiput. The pain radiated to her temples and forehead two to four times per week with accompanying photophobia, phonophobia, and nausea. The patient also had mild allodynia. The frontal pain and accompanying symptoms were consistent with episodic migraine, but the allodynia and pain in the neck and occiput were not, said Dr. Blake. A possible diagnosis was episodic migraine without aura with chronic tension-type headaches and neck pain, she added.

A 2017 study published in the Journal of Headache and Pain suggested that this headache type is problematic. Among 148 migraineurs, the researchers identified 100 patients who also had tension-type headache and chronic neck pain. Compared with healthy controls, these patients had less physical activity, less psychologic well-being, more perceived stress, and poorer self-rated health. Pain reduced these patients’ ability to perform physical activity, which could make treatment more difficult, according to the authors.

Patients with these symptoms have trigeminal and occipital pain. “These symptoms do not appear to be solely, or even primarily, central,” said Dr. Blake. The frontal pain responds to triptans, but the occipital pain, which is the more constant pain, does not. “Preventive medications do not work well in this population, and that’s why they have chronic headaches,” said Dr. Blake.

Physiologic and Pathophysiologic Mechanisms

Research by Schueler and colleagues suggested a potential physiologic explanation for combined central and peripheral involvement in headache. They applied a fluorescent tracer to proximally cut meningeal nerves in rat skulls and to distal branches of the spinosus nerve in human calvaria that was lined with dura mater. They observed that branches of the spinosus nerve travel “along the middle meningeal artery, supplying the dura, entering the cranial bone, and running through the calvarium,” said Dr. Blake. Branches of the spinosus nerve also “entered the tenderness junctions of the pericranial muscles, including in the neck.”

This work indicates a connection between intracranial and extracranial areas but does not shed light on the pathophysiology of a headache with central and peripheral symptoms, said Dr. Blake. In 2016, she and her colleagues took perivascular biopsies from healthy controls and subjects with chronic migraine and predominantly occipital headache. They found a significant increase in the expression of proinflammatory genes and a decrease in the expression of anti-inflammatory genes among migraineurs, compared with controls. “This was the first evidence of localized extracranial pathophysiology in chronic migraine,” said Dr. Blake.

This inflammation could result from compression of the occipital nerves. A 2013 study by Schmid et al found that progressive nerve compression results in chronic local and remote immune-mediated inflammation. Stress also can cause inflammation. “Many patients who present with occipital nerve compression headaches had the onset of their pain during a time of intense stress,” said Dr. Blake.

The Role of the Occipital Nerve

Occipital nerve compression headache is characterized by daily or near-daily pain in the distribution of the occipital nerve. Patients describe the pain as a tight, imploding pressure that sometimes radiates to frontal areas and becomes a throbbing pain. This headache rarely has a neuropathic component.

Allodynia is “almost a requirement of this diagnosis,” said Dr. Blake. The allodynia symptom checklist, however, does not capture it well in these patients because it focuses on pain in the trigeminal nerve distribution. Patients report that the back of the head is tender to the touch and that it hurts to rest the head on a pillow.

The cervical muscles compress the nerve and contribute to the symptoms as well. Patients often report that moving the head or neck exacerbates the pain. The headache also may have migrainous features. It takes skill and expertise to elicit an adequate history from these patients, said Dr. Blake. “Careful questioning is helpful. I often find … that a second visit is more helpful to obtain this history after reviewing the anatomy with the patient, reviewing this pathophysiology, and sending them back out to keep a careful log for two weeks.”

Nerve Blocks and Nerve Decompression

Occipital nerve blocks provide relief for these patients, but they may not be easy to administer. A large dorsal occipital nerve may be mistaken for the greater occipital nerve, for example. Physiologic abnormalities in some patients also can complicate this treatment.

Another effective treatment is nerve decompression surgery. Dr. Blake and colleagues conducted a retrospective review of patients who had undergone decompression of the greater occipital nerves at the point where they traverse the musculature of the posterior neck. The intervention provided complete relief for three to six years in one patient with new daily persistent headache and two patients with chronic posttraumatic headache. Two patients with chronic headache or migraine had partial relief. Surgery provided no relief for two patients with episodic migraine, one patient with chronic migraine, and one patient with chronic tension-type headache.

“In our experience, … 75% to 80% of patients experience a greater than 50% reduction in their headaches, measured by headache frequency and intensity,” said Dr. Blake. She and her colleagues compared outcomes between 18 chronic migraineurs with predominantly occipital pain who underwent surgical decompression of the occipital nerve and 23 patients who were referred for surgery but unable to receive it. In the surgical group, the number of predominantly occipital chronic migraine days per month decreased from 28.9 at baseline to 7.28 at a mean of 46 months later. The outcome in the control group did not change.

Correct patient selection “is the first, most important step” toward treatment success, said Dr. Blake. This process includes a preoperative psychologic evaluation that screens surgical candidates for somatic symptom disorder, mood disorders, a history of trauma, and catastrophizing. If indicated, neurologists may begin providing cognitive behavioral therapy or supportive psychotherapy before surgery. “We have a comprehensive program with postoperative management, including physical therapy and gradual taper of medications,” said Dr. Blake. Central migraine processes may contribute to headache in some of these patients. “Menstrual migraines are not going to go away with nerve decompression. Chronic migraine sometimes does not go away. This is a complex group of patients who definitely require a lot of follow-up.”

—Erik Greb

Suggested Reading

Blake P, Nir RR, Perry CJ, Burstein R. Tracking patients with chronic occipital headache after occipital nerve decompression surgery: a case series. Cephalalgia. 2018 Sep 14 [Epub ahead of print].

Krøll LS, Hammarlund CS, Westergaard ML, et al. Level of physical activity, well-being, stress and self-rated health in persons with migraine and co-existing tension-type headache and neck pain. J Headache Pain. 2017;18(1):46. Perry CJ, Blake P, Buettner C, et al. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: implications for extracranial origin of headache. Ann Neurol. 2016;79(6):1000-1013.

Schmid AB, Coppieters MW, Ruitenberg MJ, McLachlan EM. Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats. J Neuropathol Exp Neurol. 2013;72(7):662-680.

Schueler M, Neuhuber WL, De Col R, Messlinger K. Innervation of rat and human dura mater and pericranial tissues in the parieto-temporal region by meningeal afferents. Headache. 2014;54(6):996-1009.

ASHEVILLE, NC—Although neurologists tend to classify disorders as problems of either the CNS or the peripheral nervous system, patients with headache may have symptoms that indicate the involvement of both systems, according to an overview provided at the Eighth Annual Scientific Meeting of the Southern Headache Society. Research has revealed anatomic connections between extracranial and intracranial spaces that could contribute to the generation of headaches. Thus, the central and peripheral nervous systems “do not have to be two separate spaces and two separate pathologies,” said Pamela Blake, MD, Director of the Headache Center of Greater Heights in Houston.

Problems With Prevention and Acute Treatment

One patient presented to Dr. Blake with an eight-year history of throbbing headaches and constant pain and tightness in the neck and occiput. The pain radiated to her temples and forehead two to four times per week with accompanying photophobia, phonophobia, and nausea. The patient also had mild allodynia. The frontal pain and accompanying symptoms were consistent with episodic migraine, but the allodynia and pain in the neck and occiput were not, said Dr. Blake. A possible diagnosis was episodic migraine without aura with chronic tension-type headaches and neck pain, she added.

A 2017 study published in the Journal of Headache and Pain suggested that this headache type is problematic. Among 148 migraineurs, the researchers identified 100 patients who also had tension-type headache and chronic neck pain. Compared with healthy controls, these patients had less physical activity, less psychologic well-being, more perceived stress, and poorer self-rated health. Pain reduced these patients’ ability to perform physical activity, which could make treatment more difficult, according to the authors.

Patients with these symptoms have trigeminal and occipital pain. “These symptoms do not appear to be solely, or even primarily, central,” said Dr. Blake. The frontal pain responds to triptans, but the occipital pain, which is the more constant pain, does not. “Preventive medications do not work well in this population, and that’s why they have chronic headaches,” said Dr. Blake.

Physiologic and Pathophysiologic Mechanisms

Research by Schueler and colleagues suggested a potential physiologic explanation for combined central and peripheral involvement in headache. They applied a fluorescent tracer to proximally cut meningeal nerves in rat skulls and to distal branches of the spinosus nerve in human calvaria that was lined with dura mater. They observed that branches of the spinosus nerve travel “along the middle meningeal artery, supplying the dura, entering the cranial bone, and running through the calvarium,” said Dr. Blake. Branches of the spinosus nerve also “entered the tenderness junctions of the pericranial muscles, including in the neck.”

This work indicates a connection between intracranial and extracranial areas but does not shed light on the pathophysiology of a headache with central and peripheral symptoms, said Dr. Blake. In 2016, she and her colleagues took perivascular biopsies from healthy controls and subjects with chronic migraine and predominantly occipital headache. They found a significant increase in the expression of proinflammatory genes and a decrease in the expression of anti-inflammatory genes among migraineurs, compared with controls. “This was the first evidence of localized extracranial pathophysiology in chronic migraine,” said Dr. Blake.

This inflammation could result from compression of the occipital nerves. A 2013 study by Schmid et al found that progressive nerve compression results in chronic local and remote immune-mediated inflammation. Stress also can cause inflammation. “Many patients who present with occipital nerve compression headaches had the onset of their pain during a time of intense stress,” said Dr. Blake.

The Role of the Occipital Nerve

Occipital nerve compression headache is characterized by daily or near-daily pain in the distribution of the occipital nerve. Patients describe the pain as a tight, imploding pressure that sometimes radiates to frontal areas and becomes a throbbing pain. This headache rarely has a neuropathic component.

Allodynia is “almost a requirement of this diagnosis,” said Dr. Blake. The allodynia symptom checklist, however, does not capture it well in these patients because it focuses on pain in the trigeminal nerve distribution. Patients report that the back of the head is tender to the touch and that it hurts to rest the head on a pillow.

The cervical muscles compress the nerve and contribute to the symptoms as well. Patients often report that moving the head or neck exacerbates the pain. The headache also may have migrainous features. It takes skill and expertise to elicit an adequate history from these patients, said Dr. Blake. “Careful questioning is helpful. I often find … that a second visit is more helpful to obtain this history after reviewing the anatomy with the patient, reviewing this pathophysiology, and sending them back out to keep a careful log for two weeks.”

Nerve Blocks and Nerve Decompression

Occipital nerve blocks provide relief for these patients, but they may not be easy to administer. A large dorsal occipital nerve may be mistaken for the greater occipital nerve, for example. Physiologic abnormalities in some patients also can complicate this treatment.

Another effective treatment is nerve decompression surgery. Dr. Blake and colleagues conducted a retrospective review of patients who had undergone decompression of the greater occipital nerves at the point where they traverse the musculature of the posterior neck. The intervention provided complete relief for three to six years in one patient with new daily persistent headache and two patients with chronic posttraumatic headache. Two patients with chronic headache or migraine had partial relief. Surgery provided no relief for two patients with episodic migraine, one patient with chronic migraine, and one patient with chronic tension-type headache.

“In our experience, … 75% to 80% of patients experience a greater than 50% reduction in their headaches, measured by headache frequency and intensity,” said Dr. Blake. She and her colleagues compared outcomes between 18 chronic migraineurs with predominantly occipital pain who underwent surgical decompression of the occipital nerve and 23 patients who were referred for surgery but unable to receive it. In the surgical group, the number of predominantly occipital chronic migraine days per month decreased from 28.9 at baseline to 7.28 at a mean of 46 months later. The outcome in the control group did not change.

Correct patient selection “is the first, most important step” toward treatment success, said Dr. Blake. This process includes a preoperative psychologic evaluation that screens surgical candidates for somatic symptom disorder, mood disorders, a history of trauma, and catastrophizing. If indicated, neurologists may begin providing cognitive behavioral therapy or supportive psychotherapy before surgery. “We have a comprehensive program with postoperative management, including physical therapy and gradual taper of medications,” said Dr. Blake. Central migraine processes may contribute to headache in some of these patients. “Menstrual migraines are not going to go away with nerve decompression. Chronic migraine sometimes does not go away. This is a complex group of patients who definitely require a lot of follow-up.”

—Erik Greb

Suggested Reading

Blake P, Nir RR, Perry CJ, Burstein R. Tracking patients with chronic occipital headache after occipital nerve decompression surgery: a case series. Cephalalgia. 2018 Sep 14 [Epub ahead of print].

Krøll LS, Hammarlund CS, Westergaard ML, et al. Level of physical activity, well-being, stress and self-rated health in persons with migraine and co-existing tension-type headache and neck pain. J Headache Pain. 2017;18(1):46. Perry CJ, Blake P, Buettner C, et al. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: implications for extracranial origin of headache. Ann Neurol. 2016;79(6):1000-1013.

Schmid AB, Coppieters MW, Ruitenberg MJ, McLachlan EM. Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats. J Neuropathol Exp Neurol. 2013;72(7):662-680.

Schueler M, Neuhuber WL, De Col R, Messlinger K. Innervation of rat and human dura mater and pericranial tissues in the parieto-temporal region by meningeal afferents. Headache. 2014;54(6):996-1009.

ASHEVILLE, NC—Although neurologists tend to classify disorders as problems of either the CNS or the peripheral nervous system, patients with headache may have symptoms that indicate the involvement of both systems, according to an overview provided at the Eighth Annual Scientific Meeting of the Southern Headache Society. Research has revealed anatomic connections between extracranial and intracranial spaces that could contribute to the generation of headaches. Thus, the central and peripheral nervous systems “do not have to be two separate spaces and two separate pathologies,” said Pamela Blake, MD, Director of the Headache Center of Greater Heights in Houston.

Problems With Prevention and Acute Treatment

One patient presented to Dr. Blake with an eight-year history of throbbing headaches and constant pain and tightness in the neck and occiput. The pain radiated to her temples and forehead two to four times per week with accompanying photophobia, phonophobia, and nausea. The patient also had mild allodynia. The frontal pain and accompanying symptoms were consistent with episodic migraine, but the allodynia and pain in the neck and occiput were not, said Dr. Blake. A possible diagnosis was episodic migraine without aura with chronic tension-type headaches and neck pain, she added.

A 2017 study published in the Journal of Headache and Pain suggested that this headache type is problematic. Among 148 migraineurs, the researchers identified 100 patients who also had tension-type headache and chronic neck pain. Compared with healthy controls, these patients had less physical activity, less psychologic well-being, more perceived stress, and poorer self-rated health. Pain reduced these patients’ ability to perform physical activity, which could make treatment more difficult, according to the authors.

Patients with these symptoms have trigeminal and occipital pain. “These symptoms do not appear to be solely, or even primarily, central,” said Dr. Blake. The frontal pain responds to triptans, but the occipital pain, which is the more constant pain, does not. “Preventive medications do not work well in this population, and that’s why they have chronic headaches,” said Dr. Blake.

Physiologic and Pathophysiologic Mechanisms

Research by Schueler and colleagues suggested a potential physiologic explanation for combined central and peripheral involvement in headache. They applied a fluorescent tracer to proximally cut meningeal nerves in rat skulls and to distal branches of the spinosus nerve in human calvaria that was lined with dura mater. They observed that branches of the spinosus nerve travel “along the middle meningeal artery, supplying the dura, entering the cranial bone, and running through the calvarium,” said Dr. Blake. Branches of the spinosus nerve also “entered the tenderness junctions of the pericranial muscles, including in the neck.”

This work indicates a connection between intracranial and extracranial areas but does not shed light on the pathophysiology of a headache with central and peripheral symptoms, said Dr. Blake. In 2016, she and her colleagues took perivascular biopsies from healthy controls and subjects with chronic migraine and predominantly occipital headache. They found a significant increase in the expression of proinflammatory genes and a decrease in the expression of anti-inflammatory genes among migraineurs, compared with controls. “This was the first evidence of localized extracranial pathophysiology in chronic migraine,” said Dr. Blake.

This inflammation could result from compression of the occipital nerves. A 2013 study by Schmid et al found that progressive nerve compression results in chronic local and remote immune-mediated inflammation. Stress also can cause inflammation. “Many patients who present with occipital nerve compression headaches had the onset of their pain during a time of intense stress,” said Dr. Blake.

The Role of the Occipital Nerve

Occipital nerve compression headache is characterized by daily or near-daily pain in the distribution of the occipital nerve. Patients describe the pain as a tight, imploding pressure that sometimes radiates to frontal areas and becomes a throbbing pain. This headache rarely has a neuropathic component.

Allodynia is “almost a requirement of this diagnosis,” said Dr. Blake. The allodynia symptom checklist, however, does not capture it well in these patients because it focuses on pain in the trigeminal nerve distribution. Patients report that the back of the head is tender to the touch and that it hurts to rest the head on a pillow.

The cervical muscles compress the nerve and contribute to the symptoms as well. Patients often report that moving the head or neck exacerbates the pain. The headache also may have migrainous features. It takes skill and expertise to elicit an adequate history from these patients, said Dr. Blake. “Careful questioning is helpful. I often find … that a second visit is more helpful to obtain this history after reviewing the anatomy with the patient, reviewing this pathophysiology, and sending them back out to keep a careful log for two weeks.”

Nerve Blocks and Nerve Decompression

Occipital nerve blocks provide relief for these patients, but they may not be easy to administer. A large dorsal occipital nerve may be mistaken for the greater occipital nerve, for example. Physiologic abnormalities in some patients also can complicate this treatment.

Another effective treatment is nerve decompression surgery. Dr. Blake and colleagues conducted a retrospective review of patients who had undergone decompression of the greater occipital nerves at the point where they traverse the musculature of the posterior neck. The intervention provided complete relief for three to six years in one patient with new daily persistent headache and two patients with chronic posttraumatic headache. Two patients with chronic headache or migraine had partial relief. Surgery provided no relief for two patients with episodic migraine, one patient with chronic migraine, and one patient with chronic tension-type headache.

“In our experience, … 75% to 80% of patients experience a greater than 50% reduction in their headaches, measured by headache frequency and intensity,” said Dr. Blake. She and her colleagues compared outcomes between 18 chronic migraineurs with predominantly occipital pain who underwent surgical decompression of the occipital nerve and 23 patients who were referred for surgery but unable to receive it. In the surgical group, the number of predominantly occipital chronic migraine days per month decreased from 28.9 at baseline to 7.28 at a mean of 46 months later. The outcome in the control group did not change.

Correct patient selection “is the first, most important step” toward treatment success, said Dr. Blake. This process includes a preoperative psychologic evaluation that screens surgical candidates for somatic symptom disorder, mood disorders, a history of trauma, and catastrophizing. If indicated, neurologists may begin providing cognitive behavioral therapy or supportive psychotherapy before surgery. “We have a comprehensive program with postoperative management, including physical therapy and gradual taper of medications,” said Dr. Blake. Central migraine processes may contribute to headache in some of these patients. “Menstrual migraines are not going to go away with nerve decompression. Chronic migraine sometimes does not go away. This is a complex group of patients who definitely require a lot of follow-up.”

—Erik Greb

Suggested Reading

Blake P, Nir RR, Perry CJ, Burstein R. Tracking patients with chronic occipital headache after occipital nerve decompression surgery: a case series. Cephalalgia. 2018 Sep 14 [Epub ahead of print].

Krøll LS, Hammarlund CS, Westergaard ML, et al. Level of physical activity, well-being, stress and self-rated health in persons with migraine and co-existing tension-type headache and neck pain. J Headache Pain. 2017;18(1):46. Perry CJ, Blake P, Buettner C, et al. Upregulation of inflammatory gene transcripts in periosteum of chronic migraineurs: implications for extracranial origin of headache. Ann Neurol. 2016;79(6):1000-1013.

Schmid AB, Coppieters MW, Ruitenberg MJ, McLachlan EM. Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats. J Neuropathol Exp Neurol. 2013;72(7):662-680.

Schueler M, Neuhuber WL, De Col R, Messlinger K. Innervation of rat and human dura mater and pericranial tissues in the parieto-temporal region by meningeal afferents. Headache. 2014;54(6):996-1009.

Newly designed battery-free wireless dosimeters can passively, continuously, and accurately measure electromagnetic radiation in numerous environments, according to three studies of the millimeter-scale near-field communication (mm-NFC) devices.

S.Y. Heo et.al. Science Translational Medicine, 2018

“These studies highlight the differences between mm-NFC dosimeters and commercial devices in real-world, practical scenarios,” wrote lead author Seung Yun Heo of the department of biomedical engineering at the Center for Bio-Integrated Electronics at Northwestern University, Chicago, and her coauthors. “The former operate in continuous, uninterrupted modes, whereas the latter capture instantaneous values of intensity at preprogrammed intervals,”they noted. The study was published in Science Translational Medicine.

Separate studies to assess the performance of these “flexible” dosimeters took place in Rio de Janeiro, Brazil, and St. Petersburg, Fla. The Florida study included 13 healthy participants who wore skin-mounted mm-NFC ultraviolet A (UVA) dosimeters on the right back hand, left back hand, left inner arm, and left outer arm, plus a commercial dosimeter on the right wrist. The volunteers walked a 6.44-km path three times: a morning and subsequent afternoon stroll, plus an evening walk 4 days later. Four devices failed during the afternoon exercise, but otherwise, participants received data on their smartphones via the dosimeters at 30-minute intervals.

The Brazilian study was made up of nine healthy participants who wore mm-NFC UVA dosimeters on the thumbnail or the middle fingernail; commercial dosimeters were worn on the wrist of the ipsilateral side. These volunteers engaged in rooftop recreational activities that corresponded to solar zenith angles, along with showering and swimming with the use of soap and skin creams. All sensors remained functional over the 4 days of testing, and 14 of 20 devices remained adhered to the fingernail. Accumulated doses ranged widely, “as expected on the basis of the differences in behaviors,” the authors wrote. These observations imply highly variable UV-associated risks between participants, due not only to differences in Fitzpatrick skin types but also to individual behavior patterns,” they added.

The third study of mm-NFC blue light dosimeters comprised three newborns in an Urbana, Ill., neonatal ICU undergoing blue light phototherapy treatments. Nurses mounted dosimeters on the patients’ chests before phototherapy; an antenna underneath the incubator mattress transmitted continuous wireless measurements of blue intensity and dosage at 20-minute intervals for 20 hours.

The authors acknowledged that these devices and their designs have limitations, including a small detection area as compared to the surface area of a human body. The study’s results “represent localized measurements of exposure, whereas the sun irradiance profile across the body surface is not uniform and varies by position of the sun in the sky over the course of a day.” They recommended that future research could “create anatomic specific risk assessment of UV exposure” via multinodal sensing with UVA/UVB dosimeters on several parts of the body.

The Brazilian UV study was sponsored by La Roche Posay and L’Oreal California Research Center. Research was supported by the National Cancer Institute. Five of the authors reported commercial interests in the technology. Another author reported paid consultation for Aclaris Therapeutics.

SOURCE: Heo SY et al. Sci. Transl. Med. 2018 Dec 5. doi: 10.1126/scitranslmed.aau1643.

Newly designed battery-free wireless dosimeters can passively, continuously, and accurately measure electromagnetic radiation in numerous environments, according to three studies of the millimeter-scale near-field communication (mm-NFC) devices.

S.Y. Heo et.al. Science Translational Medicine, 2018

“These studies highlight the differences between mm-NFC dosimeters and commercial devices in real-world, practical scenarios,” wrote lead author Seung Yun Heo of the department of biomedical engineering at the Center for Bio-Integrated Electronics at Northwestern University, Chicago, and her coauthors. “The former operate in continuous, uninterrupted modes, whereas the latter capture instantaneous values of intensity at preprogrammed intervals,”they noted. The study was published in Science Translational Medicine.

Separate studies to assess the performance of these “flexible” dosimeters took place in Rio de Janeiro, Brazil, and St. Petersburg, Fla. The Florida study included 13 healthy participants who wore skin-mounted mm-NFC ultraviolet A (UVA) dosimeters on the right back hand, left back hand, left inner arm, and left outer arm, plus a commercial dosimeter on the right wrist. The volunteers walked a 6.44-km path three times: a morning and subsequent afternoon stroll, plus an evening walk 4 days later. Four devices failed during the afternoon exercise, but otherwise, participants received data on their smartphones via the dosimeters at 30-minute intervals.

The Brazilian study was made up of nine healthy participants who wore mm-NFC UVA dosimeters on the thumbnail or the middle fingernail; commercial dosimeters were worn on the wrist of the ipsilateral side. These volunteers engaged in rooftop recreational activities that corresponded to solar zenith angles, along with showering and swimming with the use of soap and skin creams. All sensors remained functional over the 4 days of testing, and 14 of 20 devices remained adhered to the fingernail. Accumulated doses ranged widely, “as expected on the basis of the differences in behaviors,” the authors wrote. These observations imply highly variable UV-associated risks between participants, due not only to differences in Fitzpatrick skin types but also to individual behavior patterns,” they added.

The third study of mm-NFC blue light dosimeters comprised three newborns in an Urbana, Ill., neonatal ICU undergoing blue light phototherapy treatments. Nurses mounted dosimeters on the patients’ chests before phototherapy; an antenna underneath the incubator mattress transmitted continuous wireless measurements of blue intensity and dosage at 20-minute intervals for 20 hours.

The authors acknowledged that these devices and their designs have limitations, including a small detection area as compared to the surface area of a human body. The study’s results “represent localized measurements of exposure, whereas the sun irradiance profile across the body surface is not uniform and varies by position of the sun in the sky over the course of a day.” They recommended that future research could “create anatomic specific risk assessment of UV exposure” via multinodal sensing with UVA/UVB dosimeters on several parts of the body.

The Brazilian UV study was sponsored by La Roche Posay and L’Oreal California Research Center. Research was supported by the National Cancer Institute. Five of the authors reported commercial interests in the technology. Another author reported paid consultation for Aclaris Therapeutics.

SOURCE: Heo SY et al. Sci. Transl. Med. 2018 Dec 5. doi: 10.1126/scitranslmed.aau1643.

Newly designed battery-free wireless dosimeters can passively, continuously, and accurately measure electromagnetic radiation in numerous environments, according to three studies of the millimeter-scale near-field communication (mm-NFC) devices.

S.Y. Heo et.al. Science Translational Medicine, 2018

“These studies highlight the differences between mm-NFC dosimeters and commercial devices in real-world, practical scenarios,” wrote lead author Seung Yun Heo of the department of biomedical engineering at the Center for Bio-Integrated Electronics at Northwestern University, Chicago, and her coauthors. “The former operate in continuous, uninterrupted modes, whereas the latter capture instantaneous values of intensity at preprogrammed intervals,”they noted. The study was published in Science Translational Medicine.

Separate studies to assess the performance of these “flexible” dosimeters took place in Rio de Janeiro, Brazil, and St. Petersburg, Fla. The Florida study included 13 healthy participants who wore skin-mounted mm-NFC ultraviolet A (UVA) dosimeters on the right back hand, left back hand, left inner arm, and left outer arm, plus a commercial dosimeter on the right wrist. The volunteers walked a 6.44-km path three times: a morning and subsequent afternoon stroll, plus an evening walk 4 days later. Four devices failed during the afternoon exercise, but otherwise, participants received data on their smartphones via the dosimeters at 30-minute intervals.

The Brazilian study was made up of nine healthy participants who wore mm-NFC UVA dosimeters on the thumbnail or the middle fingernail; commercial dosimeters were worn on the wrist of the ipsilateral side. These volunteers engaged in rooftop recreational activities that corresponded to solar zenith angles, along with showering and swimming with the use of soap and skin creams. All sensors remained functional over the 4 days of testing, and 14 of 20 devices remained adhered to the fingernail. Accumulated doses ranged widely, “as expected on the basis of the differences in behaviors,” the authors wrote. These observations imply highly variable UV-associated risks between participants, due not only to differences in Fitzpatrick skin types but also to individual behavior patterns,” they added.

The third study of mm-NFC blue light dosimeters comprised three newborns in an Urbana, Ill., neonatal ICU undergoing blue light phototherapy treatments. Nurses mounted dosimeters on the patients’ chests before phototherapy; an antenna underneath the incubator mattress transmitted continuous wireless measurements of blue intensity and dosage at 20-minute intervals for 20 hours.

The authors acknowledged that these devices and their designs have limitations, including a small detection area as compared to the surface area of a human body. The study’s results “represent localized measurements of exposure, whereas the sun irradiance profile across the body surface is not uniform and varies by position of the sun in the sky over the course of a day.” They recommended that future research could “create anatomic specific risk assessment of UV exposure” via multinodal sensing with UVA/UVB dosimeters on several parts of the body.

The Brazilian UV study was sponsored by La Roche Posay and L’Oreal California Research Center. Research was supported by the National Cancer Institute. Five of the authors reported commercial interests in the technology. Another author reported paid consultation for Aclaris Therapeutics.

SOURCE: Heo SY et al. Sci. Transl. Med. 2018 Dec 5. doi: 10.1126/scitranslmed.aau1643.

Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking apixaban (IRR, 0.66; 95% CI, 0.52-0.85), dabigatran (IRR, 0.49; 95% CI, 0.41-0.59), rivaroxaban (IRR, 0.75; 95% CI, 0.68-0.84), and warfarin (IRR, 0.65; 95% CI, 0.62-0.69).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking apixaban (IRR, 0.66; 95% CI, 0.52-0.85), dabigatran (IRR, 0.49; 95% CI, 0.41-0.59), rivaroxaban (IRR, 0.75; 95% CI, 0.68-0.84), and warfarin (IRR, 0.65; 95% CI, 0.62-0.69).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

Patients receiving oral anticoagulant treatment had the lowest risk of gastrointestinal bleeding when taking apixaban, compared with rivaroxaban, dabigatran, and warfarin, according to a recent study.

Further, patients who received proton pump inhibitor (PPI) cotherapy had a lower overall risk of gastrointestinal bleeding, according to Wayne A. Ray, PhD, from the department of health policy at Vanderbilt University, Nashville, Tenn., and his colleagues.

“These findings indicate the potential benefits of a gastrointestinal bleeding risk assessment before initiating anticoagulant treatment,” Dr. Ray and his colleagues wrote in their study, which was published in JAMA.

Dr. Ray and his colleagues performed a retrospective, population-based study of 1,643,123 Medicare beneficiaries (mean age, 76.4 years) who received 1,713,183 new episodes of oral anticoagulant treatment between January 2011 and September 2015. They analyzed how patients reacted to apixaban, dabigatran, rivaroxaban, or warfarin both with and without PPI cotherapy.

Overall, the risk of gastrointestinal bleeding across 754,389 person-years without PPI therapy was 115 per 10,000 person-years (95% confidence interval, 112-118) in 7,119 patients. The researchers found the risk of gastrointestinal bleeding was highest in patients taking rivaroxaban (1,278 patients; 144 per 10,000 person-years; 95% CI, 136-152) and lowest when taking apixaban (279 patients; 120 per 10,000 person-years; incidence rate ratio, 1,97; 95% CI, 1.73-2.25), compared with dabigatran (629 patients; 120 per 10,000 person-years; IRR, 1.19; 95% CI, 1.08-1.32) and warfarin (4,933 patients; 113 per 10,000 person-years; IRR, 1.27; 95% CI, 1.19-1.35). There was a significantly lower incidence of gastrointestinal bleeding for apixaban, compared with warfarin (IRR, 0.64; 95% CI, 0.57-0.73) and dabigatran (IRR, 0.61; 95% CI, 0.52-0.70).

There was a lower overall incidence of gastrointestinal bleeding when receiving PPI cotherapy (264,447 person-years; 76 per 10,000 person-years), compared with patients who received anticoagulant treatment without PPI cotherapy (IRR, 0.66; 95% CI, 0.62-0.69). This reduced incidence of gastrointestinal bleeding was also seen in patients receiving PPI cotherapy and taking apixaban (IRR, 0.66; 95% CI, 0.52-0.85), dabigatran (IRR, 0.49; 95% CI, 0.41-0.59), rivaroxaban (IRR, 0.75; 95% CI, 0.68-0.84), and warfarin (IRR, 0.65; 95% CI, 0.62-0.69).

The researchers noted that limitations in this study included potential misclassification of anticoagulant treatment, PPI cotherapy, and NSAIDs because of a reliance on filled prescription data; confounding by unmeasured factors such as aspirin exposure or Helicobacter pylori infection; and gastrointestinal bleeding being measured using a disease risk score.

This study was supported by a grant from the National Heart, Lung, and Blood Institute. The authors reported no relevant conflicts of interest.

SOURCE: Ray WA et al. JAMA. 2018 Dec 4. doi: 10.1001/jama.2018.17242.

A new federal proposal aims to move you away from the keyboard and back face-to-face with your patients.

The draft strategy from the Office of the National Coordinator for Health IT has three aims: to reduce the time and effort to record information in EHRs; to reduce the time and effort required to meet regulatory requirements; and to improve the functionality and ease of use of EHRs.

“This draft strategy includes recommendations that will allow physicians and other clinicians to provide effective care to their patients with a renewed sense of satisfaction for them and their patients,” Andrew Gettinger, MD, chief clinical officer at ONC, and Kate Goodrich, MD, chief medical officer at the Centers for Medicare & Medicaid Services, wrote in a recent blog post. “We are taking one more step toward improving the interoperability and usability of health information by establishing a goal, strategy, and recommendations to reduce regulatory and administrative burdens relating to the use of EHRs.”

To ease documentation burdens, the proposal seeks to “mitigate the EHR-related burden associated with a variety of administrative processes,” the draft strategy notes. “We are considering how reforming certain administrative requirements or optimizing out-of-date requirements for health IT–enabled health care provider work flows can reduce the burden of clinical documentation.”

Specifically, ONC proposes to reduce the overall regulatory burden, leverage data present in the electronic record to reduce the redocumentation, waive certain documentation requirements for participants in advanced alternative payment models (APMs), and promote standardized documentation for ordering and prior authorization.

To improve health IT usability, the draft strategy aims to “address how improvements in the design and use of health IT systems” can reduce burden and calls on clinicians, software developers, and other vendors to collaborate.

To do so, ONC recommends better alignment between EHR design and clinical work flow and making improvements to clinical decision support, as well as improving the presentation of clinical data within EHRs and clinical documentation functionality.

ONC also recommends standardizing basic clinical operations across all EHRs, designing EHR interfaces that are standard to health care delivery, and better integration of the EHR with the exam room.

The draft strategy also includes recommendations to help doctors better understand the financial requirements for successful implementation and optimize the log-in procedures to help reduce burden.

thinkstockphotos.com

EHR reporting strategies “are designed to address many of the programmatic, technical, and operational challenges raised by stakeholders to reduce EHR-related burden associated with program reporting.”

ONC wants to simplify scoring for the “promoting interoperability” performance category in the Merit-based Incentive Payment System (MIPS) track of the Quality Payment Program and improving other measures of health IT usage; applying additional data standards to make data access, extraction, and integration across multiple systems easier and less costly; and exploring alternate, less burdensome approaches to electronic quality measurement through pilot programs and reporting program incentives.

Finally, public health reporting strategies “look at a set of topics linked to federal, state, local, territorial, and tribal government policies and public health programs, with a specific focus on EPCS [electronic prescribing for controlled substances] and PDMPs [prescription drug monitoring programs]. Where EHR-related burden remains a key barrier to progress in these areas, there are several recommendations for how stakeholders can advance these burden reduction goals related to public health.”

In this area, ONC is recommending increasing adoption of e-prescribing of controlled substances with access to medication history to better inform prescribing of controlled substances, harmonizing reporting requirements across federally funded programs to streamline reporting requirements, and providing better guidance about HIPPA and federal confidentially requirements governing substance abuse disorder to better facilitate the electronic exchange of health information for patient care.

Comments on the report may be submitted electronically through Jan. 28, 2019.

gtwachtman@mdedge.com

A new federal proposal aims to move you away from the keyboard and back face-to-face with your patients.

The draft strategy from the Office of the National Coordinator for Health IT has three aims: to reduce the time and effort to record information in EHRs; to reduce the time and effort required to meet regulatory requirements; and to improve the functionality and ease of use of EHRs.

“This draft strategy includes recommendations that will allow physicians and other clinicians to provide effective care to their patients with a renewed sense of satisfaction for them and their patients,” Andrew Gettinger, MD, chief clinical officer at ONC, and Kate Goodrich, MD, chief medical officer at the Centers for Medicare & Medicaid Services, wrote in a recent blog post. “We are taking one more step toward improving the interoperability and usability of health information by establishing a goal, strategy, and recommendations to reduce regulatory and administrative burdens relating to the use of EHRs.”

To ease documentation burdens, the proposal seeks to “mitigate the EHR-related burden associated with a variety of administrative processes,” the draft strategy notes. “We are considering how reforming certain administrative requirements or optimizing out-of-date requirements for health IT–enabled health care provider work flows can reduce the burden of clinical documentation.”

Specifically, ONC proposes to reduce the overall regulatory burden, leverage data present in the electronic record to reduce the redocumentation, waive certain documentation requirements for participants in advanced alternative payment models (APMs), and promote standardized documentation for ordering and prior authorization.

To improve health IT usability, the draft strategy aims to “address how improvements in the design and use of health IT systems” can reduce burden and calls on clinicians, software developers, and other vendors to collaborate.

To do so, ONC recommends better alignment between EHR design and clinical work flow and making improvements to clinical decision support, as well as improving the presentation of clinical data within EHRs and clinical documentation functionality.

ONC also recommends standardizing basic clinical operations across all EHRs, designing EHR interfaces that are standard to health care delivery, and better integration of the EHR with the exam room.

The draft strategy also includes recommendations to help doctors better understand the financial requirements for successful implementation and optimize the log-in procedures to help reduce burden.

thinkstockphotos.com

EHR reporting strategies “are designed to address many of the programmatic, technical, and operational challenges raised by stakeholders to reduce EHR-related burden associated with program reporting.”

ONC wants to simplify scoring for the “promoting interoperability” performance category in the Merit-based Incentive Payment System (MIPS) track of the Quality Payment Program and improving other measures of health IT usage; applying additional data standards to make data access, extraction, and integration across multiple systems easier and less costly; and exploring alternate, less burdensome approaches to electronic quality measurement through pilot programs and reporting program incentives.

Finally, public health reporting strategies “look at a set of topics linked to federal, state, local, territorial, and tribal government policies and public health programs, with a specific focus on EPCS [electronic prescribing for controlled substances] and PDMPs [prescription drug monitoring programs]. Where EHR-related burden remains a key barrier to progress in these areas, there are several recommendations for how stakeholders can advance these burden reduction goals related to public health.”

In this area, ONC is recommending increasing adoption of e-prescribing of controlled substances with access to medication history to better inform prescribing of controlled substances, harmonizing reporting requirements across federally funded programs to streamline reporting requirements, and providing better guidance about HIPPA and federal confidentially requirements governing substance abuse disorder to better facilitate the electronic exchange of health information for patient care.

Comments on the report may be submitted electronically through Jan. 28, 2019.

gtwachtman@mdedge.com

A new federal proposal aims to move you away from the keyboard and back face-to-face with your patients.

The draft strategy from the Office of the National Coordinator for Health IT has three aims: to reduce the time and effort to record information in EHRs; to reduce the time and effort required to meet regulatory requirements; and to improve the functionality and ease of use of EHRs.

“This draft strategy includes recommendations that will allow physicians and other clinicians to provide effective care to their patients with a renewed sense of satisfaction for them and their patients,” Andrew Gettinger, MD, chief clinical officer at ONC, and Kate Goodrich, MD, chief medical officer at the Centers for Medicare & Medicaid Services, wrote in a recent blog post. “We are taking one more step toward improving the interoperability and usability of health information by establishing a goal, strategy, and recommendations to reduce regulatory and administrative burdens relating to the use of EHRs.”

To ease documentation burdens, the proposal seeks to “mitigate the EHR-related burden associated with a variety of administrative processes,” the draft strategy notes. “We are considering how reforming certain administrative requirements or optimizing out-of-date requirements for health IT–enabled health care provider work flows can reduce the burden of clinical documentation.”

Specifically, ONC proposes to reduce the overall regulatory burden, leverage data present in the electronic record to reduce the redocumentation, waive certain documentation requirements for participants in advanced alternative payment models (APMs), and promote standardized documentation for ordering and prior authorization.

To improve health IT usability, the draft strategy aims to “address how improvements in the design and use of health IT systems” can reduce burden and calls on clinicians, software developers, and other vendors to collaborate.

To do so, ONC recommends better alignment between EHR design and clinical work flow and making improvements to clinical decision support, as well as improving the presentation of clinical data within EHRs and clinical documentation functionality.

ONC also recommends standardizing basic clinical operations across all EHRs, designing EHR interfaces that are standard to health care delivery, and better integration of the EHR with the exam room.

The draft strategy also includes recommendations to help doctors better understand the financial requirements for successful implementation and optimize the log-in procedures to help reduce burden.

thinkstockphotos.com

EHR reporting strategies “are designed to address many of the programmatic, technical, and operational challenges raised by stakeholders to reduce EHR-related burden associated with program reporting.”

ONC wants to simplify scoring for the “promoting interoperability” performance category in the Merit-based Incentive Payment System (MIPS) track of the Quality Payment Program and improving other measures of health IT usage; applying additional data standards to make data access, extraction, and integration across multiple systems easier and less costly; and exploring alternate, less burdensome approaches to electronic quality measurement through pilot programs and reporting program incentives.

Finally, public health reporting strategies “look at a set of topics linked to federal, state, local, territorial, and tribal government policies and public health programs, with a specific focus on EPCS [electronic prescribing for controlled substances] and PDMPs [prescription drug monitoring programs]. Where EHR-related burden remains a key barrier to progress in these areas, there are several recommendations for how stakeholders can advance these burden reduction goals related to public health.”

In this area, ONC is recommending increasing adoption of e-prescribing of controlled substances with access to medication history to better inform prescribing of controlled substances, harmonizing reporting requirements across federally funded programs to streamline reporting requirements, and providing better guidance about HIPPA and federal confidentially requirements governing substance abuse disorder to better facilitate the electronic exchange of health information for patient care.

Comments on the report may be submitted electronically through Jan. 28, 2019.

gtwachtman@mdedge.com

SAN DIEGO – It was banner year for new hematology drug approvals, according to R. Angelo de Claro, MD, of the Food and Drug Administration.

So far in 2018 there have been 32 new malignant hematology and nonmalignant hematology drug approvals by the FDA, including 12 first-time approvals, 5 new biosimilars, and 15 new indications for previously approved drugs, Dr. de Claro, clinical team leader in the FDA’s division of hematology products in Silver Spring, Md., said during an overview of the approvals at the annual meeting of the American Society of Hematology.

These include six new approvals for first-line treatment, and eight for pediatric indications, he said.

Highlights were discussed at two ASH-FDA joint symposia at the meeting, including one focused on the malignant hematology approvals, and another on the nonmalignant hematology approvals. In a video interview, Dr. de Claro provides some additional insight into their importance and about what might lie ahead.

“I think what’s exciting is that you have drug development occurring in more common conditions such as chronic lymphocytic leukemia, as well as in rare conditions, including hairy cell leukemia – and the first-ever approval in hemophagocytic lymphohistiocytosis,” he said. “It’s been very busy at the FDA; stay tuned ... the year’s not done yet. There could be more coming and we certainly anticipate more applications in the future.”

Dr. de Claro is an FDA employee. He reported having no other relevant disclosures.

sworcester@mdedge.com

SAN DIEGO – It was banner year for new hematology drug approvals, according to R. Angelo de Claro, MD, of the Food and Drug Administration.

So far in 2018 there have been 32 new malignant hematology and nonmalignant hematology drug approvals by the FDA, including 12 first-time approvals, 5 new biosimilars, and 15 new indications for previously approved drugs, Dr. de Claro, clinical team leader in the FDA’s division of hematology products in Silver Spring, Md., said during an overview of the approvals at the annual meeting of the American Society of Hematology.

These include six new approvals for first-line treatment, and eight for pediatric indications, he said.

Highlights were discussed at two ASH-FDA joint symposia at the meeting, including one focused on the malignant hematology approvals, and another on the nonmalignant hematology approvals. In a video interview, Dr. de Claro provides some additional insight into their importance and about what might lie ahead.

“I think what’s exciting is that you have drug development occurring in more common conditions such as chronic lymphocytic leukemia, as well as in rare conditions, including hairy cell leukemia – and the first-ever approval in hemophagocytic lymphohistiocytosis,” he said. “It’s been very busy at the FDA; stay tuned ... the year’s not done yet. There could be more coming and we certainly anticipate more applications in the future.”

Dr. de Claro is an FDA employee. He reported having no other relevant disclosures.

sworcester@mdedge.com

SAN DIEGO – It was banner year for new hematology drug approvals, according to R. Angelo de Claro, MD, of the Food and Drug Administration.

So far in 2018 there have been 32 new malignant hematology and nonmalignant hematology drug approvals by the FDA, including 12 first-time approvals, 5 new biosimilars, and 15 new indications for previously approved drugs, Dr. de Claro, clinical team leader in the FDA’s division of hematology products in Silver Spring, Md., said during an overview of the approvals at the annual meeting of the American Society of Hematology.

These include six new approvals for first-line treatment, and eight for pediatric indications, he said.

Highlights were discussed at two ASH-FDA joint symposia at the meeting, including one focused on the malignant hematology approvals, and another on the nonmalignant hematology approvals. In a video interview, Dr. de Claro provides some additional insight into their importance and about what might lie ahead.

“I think what’s exciting is that you have drug development occurring in more common conditions such as chronic lymphocytic leukemia, as well as in rare conditions, including hairy cell leukemia – and the first-ever approval in hemophagocytic lymphohistiocytosis,” he said. “It’s been very busy at the FDA; stay tuned ... the year’s not done yet. There could be more coming and we certainly anticipate more applications in the future.”

Dr. de Claro is an FDA employee. He reported having no other relevant disclosures.

sworcester@mdedge.com

I’m getting old and starting to fall apart. Recently, I suffered a lumbar radiculopathy when I injured myself sneezing. (No, really, I did.)

lolostock/Thinkstock

So, as time went by and I didn’t get better, I began looking stuff up. When patients come to me for this, I go through the standard conservative regimen of NSAIDs, physical therapy, steroid tapers ... the standard stuff.

But, when I began looking these things up, I was surprised to find out how much of what we do (at least for lumbar radiculopathy) is taken on faith.

I went through UpToDate, the modern Bible of medicine.

NSAIDs and acetaminophen, to my surprise, have only marginal proof of efficacy for acute lumbosacral radiculopathy pain. Several pooled analyses showed a nonsignificant trend to support their use, and the quality of the data was considered to be low.

Likewise, physical therapy also had “no convincing evidence that such treatments are effective for this indication.” Admittedly, some of the data may be affected by the difficulty in doing sham therapy as part of a placebo controlled-trial.

An oral steroid taper? Again, similar, equivocal data. Marginal improvement in functional capabilities, no improvement in pain, and no improvement in the rate of surgery at 1 year out.

But these are the things that I, and likely most family doctors, physiatrists, and other neurologists recommend on a daily basis. And, in all likelihood, will continue to do so.

Why?

Overall, they are benign when used correctly and in the right patients. That isn’t to say everyone should get them. All drugs have issues, and patients have to be carefully matched to specific treatments.

But, in the grand scheme of “do no harm,” physical therapy, NSAIDs, acetaminophen, or a few days of steroids are reasonably harmless. There certainly are some patients who will benefit, and none of these approaches have clearly been shown to be dangerous.

There’s also patient expectations. They didn’t come to us, or shell out a copay, to be told that “nothing helps, give it time.” We’re the doctors, and they want us to DO SOMETHING. So even if these treatments may be placebos, they still help if for no other reason than (as Voltaire said) to amuse the patient while nature cures the disease.

And getting them better is, after all, a big part of our job.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m getting old and starting to fall apart. Recently, I suffered a lumbar radiculopathy when I injured myself sneezing. (No, really, I did.)

lolostock/Thinkstock

So, as time went by and I didn’t get better, I began looking stuff up. When patients come to me for this, I go through the standard conservative regimen of NSAIDs, physical therapy, steroid tapers ... the standard stuff.

But, when I began looking these things up, I was surprised to find out how much of what we do (at least for lumbar radiculopathy) is taken on faith.

I went through UpToDate, the modern Bible of medicine.

NSAIDs and acetaminophen, to my surprise, have only marginal proof of efficacy for acute lumbosacral radiculopathy pain. Several pooled analyses showed a nonsignificant trend to support their use, and the quality of the data was considered to be low.

Likewise, physical therapy also had “no convincing evidence that such treatments are effective for this indication.” Admittedly, some of the data may be affected by the difficulty in doing sham therapy as part of a placebo controlled-trial.

An oral steroid taper? Again, similar, equivocal data. Marginal improvement in functional capabilities, no improvement in pain, and no improvement in the rate of surgery at 1 year out.

But these are the things that I, and likely most family doctors, physiatrists, and other neurologists recommend on a daily basis. And, in all likelihood, will continue to do so.

Why?

Overall, they are benign when used correctly and in the right patients. That isn’t to say everyone should get them. All drugs have issues, and patients have to be carefully matched to specific treatments.

But, in the grand scheme of “do no harm,” physical therapy, NSAIDs, acetaminophen, or a few days of steroids are reasonably harmless. There certainly are some patients who will benefit, and none of these approaches have clearly been shown to be dangerous.

There’s also patient expectations. They didn’t come to us, or shell out a copay, to be told that “nothing helps, give it time.” We’re the doctors, and they want us to DO SOMETHING. So even if these treatments may be placebos, they still help if for no other reason than (as Voltaire said) to amuse the patient while nature cures the disease.

And getting them better is, after all, a big part of our job.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I’m getting old and starting to fall apart. Recently, I suffered a lumbar radiculopathy when I injured myself sneezing. (No, really, I did.)

lolostock/Thinkstock

So, as time went by and I didn’t get better, I began looking stuff up. When patients come to me for this, I go through the standard conservative regimen of NSAIDs, physical therapy, steroid tapers ... the standard stuff.

But, when I began looking these things up, I was surprised to find out how much of what we do (at least for lumbar radiculopathy) is taken on faith.

I went through UpToDate, the modern Bible of medicine.

NSAIDs and acetaminophen, to my surprise, have only marginal proof of efficacy for acute lumbosacral radiculopathy pain. Several pooled analyses showed a nonsignificant trend to support their use, and the quality of the data was considered to be low.

Likewise, physical therapy also had “no convincing evidence that such treatments are effective for this indication.” Admittedly, some of the data may be affected by the difficulty in doing sham therapy as part of a placebo controlled-trial.

An oral steroid taper? Again, similar, equivocal data. Marginal improvement in functional capabilities, no improvement in pain, and no improvement in the rate of surgery at 1 year out.

But these are the things that I, and likely most family doctors, physiatrists, and other neurologists recommend on a daily basis. And, in all likelihood, will continue to do so.

Why?

Overall, they are benign when used correctly and in the right patients. That isn’t to say everyone should get them. All drugs have issues, and patients have to be carefully matched to specific treatments.

But, in the grand scheme of “do no harm,” physical therapy, NSAIDs, acetaminophen, or a few days of steroids are reasonably harmless. There certainly are some patients who will benefit, and none of these approaches have clearly been shown to be dangerous.

There’s also patient expectations. They didn’t come to us, or shell out a copay, to be told that “nothing helps, give it time.” We’re the doctors, and they want us to DO SOMETHING. So even if these treatments may be placebos, they still help if for no other reason than (as Voltaire said) to amuse the patient while nature cures the disease.

And getting them better is, after all, a big part of our job.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Dermoscopy, the use of a handheld instrument to magnify the skin 10-fold while providing a light source, is a quick, useful, cost-effective tool for detecting melanoma in family medicine.^1-4 The device, which allows the physician to visualize structures below the stratum corneum that are not routinely discernible with the naked eye, can be attached to a smartphone so that photos can be taken and reviewed with the patient. The photo can also be reviewed after a biopsy result is obtained.

Its use among non-dermatologist US physicians appears to be relatively low, but rising. One small study of physicians working in family medicine, internal medicine, and plastic surgery found that only 15% had ever used a dermatoscope and 6% were currently using one.⁵

As a family physician, you can expand your diagnostic abilities in dermatology with the acquisition of a dermatoscope (FIGURE 1) and some time invested in learning to interpret visible patterns. With that in mind, this review focuses on the diagnosis of skin cancers and benign growths using dermoscopy. We begin with a brief look at the research on dermoscopy and how it is performed. From there, we’ll detail an algorithm to guide dermoscopic analysis. And to round things out, we provide guidance that will help you to get started. (See “Choosing a dermatoscope—and making the most of it,” and “To learn more about dermoscopy …”.)

Continue to: What the research says

Dermoscopy improves sensitivity for detecting melanoma over the naked eye alone; it also allows for the detection of melanoma at earlier stages, which improves prognosis.⁶

A meta-analysis of dermoscopy use in clinical settings showed that, following training, dermoscopy increases the average sensitivity of melanoma diagnosis from 71% to more than 90% without a significant decrease in specificity.⁷ In a study of 74 primary care physicians, there was an improvement in both clinical and dermoscopic diagnosis of melanoma among those who received training in dermoscopy, compared with a control group.⁸ Another study found that primary care physicians can reduce their baseline benign-to-melanoma ratio (the number of suspicious benign lesions biopsied to find 1 melanoma) from 9.5:1 with naked eye examination to 3.5:1 with dermoscopy.⁹

The exam begins by choosing 1 of 3 modes of dermoscopy

Dermatoscopes can have a polarized or nonpolarized light source. Some dermatoscopes combine both types of light (hybrid dermatoscopes; see “Choosing a dermatoscope—and making the most of it.”)

There are 3 modes of dermoscopy:

1. nonpolarized contact dermoscopy
2. polarized contact dermoscopy
3. polarized non-contact dermoscopy.

Dermatoscopes with nonpolarized light require direct skin contact and a liquid interface (eg, alcohol, gel, mineral oil) between the scope’s glass plate and the skin for the visualization of subsurface structures. In contrast, dermatoscopes with polarized light do not require direct skin contact or a liquid interface; however, contacting the skin and using a liquid interface will provide a sharper image.

Continue to: Two major algorithms guide dermoscopic analysis

The first of 2 major algorithms that can be used to guide dermoscopic analysis is a modified pattern analysis put forth by Kittler.¹⁰ This descriptive system based on geometric elements, patterns, colors, and clues guides the observer to a specific diagnosis without categorizing lesions as being either melanocytic or nonmelanocytic. Because this is not the preferred method of the authors, we will move on to Method 2.

The second method, a 2-step algorithm, is a qualitative system that guides the observer through differentiating melanocytic from nonmelanocytic lesions in order to differentiate nevi from melanoma (FIGURE 2). At the same time, it serves as an aid to correctly diagnose non-melanocytic lesions. The 2-step algorithm forms the foundation for the dermoscopic evaluation of skin lesions in this article.

Not all expert dermoscopists employ structured analytical systems or methods to reach a diagnosis. Because of their vast experience, many rely purely on pattern recognition. But algorithms can facilitate non-experts in dermoscopy in the differentiation of nevi from melanoma or, simply, in differentiating the benign from the malignant.

Although each algorithm has its unique criteria, all of them require training and practice and familiarity with the terms used to describe morphologic structures. The International Dermoscopy Society recently published a consensus paper designating some terms as preferred over others.¹¹

Continue to: Step 1...

Step 1 of the 2-step algorithm requires the observer to determine whether the lesion is melanocytic (ie, originates from melanocytes and, therefore, could be a melanoma) or nonmelanocytic in origin.

A melanocytic lesion usually will display at least 1 of the following structures:

• pigment network (FIGURE 3A) (This can include angulated lines.)
• negative network (FIGURE 3B) (hypopigmented lines connecting pigmented structures in a serpiginous fashion)
• streaks (FIGURE 3C)
• homogeneous blue pigmentation (FIGURE 3D)
• globules (aggregated or as a peripheral rim) (FIGURE 3E)
• pseudonetwork (facial skin) (FIGURE 3F)
• parallel pigment pattern (acral lesions) (FIGURE 3G).

Exceptions. Sometimes, nonmelanocytic lesions will present with pigment network. Dermatofibromas, for example, are one exception in which the pattern trumps the network. Two other exceptions are solar lentigo and supernumerary or accessory nipple.

If the lesion does not display any structure, it is considered structureless. In these cases, proceed to the second step to rule out a melanoma.

Doesn’t meet criteria for a melanocytic lesion?

If the lesion does not reveal any of the criteria for a melanocytic lesion, then look for structures seen in nonmelanocytic lesions: dermatofibromas; seborrheic keratosis; angiomas and angiokeratomas; sebaceous hyperplasia; clear-cell acanthomas; basal cell carcinomas (BCCs); and squamous cell carcinomas (SCCs).

Continue to: Benign nonmelanocytic lesions

Dermatofibromas are benign symmetric lesions that feel firm and may dimple upon application of lateral pressure. They are fibrotic scar-like lesions that present with 1 or more of the following dermoscopic features (FIGURE 4):

• peripheral pigment network, due to increased melanin in keratinocytes
• homogeneous brown pigmented areas
• central scar-like area
• shiny white lines
• vascular structures (ie, dotted, polymorphous vessels), usually seen within the scar-like area
• ring-like globules, usually seen in the zone between the scar-like depigmentation and the peripheral network. They correspond to widened hyperpigmented rete ridges.

Seborrheic keratosis (SK) is a benign skin growth that often has a stuck-on appearance (FIGURE 5). Features often include:

• multiple (>2) milia-like cysts
• comedo-like openings
• a network-like structure that corresponds to gyri and sulci and which in some cases can create a cerebriform pattern
• fingerprint-like structures
• moth-eaten borders
• jelly sign. This consists of semicircular u-shaped structures that have a smudged appearance and are aligned in the same direction. The appearance resembles jelly as it is spread on a piece of bread.
• hairpin (looped or twisted-looped) vessels surrounded by a white halo.

Other clues include a sharp demarcation and a negative wobble sign (which we’ll describe in a moment). The presence or absence of a wobble sign is determined by using a dermatoscope that touches the skin. Mild vertical pressure is applied to the lesion while moving the scope back and forth horizontally. If the lesion slides across the skin surface, the diagnosis of an epidermal keratinocytic tumor (ie, SK) is favored. If, on the other hand, the lesion wobbles (rolls back and forth), then the diagnosis of a neoplasm with a dermal component (ie, intradermal or compound nevus) is more likely.

Angiomas and angiokeratomas. Angiomas demonstrate lacunae that are often separated by septae (FIGURE 6). Lacunae can vary in size and color. They can be red, red-white, red-blue, maroon, blue, blue-black, or even black (when thrombosis is present).

Angiokeratomas (FIGURE 7) can reveal lacunae of varying colors including black, red, purple, and maroon. In addition, a blue-whitish veil, erythema, and hemorrhagic crusts can be present.

Continue to: Sebaceous hyperplasia...

Sebaceous hyperplasia is the overgrowth of sebaceous glands. It can mimic BCC on the face. Sebaceous hyperplasia presents with multiple vessels in a crown-like arrangement that do not cross the center of the lesion. The sebaceous glands resemble popcorn (FIGURE 8).

Clear-cell acanthoma is a benign erythematous epidermal tumor usually found on the leg with a string-of-pearls pattern. This pattern is vascular so the pearls are red in color (FIGURE 9).

Malignant nonmelanocytic lesions

BCC is the most common type of skin cancer. Features often include:

• spoke-wheel-like structures or concentric structures (FIGURE 10A)
• leaf-like areas (FIGURE 10B)
• arborizing vessels (FIGURE 10b and 10C)large blue-gray ovoid nest (FIGURE 10A)
• multiple blue-gray non-aggregated globules
• ulceration or multiple small erosions
• shiny white structures and strands (FIGURE 10C).

Additional dermoscopic clues include short, fine, superficial telangiectasias and multiple in-focus dots in a buck-shot scatter distribution.

Squamous cell carcinomas (SCCs) of the skin are keratinizing malignant tumors. Each SCC generally has some of the following features (FIGURE 11):

• dotted and/or glomerular vessels, commonly distributed focally at the periphery. They can also be diffuse or aligned linearly within the lesion.
• scale (yellow or white)
• rosettes (seen with polarized light)
• white circles or keratin pearls
• brown circles
• ulcerations
• brown dots or globules arranged in a linear configuration.

Continue to: Step 2...

Step 2: It’s melanocytic, but is it a nevus or a melanoma?

If, by following Step 1 of the algorithm, the lesion is determined to be of melanocytic origin, then one proceeds to Step 2 to decide whether the growth is a nevus, a suspicious lesion, or a melanoma. For this purpose, several additional algorithms are available.^12-17

Benign nevi tend to manifest with 1 of the following 10 patterns: (FIGURE 12)

1. diffuse reticular
2. patchy reticular
3. peripheral reticular with central hypopigmentation
4. peripheral reticular with central hyperpigmentation
5. homogeneous
6. peripheral globules/starburst. It has been suggested that lesions that show starburst morphology on dermoscopy require complete excision and follow-up since 13% of Spitzoid-looking symmetric lesions in patients older than 12 years were found to be melanoma in one study.¹⁸
7. peripheral reticular with central globules
8. globular
9. 2-component
10. symmetric multicomponent (this pattern should be interpreted with caution, and a biopsy is probably warranted for dermoscopic novices).

Melanomas tend to deviate from the benign patterns described earlier. Structures in melanomas are often distributed in an asymmetric fashion (which is the basis for diagnosis in many of the other algorithms), and most of them will reveal 1 or more of the melanoma-specific structures (FIGURE 13). The melanomas in FIGURES 14 A-H each show at least 2 melanoma-specific structures. On the face or sun-damaged skin, melanoma may present with grey color, a circle-in-circle pattern, and/or polygonal lines (FIGURE 15). Note that melanoma on the soles or palms may present with a parallel ridge pattern (FIGURE 16).

How to proceed after the evaluation of melanocytic lesions

After evaluating the lesion for benign patterns and melanoma-specific structures, there are 3 possible pathways:

1. The lesion adheres to one of the nevi patterns and does not display a melanoma-specific structure. You can reassure the patient that the lesion is benign.

2. The lesion:

A. Adheres to one nevus pattern, but also displays a melanoma-specific structure.

B. Does not adhere to any of the benign patterns and does not have any melanoma-specific structures.

This is considered a suspicious lesion, and the choices of action include performing a biopsy or short-term monitoring by comparing dermoscopic images over a 3-month interval. (Caveat: Never monitor raised lesions because nodular melanomas can grow quickly and develop a worsened prognosis in a short time. Instead you’ll want to biopsy the lesion that day or very soon thereafter.)

3. The lesion deviates from the benign patterns and has at least 1 melanoma-specific structure. Biopsy the lesion to rule out melanoma.

Continue to: A bonus...

Increasingly, dermoscopy is being used in the diagnosis of many other skin, nail, and hair problems. In fact, one great bonus to owning a dermatoscope is the accurate diagnosis of scabies. Dermoscopy can be helpful in detecting the scabies mite without having to scrape and use the microscope. Moreover, the sensitivity and specificity of a dermoscopic diagnosis is higher than for scraping and microscopy.¹⁹

What you’ll see

The anterior legs and mouth parts of the mite resemble a triangle (arrowhead, delta-wing jet) (FIGURE 17). Look for a burrow, and the mite can be seen at the end of the burrow as a faint circle with a leading darker triangle. The burrow itself has a distinctive pattern that has more morphology than an excoriation and has been described as the contrail of a jet plane. Using a dermatoscope attached to your smartphone allows you to magnify the image even further while maintaining a safe distance from the mite.

Dermoscopy, the use of a handheld instrument to magnify the skin 10-fold while providing a light source, is a quick, useful, cost-effective tool for detecting melanoma in family medicine.^1-4 The device, which allows the physician to visualize structures below the stratum corneum that are not routinely discernible with the naked eye, can be attached to a smartphone so that photos can be taken and reviewed with the patient. The photo can also be reviewed after a biopsy result is obtained.

Its use among non-dermatologist US physicians appears to be relatively low, but rising. One small study of physicians working in family medicine, internal medicine, and plastic surgery found that only 15% had ever used a dermatoscope and 6% were currently using one.⁵

As a family physician, you can expand your diagnostic abilities in dermatology with the acquisition of a dermatoscope (FIGURE 1) and some time invested in learning to interpret visible patterns. With that in mind, this review focuses on the diagnosis of skin cancers and benign growths using dermoscopy. We begin with a brief look at the research on dermoscopy and how it is performed. From there, we’ll detail an algorithm to guide dermoscopic analysis. And to round things out, we provide guidance that will help you to get started. (See “Choosing a dermatoscope—and making the most of it,” and “To learn more about dermoscopy …”.)

Continue to: What the research says

Dermoscopy improves sensitivity for detecting melanoma over the naked eye alone; it also allows for the detection of melanoma at earlier stages, which improves prognosis.⁶

A meta-analysis of dermoscopy use in clinical settings showed that, following training, dermoscopy increases the average sensitivity of melanoma diagnosis from 71% to more than 90% without a significant decrease in specificity.⁷ In a study of 74 primary care physicians, there was an improvement in both clinical and dermoscopic diagnosis of melanoma among those who received training in dermoscopy, compared with a control group.⁸ Another study found that primary care physicians can reduce their baseline benign-to-melanoma ratio (the number of suspicious benign lesions biopsied to find 1 melanoma) from 9.5:1 with naked eye examination to 3.5:1 with dermoscopy.⁹

The exam begins by choosing 1 of 3 modes of dermoscopy

Dermatoscopes can have a polarized or nonpolarized light source. Some dermatoscopes combine both types of light (hybrid dermatoscopes; see “Choosing a dermatoscope—and making the most of it.”)

There are 3 modes of dermoscopy:

1. nonpolarized contact dermoscopy
2. polarized contact dermoscopy
3. polarized non-contact dermoscopy.

Dermatoscopes with nonpolarized light require direct skin contact and a liquid interface (eg, alcohol, gel, mineral oil) between the scope’s glass plate and the skin for the visualization of subsurface structures. In contrast, dermatoscopes with polarized light do not require direct skin contact or a liquid interface; however, contacting the skin and using a liquid interface will provide a sharper image.

Continue to: Two major algorithms guide dermoscopic analysis

The first of 2 major algorithms that can be used to guide dermoscopic analysis is a modified pattern analysis put forth by Kittler.¹⁰ This descriptive system based on geometric elements, patterns, colors, and clues guides the observer to a specific diagnosis without categorizing lesions as being either melanocytic or nonmelanocytic. Because this is not the preferred method of the authors, we will move on to Method 2.

The second method, a 2-step algorithm, is a qualitative system that guides the observer through differentiating melanocytic from nonmelanocytic lesions in order to differentiate nevi from melanoma (FIGURE 2). At the same time, it serves as an aid to correctly diagnose non-melanocytic lesions. The 2-step algorithm forms the foundation for the dermoscopic evaluation of skin lesions in this article.

Not all expert dermoscopists employ structured analytical systems or methods to reach a diagnosis. Because of their vast experience, many rely purely on pattern recognition. But algorithms can facilitate non-experts in dermoscopy in the differentiation of nevi from melanoma or, simply, in differentiating the benign from the malignant.

Although each algorithm has its unique criteria, all of them require training and practice and familiarity with the terms used to describe morphologic structures. The International Dermoscopy Society recently published a consensus paper designating some terms as preferred over others.¹¹

Continue to: Step 1...

Step 1 of the 2-step algorithm requires the observer to determine whether the lesion is melanocytic (ie, originates from melanocytes and, therefore, could be a melanoma) or nonmelanocytic in origin.

A melanocytic lesion usually will display at least 1 of the following structures:

• pigment network (FIGURE 3A) (This can include angulated lines.)
• negative network (FIGURE 3B) (hypopigmented lines connecting pigmented structures in a serpiginous fashion)
• streaks (FIGURE 3C)
• homogeneous blue pigmentation (FIGURE 3D)
• globules (aggregated or as a peripheral rim) (FIGURE 3E)
• pseudonetwork (facial skin) (FIGURE 3F)
• parallel pigment pattern (acral lesions) (FIGURE 3G).

Exceptions. Sometimes, nonmelanocytic lesions will present with pigment network. Dermatofibromas, for example, are one exception in which the pattern trumps the network. Two other exceptions are solar lentigo and supernumerary or accessory nipple.

If the lesion does not display any structure, it is considered structureless. In these cases, proceed to the second step to rule out a melanoma.

Doesn’t meet criteria for a melanocytic lesion?

If the lesion does not reveal any of the criteria for a melanocytic lesion, then look for structures seen in nonmelanocytic lesions: dermatofibromas; seborrheic keratosis; angiomas and angiokeratomas; sebaceous hyperplasia; clear-cell acanthomas; basal cell carcinomas (BCCs); and squamous cell carcinomas (SCCs).

Continue to: Benign nonmelanocytic lesions

Dermatofibromas are benign symmetric lesions that feel firm and may dimple upon application of lateral pressure. They are fibrotic scar-like lesions that present with 1 or more of the following dermoscopic features (FIGURE 4):

• peripheral pigment network, due to increased melanin in keratinocytes
• homogeneous brown pigmented areas
• central scar-like area
• shiny white lines
• vascular structures (ie, dotted, polymorphous vessels), usually seen within the scar-like area
• ring-like globules, usually seen in the zone between the scar-like depigmentation and the peripheral network. They correspond to widened hyperpigmented rete ridges.

Seborrheic keratosis (SK) is a benign skin growth that often has a stuck-on appearance (FIGURE 5). Features often include:

• multiple (>2) milia-like cysts
• comedo-like openings
• a network-like structure that corresponds to gyri and sulci and which in some cases can create a cerebriform pattern
• fingerprint-like structures
• moth-eaten borders
• jelly sign. This consists of semicircular u-shaped structures that have a smudged appearance and are aligned in the same direction. The appearance resembles jelly as it is spread on a piece of bread.
• hairpin (looped or twisted-looped) vessels surrounded by a white halo.

Other clues include a sharp demarcation and a negative wobble sign (which we’ll describe in a moment). The presence or absence of a wobble sign is determined by using a dermatoscope that touches the skin. Mild vertical pressure is applied to the lesion while moving the scope back and forth horizontally. If the lesion slides across the skin surface, the diagnosis of an epidermal keratinocytic tumor (ie, SK) is favored. If, on the other hand, the lesion wobbles (rolls back and forth), then the diagnosis of a neoplasm with a dermal component (ie, intradermal or compound nevus) is more likely.

Angiomas and angiokeratomas. Angiomas demonstrate lacunae that are often separated by septae (FIGURE 6). Lacunae can vary in size and color. They can be red, red-white, red-blue, maroon, blue, blue-black, or even black (when thrombosis is present).

Angiokeratomas (FIGURE 7) can reveal lacunae of varying colors including black, red, purple, and maroon. In addition, a blue-whitish veil, erythema, and hemorrhagic crusts can be present.

Continue to: Sebaceous hyperplasia...

Sebaceous hyperplasia is the overgrowth of sebaceous glands. It can mimic BCC on the face. Sebaceous hyperplasia presents with multiple vessels in a crown-like arrangement that do not cross the center of the lesion. The sebaceous glands resemble popcorn (FIGURE 8).

Clear-cell acanthoma is a benign erythematous epidermal tumor usually found on the leg with a string-of-pearls pattern. This pattern is vascular so the pearls are red in color (FIGURE 9).

Malignant nonmelanocytic lesions

BCC is the most common type of skin cancer. Features often include:

• spoke-wheel-like structures or concentric structures (FIGURE 10A)
• leaf-like areas (FIGURE 10B)
• arborizing vessels (FIGURE 10b and 10C)large blue-gray ovoid nest (FIGURE 10A)
• multiple blue-gray non-aggregated globules
• ulceration or multiple small erosions
• shiny white structures and strands (FIGURE 10C).

Additional dermoscopic clues include short, fine, superficial telangiectasias and multiple in-focus dots in a buck-shot scatter distribution.

Squamous cell carcinomas (SCCs) of the skin are keratinizing malignant tumors. Each SCC generally has some of the following features (FIGURE 11):

• dotted and/or glomerular vessels, commonly distributed focally at the periphery. They can also be diffuse or aligned linearly within the lesion.
• scale (yellow or white)
• rosettes (seen with polarized light)
• white circles or keratin pearls
• brown circles
• ulcerations
• brown dots or globules arranged in a linear configuration.

Continue to: Step 2...

Step 2: It’s melanocytic, but is it a nevus or a melanoma?

If, by following Step 1 of the algorithm, the lesion is determined to be of melanocytic origin, then one proceeds to Step 2 to decide whether the growth is a nevus, a suspicious lesion, or a melanoma. For this purpose, several additional algorithms are available.^12-17

Benign nevi tend to manifest with 1 of the following 10 patterns: (FIGURE 12)

1. diffuse reticular
2. patchy reticular
3. peripheral reticular with central hypopigmentation
4. peripheral reticular with central hyperpigmentation
5. homogeneous
6. peripheral globules/starburst. It has been suggested that lesions that show starburst morphology on dermoscopy require complete excision and follow-up since 13% of Spitzoid-looking symmetric lesions in patients older than 12 years were found to be melanoma in one study.¹⁸
7. peripheral reticular with central globules
8. globular
9. 2-component
10. symmetric multicomponent (this pattern should be interpreted with caution, and a biopsy is probably warranted for dermoscopic novices).

Melanomas tend to deviate from the benign patterns described earlier. Structures in melanomas are often distributed in an asymmetric fashion (which is the basis for diagnosis in many of the other algorithms), and most of them will reveal 1 or more of the melanoma-specific structures (FIGURE 13). The melanomas in FIGURES 14 A-H each show at least 2 melanoma-specific structures. On the face or sun-damaged skin, melanoma may present with grey color, a circle-in-circle pattern, and/or polygonal lines (FIGURE 15). Note that melanoma on the soles or palms may present with a parallel ridge pattern (FIGURE 16).

How to proceed after the evaluation of melanocytic lesions

After evaluating the lesion for benign patterns and melanoma-specific structures, there are 3 possible pathways:

1. The lesion adheres to one of the nevi patterns and does not display a melanoma-specific structure. You can reassure the patient that the lesion is benign.

2. The lesion:

A. Adheres to one nevus pattern, but also displays a melanoma-specific structure.

B. Does not adhere to any of the benign patterns and does not have any melanoma-specific structures.

This is considered a suspicious lesion, and the choices of action include performing a biopsy or short-term monitoring by comparing dermoscopic images over a 3-month interval. (Caveat: Never monitor raised lesions because nodular melanomas can grow quickly and develop a worsened prognosis in a short time. Instead you’ll want to biopsy the lesion that day or very soon thereafter.)

3. The lesion deviates from the benign patterns and has at least 1 melanoma-specific structure. Biopsy the lesion to rule out melanoma.

Continue to: A bonus...

Increasingly, dermoscopy is being used in the diagnosis of many other skin, nail, and hair problems. In fact, one great bonus to owning a dermatoscope is the accurate diagnosis of scabies. Dermoscopy can be helpful in detecting the scabies mite without having to scrape and use the microscope. Moreover, the sensitivity and specificity of a dermoscopic diagnosis is higher than for scraping and microscopy.¹⁹

What you’ll see

The anterior legs and mouth parts of the mite resemble a triangle (arrowhead, delta-wing jet) (FIGURE 17). Look for a burrow, and the mite can be seen at the end of the burrow as a faint circle with a leading darker triangle. The burrow itself has a distinctive pattern that has more morphology than an excoriation and has been described as the contrail of a jet plane. Using a dermatoscope attached to your smartphone allows you to magnify the image even further while maintaining a safe distance from the mite.

Dermoscopy, the use of a handheld instrument to magnify the skin 10-fold while providing a light source, is a quick, useful, cost-effective tool for detecting melanoma in family medicine.^1-4 The device, which allows the physician to visualize structures below the stratum corneum that are not routinely discernible with the naked eye, can be attached to a smartphone so that photos can be taken and reviewed with the patient. The photo can also be reviewed after a biopsy result is obtained.

Its use among non-dermatologist US physicians appears to be relatively low, but rising. One small study of physicians working in family medicine, internal medicine, and plastic surgery found that only 15% had ever used a dermatoscope and 6% were currently using one.⁵

As a family physician, you can expand your diagnostic abilities in dermatology with the acquisition of a dermatoscope (FIGURE 1) and some time invested in learning to interpret visible patterns. With that in mind, this review focuses on the diagnosis of skin cancers and benign growths using dermoscopy. We begin with a brief look at the research on dermoscopy and how it is performed. From there, we’ll detail an algorithm to guide dermoscopic analysis. And to round things out, we provide guidance that will help you to get started. (See “Choosing a dermatoscope—and making the most of it,” and “To learn more about dermoscopy …”.)

Continue to: What the research says

Dermoscopy improves sensitivity for detecting melanoma over the naked eye alone; it also allows for the detection of melanoma at earlier stages, which improves prognosis.⁶

A meta-analysis of dermoscopy use in clinical settings showed that, following training, dermoscopy increases the average sensitivity of melanoma diagnosis from 71% to more than 90% without a significant decrease in specificity.⁷ In a study of 74 primary care physicians, there was an improvement in both clinical and dermoscopic diagnosis of melanoma among those who received training in dermoscopy, compared with a control group.⁸ Another study found that primary care physicians can reduce their baseline benign-to-melanoma ratio (the number of suspicious benign lesions biopsied to find 1 melanoma) from 9.5:1 with naked eye examination to 3.5:1 with dermoscopy.⁹

The exam begins by choosing 1 of 3 modes of dermoscopy

Dermatoscopes can have a polarized or nonpolarized light source. Some dermatoscopes combine both types of light (hybrid dermatoscopes; see “Choosing a dermatoscope—and making the most of it.”)

There are 3 modes of dermoscopy:

1. nonpolarized contact dermoscopy
2. polarized contact dermoscopy
3. polarized non-contact dermoscopy.

Dermatoscopes with nonpolarized light require direct skin contact and a liquid interface (eg, alcohol, gel, mineral oil) between the scope’s glass plate and the skin for the visualization of subsurface structures. In contrast, dermatoscopes with polarized light do not require direct skin contact or a liquid interface; however, contacting the skin and using a liquid interface will provide a sharper image.

Continue to: Two major algorithms guide dermoscopic analysis

The first of 2 major algorithms that can be used to guide dermoscopic analysis is a modified pattern analysis put forth by Kittler.¹⁰ This descriptive system based on geometric elements, patterns, colors, and clues guides the observer to a specific diagnosis without categorizing lesions as being either melanocytic or nonmelanocytic. Because this is not the preferred method of the authors, we will move on to Method 2.

The second method, a 2-step algorithm, is a qualitative system that guides the observer through differentiating melanocytic from nonmelanocytic lesions in order to differentiate nevi from melanoma (FIGURE 2). At the same time, it serves as an aid to correctly diagnose non-melanocytic lesions. The 2-step algorithm forms the foundation for the dermoscopic evaluation of skin lesions in this article.

Not all expert dermoscopists employ structured analytical systems or methods to reach a diagnosis. Because of their vast experience, many rely purely on pattern recognition. But algorithms can facilitate non-experts in dermoscopy in the differentiation of nevi from melanoma or, simply, in differentiating the benign from the malignant.

Although each algorithm has its unique criteria, all of them require training and practice and familiarity with the terms used to describe morphologic structures. The International Dermoscopy Society recently published a consensus paper designating some terms as preferred over others.¹¹

Continue to: Step 1...

Step 1 of the 2-step algorithm requires the observer to determine whether the lesion is melanocytic (ie, originates from melanocytes and, therefore, could be a melanoma) or nonmelanocytic in origin.

A melanocytic lesion usually will display at least 1 of the following structures:

• pigment network (FIGURE 3A) (This can include angulated lines.)
• negative network (FIGURE 3B) (hypopigmented lines connecting pigmented structures in a serpiginous fashion)
• streaks (FIGURE 3C)
• homogeneous blue pigmentation (FIGURE 3D)
• globules (aggregated or as a peripheral rim) (FIGURE 3E)
• pseudonetwork (facial skin) (FIGURE 3F)
• parallel pigment pattern (acral lesions) (FIGURE 3G).

Exceptions. Sometimes, nonmelanocytic lesions will present with pigment network. Dermatofibromas, for example, are one exception in which the pattern trumps the network. Two other exceptions are solar lentigo and supernumerary or accessory nipple.

If the lesion does not display any structure, it is considered structureless. In these cases, proceed to the second step to rule out a melanoma.

Doesn’t meet criteria for a melanocytic lesion?

If the lesion does not reveal any of the criteria for a melanocytic lesion, then look for structures seen in nonmelanocytic lesions: dermatofibromas; seborrheic keratosis; angiomas and angiokeratomas; sebaceous hyperplasia; clear-cell acanthomas; basal cell carcinomas (BCCs); and squamous cell carcinomas (SCCs).

Continue to: Benign nonmelanocytic lesions

Dermatofibromas are benign symmetric lesions that feel firm and may dimple upon application of lateral pressure. They are fibrotic scar-like lesions that present with 1 or more of the following dermoscopic features (FIGURE 4):

• peripheral pigment network, due to increased melanin in keratinocytes
• homogeneous brown pigmented areas
• central scar-like area
• shiny white lines
• vascular structures (ie, dotted, polymorphous vessels), usually seen within the scar-like area
• ring-like globules, usually seen in the zone between the scar-like depigmentation and the peripheral network. They correspond to widened hyperpigmented rete ridges.

Seborrheic keratosis (SK) is a benign skin growth that often has a stuck-on appearance (FIGURE 5). Features often include:

• multiple (>2) milia-like cysts
• comedo-like openings
• a network-like structure that corresponds to gyri and sulci and which in some cases can create a cerebriform pattern
• fingerprint-like structures
• moth-eaten borders
• jelly sign. This consists of semicircular u-shaped structures that have a smudged appearance and are aligned in the same direction. The appearance resembles jelly as it is spread on a piece of bread.
• hairpin (looped or twisted-looped) vessels surrounded by a white halo.

Other clues include a sharp demarcation and a negative wobble sign (which we’ll describe in a moment). The presence or absence of a wobble sign is determined by using a dermatoscope that touches the skin. Mild vertical pressure is applied to the lesion while moving the scope back and forth horizontally. If the lesion slides across the skin surface, the diagnosis of an epidermal keratinocytic tumor (ie, SK) is favored. If, on the other hand, the lesion wobbles (rolls back and forth), then the diagnosis of a neoplasm with a dermal component (ie, intradermal or compound nevus) is more likely.

Angiomas and angiokeratomas. Angiomas demonstrate lacunae that are often separated by septae (FIGURE 6). Lacunae can vary in size and color. They can be red, red-white, red-blue, maroon, blue, blue-black, or even black (when thrombosis is present).

Angiokeratomas (FIGURE 7) can reveal lacunae of varying colors including black, red, purple, and maroon. In addition, a blue-whitish veil, erythema, and hemorrhagic crusts can be present.

Continue to: Sebaceous hyperplasia...

Sebaceous hyperplasia is the overgrowth of sebaceous glands. It can mimic BCC on the face. Sebaceous hyperplasia presents with multiple vessels in a crown-like arrangement that do not cross the center of the lesion. The sebaceous glands resemble popcorn (FIGURE 8).

Clear-cell acanthoma is a benign erythematous epidermal tumor usually found on the leg with a string-of-pearls pattern. This pattern is vascular so the pearls are red in color (FIGURE 9).

Malignant nonmelanocytic lesions

BCC is the most common type of skin cancer. Features often include:

• spoke-wheel-like structures or concentric structures (FIGURE 10A)
• leaf-like areas (FIGURE 10B)
• arborizing vessels (FIGURE 10b and 10C)large blue-gray ovoid nest (FIGURE 10A)
• multiple blue-gray non-aggregated globules
• ulceration or multiple small erosions
• shiny white structures and strands (FIGURE 10C).

Additional dermoscopic clues include short, fine, superficial telangiectasias and multiple in-focus dots in a buck-shot scatter distribution.

Squamous cell carcinomas (SCCs) of the skin are keratinizing malignant tumors. Each SCC generally has some of the following features (FIGURE 11):

• dotted and/or glomerular vessels, commonly distributed focally at the periphery. They can also be diffuse or aligned linearly within the lesion.
• scale (yellow or white)
• rosettes (seen with polarized light)
• white circles or keratin pearls
• brown circles
• ulcerations
• brown dots or globules arranged in a linear configuration.

Continue to: Step 2...

Step 2: It’s melanocytic, but is it a nevus or a melanoma?

If, by following Step 1 of the algorithm, the lesion is determined to be of melanocytic origin, then one proceeds to Step 2 to decide whether the growth is a nevus, a suspicious lesion, or a melanoma. For this purpose, several additional algorithms are available.^12-17

Benign nevi tend to manifest with 1 of the following 10 patterns: (FIGURE 12)

1. diffuse reticular
2. patchy reticular
3. peripheral reticular with central hypopigmentation
4. peripheral reticular with central hyperpigmentation
5. homogeneous
6. peripheral globules/starburst. It has been suggested that lesions that show starburst morphology on dermoscopy require complete excision and follow-up since 13% of Spitzoid-looking symmetric lesions in patients older than 12 years were found to be melanoma in one study.¹⁸
7. peripheral reticular with central globules
8. globular
9. 2-component
10. symmetric multicomponent (this pattern should be interpreted with caution, and a biopsy is probably warranted for dermoscopic novices).

Melanomas tend to deviate from the benign patterns described earlier. Structures in melanomas are often distributed in an asymmetric fashion (which is the basis for diagnosis in many of the other algorithms), and most of them will reveal 1 or more of the melanoma-specific structures (FIGURE 13). The melanomas in FIGURES 14 A-H each show at least 2 melanoma-specific structures. On the face or sun-damaged skin, melanoma may present with grey color, a circle-in-circle pattern, and/or polygonal lines (FIGURE 15). Note that melanoma on the soles or palms may present with a parallel ridge pattern (FIGURE 16).

How to proceed after the evaluation of melanocytic lesions

After evaluating the lesion for benign patterns and melanoma-specific structures, there are 3 possible pathways:

1. The lesion adheres to one of the nevi patterns and does not display a melanoma-specific structure. You can reassure the patient that the lesion is benign.

2. The lesion:

A. Adheres to one nevus pattern, but also displays a melanoma-specific structure.

B. Does not adhere to any of the benign patterns and does not have any melanoma-specific structures.

This is considered a suspicious lesion, and the choices of action include performing a biopsy or short-term monitoring by comparing dermoscopic images over a 3-month interval. (Caveat: Never monitor raised lesions because nodular melanomas can grow quickly and develop a worsened prognosis in a short time. Instead you’ll want to biopsy the lesion that day or very soon thereafter.)

3. The lesion deviates from the benign patterns and has at least 1 melanoma-specific structure. Biopsy the lesion to rule out melanoma.

Continue to: A bonus...

Increasingly, dermoscopy is being used in the diagnosis of many other skin, nail, and hair problems. In fact, one great bonus to owning a dermatoscope is the accurate diagnosis of scabies. Dermoscopy can be helpful in detecting the scabies mite without having to scrape and use the microscope. Moreover, the sensitivity and specificity of a dermoscopic diagnosis is higher than for scraping and microscopy.¹⁹

What you’ll see

The anterior legs and mouth parts of the mite resemble a triangle (arrowhead, delta-wing jet) (FIGURE 17). Look for a burrow, and the mite can be seen at the end of the burrow as a faint circle with a leading darker triangle. The burrow itself has a distinctive pattern that has more morphology than an excoriation and has been described as the contrail of a jet plane. Using a dermatoscope attached to your smartphone allows you to magnify the image even further while maintaining a safe distance from the mite.

SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).

Sharon Worcester/MDedge News

The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.

“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.

The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.

“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.

Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.


Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.

Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.

IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.

Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.

Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.

Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.

Treatment with each agent was given at intravenous doses of 375 mg/m² weekly for 4 weeks at days 1, 8, 15, and 22.

PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.

“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.

Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.

SOURCE: Sharman J et al. ASH 2018: Abstract 394.

SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).

Sharon Worcester/MDedge News

The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.

“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.

The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.

“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.

Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.


Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.

Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.

IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.

Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.

Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.

Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.

Treatment with each agent was given at intravenous doses of 375 mg/m² weekly for 4 weeks at days 1, 8, 15, and 22.

PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.

“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.

Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.

SOURCE: Sharman J et al. ASH 2018: Abstract 394.

SAN DIEGO – The potential rituximab biosimilar drug PF-05280586 showed efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics similar to those of rituximab at up to 26 weeks in a randomized phase 3 study of treatment-naive patients with CD20-positive low tumor burden follicular lymphoma (LTB-FL).

Sharon Worcester/MDedge News

The primary endpoint of overall response rate at 26 weeks was 75.5% in 196 patients randomized to receive PF-05280586, and 70.7% in 198 patients who received a rituximab reference product sourced from the European Union (MabThera; rituximab‑EU), Jeff Sharman, MD, reported at the annual meeting of the American Society of Hematology.

“This resulted in a difference between the two arms of 4.66%,” said Dr. Sharman of Willamette Valley Cancer Institute and Research Center, Springfield, Ore.

The 95% confidence interval for this difference ... was entirely contained within the prespecified equivalence margin, he said.

“Depth of response was a key secondary endpoint, and rates of complete response were 29.3% and 30.4%, respectively,” he said, noting that rates of partial response, stable response, and progressive disease were also similar between the two study arms.

Estimated 1-year progression-free survival (PFS) rates were also highly similar at 76.4% and 81.2% in the PF-05280586 and rituximab-EU arms.


Rapid depletion in CD19-positive B-cell counts was observed in both groups after initial dosing, with recovery by week 39 and a sustained increase until the end of week 52.

Treatment-emergent adverse events (TEAEs) occurred in 78.6% vs. 72.1% of patients in the PF‑05280586 vs. rituximab‑EU arms, respectively, and the rates of serious adverse events and grade 3 events were similar in the groups, as were rates of infusion interruptions or infusion-related reactions (IRRs), Dr. Sharman said.

IRRs occurred in about 25% of patients in each arm, and most were grade 1 or 2. Grade 3 IRRs occurred in 2.6% vs. 0.5% of patients in the groups, respectively, and no grade 4 IRRs occurred.

Rates of anti-drug antibodies were also similar in the two groups, as were serum drug concentrations – regardless of anti-drug antibody status, he noted.

Study subjects were adults with a mean age of 60 years and histologically confirmed CD20-positive grade 1-3a follicular lymphoma with no prior rituximab or system therapy for B-cell non-Hodgkin lymphoma (NHL). They had Ann Arbor disease stages II (26.9%), III (44.2%) or IV (28.9%), ECOG performance status of 0-1, and at least 1 measurable disease lesion identifiable on imaging.

Risk level as assessed by the Follicular Lymphoma International Prognostic Index–2 was low in 28.4%, medium in 66%, and high in 5.6% of patients.

Treatment with each agent was given at intravenous doses of 375 mg/m² weekly for 4 weeks at days 1, 8, 15, and 22.

PF-05280586 is being developed by Pfizer, and in this 52-week double-blind study – the largest study to date of the early use of the potential rituximab biosimilar in patients with previously untreated CD20-positive LTB-FL – the primary endpoint was met, demonstrating its therapeutic equivalence with rituximab-EU for overall response rate at week 26, Dr. Sharman said.

“These results therefore confirm the biosimilarity of PF-05280586 with rituximab-EU,” he concluded.

Of note, the reporting of these findings comes on the heels of the first Food and Drug Administration approval of a biosimilar rituximab product for the treatment of NHL; Celltrion’s product Truxima (formerly CT-P10), a biosimilar of Genentech’s Rituxan (rituximab), was approved Nov. 28 to treat adults with CD20-positive, B-cell NHL, either as a single agent or in combination with chemotherapy.

The PF-0528056 study was sponsored by Pfizer. Dr. Sharman has been a consultant for, and/or received research funding and honoraria from Acerta, Pharmacyclics (an AbbVie Company), Pfizer, TG Therapeutics, Abbvie, and Genentech.

SOURCE: Sharman J et al. ASH 2018: Abstract 394.