The Diagnosis: Lichenoid and Granulomatous Dermatitis in the Setting of Secondary Syphilis  

Syphilis, an infectious disease that has risen in incidence and is most commonly reported in men who have sex with men, involves a vast array of clinical and histologic presentations.¹ Clinically, secondary syphilis involves an erythematous maculopapular eruption on the face, trunk, palms, soles, or genital area.² The characteristic histologic features for secondary syphilis include endothelial swelling, interstitial inflammatory array, irregular acanthosis, elongated rete ridges, and vacuolar interface dermatitis with lymphocytes and plasma cells.¹ Syphilitic infection has been associated with lichenoid and granulomatous dermatitis, which is an inflammatory skin disease described by Magro and Crowson.³ Lichenoid and granulomatous dermatitis has been linked to various systemic disorders, including chronic hepatitis C, Crohn disease, rheumatoid arthritis, endocrinopathy, subacute cutaneous lupus erythematosus, secondary syphilis, prior herpes infection, tuberculoid leprosy, mycobacterial infection, and human immunodeficiency virus infection.^3-7 For this patient, given histopathology findings, clinical presentation, and positive rapid plasma reagin serologies, a diagnosis of lichenoid and granulomatous dermatitis in the setting of a secondary syphilis infection was established. A comprehensive investigation should be conducted to consider secondary syphilis or other systemic diseases in patients with a histologic finding of lichenoid and granulomatous dermatitis. 

Histologically, lichenoid and granulomatous dermatitis cases show a bandlike infiltrate of lymphocytes with neighboring histiocytes along the dermoepidermal junction, accompanied by epithelial changes of dyskeratosis, vasculopathy, and colloid body formation, in addition to a dermal histiocytic component.³ Our patient's biopsy showed a lichenoid reaction pattern with vacuolar interface changes, dyskeratosis, plump endothelial cells, and small collections of plasma cells. Additionally, there was a granulomatous component in the dermis with histiocytes admixed with lymphocytes and plasma cells. The presence of spirochetes was confirmed with antitreponemal immunohistochemical stain (Figure 1). Quantitative rapid plasma reagin was 1:64 (reference range, <1:1) and Treponema pallidum antibody was reactive. 

Interstitial granulomatous dermatitis has a variable clinical presentation, often with red-purple annular plaques, hyperpigmented papules, and nodules frequently in a linear arrangement and predominantly on the trunk, thighs, groin, or buttocks.^8,9 On histopathology, there are histiocytes in the reticular dermis and/or a macrophage infiltrate in the mid to deep dermis with collections of degenerated collagen (Figure 2).^8,10 An interstitial infiltrate of eosinophils and neutrophils also may be appreciated, but mucin generally is absent.^8,11 This condition often coexists with rheumatic and systemic autoimmune diseases.^8-10  

Interstitial granuloma annulare is a noninfectious granulomatous skin condition that often presents clinically as asymptomatic annular red-brown patches, usually on the extremities.^11-13 On histopathology, an interstitial or palisaded inflammatory infiltrate with histiocytes and multinucleated giant cells may be seen along with collagen degeneration or collagen bundles without necrosis (Figure 3).⁹ Mucin often is associated with the histiocytes.¹¹ Of note, our patient's skin biopsy shows interface dermatitis, differentiating it from both interstitial granuloma annulare and interstitial granulomatous dermatitis. 

Postviral granulomatous reactions are the most frequently reported types of reactions to occur at the location of herpes zoster infection up to years after the initial disease. Wolf isotopic reaction encompasses skin reactions in the body region of formerly resolved skin disease, commonly herpesvirus infection.^14,15 This manifestation may occur due to a hypersensitivity reaction from enduring viral proteins, resident memory T cells, or local neuroimmune imbalance from herpesvirus-induced injury to dermal sensory nerve fibers.^14-17 Clinically, patients present with red-purple pruritic papules and plaques in a bandlike unilateral pattern, usually in the same region as the prior herpes infection and often accompanied by postherpetic neuralgia.^16-19 Of note, our patient's clinical findings were more diffuse than the frequently localized and often linear distribution seen in postherpetic granulomatous reaction. On histopathology, granulomatous or lichenoid tissue reaction most commonly is appreciated.¹⁵ Specifically, interstitial granulomatous dermatitis with histiocytes, lymphocytes, and multinucleated giant cells showing elastophagocytosis and an inflammatory infiltrate with lymphocytes and plasma cells around vasculature, eccrine glands, and nerves can be noted (Figure 4).¹⁹  

Lupus erythematosus is an autoimmune condition with a wide array of clinical features, including skin manifestations and systemic symptoms. Specifically, discoid lupus erythematosus presents with clearly outlined, red-pink macules or papules with scaling. Histologic features include keratotic follicular plugging, acanthosis, dermal mucin, thickening of the basement membrane zone, and dense lymphocytic infiltrate (Figure 5).²⁰  

The Diagnosis: Lichenoid and Granulomatous Dermatitis in the Setting of Secondary Syphilis  

Syphilis, an infectious disease that has risen in incidence and is most commonly reported in men who have sex with men, involves a vast array of clinical and histologic presentations.¹ Clinically, secondary syphilis involves an erythematous maculopapular eruption on the face, trunk, palms, soles, or genital area.² The characteristic histologic features for secondary syphilis include endothelial swelling, interstitial inflammatory array, irregular acanthosis, elongated rete ridges, and vacuolar interface dermatitis with lymphocytes and plasma cells.¹ Syphilitic infection has been associated with lichenoid and granulomatous dermatitis, which is an inflammatory skin disease described by Magro and Crowson.³ Lichenoid and granulomatous dermatitis has been linked to various systemic disorders, including chronic hepatitis C, Crohn disease, rheumatoid arthritis, endocrinopathy, subacute cutaneous lupus erythematosus, secondary syphilis, prior herpes infection, tuberculoid leprosy, mycobacterial infection, and human immunodeficiency virus infection.^3-7 For this patient, given histopathology findings, clinical presentation, and positive rapid plasma reagin serologies, a diagnosis of lichenoid and granulomatous dermatitis in the setting of a secondary syphilis infection was established. A comprehensive investigation should be conducted to consider secondary syphilis or other systemic diseases in patients with a histologic finding of lichenoid and granulomatous dermatitis. 

Histologically, lichenoid and granulomatous dermatitis cases show a bandlike infiltrate of lymphocytes with neighboring histiocytes along the dermoepidermal junction, accompanied by epithelial changes of dyskeratosis, vasculopathy, and colloid body formation, in addition to a dermal histiocytic component.³ Our patient's biopsy showed a lichenoid reaction pattern with vacuolar interface changes, dyskeratosis, plump endothelial cells, and small collections of plasma cells. Additionally, there was a granulomatous component in the dermis with histiocytes admixed with lymphocytes and plasma cells. The presence of spirochetes was confirmed with antitreponemal immunohistochemical stain (Figure 1). Quantitative rapid plasma reagin was 1:64 (reference range, <1:1) and Treponema pallidum antibody was reactive. 

Interstitial granulomatous dermatitis has a variable clinical presentation, often with red-purple annular plaques, hyperpigmented papules, and nodules frequently in a linear arrangement and predominantly on the trunk, thighs, groin, or buttocks.^8,9 On histopathology, there are histiocytes in the reticular dermis and/or a macrophage infiltrate in the mid to deep dermis with collections of degenerated collagen (Figure 2).^8,10 An interstitial infiltrate of eosinophils and neutrophils also may be appreciated, but mucin generally is absent.^8,11 This condition often coexists with rheumatic and systemic autoimmune diseases.^8-10  

Interstitial granuloma annulare is a noninfectious granulomatous skin condition that often presents clinically as asymptomatic annular red-brown patches, usually on the extremities.^11-13 On histopathology, an interstitial or palisaded inflammatory infiltrate with histiocytes and multinucleated giant cells may be seen along with collagen degeneration or collagen bundles without necrosis (Figure 3).⁹ Mucin often is associated with the histiocytes.¹¹ Of note, our patient's skin biopsy shows interface dermatitis, differentiating it from both interstitial granuloma annulare and interstitial granulomatous dermatitis. 

Postviral granulomatous reactions are the most frequently reported types of reactions to occur at the location of herpes zoster infection up to years after the initial disease. Wolf isotopic reaction encompasses skin reactions in the body region of formerly resolved skin disease, commonly herpesvirus infection.^14,15 This manifestation may occur due to a hypersensitivity reaction from enduring viral proteins, resident memory T cells, or local neuroimmune imbalance from herpesvirus-induced injury to dermal sensory nerve fibers.^14-17 Clinically, patients present with red-purple pruritic papules and plaques in a bandlike unilateral pattern, usually in the same region as the prior herpes infection and often accompanied by postherpetic neuralgia.^16-19 Of note, our patient's clinical findings were more diffuse than the frequently localized and often linear distribution seen in postherpetic granulomatous reaction. On histopathology, granulomatous or lichenoid tissue reaction most commonly is appreciated.¹⁵ Specifically, interstitial granulomatous dermatitis with histiocytes, lymphocytes, and multinucleated giant cells showing elastophagocytosis and an inflammatory infiltrate with lymphocytes and plasma cells around vasculature, eccrine glands, and nerves can be noted (Figure 4).¹⁹  

Lupus erythematosus is an autoimmune condition with a wide array of clinical features, including skin manifestations and systemic symptoms. Specifically, discoid lupus erythematosus presents with clearly outlined, red-pink macules or papules with scaling. Histologic features include keratotic follicular plugging, acanthosis, dermal mucin, thickening of the basement membrane zone, and dense lymphocytic infiltrate (Figure 5).²⁰  

The Diagnosis: Lichenoid and Granulomatous Dermatitis in the Setting of Secondary Syphilis  

Syphilis, an infectious disease that has risen in incidence and is most commonly reported in men who have sex with men, involves a vast array of clinical and histologic presentations.¹ Clinically, secondary syphilis involves an erythematous maculopapular eruption on the face, trunk, palms, soles, or genital area.² The characteristic histologic features for secondary syphilis include endothelial swelling, interstitial inflammatory array, irregular acanthosis, elongated rete ridges, and vacuolar interface dermatitis with lymphocytes and plasma cells.¹ Syphilitic infection has been associated with lichenoid and granulomatous dermatitis, which is an inflammatory skin disease described by Magro and Crowson.³ Lichenoid and granulomatous dermatitis has been linked to various systemic disorders, including chronic hepatitis C, Crohn disease, rheumatoid arthritis, endocrinopathy, subacute cutaneous lupus erythematosus, secondary syphilis, prior herpes infection, tuberculoid leprosy, mycobacterial infection, and human immunodeficiency virus infection.^3-7 For this patient, given histopathology findings, clinical presentation, and positive rapid plasma reagin serologies, a diagnosis of lichenoid and granulomatous dermatitis in the setting of a secondary syphilis infection was established. A comprehensive investigation should be conducted to consider secondary syphilis or other systemic diseases in patients with a histologic finding of lichenoid and granulomatous dermatitis. 

Histologically, lichenoid and granulomatous dermatitis cases show a bandlike infiltrate of lymphocytes with neighboring histiocytes along the dermoepidermal junction, accompanied by epithelial changes of dyskeratosis, vasculopathy, and colloid body formation, in addition to a dermal histiocytic component.³ Our patient's biopsy showed a lichenoid reaction pattern with vacuolar interface changes, dyskeratosis, plump endothelial cells, and small collections of plasma cells. Additionally, there was a granulomatous component in the dermis with histiocytes admixed with lymphocytes and plasma cells. The presence of spirochetes was confirmed with antitreponemal immunohistochemical stain (Figure 1). Quantitative rapid plasma reagin was 1:64 (reference range, <1:1) and Treponema pallidum antibody was reactive. 

Interstitial granulomatous dermatitis has a variable clinical presentation, often with red-purple annular plaques, hyperpigmented papules, and nodules frequently in a linear arrangement and predominantly on the trunk, thighs, groin, or buttocks.^8,9 On histopathology, there are histiocytes in the reticular dermis and/or a macrophage infiltrate in the mid to deep dermis with collections of degenerated collagen (Figure 2).^8,10 An interstitial infiltrate of eosinophils and neutrophils also may be appreciated, but mucin generally is absent.^8,11 This condition often coexists with rheumatic and systemic autoimmune diseases.^8-10  

Interstitial granuloma annulare is a noninfectious granulomatous skin condition that often presents clinically as asymptomatic annular red-brown patches, usually on the extremities.^11-13 On histopathology, an interstitial or palisaded inflammatory infiltrate with histiocytes and multinucleated giant cells may be seen along with collagen degeneration or collagen bundles without necrosis (Figure 3).⁹ Mucin often is associated with the histiocytes.¹¹ Of note, our patient's skin biopsy shows interface dermatitis, differentiating it from both interstitial granuloma annulare and interstitial granulomatous dermatitis. 

Postviral granulomatous reactions are the most frequently reported types of reactions to occur at the location of herpes zoster infection up to years after the initial disease. Wolf isotopic reaction encompasses skin reactions in the body region of formerly resolved skin disease, commonly herpesvirus infection.^14,15 This manifestation may occur due to a hypersensitivity reaction from enduring viral proteins, resident memory T cells, or local neuroimmune imbalance from herpesvirus-induced injury to dermal sensory nerve fibers.^14-17 Clinically, patients present with red-purple pruritic papules and plaques in a bandlike unilateral pattern, usually in the same region as the prior herpes infection and often accompanied by postherpetic neuralgia.^16-19 Of note, our patient's clinical findings were more diffuse than the frequently localized and often linear distribution seen in postherpetic granulomatous reaction. On histopathology, granulomatous or lichenoid tissue reaction most commonly is appreciated.¹⁵ Specifically, interstitial granulomatous dermatitis with histiocytes, lymphocytes, and multinucleated giant cells showing elastophagocytosis and an inflammatory infiltrate with lymphocytes and plasma cells around vasculature, eccrine glands, and nerves can be noted (Figure 4).¹⁹  

Lupus erythematosus is an autoimmune condition with a wide array of clinical features, including skin manifestations and systemic symptoms. Specifically, discoid lupus erythematosus presents with clearly outlined, red-pink macules or papules with scaling. Histologic features include keratotic follicular plugging, acanthosis, dermal mucin, thickening of the basement membrane zone, and dense lymphocytic infiltrate (Figure 5).²⁰  

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

rfranki@mdedge.com

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

rfranki@mdedge.com

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

rfranki@mdedge.com

Dr. John Hickner’s editorial, “Doing our part to dismantle the opioid crisis” (J Fam Pract 2019;68:308) had important inaccuracies.

The Joint Commission, for which I serve as an executive vice president, did not “dub pain assessment the ‘fifth vital sign’. ” The concept of the fifth vital sign was developed by the American Pain Society in the 1990s.¹ It gained national attention through a Veterans Health Administration initiative in 1999.² And in 2001, the Joint Commission (then the Joint Commission on Accreditation of Healthcare Organizations or JCAHO) issued its Pain Standards.

Dr. Hickner wrote that the push to assess for pain as the fifth vital sign was a central cause of the opioid epidemic; however, this is contrary to published data on the epidemic. Total opioid prescriptions had been steadily increasing in the United States for at least a decade before the Pain Standards went into effect in 2001 (FIGURE).³ Between 1991 and 1997, the number of prescriptions increased from 76 million to 97 million. The rate of increase from 1997 to 2011 appears to have been more rapid, which is likely due to the 1995 approval of the new sustained-release opioid OxyContin and the associated aggressive marketing campaigns to physicians.

Your readers should know that we, at the Joint Commission, are also “doing our part to dismantle the opioid crisis.” In 2016, we completely revised our Pain Standards, adding new criteria to help address the epidemic. Some adjustments include: requiring improved availability of nonpharmacologic therapy, encouraging engagement of patients in pain management plans, enhancing accessibility of Physician Drug Monitoring Program tools, and monitoring opioid prescribing.

David W. Baker, MD, FACP, executive vice president
The Joint Commission, Oakbrook Terrace, IL

Dr. John Hickner’s editorial, “Doing our part to dismantle the opioid crisis” (J Fam Pract 2019;68:308) had important inaccuracies.

The Joint Commission, for which I serve as an executive vice president, did not “dub pain assessment the ‘fifth vital sign’. ” The concept of the fifth vital sign was developed by the American Pain Society in the 1990s.¹ It gained national attention through a Veterans Health Administration initiative in 1999.² And in 2001, the Joint Commission (then the Joint Commission on Accreditation of Healthcare Organizations or JCAHO) issued its Pain Standards.

Dr. Hickner wrote that the push to assess for pain as the fifth vital sign was a central cause of the opioid epidemic; however, this is contrary to published data on the epidemic. Total opioid prescriptions had been steadily increasing in the United States for at least a decade before the Pain Standards went into effect in 2001 (FIGURE).³ Between 1991 and 1997, the number of prescriptions increased from 76 million to 97 million. The rate of increase from 1997 to 2011 appears to have been more rapid, which is likely due to the 1995 approval of the new sustained-release opioid OxyContin and the associated aggressive marketing campaigns to physicians.

Your readers should know that we, at the Joint Commission, are also “doing our part to dismantle the opioid crisis.” In 2016, we completely revised our Pain Standards, adding new criteria to help address the epidemic. Some adjustments include: requiring improved availability of nonpharmacologic therapy, encouraging engagement of patients in pain management plans, enhancing accessibility of Physician Drug Monitoring Program tools, and monitoring opioid prescribing.

David W. Baker, MD, FACP, executive vice president
The Joint Commission, Oakbrook Terrace, IL

Dr. John Hickner’s editorial, “Doing our part to dismantle the opioid crisis” (J Fam Pract 2019;68:308) had important inaccuracies.

The Joint Commission, for which I serve as an executive vice president, did not “dub pain assessment the ‘fifth vital sign’. ” The concept of the fifth vital sign was developed by the American Pain Society in the 1990s.¹ It gained national attention through a Veterans Health Administration initiative in 1999.² And in 2001, the Joint Commission (then the Joint Commission on Accreditation of Healthcare Organizations or JCAHO) issued its Pain Standards.

Dr. Hickner wrote that the push to assess for pain as the fifth vital sign was a central cause of the opioid epidemic; however, this is contrary to published data on the epidemic. Total opioid prescriptions had been steadily increasing in the United States for at least a decade before the Pain Standards went into effect in 2001 (FIGURE).³ Between 1991 and 1997, the number of prescriptions increased from 76 million to 97 million. The rate of increase from 1997 to 2011 appears to have been more rapid, which is likely due to the 1995 approval of the new sustained-release opioid OxyContin and the associated aggressive marketing campaigns to physicians.

Your readers should know that we, at the Joint Commission, are also “doing our part to dismantle the opioid crisis.” In 2016, we completely revised our Pain Standards, adding new criteria to help address the epidemic. Some adjustments include: requiring improved availability of nonpharmacologic therapy, encouraging engagement of patients in pain management plans, enhancing accessibility of Physician Drug Monitoring Program tools, and monitoring opioid prescribing.

David W. Baker, MD, FACP, executive vice president
The Joint Commission, Oakbrook Terrace, IL

This month’s cover story addresses a phenomenon familiar to all of us: burnout. Mohanty and colleagues provide an excellent, concise summary of what burnout is, the probable causes of it, and possible solutions.

What has puzzled me about burnout is why there was no discussion of it 30 years ago when physicians worked easily as many hours but did not complain of being “burned out.” We just described ourselves as being tired. One could argue that the disconnect is due to a change in physicians’ expectations, but that theory does not hold up because burnout is common in both older and younger physicians.

No amount of yoga, mindfulness, meditation, or exercise will be sufficient to combat physician burnout.

I think that Dr. Wendy Dean, a psychiatrist at the Henry M. Jackson Foundation for the Advancement of Military Medicine, and her colleagues are correct in identifying a different culprit. They contend that the real issue is that we are “increasingly forced to consider the demands of other stakeholders—the electronic medical record (EMR), the insurers, the hospital, the health care system, even our own financial security—before the needs of our patients.”¹ To redefine the problem of burnout, Dr. Dean uses a different term to label this phenomenon of exhaustion, demoralization, and depersonalization. She calls it “moral injury.”

“Moral injury . . . describes the challenge of simultaneously knowing what care patients need but being unable to provide it due to constraints that are beyond our control.”¹

So what needs to change? No amount of yoga, mindfulness, meditation, or exercise will be sufficient, although these are great therapeutic activities. Office redesign, however, has already been shown to be highly effective in reducing physician burnout. For example, in an intensive practice redesign project in Colorado that included hiring more medical assistants, physician burnout declined from 56% to 25% in the first practice and from 40% to 0% in the second practice!²

One of the oldest examples of using team care to reduce physician burnout was implemented by Dr. Peter Anderson in 2003.³ Dr. Anderson was on the brink of throwing in the towel when he hired a second nurse and redistributed many tasks to the nurses. In a few years he had a thriving and satisfying practice for himself, his staff, and his patients.

These are only 2 examples of many successful redesign projects around the country. If you are getting burned out, change your practice, not yourself.

This month’s cover story addresses a phenomenon familiar to all of us: burnout. Mohanty and colleagues provide an excellent, concise summary of what burnout is, the probable causes of it, and possible solutions.

What has puzzled me about burnout is why there was no discussion of it 30 years ago when physicians worked easily as many hours but did not complain of being “burned out.” We just described ourselves as being tired. One could argue that the disconnect is due to a change in physicians’ expectations, but that theory does not hold up because burnout is common in both older and younger physicians.

No amount of yoga, mindfulness, meditation, or exercise will be sufficient to combat physician burnout.

I think that Dr. Wendy Dean, a psychiatrist at the Henry M. Jackson Foundation for the Advancement of Military Medicine, and her colleagues are correct in identifying a different culprit. They contend that the real issue is that we are “increasingly forced to consider the demands of other stakeholders—the electronic medical record (EMR), the insurers, the hospital, the health care system, even our own financial security—before the needs of our patients.”¹ To redefine the problem of burnout, Dr. Dean uses a different term to label this phenomenon of exhaustion, demoralization, and depersonalization. She calls it “moral injury.”

“Moral injury . . . describes the challenge of simultaneously knowing what care patients need but being unable to provide it due to constraints that are beyond our control.”¹

So what needs to change? No amount of yoga, mindfulness, meditation, or exercise will be sufficient, although these are great therapeutic activities. Office redesign, however, has already been shown to be highly effective in reducing physician burnout. For example, in an intensive practice redesign project in Colorado that included hiring more medical assistants, physician burnout declined from 56% to 25% in the first practice and from 40% to 0% in the second practice!²

One of the oldest examples of using team care to reduce physician burnout was implemented by Dr. Peter Anderson in 2003.³ Dr. Anderson was on the brink of throwing in the towel when he hired a second nurse and redistributed many tasks to the nurses. In a few years he had a thriving and satisfying practice for himself, his staff, and his patients.

These are only 2 examples of many successful redesign projects around the country. If you are getting burned out, change your practice, not yourself.

This month’s cover story addresses a phenomenon familiar to all of us: burnout. Mohanty and colleagues provide an excellent, concise summary of what burnout is, the probable causes of it, and possible solutions.

What has puzzled me about burnout is why there was no discussion of it 30 years ago when physicians worked easily as many hours but did not complain of being “burned out.” We just described ourselves as being tired. One could argue that the disconnect is due to a change in physicians’ expectations, but that theory does not hold up because burnout is common in both older and younger physicians.

No amount of yoga, mindfulness, meditation, or exercise will be sufficient to combat physician burnout.

I think that Dr. Wendy Dean, a psychiatrist at the Henry M. Jackson Foundation for the Advancement of Military Medicine, and her colleagues are correct in identifying a different culprit. They contend that the real issue is that we are “increasingly forced to consider the demands of other stakeholders—the electronic medical record (EMR), the insurers, the hospital, the health care system, even our own financial security—before the needs of our patients.”¹ To redefine the problem of burnout, Dr. Dean uses a different term to label this phenomenon of exhaustion, demoralization, and depersonalization. She calls it “moral injury.”

“Moral injury . . . describes the challenge of simultaneously knowing what care patients need but being unable to provide it due to constraints that are beyond our control.”¹

So what needs to change? No amount of yoga, mindfulness, meditation, or exercise will be sufficient, although these are great therapeutic activities. Office redesign, however, has already been shown to be highly effective in reducing physician burnout. For example, in an intensive practice redesign project in Colorado that included hiring more medical assistants, physician burnout declined from 56% to 25% in the first practice and from 40% to 0% in the second practice!²

One of the oldest examples of using team care to reduce physician burnout was implemented by Dr. Peter Anderson in 2003.³ Dr. Anderson was on the brink of throwing in the towel when he hired a second nurse and redistributed many tasks to the nurses. In a few years he had a thriving and satisfying practice for himself, his staff, and his patients.

These are only 2 examples of many successful redesign projects around the country. If you are getting burned out, change your practice, not yourself.

EVIDENCE SUMMARY

To evaluate the longstanding belief that a short IPI after miscarriage is associated with adverse outcomes in subsequent pregnancies, a 2017 systematic review and meta-­analysis of 16 studies (3 randomized controlled trials [RCTs] and 13 retrospective cohort studies) with a total of more than 1 million patients compared IPIs shorter and longer than 6 months (miscarriage was defined as any pregnancy loss ­before 24 weeks).¹ The meta-analysis included 10 of the studies (2 RCTs and 8 cohort studies), with a total of 977,972 women and excluded 6 studies because of insufficient data. The outcomes investigated were recurrent miscarriage, preterm birth, stillbirth, pre-eclampsia, and low birthweight in the pregnancy following miscarriage.

Only 1 study reported the specific gestational age of the index miscarriage at 8.6 ± 2.8 weeks.² All studies adjusted data for age, and some considered other confounders, such as race, smoking status, and body mass index (BMI).

Women included in the meta-analysis were from Asia, Europe, South America, and the United States and had a history of at least 1 miscarriage.¹ A study of 257,908 subjects (Conde-Agudelo) also included women with a history of induced abortion from Latin American countries, where abortion is illegal, and made no distinction between spontaneous and induced abortions in those data sets.³ Women with a history of illegal abortion could be at greater risk of subsequent miscarriage than women who underwent a legally performed abortion.

IPI shorter than 6 months carries fewer risks

Excluding the Conde-Agudelo study, women with an IPI < 6 months, compared with > 6 months, had lower risks of subsequent miscarriage (7 studies, 46,313 women; risk ratio [RR] = 0.82; 95% confidence interval [CI], 0.78-0.86) and preterm delivery (7 studies, 60,772 women; RR = 0.79; 95% CI, 0.75-0.83); a higher rate of live births (4 studies, 44,586 women; RR = 1.06; 95% CI, 1.01-1.11); and no increase in stillbirths (4 studies, 44,586 women; RR = 0.88; 95% CI, 0.76-1.02), low birthweight (4 studies, 284,222 women; RR = 1.05; 95% CI, 0.48-2.29) or pre-eclampsia (5 studies, 284,899 women; RR = 0.95; 95% CI, 0.88-1.02) in the subsequent pregnancy.

Including the Conde-Agudelo study, the risk of preterm delivery was the same in women with an IPI < 6 months and > 6 months (8 studies, 318,880 women; RR = 0.93; 95% CI, 0.58-1.48).¹ Four of the 10 studies evaluated the risk of miscarriage with an IPI < 3 months compared with > 3 months and found either no difference or a lower risk of subsequent miscarriage.^2,4-6

IPI shorter than 3 months has lowest risk of all

A 2017 prospective cohort study examined the association between IPI length and risk of recurrent miscarriage in 514 women who had experienced recent miscarriage (defined as spontaneous pregnancy loss before 20 weeks of gestation).⁷ Average gestational age at the time of initial miscarriage wasn’t reported. Study participants were 30 years of age on average and predominantly white (76.8%); 12.3% were black.

The authors compared IPIs of < 3 months, 3 to 6 months, and > 18 months with IPIs of 6 to 18 months, which correlates with the IPIs recommended by the World Health Organization (WHO).⁸ They adjusted for maternal age, race, parity, BMI, and education. An IPI < 3 months was associated with the lowest risk of subsequent miscarriage (7.3% compared with 22.1%; adjusted hazard ratio = 0.33; 95% CI, 0.16-0.71). Women with IPIs of 3 to 6 months and > 18 months didn’t experience statistically significant differences in subsequent miscarriage rates compared with IPIs of 6 to 18 months.⁷

Continue to: But a short IPI after second-trimester loss increases risk of miscarriage

By including all miscarriages, the meta-analysis effectively examined IPI after first-trimester loss because first-trimester loss occurs far more frequently than does second-trimester loss.¹ A retrospective cohort study of Australian women, not included in the meta-analysis, assessed 4290 patients with a second-trimester pregnancy loss to specifically examine the association between IPI and risk of recurrent pregnancy loss.⁹

After a pregnancy loss at 14 to 19 weeks, women with an IPI < 3 months, compared with an IPI of 9 to 12 months, had an increased risk of recurrent pregnancy loss (21.9 vs 11.3%; P < .001). Women with an IPI > 9 to 12 months had rates of pregnancy loss similar to an IPI of 3 to 6 months (RR = 1.24; 95% CI, 0.89-1.7) and 6 to 9 months (RR = 1.02; 95% CI, 0.7-1.5). Women who experienced an initial loss at 20 to 23 weeks, for unclear reasons, showed no evidence that the IPI affected the risk of subsequent loss.

Short IPI may be linked to anxiety in first trimester of next pregnancy

A large cohort study of 20,308 pregnant Chinese women, including 1495 with a previous miscarriage, explored the mental health impact of IPI after miscarriage compared with no miscarriage.¹⁰ Investigators used the Self-Rating Anxiety Scale to evaluate anxiety and the Center for Epidemiologic Studies Depression Scale to evaluate depression.

An interpregnancy interval of < 6 months after miscarriage is associated with a higher live birth rate in the subsequent pregnancy than a longer IPI.

Women with an IPI of < 7 months after miscarriage were more likely to experience anxiety symptoms in the subsequent pregnancy than were women with no previous miscarriage (adjusted odds ratio [AOR] = 2.76; 95% CI, 1.4-5.5), whereas women with a history of miscarriage and IPI > 6 months weren’t. Women with IPIs < 7 months and 7 to 12 months, compared with women who had no miscarriage, had an increased risk of depression (AOR = 2.5; 95% CI, 1.4-4.5, and AOR = 2.6; 95% CI, 1.3-5.2, respectively). Women with an IPI > 12 months had no increased risk of depression compared with women with no history of miscarriage.

The odds ratios were adjusted for age, education, BMI, income, and place of residence. The higher rates of depression and anxiety didn’t persist beyond the first trimester of the subsequent pregnancy.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.¹¹

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.⁸

Editor’s takeaway

High-quality evidence now shows that shorter IPIs after first-trimester miscarriages result in safe subsequent pregnancies. However, some concern remains about second-trimester miscarriages and maternal mental health following a shorter IPI, based on lower-quality evidence.

EVIDENCE SUMMARY

To evaluate the longstanding belief that a short IPI after miscarriage is associated with adverse outcomes in subsequent pregnancies, a 2017 systematic review and meta-­analysis of 16 studies (3 randomized controlled trials [RCTs] and 13 retrospective cohort studies) with a total of more than 1 million patients compared IPIs shorter and longer than 6 months (miscarriage was defined as any pregnancy loss ­before 24 weeks).¹ The meta-analysis included 10 of the studies (2 RCTs and 8 cohort studies), with a total of 977,972 women and excluded 6 studies because of insufficient data. The outcomes investigated were recurrent miscarriage, preterm birth, stillbirth, pre-eclampsia, and low birthweight in the pregnancy following miscarriage.

Only 1 study reported the specific gestational age of the index miscarriage at 8.6 ± 2.8 weeks.² All studies adjusted data for age, and some considered other confounders, such as race, smoking status, and body mass index (BMI).

Women included in the meta-analysis were from Asia, Europe, South America, and the United States and had a history of at least 1 miscarriage.¹ A study of 257,908 subjects (Conde-Agudelo) also included women with a history of induced abortion from Latin American countries, where abortion is illegal, and made no distinction between spontaneous and induced abortions in those data sets.³ Women with a history of illegal abortion could be at greater risk of subsequent miscarriage than women who underwent a legally performed abortion.

IPI shorter than 6 months carries fewer risks

Excluding the Conde-Agudelo study, women with an IPI < 6 months, compared with > 6 months, had lower risks of subsequent miscarriage (7 studies, 46,313 women; risk ratio [RR] = 0.82; 95% confidence interval [CI], 0.78-0.86) and preterm delivery (7 studies, 60,772 women; RR = 0.79; 95% CI, 0.75-0.83); a higher rate of live births (4 studies, 44,586 women; RR = 1.06; 95% CI, 1.01-1.11); and no increase in stillbirths (4 studies, 44,586 women; RR = 0.88; 95% CI, 0.76-1.02), low birthweight (4 studies, 284,222 women; RR = 1.05; 95% CI, 0.48-2.29) or pre-eclampsia (5 studies, 284,899 women; RR = 0.95; 95% CI, 0.88-1.02) in the subsequent pregnancy.

Including the Conde-Agudelo study, the risk of preterm delivery was the same in women with an IPI < 6 months and > 6 months (8 studies, 318,880 women; RR = 0.93; 95% CI, 0.58-1.48).¹ Four of the 10 studies evaluated the risk of miscarriage with an IPI < 3 months compared with > 3 months and found either no difference or a lower risk of subsequent miscarriage.^2,4-6

IPI shorter than 3 months has lowest risk of all

A 2017 prospective cohort study examined the association between IPI length and risk of recurrent miscarriage in 514 women who had experienced recent miscarriage (defined as spontaneous pregnancy loss before 20 weeks of gestation).⁷ Average gestational age at the time of initial miscarriage wasn’t reported. Study participants were 30 years of age on average and predominantly white (76.8%); 12.3% were black.

The authors compared IPIs of < 3 months, 3 to 6 months, and > 18 months with IPIs of 6 to 18 months, which correlates with the IPIs recommended by the World Health Organization (WHO).⁸ They adjusted for maternal age, race, parity, BMI, and education. An IPI < 3 months was associated with the lowest risk of subsequent miscarriage (7.3% compared with 22.1%; adjusted hazard ratio = 0.33; 95% CI, 0.16-0.71). Women with IPIs of 3 to 6 months and > 18 months didn’t experience statistically significant differences in subsequent miscarriage rates compared with IPIs of 6 to 18 months.⁷

Continue to: But a short IPI after second-trimester loss increases risk of miscarriage

By including all miscarriages, the meta-analysis effectively examined IPI after first-trimester loss because first-trimester loss occurs far more frequently than does second-trimester loss.¹ A retrospective cohort study of Australian women, not included in the meta-analysis, assessed 4290 patients with a second-trimester pregnancy loss to specifically examine the association between IPI and risk of recurrent pregnancy loss.⁹

After a pregnancy loss at 14 to 19 weeks, women with an IPI < 3 months, compared with an IPI of 9 to 12 months, had an increased risk of recurrent pregnancy loss (21.9 vs 11.3%; P < .001). Women with an IPI > 9 to 12 months had rates of pregnancy loss similar to an IPI of 3 to 6 months (RR = 1.24; 95% CI, 0.89-1.7) and 6 to 9 months (RR = 1.02; 95% CI, 0.7-1.5). Women who experienced an initial loss at 20 to 23 weeks, for unclear reasons, showed no evidence that the IPI affected the risk of subsequent loss.

Short IPI may be linked to anxiety in first trimester of next pregnancy

A large cohort study of 20,308 pregnant Chinese women, including 1495 with a previous miscarriage, explored the mental health impact of IPI after miscarriage compared with no miscarriage.¹⁰ Investigators used the Self-Rating Anxiety Scale to evaluate anxiety and the Center for Epidemiologic Studies Depression Scale to evaluate depression.

An interpregnancy interval of < 6 months after miscarriage is associated with a higher live birth rate in the subsequent pregnancy than a longer IPI.

Women with an IPI of < 7 months after miscarriage were more likely to experience anxiety symptoms in the subsequent pregnancy than were women with no previous miscarriage (adjusted odds ratio [AOR] = 2.76; 95% CI, 1.4-5.5), whereas women with a history of miscarriage and IPI > 6 months weren’t. Women with IPIs < 7 months and 7 to 12 months, compared with women who had no miscarriage, had an increased risk of depression (AOR = 2.5; 95% CI, 1.4-4.5, and AOR = 2.6; 95% CI, 1.3-5.2, respectively). Women with an IPI > 12 months had no increased risk of depression compared with women with no history of miscarriage.

The odds ratios were adjusted for age, education, BMI, income, and place of residence. The higher rates of depression and anxiety didn’t persist beyond the first trimester of the subsequent pregnancy.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.¹¹

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.⁸

Editor’s takeaway

High-quality evidence now shows that shorter IPIs after first-trimester miscarriages result in safe subsequent pregnancies. However, some concern remains about second-trimester miscarriages and maternal mental health following a shorter IPI, based on lower-quality evidence.

EVIDENCE SUMMARY

To evaluate the longstanding belief that a short IPI after miscarriage is associated with adverse outcomes in subsequent pregnancies, a 2017 systematic review and meta-­analysis of 16 studies (3 randomized controlled trials [RCTs] and 13 retrospective cohort studies) with a total of more than 1 million patients compared IPIs shorter and longer than 6 months (miscarriage was defined as any pregnancy loss ­before 24 weeks).¹ The meta-analysis included 10 of the studies (2 RCTs and 8 cohort studies), with a total of 977,972 women and excluded 6 studies because of insufficient data. The outcomes investigated were recurrent miscarriage, preterm birth, stillbirth, pre-eclampsia, and low birthweight in the pregnancy following miscarriage.

Only 1 study reported the specific gestational age of the index miscarriage at 8.6 ± 2.8 weeks.² All studies adjusted data for age, and some considered other confounders, such as race, smoking status, and body mass index (BMI).

Women included in the meta-analysis were from Asia, Europe, South America, and the United States and had a history of at least 1 miscarriage.¹ A study of 257,908 subjects (Conde-Agudelo) also included women with a history of induced abortion from Latin American countries, where abortion is illegal, and made no distinction between spontaneous and induced abortions in those data sets.³ Women with a history of illegal abortion could be at greater risk of subsequent miscarriage than women who underwent a legally performed abortion.

IPI shorter than 6 months carries fewer risks

Excluding the Conde-Agudelo study, women with an IPI < 6 months, compared with > 6 months, had lower risks of subsequent miscarriage (7 studies, 46,313 women; risk ratio [RR] = 0.82; 95% confidence interval [CI], 0.78-0.86) and preterm delivery (7 studies, 60,772 women; RR = 0.79; 95% CI, 0.75-0.83); a higher rate of live births (4 studies, 44,586 women; RR = 1.06; 95% CI, 1.01-1.11); and no increase in stillbirths (4 studies, 44,586 women; RR = 0.88; 95% CI, 0.76-1.02), low birthweight (4 studies, 284,222 women; RR = 1.05; 95% CI, 0.48-2.29) or pre-eclampsia (5 studies, 284,899 women; RR = 0.95; 95% CI, 0.88-1.02) in the subsequent pregnancy.

Including the Conde-Agudelo study, the risk of preterm delivery was the same in women with an IPI < 6 months and > 6 months (8 studies, 318,880 women; RR = 0.93; 95% CI, 0.58-1.48).¹ Four of the 10 studies evaluated the risk of miscarriage with an IPI < 3 months compared with > 3 months and found either no difference or a lower risk of subsequent miscarriage.^2,4-6

IPI shorter than 3 months has lowest risk of all

A 2017 prospective cohort study examined the association between IPI length and risk of recurrent miscarriage in 514 women who had experienced recent miscarriage (defined as spontaneous pregnancy loss before 20 weeks of gestation).⁷ Average gestational age at the time of initial miscarriage wasn’t reported. Study participants were 30 years of age on average and predominantly white (76.8%); 12.3% were black.

The authors compared IPIs of < 3 months, 3 to 6 months, and > 18 months with IPIs of 6 to 18 months, which correlates with the IPIs recommended by the World Health Organization (WHO).⁸ They adjusted for maternal age, race, parity, BMI, and education. An IPI < 3 months was associated with the lowest risk of subsequent miscarriage (7.3% compared with 22.1%; adjusted hazard ratio = 0.33; 95% CI, 0.16-0.71). Women with IPIs of 3 to 6 months and > 18 months didn’t experience statistically significant differences in subsequent miscarriage rates compared with IPIs of 6 to 18 months.⁷

Continue to: But a short IPI after second-trimester loss increases risk of miscarriage

By including all miscarriages, the meta-analysis effectively examined IPI after first-trimester loss because first-trimester loss occurs far more frequently than does second-trimester loss.¹ A retrospective cohort study of Australian women, not included in the meta-analysis, assessed 4290 patients with a second-trimester pregnancy loss to specifically examine the association between IPI and risk of recurrent pregnancy loss.⁹

After a pregnancy loss at 14 to 19 weeks, women with an IPI < 3 months, compared with an IPI of 9 to 12 months, had an increased risk of recurrent pregnancy loss (21.9 vs 11.3%; P < .001). Women with an IPI > 9 to 12 months had rates of pregnancy loss similar to an IPI of 3 to 6 months (RR = 1.24; 95% CI, 0.89-1.7) and 6 to 9 months (RR = 1.02; 95% CI, 0.7-1.5). Women who experienced an initial loss at 20 to 23 weeks, for unclear reasons, showed no evidence that the IPI affected the risk of subsequent loss.

Short IPI may be linked to anxiety in first trimester of next pregnancy

A large cohort study of 20,308 pregnant Chinese women, including 1495 with a previous miscarriage, explored the mental health impact of IPI after miscarriage compared with no miscarriage.¹⁰ Investigators used the Self-Rating Anxiety Scale to evaluate anxiety and the Center for Epidemiologic Studies Depression Scale to evaluate depression.

An interpregnancy interval of < 6 months after miscarriage is associated with a higher live birth rate in the subsequent pregnancy than a longer IPI.

Women with an IPI of < 7 months after miscarriage were more likely to experience anxiety symptoms in the subsequent pregnancy than were women with no previous miscarriage (adjusted odds ratio [AOR] = 2.76; 95% CI, 1.4-5.5), whereas women with a history of miscarriage and IPI > 6 months weren’t. Women with IPIs < 7 months and 7 to 12 months, compared with women who had no miscarriage, had an increased risk of depression (AOR = 2.5; 95% CI, 1.4-4.5, and AOR = 2.6; 95% CI, 1.3-5.2, respectively). Women with an IPI > 12 months had no increased risk of depression compared with women with no history of miscarriage.

The odds ratios were adjusted for age, education, BMI, income, and place of residence. The higher rates of depression and anxiety didn’t persist beyond the first trimester of the subsequent pregnancy.

Continue to: RECOMMENDATIONS

RECOMMENDATIONS

The American College of Obstetricians and Gynecologists’ Practice Bulletin on Early Pregnancy Loss states that no quality data exist to support delaying conception after early pregnancy loss (defined as loss of an intrauterine pregnancy in the first trimester) to prevent subsequent pregnancy loss or other pregnancy complications.¹¹

WHO recommends a minimum IPI of at least 6 months after a spontaneous or elective abortion. This recommendation is based on a single multi-center cohort study in Latin America that included women with both spontaneous and induced abortions.⁸

Editor’s takeaway

High-quality evidence now shows that shorter IPIs after first-trimester miscarriages result in safe subsequent pregnancies. However, some concern remains about second-trimester miscarriages and maternal mental health following a shorter IPI, based on lower-quality evidence.

A 52-year-old Chinese woman presented to a tertiary hospital in Singapore with a 3-month history of persistent and intermittently painful rashes over her right calf and foot (FIGURE). The patient had pancytopenia due to ongoing chemotherapy for metastatic nasopharyngeal carcinoma. She was systemically well and denied other dermatoses. Examination demonstrated scattered crops of tense hemorrhagic vesicles, each surrounded by a livid purpuric base, over the right plantar aspect of the foot, with areas of eschar over the right medial hallux. No allodynia, hyperaesthesia, or lymphadenopathy was noted.

A punch biopsy of an intact vesicle was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes zoster

Histopathologic examination showed full-thickness epidermal necrosis with ballooning degeneration resulting in an intra-epidermal blister. Multinucleated keratinocytes with nuclear moulding were seen within the blister cavity. Grocott-Gomori methenamine-silver (GMS), acid-fast, and Gram stains were negative. Granular immunoglobulin (Ig) G, IgM, and C3 were seen intramurally. DNA analysis of vesicular fluid was positive for varicella zoster virus (VZV). A diagnosis of herpes zoster (HZ) of the right S1 dermatome with primary obliterative vasculitis was established.

Immunocompromised people—those who have impaired T-cell immunity (eg, recipients of organ or hematopoietic stem-cell transplants), take immunosuppressive therapy, or have lymphoma, leukemia, or human immunodeficiency virus (HIV) infection—have an increased risk for HZ. For example, in patients with acquired immunodeficiency syndrome (AIDS), HZ uniquely manifests as recurrent shingles. An estimated 20% to 30% of HIV-infected patients will have more than 1 episode of HZ, which may involve the same or different dermatomes.^1,2 Furthermore, HZ in this population is more commonly associated with atypical presentations.³

What an atypical presentation may look like

In immunocompromised patients, HZ may present with atypical cutaneous manifestations or with atypical generalized symptoms.

Atypical cutaneous manifestations, as in disseminated zoster, manifest with multiple hyperkeratotic papules (3-20 mm in diameter) that follow no dermatomal pattern. These lesions may be chronic, persisting for months or years, and may be associated with acyclovir-resistant strains of VZV.^2,3 Another dermatologic variant is ecthymatous VZV, which manifests with multiple large (10-30 mm) punched-out ulcerations with a central black eschar and a peripheral rim of vesicles.⁴ Viral folliculitis—in which infection is limited to the hair follicle, with no associated blisters—has also been reported in atypical HZ.⁵

It’s been proposed that in atypical presentations, the reactivated VZV spreads from adjacent nerves to the outermost layer of the arterial wall, giving lesions a vasculitic appearance.

Our patient presented with hemorrhagic vesicles mimicking vasculitic lesions, which had persisted over a 3-month period with intermittent localized pain. It has been proposed that in atypical presentations, the reactivated VZV spreads transaxonally from adjacent nerves to the outermost adventitial layer of the arterial wall, leading to a vasculitic appearance of the vesicles.⁶ Viral-induced vasculitis may also result either directly from infection of the blood vessels or secondary to vascular damage from an inflammatory immune ­complex–mediated reaction, cell-­mediated hypersensitivity, or inflammation due to immune dysregulation.^7,8

Continue to: Differential includes vesiculobullous conditions

There are several important items to consider in the differential.

Cutaneous vasculitis, in severe cases, may manifest with vesicles or bullae that resemble the lesions seen in HZ. However, its unilateral nature and distribution distinguish it.

Angioinvasive fungal infections in immunocompromised patients may manifest with scattered ulceronecrotic lesions to purpuric vesiculobullous dermatoses.⁹ However, no fungal organisms were seen on GMS staining of the biopsied tissue.

Atypical hand-foot-and-mouth disease tends to affect adults and is associated with Coxsackievirus A6 infection.¹⁰ It may manifest as generalized vesiculobullous exanthem resembling varicella. The chronic nature and restricted extent of the patient’s rash made this diagnosis unlikely.

Successful management depends on timely identification

Although most cases of HZ can be diagnosed clinically, atypical rashes may require a biopsy and direct immunofluorescence assay for VZV antigen or a polymerase-chain-reaction (PCR) assay for VZV DNA in cells from the base of blisters. Therefore, it is important to consider the diagnosis of HZ in immunocompromised patients presenting with an atypical rash to avoid misdiagnosis and costly testing.

Continue to: Our patient was treated...

Our patient was treated with oral acyclovir 800 mg 5 times/day for 10 days, with prompt resolution of her rash.

CORRESPONDENCE
Joel Hua-Liang Lim, MBBS, MRCP, MMed, 1 Mandalay Road, Singapore 308205; joellimhl@nsc.com.sg

A 52-year-old Chinese woman presented to a tertiary hospital in Singapore with a 3-month history of persistent and intermittently painful rashes over her right calf and foot (FIGURE). The patient had pancytopenia due to ongoing chemotherapy for metastatic nasopharyngeal carcinoma. She was systemically well and denied other dermatoses. Examination demonstrated scattered crops of tense hemorrhagic vesicles, each surrounded by a livid purpuric base, over the right plantar aspect of the foot, with areas of eschar over the right medial hallux. No allodynia, hyperaesthesia, or lymphadenopathy was noted.

A punch biopsy of an intact vesicle was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes zoster

Histopathologic examination showed full-thickness epidermal necrosis with ballooning degeneration resulting in an intra-epidermal blister. Multinucleated keratinocytes with nuclear moulding were seen within the blister cavity. Grocott-Gomori methenamine-silver (GMS), acid-fast, and Gram stains were negative. Granular immunoglobulin (Ig) G, IgM, and C3 were seen intramurally. DNA analysis of vesicular fluid was positive for varicella zoster virus (VZV). A diagnosis of herpes zoster (HZ) of the right S1 dermatome with primary obliterative vasculitis was established.

Immunocompromised people—those who have impaired T-cell immunity (eg, recipients of organ or hematopoietic stem-cell transplants), take immunosuppressive therapy, or have lymphoma, leukemia, or human immunodeficiency virus (HIV) infection—have an increased risk for HZ. For example, in patients with acquired immunodeficiency syndrome (AIDS), HZ uniquely manifests as recurrent shingles. An estimated 20% to 30% of HIV-infected patients will have more than 1 episode of HZ, which may involve the same or different dermatomes.^1,2 Furthermore, HZ in this population is more commonly associated with atypical presentations.³

What an atypical presentation may look like

In immunocompromised patients, HZ may present with atypical cutaneous manifestations or with atypical generalized symptoms.

Atypical cutaneous manifestations, as in disseminated zoster, manifest with multiple hyperkeratotic papules (3-20 mm in diameter) that follow no dermatomal pattern. These lesions may be chronic, persisting for months or years, and may be associated with acyclovir-resistant strains of VZV.^2,3 Another dermatologic variant is ecthymatous VZV, which manifests with multiple large (10-30 mm) punched-out ulcerations with a central black eschar and a peripheral rim of vesicles.⁴ Viral folliculitis—in which infection is limited to the hair follicle, with no associated blisters—has also been reported in atypical HZ.⁵

It’s been proposed that in atypical presentations, the reactivated VZV spreads from adjacent nerves to the outermost layer of the arterial wall, giving lesions a vasculitic appearance.

Our patient presented with hemorrhagic vesicles mimicking vasculitic lesions, which had persisted over a 3-month period with intermittent localized pain. It has been proposed that in atypical presentations, the reactivated VZV spreads transaxonally from adjacent nerves to the outermost adventitial layer of the arterial wall, leading to a vasculitic appearance of the vesicles.⁶ Viral-induced vasculitis may also result either directly from infection of the blood vessels or secondary to vascular damage from an inflammatory immune ­complex–mediated reaction, cell-­mediated hypersensitivity, or inflammation due to immune dysregulation.^7,8

Continue to: Differential includes vesiculobullous conditions

There are several important items to consider in the differential.

Cutaneous vasculitis, in severe cases, may manifest with vesicles or bullae that resemble the lesions seen in HZ. However, its unilateral nature and distribution distinguish it.

Angioinvasive fungal infections in immunocompromised patients may manifest with scattered ulceronecrotic lesions to purpuric vesiculobullous dermatoses.⁹ However, no fungal organisms were seen on GMS staining of the biopsied tissue.

Atypical hand-foot-and-mouth disease tends to affect adults and is associated with Coxsackievirus A6 infection.¹⁰ It may manifest as generalized vesiculobullous exanthem resembling varicella. The chronic nature and restricted extent of the patient’s rash made this diagnosis unlikely.

Successful management depends on timely identification

Although most cases of HZ can be diagnosed clinically, atypical rashes may require a biopsy and direct immunofluorescence assay for VZV antigen or a polymerase-chain-reaction (PCR) assay for VZV DNA in cells from the base of blisters. Therefore, it is important to consider the diagnosis of HZ in immunocompromised patients presenting with an atypical rash to avoid misdiagnosis and costly testing.

Continue to: Our patient was treated...

Our patient was treated with oral acyclovir 800 mg 5 times/day for 10 days, with prompt resolution of her rash.

CORRESPONDENCE
Joel Hua-Liang Lim, MBBS, MRCP, MMed, 1 Mandalay Road, Singapore 308205; joellimhl@nsc.com.sg

A 52-year-old Chinese woman presented to a tertiary hospital in Singapore with a 3-month history of persistent and intermittently painful rashes over her right calf and foot (FIGURE). The patient had pancytopenia due to ongoing chemotherapy for metastatic nasopharyngeal carcinoma. She was systemically well and denied other dermatoses. Examination demonstrated scattered crops of tense hemorrhagic vesicles, each surrounded by a livid purpuric base, over the right plantar aspect of the foot, with areas of eschar over the right medial hallux. No allodynia, hyperaesthesia, or lymphadenopathy was noted.

A punch biopsy of an intact vesicle was performed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes zoster

Histopathologic examination showed full-thickness epidermal necrosis with ballooning degeneration resulting in an intra-epidermal blister. Multinucleated keratinocytes with nuclear moulding were seen within the blister cavity. Grocott-Gomori methenamine-silver (GMS), acid-fast, and Gram stains were negative. Granular immunoglobulin (Ig) G, IgM, and C3 were seen intramurally. DNA analysis of vesicular fluid was positive for varicella zoster virus (VZV). A diagnosis of herpes zoster (HZ) of the right S1 dermatome with primary obliterative vasculitis was established.

Immunocompromised people—those who have impaired T-cell immunity (eg, recipients of organ or hematopoietic stem-cell transplants), take immunosuppressive therapy, or have lymphoma, leukemia, or human immunodeficiency virus (HIV) infection—have an increased risk for HZ. For example, in patients with acquired immunodeficiency syndrome (AIDS), HZ uniquely manifests as recurrent shingles. An estimated 20% to 30% of HIV-infected patients will have more than 1 episode of HZ, which may involve the same or different dermatomes.^1,2 Furthermore, HZ in this population is more commonly associated with atypical presentations.³

What an atypical presentation may look like

In immunocompromised patients, HZ may present with atypical cutaneous manifestations or with atypical generalized symptoms.

Atypical cutaneous manifestations, as in disseminated zoster, manifest with multiple hyperkeratotic papules (3-20 mm in diameter) that follow no dermatomal pattern. These lesions may be chronic, persisting for months or years, and may be associated with acyclovir-resistant strains of VZV.^2,3 Another dermatologic variant is ecthymatous VZV, which manifests with multiple large (10-30 mm) punched-out ulcerations with a central black eschar and a peripheral rim of vesicles.⁴ Viral folliculitis—in which infection is limited to the hair follicle, with no associated blisters—has also been reported in atypical HZ.⁵

It’s been proposed that in atypical presentations, the reactivated VZV spreads from adjacent nerves to the outermost layer of the arterial wall, giving lesions a vasculitic appearance.

Our patient presented with hemorrhagic vesicles mimicking vasculitic lesions, which had persisted over a 3-month period with intermittent localized pain. It has been proposed that in atypical presentations, the reactivated VZV spreads transaxonally from adjacent nerves to the outermost adventitial layer of the arterial wall, leading to a vasculitic appearance of the vesicles.⁶ Viral-induced vasculitis may also result either directly from infection of the blood vessels or secondary to vascular damage from an inflammatory immune ­complex–mediated reaction, cell-­mediated hypersensitivity, or inflammation due to immune dysregulation.^7,8

Continue to: Differential includes vesiculobullous conditions

There are several important items to consider in the differential.

Cutaneous vasculitis, in severe cases, may manifest with vesicles or bullae that resemble the lesions seen in HZ. However, its unilateral nature and distribution distinguish it.

Angioinvasive fungal infections in immunocompromised patients may manifest with scattered ulceronecrotic lesions to purpuric vesiculobullous dermatoses.⁹ However, no fungal organisms were seen on GMS staining of the biopsied tissue.

Atypical hand-foot-and-mouth disease tends to affect adults and is associated with Coxsackievirus A6 infection.¹⁰ It may manifest as generalized vesiculobullous exanthem resembling varicella. The chronic nature and restricted extent of the patient’s rash made this diagnosis unlikely.

Successful management depends on timely identification

Although most cases of HZ can be diagnosed clinically, atypical rashes may require a biopsy and direct immunofluorescence assay for VZV antigen or a polymerase-chain-reaction (PCR) assay for VZV DNA in cells from the base of blisters. Therefore, it is important to consider the diagnosis of HZ in immunocompromised patients presenting with an atypical rash to avoid misdiagnosis and costly testing.

Continue to: Our patient was treated...

Our patient was treated with oral acyclovir 800 mg 5 times/day for 10 days, with prompt resolution of her rash.

CORRESPONDENCE
Joel Hua-Liang Lim, MBBS, MRCP, MMed, 1 Mandalay Road, Singapore 308205; joellimhl@nsc.com.sg

Making a diagnosis of a salivary gland disorder can be difficult. Common presentations, such as a painful or swollen gland, can be caused by numerous disorders of strikingly variable severity and consequences, including inflammatory, infectious, and neoplastic conditions, for which treatment can differ significantly, and referral for specialty care is sometimes necessary.

Yet it is the patient’s presentation that can aid you in making the diagnosis that will guide management. Consider that acute symptoms often result from infection, for example, and chronic or recurrent symptoms are caused more often by obstructive or nonobstructive inflammatory conditions and neoplasms. Diagnosis of an apparent neoplasm, prompted by clinical findings, is made using imaging and fine-needle aspiration (FNA) biopsy. Acute infection usually resolves with antibiotics and supportive management; calculi that cause persistent symptoms warrant referral for consideration of stone or gland removal; and malignant neoplasms usually require excision as well as neck dissection and chemotherapy or radiotherapy, or both—calling for multidisciplinary care.

In this article, we clarify what can be an imprecise and perplexing path from the presentation to diagnosis to treatment of disorders of the salivary glands. To begin, see “Geography of the salivary glands,” for an overview of the location, structure, and corresponding ducts of the component salivary glands (parotid, submandibular, sublingual, and minor glands).

SIDEBAR
Geography of the salivary glands

©Stocktreck images/Science Source

The salivary glands comprise the major paired parotid, submandibular, and sublingual glands, as well as minor salivary glands that line the oropharyngeal mucosa. Secretion of saliva is modulated by both autonomic and humoral factors.

The parotid gland sits between the mastoid process, the ramus of the mandible, and the styloid process, extend- ing from the external auditory meatus superiorly to below the angle of the mandible and into the neck inferiorly. The gland is surrounded by a tough capsule. Embedded within the gland is the facial nerve, which divides into its 5 branches within the substance of the gland. The parotid (Stensen’s) duct passes anteriorly before turning medially to pierce the buccinator muscle, opening onto the mucous membrane of the cheek opposite the second upper molar.

The submandibular gland comprises (1) a large superficial part that fills the space between the mandible and the floor of the mouth and (2) a small deep part that wraps around the posterior border of the mylohyoid muscle. The submandibular (Wharton’s) duct runs anteriorly to open onto the floor of the mouth, alongside the frenulum.

The sublingual gland, the smallest of the major salivary glands, lies anteriorly in the floor of the mouth, with many small ducts opening either into the submandibular duct or directly into the mouth.

Basic secretory units of salivary glands are clusters of cells, each called an acinus. These cells secrete a fluid that contains water, electrolytes, mucous, and enzymes, all of which flow out of the acini into collecting ducts. The saliva produced by the parotid is mainly serous; by the submandibular gland, mixed; and by the sublingual and minor salivary glands, mucoid.

Presentation helps establish the differential Dx

Ask: Are the glands swollen?

Painless salivary gland swelling has a variety of causes, including neoplasm, sialadenosis, and the eating disorders bulimia and anorexia nervosa. There is significant overlap of presentations among those causes (FIGURE). Pain accompanying swelling is uncommon but not unheard of.

Neoplasms. Tumors of the salivary gland are relatively uncommon, constituting approximately 2% of head and neck neoplasms; most (80%) occur in the parotid gland, and most of those are benign.¹ Although benign and malignant salivary gland neoplasms do not usually present with pain, pain can be associated with a neoplasm secondary to suppuration, hemorrhage into a mass, or infiltration of a malignancy into adjacent tissue.

Benign tumors. The majority of benign tumors are pleomorphic adenomas of the parotid, accounting for approximately 60% of salivary gland neoplasms.^1,2 Tumors localized to the submandibular gland are often (in 50% of cases) malignant, however.³

Ultrasonography is an excellent initial imaging choice for investigating a possible salivary gland tumor.

Benign tumors are typically slow-growing and, generally, painless. On examination, they are well-circumscribed, mobile, and nontender. Patients presenting late with a large tumor might, however, experience pain secondary to stretching of the parotid capsule or compression of local structures.

Continue to: Ultrasonograhpy (US) is an excellent...

Ultrasonography (US) is an excellent initial imaging choice for investigating a possible salivary gland tumor; US is combined with FNA, which is safe and highly reliable for differentiating neoplastic and non-neoplastic disorders.⁴ (Avoid open biopsy of a neoplasm because of the risk of tumor spillage.) In patients with suspected neoplasm, contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) should also be performed, because both modalities allow delineation of the tumor mass and demonstration of any infiltration of surrounding structures.

Treatment of benign neoplasms involves complete excision because, with some tumors, particularly pleomorphic adenomas, there is risk of malignant transformation over time. Superficial parotidectomy is the most common procedure, because most benign tumors occur in the superficial lobe of the parotid gland. Delicate dissection of the facial nerve is integral to the operation, although temporary facial nerve palsy will still occur in 5% to 10% of patients undergoing superficial parotidectomy for a benign tumor, with permanent injury occurring in fewer than 1%.⁵

Malignancy. Features of a tumor that raise concern of malignancy include⁶:

• rapid growth
• pain
• tethering to underlying structures or overlying skin
• firm mass
• associated cervical lymphadenopathy
• facial-nerve palsy.

The workup of a malignant tumor is the same as it is for a benign neoplasm: US-guided FNA, essential for diagnosis, and contrast-enhanced CT or MRI to delineate the tumor.

Malignant salivary gland neoplasms usually require excision as well as neck dissection and chemotherapy or radiotherapy, or both, necessitating a multidisciplinary approach. Also, there is potential for squamous-cell carcinoma and melanoma of the head to metastasize to salivary gland lymph nodes; it is important, therefore, to examine for, and elicit any history of, cutaneous malignancy of the scalp or face.

Continue to: Sialadenosis...

Sialadenosis presents with asymptomatic bilateral hypertrophy of the salivary glands—more commonly the parotids and rarely the submandibular glands. Swelling is persistent, symmetrical, painless, and of normal tone on palpation.

Causes of sialadenosis include alcoholism and, less commonly, diabetes mellitus and malnutrition; some cases are idiopathic. An autonomic neuropathy, causing excessive salivary acinar protein synthesis or failure of adequate secretion, or both, is common to alcoholism, diabetes, and malnutrition.⁷ Subsequent engorgement of acinar cells leads to clinical parotid hypertrophy.

Diagnosis is based on history and examination, as well as on the findings of US or CT, which will reveal bilateral gland enlargement and increased density. The glands appear dense because adipose cells are displaced by acinar cell hypertrophy; however, end-stage changes can result in the opposite appearance: a lucent enlargement caused by fatty infiltration.² FNA is unnecessary, unless there is suspicion of neoplasm, as there would be in patients with asymmetrical parotid enlargement, pain, lymph node enlargement, or facial-nerve involvement. In patients with sialadenosis, in contrast, acinar cell hypertrophy alone will be present.

Treatment of sialadenosis is best aimed at rectifying the underlying medical condition, which might, over time, lead to some reduction in the size of the gland. There is no specific effective therapy for elimination of glandular swelling.

Bulimia and anorexia nervosa. Bulimia nervosa, the induction of vomiting after binge eating, can be associated with bilateral or occasionally unilateral parotid swelling. Anorexia, a form of self-starvation, can occur in association with bulimia, with patients also presenting with parotid swelling. Associated parotid swelling is similar to what is seen in sialadenosis: painless, persistent, and of nonpathologic consistency.

The pathophysiology of bulimia- and anorexia-associated parotid-gland swelling is identical to what is seen in sialadenosis: dysregulation of acinar cell sympathetic nerve supply that leads to enlargement of individual parenchymal cells.⁸ Contrast-enhanced CT can reveal increased vascularity associated with active bulimia. FNA and CT, however, are required only in patients in whom the diagnosis is not clear and when neoplasm is suspected.

Continue to: Treatment includes...

Treatment includes correcting electrolyte abnormalities and, more importantly, addressing underlying emotional issues to stop purging episodes. Psychiatric input and social support are invaluable. Parotid gland swelling generally improves with cessation of vomiting episodes.

Ask: Is the patient in pain?

Causes of salivary gland pain include sialolithiasis, sialadenitis, and recurrent parotitis of childhood. Pain occurs secondary to stretching of the fibrous capsule in which the parotid or submandibular gland is surrounded, compression of pain fibers by an expanding mass, or infiltration of nerves by neoplasia.

Sialolithiasis. Sialolithiasis, or salivary stones, are primarily calcium carbonate concentrations within the salivary ductal system. More than 80% occur in the submandibular gland or duct⁹ as a result of production of mixed mucoid and serous saliva and a tortuous duct path.

For a submandibular duct stone, bimanual palpation might reveal its position if it’s located distally in the floor of the mouth; a proximal stone might not be palpable.

Patients usually present with a history of intermittent swelling and pain of the involved gland associated with eating. Increased production of saliva during meals, which then passes through a partially obstructed salivary duct, leads to salivary retention and glandular swelling. Thus, a recurring pattern can develop, with varying periods of remission,⁷ eventually leading to an acute suppurative process or sialadenitis (described below). Chronic salivary disease can also be caused by stricture of a duct or, rarely, external compression by a tumor mass.

Examination often reveals an enlarged and often tender gland; conversely, chronic disease can lead to gland atrophy. Usually, only minimal saliva is able to be expressed from an obstructed duct. For a submandibular duct stone, bimanual palpation might reveal its position if it is located distally in the floor of the mouth; a proximal stone might not be palpable.

Continue to: Although US is operator-dependent...

Although US is operator-dependent, it is the imaging modality of choice for identifying sialolithiasis¹⁰ because it can identify gland architecture, duct dilation, and both radiolucent and radiopaque stones. For patients in whom US findings are normal despite a convincing clinical presentation of sialolithiasis, CT should be performed because small stones can be missed on US.¹¹

Supportive measures for sialolithiasis are listed in the TABLE. Reserve antibiotics for patients who have signs or symptoms of infection, including pyrexia, trismus, and malaise. A beta-lactam antibiotic, such as amoxicillin–clavulanate, 875 mg orally bid, or a cephalosporin, such as cephalexin, 500 mg orally qid, are appropriate first-line options. Clindamycin, 300 mg orally tid, or metronidazole, 500 mg orally tid, are acceptable alternatives. When signs or symptoms are persistent or recurrent, refer the patient for a surgical opinion.

Stones located in the floor of the mouth are usually excised through an intraoral approach. In the past, gland excision was advocated when a sialolith was found more proximally within the gland parenchyma. More recently, however, sialendoscopy, involving insertion of a small, semirigid endoscope into the salivary duct, has been shown safe and effective for removing a stone; successful removal, in as many as 80% of cases, increases to 90% when performed using a minimally invasive surgical technique.¹² Although sialendoscopy is effective, the technique cannot always treat the underlying abnormality of the salivary gland; gland excision is therefore warranted in some cases.

Last, extracorporeal shock wave therapy is aimed at fragmenting salivary stones before retrieval. Results are variable, however, and treatment should be guided by an otolaryngologist.^13,14

Sialadenitis (bacterial and viral infection). Acute suppurative sialadenitis occurs secondary to retrograde ductal bacterial infection. The parotid gland is most frequently involved,¹⁵ although submandibular sialadenitis is not uncommon. Patients usually present with sudden-onset unilateral, painful swelling.

Continue to: Pathophysiology involves...

Pathophysiology involves dehydration or decreased oral intake leading to salivary stasis and subsequent bacterial migration into the gland. Medically debilitated and postoperative patients are therefore at greater risk; so are patients with diabetes mellitus, poor oral hygiene, Sjögren’s syndrome, hypothyroidism, or renal failure.¹⁶ Certain medications, including anticholinergics, can also predispose to hyposalivation.¹⁷

(As discussed, sialolithiasis and stricture of salivary ducts can also cause acute bacterial infection; in such cases, however, the typical presentation is one of chronic or recurrent infection.)

In sialolithiasis, reserve antibiotics for patients who have signs or symptoms of infection, including pyrexia, trismus, and malaise.

Examination might reveal an exquisitely tender, indurated, and inflamed gland; pus can often be expressed from the respective intraoral orifice. Any expressed pus should be sent for culture to guide antibiotic therapy.

Treatment should focus on hydration, oral hygiene, and antibiotics, while reversing or minimizing any underlying contributing medical condition. Warm compresses applied to the involved gland, massage, and sialagogues, such as lemon drops or sugar-free lollipops, can stimulate salivary flow and prevent stasis.

More than 80% of infections are caused by Staphylococcus aureus¹⁷; anaerobic and mixed infections have also been recognized.A beta-lactam penicillin, such as amoxicillin-clavulanate, is the antibiotic of choice. A patient who is systemically unwell should be treated as an inpatient with nafcillin and metronidazole. Methicillin-resistant S aureus must also be considered in patients with comorbid disease, such as diabetes mellitus or intravenous drug use, or in patients residing in an area of substantial incidence of methicillin-resistant S aureus. In those cases, substitute vancomycin or linezolid for nafcillin.¹⁸

Continue to: Less commonly...

Less commonly, abscess can form, with the patient presenting as systemically unwell with a fluctuant mass. If the diagnosis is unclear or the patient does not improve, abscess can be confirmed by US. Expedient surgical review and inpatient admission can then be arranged.

Unlike bacterial sialadenitis, causes of viral sialadenitis are often bilateral. Mumps (a paramyxovirus) is the most common viral cause, affecting primarily children < 15 years.¹⁹ The parotid glands are most often involved, with inflammation and edema causing significant pain because of increasing intraparotid pressure as expansion of the gland is limited by its tense fibrous capsule. Complications of mumps include orchitis, meningitis, pancreatitis, and oophoritis.

Mumps is highly contagious; it is spread through contact with airborne saliva droplets, with viral entry through the nose or mouth, followed by proliferation in the salivary glands or on surface epithelium of the respiratory tract.⁷ Diagnosis is confirmed by viral serology. A positive test of serum immunoglobulin M confirms the diagnosis, but this test should not be performed until 3 days after onset of symptoms because a false-negative result is otherwise possible.²⁰ Immunoglobulin G serologic testing can further aid diagnosis; the titer is measured approximately 4 days after onset of symptoms and again 2 to 3 weeks later. A 4-fold rise in titer confirms mumps.

Other viral infections that can cause sialadenitis include Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, coxsackievirus, and influenza. Treatment is supportive: analgesia, hydration, oral hygiene, and rest. Inflammation might take weeks to resolve, but expect complete resolution. For a patient who has significant trismus, poor oral intake, or a potentially threatened airway, inpatient care should be provided.

Recurrent parotitis of childhood is an inflammatory condition that usually affects one, but at times both, parotid glands. It is characterized by episodes of painful swelling. Incidence peaks at 3 to 6 years of age.⁷ Episodes can be frequent, occurring 1 to 5 times a year and lasting 3 to 7 days—sometimes longer—and usually resolving without treatment.

Continue to: The precise etiology...

The precise etiology of recurrent parotitis of childhood is unclear; possibly, saliva aggregates to form obstructive mucous plugs, thus causing stasis and swelling of the gland. As pressure builds, spontaneous plug extrusion occurs and symptoms resolve, provided infection is not a factor. US demonstrates multiple round, hypoechoic areas consistent with duct dilation, and surrounding infiltration by lymphocytes.¹

Pus can often be expressed from the respective intraoral orifice in sialadenitis. Send expressed pus for culture to guide antibiotic therapy.

Supportive care—adequate hydration, gland massage, warm compresses, and sialogogues—are mainstays of treatment. Fever and malaise warrant treatment with oral antibiotics. Sialadenoscopy, which can be considered in children with frequent episodes, can decrease the frequency and severity of episodes.²¹ The condition usually resolves spontaneously at puberty.

Ask: Does the patient have dry mouth?

In-depth review of xerostomia is beyond the scope of this article. Causes include Sjögren's syndrome, immunoglobulin G4-related sialadenitis, sarcoidosis, radiation therapy, diabetes, chronic infection, and medications—in particular those with anticholinergic effects.

Treatment of xerostomia includes saliva substitutes, sialagogues, and, for oral candidiasis, antifungals. Muscarinic cholinergic stimulators, such as pilocarpine, 5 mg qid have been used with some success²²; patients should be advised of potential adverse effects with these agents, including sweating, urinary frequency, flushing, and chills.

CORRESPONDENCE
Shankar Haran, MBBS, ENT Department, Townsville Hospital, 100 Angus Smith Dr, Douglas, Queensland, Australia 4814; Shankar.haran01@gmail.com.

Making a diagnosis of a salivary gland disorder can be difficult. Common presentations, such as a painful or swollen gland, can be caused by numerous disorders of strikingly variable severity and consequences, including inflammatory, infectious, and neoplastic conditions, for which treatment can differ significantly, and referral for specialty care is sometimes necessary.

Yet it is the patient’s presentation that can aid you in making the diagnosis that will guide management. Consider that acute symptoms often result from infection, for example, and chronic or recurrent symptoms are caused more often by obstructive or nonobstructive inflammatory conditions and neoplasms. Diagnosis of an apparent neoplasm, prompted by clinical findings, is made using imaging and fine-needle aspiration (FNA) biopsy. Acute infection usually resolves with antibiotics and supportive management; calculi that cause persistent symptoms warrant referral for consideration of stone or gland removal; and malignant neoplasms usually require excision as well as neck dissection and chemotherapy or radiotherapy, or both—calling for multidisciplinary care.

In this article, we clarify what can be an imprecise and perplexing path from the presentation to diagnosis to treatment of disorders of the salivary glands. To begin, see “Geography of the salivary glands,” for an overview of the location, structure, and corresponding ducts of the component salivary glands (parotid, submandibular, sublingual, and minor glands).

SIDEBAR
Geography of the salivary glands

©Stocktreck images/Science Source

The salivary glands comprise the major paired parotid, submandibular, and sublingual glands, as well as minor salivary glands that line the oropharyngeal mucosa. Secretion of saliva is modulated by both autonomic and humoral factors.

The parotid gland sits between the mastoid process, the ramus of the mandible, and the styloid process, extend- ing from the external auditory meatus superiorly to below the angle of the mandible and into the neck inferiorly. The gland is surrounded by a tough capsule. Embedded within the gland is the facial nerve, which divides into its 5 branches within the substance of the gland. The parotid (Stensen’s) duct passes anteriorly before turning medially to pierce the buccinator muscle, opening onto the mucous membrane of the cheek opposite the second upper molar.

The submandibular gland comprises (1) a large superficial part that fills the space between the mandible and the floor of the mouth and (2) a small deep part that wraps around the posterior border of the mylohyoid muscle. The submandibular (Wharton’s) duct runs anteriorly to open onto the floor of the mouth, alongside the frenulum.

The sublingual gland, the smallest of the major salivary glands, lies anteriorly in the floor of the mouth, with many small ducts opening either into the submandibular duct or directly into the mouth.

Basic secretory units of salivary glands are clusters of cells, each called an acinus. These cells secrete a fluid that contains water, electrolytes, mucous, and enzymes, all of which flow out of the acini into collecting ducts. The saliva produced by the parotid is mainly serous; by the submandibular gland, mixed; and by the sublingual and minor salivary glands, mucoid.

Presentation helps establish the differential Dx

Ask: Are the glands swollen?

Painless salivary gland swelling has a variety of causes, including neoplasm, sialadenosis, and the eating disorders bulimia and anorexia nervosa. There is significant overlap of presentations among those causes (FIGURE). Pain accompanying swelling is uncommon but not unheard of.

Neoplasms. Tumors of the salivary gland are relatively uncommon, constituting approximately 2% of head and neck neoplasms; most (80%) occur in the parotid gland, and most of those are benign.¹ Although benign and malignant salivary gland neoplasms do not usually present with pain, pain can be associated with a neoplasm secondary to suppuration, hemorrhage into a mass, or infiltration of a malignancy into adjacent tissue.

Benign tumors. The majority of benign tumors are pleomorphic adenomas of the parotid, accounting for approximately 60% of salivary gland neoplasms.^1,2 Tumors localized to the submandibular gland are often (in 50% of cases) malignant, however.³

Ultrasonography is an excellent initial imaging choice for investigating a possible salivary gland tumor.

Benign tumors are typically slow-growing and, generally, painless. On examination, they are well-circumscribed, mobile, and nontender. Patients presenting late with a large tumor might, however, experience pain secondary to stretching of the parotid capsule or compression of local structures.

Continue to: Ultrasonograhpy (US) is an excellent...

Ultrasonography (US) is an excellent initial imaging choice for investigating a possible salivary gland tumor; US is combined with FNA, which is safe and highly reliable for differentiating neoplastic and non-neoplastic disorders.⁴ (Avoid open biopsy of a neoplasm because of the risk of tumor spillage.) In patients with suspected neoplasm, contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) should also be performed, because both modalities allow delineation of the tumor mass and demonstration of any infiltration of surrounding structures.

Treatment of benign neoplasms involves complete excision because, with some tumors, particularly pleomorphic adenomas, there is risk of malignant transformation over time. Superficial parotidectomy is the most common procedure, because most benign tumors occur in the superficial lobe of the parotid gland. Delicate dissection of the facial nerve is integral to the operation, although temporary facial nerve palsy will still occur in 5% to 10% of patients undergoing superficial parotidectomy for a benign tumor, with permanent injury occurring in fewer than 1%.⁵

Malignancy. Features of a tumor that raise concern of malignancy include⁶:

• rapid growth
• pain
• tethering to underlying structures or overlying skin
• firm mass
• associated cervical lymphadenopathy
• facial-nerve palsy.

The workup of a malignant tumor is the same as it is for a benign neoplasm: US-guided FNA, essential for diagnosis, and contrast-enhanced CT or MRI to delineate the tumor.

Malignant salivary gland neoplasms usually require excision as well as neck dissection and chemotherapy or radiotherapy, or both, necessitating a multidisciplinary approach. Also, there is potential for squamous-cell carcinoma and melanoma of the head to metastasize to salivary gland lymph nodes; it is important, therefore, to examine for, and elicit any history of, cutaneous malignancy of the scalp or face.

Continue to: Sialadenosis...

Sialadenosis presents with asymptomatic bilateral hypertrophy of the salivary glands—more commonly the parotids and rarely the submandibular glands. Swelling is persistent, symmetrical, painless, and of normal tone on palpation.

Causes of sialadenosis include alcoholism and, less commonly, diabetes mellitus and malnutrition; some cases are idiopathic. An autonomic neuropathy, causing excessive salivary acinar protein synthesis or failure of adequate secretion, or both, is common to alcoholism, diabetes, and malnutrition.⁷ Subsequent engorgement of acinar cells leads to clinical parotid hypertrophy.

Diagnosis is based on history and examination, as well as on the findings of US or CT, which will reveal bilateral gland enlargement and increased density. The glands appear dense because adipose cells are displaced by acinar cell hypertrophy; however, end-stage changes can result in the opposite appearance: a lucent enlargement caused by fatty infiltration.² FNA is unnecessary, unless there is suspicion of neoplasm, as there would be in patients with asymmetrical parotid enlargement, pain, lymph node enlargement, or facial-nerve involvement. In patients with sialadenosis, in contrast, acinar cell hypertrophy alone will be present.

Treatment of sialadenosis is best aimed at rectifying the underlying medical condition, which might, over time, lead to some reduction in the size of the gland. There is no specific effective therapy for elimination of glandular swelling.

Bulimia and anorexia nervosa. Bulimia nervosa, the induction of vomiting after binge eating, can be associated with bilateral or occasionally unilateral parotid swelling. Anorexia, a form of self-starvation, can occur in association with bulimia, with patients also presenting with parotid swelling. Associated parotid swelling is similar to what is seen in sialadenosis: painless, persistent, and of nonpathologic consistency.

The pathophysiology of bulimia- and anorexia-associated parotid-gland swelling is identical to what is seen in sialadenosis: dysregulation of acinar cell sympathetic nerve supply that leads to enlargement of individual parenchymal cells.⁸ Contrast-enhanced CT can reveal increased vascularity associated with active bulimia. FNA and CT, however, are required only in patients in whom the diagnosis is not clear and when neoplasm is suspected.

Continue to: Treatment includes...

Treatment includes correcting electrolyte abnormalities and, more importantly, addressing underlying emotional issues to stop purging episodes. Psychiatric input and social support are invaluable. Parotid gland swelling generally improves with cessation of vomiting episodes.

Ask: Is the patient in pain?

Causes of salivary gland pain include sialolithiasis, sialadenitis, and recurrent parotitis of childhood. Pain occurs secondary to stretching of the fibrous capsule in which the parotid or submandibular gland is surrounded, compression of pain fibers by an expanding mass, or infiltration of nerves by neoplasia.

Sialolithiasis. Sialolithiasis, or salivary stones, are primarily calcium carbonate concentrations within the salivary ductal system. More than 80% occur in the submandibular gland or duct⁹ as a result of production of mixed mucoid and serous saliva and a tortuous duct path.

For a submandibular duct stone, bimanual palpation might reveal its position if it’s located distally in the floor of the mouth; a proximal stone might not be palpable.

Patients usually present with a history of intermittent swelling and pain of the involved gland associated with eating. Increased production of saliva during meals, which then passes through a partially obstructed salivary duct, leads to salivary retention and glandular swelling. Thus, a recurring pattern can develop, with varying periods of remission,⁷ eventually leading to an acute suppurative process or sialadenitis (described below). Chronic salivary disease can also be caused by stricture of a duct or, rarely, external compression by a tumor mass.

Examination often reveals an enlarged and often tender gland; conversely, chronic disease can lead to gland atrophy. Usually, only minimal saliva is able to be expressed from an obstructed duct. For a submandibular duct stone, bimanual palpation might reveal its position if it is located distally in the floor of the mouth; a proximal stone might not be palpable.

Continue to: Although US is operator-dependent...

Although US is operator-dependent, it is the imaging modality of choice for identifying sialolithiasis¹⁰ because it can identify gland architecture, duct dilation, and both radiolucent and radiopaque stones. For patients in whom US findings are normal despite a convincing clinical presentation of sialolithiasis, CT should be performed because small stones can be missed on US.¹¹

Supportive measures for sialolithiasis are listed in the TABLE. Reserve antibiotics for patients who have signs or symptoms of infection, including pyrexia, trismus, and malaise. A beta-lactam antibiotic, such as amoxicillin–clavulanate, 875 mg orally bid, or a cephalosporin, such as cephalexin, 500 mg orally qid, are appropriate first-line options. Clindamycin, 300 mg orally tid, or metronidazole, 500 mg orally tid, are acceptable alternatives. When signs or symptoms are persistent or recurrent, refer the patient for a surgical opinion.

Stones located in the floor of the mouth are usually excised through an intraoral approach. In the past, gland excision was advocated when a sialolith was found more proximally within the gland parenchyma. More recently, however, sialendoscopy, involving insertion of a small, semirigid endoscope into the salivary duct, has been shown safe and effective for removing a stone; successful removal, in as many as 80% of cases, increases to 90% when performed using a minimally invasive surgical technique.¹² Although sialendoscopy is effective, the technique cannot always treat the underlying abnormality of the salivary gland; gland excision is therefore warranted in some cases.

Last, extracorporeal shock wave therapy is aimed at fragmenting salivary stones before retrieval. Results are variable, however, and treatment should be guided by an otolaryngologist.^13,14

Sialadenitis (bacterial and viral infection). Acute suppurative sialadenitis occurs secondary to retrograde ductal bacterial infection. The parotid gland is most frequently involved,¹⁵ although submandibular sialadenitis is not uncommon. Patients usually present with sudden-onset unilateral, painful swelling.

Continue to: Pathophysiology involves...

Pathophysiology involves dehydration or decreased oral intake leading to salivary stasis and subsequent bacterial migration into the gland. Medically debilitated and postoperative patients are therefore at greater risk; so are patients with diabetes mellitus, poor oral hygiene, Sjögren’s syndrome, hypothyroidism, or renal failure.¹⁶ Certain medications, including anticholinergics, can also predispose to hyposalivation.¹⁷

(As discussed, sialolithiasis and stricture of salivary ducts can also cause acute bacterial infection; in such cases, however, the typical presentation is one of chronic or recurrent infection.)

In sialolithiasis, reserve antibiotics for patients who have signs or symptoms of infection, including pyrexia, trismus, and malaise.

Examination might reveal an exquisitely tender, indurated, and inflamed gland; pus can often be expressed from the respective intraoral orifice. Any expressed pus should be sent for culture to guide antibiotic therapy.

Treatment should focus on hydration, oral hygiene, and antibiotics, while reversing or minimizing any underlying contributing medical condition. Warm compresses applied to the involved gland, massage, and sialagogues, such as lemon drops or sugar-free lollipops, can stimulate salivary flow and prevent stasis.

More than 80% of infections are caused by Staphylococcus aureus¹⁷; anaerobic and mixed infections have also been recognized.A beta-lactam penicillin, such as amoxicillin-clavulanate, is the antibiotic of choice. A patient who is systemically unwell should be treated as an inpatient with nafcillin and metronidazole. Methicillin-resistant S aureus must also be considered in patients with comorbid disease, such as diabetes mellitus or intravenous drug use, or in patients residing in an area of substantial incidence of methicillin-resistant S aureus. In those cases, substitute vancomycin or linezolid for nafcillin.¹⁸

Continue to: Less commonly...

Less commonly, abscess can form, with the patient presenting as systemically unwell with a fluctuant mass. If the diagnosis is unclear or the patient does not improve, abscess can be confirmed by US. Expedient surgical review and inpatient admission can then be arranged.

Unlike bacterial sialadenitis, causes of viral sialadenitis are often bilateral. Mumps (a paramyxovirus) is the most common viral cause, affecting primarily children < 15 years.¹⁹ The parotid glands are most often involved, with inflammation and edema causing significant pain because of increasing intraparotid pressure as expansion of the gland is limited by its tense fibrous capsule. Complications of mumps include orchitis, meningitis, pancreatitis, and oophoritis.

Mumps is highly contagious; it is spread through contact with airborne saliva droplets, with viral entry through the nose or mouth, followed by proliferation in the salivary glands or on surface epithelium of the respiratory tract.⁷ Diagnosis is confirmed by viral serology. A positive test of serum immunoglobulin M confirms the diagnosis, but this test should not be performed until 3 days after onset of symptoms because a false-negative result is otherwise possible.²⁰ Immunoglobulin G serologic testing can further aid diagnosis; the titer is measured approximately 4 days after onset of symptoms and again 2 to 3 weeks later. A 4-fold rise in titer confirms mumps.

Other viral infections that can cause sialadenitis include Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, coxsackievirus, and influenza. Treatment is supportive: analgesia, hydration, oral hygiene, and rest. Inflammation might take weeks to resolve, but expect complete resolution. For a patient who has significant trismus, poor oral intake, or a potentially threatened airway, inpatient care should be provided.

Recurrent parotitis of childhood is an inflammatory condition that usually affects one, but at times both, parotid glands. It is characterized by episodes of painful swelling. Incidence peaks at 3 to 6 years of age.⁷ Episodes can be frequent, occurring 1 to 5 times a year and lasting 3 to 7 days—sometimes longer—and usually resolving without treatment.

Continue to: The precise etiology...

The precise etiology of recurrent parotitis of childhood is unclear; possibly, saliva aggregates to form obstructive mucous plugs, thus causing stasis and swelling of the gland. As pressure builds, spontaneous plug extrusion occurs and symptoms resolve, provided infection is not a factor. US demonstrates multiple round, hypoechoic areas consistent with duct dilation, and surrounding infiltration by lymphocytes.¹

Pus can often be expressed from the respective intraoral orifice in sialadenitis. Send expressed pus for culture to guide antibiotic therapy.

Supportive care—adequate hydration, gland massage, warm compresses, and sialogogues—are mainstays of treatment. Fever and malaise warrant treatment with oral antibiotics. Sialadenoscopy, which can be considered in children with frequent episodes, can decrease the frequency and severity of episodes.²¹ The condition usually resolves spontaneously at puberty.

Ask: Does the patient have dry mouth?

In-depth review of xerostomia is beyond the scope of this article. Causes include Sjögren's syndrome, immunoglobulin G4-related sialadenitis, sarcoidosis, radiation therapy, diabetes, chronic infection, and medications—in particular those with anticholinergic effects.

Treatment of xerostomia includes saliva substitutes, sialagogues, and, for oral candidiasis, antifungals. Muscarinic cholinergic stimulators, such as pilocarpine, 5 mg qid have been used with some success²²; patients should be advised of potential adverse effects with these agents, including sweating, urinary frequency, flushing, and chills.

CORRESPONDENCE
Shankar Haran, MBBS, ENT Department, Townsville Hospital, 100 Angus Smith Dr, Douglas, Queensland, Australia 4814; Shankar.haran01@gmail.com.

Making a diagnosis of a salivary gland disorder can be difficult. Common presentations, such as a painful or swollen gland, can be caused by numerous disorders of strikingly variable severity and consequences, including inflammatory, infectious, and neoplastic conditions, for which treatment can differ significantly, and referral for specialty care is sometimes necessary.

Yet it is the patient’s presentation that can aid you in making the diagnosis that will guide management. Consider that acute symptoms often result from infection, for example, and chronic or recurrent symptoms are caused more often by obstructive or nonobstructive inflammatory conditions and neoplasms. Diagnosis of an apparent neoplasm, prompted by clinical findings, is made using imaging and fine-needle aspiration (FNA) biopsy. Acute infection usually resolves with antibiotics and supportive management; calculi that cause persistent symptoms warrant referral for consideration of stone or gland removal; and malignant neoplasms usually require excision as well as neck dissection and chemotherapy or radiotherapy, or both—calling for multidisciplinary care.

In this article, we clarify what can be an imprecise and perplexing path from the presentation to diagnosis to treatment of disorders of the salivary glands. To begin, see “Geography of the salivary glands,” for an overview of the location, structure, and corresponding ducts of the component salivary glands (parotid, submandibular, sublingual, and minor glands).

SIDEBAR
Geography of the salivary glands

©Stocktreck images/Science Source

The salivary glands comprise the major paired parotid, submandibular, and sublingual glands, as well as minor salivary glands that line the oropharyngeal mucosa. Secretion of saliva is modulated by both autonomic and humoral factors.

The parotid gland sits between the mastoid process, the ramus of the mandible, and the styloid process, extend- ing from the external auditory meatus superiorly to below the angle of the mandible and into the neck inferiorly. The gland is surrounded by a tough capsule. Embedded within the gland is the facial nerve, which divides into its 5 branches within the substance of the gland. The parotid (Stensen’s) duct passes anteriorly before turning medially to pierce the buccinator muscle, opening onto the mucous membrane of the cheek opposite the second upper molar.

The submandibular gland comprises (1) a large superficial part that fills the space between the mandible and the floor of the mouth and (2) a small deep part that wraps around the posterior border of the mylohyoid muscle. The submandibular (Wharton’s) duct runs anteriorly to open onto the floor of the mouth, alongside the frenulum.

The sublingual gland, the smallest of the major salivary glands, lies anteriorly in the floor of the mouth, with many small ducts opening either into the submandibular duct or directly into the mouth.

Basic secretory units of salivary glands are clusters of cells, each called an acinus. These cells secrete a fluid that contains water, electrolytes, mucous, and enzymes, all of which flow out of the acini into collecting ducts. The saliva produced by the parotid is mainly serous; by the submandibular gland, mixed; and by the sublingual and minor salivary glands, mucoid.

Presentation helps establish the differential Dx

Ask: Are the glands swollen?

Painless salivary gland swelling has a variety of causes, including neoplasm, sialadenosis, and the eating disorders bulimia and anorexia nervosa. There is significant overlap of presentations among those causes (FIGURE). Pain accompanying swelling is uncommon but not unheard of.

Neoplasms. Tumors of the salivary gland are relatively uncommon, constituting approximately 2% of head and neck neoplasms; most (80%) occur in the parotid gland, and most of those are benign.¹ Although benign and malignant salivary gland neoplasms do not usually present with pain, pain can be associated with a neoplasm secondary to suppuration, hemorrhage into a mass, or infiltration of a malignancy into adjacent tissue.

Benign tumors. The majority of benign tumors are pleomorphic adenomas of the parotid, accounting for approximately 60% of salivary gland neoplasms.^1,2 Tumors localized to the submandibular gland are often (in 50% of cases) malignant, however.³

Ultrasonography is an excellent initial imaging choice for investigating a possible salivary gland tumor.

Benign tumors are typically slow-growing and, generally, painless. On examination, they are well-circumscribed, mobile, and nontender. Patients presenting late with a large tumor might, however, experience pain secondary to stretching of the parotid capsule or compression of local structures.

Continue to: Ultrasonograhpy (US) is an excellent...

Ultrasonography (US) is an excellent initial imaging choice for investigating a possible salivary gland tumor; US is combined with FNA, which is safe and highly reliable for differentiating neoplastic and non-neoplastic disorders.⁴ (Avoid open biopsy of a neoplasm because of the risk of tumor spillage.) In patients with suspected neoplasm, contrast-enhanced computed tomography (CT) or magnetic resonance imaging (MRI) should also be performed, because both modalities allow delineation of the tumor mass and demonstration of any infiltration of surrounding structures.

Treatment of benign neoplasms involves complete excision because, with some tumors, particularly pleomorphic adenomas, there is risk of malignant transformation over time. Superficial parotidectomy is the most common procedure, because most benign tumors occur in the superficial lobe of the parotid gland. Delicate dissection of the facial nerve is integral to the operation, although temporary facial nerve palsy will still occur in 5% to 10% of patients undergoing superficial parotidectomy for a benign tumor, with permanent injury occurring in fewer than 1%.⁵

Malignancy. Features of a tumor that raise concern of malignancy include⁶:

• rapid growth
• pain
• tethering to underlying structures or overlying skin
• firm mass
• associated cervical lymphadenopathy
• facial-nerve palsy.

The workup of a malignant tumor is the same as it is for a benign neoplasm: US-guided FNA, essential for diagnosis, and contrast-enhanced CT or MRI to delineate the tumor.

Malignant salivary gland neoplasms usually require excision as well as neck dissection and chemotherapy or radiotherapy, or both, necessitating a multidisciplinary approach. Also, there is potential for squamous-cell carcinoma and melanoma of the head to metastasize to salivary gland lymph nodes; it is important, therefore, to examine for, and elicit any history of, cutaneous malignancy of the scalp or face.

Continue to: Sialadenosis...

Sialadenosis presents with asymptomatic bilateral hypertrophy of the salivary glands—more commonly the parotids and rarely the submandibular glands. Swelling is persistent, symmetrical, painless, and of normal tone on palpation.

Causes of sialadenosis include alcoholism and, less commonly, diabetes mellitus and malnutrition; some cases are idiopathic. An autonomic neuropathy, causing excessive salivary acinar protein synthesis or failure of adequate secretion, or both, is common to alcoholism, diabetes, and malnutrition.⁷ Subsequent engorgement of acinar cells leads to clinical parotid hypertrophy.

Diagnosis is based on history and examination, as well as on the findings of US or CT, which will reveal bilateral gland enlargement and increased density. The glands appear dense because adipose cells are displaced by acinar cell hypertrophy; however, end-stage changes can result in the opposite appearance: a lucent enlargement caused by fatty infiltration.² FNA is unnecessary, unless there is suspicion of neoplasm, as there would be in patients with asymmetrical parotid enlargement, pain, lymph node enlargement, or facial-nerve involvement. In patients with sialadenosis, in contrast, acinar cell hypertrophy alone will be present.

Treatment of sialadenosis is best aimed at rectifying the underlying medical condition, which might, over time, lead to some reduction in the size of the gland. There is no specific effective therapy for elimination of glandular swelling.

Bulimia and anorexia nervosa. Bulimia nervosa, the induction of vomiting after binge eating, can be associated with bilateral or occasionally unilateral parotid swelling. Anorexia, a form of self-starvation, can occur in association with bulimia, with patients also presenting with parotid swelling. Associated parotid swelling is similar to what is seen in sialadenosis: painless, persistent, and of nonpathologic consistency.

The pathophysiology of bulimia- and anorexia-associated parotid-gland swelling is identical to what is seen in sialadenosis: dysregulation of acinar cell sympathetic nerve supply that leads to enlargement of individual parenchymal cells.⁸ Contrast-enhanced CT can reveal increased vascularity associated with active bulimia. FNA and CT, however, are required only in patients in whom the diagnosis is not clear and when neoplasm is suspected.

Continue to: Treatment includes...

Treatment includes correcting electrolyte abnormalities and, more importantly, addressing underlying emotional issues to stop purging episodes. Psychiatric input and social support are invaluable. Parotid gland swelling generally improves with cessation of vomiting episodes.

Ask: Is the patient in pain?

Causes of salivary gland pain include sialolithiasis, sialadenitis, and recurrent parotitis of childhood. Pain occurs secondary to stretching of the fibrous capsule in which the parotid or submandibular gland is surrounded, compression of pain fibers by an expanding mass, or infiltration of nerves by neoplasia.

Sialolithiasis. Sialolithiasis, or salivary stones, are primarily calcium carbonate concentrations within the salivary ductal system. More than 80% occur in the submandibular gland or duct⁹ as a result of production of mixed mucoid and serous saliva and a tortuous duct path.

For a submandibular duct stone, bimanual palpation might reveal its position if it’s located distally in the floor of the mouth; a proximal stone might not be palpable.

Patients usually present with a history of intermittent swelling and pain of the involved gland associated with eating. Increased production of saliva during meals, which then passes through a partially obstructed salivary duct, leads to salivary retention and glandular swelling. Thus, a recurring pattern can develop, with varying periods of remission,⁷ eventually leading to an acute suppurative process or sialadenitis (described below). Chronic salivary disease can also be caused by stricture of a duct or, rarely, external compression by a tumor mass.

Examination often reveals an enlarged and often tender gland; conversely, chronic disease can lead to gland atrophy. Usually, only minimal saliva is able to be expressed from an obstructed duct. For a submandibular duct stone, bimanual palpation might reveal its position if it is located distally in the floor of the mouth; a proximal stone might not be palpable.

Continue to: Although US is operator-dependent...

Although US is operator-dependent, it is the imaging modality of choice for identifying sialolithiasis¹⁰ because it can identify gland architecture, duct dilation, and both radiolucent and radiopaque stones. For patients in whom US findings are normal despite a convincing clinical presentation of sialolithiasis, CT should be performed because small stones can be missed on US.¹¹

Supportive measures for sialolithiasis are listed in the TABLE. Reserve antibiotics for patients who have signs or symptoms of infection, including pyrexia, trismus, and malaise. A beta-lactam antibiotic, such as amoxicillin–clavulanate, 875 mg orally bid, or a cephalosporin, such as cephalexin, 500 mg orally qid, are appropriate first-line options. Clindamycin, 300 mg orally tid, or metronidazole, 500 mg orally tid, are acceptable alternatives. When signs or symptoms are persistent or recurrent, refer the patient for a surgical opinion.

Stones located in the floor of the mouth are usually excised through an intraoral approach. In the past, gland excision was advocated when a sialolith was found more proximally within the gland parenchyma. More recently, however, sialendoscopy, involving insertion of a small, semirigid endoscope into the salivary duct, has been shown safe and effective for removing a stone; successful removal, in as many as 80% of cases, increases to 90% when performed using a minimally invasive surgical technique.¹² Although sialendoscopy is effective, the technique cannot always treat the underlying abnormality of the salivary gland; gland excision is therefore warranted in some cases.

Last, extracorporeal shock wave therapy is aimed at fragmenting salivary stones before retrieval. Results are variable, however, and treatment should be guided by an otolaryngologist.^13,14

Sialadenitis (bacterial and viral infection). Acute suppurative sialadenitis occurs secondary to retrograde ductal bacterial infection. The parotid gland is most frequently involved,¹⁵ although submandibular sialadenitis is not uncommon. Patients usually present with sudden-onset unilateral, painful swelling.

Continue to: Pathophysiology involves...

Pathophysiology involves dehydration or decreased oral intake leading to salivary stasis and subsequent bacterial migration into the gland. Medically debilitated and postoperative patients are therefore at greater risk; so are patients with diabetes mellitus, poor oral hygiene, Sjögren’s syndrome, hypothyroidism, or renal failure.¹⁶ Certain medications, including anticholinergics, can also predispose to hyposalivation.¹⁷

(As discussed, sialolithiasis and stricture of salivary ducts can also cause acute bacterial infection; in such cases, however, the typical presentation is one of chronic or recurrent infection.)

In sialolithiasis, reserve antibiotics for patients who have signs or symptoms of infection, including pyrexia, trismus, and malaise.

Examination might reveal an exquisitely tender, indurated, and inflamed gland; pus can often be expressed from the respective intraoral orifice. Any expressed pus should be sent for culture to guide antibiotic therapy.

Treatment should focus on hydration, oral hygiene, and antibiotics, while reversing or minimizing any underlying contributing medical condition. Warm compresses applied to the involved gland, massage, and sialagogues, such as lemon drops or sugar-free lollipops, can stimulate salivary flow and prevent stasis.

More than 80% of infections are caused by Staphylococcus aureus¹⁷; anaerobic and mixed infections have also been recognized.A beta-lactam penicillin, such as amoxicillin-clavulanate, is the antibiotic of choice. A patient who is systemically unwell should be treated as an inpatient with nafcillin and metronidazole. Methicillin-resistant S aureus must also be considered in patients with comorbid disease, such as diabetes mellitus or intravenous drug use, or in patients residing in an area of substantial incidence of methicillin-resistant S aureus. In those cases, substitute vancomycin or linezolid for nafcillin.¹⁸

Continue to: Less commonly...

Less commonly, abscess can form, with the patient presenting as systemically unwell with a fluctuant mass. If the diagnosis is unclear or the patient does not improve, abscess can be confirmed by US. Expedient surgical review and inpatient admission can then be arranged.

Unlike bacterial sialadenitis, causes of viral sialadenitis are often bilateral. Mumps (a paramyxovirus) is the most common viral cause, affecting primarily children < 15 years.¹⁹ The parotid glands are most often involved, with inflammation and edema causing significant pain because of increasing intraparotid pressure as expansion of the gland is limited by its tense fibrous capsule. Complications of mumps include orchitis, meningitis, pancreatitis, and oophoritis.

Mumps is highly contagious; it is spread through contact with airborne saliva droplets, with viral entry through the nose or mouth, followed by proliferation in the salivary glands or on surface epithelium of the respiratory tract.⁷ Diagnosis is confirmed by viral serology. A positive test of serum immunoglobulin M confirms the diagnosis, but this test should not be performed until 3 days after onset of symptoms because a false-negative result is otherwise possible.²⁰ Immunoglobulin G serologic testing can further aid diagnosis; the titer is measured approximately 4 days after onset of symptoms and again 2 to 3 weeks later. A 4-fold rise in titer confirms mumps.

Other viral infections that can cause sialadenitis include Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus, coxsackievirus, and influenza. Treatment is supportive: analgesia, hydration, oral hygiene, and rest. Inflammation might take weeks to resolve, but expect complete resolution. For a patient who has significant trismus, poor oral intake, or a potentially threatened airway, inpatient care should be provided.

Recurrent parotitis of childhood is an inflammatory condition that usually affects one, but at times both, parotid glands. It is characterized by episodes of painful swelling. Incidence peaks at 3 to 6 years of age.⁷ Episodes can be frequent, occurring 1 to 5 times a year and lasting 3 to 7 days—sometimes longer—and usually resolving without treatment.

Continue to: The precise etiology...

The precise etiology of recurrent parotitis of childhood is unclear; possibly, saliva aggregates to form obstructive mucous plugs, thus causing stasis and swelling of the gland. As pressure builds, spontaneous plug extrusion occurs and symptoms resolve, provided infection is not a factor. US demonstrates multiple round, hypoechoic areas consistent with duct dilation, and surrounding infiltration by lymphocytes.¹

Pus can often be expressed from the respective intraoral orifice in sialadenitis. Send expressed pus for culture to guide antibiotic therapy.

Supportive care—adequate hydration, gland massage, warm compresses, and sialogogues—are mainstays of treatment. Fever and malaise warrant treatment with oral antibiotics. Sialadenoscopy, which can be considered in children with frequent episodes, can decrease the frequency and severity of episodes.²¹ The condition usually resolves spontaneously at puberty.

Ask: Does the patient have dry mouth?

In-depth review of xerostomia is beyond the scope of this article. Causes include Sjögren's syndrome, immunoglobulin G4-related sialadenitis, sarcoidosis, radiation therapy, diabetes, chronic infection, and medications—in particular those with anticholinergic effects.

Treatment of xerostomia includes saliva substitutes, sialagogues, and, for oral candidiasis, antifungals. Muscarinic cholinergic stimulators, such as pilocarpine, 5 mg qid have been used with some success²²; patients should be advised of potential adverse effects with these agents, including sweating, urinary frequency, flushing, and chills.

CORRESPONDENCE
Shankar Haran, MBBS, ENT Department, Townsville Hospital, 100 Angus Smith Dr, Douglas, Queensland, Australia 4814; Shankar.haran01@gmail.com.

A 29-year-old man with no prior history of mouth sores abruptly developed many 1- to 1.5-mm blisters on the gingiva (FIGURE 1A),tongue (FIGURE 1B), and buccal mucosa ­(FIGURE 1C), which evolved into small erosions accompanied by a low-grade fever 5 days prior to presentation. The patient had no history of any dermatologic conditions or systemic illnesses and was taking no medication.

IMAGES COURTESY OF ROBERT T. BRODELL, MD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes simplex virus (HSV) is the causative agent for acute primary herpetic gingivostomatitis.¹ HSV-1 is primarily responsible for oral mucosal infections, while HSV-2 is implicated in most genital and cutaneous lower body lesions.¹ Herpetic gingivostomatitis often presents as a sudden vesiculoulcerative eruption anywhere in the mouth, including the perioral skin, vermillion border, gingiva, tongue, or buccal mucosa.² Associated symptoms include malaise, headache, fever, and cervical lymphadenopathy; however, most ­occurrences are subclinical or asymptomatic.²

A diagnosis that’s more common in children. Primary HSV occurs in people who have not previously been exposed to the virus. While it is an infection that classically presents in childhood, it is not limited to this group. Manifestations often are more severe in adults.¹

Utilize PCR for the diagnosis of herpetic gingivostomatitis because of its sensitivity, specificity, and rapid turnaround time.

Following an incubation period of a few days to 3 weeks, the primary infection typically lasts 10 to 14 days.^1,2 Recurrence is highly variable and generally less severe than primary infection, with grouped vesicles often recurring in the same spot with each recurrence on the vermillion border of the lip. Triggers for reactivation include immunosuppression, pregnancy, fever, UV radiation, or trauma.^1,2

Differential includes other conditions with mucosal lesions

Acute herpetic gingivostomatitis must be distinguished from other disease processes that cause ulcerative mucosal lesions.

Aphthous stomatitis (canker sores) is the most common ulcerative disease of the oral mucosa.³ It presents as painful, punched-out, shallow ulcers with a yellowish gray pseudomembranous center and surrounding erythema.³ No definitive etiology has been established; however, aphthae often occur after trauma.

Continue to: Herpangina...

Herpangina is caused by coxsackie A virus and primarily is seen in infants and children younger than 5.⁴ The papulovesicular lesions primarily affect the posterior oral cavity, including the soft palate, anterior tonsillar pillars, and uvula.⁴

Allergic contact dermatitis is precipitated by contact with an allergen and presents with pain or pruritus. Lesions are erythematous with vesicles, erosions, ulcers, or hyperkeratosis that gradually resolve after withdrawal of the causative allergen.⁵

Pemphigus vulgaris. Oral ulcerations of the buccal mucosa and gingiva are the first manifestation of pemphigus vulgaris in the majority of patients, with skin blisters occurring months to years later over areas exposed to frictional stress.⁶ Skin sloughs may be seen in response to frictional stress (Nikolsky sign).⁶

The new Dx gold standard is PCR

Acute herpetic gingivostomatitis usually is diagnosed by history and hallmark clinical signs and symptoms.¹ In this case, our patient presented with a sudden eruption of painful blisters on multiple areas of the oral mucosa associated with fever. The diagnosis can be confirmed by viral culture, serology with anti-HSV IgM and IgG, Tzanck preparation, immunofluorescence, and polymerase chain reaction (PCR).¹ Viral culture has been the gold standard for mucosal HSV diagnosis; however, PCR is emerging as the new gold standard because of its unrivaled sensitivity, specificity, and rapid turnaround time.^7,8 Specimens for PCR are submitted using a swab of infected cells placed in the same viral transport ­medium used for HSV cultures.

Our patient’s culture was positive for HSV-1.

Continue to: Prompt use of antivirals is key

Treatment of acute HSV gingivostomatitis involves symptomatic management with topical anesthetics, oral analgesics, and normal saline rinses.¹ Acyclovir is an established therapy; however, it has poor bioavailability and gastrointestinal absorption.¹ Valacyclovir has improved bioavailability and is well tolerated.¹ For primary herpes gingivostomatitis, we favor 1 g twice daily for 7 days.¹ Our patient responded well to this valacyclovir regimen and healed completely in 1 week.

CORRESPONDENCE
Robert T. Brodell, MD, 2500 N State St, Jackson, MS 39216; rbrodell@umc.edu

A 29-year-old man with no prior history of mouth sores abruptly developed many 1- to 1.5-mm blisters on the gingiva (FIGURE 1A),tongue (FIGURE 1B), and buccal mucosa ­(FIGURE 1C), which evolved into small erosions accompanied by a low-grade fever 5 days prior to presentation. The patient had no history of any dermatologic conditions or systemic illnesses and was taking no medication.

IMAGES COURTESY OF ROBERT T. BRODELL, MD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes simplex virus (HSV) is the causative agent for acute primary herpetic gingivostomatitis.¹ HSV-1 is primarily responsible for oral mucosal infections, while HSV-2 is implicated in most genital and cutaneous lower body lesions.¹ Herpetic gingivostomatitis often presents as a sudden vesiculoulcerative eruption anywhere in the mouth, including the perioral skin, vermillion border, gingiva, tongue, or buccal mucosa.² Associated symptoms include malaise, headache, fever, and cervical lymphadenopathy; however, most ­occurrences are subclinical or asymptomatic.²

A diagnosis that’s more common in children. Primary HSV occurs in people who have not previously been exposed to the virus. While it is an infection that classically presents in childhood, it is not limited to this group. Manifestations often are more severe in adults.¹

Utilize PCR for the diagnosis of herpetic gingivostomatitis because of its sensitivity, specificity, and rapid turnaround time.

Following an incubation period of a few days to 3 weeks, the primary infection typically lasts 10 to 14 days.^1,2 Recurrence is highly variable and generally less severe than primary infection, with grouped vesicles often recurring in the same spot with each recurrence on the vermillion border of the lip. Triggers for reactivation include immunosuppression, pregnancy, fever, UV radiation, or trauma.^1,2

Differential includes other conditions with mucosal lesions

Acute herpetic gingivostomatitis must be distinguished from other disease processes that cause ulcerative mucosal lesions.

Aphthous stomatitis (canker sores) is the most common ulcerative disease of the oral mucosa.³ It presents as painful, punched-out, shallow ulcers with a yellowish gray pseudomembranous center and surrounding erythema.³ No definitive etiology has been established; however, aphthae often occur after trauma.

Continue to: Herpangina...

Herpangina is caused by coxsackie A virus and primarily is seen in infants and children younger than 5.⁴ The papulovesicular lesions primarily affect the posterior oral cavity, including the soft palate, anterior tonsillar pillars, and uvula.⁴

Allergic contact dermatitis is precipitated by contact with an allergen and presents with pain or pruritus. Lesions are erythematous with vesicles, erosions, ulcers, or hyperkeratosis that gradually resolve after withdrawal of the causative allergen.⁵

Pemphigus vulgaris. Oral ulcerations of the buccal mucosa and gingiva are the first manifestation of pemphigus vulgaris in the majority of patients, with skin blisters occurring months to years later over areas exposed to frictional stress.⁶ Skin sloughs may be seen in response to frictional stress (Nikolsky sign).⁶

The new Dx gold standard is PCR

Acute herpetic gingivostomatitis usually is diagnosed by history and hallmark clinical signs and symptoms.¹ In this case, our patient presented with a sudden eruption of painful blisters on multiple areas of the oral mucosa associated with fever. The diagnosis can be confirmed by viral culture, serology with anti-HSV IgM and IgG, Tzanck preparation, immunofluorescence, and polymerase chain reaction (PCR).¹ Viral culture has been the gold standard for mucosal HSV diagnosis; however, PCR is emerging as the new gold standard because of its unrivaled sensitivity, specificity, and rapid turnaround time.^7,8 Specimens for PCR are submitted using a swab of infected cells placed in the same viral transport ­medium used for HSV cultures.

Our patient’s culture was positive for HSV-1.

Continue to: Prompt use of antivirals is key

Treatment of acute HSV gingivostomatitis involves symptomatic management with topical anesthetics, oral analgesics, and normal saline rinses.¹ Acyclovir is an established therapy; however, it has poor bioavailability and gastrointestinal absorption.¹ Valacyclovir has improved bioavailability and is well tolerated.¹ For primary herpes gingivostomatitis, we favor 1 g twice daily for 7 days.¹ Our patient responded well to this valacyclovir regimen and healed completely in 1 week.

CORRESPONDENCE
Robert T. Brodell, MD, 2500 N State St, Jackson, MS 39216; rbrodell@umc.edu

A 29-year-old man with no prior history of mouth sores abruptly developed many 1- to 1.5-mm blisters on the gingiva (FIGURE 1A),tongue (FIGURE 1B), and buccal mucosa ­(FIGURE 1C), which evolved into small erosions accompanied by a low-grade fever 5 days prior to presentation. The patient had no history of any dermatologic conditions or systemic illnesses and was taking no medication.

IMAGES COURTESY OF ROBERT T. BRODELL, MD

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Herpes simplex virus (HSV) is the causative agent for acute primary herpetic gingivostomatitis.¹ HSV-1 is primarily responsible for oral mucosal infections, while HSV-2 is implicated in most genital and cutaneous lower body lesions.¹ Herpetic gingivostomatitis often presents as a sudden vesiculoulcerative eruption anywhere in the mouth, including the perioral skin, vermillion border, gingiva, tongue, or buccal mucosa.² Associated symptoms include malaise, headache, fever, and cervical lymphadenopathy; however, most ­occurrences are subclinical or asymptomatic.²

A diagnosis that’s more common in children. Primary HSV occurs in people who have not previously been exposed to the virus. While it is an infection that classically presents in childhood, it is not limited to this group. Manifestations often are more severe in adults.¹

Utilize PCR for the diagnosis of herpetic gingivostomatitis because of its sensitivity, specificity, and rapid turnaround time.

Following an incubation period of a few days to 3 weeks, the primary infection typically lasts 10 to 14 days.^1,2 Recurrence is highly variable and generally less severe than primary infection, with grouped vesicles often recurring in the same spot with each recurrence on the vermillion border of the lip. Triggers for reactivation include immunosuppression, pregnancy, fever, UV radiation, or trauma.^1,2

Differential includes other conditions with mucosal lesions

Acute herpetic gingivostomatitis must be distinguished from other disease processes that cause ulcerative mucosal lesions.

Aphthous stomatitis (canker sores) is the most common ulcerative disease of the oral mucosa.³ It presents as painful, punched-out, shallow ulcers with a yellowish gray pseudomembranous center and surrounding erythema.³ No definitive etiology has been established; however, aphthae often occur after trauma.

Continue to: Herpangina...

Herpangina is caused by coxsackie A virus and primarily is seen in infants and children younger than 5.⁴ The papulovesicular lesions primarily affect the posterior oral cavity, including the soft palate, anterior tonsillar pillars, and uvula.⁴

Allergic contact dermatitis is precipitated by contact with an allergen and presents with pain or pruritus. Lesions are erythematous with vesicles, erosions, ulcers, or hyperkeratosis that gradually resolve after withdrawal of the causative allergen.⁵

Pemphigus vulgaris. Oral ulcerations of the buccal mucosa and gingiva are the first manifestation of pemphigus vulgaris in the majority of patients, with skin blisters occurring months to years later over areas exposed to frictional stress.⁶ Skin sloughs may be seen in response to frictional stress (Nikolsky sign).⁶

The new Dx gold standard is PCR

Acute herpetic gingivostomatitis usually is diagnosed by history and hallmark clinical signs and symptoms.¹ In this case, our patient presented with a sudden eruption of painful blisters on multiple areas of the oral mucosa associated with fever. The diagnosis can be confirmed by viral culture, serology with anti-HSV IgM and IgG, Tzanck preparation, immunofluorescence, and polymerase chain reaction (PCR).¹ Viral culture has been the gold standard for mucosal HSV diagnosis; however, PCR is emerging as the new gold standard because of its unrivaled sensitivity, specificity, and rapid turnaround time.^7,8 Specimens for PCR are submitted using a swab of infected cells placed in the same viral transport ­medium used for HSV cultures.

Our patient’s culture was positive for HSV-1.

Continue to: Prompt use of antivirals is key

Treatment of acute HSV gingivostomatitis involves symptomatic management with topical anesthetics, oral analgesics, and normal saline rinses.¹ Acyclovir is an established therapy; however, it has poor bioavailability and gastrointestinal absorption.¹ Valacyclovir has improved bioavailability and is well tolerated.¹ For primary herpes gingivostomatitis, we favor 1 g twice daily for 7 days.¹ Our patient responded well to this valacyclovir regimen and healed completely in 1 week.

CORRESPONDENCE
Robert T. Brodell, MD, 2500 N State St, Jackson, MS 39216; rbrodell@umc.edu

THE CASE

A 20-year-old man presented to our family medicine clinic with right wrist pain 4 days after falling on his wrist and hand while playing basketball. He denied any other previous injury or trauma. The pain was unchanged since the injury occurred.

Examination demonstrated mild edema over the palmar and ulnar aspect of the patient’s right wrist with no apparent ecchymosis. He had normal range of motion of his right wrist and hand. However, he experienced pain with active and passive wrist extension and ulnar deviation. There was significant tenderness in the palmar and ulnar aspects of his right wrist just distal to the ulnar styloid process.

THE DIAGNOSIS

Standard plain x-rays of the right wrist revealed an isolated fracture of the body of the triquetrum (FIGURE 1). Since the patient refused to have a cast placed, his wrist was immobilized with a wrist brace. By Day 16 post injury, the pain and edema had improved significantly. After talking with the patient about the potential risks and benefits of continuing to play basketball—and despite our recommendation that he not play—he decided to continue playing since he was a college basketball prospect.

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

At 4 weeks post injury, x-rays demonstrated mild interval healing (FIGURE 2). At the 8-week visit, the patient had only very mild pain and tenderness, and x-ray images showed improvement (FIGURE 3). Within a few months, his symptoms resolved completely. No further imaging was performed.

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

DISCUSSION

In general, carpal fractures are uncommon.¹ The triquetrum is the second most commonly injured carpal bone, involved in up to 18% of all carpal fractures.^2,3 Triquetrum fractures most commonly occur as isolated injuries and are typically classified in 2 general categories: avulsion fractures (dorsal cortex or volar cortex) and fractures of the triquetrum body.^4-8 Isolated avulsion fractures of the triquetral dorsal cortex are relatively common, occurring in about 95% of triquetrum injuries.^4-9 Isolated fractures of the triquetrum body are less common, occurring in about 4% of triquetrum injuries, and can go unnoticed on conventional x-rays.^4-9

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

Basketball presents a unique risk for hand or wrist fracture due to its high-impact nature, hard playing surfaces, and frequent use of the hands for dribbling, shooting, rebounding, and passing the ball.

In a retrospective study of sports-related fractures conducted at the Royal Infirmary of Edinburgh, basketball had the highest incidence of carpal injuries compared with other sports, including football, rugby, skiing, snowboarding, and ice-skating.⁴ Similarly, a retrospective study conducted at the University of California, Los Angeles, found that of all Division 1 collegiate athletes at the school, basketball players had the highest incidence of primary fractures, and the most common fracture location was the hand.¹⁰

Continue to: An injury that's easy to miss

Because the incidence of hand and wrist injuries is high among basketball players, it is imperative that triquetrum body fractures are not missed or misdiagnosed as more common hand and wrist injuries, such as triquetral dorsal avulsion fractures.

Our patient, who had an isolated triquetrum body fracture, presented with focal tenderness on the palmar and ulnar aspects of his wrist and pain with ulnar deviation. Since triquetral body fractures often have a clinical presentation quite similar to that of triquetral dorsal avulsion fractures, patients presenting with symptoms of wrist tenderness and pain should be treated with a high degree of clinical suspicion.

Triquetral fractures can be missed in up to 20% of x-rays.

With our patient, anteroposterior and lateral x-rays were sufficient to demonstrate an isolated triquetrum body fracture; however, triquetral fractures can be missed in up to 20% of x-rays.⁴ Both magnetic resonance imaging and computerized tomography are useful in diagnosing occult triquetrum fractures and should be used to confirm clinical suspicion when traditional x-rays are inconclusive.^11,12

Management varies

Management of isolated triquetrum body fractures varies depending on the fracture pattern and the status of bone consolidation. Triquetral body fractures typically heal well; it’s very rare that there is a nonunion. As our patient’s fracture was nondisplaced and stable, brace immobilization for 4 weeks was sufficient to facilitate healing and restore long-term hand and wrist functionality. This course of treatment is consistent with other cases of nondisplaced triquetrum body fractures reported in the literature.¹³

Long-term outcomes. The literature is sparse regarding the long-term functional outcome of nonsurgical treatment for nondisplaced triquetrum body fractures. Multiple carpal fractures, displaced triquetrum body fractures, and persistent pain for multiple months after nonsurgical management all indicate the need for referral to orthopedic surgery. In instances of fracture displacement or nonunion, management tends to be surgical, with open reduction and internal fixation (ORIF) used in multiple cases of nonunion for isolated triquetrum body fractures.^3,14 Any diagnostic imaging that reveals displacement, malunion, or nonunion of the fracture is an indication for referral to an orthopedic surgeon.

Continue to: Return to play

Return to play. There is no evidence-based return-to-play recommendation for patients with a triquetrum fracture. However, our patient continued to play basketball through the early stages of injury management because he was a collegiate prospect. While medical, social, and economic factors should be considered when discussing treatment options with athletes, injuries should be managed so that there is no long-term loss of function or risk of injury exacerbation. When discussing early return from injury with athletes who have outside pressure to return to play, it’s important to make them aware of the associated long- and short-term risks.¹⁵

THE TAKEAWAY

Management of an isolated triquetrum body fracture is typically straightforward; however, if the fracture is displaced, refer the patient to an orthopedic surgeon as ORIF may be required. For this reason, it’s important to be able to promptly identify isolated triquetrum body fractures and to avoid confusing them with triquetrum dorsal avulsion fractures.

Depending on the sport played and the severity of the injury, athletes with conservatively managed nondisplaced triquetral body fractures may be candidates for early return to play. Nonetheless, athletes should understand both the short- and the long-term risks of playing with an injury, and they should never be advised to continue playing with an injury if it jeopardizes their well-being or the long-term functionality of the affected body part.

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, AFW Clinic, 3055 Roslyn Street, Denver, CO 80238; Morteza.Khodaee@cuanschutz.edu

THE CASE

A 20-year-old man presented to our family medicine clinic with right wrist pain 4 days after falling on his wrist and hand while playing basketball. He denied any other previous injury or trauma. The pain was unchanged since the injury occurred.

Examination demonstrated mild edema over the palmar and ulnar aspect of the patient’s right wrist with no apparent ecchymosis. He had normal range of motion of his right wrist and hand. However, he experienced pain with active and passive wrist extension and ulnar deviation. There was significant tenderness in the palmar and ulnar aspects of his right wrist just distal to the ulnar styloid process.

THE DIAGNOSIS

Standard plain x-rays of the right wrist revealed an isolated fracture of the body of the triquetrum (FIGURE 1). Since the patient refused to have a cast placed, his wrist was immobilized with a wrist brace. By Day 16 post injury, the pain and edema had improved significantly. After talking with the patient about the potential risks and benefits of continuing to play basketball—and despite our recommendation that he not play—he decided to continue playing since he was a college basketball prospect.

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

At 4 weeks post injury, x-rays demonstrated mild interval healing (FIGURE 2). At the 8-week visit, the patient had only very mild pain and tenderness, and x-ray images showed improvement (FIGURE 3). Within a few months, his symptoms resolved completely. No further imaging was performed.

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

DISCUSSION

In general, carpal fractures are uncommon.¹ The triquetrum is the second most commonly injured carpal bone, involved in up to 18% of all carpal fractures.^2,3 Triquetrum fractures most commonly occur as isolated injuries and are typically classified in 2 general categories: avulsion fractures (dorsal cortex or volar cortex) and fractures of the triquetrum body.^4-8 Isolated avulsion fractures of the triquetral dorsal cortex are relatively common, occurring in about 95% of triquetrum injuries.^4-9 Isolated fractures of the triquetrum body are less common, occurring in about 4% of triquetrum injuries, and can go unnoticed on conventional x-rays.^4-9

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

Basketball presents a unique risk for hand or wrist fracture due to its high-impact nature, hard playing surfaces, and frequent use of the hands for dribbling, shooting, rebounding, and passing the ball.

In a retrospective study of sports-related fractures conducted at the Royal Infirmary of Edinburgh, basketball had the highest incidence of carpal injuries compared with other sports, including football, rugby, skiing, snowboarding, and ice-skating.⁴ Similarly, a retrospective study conducted at the University of California, Los Angeles, found that of all Division 1 collegiate athletes at the school, basketball players had the highest incidence of primary fractures, and the most common fracture location was the hand.¹⁰

Continue to: An injury that's easy to miss

Because the incidence of hand and wrist injuries is high among basketball players, it is imperative that triquetrum body fractures are not missed or misdiagnosed as more common hand and wrist injuries, such as triquetral dorsal avulsion fractures.

Our patient, who had an isolated triquetrum body fracture, presented with focal tenderness on the palmar and ulnar aspects of his wrist and pain with ulnar deviation. Since triquetral body fractures often have a clinical presentation quite similar to that of triquetral dorsal avulsion fractures, patients presenting with symptoms of wrist tenderness and pain should be treated with a high degree of clinical suspicion.

Triquetral fractures can be missed in up to 20% of x-rays.

With our patient, anteroposterior and lateral x-rays were sufficient to demonstrate an isolated triquetrum body fracture; however, triquetral fractures can be missed in up to 20% of x-rays.⁴ Both magnetic resonance imaging and computerized tomography are useful in diagnosing occult triquetrum fractures and should be used to confirm clinical suspicion when traditional x-rays are inconclusive.^11,12

Management varies

Management of isolated triquetrum body fractures varies depending on the fracture pattern and the status of bone consolidation. Triquetral body fractures typically heal well; it’s very rare that there is a nonunion. As our patient’s fracture was nondisplaced and stable, brace immobilization for 4 weeks was sufficient to facilitate healing and restore long-term hand and wrist functionality. This course of treatment is consistent with other cases of nondisplaced triquetrum body fractures reported in the literature.¹³

Long-term outcomes. The literature is sparse regarding the long-term functional outcome of nonsurgical treatment for nondisplaced triquetrum body fractures. Multiple carpal fractures, displaced triquetrum body fractures, and persistent pain for multiple months after nonsurgical management all indicate the need for referral to orthopedic surgery. In instances of fracture displacement or nonunion, management tends to be surgical, with open reduction and internal fixation (ORIF) used in multiple cases of nonunion for isolated triquetrum body fractures.^3,14 Any diagnostic imaging that reveals displacement, malunion, or nonunion of the fracture is an indication for referral to an orthopedic surgeon.

Continue to: Return to play

Return to play. There is no evidence-based return-to-play recommendation for patients with a triquetrum fracture. However, our patient continued to play basketball through the early stages of injury management because he was a collegiate prospect. While medical, social, and economic factors should be considered when discussing treatment options with athletes, injuries should be managed so that there is no long-term loss of function or risk of injury exacerbation. When discussing early return from injury with athletes who have outside pressure to return to play, it’s important to make them aware of the associated long- and short-term risks.¹⁵

THE TAKEAWAY

Management of an isolated triquetrum body fracture is typically straightforward; however, if the fracture is displaced, refer the patient to an orthopedic surgeon as ORIF may be required. For this reason, it’s important to be able to promptly identify isolated triquetrum body fractures and to avoid confusing them with triquetrum dorsal avulsion fractures.

Depending on the sport played and the severity of the injury, athletes with conservatively managed nondisplaced triquetral body fractures may be candidates for early return to play. Nonetheless, athletes should understand both the short- and the long-term risks of playing with an injury, and they should never be advised to continue playing with an injury if it jeopardizes their well-being or the long-term functionality of the affected body part.

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, AFW Clinic, 3055 Roslyn Street, Denver, CO 80238; Morteza.Khodaee@cuanschutz.edu

THE CASE

A 20-year-old man presented to our family medicine clinic with right wrist pain 4 days after falling on his wrist and hand while playing basketball. He denied any other previous injury or trauma. The pain was unchanged since the injury occurred.

Examination demonstrated mild edema over the palmar and ulnar aspect of the patient’s right wrist with no apparent ecchymosis. He had normal range of motion of his right wrist and hand. However, he experienced pain with active and passive wrist extension and ulnar deviation. There was significant tenderness in the palmar and ulnar aspects of his right wrist just distal to the ulnar styloid process.

THE DIAGNOSIS

Standard plain x-rays of the right wrist revealed an isolated fracture of the body of the triquetrum (FIGURE 1). Since the patient refused to have a cast placed, his wrist was immobilized with a wrist brace. By Day 16 post injury, the pain and edema had improved significantly. After talking with the patient about the potential risks and benefits of continuing to play basketball—and despite our recommendation that he not play—he decided to continue playing since he was a college basketball prospect.

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

At 4 weeks post injury, x-rays demonstrated mild interval healing (FIGURE 2). At the 8-week visit, the patient had only very mild pain and tenderness, and x-ray images showed improvement (FIGURE 3). Within a few months, his symptoms resolved completely. No further imaging was performed.

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

DISCUSSION

In general, carpal fractures are uncommon.¹ The triquetrum is the second most commonly injured carpal bone, involved in up to 18% of all carpal fractures.^2,3 Triquetrum fractures most commonly occur as isolated injuries and are typically classified in 2 general categories: avulsion fractures (dorsal cortex or volar cortex) and fractures of the triquetrum body.^4-8 Isolated avulsion fractures of the triquetral dorsal cortex are relatively common, occurring in about 95% of triquetrum injuries.^4-9 Isolated fractures of the triquetrum body are less common, occurring in about 4% of triquetrum injuries, and can go unnoticed on conventional x-rays.^4-9

IMAGES COURTESY OF UNIVERSITY OF COLORADO, DENVER

Basketball presents a unique risk for hand or wrist fracture due to its high-impact nature, hard playing surfaces, and frequent use of the hands for dribbling, shooting, rebounding, and passing the ball.

In a retrospective study of sports-related fractures conducted at the Royal Infirmary of Edinburgh, basketball had the highest incidence of carpal injuries compared with other sports, including football, rugby, skiing, snowboarding, and ice-skating.⁴ Similarly, a retrospective study conducted at the University of California, Los Angeles, found that of all Division 1 collegiate athletes at the school, basketball players had the highest incidence of primary fractures, and the most common fracture location was the hand.¹⁰

Continue to: An injury that's easy to miss

Because the incidence of hand and wrist injuries is high among basketball players, it is imperative that triquetrum body fractures are not missed or misdiagnosed as more common hand and wrist injuries, such as triquetral dorsal avulsion fractures.

Our patient, who had an isolated triquetrum body fracture, presented with focal tenderness on the palmar and ulnar aspects of his wrist and pain with ulnar deviation. Since triquetral body fractures often have a clinical presentation quite similar to that of triquetral dorsal avulsion fractures, patients presenting with symptoms of wrist tenderness and pain should be treated with a high degree of clinical suspicion.

Triquetral fractures can be missed in up to 20% of x-rays.

With our patient, anteroposterior and lateral x-rays were sufficient to demonstrate an isolated triquetrum body fracture; however, triquetral fractures can be missed in up to 20% of x-rays.⁴ Both magnetic resonance imaging and computerized tomography are useful in diagnosing occult triquetrum fractures and should be used to confirm clinical suspicion when traditional x-rays are inconclusive.^11,12

Management varies

Management of isolated triquetrum body fractures varies depending on the fracture pattern and the status of bone consolidation. Triquetral body fractures typically heal well; it’s very rare that there is a nonunion. As our patient’s fracture was nondisplaced and stable, brace immobilization for 4 weeks was sufficient to facilitate healing and restore long-term hand and wrist functionality. This course of treatment is consistent with other cases of nondisplaced triquetrum body fractures reported in the literature.¹³

Long-term outcomes. The literature is sparse regarding the long-term functional outcome of nonsurgical treatment for nondisplaced triquetrum body fractures. Multiple carpal fractures, displaced triquetrum body fractures, and persistent pain for multiple months after nonsurgical management all indicate the need for referral to orthopedic surgery. In instances of fracture displacement or nonunion, management tends to be surgical, with open reduction and internal fixation (ORIF) used in multiple cases of nonunion for isolated triquetrum body fractures.^3,14 Any diagnostic imaging that reveals displacement, malunion, or nonunion of the fracture is an indication for referral to an orthopedic surgeon.

Continue to: Return to play

Return to play. There is no evidence-based return-to-play recommendation for patients with a triquetrum fracture. However, our patient continued to play basketball through the early stages of injury management because he was a collegiate prospect. While medical, social, and economic factors should be considered when discussing treatment options with athletes, injuries should be managed so that there is no long-term loss of function or risk of injury exacerbation. When discussing early return from injury with athletes who have outside pressure to return to play, it’s important to make them aware of the associated long- and short-term risks.¹⁵

THE TAKEAWAY

Management of an isolated triquetrum body fracture is typically straightforward; however, if the fracture is displaced, refer the patient to an orthopedic surgeon as ORIF may be required. For this reason, it’s important to be able to promptly identify isolated triquetrum body fractures and to avoid confusing them with triquetrum dorsal avulsion fractures.

Depending on the sport played and the severity of the injury, athletes with conservatively managed nondisplaced triquetral body fractures may be candidates for early return to play. Nonetheless, athletes should understand both the short- and the long-term risks of playing with an injury, and they should never be advised to continue playing with an injury if it jeopardizes their well-being or the long-term functionality of the affected body part.

CORRESPONDENCE
Morteza Khodaee, MD, MPH, University of Colorado School of Medicine, AFW Clinic, 3055 Roslyn Street, Denver, CO 80238; Morteza.Khodaee@cuanschutz.edu

ILLUSTRATIVE CASE

A 50-year-old overweight male with a history of hypertension presents to your office for a yearly physical. On review of symptoms, he notes feeling constantly tired, despite reported good sleep hygiene practices. He scores 11 on the Epworth Sleepiness Scale, and his wife complains about his snoring. You have a high suspicion of obstructive sleep apnea. What is your next step?

Obstructive sleep apnea (OSA) is quite common, affecting at least 2% to 4% of the general adult population.² The gold standard for OSA diagnosis has been laboratory polysomnography (PSG) to measure the apnea-hypopnea index (AHI), which is the average number of apneas and hypopneas per hour of sleep, and the respiratory event index (REI), which is the average number of apneas, hypopneas, and respiratory effort-related arousals per hour of sleep. A minimum of 5 on the AHI or REI, along with clinical symptoms, is required for diagnosis.

Many adults go undiagnosed and untreated, however, due to barriers to diagnosis including the inconvenience of laboratory PSG.³ Sleep laboratories often have a significant wait time for evaluation, and sleeping in an unfamiliar place can be inconvenient or intolerable for some patients, making diagnosis difficult despite high clinical suspicion. Untreated sleep apnea is associated with an increased risk of hypertension, coronary artery disease, congestive heart failure, stroke, atrial fibrillation, and type 2 diabetes.⁴

Home sleep studies are an alternative for patients with a high risk of OSA without comorbid sleep conditions, heart failure, or chronic obstructive pulmonary disease (COPD). This study investigated the long-term effectiveness of diagnosis by home respiratory polygraphy (HRP) vs laboratory PSG in patients with an intermediate to high clinical suspicion for OSA.

STUDY SUMMARY

Home Dx is noninferior to lab Dx in all aspects studied

This multicenter, noninferiority randomized controlled trial and cost analysis study conducted in Spain randomized 430 adults referred to pulmonology for suspected OSA to receive either in-lab PSG or HRP. Patients received treatment with continuous positive airway pressure (CPAP) if their REI was ≥ 5 for HRP or their AHI was ≥ 5 for PSG with significant clinical symptoms, which is consistent with the Spanish Sleep Network guidelines.⁵ All patients in both arms received sleep hygiene instruction, nutrition education, and single-session auto-CPAP titration, and were evaluated at 1 and 3 months to assess for compliance. At 6 months, all patients were evaluated with PSG.

Home respiratory polygraphy was found to be more cost-effective than laboratory polysomnography, with a savings equivalent to more than half the cost of PSG—or about $450 per study.

HRP was found to be non-inferior to PSG based on Epworth Sleepiness Scale (ESS) scores evaluated at baseline and at 6-month follow-up (HRP mean = -4.2 points; 95% confidence interval [CI], -4.8 to -3.6 and PSG mean -4.9; 95% CI, -5.4 to -4.3; P = .14). Both groups had similar secondary outcomes. Quality-of-life as measured by the 30-point Functional Outcomes of Sleep Questionnaire improved by an average of 6.7 (standard deviation [SD] = 16.7) in the HRP group vs 6.5 (SD = 18.1) in the PSG group (P = .92). Systolic and diastolic blood pressure improved significantly in both groups without any statistically significant difference between the groups. HRP was also found to be more cost-effective than PSG with a savings equivalent to more than half the cost of PSG, or about $450 per study (depending on the exchange rate).

WHAT’S NEW

HRP offers advantages for low-risk patients

In the majority of patients, OSA can be diagnosed at home with outcomes similar to those for lab diagnosis, decreased cost, and decreased time from suspected diagnosis to treatment. HRP is acceptable for patients with a high probability of OSA without significant comorbidities if monitoring includes at least airflow, respiratory effort, and blood oxygenation.⁶

Continue to: CAVEATS

Recommendations are somewhat ambiguous

This study, as well as current guidelines, recommend home sleep studies for patients with a high clinical suspicion or high pre-test probability of OSA and who lack comorbid conditions that could affect sleep. The comorbid conditions are well identified: COPD, heart failure hypoventilation syndromes, insomnia, hypersomnia, parasomnia, periodic limb movement disorder, narcolepsy, and chronic opioid use.⁶ However, what constitutes “a high clinical suspicion” or “high pre-test probability” was not well defined in this study.

Several clinical screening tools are available and include the ESS, Berlin Questionnaire, and STOP-BANG Scoring System (Snoring, Tiredness, Observed apnea, Pressure [systemic hypertension], Body mass index > 35, Age > 50 years, Neck circumference > 16 inches, male Gender). An ESS score ≥ 10 warrants further evaluation, but is not very sensitive. Two or more positive categories on the Berlin Questionnaire indicates a high risk of OSA with a sensitivity of 76%, 77%, and 77% for mild, moderate, and severe OSA, respectively.⁷ A score of ≥ 3 on the STOP-BANG Scoring System has been validated and has a sensitivity of 83.6%, 92.9%, and 100% for an AHI > 5, > 15, and > 30, respectively.⁸

Home sleep studies should not be used to screen the general population.

CHALLENGES TO IMPLEMENTATION

Recommendations may present a challenge but insurance should not

The American Academy of Sleep Medicine recommends that portable monitoring must record airflow, respiratory effort, and blood oxygenation, and the device must be able to display the raw data to be interpreted by a board-certified sleep medicine physician according to current published standards.⁶ Implementation would require appropriate selection of a home monitoring device, consultation with a sleep medicine specialist, and significant patient education to ensure interpretable results.

Insurance should not be a barrier to implementation as the Centers for Medicare and Medicaid Services accept home sleep apnea testing results for CPAP prescriptions.⁹ However, variability currently exists regarding the extent to which private insurers provide coverage for home sleep apnea testing.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 50-year-old overweight male with a history of hypertension presents to your office for a yearly physical. On review of symptoms, he notes feeling constantly tired, despite reported good sleep hygiene practices. He scores 11 on the Epworth Sleepiness Scale, and his wife complains about his snoring. You have a high suspicion of obstructive sleep apnea. What is your next step?

Obstructive sleep apnea (OSA) is quite common, affecting at least 2% to 4% of the general adult population.² The gold standard for OSA diagnosis has been laboratory polysomnography (PSG) to measure the apnea-hypopnea index (AHI), which is the average number of apneas and hypopneas per hour of sleep, and the respiratory event index (REI), which is the average number of apneas, hypopneas, and respiratory effort-related arousals per hour of sleep. A minimum of 5 on the AHI or REI, along with clinical symptoms, is required for diagnosis.

Many adults go undiagnosed and untreated, however, due to barriers to diagnosis including the inconvenience of laboratory PSG.³ Sleep laboratories often have a significant wait time for evaluation, and sleeping in an unfamiliar place can be inconvenient or intolerable for some patients, making diagnosis difficult despite high clinical suspicion. Untreated sleep apnea is associated with an increased risk of hypertension, coronary artery disease, congestive heart failure, stroke, atrial fibrillation, and type 2 diabetes.⁴

Home sleep studies are an alternative for patients with a high risk of OSA without comorbid sleep conditions, heart failure, or chronic obstructive pulmonary disease (COPD). This study investigated the long-term effectiveness of diagnosis by home respiratory polygraphy (HRP) vs laboratory PSG in patients with an intermediate to high clinical suspicion for OSA.

STUDY SUMMARY

Home Dx is noninferior to lab Dx in all aspects studied

This multicenter, noninferiority randomized controlled trial and cost analysis study conducted in Spain randomized 430 adults referred to pulmonology for suspected OSA to receive either in-lab PSG or HRP. Patients received treatment with continuous positive airway pressure (CPAP) if their REI was ≥ 5 for HRP or their AHI was ≥ 5 for PSG with significant clinical symptoms, which is consistent with the Spanish Sleep Network guidelines.⁵ All patients in both arms received sleep hygiene instruction, nutrition education, and single-session auto-CPAP titration, and were evaluated at 1 and 3 months to assess for compliance. At 6 months, all patients were evaluated with PSG.

Home respiratory polygraphy was found to be more cost-effective than laboratory polysomnography, with a savings equivalent to more than half the cost of PSG—or about $450 per study.

HRP was found to be non-inferior to PSG based on Epworth Sleepiness Scale (ESS) scores evaluated at baseline and at 6-month follow-up (HRP mean = -4.2 points; 95% confidence interval [CI], -4.8 to -3.6 and PSG mean -4.9; 95% CI, -5.4 to -4.3; P = .14). Both groups had similar secondary outcomes. Quality-of-life as measured by the 30-point Functional Outcomes of Sleep Questionnaire improved by an average of 6.7 (standard deviation [SD] = 16.7) in the HRP group vs 6.5 (SD = 18.1) in the PSG group (P = .92). Systolic and diastolic blood pressure improved significantly in both groups without any statistically significant difference between the groups. HRP was also found to be more cost-effective than PSG with a savings equivalent to more than half the cost of PSG, or about $450 per study (depending on the exchange rate).

WHAT’S NEW

HRP offers advantages for low-risk patients

In the majority of patients, OSA can be diagnosed at home with outcomes similar to those for lab diagnosis, decreased cost, and decreased time from suspected diagnosis to treatment. HRP is acceptable for patients with a high probability of OSA without significant comorbidities if monitoring includes at least airflow, respiratory effort, and blood oxygenation.⁶

Continue to: CAVEATS

Recommendations are somewhat ambiguous

This study, as well as current guidelines, recommend home sleep studies for patients with a high clinical suspicion or high pre-test probability of OSA and who lack comorbid conditions that could affect sleep. The comorbid conditions are well identified: COPD, heart failure hypoventilation syndromes, insomnia, hypersomnia, parasomnia, periodic limb movement disorder, narcolepsy, and chronic opioid use.⁶ However, what constitutes “a high clinical suspicion” or “high pre-test probability” was not well defined in this study.

Several clinical screening tools are available and include the ESS, Berlin Questionnaire, and STOP-BANG Scoring System (Snoring, Tiredness, Observed apnea, Pressure [systemic hypertension], Body mass index > 35, Age > 50 years, Neck circumference > 16 inches, male Gender). An ESS score ≥ 10 warrants further evaluation, but is not very sensitive. Two or more positive categories on the Berlin Questionnaire indicates a high risk of OSA with a sensitivity of 76%, 77%, and 77% for mild, moderate, and severe OSA, respectively.⁷ A score of ≥ 3 on the STOP-BANG Scoring System has been validated and has a sensitivity of 83.6%, 92.9%, and 100% for an AHI > 5, > 15, and > 30, respectively.⁸

Home sleep studies should not be used to screen the general population.

CHALLENGES TO IMPLEMENTATION

Recommendations may present a challenge but insurance should not

The American Academy of Sleep Medicine recommends that portable monitoring must record airflow, respiratory effort, and blood oxygenation, and the device must be able to display the raw data to be interpreted by a board-certified sleep medicine physician according to current published standards.⁶ Implementation would require appropriate selection of a home monitoring device, consultation with a sleep medicine specialist, and significant patient education to ensure interpretable results.

Insurance should not be a barrier to implementation as the Centers for Medicare and Medicaid Services accept home sleep apnea testing results for CPAP prescriptions.⁹ However, variability currently exists regarding the extent to which private insurers provide coverage for home sleep apnea testing.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

A 50-year-old overweight male with a history of hypertension presents to your office for a yearly physical. On review of symptoms, he notes feeling constantly tired, despite reported good sleep hygiene practices. He scores 11 on the Epworth Sleepiness Scale, and his wife complains about his snoring. You have a high suspicion of obstructive sleep apnea. What is your next step?

Obstructive sleep apnea (OSA) is quite common, affecting at least 2% to 4% of the general adult population.² The gold standard for OSA diagnosis has been laboratory polysomnography (PSG) to measure the apnea-hypopnea index (AHI), which is the average number of apneas and hypopneas per hour of sleep, and the respiratory event index (REI), which is the average number of apneas, hypopneas, and respiratory effort-related arousals per hour of sleep. A minimum of 5 on the AHI or REI, along with clinical symptoms, is required for diagnosis.

Many adults go undiagnosed and untreated, however, due to barriers to diagnosis including the inconvenience of laboratory PSG.³ Sleep laboratories often have a significant wait time for evaluation, and sleeping in an unfamiliar place can be inconvenient or intolerable for some patients, making diagnosis difficult despite high clinical suspicion. Untreated sleep apnea is associated with an increased risk of hypertension, coronary artery disease, congestive heart failure, stroke, atrial fibrillation, and type 2 diabetes.⁴

Home sleep studies are an alternative for patients with a high risk of OSA without comorbid sleep conditions, heart failure, or chronic obstructive pulmonary disease (COPD). This study investigated the long-term effectiveness of diagnosis by home respiratory polygraphy (HRP) vs laboratory PSG in patients with an intermediate to high clinical suspicion for OSA.

STUDY SUMMARY

Home Dx is noninferior to lab Dx in all aspects studied

This multicenter, noninferiority randomized controlled trial and cost analysis study conducted in Spain randomized 430 adults referred to pulmonology for suspected OSA to receive either in-lab PSG or HRP. Patients received treatment with continuous positive airway pressure (CPAP) if their REI was ≥ 5 for HRP or their AHI was ≥ 5 for PSG with significant clinical symptoms, which is consistent with the Spanish Sleep Network guidelines.⁵ All patients in both arms received sleep hygiene instruction, nutrition education, and single-session auto-CPAP titration, and were evaluated at 1 and 3 months to assess for compliance. At 6 months, all patients were evaluated with PSG.

Home respiratory polygraphy was found to be more cost-effective than laboratory polysomnography, with a savings equivalent to more than half the cost of PSG—or about $450 per study.

HRP was found to be non-inferior to PSG based on Epworth Sleepiness Scale (ESS) scores evaluated at baseline and at 6-month follow-up (HRP mean = -4.2 points; 95% confidence interval [CI], -4.8 to -3.6 and PSG mean -4.9; 95% CI, -5.4 to -4.3; P = .14). Both groups had similar secondary outcomes. Quality-of-life as measured by the 30-point Functional Outcomes of Sleep Questionnaire improved by an average of 6.7 (standard deviation [SD] = 16.7) in the HRP group vs 6.5 (SD = 18.1) in the PSG group (P = .92). Systolic and diastolic blood pressure improved significantly in both groups without any statistically significant difference between the groups. HRP was also found to be more cost-effective than PSG with a savings equivalent to more than half the cost of PSG, or about $450 per study (depending on the exchange rate).

WHAT’S NEW

HRP offers advantages for low-risk patients

In the majority of patients, OSA can be diagnosed at home with outcomes similar to those for lab diagnosis, decreased cost, and decreased time from suspected diagnosis to treatment. HRP is acceptable for patients with a high probability of OSA without significant comorbidities if monitoring includes at least airflow, respiratory effort, and blood oxygenation.⁶

Continue to: CAVEATS

Recommendations are somewhat ambiguous

This study, as well as current guidelines, recommend home sleep studies for patients with a high clinical suspicion or high pre-test probability of OSA and who lack comorbid conditions that could affect sleep. The comorbid conditions are well identified: COPD, heart failure hypoventilation syndromes, insomnia, hypersomnia, parasomnia, periodic limb movement disorder, narcolepsy, and chronic opioid use.⁶ However, what constitutes “a high clinical suspicion” or “high pre-test probability” was not well defined in this study.

Several clinical screening tools are available and include the ESS, Berlin Questionnaire, and STOP-BANG Scoring System (Snoring, Tiredness, Observed apnea, Pressure [systemic hypertension], Body mass index > 35, Age > 50 years, Neck circumference > 16 inches, male Gender). An ESS score ≥ 10 warrants further evaluation, but is not very sensitive. Two or more positive categories on the Berlin Questionnaire indicates a high risk of OSA with a sensitivity of 76%, 77%, and 77% for mild, moderate, and severe OSA, respectively.⁷ A score of ≥ 3 on the STOP-BANG Scoring System has been validated and has a sensitivity of 83.6%, 92.9%, and 100% for an AHI > 5, > 15, and > 30, respectively.⁸

Home sleep studies should not be used to screen the general population.

CHALLENGES TO IMPLEMENTATION

Recommendations may present a challenge but insurance should not

The American Academy of Sleep Medicine recommends that portable monitoring must record airflow, respiratory effort, and blood oxygenation, and the device must be able to display the raw data to be interpreted by a board-certified sleep medicine physician according to current published standards.⁶ Implementation would require appropriate selection of a home monitoring device, consultation with a sleep medicine specialist, and significant patient education to ensure interpretable results.

Insurance should not be a barrier to implementation as the Centers for Medicare and Medicaid Services accept home sleep apnea testing results for CPAP prescriptions.⁹ However, variability currently exists regarding the extent to which private insurers provide coverage for home sleep apnea testing.

ACKNOWLEDGMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.