CHICAGO—An Alzheimer’s Association workgroup has developed 20 recommendations for the clinical evaluation of patients with cognitive or behavioral complaints. All middle-aged or older individuals who report or whose care partner or clinician reports cognitive, behavioral, or functional changes should undergo a timely evaluation, the guidelines advise. A care partner almost always should be involved the evaluation, according to the guidelines.

The recommendations cover the recognition and evaluation of symptoms, selection of brain imaging and other tests, and communication with and support of affected individuals and their caregivers.

Cognitive Behavioral Syndromes

The clinical practice guidelines recognize a broad category of cognitive behavioral syndromes marked by memory and thinking symptoms as well as changes in sleep, anxiety, personality, and relationships.

The Alzheimer’s Association in 2017 convened a Diagnostic Evaluation Clinical Practice Guideline workgroup to develop evidence-based guidelines. The group includes experts in medical, neuropsychologic, and nursing specialties. The members conducted a systematic review of the literature and made recommendations using a modified Delphi consensus process. They graded the recommendations as “A” (must be done; will improve outcomes in almost all cases), “B” (should be done), and “C” (may be done).

The recommendations emphasize obtaining a history from not only the patient, but also from someone who knows the patient well to establish the presence and characteristics of any substantial changes and to categorize the cognitive behavioral syndrome.

Other recommendations for evaluating patients with cognitive behavioral syndromes include the following:

• For patients with atypical or rapidly progressive cognitive behavioral symptoms, the clinician should expedite an evaluation and strongly consider referral to a specialist. (Level A)
• The evaluation process should use tiers of assessments and tests based on a patient’s presentation, risk factors, and profile. (Level A)
• The clinician should involve an informant to obtain reliable information about changes in cognition, activities of daily living, mood and other neuropsychiatric symptoms, and sensory and motor function. Use of structured instruments for assessing these domains is helpful. (Level A)
• Clinicians should use validated tools to assess cognition. (Level A)
• When office-based cognitive assessment is not sufficiently informative (eg, when interpretation of results is uncertain due to a complex clinical profile or confounding demographic characteristics), neuropsychologic evaluation is recommended. (Level A)
• The clinician should obtain MRI as a first-tier approach to aid in establishing etiology. If MRI is not available or is contraindicated, CT should be obtained. (Level B)
• If etiology remains uncertain after interpretation of structural imaging, a dementia specialist can obtain molecular imaging with FDG-PET to improve diagnostic accuracy. (Level B)
• In cases with continued diagnostic uncertainty, a dementia specialist can obtain CSF according to appropriate use criteria for analysis of aβ42 amyloid and tau/p-tau profiles to evaluate for Alzheimer’s disease pathology. (Level C)
• If diagnostic uncertainty remains after obtaining structural imaging and FDG-PET, and CSF aβ and tau/p-tau profiles are unavailable or uninterpretable, the dementia specialist can obtain an amyloid PET scan according to the appropriate use criteria. (Level C)
• In a patient with an established cognitive behavioral syndrome and a likely autosomal dominant family history, the dementia specialist should consider whether genetic testing is warranted. A genetic counselor should be involved throughout the process. (Level A)

A Tool for Medical Professionals

According to the workgroup, a timely and accurate diagnosis of Alzheimer’s disease and related dementias increases patient autonomy when he or she is most able to participate in goals of treatment and life and care decisions. It also allows for early intervention to maximize support opportunities and treatment outcomes.

“These new guidelines will provide an important new tool for medical professionals to more accurately diagnose Alzheimer’s [disease] and other dementias. As a result, people will get the right care and appropriate treatments; families will get the right support and be able to plan for the future,” said James Hendrix, PhD, Alzheimer’s Association Director of Global Science Initiatives and a member of the workgroup. “Too often, cognitive and behavioral symptoms due to Alzheimer’s disease and other dementias are unrecognized or attributed to something else.”

“The guidelines can empower patients, families, and clinicians to expect that symptoms will be evaluated in a patient-centered, structured, and collaborative manner,” Dr. Atri said. “In addition, they help to ensure that, regardless of the specific diagnosis, the results are communicated in a timely and compassionate way to help patients and families live the best lives possible.”

CHICAGO—An Alzheimer’s Association workgroup has developed 20 recommendations for the clinical evaluation of patients with cognitive or behavioral complaints. All middle-aged or older individuals who report or whose care partner or clinician reports cognitive, behavioral, or functional changes should undergo a timely evaluation, the guidelines advise. A care partner almost always should be involved the evaluation, according to the guidelines.

The recommendations cover the recognition and evaluation of symptoms, selection of brain imaging and other tests, and communication with and support of affected individuals and their caregivers.

Cognitive Behavioral Syndromes

The clinical practice guidelines recognize a broad category of cognitive behavioral syndromes marked by memory and thinking symptoms as well as changes in sleep, anxiety, personality, and relationships.

The Alzheimer’s Association in 2017 convened a Diagnostic Evaluation Clinical Practice Guideline workgroup to develop evidence-based guidelines. The group includes experts in medical, neuropsychologic, and nursing specialties. The members conducted a systematic review of the literature and made recommendations using a modified Delphi consensus process. They graded the recommendations as “A” (must be done; will improve outcomes in almost all cases), “B” (should be done), and “C” (may be done).

The recommendations emphasize obtaining a history from not only the patient, but also from someone who knows the patient well to establish the presence and characteristics of any substantial changes and to categorize the cognitive behavioral syndrome.

Other recommendations for evaluating patients with cognitive behavioral syndromes include the following:

• For patients with atypical or rapidly progressive cognitive behavioral symptoms, the clinician should expedite an evaluation and strongly consider referral to a specialist. (Level A)
• The evaluation process should use tiers of assessments and tests based on a patient’s presentation, risk factors, and profile. (Level A)
• The clinician should involve an informant to obtain reliable information about changes in cognition, activities of daily living, mood and other neuropsychiatric symptoms, and sensory and motor function. Use of structured instruments for assessing these domains is helpful. (Level A)
• Clinicians should use validated tools to assess cognition. (Level A)
• When office-based cognitive assessment is not sufficiently informative (eg, when interpretation of results is uncertain due to a complex clinical profile or confounding demographic characteristics), neuropsychologic evaluation is recommended. (Level A)
• The clinician should obtain MRI as a first-tier approach to aid in establishing etiology. If MRI is not available or is contraindicated, CT should be obtained. (Level B)
• If etiology remains uncertain after interpretation of structural imaging, a dementia specialist can obtain molecular imaging with FDG-PET to improve diagnostic accuracy. (Level B)
• In cases with continued diagnostic uncertainty, a dementia specialist can obtain CSF according to appropriate use criteria for analysis of aβ42 amyloid and tau/p-tau profiles to evaluate for Alzheimer’s disease pathology. (Level C)
• If diagnostic uncertainty remains after obtaining structural imaging and FDG-PET, and CSF aβ and tau/p-tau profiles are unavailable or uninterpretable, the dementia specialist can obtain an amyloid PET scan according to the appropriate use criteria. (Level C)
• In a patient with an established cognitive behavioral syndrome and a likely autosomal dominant family history, the dementia specialist should consider whether genetic testing is warranted. A genetic counselor should be involved throughout the process. (Level A)

A Tool for Medical Professionals

According to the workgroup, a timely and accurate diagnosis of Alzheimer’s disease and related dementias increases patient autonomy when he or she is most able to participate in goals of treatment and life and care decisions. It also allows for early intervention to maximize support opportunities and treatment outcomes.

“These new guidelines will provide an important new tool for medical professionals to more accurately diagnose Alzheimer’s [disease] and other dementias. As a result, people will get the right care and appropriate treatments; families will get the right support and be able to plan for the future,” said James Hendrix, PhD, Alzheimer’s Association Director of Global Science Initiatives and a member of the workgroup. “Too often, cognitive and behavioral symptoms due to Alzheimer’s disease and other dementias are unrecognized or attributed to something else.”

“The guidelines can empower patients, families, and clinicians to expect that symptoms will be evaluated in a patient-centered, structured, and collaborative manner,” Dr. Atri said. “In addition, they help to ensure that, regardless of the specific diagnosis, the results are communicated in a timely and compassionate way to help patients and families live the best lives possible.”

CHICAGO—An Alzheimer’s Association workgroup has developed 20 recommendations for the clinical evaluation of patients with cognitive or behavioral complaints. All middle-aged or older individuals who report or whose care partner or clinician reports cognitive, behavioral, or functional changes should undergo a timely evaluation, the guidelines advise. A care partner almost always should be involved the evaluation, according to the guidelines.

The recommendations cover the recognition and evaluation of symptoms, selection of brain imaging and other tests, and communication with and support of affected individuals and their caregivers.

Cognitive Behavioral Syndromes

The clinical practice guidelines recognize a broad category of cognitive behavioral syndromes marked by memory and thinking symptoms as well as changes in sleep, anxiety, personality, and relationships.

The Alzheimer’s Association in 2017 convened a Diagnostic Evaluation Clinical Practice Guideline workgroup to develop evidence-based guidelines. The group includes experts in medical, neuropsychologic, and nursing specialties. The members conducted a systematic review of the literature and made recommendations using a modified Delphi consensus process. They graded the recommendations as “A” (must be done; will improve outcomes in almost all cases), “B” (should be done), and “C” (may be done).

The recommendations emphasize obtaining a history from not only the patient, but also from someone who knows the patient well to establish the presence and characteristics of any substantial changes and to categorize the cognitive behavioral syndrome.

Other recommendations for evaluating patients with cognitive behavioral syndromes include the following:

• For patients with atypical or rapidly progressive cognitive behavioral symptoms, the clinician should expedite an evaluation and strongly consider referral to a specialist. (Level A)
• The evaluation process should use tiers of assessments and tests based on a patient’s presentation, risk factors, and profile. (Level A)
• The clinician should involve an informant to obtain reliable information about changes in cognition, activities of daily living, mood and other neuropsychiatric symptoms, and sensory and motor function. Use of structured instruments for assessing these domains is helpful. (Level A)
• Clinicians should use validated tools to assess cognition. (Level A)
• When office-based cognitive assessment is not sufficiently informative (eg, when interpretation of results is uncertain due to a complex clinical profile or confounding demographic characteristics), neuropsychologic evaluation is recommended. (Level A)
• The clinician should obtain MRI as a first-tier approach to aid in establishing etiology. If MRI is not available or is contraindicated, CT should be obtained. (Level B)
• If etiology remains uncertain after interpretation of structural imaging, a dementia specialist can obtain molecular imaging with FDG-PET to improve diagnostic accuracy. (Level B)
• In cases with continued diagnostic uncertainty, a dementia specialist can obtain CSF according to appropriate use criteria for analysis of aβ42 amyloid and tau/p-tau profiles to evaluate for Alzheimer’s disease pathology. (Level C)
• If diagnostic uncertainty remains after obtaining structural imaging and FDG-PET, and CSF aβ and tau/p-tau profiles are unavailable or uninterpretable, the dementia specialist can obtain an amyloid PET scan according to the appropriate use criteria. (Level C)
• In a patient with an established cognitive behavioral syndrome and a likely autosomal dominant family history, the dementia specialist should consider whether genetic testing is warranted. A genetic counselor should be involved throughout the process. (Level A)

A Tool for Medical Professionals

According to the workgroup, a timely and accurate diagnosis of Alzheimer’s disease and related dementias increases patient autonomy when he or she is most able to participate in goals of treatment and life and care decisions. It also allows for early intervention to maximize support opportunities and treatment outcomes.

“These new guidelines will provide an important new tool for medical professionals to more accurately diagnose Alzheimer’s [disease] and other dementias. As a result, people will get the right care and appropriate treatments; families will get the right support and be able to plan for the future,” said James Hendrix, PhD, Alzheimer’s Association Director of Global Science Initiatives and a member of the workgroup. “Too often, cognitive and behavioral symptoms due to Alzheimer’s disease and other dementias are unrecognized or attributed to something else.”

“The guidelines can empower patients, families, and clinicians to expect that symptoms will be evaluated in a patient-centered, structured, and collaborative manner,” Dr. Atri said. “In addition, they help to ensure that, regardless of the specific diagnosis, the results are communicated in a timely and compassionate way to help patients and families live the best lives possible.”

Case Report

Four-year-old identical triplet girls with numerous asymptomatic scattered papules on the chest of 4 months’ duration were referred to a dermatologist by their pediatrician for molluscum contagiosum. The patients’ father reported that there was no history of trauma, irritation, or manipulation to the affected area. Their medical history was notable for prematurity at 32 weeks’ gestation and congenital dermal melanocytosis. Family history was notable for their father having acne and similar papules on the chest during adolescence that resolved with isotretinoin therapy.

On physical examination there were multiple smooth, hyperpigmented to erythematous, comedonal, 1- to 2-mm papules dispersed on the anterior central chest of all 3 patients (Figure 1). Clinically, these lesions were fairly indistinguishable from other common dermatologic conditions such as acne or milia. Dermoscopic examination revealed homogenous yellow-white areas surrounded by light brown to erythematous halos (Figure 2). Histopathologic examination was not performed given the benign clinical diagnosis and avoidance of biopsy in pediatric populations. Based on dermoscopic features and history, a diagnosis of eruptive vellus hair cysts (EVHCs) in identical triplets was made.

Comment

Pathogenesis
Eruptive vellus hair cysts, first introduced by Esterly et al¹ in 1977, are uncommon benign lesions presumed to be caused by an abnormal development of the infundibular portion of the hair follicle.² They are usually 1- to 3-mm, reddish brown, monomorphous papules overlapping with pilosebaceous and apocrine units.³ Although the lesions typically are located on the chest and extremities, they may occur on the face, abdomen, axillae, buttocks, or genital area.^1,3 The inheritance of EVHCs is unclear. The majority of reported cases are sporadic; however, the literature mentions 19 families affected by autosomal-dominant EVHCs based on phylogeny.³ In 2015, EVHCs were reported in identical twins, further supporting the case for a genetic mutation.⁴ We augment this autosomal-dominant inheritance pattern by presenting a case of identical triplets with EVHCs. The patients’ father reported similar lesions in childhood, further underscoring a genetic basis.

The pathogenesis of EVHC is uncertain, with 2 main theories. Some propose retention of vellus hair and keratin in a cavity formed by an abnormal vellus hair follicle causing infundibular occlusion. Others consider the growth of benign follicular hamartomas that differentiate to become vellus hairs.¹

Clinical Presentation
The sporadic form of EVHCs is noted to be more common and clinically presents later, with an average age at onset of 16 years and an average age at diagnosis of 24 years.³ The sporadic form occurs without trauma or manipulation as a precursor. Less commonly, lesions present at birth or in early infancy and may show an autosomal-dominant inheritance pattern with a similar distribution across relatives.³

Other variants of EVHCs have been described. Late-onset EVHC usually occurs at 35 years or older (average age, 57 years), with a female to male predominance of 2.5 to 1.³ This late onset may be attributed to proliferation of ductal follicular keratinocytes or loss of perifollicular elastic fibers exacerbated by exogenous factors such as manipulation, UV rays, or trauma.⁵

For unilesional EVHC, the average age at diagnosis is 27 years.³ Some of these lesions may be pedunculated and greater than 8 mm. There is a female to male predominance of 2 to 1. Eruptive vellus hair cysts with steatocystoma multiplex can be seen with an average age at onset of 19 years and a female to male predominance of 0.2 to 1. There may be a family history of this subset, as reported in 3 patients with this pattern.³

Diagnosis
The recommended workup for EVHCs varies by patient and age. Eruptive vellus hair cysts present an opportunity to utilize noninvasive diagnostic procedures, especially for the pediatric population, to avoid scarring and pain from manipulation or biopsies. Although many practitioners may comfortably diagnose EVHCs clinically, 6 cases were misdiagnosed as steatocystoma multiplex, keratosis pilaris, or milia prior to histopathology revealing vellus hair cysts.⁶

Dermoscopy presents as a useful diagnostic aid. Eruptive vellus hair cysts exhibit light yellow homogenous circular structures with a maroon or erythematous halo.^2,7 A central gray-blue color point may be seen due to melanin in the pigmented hair shaft.⁷ A dermoscopy review of EVHCs reported radiating capillaries.² Occasionally, nonfollicular homogenous blue pigmentation may be seen due to a connection to atrophic hair follicles in the mid dermis and no normal hair follicle around the cysts.⁸ In comparison, dermoscopic characteristics of molluscum contagiosum demonstrated a polylobular, white-yellow, amorphous structure at the center with a hardened central umbilicated core and a crown of hairpin vessels at the periphery. Additionally, comedonal acne, commonly mistaken for EVHCs, reveals a brown-yellow hard central plug with sparse inflammation under dermoscopy.² Thus, differentiation of these entities with dermoscopy should be highly prioritized to better aid in the diagnosis of pediatric dermatologic conditions using painless noninvasive techniques.

Treatment
The main indication for treatment of EVHCs is cosmetic concern. Twenty-five percent of EVHCs spontaneously resolve with transepidermal hair elimination or a granulomatous reaction.^4,5 A case report of 4 siblings with congenital EVHCs also described a mother with similar lesions that resolved spontaneously in early adulthood,³ as our patients’ father also noted. Treatment modalities including topical keratolytic agents such as urea 10%, retinoic acid 0.05%, tazarotene cream 0.1%, and lactic acid 12%; incision and drainage; CO₂ laser; or erbium-doped YAG laser ablation have been tried with minimal improvement.⁹ Of note, tazarotene cream 0.1% has demonstrated better results than both erbium-doped YAG laser and drainage and incision of EVHCs.⁴ Additionally, another report evidenced partial improvement with calcipotriene within 2 months with some lesions completely resolved and others flattened, which may be attributed to the antiproliferative and prodifferentiating effects on the ductal follicular keratinocytes by calcipotriene.⁵ Lastly, an additional study indicated that isotretinoin and vitamin A derivatives were ineffective for clearing EVHCs.¹⁰

Conclusion

We presented 3 identical triplets with the classic pediatric onset and dermoscopic findings of EVHCs on the trunk. Although the definitive diagnosis of EVHCs relies on histopathology, we argue that their unique dermoscopic findings combined with a thorough clinical examination is sufficient to recognize this benign condition and avoid painful procedures in the pediatric population.

Case Report

Four-year-old identical triplet girls with numerous asymptomatic scattered papules on the chest of 4 months’ duration were referred to a dermatologist by their pediatrician for molluscum contagiosum. The patients’ father reported that there was no history of trauma, irritation, or manipulation to the affected area. Their medical history was notable for prematurity at 32 weeks’ gestation and congenital dermal melanocytosis. Family history was notable for their father having acne and similar papules on the chest during adolescence that resolved with isotretinoin therapy.

On physical examination there were multiple smooth, hyperpigmented to erythematous, comedonal, 1- to 2-mm papules dispersed on the anterior central chest of all 3 patients (Figure 1). Clinically, these lesions were fairly indistinguishable from other common dermatologic conditions such as acne or milia. Dermoscopic examination revealed homogenous yellow-white areas surrounded by light brown to erythematous halos (Figure 2). Histopathologic examination was not performed given the benign clinical diagnosis and avoidance of biopsy in pediatric populations. Based on dermoscopic features and history, a diagnosis of eruptive vellus hair cysts (EVHCs) in identical triplets was made.

Comment

Pathogenesis
Eruptive vellus hair cysts, first introduced by Esterly et al¹ in 1977, are uncommon benign lesions presumed to be caused by an abnormal development of the infundibular portion of the hair follicle.² They are usually 1- to 3-mm, reddish brown, monomorphous papules overlapping with pilosebaceous and apocrine units.³ Although the lesions typically are located on the chest and extremities, they may occur on the face, abdomen, axillae, buttocks, or genital area.^1,3 The inheritance of EVHCs is unclear. The majority of reported cases are sporadic; however, the literature mentions 19 families affected by autosomal-dominant EVHCs based on phylogeny.³ In 2015, EVHCs were reported in identical twins, further supporting the case for a genetic mutation.⁴ We augment this autosomal-dominant inheritance pattern by presenting a case of identical triplets with EVHCs. The patients’ father reported similar lesions in childhood, further underscoring a genetic basis.

The pathogenesis of EVHC is uncertain, with 2 main theories. Some propose retention of vellus hair and keratin in a cavity formed by an abnormal vellus hair follicle causing infundibular occlusion. Others consider the growth of benign follicular hamartomas that differentiate to become vellus hairs.¹

Clinical Presentation
The sporadic form of EVHCs is noted to be more common and clinically presents later, with an average age at onset of 16 years and an average age at diagnosis of 24 years.³ The sporadic form occurs without trauma or manipulation as a precursor. Less commonly, lesions present at birth or in early infancy and may show an autosomal-dominant inheritance pattern with a similar distribution across relatives.³

Other variants of EVHCs have been described. Late-onset EVHC usually occurs at 35 years or older (average age, 57 years), with a female to male predominance of 2.5 to 1.³ This late onset may be attributed to proliferation of ductal follicular keratinocytes or loss of perifollicular elastic fibers exacerbated by exogenous factors such as manipulation, UV rays, or trauma.⁵

For unilesional EVHC, the average age at diagnosis is 27 years.³ Some of these lesions may be pedunculated and greater than 8 mm. There is a female to male predominance of 2 to 1. Eruptive vellus hair cysts with steatocystoma multiplex can be seen with an average age at onset of 19 years and a female to male predominance of 0.2 to 1. There may be a family history of this subset, as reported in 3 patients with this pattern.³

Diagnosis
The recommended workup for EVHCs varies by patient and age. Eruptive vellus hair cysts present an opportunity to utilize noninvasive diagnostic procedures, especially for the pediatric population, to avoid scarring and pain from manipulation or biopsies. Although many practitioners may comfortably diagnose EVHCs clinically, 6 cases were misdiagnosed as steatocystoma multiplex, keratosis pilaris, or milia prior to histopathology revealing vellus hair cysts.⁶

Dermoscopy presents as a useful diagnostic aid. Eruptive vellus hair cysts exhibit light yellow homogenous circular structures with a maroon or erythematous halo.^2,7 A central gray-blue color point may be seen due to melanin in the pigmented hair shaft.⁷ A dermoscopy review of EVHCs reported radiating capillaries.² Occasionally, nonfollicular homogenous blue pigmentation may be seen due to a connection to atrophic hair follicles in the mid dermis and no normal hair follicle around the cysts.⁸ In comparison, dermoscopic characteristics of molluscum contagiosum demonstrated a polylobular, white-yellow, amorphous structure at the center with a hardened central umbilicated core and a crown of hairpin vessels at the periphery. Additionally, comedonal acne, commonly mistaken for EVHCs, reveals a brown-yellow hard central plug with sparse inflammation under dermoscopy.² Thus, differentiation of these entities with dermoscopy should be highly prioritized to better aid in the diagnosis of pediatric dermatologic conditions using painless noninvasive techniques.

Treatment
The main indication for treatment of EVHCs is cosmetic concern. Twenty-five percent of EVHCs spontaneously resolve with transepidermal hair elimination or a granulomatous reaction.^4,5 A case report of 4 siblings with congenital EVHCs also described a mother with similar lesions that resolved spontaneously in early adulthood,³ as our patients’ father also noted. Treatment modalities including topical keratolytic agents such as urea 10%, retinoic acid 0.05%, tazarotene cream 0.1%, and lactic acid 12%; incision and drainage; CO₂ laser; or erbium-doped YAG laser ablation have been tried with minimal improvement.⁹ Of note, tazarotene cream 0.1% has demonstrated better results than both erbium-doped YAG laser and drainage and incision of EVHCs.⁴ Additionally, another report evidenced partial improvement with calcipotriene within 2 months with some lesions completely resolved and others flattened, which may be attributed to the antiproliferative and prodifferentiating effects on the ductal follicular keratinocytes by calcipotriene.⁵ Lastly, an additional study indicated that isotretinoin and vitamin A derivatives were ineffective for clearing EVHCs.¹⁰

Conclusion

We presented 3 identical triplets with the classic pediatric onset and dermoscopic findings of EVHCs on the trunk. Although the definitive diagnosis of EVHCs relies on histopathology, we argue that their unique dermoscopic findings combined with a thorough clinical examination is sufficient to recognize this benign condition and avoid painful procedures in the pediatric population.

Case Report

Four-year-old identical triplet girls with numerous asymptomatic scattered papules on the chest of 4 months’ duration were referred to a dermatologist by their pediatrician for molluscum contagiosum. The patients’ father reported that there was no history of trauma, irritation, or manipulation to the affected area. Their medical history was notable for prematurity at 32 weeks’ gestation and congenital dermal melanocytosis. Family history was notable for their father having acne and similar papules on the chest during adolescence that resolved with isotretinoin therapy.

On physical examination there were multiple smooth, hyperpigmented to erythematous, comedonal, 1- to 2-mm papules dispersed on the anterior central chest of all 3 patients (Figure 1). Clinically, these lesions were fairly indistinguishable from other common dermatologic conditions such as acne or milia. Dermoscopic examination revealed homogenous yellow-white areas surrounded by light brown to erythematous halos (Figure 2). Histopathologic examination was not performed given the benign clinical diagnosis and avoidance of biopsy in pediatric populations. Based on dermoscopic features and history, a diagnosis of eruptive vellus hair cysts (EVHCs) in identical triplets was made.

Comment

Pathogenesis
Eruptive vellus hair cysts, first introduced by Esterly et al¹ in 1977, are uncommon benign lesions presumed to be caused by an abnormal development of the infundibular portion of the hair follicle.² They are usually 1- to 3-mm, reddish brown, monomorphous papules overlapping with pilosebaceous and apocrine units.³ Although the lesions typically are located on the chest and extremities, they may occur on the face, abdomen, axillae, buttocks, or genital area.^1,3 The inheritance of EVHCs is unclear. The majority of reported cases are sporadic; however, the literature mentions 19 families affected by autosomal-dominant EVHCs based on phylogeny.³ In 2015, EVHCs were reported in identical twins, further supporting the case for a genetic mutation.⁴ We augment this autosomal-dominant inheritance pattern by presenting a case of identical triplets with EVHCs. The patients’ father reported similar lesions in childhood, further underscoring a genetic basis.

The pathogenesis of EVHC is uncertain, with 2 main theories. Some propose retention of vellus hair and keratin in a cavity formed by an abnormal vellus hair follicle causing infundibular occlusion. Others consider the growth of benign follicular hamartomas that differentiate to become vellus hairs.¹

Clinical Presentation
The sporadic form of EVHCs is noted to be more common and clinically presents later, with an average age at onset of 16 years and an average age at diagnosis of 24 years.³ The sporadic form occurs without trauma or manipulation as a precursor. Less commonly, lesions present at birth or in early infancy and may show an autosomal-dominant inheritance pattern with a similar distribution across relatives.³

Other variants of EVHCs have been described. Late-onset EVHC usually occurs at 35 years or older (average age, 57 years), with a female to male predominance of 2.5 to 1.³ This late onset may be attributed to proliferation of ductal follicular keratinocytes or loss of perifollicular elastic fibers exacerbated by exogenous factors such as manipulation, UV rays, or trauma.⁵

For unilesional EVHC, the average age at diagnosis is 27 years.³ Some of these lesions may be pedunculated and greater than 8 mm. There is a female to male predominance of 2 to 1. Eruptive vellus hair cysts with steatocystoma multiplex can be seen with an average age at onset of 19 years and a female to male predominance of 0.2 to 1. There may be a family history of this subset, as reported in 3 patients with this pattern.³

Diagnosis
The recommended workup for EVHCs varies by patient and age. Eruptive vellus hair cysts present an opportunity to utilize noninvasive diagnostic procedures, especially for the pediatric population, to avoid scarring and pain from manipulation or biopsies. Although many practitioners may comfortably diagnose EVHCs clinically, 6 cases were misdiagnosed as steatocystoma multiplex, keratosis pilaris, or milia prior to histopathology revealing vellus hair cysts.⁶

Dermoscopy presents as a useful diagnostic aid. Eruptive vellus hair cysts exhibit light yellow homogenous circular structures with a maroon or erythematous halo.^2,7 A central gray-blue color point may be seen due to melanin in the pigmented hair shaft.⁷ A dermoscopy review of EVHCs reported radiating capillaries.² Occasionally, nonfollicular homogenous blue pigmentation may be seen due to a connection to atrophic hair follicles in the mid dermis and no normal hair follicle around the cysts.⁸ In comparison, dermoscopic characteristics of molluscum contagiosum demonstrated a polylobular, white-yellow, amorphous structure at the center with a hardened central umbilicated core and a crown of hairpin vessels at the periphery. Additionally, comedonal acne, commonly mistaken for EVHCs, reveals a brown-yellow hard central plug with sparse inflammation under dermoscopy.² Thus, differentiation of these entities with dermoscopy should be highly prioritized to better aid in the diagnosis of pediatric dermatologic conditions using painless noninvasive techniques.

Treatment
The main indication for treatment of EVHCs is cosmetic concern. Twenty-five percent of EVHCs spontaneously resolve with transepidermal hair elimination or a granulomatous reaction.^4,5 A case report of 4 siblings with congenital EVHCs also described a mother with similar lesions that resolved spontaneously in early adulthood,³ as our patients’ father also noted. Treatment modalities including topical keratolytic agents such as urea 10%, retinoic acid 0.05%, tazarotene cream 0.1%, and lactic acid 12%; incision and drainage; CO₂ laser; or erbium-doped YAG laser ablation have been tried with minimal improvement.⁹ Of note, tazarotene cream 0.1% has demonstrated better results than both erbium-doped YAG laser and drainage and incision of EVHCs.⁴ Additionally, another report evidenced partial improvement with calcipotriene within 2 months with some lesions completely resolved and others flattened, which may be attributed to the antiproliferative and prodifferentiating effects on the ductal follicular keratinocytes by calcipotriene.⁵ Lastly, an additional study indicated that isotretinoin and vitamin A derivatives were ineffective for clearing EVHCs.¹⁰

Conclusion

We presented 3 identical triplets with the classic pediatric onset and dermoscopic findings of EVHCs on the trunk. Although the definitive diagnosis of EVHCs relies on histopathology, we argue that their unique dermoscopic findings combined with a thorough clinical examination is sufficient to recognize this benign condition and avoid painful procedures in the pediatric population.

Figure 1

The FP suspected that this was a nodular basal cell carcinoma (BCC) with pigmentation. The physical exam was suspicious because of the pearly appearance, superficial ulcerations, and presence of telangiectasias with a loss of the normal pore pattern. Dermoscopy gave further evidence for a nodular BCC by revealing arborizing “tree-like” telangiectasias, ulcerations, shiny white areas, and gray-blue globules. Skin cancers often produce their own vascular supply and also ulcerate. The shiny white areas (which are the result of collagen deposition and occur in many skin cancers) are best seen with polarized dermoscopy.

The FP recommended a shave biopsy and performed one immediately after obtaining patient consent. (See the Watch & Learn video on “Shave biopsy.”) Knowing that the BCC would be vascular, the FP injected 1% lidocaine with epinephrine and waited 15 minutes for the epinephrine to work.

After seeing another patient, he performed the shave biopsy with a Dermablade, and used a cotton-tipped applicator to vigorously apply the aluminum chloride to the site. He used a twisting motion and pressure to stop most of the bleeding and then used his electrosurgical instrument—with a sharp tipped electrode—to stop recalcitrant bleeders.

The patient was given a diagnosis of BCC on the follow-up visit. The FP referred the patient for Mohs surgery because of the large size and location of the tumor.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Figure 1

The FP suspected that this was a nodular basal cell carcinoma (BCC) with pigmentation. The physical exam was suspicious because of the pearly appearance, superficial ulcerations, and presence of telangiectasias with a loss of the normal pore pattern. Dermoscopy gave further evidence for a nodular BCC by revealing arborizing “tree-like” telangiectasias, ulcerations, shiny white areas, and gray-blue globules. Skin cancers often produce their own vascular supply and also ulcerate. The shiny white areas (which are the result of collagen deposition and occur in many skin cancers) are best seen with polarized dermoscopy.

The FP recommended a shave biopsy and performed one immediately after obtaining patient consent. (See the Watch & Learn video on “Shave biopsy.”) Knowing that the BCC would be vascular, the FP injected 1% lidocaine with epinephrine and waited 15 minutes for the epinephrine to work.

After seeing another patient, he performed the shave biopsy with a Dermablade, and used a cotton-tipped applicator to vigorously apply the aluminum chloride to the site. He used a twisting motion and pressure to stop most of the bleeding and then used his electrosurgical instrument—with a sharp tipped electrode—to stop recalcitrant bleeders.

The patient was given a diagnosis of BCC on the follow-up visit. The FP referred the patient for Mohs surgery because of the large size and location of the tumor.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Figure 1

The FP suspected that this was a nodular basal cell carcinoma (BCC) with pigmentation. The physical exam was suspicious because of the pearly appearance, superficial ulcerations, and presence of telangiectasias with a loss of the normal pore pattern. Dermoscopy gave further evidence for a nodular BCC by revealing arborizing “tree-like” telangiectasias, ulcerations, shiny white areas, and gray-blue globules. Skin cancers often produce their own vascular supply and also ulcerate. The shiny white areas (which are the result of collagen deposition and occur in many skin cancers) are best seen with polarized dermoscopy.

The FP recommended a shave biopsy and performed one immediately after obtaining patient consent. (See the Watch & Learn video on “Shave biopsy.”) Knowing that the BCC would be vascular, the FP injected 1% lidocaine with epinephrine and waited 15 minutes for the epinephrine to work.

After seeing another patient, he performed the shave biopsy with a Dermablade, and used a cotton-tipped applicator to vigorously apply the aluminum chloride to the site. He used a twisting motion and pressure to stop most of the bleeding and then used his electrosurgical instrument—with a sharp tipped electrode—to stop recalcitrant bleeders.

The patient was given a diagnosis of BCC on the follow-up visit. The FP referred the patient for Mohs surgery because of the large size and location of the tumor.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Karnes J, Usatine R. Basal cell carcinoma. In: Usatine R, Smith M, Mayeaux EJ, et al. Color Atlas of Family Medicine. 2nd ed. New York, NY: McGraw-Hill; 2013:989-998.

To learn more about the Color Atlas of Family Medicine, see: www.amazon.com/Color-Family-Medicine-Richard-Usatine/dp/0071769641/.

You can now get the second edition of the Color Atlas of Family Medicine as an app by clicking on this link: usatinemedia.com.

Blastomycosis is a polymorphic disease caused by the thermally dimorphic fungus Blastomyces dermatitidis, which is naturally occurring worldwide but particularly prominent in the Great Lakes, Mississippi, and Ohio River areas of the United States. The disease was first described by Thomas Caspar Gilchrist in 1894 and historically has been referred to as Gilchrist disease, North American blastomycosis, or Chicago disease.^1,2 Cutaneous blastomycosis can occur by dissemination of yeast to the skin from systemic and pulmonary disease or rarely via direct inoculation of the skin resulting in primary cutaneous disease. Clinically, the lesions are polymorphic and may appear as well-demarcated verrucous plaques containing foci of pustules or ulcerations. Lesions typically heal centrifugally with a cribriform scar.³

We describe an adolescent with a unique history of inoculation 2 weeks prior to the development of a biopsy-confirmed lesion of cutaneous blastomycosis on the left chest wall that clinically resolved following 6 months of itraconazole.

Case Report

A 16-year-old adolescent boy with a history of morbid obesity, asthma, and seasonal allergies presented for evaluation of a painful, slowly enlarging skin lesion on the left chest wall of 2 months’ duration. According to the patient, a “small pimple” appeared at the site of impact 2 weeks following a fall into a muddy flowerbed in Madison, Wisconsin. The patient recalled that although he had soiled his clothing, there was no identifiable puncture of the skin. Despite daily application of hydrogen peroxide and a 1-week course of trimethoprim-sulfamethoxazole, the lesion gradually enlarged. Complete review of systems as well as exposure and travel history were otherwise negative.

Physical examination revealed a 5.0×2.5-cm exophytic, firm, well-circumscribed plaque with a papillated crusted surface on the left side of the chest near the posterior axillary line (Figure 1). There was no palpable regional lymphadenopathy. Pulmonary examination was unremarkable. Diagnostic workup, including complete blood cell count with differential, hemoglobin A_1c, human immunodeficiency virus antibody/antigen testing, interferon-gamma release assay, and chest radiograph were all within normal limits.

Histologic examination of a biopsy specimen showed pseudoepitheliomatous hyperplasia of the epidermis with a brisk mixed inflammatory infiltrate (Figure 2). Displayed in Figure 3 is the Grocott-Gomori methenamine-silver stain that highlighted the thick double-contoured wall-budding yeasts.

The patient was diagnosed with primary cutaneous blastomycosis. Treatment was initiated with itraconazole 200 mg 3 times daily for 3 days, followed by 200 mg 2 times daily for 6 months. Following 3 months of therapy, the lesion had markedly improved with violaceous dyschromia and no residual surface changes. After 5 months of itraconazole, the patient stopped taking the medication for 2 months due to pharmacy issues and then resumed. After 6 total months of therapy, the lesion healed with only residual dyschromia and itraconazole was discontinued.

Comment

Epidemiology
Blastomycosis is a polymorphic pyogranulomatous disease caused by the dimorphic fungus B dermatitidis, naturally occurring in the soil with a worldwide distribution.⁴ Individuals affected by the disease often reside in locations where the fungus is endemic, specifically in areas that border the Mississippi and Ohio rivers, the Great Lakes, and Canadian provinces near the Saint Lawrence Seaway. More recently there has been an increased incidence of blastomycosis, with the highest proportion found in Wisconsin and Michigan.^1,2 Exposures often are associated with recreational and occupational activities near streams or rivers where there may be decaying vegetation.¹ Despite the ubiquitous presence of B dermatitidis in regions where the species is endemic, it is likely that many individuals who are exposed to the organism do not develop infection.

Pathogenesis
The exact pathogenesis for the development of disease in a particular individual remains unclear. Immunosuppression is not a prerequisite for susceptibility, as evidenced by a review of 123 cases of blastomycosis in which a preceding immunodepressive disorder was present in only 25% of patients. The same study found that it was almost equally common as diabetes mellitus and present in 22% of patients.⁵ The organism is considered a true pathogen given its ability to affect healthy individuals and the presence of a newly identified novel 120-kD glycoprotein antigen (WI-1) on the cell wall that may confer virulence via extracellular matrix and macrophage binding. Intact cell-mediated immunity that prevents the conversion of conidia (the infectious agent) to yeast (the form that exists at body temperature) plays a key role in conferring natural resistance.^6,7

Cutaneous infection may occur by either dissemination of yeast to the skin from systemic disease or less commonly via direct inoculation of the skin, resulting in primary cutaneous disease. With respect to systemic disease, infection occurs through inhalation of conidia from moist soil containing organic debris, with an incubation period of 4 to 6 weeks. In the lungs, in a process largely dependent on host cell-mediated immunity, the mold quickly converts to yeast and may then either multiply or be phagocytized.^2,6,7 Transmission does not occur from person to person.⁷ Asymptomatic infection may occur in at least 50% of patients, often leading to a delay in diagnosis. Symptomatic pulmonary disease may range from mild flulike symptoms to overt pneumonia, clinically indistinguishable from community-acquired bacterial pneumonia, tuberculosis, other fungal infections, and cancer. Of patients with primary pulmonary disease, 25% to 80% have been reported to develop secondary organ involvement via lymphohematogenous spread most commonly to the skin, followed respectively by the skeletal, genitourinary, and central nervous systems. Currently, there are 54 documented cases of secondary disseminated cutaneous blastomycosis in children reported in the literature.^3,8-14

Presentation
Primary cutaneous disease resulting from direct cutaneous inoculation is rare, especially among children.¹⁴ Of 28 cases of isolated cutaneous blastomycosis reported in the literature, 12 (42%) were pediatric.^3,8-21 Inoculation blastomycosis typically presents as a papule that expands to a well-demarcated verrucous plaque, often up to several centimeters in diameter, and is located on the skin at the site of contact. The lesion may exhibit a myriad of features ranging from pustules or nodules to focal ulcerations, either present centrally or within raised borders that ultimately may communicate via sinus tracking.⁷ Lesions that are purely pustular in morphology also have been reported. Healing typically begins centrally and expands centrifugally, often with cribriform scarring.^2,4,22 Histologic features of primary and secondary blastomycosis include pseudoepitheliomatous hyperplasia, intraepidermal microabscesses, and dermal suppurative granulomatous inflammation.⁴ Classically, broad-based budding yeast are identified with a doubly refractile cell wall that is best visualized on periodic acid–Schiff staining.²

Diagnosis
In approximately 50% of patients with cutaneous blastomycosis resulting from secondary spread, there may be an absence of clinically active pulmonary disease, posing a diagnostic dilemma when differentiating from primary cutaneous disease.^1,2,4 Furthermore, the skin findings exhibited in primary and secondary cutaneous blastomycosis cannot be distinguished by clinical inspection.¹⁹ To fulfill the criteria for diagnosis of primary cutaneous blastomycosis, there must be an identifiable source of infection from the environment, a lesion at the site of contact, a proven absence of systemic infection, and visualization and/or isolation of fungus from the lesion.^4,12 The incubation period of lesions is shorter in primary cutaneous disease (2 weeks) and may aid in its differentiation from secondary disease, which typically is longer with lesions presenting 4 to 6 weeks following initial exposure.⁴

Treatment
Under the current 2015 guidelines from the American Academy of Pediatrics Committee on Infectious Diseases, 6 to 12 months of itraconazole is the treatment recommendation for mild to moderate pulmonary systemic disease without central nervous system involvement.⁷ Central nervous system disease and moderate to severe pulmonary and systemic disease are treated with intravenous amphotericin B followed by 12 months of oral itraconazole.^1,7 Primary cutaneous disease, unlike secondary disease, may self-resolve; however, primary cutaneous disease usually is treated with 6 months of itraconazole, though successful therapy with surgical excision, radiation therapy, and incision and drainage have been reported.¹⁹

Unlike secondary cutaneous blastomycosis, primary inoculation disease may be self-limited; however, as treatment with antifungal therapy has become the standard of care, the disease’s propensity to self-resolve has not been well studied.⁴ Oral itraconazole for 6 to 12 months is the treatment of choice for mild to moderate cutaneous disease.^1,22 Effective treatment duration may be difficult to definitively assess because of the self-limited nature of the disease. Our patient showed marked improvement after 3 months and resolution of the skin lesion following 6 months of itraconazole therapy. Our findings support the previously documented observation that systemic therapy might potentially be needed only for the time required to eliminate the clinical evidence of cutaneous disease.¹⁹ Our patient received the full 6 months of treatment according to current guidelines. Among a review of 22 cases of primary inoculation blastomycosis, the 5 patients who were treated with an azole agent alone showed disease clearance with an average treatment course of 3.2 months, ranging from 1 to 6 months.¹⁹ Further studies that assess the time to clearance with antifungal therapy and subsequent recurrence rates may be warranted.

Conclusion

Pediatric primary cutaneous blastomycosis is a rare cutaneous disease. Identifying sources of probable inoculation from the environment for this patient was unique in that the patient fell into a muddy puddle within a flowerbed. Given the patient’s atopic history, a predominance of humoral over cell-mediated immunity may have placed him at risk. He responded well to 6 months of oral itraconazole and there was no ulceration or scar formation. An increased awareness of this infection, particularly in geographic areas where its reported incidence is on the rise, could be helpful in reducing delays in diagnosis and treatment.

Acknowledgments
We thank Wenhua Liu, MD (Libertyville, Illinois), for reviewing the pathology and Pravin Muniyappa, MD (Chicago, Illinois), for referring the case.

Blastomycosis is a polymorphic disease caused by the thermally dimorphic fungus Blastomyces dermatitidis, which is naturally occurring worldwide but particularly prominent in the Great Lakes, Mississippi, and Ohio River areas of the United States. The disease was first described by Thomas Caspar Gilchrist in 1894 and historically has been referred to as Gilchrist disease, North American blastomycosis, or Chicago disease.^1,2 Cutaneous blastomycosis can occur by dissemination of yeast to the skin from systemic and pulmonary disease or rarely via direct inoculation of the skin resulting in primary cutaneous disease. Clinically, the lesions are polymorphic and may appear as well-demarcated verrucous plaques containing foci of pustules or ulcerations. Lesions typically heal centrifugally with a cribriform scar.³

We describe an adolescent with a unique history of inoculation 2 weeks prior to the development of a biopsy-confirmed lesion of cutaneous blastomycosis on the left chest wall that clinically resolved following 6 months of itraconazole.

Case Report

A 16-year-old adolescent boy with a history of morbid obesity, asthma, and seasonal allergies presented for evaluation of a painful, slowly enlarging skin lesion on the left chest wall of 2 months’ duration. According to the patient, a “small pimple” appeared at the site of impact 2 weeks following a fall into a muddy flowerbed in Madison, Wisconsin. The patient recalled that although he had soiled his clothing, there was no identifiable puncture of the skin. Despite daily application of hydrogen peroxide and a 1-week course of trimethoprim-sulfamethoxazole, the lesion gradually enlarged. Complete review of systems as well as exposure and travel history were otherwise negative.

Physical examination revealed a 5.0×2.5-cm exophytic, firm, well-circumscribed plaque with a papillated crusted surface on the left side of the chest near the posterior axillary line (Figure 1). There was no palpable regional lymphadenopathy. Pulmonary examination was unremarkable. Diagnostic workup, including complete blood cell count with differential, hemoglobin A_1c, human immunodeficiency virus antibody/antigen testing, interferon-gamma release assay, and chest radiograph were all within normal limits.

Histologic examination of a biopsy specimen showed pseudoepitheliomatous hyperplasia of the epidermis with a brisk mixed inflammatory infiltrate (Figure 2). Displayed in Figure 3 is the Grocott-Gomori methenamine-silver stain that highlighted the thick double-contoured wall-budding yeasts.

The patient was diagnosed with primary cutaneous blastomycosis. Treatment was initiated with itraconazole 200 mg 3 times daily for 3 days, followed by 200 mg 2 times daily for 6 months. Following 3 months of therapy, the lesion had markedly improved with violaceous dyschromia and no residual surface changes. After 5 months of itraconazole, the patient stopped taking the medication for 2 months due to pharmacy issues and then resumed. After 6 total months of therapy, the lesion healed with only residual dyschromia and itraconazole was discontinued.

Comment

Epidemiology
Blastomycosis is a polymorphic pyogranulomatous disease caused by the dimorphic fungus B dermatitidis, naturally occurring in the soil with a worldwide distribution.⁴ Individuals affected by the disease often reside in locations where the fungus is endemic, specifically in areas that border the Mississippi and Ohio rivers, the Great Lakes, and Canadian provinces near the Saint Lawrence Seaway. More recently there has been an increased incidence of blastomycosis, with the highest proportion found in Wisconsin and Michigan.^1,2 Exposures often are associated with recreational and occupational activities near streams or rivers where there may be decaying vegetation.¹ Despite the ubiquitous presence of B dermatitidis in regions where the species is endemic, it is likely that many individuals who are exposed to the organism do not develop infection.

Pathogenesis
The exact pathogenesis for the development of disease in a particular individual remains unclear. Immunosuppression is not a prerequisite for susceptibility, as evidenced by a review of 123 cases of blastomycosis in which a preceding immunodepressive disorder was present in only 25% of patients. The same study found that it was almost equally common as diabetes mellitus and present in 22% of patients.⁵ The organism is considered a true pathogen given its ability to affect healthy individuals and the presence of a newly identified novel 120-kD glycoprotein antigen (WI-1) on the cell wall that may confer virulence via extracellular matrix and macrophage binding. Intact cell-mediated immunity that prevents the conversion of conidia (the infectious agent) to yeast (the form that exists at body temperature) plays a key role in conferring natural resistance.^6,7

Cutaneous infection may occur by either dissemination of yeast to the skin from systemic disease or less commonly via direct inoculation of the skin, resulting in primary cutaneous disease. With respect to systemic disease, infection occurs through inhalation of conidia from moist soil containing organic debris, with an incubation period of 4 to 6 weeks. In the lungs, in a process largely dependent on host cell-mediated immunity, the mold quickly converts to yeast and may then either multiply or be phagocytized.^2,6,7 Transmission does not occur from person to person.⁷ Asymptomatic infection may occur in at least 50% of patients, often leading to a delay in diagnosis. Symptomatic pulmonary disease may range from mild flulike symptoms to overt pneumonia, clinically indistinguishable from community-acquired bacterial pneumonia, tuberculosis, other fungal infections, and cancer. Of patients with primary pulmonary disease, 25% to 80% have been reported to develop secondary organ involvement via lymphohematogenous spread most commonly to the skin, followed respectively by the skeletal, genitourinary, and central nervous systems. Currently, there are 54 documented cases of secondary disseminated cutaneous blastomycosis in children reported in the literature.^3,8-14

Presentation
Primary cutaneous disease resulting from direct cutaneous inoculation is rare, especially among children.¹⁴ Of 28 cases of isolated cutaneous blastomycosis reported in the literature, 12 (42%) were pediatric.^3,8-21 Inoculation blastomycosis typically presents as a papule that expands to a well-demarcated verrucous plaque, often up to several centimeters in diameter, and is located on the skin at the site of contact. The lesion may exhibit a myriad of features ranging from pustules or nodules to focal ulcerations, either present centrally or within raised borders that ultimately may communicate via sinus tracking.⁷ Lesions that are purely pustular in morphology also have been reported. Healing typically begins centrally and expands centrifugally, often with cribriform scarring.^2,4,22 Histologic features of primary and secondary blastomycosis include pseudoepitheliomatous hyperplasia, intraepidermal microabscesses, and dermal suppurative granulomatous inflammation.⁴ Classically, broad-based budding yeast are identified with a doubly refractile cell wall that is best visualized on periodic acid–Schiff staining.²

Diagnosis
In approximately 50% of patients with cutaneous blastomycosis resulting from secondary spread, there may be an absence of clinically active pulmonary disease, posing a diagnostic dilemma when differentiating from primary cutaneous disease.^1,2,4 Furthermore, the skin findings exhibited in primary and secondary cutaneous blastomycosis cannot be distinguished by clinical inspection.¹⁹ To fulfill the criteria for diagnosis of primary cutaneous blastomycosis, there must be an identifiable source of infection from the environment, a lesion at the site of contact, a proven absence of systemic infection, and visualization and/or isolation of fungus from the lesion.^4,12 The incubation period of lesions is shorter in primary cutaneous disease (2 weeks) and may aid in its differentiation from secondary disease, which typically is longer with lesions presenting 4 to 6 weeks following initial exposure.⁴

Treatment
Under the current 2015 guidelines from the American Academy of Pediatrics Committee on Infectious Diseases, 6 to 12 months of itraconazole is the treatment recommendation for mild to moderate pulmonary systemic disease without central nervous system involvement.⁷ Central nervous system disease and moderate to severe pulmonary and systemic disease are treated with intravenous amphotericin B followed by 12 months of oral itraconazole.^1,7 Primary cutaneous disease, unlike secondary disease, may self-resolve; however, primary cutaneous disease usually is treated with 6 months of itraconazole, though successful therapy with surgical excision, radiation therapy, and incision and drainage have been reported.¹⁹

Unlike secondary cutaneous blastomycosis, primary inoculation disease may be self-limited; however, as treatment with antifungal therapy has become the standard of care, the disease’s propensity to self-resolve has not been well studied.⁴ Oral itraconazole for 6 to 12 months is the treatment of choice for mild to moderate cutaneous disease.^1,22 Effective treatment duration may be difficult to definitively assess because of the self-limited nature of the disease. Our patient showed marked improvement after 3 months and resolution of the skin lesion following 6 months of itraconazole therapy. Our findings support the previously documented observation that systemic therapy might potentially be needed only for the time required to eliminate the clinical evidence of cutaneous disease.¹⁹ Our patient received the full 6 months of treatment according to current guidelines. Among a review of 22 cases of primary inoculation blastomycosis, the 5 patients who were treated with an azole agent alone showed disease clearance with an average treatment course of 3.2 months, ranging from 1 to 6 months.¹⁹ Further studies that assess the time to clearance with antifungal therapy and subsequent recurrence rates may be warranted.

Conclusion

Pediatric primary cutaneous blastomycosis is a rare cutaneous disease. Identifying sources of probable inoculation from the environment for this patient was unique in that the patient fell into a muddy puddle within a flowerbed. Given the patient’s atopic history, a predominance of humoral over cell-mediated immunity may have placed him at risk. He responded well to 6 months of oral itraconazole and there was no ulceration or scar formation. An increased awareness of this infection, particularly in geographic areas where its reported incidence is on the rise, could be helpful in reducing delays in diagnosis and treatment.

Acknowledgments
We thank Wenhua Liu, MD (Libertyville, Illinois), for reviewing the pathology and Pravin Muniyappa, MD (Chicago, Illinois), for referring the case.

Blastomycosis is a polymorphic disease caused by the thermally dimorphic fungus Blastomyces dermatitidis, which is naturally occurring worldwide but particularly prominent in the Great Lakes, Mississippi, and Ohio River areas of the United States. The disease was first described by Thomas Caspar Gilchrist in 1894 and historically has been referred to as Gilchrist disease, North American blastomycosis, or Chicago disease.^1,2 Cutaneous blastomycosis can occur by dissemination of yeast to the skin from systemic and pulmonary disease or rarely via direct inoculation of the skin resulting in primary cutaneous disease. Clinically, the lesions are polymorphic and may appear as well-demarcated verrucous plaques containing foci of pustules or ulcerations. Lesions typically heal centrifugally with a cribriform scar.³

We describe an adolescent with a unique history of inoculation 2 weeks prior to the development of a biopsy-confirmed lesion of cutaneous blastomycosis on the left chest wall that clinically resolved following 6 months of itraconazole.

Case Report

A 16-year-old adolescent boy with a history of morbid obesity, asthma, and seasonal allergies presented for evaluation of a painful, slowly enlarging skin lesion on the left chest wall of 2 months’ duration. According to the patient, a “small pimple” appeared at the site of impact 2 weeks following a fall into a muddy flowerbed in Madison, Wisconsin. The patient recalled that although he had soiled his clothing, there was no identifiable puncture of the skin. Despite daily application of hydrogen peroxide and a 1-week course of trimethoprim-sulfamethoxazole, the lesion gradually enlarged. Complete review of systems as well as exposure and travel history were otherwise negative.

Physical examination revealed a 5.0×2.5-cm exophytic, firm, well-circumscribed plaque with a papillated crusted surface on the left side of the chest near the posterior axillary line (Figure 1). There was no palpable regional lymphadenopathy. Pulmonary examination was unremarkable. Diagnostic workup, including complete blood cell count with differential, hemoglobin A_1c, human immunodeficiency virus antibody/antigen testing, interferon-gamma release assay, and chest radiograph were all within normal limits.

Histologic examination of a biopsy specimen showed pseudoepitheliomatous hyperplasia of the epidermis with a brisk mixed inflammatory infiltrate (Figure 2). Displayed in Figure 3 is the Grocott-Gomori methenamine-silver stain that highlighted the thick double-contoured wall-budding yeasts.

The patient was diagnosed with primary cutaneous blastomycosis. Treatment was initiated with itraconazole 200 mg 3 times daily for 3 days, followed by 200 mg 2 times daily for 6 months. Following 3 months of therapy, the lesion had markedly improved with violaceous dyschromia and no residual surface changes. After 5 months of itraconazole, the patient stopped taking the medication for 2 months due to pharmacy issues and then resumed. After 6 total months of therapy, the lesion healed with only residual dyschromia and itraconazole was discontinued.

Comment

Epidemiology
Blastomycosis is a polymorphic pyogranulomatous disease caused by the dimorphic fungus B dermatitidis, naturally occurring in the soil with a worldwide distribution.⁴ Individuals affected by the disease often reside in locations where the fungus is endemic, specifically in areas that border the Mississippi and Ohio rivers, the Great Lakes, and Canadian provinces near the Saint Lawrence Seaway. More recently there has been an increased incidence of blastomycosis, with the highest proportion found in Wisconsin and Michigan.^1,2 Exposures often are associated with recreational and occupational activities near streams or rivers where there may be decaying vegetation.¹ Despite the ubiquitous presence of B dermatitidis in regions where the species is endemic, it is likely that many individuals who are exposed to the organism do not develop infection.

Pathogenesis
The exact pathogenesis for the development of disease in a particular individual remains unclear. Immunosuppression is not a prerequisite for susceptibility, as evidenced by a review of 123 cases of blastomycosis in which a preceding immunodepressive disorder was present in only 25% of patients. The same study found that it was almost equally common as diabetes mellitus and present in 22% of patients.⁵ The organism is considered a true pathogen given its ability to affect healthy individuals and the presence of a newly identified novel 120-kD glycoprotein antigen (WI-1) on the cell wall that may confer virulence via extracellular matrix and macrophage binding. Intact cell-mediated immunity that prevents the conversion of conidia (the infectious agent) to yeast (the form that exists at body temperature) plays a key role in conferring natural resistance.^6,7

Cutaneous infection may occur by either dissemination of yeast to the skin from systemic disease or less commonly via direct inoculation of the skin, resulting in primary cutaneous disease. With respect to systemic disease, infection occurs through inhalation of conidia from moist soil containing organic debris, with an incubation period of 4 to 6 weeks. In the lungs, in a process largely dependent on host cell-mediated immunity, the mold quickly converts to yeast and may then either multiply or be phagocytized.^2,6,7 Transmission does not occur from person to person.⁷ Asymptomatic infection may occur in at least 50% of patients, often leading to a delay in diagnosis. Symptomatic pulmonary disease may range from mild flulike symptoms to overt pneumonia, clinically indistinguishable from community-acquired bacterial pneumonia, tuberculosis, other fungal infections, and cancer. Of patients with primary pulmonary disease, 25% to 80% have been reported to develop secondary organ involvement via lymphohematogenous spread most commonly to the skin, followed respectively by the skeletal, genitourinary, and central nervous systems. Currently, there are 54 documented cases of secondary disseminated cutaneous blastomycosis in children reported in the literature.^3,8-14

Presentation
Primary cutaneous disease resulting from direct cutaneous inoculation is rare, especially among children.¹⁴ Of 28 cases of isolated cutaneous blastomycosis reported in the literature, 12 (42%) were pediatric.^3,8-21 Inoculation blastomycosis typically presents as a papule that expands to a well-demarcated verrucous plaque, often up to several centimeters in diameter, and is located on the skin at the site of contact. The lesion may exhibit a myriad of features ranging from pustules or nodules to focal ulcerations, either present centrally or within raised borders that ultimately may communicate via sinus tracking.⁷ Lesions that are purely pustular in morphology also have been reported. Healing typically begins centrally and expands centrifugally, often with cribriform scarring.^2,4,22 Histologic features of primary and secondary blastomycosis include pseudoepitheliomatous hyperplasia, intraepidermal microabscesses, and dermal suppurative granulomatous inflammation.⁴ Classically, broad-based budding yeast are identified with a doubly refractile cell wall that is best visualized on periodic acid–Schiff staining.²

Diagnosis
In approximately 50% of patients with cutaneous blastomycosis resulting from secondary spread, there may be an absence of clinically active pulmonary disease, posing a diagnostic dilemma when differentiating from primary cutaneous disease.^1,2,4 Furthermore, the skin findings exhibited in primary and secondary cutaneous blastomycosis cannot be distinguished by clinical inspection.¹⁹ To fulfill the criteria for diagnosis of primary cutaneous blastomycosis, there must be an identifiable source of infection from the environment, a lesion at the site of contact, a proven absence of systemic infection, and visualization and/or isolation of fungus from the lesion.^4,12 The incubation period of lesions is shorter in primary cutaneous disease (2 weeks) and may aid in its differentiation from secondary disease, which typically is longer with lesions presenting 4 to 6 weeks following initial exposure.⁴

Treatment
Under the current 2015 guidelines from the American Academy of Pediatrics Committee on Infectious Diseases, 6 to 12 months of itraconazole is the treatment recommendation for mild to moderate pulmonary systemic disease without central nervous system involvement.⁷ Central nervous system disease and moderate to severe pulmonary and systemic disease are treated with intravenous amphotericin B followed by 12 months of oral itraconazole.^1,7 Primary cutaneous disease, unlike secondary disease, may self-resolve; however, primary cutaneous disease usually is treated with 6 months of itraconazole, though successful therapy with surgical excision, radiation therapy, and incision and drainage have been reported.¹⁹

Unlike secondary cutaneous blastomycosis, primary inoculation disease may be self-limited; however, as treatment with antifungal therapy has become the standard of care, the disease’s propensity to self-resolve has not been well studied.⁴ Oral itraconazole for 6 to 12 months is the treatment of choice for mild to moderate cutaneous disease.^1,22 Effective treatment duration may be difficult to definitively assess because of the self-limited nature of the disease. Our patient showed marked improvement after 3 months and resolution of the skin lesion following 6 months of itraconazole therapy. Our findings support the previously documented observation that systemic therapy might potentially be needed only for the time required to eliminate the clinical evidence of cutaneous disease.¹⁹ Our patient received the full 6 months of treatment according to current guidelines. Among a review of 22 cases of primary inoculation blastomycosis, the 5 patients who were treated with an azole agent alone showed disease clearance with an average treatment course of 3.2 months, ranging from 1 to 6 months.¹⁹ Further studies that assess the time to clearance with antifungal therapy and subsequent recurrence rates may be warranted.

Conclusion

Pediatric primary cutaneous blastomycosis is a rare cutaneous disease. Identifying sources of probable inoculation from the environment for this patient was unique in that the patient fell into a muddy puddle within a flowerbed. Given the patient’s atopic history, a predominance of humoral over cell-mediated immunity may have placed him at risk. He responded well to 6 months of oral itraconazole and there was no ulceration or scar formation. An increased awareness of this infection, particularly in geographic areas where its reported incidence is on the rise, could be helpful in reducing delays in diagnosis and treatment.

Acknowledgments
We thank Wenhua Liu, MD (Libertyville, Illinois), for reviewing the pathology and Pravin Muniyappa, MD (Chicago, Illinois), for referring the case.

Acute hemorrhagic edema of infancy (AHEI) is an uncommon leukocytoclastic vasculitis affecting children aged 6 to 24 months; Henoch-Schönlein purpura (HSP) is the most common misdiagnosis. The 2 entities should be differentiated, as HSP may have renal and gastrointestinal (GI) comorbidities that need serial follow-up, whereas AHEI follows a benign course without systemic sequelae. Patient history and physical examination are the most important factors in differentiating the 2 diseases; histopathologic and direct immunofluorescence (DIF) analyses may lend further diagnostic confidence.

We report the case of a 10-month-old previously healthy boy who presented with acute rash, edema, and low-grade fever in the setting of recent diarrhea. We differentiate between AHEI and HSP to help prevent misdiagnosis by health care providers.

Case Report

A 10-month-old previously healthy boy presented to the emergency department (ED) for evaluation of a rash and swelling of 4 days’ duration. He had nonbloody diarrhea 1 week prior; soon after, he developed bilateral lower leg edema and rash. On evaluation in a different ED, he had a low-grade fever (rectal temperature, 38.0°C) but normal blood work, including complete blood cell count, basic metabolic panel, and coagulation studies. The patient was discharged to outpatient follow-up with his pediatrician who reported normal urinalysis.

Due to progression of the rash, the patient presented to our ED 3 days after his initial ED assessment. Dermatology was consulted. At the time of presentation, he was afebrile but with GI upset and fussiness. His parents denied additional symptoms or blood in urine or stool. Physical examination revealed a nontoxic-appearing infant with scattered palpable, annular, purpuric papules coalescing into plaques on both legs and feet (Figure 1), with sparse petechiae noted on the lower abdomen. The cheeks had scattered purpuric papules and plaques bilaterally, a few with a small central crust (Figure 2), and the right superior helix had a faint purpuric macule. The hands had a few pink edematous coalescing papules.

Histopathologic analyses with hematoxylin and eosin staining (Figure 3) and DIF (Figure 4) were performed from within a representative purpuric plaque on the right hip. Direct immunofluorescence was performed to evaluate for an IgA vasculitis versus an alternative type of vasculitis. The hematoxylin and eosin–stained specimen demonstrated a dermal perivascular infiltrate involving superficial and deep vessels with neutrophils, karyorrhexis, and erythrocyte extravasation. The endothelium was intact, with a mild suggestion of fibrinoid change of the blood vessel walls. Direct immunofluorescence revealed granular deposition of IgA, C3, and fibrinogen in multiple dermal blood vessels. Combined, the specimens were interpreted as evolving IgA-associated leukocytoclastic vasculitis.

The case was reviewed with our 2 department pediatric dermatologists; a diagnosis of AHEI was made based on the clinical and supportive histopathological presentations. The patient’s parents chose active treatment with a 2-week taper of oral prednisone because of the patient’s discomfort with edema. No GI or adverse renal sequelae, including findings on urinalysis, were reported at 1-month hospital follow-up with dermatology and pediatrics.

Comment

Incidence and Clinical Characteristics
Acute hemorrhagic edema of infancy is an uncommon leukocytoclastic vasculitis first described in the United States by Snow¹ in 1913. Other names for the disorder include acute hemorrhagic edema of young children, cockade purpura and edema, Finkelstein disease, and Seidlmayer disease.² Boys are affected more often than girls, with most children presenting at 6 to 24 months of age. Most affected children experience a prodrome of simple respiratory tract illness (most common), diarrhea (as in our case), or urinary tract infection.² The exact pathophysiology behind AHEI is unknown, but it is thought to be an immune complex–mediated disease evidenced by the fact that infection, use of medication, or immunization precedes most cases.^3,4

Diagnosis
Acute hemorrhagic edema of infancy is diagnosed clinically, with or without the support of skin biopsy. It should be differentiated from HSP because of renal and GI sequelae that HSP portends compared to the benign course of AHEI.² Notably, some health care providers consider AHEI a benign variant of HSP.^2,3

Characteristically, AHEI patients are nontoxic-appearing infants with a low-grade fever who develop relatively large (1–5 cm) targetoid purpuric lesions and indurated nonpitting edema of the extremities.^2,5 Purpura in AHEI frequently occurs on the face, ears, and upper and lower extremities, whereas purpura in HSP most commonly presents on the buttocks and extensor legs with sparing of the face. Henoch-Schönlein purpura most often affects children aged 3 to 6 years compared to AHEI’s younger demographic (age <2 years).^4,5 Clinically, HSP presents with palpable purpura and 1 or more of the following features: diffuse abdominal pain, arthritis/arthralgia, renal involvement, and skin or renal biopsy showing predominant IgA deposition.^2,6

Both AHEI and HSP show leukocytoclastic vasculitis on histopathology.^2-4,6,7 Positive perivascular IgA staining on DIF is strongly associated with HSP, but nearly one-quarter of AHEI cases also show this deposition pattern^2,4,7; therefore, DIF alone cannot exclude a diagnosis of AHEI.

Differential Diagnosis
Alternative diagnoses to consider with AHEI include drug-induced vasculitis, erythema multiforme, HSP, Kawasaki disease, meningococcemia, nonaccidental skin bruising, Rocky Mountain spotted fever, septic vasculitis, and urticarial vasculitis (Table).^2-4,6-8

Treatment
Acute hemorrhagic edema of infancy is self-limited, with only rare reports of extracutaneous involvement. Supportive treatment is indicated because spontaneous recovery without sequelae is expected within 21 days.^2,3,6 If edema is symptomatic, as was the case with our patient, corticosteroids may shorten the disease course.³

Conclusion

Our case highlights the need to combine clinical history, physical examination, and histopathologic analysis to differentiate between AHEI and HSP, which is important for 2 reasons: (1) it helps with the decision to undertake active or observational treatment, and (2) it helps the clinician counsel the patient and guardians regarding potential associated renal and GI risks.

Acute hemorrhagic edema of infancy (AHEI) is an uncommon leukocytoclastic vasculitis affecting children aged 6 to 24 months; Henoch-Schönlein purpura (HSP) is the most common misdiagnosis. The 2 entities should be differentiated, as HSP may have renal and gastrointestinal (GI) comorbidities that need serial follow-up, whereas AHEI follows a benign course without systemic sequelae. Patient history and physical examination are the most important factors in differentiating the 2 diseases; histopathologic and direct immunofluorescence (DIF) analyses may lend further diagnostic confidence.

We report the case of a 10-month-old previously healthy boy who presented with acute rash, edema, and low-grade fever in the setting of recent diarrhea. We differentiate between AHEI and HSP to help prevent misdiagnosis by health care providers.

Case Report

A 10-month-old previously healthy boy presented to the emergency department (ED) for evaluation of a rash and swelling of 4 days’ duration. He had nonbloody diarrhea 1 week prior; soon after, he developed bilateral lower leg edema and rash. On evaluation in a different ED, he had a low-grade fever (rectal temperature, 38.0°C) but normal blood work, including complete blood cell count, basic metabolic panel, and coagulation studies. The patient was discharged to outpatient follow-up with his pediatrician who reported normal urinalysis.

Due to progression of the rash, the patient presented to our ED 3 days after his initial ED assessment. Dermatology was consulted. At the time of presentation, he was afebrile but with GI upset and fussiness. His parents denied additional symptoms or blood in urine or stool. Physical examination revealed a nontoxic-appearing infant with scattered palpable, annular, purpuric papules coalescing into plaques on both legs and feet (Figure 1), with sparse petechiae noted on the lower abdomen. The cheeks had scattered purpuric papules and plaques bilaterally, a few with a small central crust (Figure 2), and the right superior helix had a faint purpuric macule. The hands had a few pink edematous coalescing papules.

Histopathologic analyses with hematoxylin and eosin staining (Figure 3) and DIF (Figure 4) were performed from within a representative purpuric plaque on the right hip. Direct immunofluorescence was performed to evaluate for an IgA vasculitis versus an alternative type of vasculitis. The hematoxylin and eosin–stained specimen demonstrated a dermal perivascular infiltrate involving superficial and deep vessels with neutrophils, karyorrhexis, and erythrocyte extravasation. The endothelium was intact, with a mild suggestion of fibrinoid change of the blood vessel walls. Direct immunofluorescence revealed granular deposition of IgA, C3, and fibrinogen in multiple dermal blood vessels. Combined, the specimens were interpreted as evolving IgA-associated leukocytoclastic vasculitis.

The case was reviewed with our 2 department pediatric dermatologists; a diagnosis of AHEI was made based on the clinical and supportive histopathological presentations. The patient’s parents chose active treatment with a 2-week taper of oral prednisone because of the patient’s discomfort with edema. No GI or adverse renal sequelae, including findings on urinalysis, were reported at 1-month hospital follow-up with dermatology and pediatrics.

Comment

Incidence and Clinical Characteristics
Acute hemorrhagic edema of infancy is an uncommon leukocytoclastic vasculitis first described in the United States by Snow¹ in 1913. Other names for the disorder include acute hemorrhagic edema of young children, cockade purpura and edema, Finkelstein disease, and Seidlmayer disease.² Boys are affected more often than girls, with most children presenting at 6 to 24 months of age. Most affected children experience a prodrome of simple respiratory tract illness (most common), diarrhea (as in our case), or urinary tract infection.² The exact pathophysiology behind AHEI is unknown, but it is thought to be an immune complex–mediated disease evidenced by the fact that infection, use of medication, or immunization precedes most cases.^3,4

Diagnosis
Acute hemorrhagic edema of infancy is diagnosed clinically, with or without the support of skin biopsy. It should be differentiated from HSP because of renal and GI sequelae that HSP portends compared to the benign course of AHEI.² Notably, some health care providers consider AHEI a benign variant of HSP.^2,3

Characteristically, AHEI patients are nontoxic-appearing infants with a low-grade fever who develop relatively large (1–5 cm) targetoid purpuric lesions and indurated nonpitting edema of the extremities.^2,5 Purpura in AHEI frequently occurs on the face, ears, and upper and lower extremities, whereas purpura in HSP most commonly presents on the buttocks and extensor legs with sparing of the face. Henoch-Schönlein purpura most often affects children aged 3 to 6 years compared to AHEI’s younger demographic (age <2 years).^4,5 Clinically, HSP presents with palpable purpura and 1 or more of the following features: diffuse abdominal pain, arthritis/arthralgia, renal involvement, and skin or renal biopsy showing predominant IgA deposition.^2,6

Both AHEI and HSP show leukocytoclastic vasculitis on histopathology.^2-4,6,7 Positive perivascular IgA staining on DIF is strongly associated with HSP, but nearly one-quarter of AHEI cases also show this deposition pattern^2,4,7; therefore, DIF alone cannot exclude a diagnosis of AHEI.

Differential Diagnosis
Alternative diagnoses to consider with AHEI include drug-induced vasculitis, erythema multiforme, HSP, Kawasaki disease, meningococcemia, nonaccidental skin bruising, Rocky Mountain spotted fever, septic vasculitis, and urticarial vasculitis (Table).^2-4,6-8

Treatment
Acute hemorrhagic edema of infancy is self-limited, with only rare reports of extracutaneous involvement. Supportive treatment is indicated because spontaneous recovery without sequelae is expected within 21 days.^2,3,6 If edema is symptomatic, as was the case with our patient, corticosteroids may shorten the disease course.³

Conclusion

Our case highlights the need to combine clinical history, physical examination, and histopathologic analysis to differentiate between AHEI and HSP, which is important for 2 reasons: (1) it helps with the decision to undertake active or observational treatment, and (2) it helps the clinician counsel the patient and guardians regarding potential associated renal and GI risks.

Acute hemorrhagic edema of infancy (AHEI) is an uncommon leukocytoclastic vasculitis affecting children aged 6 to 24 months; Henoch-Schönlein purpura (HSP) is the most common misdiagnosis. The 2 entities should be differentiated, as HSP may have renal and gastrointestinal (GI) comorbidities that need serial follow-up, whereas AHEI follows a benign course without systemic sequelae. Patient history and physical examination are the most important factors in differentiating the 2 diseases; histopathologic and direct immunofluorescence (DIF) analyses may lend further diagnostic confidence.

We report the case of a 10-month-old previously healthy boy who presented with acute rash, edema, and low-grade fever in the setting of recent diarrhea. We differentiate between AHEI and HSP to help prevent misdiagnosis by health care providers.

Case Report

A 10-month-old previously healthy boy presented to the emergency department (ED) for evaluation of a rash and swelling of 4 days’ duration. He had nonbloody diarrhea 1 week prior; soon after, he developed bilateral lower leg edema and rash. On evaluation in a different ED, he had a low-grade fever (rectal temperature, 38.0°C) but normal blood work, including complete blood cell count, basic metabolic panel, and coagulation studies. The patient was discharged to outpatient follow-up with his pediatrician who reported normal urinalysis.

Due to progression of the rash, the patient presented to our ED 3 days after his initial ED assessment. Dermatology was consulted. At the time of presentation, he was afebrile but with GI upset and fussiness. His parents denied additional symptoms or blood in urine or stool. Physical examination revealed a nontoxic-appearing infant with scattered palpable, annular, purpuric papules coalescing into plaques on both legs and feet (Figure 1), with sparse petechiae noted on the lower abdomen. The cheeks had scattered purpuric papules and plaques bilaterally, a few with a small central crust (Figure 2), and the right superior helix had a faint purpuric macule. The hands had a few pink edematous coalescing papules.

Histopathologic analyses with hematoxylin and eosin staining (Figure 3) and DIF (Figure 4) were performed from within a representative purpuric plaque on the right hip. Direct immunofluorescence was performed to evaluate for an IgA vasculitis versus an alternative type of vasculitis. The hematoxylin and eosin–stained specimen demonstrated a dermal perivascular infiltrate involving superficial and deep vessels with neutrophils, karyorrhexis, and erythrocyte extravasation. The endothelium was intact, with a mild suggestion of fibrinoid change of the blood vessel walls. Direct immunofluorescence revealed granular deposition of IgA, C3, and fibrinogen in multiple dermal blood vessels. Combined, the specimens were interpreted as evolving IgA-associated leukocytoclastic vasculitis.

The case was reviewed with our 2 department pediatric dermatologists; a diagnosis of AHEI was made based on the clinical and supportive histopathological presentations. The patient’s parents chose active treatment with a 2-week taper of oral prednisone because of the patient’s discomfort with edema. No GI or adverse renal sequelae, including findings on urinalysis, were reported at 1-month hospital follow-up with dermatology and pediatrics.

Comment

Incidence and Clinical Characteristics
Acute hemorrhagic edema of infancy is an uncommon leukocytoclastic vasculitis first described in the United States by Snow¹ in 1913. Other names for the disorder include acute hemorrhagic edema of young children, cockade purpura and edema, Finkelstein disease, and Seidlmayer disease.² Boys are affected more often than girls, with most children presenting at 6 to 24 months of age. Most affected children experience a prodrome of simple respiratory tract illness (most common), diarrhea (as in our case), or urinary tract infection.² The exact pathophysiology behind AHEI is unknown, but it is thought to be an immune complex–mediated disease evidenced by the fact that infection, use of medication, or immunization precedes most cases.^3,4

Diagnosis
Acute hemorrhagic edema of infancy is diagnosed clinically, with or without the support of skin biopsy. It should be differentiated from HSP because of renal and GI sequelae that HSP portends compared to the benign course of AHEI.² Notably, some health care providers consider AHEI a benign variant of HSP.^2,3

Characteristically, AHEI patients are nontoxic-appearing infants with a low-grade fever who develop relatively large (1–5 cm) targetoid purpuric lesions and indurated nonpitting edema of the extremities.^2,5 Purpura in AHEI frequently occurs on the face, ears, and upper and lower extremities, whereas purpura in HSP most commonly presents on the buttocks and extensor legs with sparing of the face. Henoch-Schönlein purpura most often affects children aged 3 to 6 years compared to AHEI’s younger demographic (age <2 years).^4,5 Clinically, HSP presents with palpable purpura and 1 or more of the following features: diffuse abdominal pain, arthritis/arthralgia, renal involvement, and skin or renal biopsy showing predominant IgA deposition.^2,6

Both AHEI and HSP show leukocytoclastic vasculitis on histopathology.^2-4,6,7 Positive perivascular IgA staining on DIF is strongly associated with HSP, but nearly one-quarter of AHEI cases also show this deposition pattern^2,4,7; therefore, DIF alone cannot exclude a diagnosis of AHEI.

Differential Diagnosis
Alternative diagnoses to consider with AHEI include drug-induced vasculitis, erythema multiforme, HSP, Kawasaki disease, meningococcemia, nonaccidental skin bruising, Rocky Mountain spotted fever, septic vasculitis, and urticarial vasculitis (Table).^2-4,6-8

Treatment
Acute hemorrhagic edema of infancy is self-limited, with only rare reports of extracutaneous involvement. Supportive treatment is indicated because spontaneous recovery without sequelae is expected within 21 days.^2,3,6 If edema is symptomatic, as was the case with our patient, corticosteroids may shorten the disease course.³

Conclusion

Our case highlights the need to combine clinical history, physical examination, and histopathologic analysis to differentiate between AHEI and HSP, which is important for 2 reasons: (1) it helps with the decision to undertake active or observational treatment, and (2) it helps the clinician counsel the patient and guardians regarding potential associated renal and GI risks.

BOSTON – When pancreatitis symptoms don’t resolve within a month, patients need some sort of surgical intervention, according to Steven Hughes, MD, FACS, professor and chief of surgical oncology at the University of Florida, Gainesville.

Pancreatitis management has been evolving in recent years. Prophylactic antibiotics and total parenteral nutrition are out; tube feeds are in, and there’s compelling evidence to take the gallbladder out, regardless of etiology, he said at the annual clinical congress of the American College of Surgeons.

However, too many patients get drains placed in the first 2 weeks; it’s the wrong move because it consigns to surgery a lot of patients who otherwise would have recovered on their own. “In the first 2 weeks, please do not place drains. Once you place the drain, you have committed the patient to a very different clinical course,” Dr. Hughes said.

Surgery generally comes a month or more after the initial presentation. Infection is inevitable at that point; the delay gives the lesion time to consolidate and wall itself off, making for a cleaner, safer operation.

Transgastric necrosectomy is the go-to when pancreatic lesions are toward the midline. It’s Dr. Hughes’s favored approach when the anatomy is appropriate; he shared his thoughts at the meeting.

Transgastric necrosectomy provides “single-stop shopping. You can get a thorough debridement in a single procedure,” and durable internal drainage. “Most importantly, from a patient’s perspective, it leaves them without external drains. You can transition a patient who’s been percutaneously drained to no external drainage at the time of this operation,” he said.

Additional pluses include cholecystectomy either before or after necrosectomy and the ability to place enteric feeding systems. “I like to use a combination G-J tube that allows drainage of the emptying stomach along with distal tube feeds,” he said.

Laparoscopic and endoscopic approaches are possible, but Dr. Hughes favors an open procedure “because the finger is the best debriding tool I have found.” There’s an anterior and then posterior gastric incision to dig out the necroma. The anterior incision is closed, but the posterior cut is sealed open to the necroma with a running hemostatic suture to allow for a “large cavity between the cavity and the stomach” for ongoing drainage.

“I have ultrasound on the field, but typically finding the necroma is like falling out of a canoe and finding water.” Even so, “I like to bring a 10-mm straight scope for direct viewing onto the field to explore the necrotic cavity and ensure I’ve done an adequate necrosectomy,” he said.

“I do think that this operation can be performed in patients who have some retrocolic extension even over into the pancreatic head and down the right paracolic gutter, but certainly if the collection extends down towards the pelvis, the notion that this is going to be adequate in and of itself requires further investigation,” he said.

In a cohort of 18 patients he and his colleagues followed for at least 2 years, “I was impressed that this operation is rather durable,” with rapid resolution of disease, Dr. Hughes said. Just a couple people needed additional operations. “The majority created persistent fistulas between the pancreatic body tail and the stomach.”

He cautioned that the procedure “is not for the faint of heart. The splenic vein and the splenic artery as well the celiac axis and portal vein are at risk during this procedure, and if you get into them, you have got a wolf by both ears. I would encourage you to consider referral for these patients.”

Dr. Hughes strongly encouraged surgeons to “ make sure your interventional radiologists and advanced endoscopists are on board, whether for the postop pseudoaneurysm bleeding or recurrent sepsis.”

Dr. Hughes had no relevant disclosures to report.

[email protected]

BOSTON – When pancreatitis symptoms don’t resolve within a month, patients need some sort of surgical intervention, according to Steven Hughes, MD, FACS, professor and chief of surgical oncology at the University of Florida, Gainesville.

Pancreatitis management has been evolving in recent years. Prophylactic antibiotics and total parenteral nutrition are out; tube feeds are in, and there’s compelling evidence to take the gallbladder out, regardless of etiology, he said at the annual clinical congress of the American College of Surgeons.

However, too many patients get drains placed in the first 2 weeks; it’s the wrong move because it consigns to surgery a lot of patients who otherwise would have recovered on their own. “In the first 2 weeks, please do not place drains. Once you place the drain, you have committed the patient to a very different clinical course,” Dr. Hughes said.

Surgery generally comes a month or more after the initial presentation. Infection is inevitable at that point; the delay gives the lesion time to consolidate and wall itself off, making for a cleaner, safer operation.

Transgastric necrosectomy is the go-to when pancreatic lesions are toward the midline. It’s Dr. Hughes’s favored approach when the anatomy is appropriate; he shared his thoughts at the meeting.

Transgastric necrosectomy provides “single-stop shopping. You can get a thorough debridement in a single procedure,” and durable internal drainage. “Most importantly, from a patient’s perspective, it leaves them without external drains. You can transition a patient who’s been percutaneously drained to no external drainage at the time of this operation,” he said.

Additional pluses include cholecystectomy either before or after necrosectomy and the ability to place enteric feeding systems. “I like to use a combination G-J tube that allows drainage of the emptying stomach along with distal tube feeds,” he said.

Laparoscopic and endoscopic approaches are possible, but Dr. Hughes favors an open procedure “because the finger is the best debriding tool I have found.” There’s an anterior and then posterior gastric incision to dig out the necroma. The anterior incision is closed, but the posterior cut is sealed open to the necroma with a running hemostatic suture to allow for a “large cavity between the cavity and the stomach” for ongoing drainage.

“I have ultrasound on the field, but typically finding the necroma is like falling out of a canoe and finding water.” Even so, “I like to bring a 10-mm straight scope for direct viewing onto the field to explore the necrotic cavity and ensure I’ve done an adequate necrosectomy,” he said.

“I do think that this operation can be performed in patients who have some retrocolic extension even over into the pancreatic head and down the right paracolic gutter, but certainly if the collection extends down towards the pelvis, the notion that this is going to be adequate in and of itself requires further investigation,” he said.

In a cohort of 18 patients he and his colleagues followed for at least 2 years, “I was impressed that this operation is rather durable,” with rapid resolution of disease, Dr. Hughes said. Just a couple people needed additional operations. “The majority created persistent fistulas between the pancreatic body tail and the stomach.”

He cautioned that the procedure “is not for the faint of heart. The splenic vein and the splenic artery as well the celiac axis and portal vein are at risk during this procedure, and if you get into them, you have got a wolf by both ears. I would encourage you to consider referral for these patients.”

Dr. Hughes strongly encouraged surgeons to “ make sure your interventional radiologists and advanced endoscopists are on board, whether for the postop pseudoaneurysm bleeding or recurrent sepsis.”

Dr. Hughes had no relevant disclosures to report.

[email protected]

BOSTON – When pancreatitis symptoms don’t resolve within a month, patients need some sort of surgical intervention, according to Steven Hughes, MD, FACS, professor and chief of surgical oncology at the University of Florida, Gainesville.

Pancreatitis management has been evolving in recent years. Prophylactic antibiotics and total parenteral nutrition are out; tube feeds are in, and there’s compelling evidence to take the gallbladder out, regardless of etiology, he said at the annual clinical congress of the American College of Surgeons.

However, too many patients get drains placed in the first 2 weeks; it’s the wrong move because it consigns to surgery a lot of patients who otherwise would have recovered on their own. “In the first 2 weeks, please do not place drains. Once you place the drain, you have committed the patient to a very different clinical course,” Dr. Hughes said.

Surgery generally comes a month or more after the initial presentation. Infection is inevitable at that point; the delay gives the lesion time to consolidate and wall itself off, making for a cleaner, safer operation.

Transgastric necrosectomy is the go-to when pancreatic lesions are toward the midline. It’s Dr. Hughes’s favored approach when the anatomy is appropriate; he shared his thoughts at the meeting.

Transgastric necrosectomy provides “single-stop shopping. You can get a thorough debridement in a single procedure,” and durable internal drainage. “Most importantly, from a patient’s perspective, it leaves them without external drains. You can transition a patient who’s been percutaneously drained to no external drainage at the time of this operation,” he said.

Additional pluses include cholecystectomy either before or after necrosectomy and the ability to place enteric feeding systems. “I like to use a combination G-J tube that allows drainage of the emptying stomach along with distal tube feeds,” he said.

Laparoscopic and endoscopic approaches are possible, but Dr. Hughes favors an open procedure “because the finger is the best debriding tool I have found.” There’s an anterior and then posterior gastric incision to dig out the necroma. The anterior incision is closed, but the posterior cut is sealed open to the necroma with a running hemostatic suture to allow for a “large cavity between the cavity and the stomach” for ongoing drainage.

“I have ultrasound on the field, but typically finding the necroma is like falling out of a canoe and finding water.” Even so, “I like to bring a 10-mm straight scope for direct viewing onto the field to explore the necrotic cavity and ensure I’ve done an adequate necrosectomy,” he said.

“I do think that this operation can be performed in patients who have some retrocolic extension even over into the pancreatic head and down the right paracolic gutter, but certainly if the collection extends down towards the pelvis, the notion that this is going to be adequate in and of itself requires further investigation,” he said.

In a cohort of 18 patients he and his colleagues followed for at least 2 years, “I was impressed that this operation is rather durable,” with rapid resolution of disease, Dr. Hughes said. Just a couple people needed additional operations. “The majority created persistent fistulas between the pancreatic body tail and the stomach.”

He cautioned that the procedure “is not for the faint of heart. The splenic vein and the splenic artery as well the celiac axis and portal vein are at risk during this procedure, and if you get into them, you have got a wolf by both ears. I would encourage you to consider referral for these patients.”

Dr. Hughes strongly encouraged surgeons to “ make sure your interventional radiologists and advanced endoscopists are on board, whether for the postop pseudoaneurysm bleeding or recurrent sepsis.”

Dr. Hughes had no relevant disclosures to report.

[email protected]

Neurologists can expect decreased reimbursement under a proposal by the Centers for Medicare & Medicaid Services that would change how the agency pays for evaluation and management services (E/M), according to an analysis published in JAMA Neurology.

Sripfoto/Thinkstock

The CMS recommendation, issued as part of the agency’s 2019 proposed Physician Fee Schedule, would collapse payments for new and established patients for office/outpatient E/M levels 2-5 (currently between $45 and $211) into single payments. The proposed single payments (return visits $93; new patients $135) are between current rates for levels 3-4. In its proposal, CMS officials said the change would improve payment accuracy and simplify documentation.

If approved, neurologists stand to lose the most money under the payment scheme since the majority of their Medicare payments stem from these services, while specialists who use the services less often would benefit from the modification. Specifically, neurologists would lose a median of $3,226 annually under the CMS proposal and cardiologists would lose a median of $3,203 per year, while dermatologists would gain an annual median of $16,655 and orthopedists would gain a median of $6,239, according to the study.

Lead author Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues evaluated the 2013 Medicare Physician and Other Supplier File to determine the distribution of outpatient E/M codes for levels 2-5 used by different specialists and the proportion of total payments for all physician services attributable to these outpatient codes. Investigators estimated the financial impact of collapsed payments by calculating the difference of actual annual payments for outpatient E/M work and the projected annual payments with the proposed policy change.

Results showed that in 2013 the proportion of outpatient E/M codes billed at levels 4-5 varied widely by specialty. Neurologists for example, billed 70% of their outpatient physician E/M codes under levels 4-5, the highest of any specialty. Cardiologists were also high utilizers of the codes with 65% of their outpatient E/M codes falling between levels 4 and 5. The lowest users for levels 4-5 were dermatologists (11%), orthopedists (22%), and otolaryngologists (25%). Taking into account the distribution and volumes of E/M services, the investigators concluded that CMS’ proposed payment change would be most favorable for surgical specialists, neutral for generalists, and most unfavorable for neurologists.

Dr. Callaghan and colleagues wrote that collapsing E/M payments would likely incentivize all physicians to shorten visit times, which could negatively impact doctor-patient relationships and patient care.

“Given that longer visit times are associated with higher patient satisfaction and important elements of care, the CMS proposal would likely have negative consequence,” Dr. Callaghan and his coauthors wrote. “Current E/M payments strongly undervalue the cognitive work of physicians, compared with procedural-based payments. Based on our data, the recent proposal to collapse E/M payment levels would further undervalue these important services, particularly for neurologists.”

The authors reported receiving grants and fees from organizations, companies, and government agencies outside the published study.

SOURCE: Callaghan B et al. JAMA Neurol. 2018 Oct 31. doi: 10.1001/jamaneurol.2018.3794.

Neurologists can expect decreased reimbursement under a proposal by the Centers for Medicare & Medicaid Services that would change how the agency pays for evaluation and management services (E/M), according to an analysis published in JAMA Neurology.

Sripfoto/Thinkstock

The CMS recommendation, issued as part of the agency’s 2019 proposed Physician Fee Schedule, would collapse payments for new and established patients for office/outpatient E/M levels 2-5 (currently between $45 and $211) into single payments. The proposed single payments (return visits $93; new patients $135) are between current rates for levels 3-4. In its proposal, CMS officials said the change would improve payment accuracy and simplify documentation.

If approved, neurologists stand to lose the most money under the payment scheme since the majority of their Medicare payments stem from these services, while specialists who use the services less often would benefit from the modification. Specifically, neurologists would lose a median of $3,226 annually under the CMS proposal and cardiologists would lose a median of $3,203 per year, while dermatologists would gain an annual median of $16,655 and orthopedists would gain a median of $6,239, according to the study.

Lead author Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues evaluated the 2013 Medicare Physician and Other Supplier File to determine the distribution of outpatient E/M codes for levels 2-5 used by different specialists and the proportion of total payments for all physician services attributable to these outpatient codes. Investigators estimated the financial impact of collapsed payments by calculating the difference of actual annual payments for outpatient E/M work and the projected annual payments with the proposed policy change.

Results showed that in 2013 the proportion of outpatient E/M codes billed at levels 4-5 varied widely by specialty. Neurologists for example, billed 70% of their outpatient physician E/M codes under levels 4-5, the highest of any specialty. Cardiologists were also high utilizers of the codes with 65% of their outpatient E/M codes falling between levels 4 and 5. The lowest users for levels 4-5 were dermatologists (11%), orthopedists (22%), and otolaryngologists (25%). Taking into account the distribution and volumes of E/M services, the investigators concluded that CMS’ proposed payment change would be most favorable for surgical specialists, neutral for generalists, and most unfavorable for neurologists.

Dr. Callaghan and colleagues wrote that collapsing E/M payments would likely incentivize all physicians to shorten visit times, which could negatively impact doctor-patient relationships and patient care.

“Given that longer visit times are associated with higher patient satisfaction and important elements of care, the CMS proposal would likely have negative consequence,” Dr. Callaghan and his coauthors wrote. “Current E/M payments strongly undervalue the cognitive work of physicians, compared with procedural-based payments. Based on our data, the recent proposal to collapse E/M payment levels would further undervalue these important services, particularly for neurologists.”

The authors reported receiving grants and fees from organizations, companies, and government agencies outside the published study.

SOURCE: Callaghan B et al. JAMA Neurol. 2018 Oct 31. doi: 10.1001/jamaneurol.2018.3794.

Neurologists can expect decreased reimbursement under a proposal by the Centers for Medicare & Medicaid Services that would change how the agency pays for evaluation and management services (E/M), according to an analysis published in JAMA Neurology.

Sripfoto/Thinkstock

The CMS recommendation, issued as part of the agency’s 2019 proposed Physician Fee Schedule, would collapse payments for new and established patients for office/outpatient E/M levels 2-5 (currently between $45 and $211) into single payments. The proposed single payments (return visits $93; new patients $135) are between current rates for levels 3-4. In its proposal, CMS officials said the change would improve payment accuracy and simplify documentation.

If approved, neurologists stand to lose the most money under the payment scheme since the majority of their Medicare payments stem from these services, while specialists who use the services less often would benefit from the modification. Specifically, neurologists would lose a median of $3,226 annually under the CMS proposal and cardiologists would lose a median of $3,203 per year, while dermatologists would gain an annual median of $16,655 and orthopedists would gain a median of $6,239, according to the study.

Lead author Brian C. Callaghan, MD, of the University of Michigan, Ann Arbor, and colleagues evaluated the 2013 Medicare Physician and Other Supplier File to determine the distribution of outpatient E/M codes for levels 2-5 used by different specialists and the proportion of total payments for all physician services attributable to these outpatient codes. Investigators estimated the financial impact of collapsed payments by calculating the difference of actual annual payments for outpatient E/M work and the projected annual payments with the proposed policy change.

Results showed that in 2013 the proportion of outpatient E/M codes billed at levels 4-5 varied widely by specialty. Neurologists for example, billed 70% of their outpatient physician E/M codes under levels 4-5, the highest of any specialty. Cardiologists were also high utilizers of the codes with 65% of their outpatient E/M codes falling between levels 4 and 5. The lowest users for levels 4-5 were dermatologists (11%), orthopedists (22%), and otolaryngologists (25%). Taking into account the distribution and volumes of E/M services, the investigators concluded that CMS’ proposed payment change would be most favorable for surgical specialists, neutral for generalists, and most unfavorable for neurologists.

Dr. Callaghan and colleagues wrote that collapsing E/M payments would likely incentivize all physicians to shorten visit times, which could negatively impact doctor-patient relationships and patient care.

“Given that longer visit times are associated with higher patient satisfaction and important elements of care, the CMS proposal would likely have negative consequence,” Dr. Callaghan and his coauthors wrote. “Current E/M payments strongly undervalue the cognitive work of physicians, compared with procedural-based payments. Based on our data, the recent proposal to collapse E/M payment levels would further undervalue these important services, particularly for neurologists.”

The authors reported receiving grants and fees from organizations, companies, and government agencies outside the published study.

SOURCE: Callaghan B et al. JAMA Neurol. 2018 Oct 31. doi: 10.1001/jamaneurol.2018.3794.

Hand-foot-and-mouth disease (HFMD) is a viral illness caused by several enteroviruses, most commonly coxsackievirus A16 (CVA16) and enterovirus 71 (EV71). The disease is generally seen in children younger than 5 years, characterized by lesions of the oral mucosa, palms, and soles, usually lasting 7 to 10 days. Other coxsackie type A viruses, including CVA6, CVA9, and CVA10, also are associated with HFMD.^1-5 Although CVA16 has traditionally been the primary strain causing HFMD, CVA6 has become a major cause of HFMD outbreaks in the United States and worldwide in recent years.^6-12 Interestingly, CVA6 also has been found to be associated with adult HFMD, which has increased in incidence. The CVA6 strain was first identified in association with the disease during HFMD outbreaks in Finland and Singapore in 2008,^13,14 with similar strains detected in subsequent outbreaks in Taiwan, Japan, Spain, France, China, India, and the United States.^12,15-25 Most cases took place in warmer months, with one winter outbreak in Massachusetts in 2012.²⁴

Herein, we review the incidence of CVA6, as well as its atypical presentation, diagnosis, and treatment to aid dermatologists. Given the increasing incidence of HFMD caused by CVA6 and its often atypical presentation, it is important for dermatologists to be aware of this increasingly notable disease state and its viral cause.

Incidence of CVA6

Coxsackievirus A6 has been identified as the cause of many reported outbreaks of HFMD since it was first identified in 2008, and it is known to cause both pediatric and adult outbreaks.^7-12 It may even be surpassing other strains in frequency in certain areas. In Tianjin, China, for example, EV71 and CVA16 were the most common serotypes causing HFMD from 2008 to 2012; however, in 2013, CVA6 was the most prevalent strain.²⁶ According to one study, “[n]early every Chinese city showed a sharp rise in [CVA6].”²⁷

The incidence of CVA6 also has been increasing in other areas.²⁸ In Spain, CVA6 overtook CVA16 as the dominant cause of HFMD during 2011 and 2012 outbreaks.²⁹ From 2011 to 2012, there was a CVA6-associated HFMD outbreak in North America, with 63 cases reported to the Centers for Disease Control and Prevention (CDC), including 15 adult cases, with approximately 50% having been exposed to children with HFMD.⁹ In 2014, a Minnesota college with approximately 1000 students reported 9 suspected cases of HFMD to the Minnesota Department of Health. Coxsackievirus A6 was isolated, sequenced, and identified by the CDC in 5 of 9 patients (age range, 19–47 years).⁹

In 2015, an outbreak of HFMD took place at Lackland Air Force Base in Texas during a basic military training. Eight cases were confirmed and 45 cases were suspected. The rate of infection was 0.4% (50/12,270) among trainees and 0.3% (2/602) among instructors.⁷ Eight of 12 nasopharyngeal swabs tested positive for EV by way of local real-time reverse transcription–polymerase chain reaction (RT-PCR). Four nasopharyngeal swabs were sent to the CDC for evaluation and all were positive for CVA6.⁷

Presentation

Because the prevalence of CVA6 has increased, it is important to be able to identify the presentation of HFMD caused by this strain. Coxsackievirus A6 has been found to affect a broader demographic and cause more severe cases of HFMD with its unique constellation of findings compared to other known strains. Patients present with flulike symptoms; higher fever than present in typical HFMD; and a longer duration of disease, typically lasting 2 weeks. Patients also may present with more severe skin disease compared to classic HFMD, not only including vesicles but also large bullae, erosions, and ulcers on the dorsal and plantar feet (Figure 1). Skin lesions often are painful and spread to a wider distribution than typical of HFMD, which can include the face, proximal extremities, lips, perianal and groin skin, scalp, and dorsal feet and hands (Figure 2). These areas are classically spared in the prototypical presentation of HFMD in children.^2,6,24,30-33 Vesicles that are typically football shaped (Figure 3) are a diagnostic clue of the disease. After patients have recovered from the disease, they can have delayed-onset palmar and plantar desquamation that usually presents 1 to 3 weeks after the disease. Additionally, another postsyndrome finding is onychomadesis, or detachment of the nail plate from the nail matrix.^6,34-37 This process likely occurs due to direct cytopathic effect to the nail matrix from the viral infection.^24,37 Blistering may be severe and can form hemorrhagic bullae.²⁴ Although cutaneous findings are more severe, neurologic involvement actually is more rare in the CVA6 strain compared to other viral strains known to cause HFMD, specifically EV71. One study found only 2.4% of 141 patients infected with CVA6 had central nervous system involvement, specifically aseptic meningitis or encephalitis.^21,24

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

In patients with atopic dermatitis, CVA6 also shows a predilection to appear in areas of skin disease, such as the flexural regions of the arms and legs, and is referred to as eczema coxsackium.^24,38,39 It can mimic eczema herpeticum or varicella superinfection, which are important considerations to include in the differential diagnosis. Additionally, CVA6-induced lesions often show up in previously irritated or traumatized areas such as sunburns, fungal infections, and diaper dermatitis in children. Lesions have been described to sometimes mimic Gianotti-Crosti syndrome, with involvement of the extensor surfaces, buttocks, and cheeks, and sparing of the trunk.²⁴

Clinical Diagnosis

Because HFMD is uncommon and atypical in adults, skin biopsies may be used in the initial workup and evaluation of patients. It is important to understand the histologic features associated with HFMD, including spongiosis with exocytosis of neutrophils as well as keratinocyte necrosis and pallor with associated shadow cells.⁶ In one series, the most extensively involved areas of keratinocyte necrosis were the stratum granulosum and upper half of the stratum spinosum.⁴⁰ In the dermis, vascular involvement may be present on a spectrum with the extravasation of red blood cells and leukocytoclasis or true leukocytoclastic vasculitis.^6,40 Vesicular lesions show severe dermal edema and inflammatory infiltrate.^6,41 CD3⁺ and CD8⁺ lymphocytes predominate. Cytotoxic T lymphocytes are present and express granzyme B and granulysin, both important mediators of apoptosis in virally infected keratinocytes.⁶

Adult HFMD primarily is a clinical diagnosis, and histopathologic analysis can be a useful tool in certain cases. Coxsackievirus A6 does not grow well on culture and is not detected by standard serologic testing laboratories, necessitating the use of quantitative RT-PCR analysis.^41,42 In one study, culture was able to detect only 14% to 16% of samples that tested positive by quantitative RT-PCR.⁴³ This form of PCR identifies viral subtype through amplification of enterovirus viral protein 1 capsid gene sequence.²⁴ Unfortunately, this testing often is not offered in most readily available laboratories and often necessitates being sent out to more well-equipped laboratories.^2,24

Treatment

Hand-foot-and-mouth disease is a self-limited illness and requires only supportive care with a focus on hydration and pain management. Lesions heal without scarring but may leave notable postinflammatory pigment alteration that may last months to years, depending on extent of disease and skin type. Secondarily infected individuals should be treated with appropriate antibiotics or antivirals depending on the infectious agent. Hand hygiene is of great importance, and hospitalized patients should be put on strict contact precautions. It also is important to isolate patients from vulnerable individuals, especially pregnant women, as coxsackievirus has been linked to intrauterine infections and loss of pregnancy.²⁴

Genetic Analysis

Genetic studies of the virus have suggested that nonstructural genes may be playing an interesting role in clinical phenotypes and outcomes of CVA6 infection.⁴⁴ These genetic studies also are being implemented into the understanding of the virus’ evolution as well as the construction of vaccinations.^27,44

Conclusion

With the increasing prevalence of CVA6-associated HFMD, it is important to understand the clinical presentation and histologic findings associated with this atypical presentation of the disease as well as the changing epidemiology of the viral strains causing HFMD.

Hand-foot-and-mouth disease (HFMD) is a viral illness caused by several enteroviruses, most commonly coxsackievirus A16 (CVA16) and enterovirus 71 (EV71). The disease is generally seen in children younger than 5 years, characterized by lesions of the oral mucosa, palms, and soles, usually lasting 7 to 10 days. Other coxsackie type A viruses, including CVA6, CVA9, and CVA10, also are associated with HFMD.^1-5 Although CVA16 has traditionally been the primary strain causing HFMD, CVA6 has become a major cause of HFMD outbreaks in the United States and worldwide in recent years.^6-12 Interestingly, CVA6 also has been found to be associated with adult HFMD, which has increased in incidence. The CVA6 strain was first identified in association with the disease during HFMD outbreaks in Finland and Singapore in 2008,^13,14 with similar strains detected in subsequent outbreaks in Taiwan, Japan, Spain, France, China, India, and the United States.^12,15-25 Most cases took place in warmer months, with one winter outbreak in Massachusetts in 2012.²⁴

Herein, we review the incidence of CVA6, as well as its atypical presentation, diagnosis, and treatment to aid dermatologists. Given the increasing incidence of HFMD caused by CVA6 and its often atypical presentation, it is important for dermatologists to be aware of this increasingly notable disease state and its viral cause.

Incidence of CVA6

Coxsackievirus A6 has been identified as the cause of many reported outbreaks of HFMD since it was first identified in 2008, and it is known to cause both pediatric and adult outbreaks.^7-12 It may even be surpassing other strains in frequency in certain areas. In Tianjin, China, for example, EV71 and CVA16 were the most common serotypes causing HFMD from 2008 to 2012; however, in 2013, CVA6 was the most prevalent strain.²⁶ According to one study, “[n]early every Chinese city showed a sharp rise in [CVA6].”²⁷

The incidence of CVA6 also has been increasing in other areas.²⁸ In Spain, CVA6 overtook CVA16 as the dominant cause of HFMD during 2011 and 2012 outbreaks.²⁹ From 2011 to 2012, there was a CVA6-associated HFMD outbreak in North America, with 63 cases reported to the Centers for Disease Control and Prevention (CDC), including 15 adult cases, with approximately 50% having been exposed to children with HFMD.⁹ In 2014, a Minnesota college with approximately 1000 students reported 9 suspected cases of HFMD to the Minnesota Department of Health. Coxsackievirus A6 was isolated, sequenced, and identified by the CDC in 5 of 9 patients (age range, 19–47 years).⁹

In 2015, an outbreak of HFMD took place at Lackland Air Force Base in Texas during a basic military training. Eight cases were confirmed and 45 cases were suspected. The rate of infection was 0.4% (50/12,270) among trainees and 0.3% (2/602) among instructors.⁷ Eight of 12 nasopharyngeal swabs tested positive for EV by way of local real-time reverse transcription–polymerase chain reaction (RT-PCR). Four nasopharyngeal swabs were sent to the CDC for evaluation and all were positive for CVA6.⁷

Presentation

Because the prevalence of CVA6 has increased, it is important to be able to identify the presentation of HFMD caused by this strain. Coxsackievirus A6 has been found to affect a broader demographic and cause more severe cases of HFMD with its unique constellation of findings compared to other known strains. Patients present with flulike symptoms; higher fever than present in typical HFMD; and a longer duration of disease, typically lasting 2 weeks. Patients also may present with more severe skin disease compared to classic HFMD, not only including vesicles but also large bullae, erosions, and ulcers on the dorsal and plantar feet (Figure 1). Skin lesions often are painful and spread to a wider distribution than typical of HFMD, which can include the face, proximal extremities, lips, perianal and groin skin, scalp, and dorsal feet and hands (Figure 2). These areas are classically spared in the prototypical presentation of HFMD in children.^2,6,24,30-33 Vesicles that are typically football shaped (Figure 3) are a diagnostic clue of the disease. After patients have recovered from the disease, they can have delayed-onset palmar and plantar desquamation that usually presents 1 to 3 weeks after the disease. Additionally, another postsyndrome finding is onychomadesis, or detachment of the nail plate from the nail matrix.^6,34-37 This process likely occurs due to direct cytopathic effect to the nail matrix from the viral infection.^24,37 Blistering may be severe and can form hemorrhagic bullae.²⁴ Although cutaneous findings are more severe, neurologic involvement actually is more rare in the CVA6 strain compared to other viral strains known to cause HFMD, specifically EV71. One study found only 2.4% of 141 patients infected with CVA6 had central nervous system involvement, specifically aseptic meningitis or encephalitis.^21,24

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

In patients with atopic dermatitis, CVA6 also shows a predilection to appear in areas of skin disease, such as the flexural regions of the arms and legs, and is referred to as eczema coxsackium.^24,38,39 It can mimic eczema herpeticum or varicella superinfection, which are important considerations to include in the differential diagnosis. Additionally, CVA6-induced lesions often show up in previously irritated or traumatized areas such as sunburns, fungal infections, and diaper dermatitis in children. Lesions have been described to sometimes mimic Gianotti-Crosti syndrome, with involvement of the extensor surfaces, buttocks, and cheeks, and sparing of the trunk.²⁴

Clinical Diagnosis

Because HFMD is uncommon and atypical in adults, skin biopsies may be used in the initial workup and evaluation of patients. It is important to understand the histologic features associated with HFMD, including spongiosis with exocytosis of neutrophils as well as keratinocyte necrosis and pallor with associated shadow cells.⁶ In one series, the most extensively involved areas of keratinocyte necrosis were the stratum granulosum and upper half of the stratum spinosum.⁴⁰ In the dermis, vascular involvement may be present on a spectrum with the extravasation of red blood cells and leukocytoclasis or true leukocytoclastic vasculitis.^6,40 Vesicular lesions show severe dermal edema and inflammatory infiltrate.^6,41 CD3⁺ and CD8⁺ lymphocytes predominate. Cytotoxic T lymphocytes are present and express granzyme B and granulysin, both important mediators of apoptosis in virally infected keratinocytes.⁶

Adult HFMD primarily is a clinical diagnosis, and histopathologic analysis can be a useful tool in certain cases. Coxsackievirus A6 does not grow well on culture and is not detected by standard serologic testing laboratories, necessitating the use of quantitative RT-PCR analysis.^41,42 In one study, culture was able to detect only 14% to 16% of samples that tested positive by quantitative RT-PCR.⁴³ This form of PCR identifies viral subtype through amplification of enterovirus viral protein 1 capsid gene sequence.²⁴ Unfortunately, this testing often is not offered in most readily available laboratories and often necessitates being sent out to more well-equipped laboratories.^2,24

Treatment

Hand-foot-and-mouth disease is a self-limited illness and requires only supportive care with a focus on hydration and pain management. Lesions heal without scarring but may leave notable postinflammatory pigment alteration that may last months to years, depending on extent of disease and skin type. Secondarily infected individuals should be treated with appropriate antibiotics or antivirals depending on the infectious agent. Hand hygiene is of great importance, and hospitalized patients should be put on strict contact precautions. It also is important to isolate patients from vulnerable individuals, especially pregnant women, as coxsackievirus has been linked to intrauterine infections and loss of pregnancy.²⁴

Genetic Analysis

Genetic studies of the virus have suggested that nonstructural genes may be playing an interesting role in clinical phenotypes and outcomes of CVA6 infection.⁴⁴ These genetic studies also are being implemented into the understanding of the virus’ evolution as well as the construction of vaccinations.^27,44

Conclusion

With the increasing prevalence of CVA6-associated HFMD, it is important to understand the clinical presentation and histologic findings associated with this atypical presentation of the disease as well as the changing epidemiology of the viral strains causing HFMD.

Hand-foot-and-mouth disease (HFMD) is a viral illness caused by several enteroviruses, most commonly coxsackievirus A16 (CVA16) and enterovirus 71 (EV71). The disease is generally seen in children younger than 5 years, characterized by lesions of the oral mucosa, palms, and soles, usually lasting 7 to 10 days. Other coxsackie type A viruses, including CVA6, CVA9, and CVA10, also are associated with HFMD.^1-5 Although CVA16 has traditionally been the primary strain causing HFMD, CVA6 has become a major cause of HFMD outbreaks in the United States and worldwide in recent years.^6-12 Interestingly, CVA6 also has been found to be associated with adult HFMD, which has increased in incidence. The CVA6 strain was first identified in association with the disease during HFMD outbreaks in Finland and Singapore in 2008,^13,14 with similar strains detected in subsequent outbreaks in Taiwan, Japan, Spain, France, China, India, and the United States.^12,15-25 Most cases took place in warmer months, with one winter outbreak in Massachusetts in 2012.²⁴

Herein, we review the incidence of CVA6, as well as its atypical presentation, diagnosis, and treatment to aid dermatologists. Given the increasing incidence of HFMD caused by CVA6 and its often atypical presentation, it is important for dermatologists to be aware of this increasingly notable disease state and its viral cause.

Incidence of CVA6

Coxsackievirus A6 has been identified as the cause of many reported outbreaks of HFMD since it was first identified in 2008, and it is known to cause both pediatric and adult outbreaks.^7-12 It may even be surpassing other strains in frequency in certain areas. In Tianjin, China, for example, EV71 and CVA16 were the most common serotypes causing HFMD from 2008 to 2012; however, in 2013, CVA6 was the most prevalent strain.²⁶ According to one study, “[n]early every Chinese city showed a sharp rise in [CVA6].”²⁷

The incidence of CVA6 also has been increasing in other areas.²⁸ In Spain, CVA6 overtook CVA16 as the dominant cause of HFMD during 2011 and 2012 outbreaks.²⁹ From 2011 to 2012, there was a CVA6-associated HFMD outbreak in North America, with 63 cases reported to the Centers for Disease Control and Prevention (CDC), including 15 adult cases, with approximately 50% having been exposed to children with HFMD.⁹ In 2014, a Minnesota college with approximately 1000 students reported 9 suspected cases of HFMD to the Minnesota Department of Health. Coxsackievirus A6 was isolated, sequenced, and identified by the CDC in 5 of 9 patients (age range, 19–47 years).⁹

In 2015, an outbreak of HFMD took place at Lackland Air Force Base in Texas during a basic military training. Eight cases were confirmed and 45 cases were suspected. The rate of infection was 0.4% (50/12,270) among trainees and 0.3% (2/602) among instructors.⁷ Eight of 12 nasopharyngeal swabs tested positive for EV by way of local real-time reverse transcription–polymerase chain reaction (RT-PCR). Four nasopharyngeal swabs were sent to the CDC for evaluation and all were positive for CVA6.⁷

Presentation

Because the prevalence of CVA6 has increased, it is important to be able to identify the presentation of HFMD caused by this strain. Coxsackievirus A6 has been found to affect a broader demographic and cause more severe cases of HFMD with its unique constellation of findings compared to other known strains. Patients present with flulike symptoms; higher fever than present in typical HFMD; and a longer duration of disease, typically lasting 2 weeks. Patients also may present with more severe skin disease compared to classic HFMD, not only including vesicles but also large bullae, erosions, and ulcers on the dorsal and plantar feet (Figure 1). Skin lesions often are painful and spread to a wider distribution than typical of HFMD, which can include the face, proximal extremities, lips, perianal and groin skin, scalp, and dorsal feet and hands (Figure 2). These areas are classically spared in the prototypical presentation of HFMD in children.^2,6,24,30-33 Vesicles that are typically football shaped (Figure 3) are a diagnostic clue of the disease. After patients have recovered from the disease, they can have delayed-onset palmar and plantar desquamation that usually presents 1 to 3 weeks after the disease. Additionally, another postsyndrome finding is onychomadesis, or detachment of the nail plate from the nail matrix.^6,34-37 This process likely occurs due to direct cytopathic effect to the nail matrix from the viral infection.^24,37 Blistering may be severe and can form hemorrhagic bullae.²⁴ Although cutaneous findings are more severe, neurologic involvement actually is more rare in the CVA6 strain compared to other viral strains known to cause HFMD, specifically EV71. One study found only 2.4% of 141 patients infected with CVA6 had central nervous system involvement, specifically aseptic meningitis or encephalitis.^21,24

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

Photograph courtesy of Lauren Snitzer, MD (Houston, Texas).

In patients with atopic dermatitis, CVA6 also shows a predilection to appear in areas of skin disease, such as the flexural regions of the arms and legs, and is referred to as eczema coxsackium.^24,38,39 It can mimic eczema herpeticum or varicella superinfection, which are important considerations to include in the differential diagnosis. Additionally, CVA6-induced lesions often show up in previously irritated or traumatized areas such as sunburns, fungal infections, and diaper dermatitis in children. Lesions have been described to sometimes mimic Gianotti-Crosti syndrome, with involvement of the extensor surfaces, buttocks, and cheeks, and sparing of the trunk.²⁴

Clinical Diagnosis

Because HFMD is uncommon and atypical in adults, skin biopsies may be used in the initial workup and evaluation of patients. It is important to understand the histologic features associated with HFMD, including spongiosis with exocytosis of neutrophils as well as keratinocyte necrosis and pallor with associated shadow cells.⁶ In one series, the most extensively involved areas of keratinocyte necrosis were the stratum granulosum and upper half of the stratum spinosum.⁴⁰ In the dermis, vascular involvement may be present on a spectrum with the extravasation of red blood cells and leukocytoclasis or true leukocytoclastic vasculitis.^6,40 Vesicular lesions show severe dermal edema and inflammatory infiltrate.^6,41 CD3⁺ and CD8⁺ lymphocytes predominate. Cytotoxic T lymphocytes are present and express granzyme B and granulysin, both important mediators of apoptosis in virally infected keratinocytes.⁶

Adult HFMD primarily is a clinical diagnosis, and histopathologic analysis can be a useful tool in certain cases. Coxsackievirus A6 does not grow well on culture and is not detected by standard serologic testing laboratories, necessitating the use of quantitative RT-PCR analysis.^41,42 In one study, culture was able to detect only 14% to 16% of samples that tested positive by quantitative RT-PCR.⁴³ This form of PCR identifies viral subtype through amplification of enterovirus viral protein 1 capsid gene sequence.²⁴ Unfortunately, this testing often is not offered in most readily available laboratories and often necessitates being sent out to more well-equipped laboratories.^2,24

Treatment

Hand-foot-and-mouth disease is a self-limited illness and requires only supportive care with a focus on hydration and pain management. Lesions heal without scarring but may leave notable postinflammatory pigment alteration that may last months to years, depending on extent of disease and skin type. Secondarily infected individuals should be treated with appropriate antibiotics or antivirals depending on the infectious agent. Hand hygiene is of great importance, and hospitalized patients should be put on strict contact precautions. It also is important to isolate patients from vulnerable individuals, especially pregnant women, as coxsackievirus has been linked to intrauterine infections and loss of pregnancy.²⁴

Genetic Analysis

Genetic studies of the virus have suggested that nonstructural genes may be playing an interesting role in clinical phenotypes and outcomes of CVA6 infection.⁴⁴ These genetic studies also are being implemented into the understanding of the virus’ evolution as well as the construction of vaccinations.^27,44

Conclusion

With the increasing prevalence of CVA6-associated HFMD, it is important to understand the clinical presentation and histologic findings associated with this atypical presentation of the disease as well as the changing epidemiology of the viral strains causing HFMD.

I have written previously about Current Procedural Terminology (CPT) procedure codes submitted on the same date of service as evaluation and management (E/M) services in the context of modifier -25.¹ Billing same-day procedures and E/M services is under close scrutiny by insurers, and accurate and complete documentation is a must.² An understanding of what aspects of evaluation are included in the global surgical package is critical in deciding whether a separate and distinct same-day evaluation was performed. In general, the decision to perform a procedure is included in the payment for the procedure itself, as is the examination of the body site in question, diagnosis of the medical condition, discussion of treatment options, and postoperative services related to the procedure. This is true for CPT codes that contain physician work, which constitute the majority of CPT codes reported by dermatologists.³

However, there is one set of codes where these principles do not apply: the practice expense (PE)–only codes, or no physician work codes. These codes are defined by CPT and the Relative Value Scale Update Committee (RUC) of the American Medical Association as containing no physician work. Their valuations are based only on staff/nursing time and the other aspects of direct and indirect practice costs included in providing the service, such as gauze, sutures, equipment, office rent, and utilities.⁴ Examples of PE-only codes include the nonphysician-performed photodynamic therapy code 96567; phototherapy codes 96900, 96910, and 96912; and patch testing and photopatch testing codes 95044, 95052, and 95056.

For PE-only codes, only the provision of the service by staff is included in the code reimbursement; there is no physician time or work built into these codes. Thus, neither the initial evaluation of the patient by the physician, the decision to perform the procedure, nor the evaluation of therapy effectiveness or side effects or interpretation of the results is included. Understanding that there is no physician involvement in PE-only codes is critical in deciding whether an E/M service should be billed on the same day as a PE-only code. To that end, although a physician does not actually have to personally evaluate the patient on the day of service to bill PE-only codes, the Centers for Medicare & Medicaid Services has indicated that a physician or qualified medical provider must be on premises.⁵ Billing for PE-only services when no provider is present will be interpreted as a false claim or fraudulent billing practice.

Because PE-only codes do not include physician work, an E/M service will be billed in addition to the treatment almost any time a same-day physician evaluation is performed. For example, if a patient presents with a changing mole that is evaluated on the same date of service as phototherapy for the treatment of psoriasis, that service is clearly reportable with an E/M code because the mole check is separate and distinct from the phototherapy treatment. A more common scenario is for the physician to see a patient with a rash consistent with an allergic contact dermatitis and the decision to perform same-day patch testing is made. In this circumstance, the E/M service is still reportable because the evaluation of the rash and the decision to perform patch testing are not included in this PE-only code.

Phototherapy typically is provided as a prolonged course of multiple treatments, and reporting of same-day E/M services during the course of therapy is common. Phototherapy must be monitored by the physician for clinical effectiveness, dose changes, and side effects, as well as to determine whether to continue therapy. A standard operating procedure should be created to document that the physician typically evaluates the patient’s progress at set intervals or as dictated by patient or staff concerns. Reporting an E/M service with every phototherapy session is not considered medically necessary. Moreover, a nurse evaluation of the patient prior to each phototherapy treatment, including questions on disease severity, how the patient did with the last treatment, and whether medications have changed, is included in the payment for the phototherapy codes. Only formal and medically necessary physician E/M services should be billed, not drive-by visits in which the physician pops in just to see how the patient is doing.

Final Thoughts

Practice expense–only codes include no payment for physician time or work but require the presence of a qualified health care provider on premises to bill. Medically necessary physician evaluations on the same day as PE-only services will typically result in both an E/M service and the procedure being reported. Understanding performance and documentation requirements of PE-only codes is critical for proper reimbursement for a dermatology practice.

I have written previously about Current Procedural Terminology (CPT) procedure codes submitted on the same date of service as evaluation and management (E/M) services in the context of modifier -25.¹ Billing same-day procedures and E/M services is under close scrutiny by insurers, and accurate and complete documentation is a must.² An understanding of what aspects of evaluation are included in the global surgical package is critical in deciding whether a separate and distinct same-day evaluation was performed. In general, the decision to perform a procedure is included in the payment for the procedure itself, as is the examination of the body site in question, diagnosis of the medical condition, discussion of treatment options, and postoperative services related to the procedure. This is true for CPT codes that contain physician work, which constitute the majority of CPT codes reported by dermatologists.³

However, there is one set of codes where these principles do not apply: the practice expense (PE)–only codes, or no physician work codes. These codes are defined by CPT and the Relative Value Scale Update Committee (RUC) of the American Medical Association as containing no physician work. Their valuations are based only on staff/nursing time and the other aspects of direct and indirect practice costs included in providing the service, such as gauze, sutures, equipment, office rent, and utilities.⁴ Examples of PE-only codes include the nonphysician-performed photodynamic therapy code 96567; phototherapy codes 96900, 96910, and 96912; and patch testing and photopatch testing codes 95044, 95052, and 95056.

For PE-only codes, only the provision of the service by staff is included in the code reimbursement; there is no physician time or work built into these codes. Thus, neither the initial evaluation of the patient by the physician, the decision to perform the procedure, nor the evaluation of therapy effectiveness or side effects or interpretation of the results is included. Understanding that there is no physician involvement in PE-only codes is critical in deciding whether an E/M service should be billed on the same day as a PE-only code. To that end, although a physician does not actually have to personally evaluate the patient on the day of service to bill PE-only codes, the Centers for Medicare & Medicaid Services has indicated that a physician or qualified medical provider must be on premises.⁵ Billing for PE-only services when no provider is present will be interpreted as a false claim or fraudulent billing practice.

Because PE-only codes do not include physician work, an E/M service will be billed in addition to the treatment almost any time a same-day physician evaluation is performed. For example, if a patient presents with a changing mole that is evaluated on the same date of service as phototherapy for the treatment of psoriasis, that service is clearly reportable with an E/M code because the mole check is separate and distinct from the phototherapy treatment. A more common scenario is for the physician to see a patient with a rash consistent with an allergic contact dermatitis and the decision to perform same-day patch testing is made. In this circumstance, the E/M service is still reportable because the evaluation of the rash and the decision to perform patch testing are not included in this PE-only code.

Phototherapy typically is provided as a prolonged course of multiple treatments, and reporting of same-day E/M services during the course of therapy is common. Phototherapy must be monitored by the physician for clinical effectiveness, dose changes, and side effects, as well as to determine whether to continue therapy. A standard operating procedure should be created to document that the physician typically evaluates the patient’s progress at set intervals or as dictated by patient or staff concerns. Reporting an E/M service with every phototherapy session is not considered medically necessary. Moreover, a nurse evaluation of the patient prior to each phototherapy treatment, including questions on disease severity, how the patient did with the last treatment, and whether medications have changed, is included in the payment for the phototherapy codes. Only formal and medically necessary physician E/M services should be billed, not drive-by visits in which the physician pops in just to see how the patient is doing.

Final Thoughts

Practice expense–only codes include no payment for physician time or work but require the presence of a qualified health care provider on premises to bill. Medically necessary physician evaluations on the same day as PE-only services will typically result in both an E/M service and the procedure being reported. Understanding performance and documentation requirements of PE-only codes is critical for proper reimbursement for a dermatology practice.

I have written previously about Current Procedural Terminology (CPT) procedure codes submitted on the same date of service as evaluation and management (E/M) services in the context of modifier -25.¹ Billing same-day procedures and E/M services is under close scrutiny by insurers, and accurate and complete documentation is a must.² An understanding of what aspects of evaluation are included in the global surgical package is critical in deciding whether a separate and distinct same-day evaluation was performed. In general, the decision to perform a procedure is included in the payment for the procedure itself, as is the examination of the body site in question, diagnosis of the medical condition, discussion of treatment options, and postoperative services related to the procedure. This is true for CPT codes that contain physician work, which constitute the majority of CPT codes reported by dermatologists.³

However, there is one set of codes where these principles do not apply: the practice expense (PE)–only codes, or no physician work codes. These codes are defined by CPT and the Relative Value Scale Update Committee (RUC) of the American Medical Association as containing no physician work. Their valuations are based only on staff/nursing time and the other aspects of direct and indirect practice costs included in providing the service, such as gauze, sutures, equipment, office rent, and utilities.⁴ Examples of PE-only codes include the nonphysician-performed photodynamic therapy code 96567; phototherapy codes 96900, 96910, and 96912; and patch testing and photopatch testing codes 95044, 95052, and 95056.

For PE-only codes, only the provision of the service by staff is included in the code reimbursement; there is no physician time or work built into these codes. Thus, neither the initial evaluation of the patient by the physician, the decision to perform the procedure, nor the evaluation of therapy effectiveness or side effects or interpretation of the results is included. Understanding that there is no physician involvement in PE-only codes is critical in deciding whether an E/M service should be billed on the same day as a PE-only code. To that end, although a physician does not actually have to personally evaluate the patient on the day of service to bill PE-only codes, the Centers for Medicare & Medicaid Services has indicated that a physician or qualified medical provider must be on premises.⁵ Billing for PE-only services when no provider is present will be interpreted as a false claim or fraudulent billing practice.

Because PE-only codes do not include physician work, an E/M service will be billed in addition to the treatment almost any time a same-day physician evaluation is performed. For example, if a patient presents with a changing mole that is evaluated on the same date of service as phototherapy for the treatment of psoriasis, that service is clearly reportable with an E/M code because the mole check is separate and distinct from the phototherapy treatment. A more common scenario is for the physician to see a patient with a rash consistent with an allergic contact dermatitis and the decision to perform same-day patch testing is made. In this circumstance, the E/M service is still reportable because the evaluation of the rash and the decision to perform patch testing are not included in this PE-only code.

Phototherapy typically is provided as a prolonged course of multiple treatments, and reporting of same-day E/M services during the course of therapy is common. Phototherapy must be monitored by the physician for clinical effectiveness, dose changes, and side effects, as well as to determine whether to continue therapy. A standard operating procedure should be created to document that the physician typically evaluates the patient’s progress at set intervals or as dictated by patient or staff concerns. Reporting an E/M service with every phototherapy session is not considered medically necessary. Moreover, a nurse evaluation of the patient prior to each phototherapy treatment, including questions on disease severity, how the patient did with the last treatment, and whether medications have changed, is included in the payment for the phototherapy codes. Only formal and medically necessary physician E/M services should be billed, not drive-by visits in which the physician pops in just to see how the patient is doing.

Final Thoughts

Practice expense–only codes include no payment for physician time or work but require the presence of a qualified health care provider on premises to bill. Medically necessary physician evaluations on the same day as PE-only services will typically result in both an E/M service and the procedure being reported. Understanding performance and documentation requirements of PE-only codes is critical for proper reimbursement for a dermatology practice.

Case Report

An 11-year-old boy presented with atraumatic thickening of the skin on the bilateral distal and proximal interphalangeal joints of 1 year’s duration. The patient also noted small bumps of unknown duration across the bilateral palms and soles with prominence on the lateral aspects. The patient previously used over-the-counter topical wart removal treatment and topical salicylic acid with minimal improvement. The patient reported no pertinent medical or surgical history, although there was a family history of Alport syndrome, predominantly in male relatives. The patient’s father and paternal grandfather were noted to have similar lesions on the palms.

On physical examination, multiple pink to flesh-colored hyperkeratotic plaques were noted over the proximal and distal interphalangeal joints of the bilateral hands (Figure 1A). Upon close inspection, there were small flesh-colored and slightly translucent papules in a linear distribution on the palmar surfaces of the hands (Figure 2A) with predominance on the thenar and hypothenar eminences. The flexural creases of the bilateral wrists also revealed linear flesh-colored papules. The same small flesh-colored and translucent papules also were noted on the plantar surfaces of the bilateral feet (Figure 2B).

A biopsy was obtained from one of the small translucent papules on the left palm. Hematoxylin and eosin–stained sections revealed elevated compact orthokeratosis with an underlying central epidermal dell (Figure 3). A diagnosis of marginal papular keratoderma was made and further elastin staining was completed. Elastin stains showed marked thinning of the elastin fibers throughout the reticular dermis. Many elastin fibers in the reticular dermis demonstrated a fine arborizing pattern that normally is only evident in the papillary dermis (Figure 4). Acrokeratoelastoidosis (AKE) was diagnosed histopathologically, and knuckle pads were diagnosed clinically.

Because the patient was asymptomatic, he did not want treatment of AKE. He had marked improvement of the knuckle pads after 1 month with daily application of urea cream 10% (Figure 1B), and intermittent use was required for maintenance.

Comment

Etiology
Acrokeratoelastoidosis was first described in 1953 and is considered a type of palmoplantar marginal papular keratoderma.¹ There is overlap within the marginal papular keratodermas that makes precise diagnosis difficult within this group. The marginal papular keratodermas on the palms and soles are a group of disorders that include AKE, focal acral hyperkeratosis (FAH), mosaic acral keratosis, degenerative collagenous plaques on the hands, and digital papular calcific elastosis. These diseases are similar in clinical and histopathological features; some argue these diseases are the same entity.²

Acrokeratoelastoidosis has been hypothesized to originate from altered elastic fiber synthesis from fibroblasts.³ Because AKE is rare, most cases of common knuckle pads do not coexist with AKE; therefore, it is unknown if the underlying etiology remains the same for both entities. Unlike AKE, knuckle pads are often associated with Dupuytren contractures, repetitive trauma, or friction to the area.^1,2

Presentation
Acrokeratoelastoidosis is a rare disease with onset in childhood or young adulthood. Childhood cases are inherited in an autosomal-dominant fashion.¹ Adulthood onset suggests a sporadic form of inheritance. Acrokeratoelastoidosis has no gender or racial predilection.⁴ It presents over the thenar and hypothenar eminences, as well as the lateral digits, calcaneal tendon, and dorsal digits.¹ Most often, AKE occurs symmetrically along the border separating the ventral and dorsal aspects on the palms and soles. These lesions present as small, firm, translucent papules that align linearly on the ventral-dorsal palmoplantar junction in a pattern resembling paving stones.¹ Coalescence of papules into plaques has been reported. Extension of lesions to the dorsal and palmar surfaces can occur. Small circumscribed callosities may develop over the metacarpophalangeal and interphalangeal joints resembling knuckle pads.²

Histopathology
Histopathologically, AKE is distinguished by elastorrhexis—thinning, fragmenting, and rarefaction of elastin fibers—in the epidermis and reticular dermis layers.³ Acrokeratoelastoidosis also presents with orthokeratosis overlying a cuplike epithelial depression and possible epithelial acanthosis.^2,5 Many cases exhibit hypergranulosis at the base of the epidermal dell. Dense basophilic granules may be seen in the peripheral cytoplasm of fibroblast cells coming from the hypothesized defect in elastin secretion.^1,3,4

Differential Diagnosis
The main differential diagnosis of AKE is FAH. Clinically and histopathologically they appear identical; both diseases have cuplike epidermal depressions with overlying orthohyperkeratosis and prominent hypergranulosis.⁵ The elastin stains, Verhoeff-van Gieson or acid orcein stain, are imperative for distinguishing these two diseases. Although AKE demonstrates elastorrhexis and reduced elastic fibers, FAH reveals no alteration of elastic fibers. It has been suggested that FAH is a clinical variant of AKE and should be titled AKE without elastorrhexis.¹

Treatment
Acrokeratoelastoidosis is asymptomatic except for mild palmoplantar hyperhidrosis and typically does not require treatment⁴; however, the condition can be of cosmetic concern for patients. Lesions can be treated topically with keratolytics such as tretinoin and salicylic acid. A wide variety of systemic treatments including methotrexate, prednisolone, dapsone, and acitretin have been reported with variable clinical response.^2-4 Copresenting knuckle pads can be treated with urea cream, salicylic acid cream, or intralesional corticosteroids.¹

Case Report

An 11-year-old boy presented with atraumatic thickening of the skin on the bilateral distal and proximal interphalangeal joints of 1 year’s duration. The patient also noted small bumps of unknown duration across the bilateral palms and soles with prominence on the lateral aspects. The patient previously used over-the-counter topical wart removal treatment and topical salicylic acid with minimal improvement. The patient reported no pertinent medical or surgical history, although there was a family history of Alport syndrome, predominantly in male relatives. The patient’s father and paternal grandfather were noted to have similar lesions on the palms.

On physical examination, multiple pink to flesh-colored hyperkeratotic plaques were noted over the proximal and distal interphalangeal joints of the bilateral hands (Figure 1A). Upon close inspection, there were small flesh-colored and slightly translucent papules in a linear distribution on the palmar surfaces of the hands (Figure 2A) with predominance on the thenar and hypothenar eminences. The flexural creases of the bilateral wrists also revealed linear flesh-colored papules. The same small flesh-colored and translucent papules also were noted on the plantar surfaces of the bilateral feet (Figure 2B).

A biopsy was obtained from one of the small translucent papules on the left palm. Hematoxylin and eosin–stained sections revealed elevated compact orthokeratosis with an underlying central epidermal dell (Figure 3). A diagnosis of marginal papular keratoderma was made and further elastin staining was completed. Elastin stains showed marked thinning of the elastin fibers throughout the reticular dermis. Many elastin fibers in the reticular dermis demonstrated a fine arborizing pattern that normally is only evident in the papillary dermis (Figure 4). Acrokeratoelastoidosis (AKE) was diagnosed histopathologically, and knuckle pads were diagnosed clinically.

Because the patient was asymptomatic, he did not want treatment of AKE. He had marked improvement of the knuckle pads after 1 month with daily application of urea cream 10% (Figure 1B), and intermittent use was required for maintenance.

Comment

Etiology
Acrokeratoelastoidosis was first described in 1953 and is considered a type of palmoplantar marginal papular keratoderma.¹ There is overlap within the marginal papular keratodermas that makes precise diagnosis difficult within this group. The marginal papular keratodermas on the palms and soles are a group of disorders that include AKE, focal acral hyperkeratosis (FAH), mosaic acral keratosis, degenerative collagenous plaques on the hands, and digital papular calcific elastosis. These diseases are similar in clinical and histopathological features; some argue these diseases are the same entity.²

Acrokeratoelastoidosis has been hypothesized to originate from altered elastic fiber synthesis from fibroblasts.³ Because AKE is rare, most cases of common knuckle pads do not coexist with AKE; therefore, it is unknown if the underlying etiology remains the same for both entities. Unlike AKE, knuckle pads are often associated with Dupuytren contractures, repetitive trauma, or friction to the area.^1,2

Presentation
Acrokeratoelastoidosis is a rare disease with onset in childhood or young adulthood. Childhood cases are inherited in an autosomal-dominant fashion.¹ Adulthood onset suggests a sporadic form of inheritance. Acrokeratoelastoidosis has no gender or racial predilection.⁴ It presents over the thenar and hypothenar eminences, as well as the lateral digits, calcaneal tendon, and dorsal digits.¹ Most often, AKE occurs symmetrically along the border separating the ventral and dorsal aspects on the palms and soles. These lesions present as small, firm, translucent papules that align linearly on the ventral-dorsal palmoplantar junction in a pattern resembling paving stones.¹ Coalescence of papules into plaques has been reported. Extension of lesions to the dorsal and palmar surfaces can occur. Small circumscribed callosities may develop over the metacarpophalangeal and interphalangeal joints resembling knuckle pads.²

Histopathology
Histopathologically, AKE is distinguished by elastorrhexis—thinning, fragmenting, and rarefaction of elastin fibers—in the epidermis and reticular dermis layers.³ Acrokeratoelastoidosis also presents with orthokeratosis overlying a cuplike epithelial depression and possible epithelial acanthosis.^2,5 Many cases exhibit hypergranulosis at the base of the epidermal dell. Dense basophilic granules may be seen in the peripheral cytoplasm of fibroblast cells coming from the hypothesized defect in elastin secretion.^1,3,4

Differential Diagnosis
The main differential diagnosis of AKE is FAH. Clinically and histopathologically they appear identical; both diseases have cuplike epidermal depressions with overlying orthohyperkeratosis and prominent hypergranulosis.⁵ The elastin stains, Verhoeff-van Gieson or acid orcein stain, are imperative for distinguishing these two diseases. Although AKE demonstrates elastorrhexis and reduced elastic fibers, FAH reveals no alteration of elastic fibers. It has been suggested that FAH is a clinical variant of AKE and should be titled AKE without elastorrhexis.¹

Treatment
Acrokeratoelastoidosis is asymptomatic except for mild palmoplantar hyperhidrosis and typically does not require treatment⁴; however, the condition can be of cosmetic concern for patients. Lesions can be treated topically with keratolytics such as tretinoin and salicylic acid. A wide variety of systemic treatments including methotrexate, prednisolone, dapsone, and acitretin have been reported with variable clinical response.^2-4 Copresenting knuckle pads can be treated with urea cream, salicylic acid cream, or intralesional corticosteroids.¹

Case Report

An 11-year-old boy presented with atraumatic thickening of the skin on the bilateral distal and proximal interphalangeal joints of 1 year’s duration. The patient also noted small bumps of unknown duration across the bilateral palms and soles with prominence on the lateral aspects. The patient previously used over-the-counter topical wart removal treatment and topical salicylic acid with minimal improvement. The patient reported no pertinent medical or surgical history, although there was a family history of Alport syndrome, predominantly in male relatives. The patient’s father and paternal grandfather were noted to have similar lesions on the palms.

On physical examination, multiple pink to flesh-colored hyperkeratotic plaques were noted over the proximal and distal interphalangeal joints of the bilateral hands (Figure 1A). Upon close inspection, there were small flesh-colored and slightly translucent papules in a linear distribution on the palmar surfaces of the hands (Figure 2A) with predominance on the thenar and hypothenar eminences. The flexural creases of the bilateral wrists also revealed linear flesh-colored papules. The same small flesh-colored and translucent papules also were noted on the plantar surfaces of the bilateral feet (Figure 2B).

A biopsy was obtained from one of the small translucent papules on the left palm. Hematoxylin and eosin–stained sections revealed elevated compact orthokeratosis with an underlying central epidermal dell (Figure 3). A diagnosis of marginal papular keratoderma was made and further elastin staining was completed. Elastin stains showed marked thinning of the elastin fibers throughout the reticular dermis. Many elastin fibers in the reticular dermis demonstrated a fine arborizing pattern that normally is only evident in the papillary dermis (Figure 4). Acrokeratoelastoidosis (AKE) was diagnosed histopathologically, and knuckle pads were diagnosed clinically.

Because the patient was asymptomatic, he did not want treatment of AKE. He had marked improvement of the knuckle pads after 1 month with daily application of urea cream 10% (Figure 1B), and intermittent use was required for maintenance.

Comment

Etiology
Acrokeratoelastoidosis was first described in 1953 and is considered a type of palmoplantar marginal papular keratoderma.¹ There is overlap within the marginal papular keratodermas that makes precise diagnosis difficult within this group. The marginal papular keratodermas on the palms and soles are a group of disorders that include AKE, focal acral hyperkeratosis (FAH), mosaic acral keratosis, degenerative collagenous plaques on the hands, and digital papular calcific elastosis. These diseases are similar in clinical and histopathological features; some argue these diseases are the same entity.²

Acrokeratoelastoidosis has been hypothesized to originate from altered elastic fiber synthesis from fibroblasts.³ Because AKE is rare, most cases of common knuckle pads do not coexist with AKE; therefore, it is unknown if the underlying etiology remains the same for both entities. Unlike AKE, knuckle pads are often associated with Dupuytren contractures, repetitive trauma, or friction to the area.^1,2

Presentation
Acrokeratoelastoidosis is a rare disease with onset in childhood or young adulthood. Childhood cases are inherited in an autosomal-dominant fashion.¹ Adulthood onset suggests a sporadic form of inheritance. Acrokeratoelastoidosis has no gender or racial predilection.⁴ It presents over the thenar and hypothenar eminences, as well as the lateral digits, calcaneal tendon, and dorsal digits.¹ Most often, AKE occurs symmetrically along the border separating the ventral and dorsal aspects on the palms and soles. These lesions present as small, firm, translucent papules that align linearly on the ventral-dorsal palmoplantar junction in a pattern resembling paving stones.¹ Coalescence of papules into plaques has been reported. Extension of lesions to the dorsal and palmar surfaces can occur. Small circumscribed callosities may develop over the metacarpophalangeal and interphalangeal joints resembling knuckle pads.²

Histopathology
Histopathologically, AKE is distinguished by elastorrhexis—thinning, fragmenting, and rarefaction of elastin fibers—in the epidermis and reticular dermis layers.³ Acrokeratoelastoidosis also presents with orthokeratosis overlying a cuplike epithelial depression and possible epithelial acanthosis.^2,5 Many cases exhibit hypergranulosis at the base of the epidermal dell. Dense basophilic granules may be seen in the peripheral cytoplasm of fibroblast cells coming from the hypothesized defect in elastin secretion.^1,3,4

Differential Diagnosis
The main differential diagnosis of AKE is FAH. Clinically and histopathologically they appear identical; both diseases have cuplike epidermal depressions with overlying orthohyperkeratosis and prominent hypergranulosis.⁵ The elastin stains, Verhoeff-van Gieson or acid orcein stain, are imperative for distinguishing these two diseases. Although AKE demonstrates elastorrhexis and reduced elastic fibers, FAH reveals no alteration of elastic fibers. It has been suggested that FAH is a clinical variant of AKE and should be titled AKE without elastorrhexis.¹

Treatment
Acrokeratoelastoidosis is asymptomatic except for mild palmoplantar hyperhidrosis and typically does not require treatment⁴; however, the condition can be of cosmetic concern for patients. Lesions can be treated topically with keratolytics such as tretinoin and salicylic acid. A wide variety of systemic treatments including methotrexate, prednisolone, dapsone, and acitretin have been reported with variable clinical response.^2-4 Copresenting knuckle pads can be treated with urea cream, salicylic acid cream, or intralesional corticosteroids.¹