Pediatric Dermatology Consult

Given the history of sudden hair loss, with the exam revealing a well-circumscribed patch of focal alopecia without cutaneous inflammation, hairs with a narrow base and broad distal shaft, the diagnosis is alopecia areata (AA).

Alopecia areata (AA) is a nonscarring alopecia, within a set of diseases characterized by the preservation of hair follicles and therefore the potential for future hair regrowth.¹ AA is believed to be caused by a breakdown of the immune-privileged nature of hair follicles, resulting in T-lymphocytes targeting the hair follicle directly, shifting follicles to early catagen or telogen phase, but sparing follicular stem cells, thereby allowing the follicle to regenerate in the future.^1-3 Risk factors include family history of AA, thyroid disorders, as well as iron and vitamin D deficiency.^4,5 It characteristically presents with focal, well-demarcated patches of hair loss in the scalp, typically with background skin normal to slightly pink.^3,6 Exam can show “exclamation point” hairs consisting of hairs that are narrow at their base and wide at the distal end.^3,7 Patients may also exhibit eyebrow and eyelash loss as well as nail changes including nail pitting and splitting.⁸ Diagnosis is typically made clinically but is supported by a positive hair pull test, where hairs are pulled from the periphery of an alopecic lesion; the presence of greater than 10% of hairs plucked from the scalp indicates a positive result.^9,10

What’s the differential diagnosis?

The differential diagnosis of AA includes other nonscarring alopecias such as trichotillomania and telogen effluvium. Other possible diagnoses include lichen planopilaris and tinea capitis.

Trichotillomania results in irregularly bordered hair loss and broken hairs of different lengths because of an internal urge to remove one’s hair, resulting in nonscarring alopecia. It can be associated with obsessive-compulsive disorder, anxiety, or other body-altering behaviors like skin picking and nail biting (characterized as body-focused repetitive behavior disorders). Treatments include reassurance and education, behavior modification, or systemic therapy including tricyclic antidepressants or SSRIs. Toddlers can engage in hair pulling behavior and trichotillomania can be difficult to differentiate from AA. However, the absence of broken hairs of varying lengths makes trichotillomania less likely in this patient.

Telogen effluvium is another form of nonscarring alopecia that presents as diffuse hair thinning across the entire scalp in response to acute psychological or physiological stress, hormonal changes, certain medications, systemic illness, or nutritional deficiency. The timing between the triggering event and hair loss can vary from weeks to months. Diagnosis requires detailed history-taking and may include evaluation for endocrinologic hair thinning (e.g. thyroid function tests) to identify reversible causes. Treatment involves directing therapy to the underlying etiology and most cases of telogen effluvium are self-limited. The presence of a well-circumscribed patch of hair loss in this patient makes AA more likely.

What’s the management plan?

The diagnosis of AA is usually a clinical one, though assessment of alternative diagnoses is appropriate dependent on signs and symptoms. Workup of AA can include thyroid studies because of the association with autoimmune thyroid disease, though studies suggest limited screening benefits in children.¹¹ Given its variable and unpredictable course, management can include “watchful waiting” because of its potential for spontaneous remission.⁶ For limited patchy loss, active treatment with mid to superpotent topical steroids or intralesional triamcinolone acetonide in older children and adolescents is reasonable.¹² Other treatment options include topical or low-dose oral minoxidil and immunotherapy with diphenylcyclopropenone or squaric acid (inducing an allergic contact dermatitis).¹² Management of therapies for more extensive AA is evolving, with ongoing studies of oral JAK-inhibitors and biologic agents.^12,13

Our patient was started on topical fluocinonide 0.05% solution and achieved good disease control and hair regrowth over the course of 3 months.

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology at the university and Rady Children’s Hospital. They had no disclosures.

References

1. Bernardez C et al. Actas Dermosifiliogr. 2015;106(3):158-67.

2. Rajabi F et al. Br J Dermatol. 2018;179(5):1033-48.

3. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):1-12.

4. Lee S et al. J Am Acad Dermatol. 2019;80(2):466-77 e16.

5. MacLean KJ and Tidman MJ. Practitioner. 2013;257(1764):29-32, 3.

6. Pratt CH et al. Nat Rev Dis Primers. 2017;3:17011.

7. Gilhar A et al. N Engl J Med. 2012;366(16):1515-25.

8. Wyrwich KW et al. Am J Clin Dermatol. 2020;21(5):725-32.

9. Spano F and Donovan JC. Can Fam Physician. 2015;61(9):751-5.

10. Mounsey AL and Reed SW. Am Fam Physician. 2009;80(4):356-62.

11. Hordinsky MK. J Investig Dermatol Symp Proc. 2015;17(2):44-6.

12. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):15-24.

13. Zhou C et al. Clin Rev Allergy Immunol. 2021;61(3):403-23.

Given the history of sudden hair loss, with the exam revealing a well-circumscribed patch of focal alopecia without cutaneous inflammation, hairs with a narrow base and broad distal shaft, the diagnosis is alopecia areata (AA).

Alopecia areata (AA) is a nonscarring alopecia, within a set of diseases characterized by the preservation of hair follicles and therefore the potential for future hair regrowth.¹ AA is believed to be caused by a breakdown of the immune-privileged nature of hair follicles, resulting in T-lymphocytes targeting the hair follicle directly, shifting follicles to early catagen or telogen phase, but sparing follicular stem cells, thereby allowing the follicle to regenerate in the future.^1-3 Risk factors include family history of AA, thyroid disorders, as well as iron and vitamin D deficiency.^4,5 It characteristically presents with focal, well-demarcated patches of hair loss in the scalp, typically with background skin normal to slightly pink.^3,6 Exam can show “exclamation point” hairs consisting of hairs that are narrow at their base and wide at the distal end.^3,7 Patients may also exhibit eyebrow and eyelash loss as well as nail changes including nail pitting and splitting.⁸ Diagnosis is typically made clinically but is supported by a positive hair pull test, where hairs are pulled from the periphery of an alopecic lesion; the presence of greater than 10% of hairs plucked from the scalp indicates a positive result.^9,10

What’s the differential diagnosis?

The differential diagnosis of AA includes other nonscarring alopecias such as trichotillomania and telogen effluvium. Other possible diagnoses include lichen planopilaris and tinea capitis.

Trichotillomania results in irregularly bordered hair loss and broken hairs of different lengths because of an internal urge to remove one’s hair, resulting in nonscarring alopecia. It can be associated with obsessive-compulsive disorder, anxiety, or other body-altering behaviors like skin picking and nail biting (characterized as body-focused repetitive behavior disorders). Treatments include reassurance and education, behavior modification, or systemic therapy including tricyclic antidepressants or SSRIs. Toddlers can engage in hair pulling behavior and trichotillomania can be difficult to differentiate from AA. However, the absence of broken hairs of varying lengths makes trichotillomania less likely in this patient.

Telogen effluvium is another form of nonscarring alopecia that presents as diffuse hair thinning across the entire scalp in response to acute psychological or physiological stress, hormonal changes, certain medications, systemic illness, or nutritional deficiency. The timing between the triggering event and hair loss can vary from weeks to months. Diagnosis requires detailed history-taking and may include evaluation for endocrinologic hair thinning (e.g. thyroid function tests) to identify reversible causes. Treatment involves directing therapy to the underlying etiology and most cases of telogen effluvium are self-limited. The presence of a well-circumscribed patch of hair loss in this patient makes AA more likely.

What’s the management plan?

The diagnosis of AA is usually a clinical one, though assessment of alternative diagnoses is appropriate dependent on signs and symptoms. Workup of AA can include thyroid studies because of the association with autoimmune thyroid disease, though studies suggest limited screening benefits in children.¹¹ Given its variable and unpredictable course, management can include “watchful waiting” because of its potential for spontaneous remission.⁶ For limited patchy loss, active treatment with mid to superpotent topical steroids or intralesional triamcinolone acetonide in older children and adolescents is reasonable.¹² Other treatment options include topical or low-dose oral minoxidil and immunotherapy with diphenylcyclopropenone or squaric acid (inducing an allergic contact dermatitis).¹² Management of therapies for more extensive AA is evolving, with ongoing studies of oral JAK-inhibitors and biologic agents.^12,13

Our patient was started on topical fluocinonide 0.05% solution and achieved good disease control and hair regrowth over the course of 3 months.

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology at the university and Rady Children’s Hospital. They had no disclosures.

References

1. Bernardez C et al. Actas Dermosifiliogr. 2015;106(3):158-67.

2. Rajabi F et al. Br J Dermatol. 2018;179(5):1033-48.

3. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):1-12.

4. Lee S et al. J Am Acad Dermatol. 2019;80(2):466-77 e16.

5. MacLean KJ and Tidman MJ. Practitioner. 2013;257(1764):29-32, 3.

6. Pratt CH et al. Nat Rev Dis Primers. 2017;3:17011.

7. Gilhar A et al. N Engl J Med. 2012;366(16):1515-25.

8. Wyrwich KW et al. Am J Clin Dermatol. 2020;21(5):725-32.

9. Spano F and Donovan JC. Can Fam Physician. 2015;61(9):751-5.

10. Mounsey AL and Reed SW. Am Fam Physician. 2009;80(4):356-62.

11. Hordinsky MK. J Investig Dermatol Symp Proc. 2015;17(2):44-6.

12. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):15-24.

13. Zhou C et al. Clin Rev Allergy Immunol. 2021;61(3):403-23.

Given the history of sudden hair loss, with the exam revealing a well-circumscribed patch of focal alopecia without cutaneous inflammation, hairs with a narrow base and broad distal shaft, the diagnosis is alopecia areata (AA).

Alopecia areata (AA) is a nonscarring alopecia, within a set of diseases characterized by the preservation of hair follicles and therefore the potential for future hair regrowth.¹ AA is believed to be caused by a breakdown of the immune-privileged nature of hair follicles, resulting in T-lymphocytes targeting the hair follicle directly, shifting follicles to early catagen or telogen phase, but sparing follicular stem cells, thereby allowing the follicle to regenerate in the future.^1-3 Risk factors include family history of AA, thyroid disorders, as well as iron and vitamin D deficiency.^4,5 It characteristically presents with focal, well-demarcated patches of hair loss in the scalp, typically with background skin normal to slightly pink.^3,6 Exam can show “exclamation point” hairs consisting of hairs that are narrow at their base and wide at the distal end.^3,7 Patients may also exhibit eyebrow and eyelash loss as well as nail changes including nail pitting and splitting.⁸ Diagnosis is typically made clinically but is supported by a positive hair pull test, where hairs are pulled from the periphery of an alopecic lesion; the presence of greater than 10% of hairs plucked from the scalp indicates a positive result.^9,10

What’s the differential diagnosis?

The differential diagnosis of AA includes other nonscarring alopecias such as trichotillomania and telogen effluvium. Other possible diagnoses include lichen planopilaris and tinea capitis.

Trichotillomania results in irregularly bordered hair loss and broken hairs of different lengths because of an internal urge to remove one’s hair, resulting in nonscarring alopecia. It can be associated with obsessive-compulsive disorder, anxiety, or other body-altering behaviors like skin picking and nail biting (characterized as body-focused repetitive behavior disorders). Treatments include reassurance and education, behavior modification, or systemic therapy including tricyclic antidepressants or SSRIs. Toddlers can engage in hair pulling behavior and trichotillomania can be difficult to differentiate from AA. However, the absence of broken hairs of varying lengths makes trichotillomania less likely in this patient.

Telogen effluvium is another form of nonscarring alopecia that presents as diffuse hair thinning across the entire scalp in response to acute psychological or physiological stress, hormonal changes, certain medications, systemic illness, or nutritional deficiency. The timing between the triggering event and hair loss can vary from weeks to months. Diagnosis requires detailed history-taking and may include evaluation for endocrinologic hair thinning (e.g. thyroid function tests) to identify reversible causes. Treatment involves directing therapy to the underlying etiology and most cases of telogen effluvium are self-limited. The presence of a well-circumscribed patch of hair loss in this patient makes AA more likely.

What’s the management plan?

The diagnosis of AA is usually a clinical one, though assessment of alternative diagnoses is appropriate dependent on signs and symptoms. Workup of AA can include thyroid studies because of the association with autoimmune thyroid disease, though studies suggest limited screening benefits in children.¹¹ Given its variable and unpredictable course, management can include “watchful waiting” because of its potential for spontaneous remission.⁶ For limited patchy loss, active treatment with mid to superpotent topical steroids or intralesional triamcinolone acetonide in older children and adolescents is reasonable.¹² Other treatment options include topical or low-dose oral minoxidil and immunotherapy with diphenylcyclopropenone or squaric acid (inducing an allergic contact dermatitis).¹² Management of therapies for more extensive AA is evolving, with ongoing studies of oral JAK-inhibitors and biologic agents.^12,13

Our patient was started on topical fluocinonide 0.05% solution and achieved good disease control and hair regrowth over the course of 3 months.

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Haft is an inflammatory skin disease fellow in the division of pediatric and adolescent dermatology at the university and Rady Children’s Hospital. They had no disclosures.

References

1. Bernardez C et al. Actas Dermosifiliogr. 2015;106(3):158-67.

2. Rajabi F et al. Br J Dermatol. 2018;179(5):1033-48.

3. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):1-12.

4. Lee S et al. J Am Acad Dermatol. 2019;80(2):466-77 e16.

5. MacLean KJ and Tidman MJ. Practitioner. 2013;257(1764):29-32, 3.

6. Pratt CH et al. Nat Rev Dis Primers. 2017;3:17011.

7. Gilhar A et al. N Engl J Med. 2012;366(16):1515-25.

8. Wyrwich KW et al. Am J Clin Dermatol. 2020;21(5):725-32.

9. Spano F and Donovan JC. Can Fam Physician. 2015;61(9):751-5.

10. Mounsey AL and Reed SW. Am Fam Physician. 2009;80(4):356-62.

11. Hordinsky MK. J Investig Dermatol Symp Proc. 2015;17(2):44-6.

12. Strazzulla LC et al. J Am Acad Dermatol. 2018;78(1):15-24.

13. Zhou C et al. Clin Rev Allergy Immunol. 2021;61(3):403-23.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

The Diagnosis: Molluscum Contagiosum

A tangential shave removal with electrocautery was performed. Histopathology demonstrated numerous eosinophilic intracytoplasmic inclusion bodies (Figure), confirming a diagnosis of molluscum contagiosum (MC).

Molluscum contagiosum is a common poxvirus infection that is transmitted through fomites, contact, or self-inoculation.1 This infection most frequently occurs in school-aged children younger than 8 years^1-3; peak incidence is 6 years of age.^2,3 The worldwide estimated prevalence in children is 5.1% to 11.5%.^1,3 In children cohabitating with others infected by MC, approximately 40% of households experienced a spread of infection; the risk of transmission is not associated with greater number of lesions.⁴ In adults, infection most commonly occurs in the setting of immunodeficiency or as a sexually transmitted infection in immunocompetent patients.³ Molluscum contagiosum infection classically presents as 1- to 3-mm, flesh- or white-colored, dome-shaped, smooth papules with central umbilication.¹ Lesions often occur in clusters or lines, indicating local spread. The trunk, extremities, and face are areas that frequently are involved.^2,3

Atypical presentations of MC infection can occur, as demonstrated by our case. Involvement of hair follicles by the infection can result in follicular induction.^1,5 Secondary infection can mimic abscess formation.¹ Inflamed MC lesions demonstrating the “beginning of the end” sign often are mistaken for primary infection, which is thought to be an inflammatory immune response to the virus.⁶ Lesions located on the eye or eyelid can present as unilateral conjunctivitis, conjunctival or corneal nodules, eyelid abscesses, or chalazions.¹ Giant MC is a nodular variant of this infection measuring larger than 1 cm in size that can present similar to epidermoid cysts, condyloma acuminatum, or verruca vulgaris.^1,7 Other reported mimicked conditions include basal cell carcinoma, trichoepithelioma, appendageal tumors, keratoacanthoma, foreign body granulomas, nevus sebaceous, or ecthyma.^1,3 Molluscum contagiosum also has been reported to present as large ulcerative growths.⁸ In immunocompromised patients, deep fungal infection is another mimicker.1 Lesions on the plantar surfaces of the feet often are misdiagnosed as plantar verruca and present with pain during ambulation.⁹

The diagnosis of MC is clinical, with additional diagnostic tools reserved for more challenging situations.¹ In cases with atypical presentations, dermoscopy may aid diagnosis through visualization of orifices and vascular patterns including crown, radial, and punctiform vessels.¹⁰ Biopsy or fine-needle aspiration also can be utilized as a diagnostic tool. Histopathology often reveals pathognomonic intracytoplasmic inclusions or Henderson-Paterson bodies.^8,10 The appearance of MC can mimic other conditions that should be included in the differential diagnosis. Pyogenic granuloma often presents as a benign red papule that may grow rapidly and become pedunculated, sometimes with bleeding and crusting, though histology reveals groups of proliferating capillaries.¹¹ More than half of amelanotic melanomas present in the papulonodular form as vascular or ulcerated nodules, and others may appear as erythematous macules. Diagnosis of amelanotic melanoma is made through histologic examination, which reveals atypical melanocytes in nests or cords, in conjunction with immunohistochemical stains such as S-100.12 Spitz nevi often appear as round, dome-shaped papules that most commonly are red, pink, or fleshcolored. They appear histologically similar to melanoma with nests of atypical melanocytes and nuclear atypia.¹³

A variety of treatment modalities can be used for MC including cantharidin, curettage, and cryotherapy.¹⁴ Imiquimod no longer is recommended due to a lack of demonstrated superiority over placebo in recent studies as well as its adverse effects.³ Topical retinoids have been recommended; however, their use frequently is limited by local irritation.^3,14 Cantharidin is the most frequently utilized treatment by pediatric dermatologists. Most health care providers report subjective satisfaction with its results and efficacy, though some side effects may occur including discomfort and temporary changes in pigmentation. Treatment for MC is not required, as the condition is self-limiting.¹⁴ Therapy often is reserved for those with extensive disease, complications from lesions, cosmetic or psychological concerns, or genital involvement given the potential for sexual transmission.³ Time to resolution without treatment varies and is more prolonged in immunocompromised patients. Mean time to resolution in immunocompetent hosts has been reported as 13.3 months, but most infections are noted to clear within 2 to 4 years.^1,4 Although resolution without treatment occurs, transmission to others and negative impact on quality of life (QOL) can occur and support the need for treatment. Greater impact on QOL was observed in females, those with more lesions, and patients with a longer duration of symptoms. Moderate impact on QOL was reported in 28% of patients (n=301), and severe effects were reported in 11%.⁴

In conclusion, MC is a common, benign, treatable cutaneous viral infection that often presents as small, flesh-colored papules in children. Its appearance can mimic a variety of other conditions. In cases with abnormal presentations, definitive diagnosis with pathology can be important to differentiate MC from more dangerous etiologies that may require further treatment.

Erythema annulare centrifugum

A thorough body examination failed to reveal any other rashes or lesions suggestive of a fungal infection. A blood count and urinalysis were within normal limits. She had no lymphadenopathy or hepatosplenomegaly. A potassium hydroxide analysis of skin scrapings was negative for fungal elements. Punch biopsy of the skin on the left arm revealed focal intermittent parakeratosis, mildly acanthotic and spongiotic epidermis, and a tight superficial perivascular chronic dermatitis consisting of lymphocytes and histiocytes (Figures). Given these findings, a diagnosis of erythema annulare centrifugum (EAC) was rendered.

Courtesy Dr. Stephen F. Kirschbaum

Courtesy Dr. Stephen F. Kirschbaum

EAC is a rare, reactive skin rash characterized by redness (erythema) and ring-shaped lesions (annulare) that slowly spread from the center (centrifugum). The lesions present with a characteristic trailing scale on the inner border of the erythematous ring. Lesions may be asymptomatic or mildly pruritic and commonly involve the trunk, buttocks, hips, and upper legs. It is important to note that its duration is highly variable, ranging from weeks to decades, with most cases persisting for 9 months. EAC typically affects young or middle-aged adults but can occur at any age.

Courtesy Dr. Catalina Matiz

Erythema marginatum is a rare skin rash commonly seen with acute rheumatic fever secondary to streptococcal infection. It presents as annular erythematous lesions on the trunk and proximal extremities that are exacerbated by heat. It is often associated with active carditis related to rheumatic fever. This self-limited rash usually resolves in 2-3 days. Our patient was asymptomatic without involvement of other organs.

Like EAC, granuloma annulare is a benign chronic skin condition that presents with ring-shaped lesions. Its etiology is unknown, and lesions may be asymptomatic or mildly pruritic. Localized granuloma annulare typically presents as reddish-brown papules or plaques on the fingers, hands, elbows, dorsal feet, or ankles. The distinguishing feature of granuloma annulare from other annular lesions is its absence of scale.

Urticaria multiforme is an allergic hypersensitivity reaction commonly linked to viral infections, medications, and immunizations. Clinical features include blanchable annular/polycyclic lesions with a central purplish or dusky hue. Diagnostic pearls include the presence of pruritus, dermatographism, and individual lesions that resolve within 24 hours, all of which were not found in our patient’s case.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Laborada and Dr. Matiz have no relevant financial disclosures.

References

1. Paller A and Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. Philadelphia: Elsevier Saunders, 2011.

2. McDaniel B and Cook C. “Erythema annulare centrifugum” 2021 Aug 27. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing, 2022 Jan. PMID: 29494101.

3. Leung AK e al. Drugs Context. 2020 Jul 20;9:5-6.

4. Majmundar VD and Nagalli S. “Erythema marginatum” 2022 May 8. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing, 2022 Jan.

5. Piette EW and Rosenbach M. J Am Acad Dermatol. 2016 Sep;75(3):467-79.

6. Barros M et al. BMJ Case Rep. 2021 Jan 28;14(1):e241011.

Erythema annulare centrifugum

A thorough body examination failed to reveal any other rashes or lesions suggestive of a fungal infection. A blood count and urinalysis were within normal limits. She had no lymphadenopathy or hepatosplenomegaly. A potassium hydroxide analysis of skin scrapings was negative for fungal elements. Punch biopsy of the skin on the left arm revealed focal intermittent parakeratosis, mildly acanthotic and spongiotic epidermis, and a tight superficial perivascular chronic dermatitis consisting of lymphocytes and histiocytes (Figures). Given these findings, a diagnosis of erythema annulare centrifugum (EAC) was rendered.

Courtesy Dr. Stephen F. Kirschbaum

Courtesy Dr. Stephen F. Kirschbaum

EAC is a rare, reactive skin rash characterized by redness (erythema) and ring-shaped lesions (annulare) that slowly spread from the center (centrifugum). The lesions present with a characteristic trailing scale on the inner border of the erythematous ring. Lesions may be asymptomatic or mildly pruritic and commonly involve the trunk, buttocks, hips, and upper legs. It is important to note that its duration is highly variable, ranging from weeks to decades, with most cases persisting for 9 months. EAC typically affects young or middle-aged adults but can occur at any age.

Courtesy Dr. Catalina Matiz

Erythema marginatum is a rare skin rash commonly seen with acute rheumatic fever secondary to streptococcal infection. It presents as annular erythematous lesions on the trunk and proximal extremities that are exacerbated by heat. It is often associated with active carditis related to rheumatic fever. This self-limited rash usually resolves in 2-3 days. Our patient was asymptomatic without involvement of other organs.

Like EAC, granuloma annulare is a benign chronic skin condition that presents with ring-shaped lesions. Its etiology is unknown, and lesions may be asymptomatic or mildly pruritic. Localized granuloma annulare typically presents as reddish-brown papules or plaques on the fingers, hands, elbows, dorsal feet, or ankles. The distinguishing feature of granuloma annulare from other annular lesions is its absence of scale.

Urticaria multiforme is an allergic hypersensitivity reaction commonly linked to viral infections, medications, and immunizations. Clinical features include blanchable annular/polycyclic lesions with a central purplish or dusky hue. Diagnostic pearls include the presence of pruritus, dermatographism, and individual lesions that resolve within 24 hours, all of which were not found in our patient’s case.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Laborada and Dr. Matiz have no relevant financial disclosures.

References

1. Paller A and Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. Philadelphia: Elsevier Saunders, 2011.

2. McDaniel B and Cook C. “Erythema annulare centrifugum” 2021 Aug 27. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing, 2022 Jan. PMID: 29494101.

3. Leung AK e al. Drugs Context. 2020 Jul 20;9:5-6.

4. Majmundar VD and Nagalli S. “Erythema marginatum” 2022 May 8. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing, 2022 Jan.

5. Piette EW and Rosenbach M. J Am Acad Dermatol. 2016 Sep;75(3):467-79.

6. Barros M et al. BMJ Case Rep. 2021 Jan 28;14(1):e241011.

Erythema annulare centrifugum

A thorough body examination failed to reveal any other rashes or lesions suggestive of a fungal infection. A blood count and urinalysis were within normal limits. She had no lymphadenopathy or hepatosplenomegaly. A potassium hydroxide analysis of skin scrapings was negative for fungal elements. Punch biopsy of the skin on the left arm revealed focal intermittent parakeratosis, mildly acanthotic and spongiotic epidermis, and a tight superficial perivascular chronic dermatitis consisting of lymphocytes and histiocytes (Figures). Given these findings, a diagnosis of erythema annulare centrifugum (EAC) was rendered.

Courtesy Dr. Stephen F. Kirschbaum

Courtesy Dr. Stephen F. Kirschbaum

EAC is a rare, reactive skin rash characterized by redness (erythema) and ring-shaped lesions (annulare) that slowly spread from the center (centrifugum). The lesions present with a characteristic trailing scale on the inner border of the erythematous ring. Lesions may be asymptomatic or mildly pruritic and commonly involve the trunk, buttocks, hips, and upper legs. It is important to note that its duration is highly variable, ranging from weeks to decades, with most cases persisting for 9 months. EAC typically affects young or middle-aged adults but can occur at any age.

Courtesy Dr. Catalina Matiz

Erythema marginatum is a rare skin rash commonly seen with acute rheumatic fever secondary to streptococcal infection. It presents as annular erythematous lesions on the trunk and proximal extremities that are exacerbated by heat. It is often associated with active carditis related to rheumatic fever. This self-limited rash usually resolves in 2-3 days. Our patient was asymptomatic without involvement of other organs.

Like EAC, granuloma annulare is a benign chronic skin condition that presents with ring-shaped lesions. Its etiology is unknown, and lesions may be asymptomatic or mildly pruritic. Localized granuloma annulare typically presents as reddish-brown papules or plaques on the fingers, hands, elbows, dorsal feet, or ankles. The distinguishing feature of granuloma annulare from other annular lesions is its absence of scale.

Urticaria multiforme is an allergic hypersensitivity reaction commonly linked to viral infections, medications, and immunizations. Clinical features include blanchable annular/polycyclic lesions with a central purplish or dusky hue. Diagnostic pearls include the presence of pruritus, dermatographism, and individual lesions that resolve within 24 hours, all of which were not found in our patient’s case.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Laborada and Dr. Matiz have no relevant financial disclosures.

References

1. Paller A and Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood and Adolescence. 4th ed. Philadelphia: Elsevier Saunders, 2011.

2. McDaniel B and Cook C. “Erythema annulare centrifugum” 2021 Aug 27. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing, 2022 Jan. PMID: 29494101.

3. Leung AK e al. Drugs Context. 2020 Jul 20;9:5-6.

4. Majmundar VD and Nagalli S. “Erythema marginatum” 2022 May 8. In: StatPearls [Internet]. Treasure Island, Fla.: StatPearls Publishing, 2022 Jan.

5. Piette EW and Rosenbach M. J Am Acad Dermatol. 2016 Sep;75(3):467-79.

6. Barros M et al. BMJ Case Rep. 2021 Jan 28;14(1):e241011.

The finding of individual, 1- to 4-mm firm, red papules depicted in the image are consistent with facial angiofibromas, which are most commonly seen in pediatric patients as a manifestation of tuberous sclerosis (TSC). Angiofibromas, previously called adenoma sebaceum, a misnomer, are seen in TSC as smooth papules, nodules, and occasionally plaques that typically involve the malar region of the face. These lesions usually develop in childhood and adolescence and can be misdiagnosed as lesions of acne. The number of lesions tend to increase with age, though there is no significant risk of malignant transformation. Ultraviolet-induced DNA damage is thought to play a role in the development of facial angiofibromas, so sun protection is called for.¹ Patients may seek treatment to minimize deformity and the stigma of angiofibromas. Recently, the mammalian target of rapamycin inhibitor sirolimus (rapamycin) topical gel received Food and Drug Administration approval for the treatment of facial angiofibromas associated with TSC in patients age at least 6 years.²

The presence of angiofibromas should prompt consideration of TSC and as such, a thorough family history, medical history, and full-body skin examination. TSC is a rare autosomal-dominant genetic disorder, caused by a pathogenic variant in either the TSC1 or TSC2 gene. This neurocutaneous disorder is characterized by the development of multiple benign hamartomas across many organ systems including the brain, eyes, heart, lung, liver, kidney, and skin. The phenotypic expression of TSC is highly variable. Besides angiofibromas, some other characteristic dermatological findings in TSC include periungual fibromas, hypopigmented macules usually elliptical in shape (known as ash-leaf spots), and irregularly shaped elevated flesh-colored fibrous tissue most often found over the lower back (known as shagreen patches).³

What is on the differential?

Agminated spitz nevi refers to multiple spitz nevi in a localized area. Spitz nevi present as a well-circumscribed, dome-shaped, pink-red or brown papules, most commonly located on the face or lower extremities.⁴ The finding of agminated spitz nevi is very rare and less likely for this patient given the concomitant skin findings of dental pitting, renal cysts, and cortical tubers.

Juvenile xanthogranulomas are benign,proliferations of histiocytic cells that present as reddish or yellowish-to-brown papules, plaques, or nodules that typically develop in young children around the age of 1. With time, juvenile xanthogranulomas may flatten and become more yellow.

Basal cell carcinomas present as dome-shaped lesions with centralized erosions on sun-exposed areas of the skin. They are remarkably uncommon in children but are occasionally seen in basal cell nevus syndrome (also known as nevoid basal cell carcinoma syndrome or Gorlin syndrome). Affected patients may have other findings such as developmental anomalies, bifid ribs, palmar and plantar pitting, odontogenic keratocysts, and/or medulloblastomas.⁵

Flat warts commonly occur in children and occur by direct skin contact with human papillomavirus. Of the various types of warts, flat warts are smaller and tend to be smooth on top. The diagnosis of cutaneous warts is based on clinical appearance, showing thrombosed capillaries underneath the overlying hyperkeratotic debris. Our patient’s history of having a common wart on her hands raises suspicion for inoculation onto her face, but the morphology, distribution, and lack of response to tretinoin makes this diagnosis much less likely.

Disease workup and course

Our patient’s physical exam revealed dental pits but no evidence of hypopigmented macules, shagreen patches, or periungual lesions. Ultrasound of the kidney displayed renal cortical cysts and brain MRI showed cortical tubers, confirming extracutaneous TSC involvement. Over time, our patient developed angiofibromas on the forehead and was ultimately started on topical sirolimus, which led to marked improvement within months.

Ms. Kleinman is a pediatric dermatology research associate, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, also in San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. They have no relevant financial disclosures.

References

1. Tyburczy ME et al. Hum Molec Genet. 2014;23(8):2023-9.

2. Food & Drug Administration. New drug application (NDA) approval for Hyftor (sirolimus topical gel). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/213478Orig1s000ltr.pdf.

3. Webb DW et al. Br J Dermatol. 1996;135(1):1-5.

4. Ricci F et al. Eur J Dermatol. 2017;27(1):59-62.

5. Evans DG and Farndon PA. Nevoid basal cell carcinoma syndrome, in “GeneReviews®.” Seattle: University of Washington, 2002.

The finding of individual, 1- to 4-mm firm, red papules depicted in the image are consistent with facial angiofibromas, which are most commonly seen in pediatric patients as a manifestation of tuberous sclerosis (TSC). Angiofibromas, previously called adenoma sebaceum, a misnomer, are seen in TSC as smooth papules, nodules, and occasionally plaques that typically involve the malar region of the face. These lesions usually develop in childhood and adolescence and can be misdiagnosed as lesions of acne. The number of lesions tend to increase with age, though there is no significant risk of malignant transformation. Ultraviolet-induced DNA damage is thought to play a role in the development of facial angiofibromas, so sun protection is called for.¹ Patients may seek treatment to minimize deformity and the stigma of angiofibromas. Recently, the mammalian target of rapamycin inhibitor sirolimus (rapamycin) topical gel received Food and Drug Administration approval for the treatment of facial angiofibromas associated with TSC in patients age at least 6 years.²

The presence of angiofibromas should prompt consideration of TSC and as such, a thorough family history, medical history, and full-body skin examination. TSC is a rare autosomal-dominant genetic disorder, caused by a pathogenic variant in either the TSC1 or TSC2 gene. This neurocutaneous disorder is characterized by the development of multiple benign hamartomas across many organ systems including the brain, eyes, heart, lung, liver, kidney, and skin. The phenotypic expression of TSC is highly variable. Besides angiofibromas, some other characteristic dermatological findings in TSC include periungual fibromas, hypopigmented macules usually elliptical in shape (known as ash-leaf spots), and irregularly shaped elevated flesh-colored fibrous tissue most often found over the lower back (known as shagreen patches).³

What is on the differential?

Agminated spitz nevi refers to multiple spitz nevi in a localized area. Spitz nevi present as a well-circumscribed, dome-shaped, pink-red or brown papules, most commonly located on the face or lower extremities.⁴ The finding of agminated spitz nevi is very rare and less likely for this patient given the concomitant skin findings of dental pitting, renal cysts, and cortical tubers.

Juvenile xanthogranulomas are benign,proliferations of histiocytic cells that present as reddish or yellowish-to-brown papules, plaques, or nodules that typically develop in young children around the age of 1. With time, juvenile xanthogranulomas may flatten and become more yellow.

Basal cell carcinomas present as dome-shaped lesions with centralized erosions on sun-exposed areas of the skin. They are remarkably uncommon in children but are occasionally seen in basal cell nevus syndrome (also known as nevoid basal cell carcinoma syndrome or Gorlin syndrome). Affected patients may have other findings such as developmental anomalies, bifid ribs, palmar and plantar pitting, odontogenic keratocysts, and/or medulloblastomas.⁵

Flat warts commonly occur in children and occur by direct skin contact with human papillomavirus. Of the various types of warts, flat warts are smaller and tend to be smooth on top. The diagnosis of cutaneous warts is based on clinical appearance, showing thrombosed capillaries underneath the overlying hyperkeratotic debris. Our patient’s history of having a common wart on her hands raises suspicion for inoculation onto her face, but the morphology, distribution, and lack of response to tretinoin makes this diagnosis much less likely.

Disease workup and course

Our patient’s physical exam revealed dental pits but no evidence of hypopigmented macules, shagreen patches, or periungual lesions. Ultrasound of the kidney displayed renal cortical cysts and brain MRI showed cortical tubers, confirming extracutaneous TSC involvement. Over time, our patient developed angiofibromas on the forehead and was ultimately started on topical sirolimus, which led to marked improvement within months.

Ms. Kleinman is a pediatric dermatology research associate, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, also in San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. They have no relevant financial disclosures.

References

1. Tyburczy ME et al. Hum Molec Genet. 2014;23(8):2023-9.

2. Food & Drug Administration. New drug application (NDA) approval for Hyftor (sirolimus topical gel). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/213478Orig1s000ltr.pdf.

3. Webb DW et al. Br J Dermatol. 1996;135(1):1-5.

4. Ricci F et al. Eur J Dermatol. 2017;27(1):59-62.

5. Evans DG and Farndon PA. Nevoid basal cell carcinoma syndrome, in “GeneReviews®.” Seattle: University of Washington, 2002.

The finding of individual, 1- to 4-mm firm, red papules depicted in the image are consistent with facial angiofibromas, which are most commonly seen in pediatric patients as a manifestation of tuberous sclerosis (TSC). Angiofibromas, previously called adenoma sebaceum, a misnomer, are seen in TSC as smooth papules, nodules, and occasionally plaques that typically involve the malar region of the face. These lesions usually develop in childhood and adolescence and can be misdiagnosed as lesions of acne. The number of lesions tend to increase with age, though there is no significant risk of malignant transformation. Ultraviolet-induced DNA damage is thought to play a role in the development of facial angiofibromas, so sun protection is called for.¹ Patients may seek treatment to minimize deformity and the stigma of angiofibromas. Recently, the mammalian target of rapamycin inhibitor sirolimus (rapamycin) topical gel received Food and Drug Administration approval for the treatment of facial angiofibromas associated with TSC in patients age at least 6 years.²

The presence of angiofibromas should prompt consideration of TSC and as such, a thorough family history, medical history, and full-body skin examination. TSC is a rare autosomal-dominant genetic disorder, caused by a pathogenic variant in either the TSC1 or TSC2 gene. This neurocutaneous disorder is characterized by the development of multiple benign hamartomas across many organ systems including the brain, eyes, heart, lung, liver, kidney, and skin. The phenotypic expression of TSC is highly variable. Besides angiofibromas, some other characteristic dermatological findings in TSC include periungual fibromas, hypopigmented macules usually elliptical in shape (known as ash-leaf spots), and irregularly shaped elevated flesh-colored fibrous tissue most often found over the lower back (known as shagreen patches).³

What is on the differential?

Agminated spitz nevi refers to multiple spitz nevi in a localized area. Spitz nevi present as a well-circumscribed, dome-shaped, pink-red or brown papules, most commonly located on the face or lower extremities.⁴ The finding of agminated spitz nevi is very rare and less likely for this patient given the concomitant skin findings of dental pitting, renal cysts, and cortical tubers.

Juvenile xanthogranulomas are benign,proliferations of histiocytic cells that present as reddish or yellowish-to-brown papules, plaques, or nodules that typically develop in young children around the age of 1. With time, juvenile xanthogranulomas may flatten and become more yellow.

Basal cell carcinomas present as dome-shaped lesions with centralized erosions on sun-exposed areas of the skin. They are remarkably uncommon in children but are occasionally seen in basal cell nevus syndrome (also known as nevoid basal cell carcinoma syndrome or Gorlin syndrome). Affected patients may have other findings such as developmental anomalies, bifid ribs, palmar and plantar pitting, odontogenic keratocysts, and/or medulloblastomas.⁵

Flat warts commonly occur in children and occur by direct skin contact with human papillomavirus. Of the various types of warts, flat warts are smaller and tend to be smooth on top. The diagnosis of cutaneous warts is based on clinical appearance, showing thrombosed capillaries underneath the overlying hyperkeratotic debris. Our patient’s history of having a common wart on her hands raises suspicion for inoculation onto her face, but the morphology, distribution, and lack of response to tretinoin makes this diagnosis much less likely.

Disease workup and course

Our patient’s physical exam revealed dental pits but no evidence of hypopigmented macules, shagreen patches, or periungual lesions. Ultrasound of the kidney displayed renal cortical cysts and brain MRI showed cortical tubers, confirming extracutaneous TSC involvement. Over time, our patient developed angiofibromas on the forehead and was ultimately started on topical sirolimus, which led to marked improvement within months.

Ms. Kleinman is a pediatric dermatology research associate, division of pediatric and adolescent dermatology, University of California, San Diego, and Rady Children’s Hospital, also in San Diego. Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. They have no relevant financial disclosures.

References

1. Tyburczy ME et al. Hum Molec Genet. 2014;23(8):2023-9.

2. Food & Drug Administration. New drug application (NDA) approval for Hyftor (sirolimus topical gel). https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2022/213478Orig1s000ltr.pdf.

3. Webb DW et al. Br J Dermatol. 1996;135(1):1-5.

4. Ricci F et al. Eur J Dermatol. 2017;27(1):59-62.

5. Evans DG and Farndon PA. Nevoid basal cell carcinoma syndrome, in “GeneReviews®.” Seattle: University of Washington, 2002.

The Diagnosis: Epidermolysis Bullosa

Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.¹ Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.²

In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.³ Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.⁴ Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.⁵

High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.⁶ In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.⁶

Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.⁷

In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).⁶KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.⁷

Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).

Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.⁸ Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.⁸ In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.

The Diagnosis: Epidermolysis Bullosa

Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.¹ Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.²

In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.³ Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.⁴ Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.⁵

High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.⁶ In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.⁶

Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.⁷

In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).⁶KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.⁷

Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).

Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.⁸ Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.⁸ In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.

The Diagnosis: Epidermolysis Bullosa

Our patient was found to have epidermolysis bullosa (EB), a rare genetic disease in which the superficial layers of the skin separate to form vesicles or bullae due to a mutation in the keratin 14 gene, KRT14. Separation of the skin occurs due to cleavage of various proteins that connect the epidermis to the dermis. A genetic mutation in KRT14, one of the more common genetic mutations associated with EB, results in cleavage at the basal epidermal protein keratin 14. The skin of individuals with EB typically is fragile and cannot tolerate friction or manipulation due to the risk for new bullae formation.¹ Epidermolysis bullosa is rare, affecting approximately 20 children per 1 million births in the United States, and is not commonly seen by most general adult dermatologists.²

In our patient, the differential diagnoses included staphylococcal scalded skin syndrome (SSSS), Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), herpes simplex virus (HSV), and bullous pemphigoid (BP). Symptoms of SSSS can range from mild and localized to full-body exfoliation of the skin. Although SSSS can resemble other bullous disorders, its etiology arises from the Staphylococcus exotoxin targeting desmoglein in the stratum granulosum— the layer of the epidermis between the stratum corneum and stratum spinosum.³ Lesions start on the face, neck, and body folds, which was consistent with our patient’s presentation. However, bullae continued to develop in our patient despite antibiotic therapy, which reduced the likelihood of SSSS. Stevens-Johnson syndrome/toxic epidermal necrolysis develops rapidly and often involves the mucosa, which our patient initially did not have. In children, SJS/TEN can develop secondary to infection, whereas in adults it more commonly is associated with medication administration.⁴ Although the mother tested negative for HSV, the infant was started on acyclovir, which ultimately was discontinued due to low clinical suspicion. The clinical presentation of HSV (ie, clustered vesicles) was not consistent with our patient’s presentation. Bullous pemphigoid is a subepithelial blistering disease seen in older adults. Tense, fluidfilled blisters primarily are seen on the trunk and flexures. Although infantile BP can occur, it usually does not present in the neonatal period but rather at approximately 3 to 5 months of age.⁵

High clinical suspicion for EB due to the common characteristics of bullae location and formation following skin manipulation led to genetic testing in our patient. Mild forms of EB simplex typically appear on the upper and lower extremities with sparing of the trunk. In more severe cases of EB simplex, truncal and mucosal involvement may occur.⁶ In our case, the infant had a classic distribution of arm and leg blisters with truncal sparing. Epidermolysis bullosa may not be diagnosed in the neonatal period because of its similarities to other more common diseases, such as HSV or bullous impetigo, or other genetic blistering diseases, such as epidermolytic ichthyosis and incontinentia pigmenti.⁶

Epidermolysis bullosa can be inherited in an autosomal-dominant or autosomal-recessive fashion or with de novo mutations and is classified based on the location of cleavage in the skin. The 4 classical subtypes— simplex, junctional, dystrophic, and Kindler—have now been further subclassified. Epidermolysis bullosa simplex (intraepidermal split) is now separated into basal and suprabasal, with further subclassification including the distribution of blisters (generalized or localized) and the severity of cutaneous or extracutaneous involvement.⁷

In our case, the infant was found to have intraepidermal EB (simplex) due to a KRT14 mutation (missense mutation).⁶KRT14 (17q21.2) and KRT5 (12q13.3) are the 2 most common mutations causing cleavage at the basal intraepidermal layer. Thickening of the palms, soles, and nails can be seen; however, blisters heal well without scarring, as seen in our patient. Junctional EB due to cleavage at the intralamina lucida often involves mutations in laminin 332, plectin, and α6β4 integrin. Infants with junctional EB often die from severe infection, dehydration, or malnutrition due to mucosal involvement. Dystrophic EB occurs due to a collagen VII mutation in the dermis, leading to blisters at the sublamina densa and more severe symptoms in the recessive form.⁷

Newborn management for infants with EB differs from normal newborn care due to increased skin fragility with physical manipulation. Minimal skin manipulation and proper wound care are essential from the first day of life. For new bullae formation, bullae should be ruptured with a needle at the base of the blister and drained. The remaining skin overlying the wound should remain in place as a natural wound barrier. Patients with EB should not have tape or adhesive bandages applied directly to the skin. Instead, nonadhesive dressings can be placed directly on wounds and covered in soft wraps circumferentially. Dressings can be taped together without involving the skin. The cost for supplies for families to manage bullae is expensive. Fortunately, there are resources available for supplies and support for families, including the EB Research Partnership (https://www.ebresearch.org/) and DEBRA of America (https://www.debra.org/).

Currently, there is no cure for EB. Current treatment involves wound care, prevention, and symptomatic relief. Prevention includes avoiding activities that may result in increased friction of the skin and ensuring careful manipulation. Children with EB may have pain or itching from their blisters, which can be treated with oral acetaminophen or ibuprofen and diphenhydramine, respectively. Other complications of EB include anemia, dehydration, constipation, infection, and malnutrition. In more severe forms of EB, complications including eye problems, mucosal strictures, and skin cancer may occur.⁸ Future treatment directions include gene therapy, bone marrow transplantation, protein replacement therapies, and cell-based therapies. Prognosis for infants with EB due to KRT14 mutation is good, as it is a milder subtype of EB with a full life expectancy and improvement of blistering skin with age. The most at-risk time for early death is during infancy due to increased risk for infection.⁸ In this case, our patient showed full healing with no scar formation, which suggested a reassuring prognosis.

Photosensitivity due to doxycycline

As the patient’s rash presented in sun-exposed areas with both skin and nail changes, our patient was diagnosed with a phototoxic reaction to doxycycline, the oral antibiotic used to treat his acne.

Photosensitive cutaneous drug eruptions are reactions that occur after exposure to a medication and subsequent exposure to UV radiation or visible light. Reactions can be classified into two ways based on their mechanism of action: phototoxic or photoallergic.¹ Phototoxic reactions are more common and are a result of direct keratinocyte damage and cellular necrosis. Many classes of medications may cause this adverse effect, but the tetracycline class of antibiotics is a common culprit.² Photoallergic reactions are less common and are a result of a type IV immune reaction to the offending agent.¹

Courtesy Dr. Catalina Matiz

Phototoxic reactions generally present shortly after sun or UV exposure with a photo-distributed eruption pattern.³ Commonly involved areas include the face, the neck, and the extensor surfaces of extremities, with sparing of relatively protected skin such as the upper eyelids and the skin folds.² Erythema may initially develop in the exposed skin areas, followed by appearance of edema, vesicles, or bullae.^1-3 The eruption may be painful and itchy, with some patients reporting severe pain.³

Courtesy Dr. Catalina Matiz

Doxycycline phototoxicity may also cause onycholysis of the nails.² The reaction is dose dependent, with higher doses of medication leading to a higher likelihood of symptoms.^1,2 It is also more prevalent in patients with Fitzpatrick skin type I and II. The usual UVA wavelength required to induce this reaction appears to be in the 320-400 nm range of the UV spectrum.⁴ By contrast, photoallergic reactions are dose independent, and require a sensitization period prior to the eruption.¹ An eczematous eruption is most commonly seen with photoallergic reactions.³

Treatment of drug-induced photosensitivity reactions requires proper identification of the diagnosis and the offending agent, followed by cessation of the medication. If cessation is not possible, then lowering the dose can help to minimize worsening of the condition. However, for photoallergic reactions, the reaction is dose independent so switching to another tolerated agent is likely required. For persistent symptoms following medication withdrawal, topical or systemic steroids and oral antihistamine can help with symptom management.¹ For patients with photo-onycholysis, treatment involves stopping the medication and waiting for the intact nail plate to grow.

Courtesy Dr. Catalina Matiz

Dermatomyositis

Dermatomyositis is an autoimmune condition that presents with skin lesions as well as systemic findings such as myositis. The cutaneous findings are variable, but pathognomonic findings include Gottron papules of the hands, Gottron’s sign on the elbows, knees, and ankles, and the heliotrope rash of the face. Eighty percent of patients have myopathy presenting as muscle weakness, and commonly have elevated creatine kinase, aspartate transaminase, and alanine transaminase values.⁵ Diagnosis may be confirmed through skin or muscle biopsy, though antibody studies can also play a helpful role in diagnosis. Treatment is generally with oral corticosteroids or other immunosuppressants as well as sun protection.⁶ The rash seen in our patient could have been seen in patients with dermatomyositis, though it was not in the typical location on the knuckles (Gottron papules) as it also affected the lateral sides of the fingers.

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by systemic and cutaneous manifestations. Systemic symptoms may include weight loss, fever, fatigue, arthralgia, or arthritis; patients are at risk of renal, cardiovascular, pulmonary, and neurologic complications of SLE.⁷ The most common cutaneous finding is malar rash, though there are myriad dermatologic manifestations that can occur associated with photosensitivity. Diagnosis is made based on history, physical, and laboratory testing. Treatment options include NSAIDs, oral glucocorticoids, antimalarial drugs, and immunosuppressants.⁷ Though our patient exhibited photosensitivity, he had none of the systemic findings associated with SLE, making this diagnosis unlikely.

Allergic contact dermatitis

Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction, and may present as acute, subacute, or chronic dermatitis. The clinical findings vary based on chronicity. Acute ACD presents as pruritic erythematous papules and vesicles or bullae, similar to how it occurred in our patient, though our patient’s lesions were more tender than pruritic. Chronic ACD presents with erythematous lesions with pruritis, lichenification, scaling, and/or fissuring. Observing shapes or sharp demarcation of lesions may help with diagnosis. Patch testing is also useful in the diagnosis of ACD.

Treatment generally involves avoiding the offending agent with topical corticosteroids for symptom management.⁸

Polymorphous light eruption

Polymorphous light eruption (PLE) is a delayed, type IV hypersensitivity reaction to UV-induced antigens, though these antigens are unknown. PLE presents hours to days following solar or UV exposure and presents only in sun-exposed areas. Itching and burning are always present, but lesion morphology varies from erythema and papules to vesico-papules and blisters. Notably, PLE must be distinguished from drug photosensitivity through history. Treatment generally involves symptom management with topical steroids and sun protective measures for prevention.⁹ While PLE may present similarly to drug photosensitivity reactions, our patient’s use of a known phototoxic agent makes PLE a less likely diagnosis.

Ms. Appiah is a pediatric dermatology research associate and medical student at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Neither Dr. Matiz nor Ms. Appiah has any relevant financial disclosures.

References

1. Montgomery S et al. Clin Dermatol. 2022;40(1):57-63.

2. Blakely KM et al. Drug Saf. 2019;42(7):827-47.

3. Goetze S et al. Skin Pharmacol Physiol. 2017;30(2):76-80.

4. Odorici G et al. Dermatol Ther. 2021;34(4):e14978.

5. DeWane ME et al. J Am Acad Dermatol. 2020;82(2):267-81.

6. Waldman R et al. J Am Acad Dermatol. 2020;82(2):283-96.

7. Kiriakidou M et al. Ann Intern Med. 2020;172(11):ITC81-ITC96.

8. Nassau S et al. Med Clin North Am. 2020;104(1):61-76.

9. Guarrera M. Adv Exp Med Biol. 2017;996:61-70.

Photosensitivity due to doxycycline

As the patient’s rash presented in sun-exposed areas with both skin and nail changes, our patient was diagnosed with a phototoxic reaction to doxycycline, the oral antibiotic used to treat his acne.

Photosensitive cutaneous drug eruptions are reactions that occur after exposure to a medication and subsequent exposure to UV radiation or visible light. Reactions can be classified into two ways based on their mechanism of action: phototoxic or photoallergic.¹ Phototoxic reactions are more common and are a result of direct keratinocyte damage and cellular necrosis. Many classes of medications may cause this adverse effect, but the tetracycline class of antibiotics is a common culprit.² Photoallergic reactions are less common and are a result of a type IV immune reaction to the offending agent.¹

Courtesy Dr. Catalina Matiz

Phototoxic reactions generally present shortly after sun or UV exposure with a photo-distributed eruption pattern.³ Commonly involved areas include the face, the neck, and the extensor surfaces of extremities, with sparing of relatively protected skin such as the upper eyelids and the skin folds.² Erythema may initially develop in the exposed skin areas, followed by appearance of edema, vesicles, or bullae.^1-3 The eruption may be painful and itchy, with some patients reporting severe pain.³

Courtesy Dr. Catalina Matiz

Doxycycline phototoxicity may also cause onycholysis of the nails.² The reaction is dose dependent, with higher doses of medication leading to a higher likelihood of symptoms.^1,2 It is also more prevalent in patients with Fitzpatrick skin type I and II. The usual UVA wavelength required to induce this reaction appears to be in the 320-400 nm range of the UV spectrum.⁴ By contrast, photoallergic reactions are dose independent, and require a sensitization period prior to the eruption.¹ An eczematous eruption is most commonly seen with photoallergic reactions.³

Treatment of drug-induced photosensitivity reactions requires proper identification of the diagnosis and the offending agent, followed by cessation of the medication. If cessation is not possible, then lowering the dose can help to minimize worsening of the condition. However, for photoallergic reactions, the reaction is dose independent so switching to another tolerated agent is likely required. For persistent symptoms following medication withdrawal, topical or systemic steroids and oral antihistamine can help with symptom management.¹ For patients with photo-onycholysis, treatment involves stopping the medication and waiting for the intact nail plate to grow.

Courtesy Dr. Catalina Matiz

Dermatomyositis

Dermatomyositis is an autoimmune condition that presents with skin lesions as well as systemic findings such as myositis. The cutaneous findings are variable, but pathognomonic findings include Gottron papules of the hands, Gottron’s sign on the elbows, knees, and ankles, and the heliotrope rash of the face. Eighty percent of patients have myopathy presenting as muscle weakness, and commonly have elevated creatine kinase, aspartate transaminase, and alanine transaminase values.⁵ Diagnosis may be confirmed through skin or muscle biopsy, though antibody studies can also play a helpful role in diagnosis. Treatment is generally with oral corticosteroids or other immunosuppressants as well as sun protection.⁶ The rash seen in our patient could have been seen in patients with dermatomyositis, though it was not in the typical location on the knuckles (Gottron papules) as it also affected the lateral sides of the fingers.

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by systemic and cutaneous manifestations. Systemic symptoms may include weight loss, fever, fatigue, arthralgia, or arthritis; patients are at risk of renal, cardiovascular, pulmonary, and neurologic complications of SLE.⁷ The most common cutaneous finding is malar rash, though there are myriad dermatologic manifestations that can occur associated with photosensitivity. Diagnosis is made based on history, physical, and laboratory testing. Treatment options include NSAIDs, oral glucocorticoids, antimalarial drugs, and immunosuppressants.⁷ Though our patient exhibited photosensitivity, he had none of the systemic findings associated with SLE, making this diagnosis unlikely.

Allergic contact dermatitis

Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction, and may present as acute, subacute, or chronic dermatitis. The clinical findings vary based on chronicity. Acute ACD presents as pruritic erythematous papules and vesicles or bullae, similar to how it occurred in our patient, though our patient’s lesions were more tender than pruritic. Chronic ACD presents with erythematous lesions with pruritis, lichenification, scaling, and/or fissuring. Observing shapes or sharp demarcation of lesions may help with diagnosis. Patch testing is also useful in the diagnosis of ACD.

Treatment generally involves avoiding the offending agent with topical corticosteroids for symptom management.⁸

Polymorphous light eruption

Polymorphous light eruption (PLE) is a delayed, type IV hypersensitivity reaction to UV-induced antigens, though these antigens are unknown. PLE presents hours to days following solar or UV exposure and presents only in sun-exposed areas. Itching and burning are always present, but lesion morphology varies from erythema and papules to vesico-papules and blisters. Notably, PLE must be distinguished from drug photosensitivity through history. Treatment generally involves symptom management with topical steroids and sun protective measures for prevention.⁹ While PLE may present similarly to drug photosensitivity reactions, our patient’s use of a known phototoxic agent makes PLE a less likely diagnosis.

Ms. Appiah is a pediatric dermatology research associate and medical student at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Neither Dr. Matiz nor Ms. Appiah has any relevant financial disclosures.

References

1. Montgomery S et al. Clin Dermatol. 2022;40(1):57-63.

2. Blakely KM et al. Drug Saf. 2019;42(7):827-47.

3. Goetze S et al. Skin Pharmacol Physiol. 2017;30(2):76-80.

4. Odorici G et al. Dermatol Ther. 2021;34(4):e14978.

5. DeWane ME et al. J Am Acad Dermatol. 2020;82(2):267-81.

6. Waldman R et al. J Am Acad Dermatol. 2020;82(2):283-96.

7. Kiriakidou M et al. Ann Intern Med. 2020;172(11):ITC81-ITC96.

8. Nassau S et al. Med Clin North Am. 2020;104(1):61-76.

9. Guarrera M. Adv Exp Med Biol. 2017;996:61-70.

Photosensitivity due to doxycycline

As the patient’s rash presented in sun-exposed areas with both skin and nail changes, our patient was diagnosed with a phototoxic reaction to doxycycline, the oral antibiotic used to treat his acne.

Photosensitive cutaneous drug eruptions are reactions that occur after exposure to a medication and subsequent exposure to UV radiation or visible light. Reactions can be classified into two ways based on their mechanism of action: phototoxic or photoallergic.¹ Phototoxic reactions are more common and are a result of direct keratinocyte damage and cellular necrosis. Many classes of medications may cause this adverse effect, but the tetracycline class of antibiotics is a common culprit.² Photoallergic reactions are less common and are a result of a type IV immune reaction to the offending agent.¹

Courtesy Dr. Catalina Matiz

Phototoxic reactions generally present shortly after sun or UV exposure with a photo-distributed eruption pattern.³ Commonly involved areas include the face, the neck, and the extensor surfaces of extremities, with sparing of relatively protected skin such as the upper eyelids and the skin folds.² Erythema may initially develop in the exposed skin areas, followed by appearance of edema, vesicles, or bullae.^1-3 The eruption may be painful and itchy, with some patients reporting severe pain.³

Courtesy Dr. Catalina Matiz

Doxycycline phototoxicity may also cause onycholysis of the nails.² The reaction is dose dependent, with higher doses of medication leading to a higher likelihood of symptoms.^1,2 It is also more prevalent in patients with Fitzpatrick skin type I and II. The usual UVA wavelength required to induce this reaction appears to be in the 320-400 nm range of the UV spectrum.⁴ By contrast, photoallergic reactions are dose independent, and require a sensitization period prior to the eruption.¹ An eczematous eruption is most commonly seen with photoallergic reactions.³

Treatment of drug-induced photosensitivity reactions requires proper identification of the diagnosis and the offending agent, followed by cessation of the medication. If cessation is not possible, then lowering the dose can help to minimize worsening of the condition. However, for photoallergic reactions, the reaction is dose independent so switching to another tolerated agent is likely required. For persistent symptoms following medication withdrawal, topical or systemic steroids and oral antihistamine can help with symptom management.¹ For patients with photo-onycholysis, treatment involves stopping the medication and waiting for the intact nail plate to grow.

Courtesy Dr. Catalina Matiz

Dermatomyositis

Dermatomyositis is an autoimmune condition that presents with skin lesions as well as systemic findings such as myositis. The cutaneous findings are variable, but pathognomonic findings include Gottron papules of the hands, Gottron’s sign on the elbows, knees, and ankles, and the heliotrope rash of the face. Eighty percent of patients have myopathy presenting as muscle weakness, and commonly have elevated creatine kinase, aspartate transaminase, and alanine transaminase values.⁵ Diagnosis may be confirmed through skin or muscle biopsy, though antibody studies can also play a helpful role in diagnosis. Treatment is generally with oral corticosteroids or other immunosuppressants as well as sun protection.⁶ The rash seen in our patient could have been seen in patients with dermatomyositis, though it was not in the typical location on the knuckles (Gottron papules) as it also affected the lateral sides of the fingers.

Systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune condition characterized by systemic and cutaneous manifestations. Systemic symptoms may include weight loss, fever, fatigue, arthralgia, or arthritis; patients are at risk of renal, cardiovascular, pulmonary, and neurologic complications of SLE.⁷ The most common cutaneous finding is malar rash, though there are myriad dermatologic manifestations that can occur associated with photosensitivity. Diagnosis is made based on history, physical, and laboratory testing. Treatment options include NSAIDs, oral glucocorticoids, antimalarial drugs, and immunosuppressants.⁷ Though our patient exhibited photosensitivity, he had none of the systemic findings associated with SLE, making this diagnosis unlikely.

Allergic contact dermatitis

Allergic contact dermatitis (ACD) is a type IV hypersensitivity reaction, and may present as acute, subacute, or chronic dermatitis. The clinical findings vary based on chronicity. Acute ACD presents as pruritic erythematous papules and vesicles or bullae, similar to how it occurred in our patient, though our patient’s lesions were more tender than pruritic. Chronic ACD presents with erythematous lesions with pruritis, lichenification, scaling, and/or fissuring. Observing shapes or sharp demarcation of lesions may help with diagnosis. Patch testing is also useful in the diagnosis of ACD.

Treatment generally involves avoiding the offending agent with topical corticosteroids for symptom management.⁸

Polymorphous light eruption

Polymorphous light eruption (PLE) is a delayed, type IV hypersensitivity reaction to UV-induced antigens, though these antigens are unknown. PLE presents hours to days following solar or UV exposure and presents only in sun-exposed areas. Itching and burning are always present, but lesion morphology varies from erythema and papules to vesico-papules and blisters. Notably, PLE must be distinguished from drug photosensitivity through history. Treatment generally involves symptom management with topical steroids and sun protective measures for prevention.⁹ While PLE may present similarly to drug photosensitivity reactions, our patient’s use of a known phototoxic agent makes PLE a less likely diagnosis.

Ms. Appiah is a pediatric dermatology research associate and medical student at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Neither Dr. Matiz nor Ms. Appiah has any relevant financial disclosures.

References

1. Montgomery S et al. Clin Dermatol. 2022;40(1):57-63.

2. Blakely KM et al. Drug Saf. 2019;42(7):827-47.

3. Goetze S et al. Skin Pharmacol Physiol. 2017;30(2):76-80.

4. Odorici G et al. Dermatol Ther. 2021;34(4):e14978.

5. DeWane ME et al. J Am Acad Dermatol. 2020;82(2):267-81.

6. Waldman R et al. J Am Acad Dermatol. 2020;82(2):283-96.

7. Kiriakidou M et al. Ann Intern Med. 2020;172(11):ITC81-ITC96.

8. Nassau S et al. Med Clin North Am. 2020;104(1):61-76.

9. Guarrera M. Adv Exp Med Biol. 2017;996:61-70.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Becker’s nevus

The history and physical exam are most consistent with Becker’s nevus, also known as Becker’s melanosis. This is a benign cutaneous hamartoma, usually found in males, characterized by a large, irregularly shaped brown patch, often with hypertrichosis.¹ Becker’s nevus can be congenital but is more commonly noticed in late childhood or early adolescence, with thickening, increased pigmentation, and hair growth. Becker’s nevus is considered an overgrowth of epidermal pigment cells and hair follicles and is thought to be attributable to postzygotic mutations (with ACTB mutations most reported).¹ It is often located unilaterally on the upper trunk but is occasionally present elsewhere on the body. Acne may occasionally develop within the nevus, which is believed to be triggered by puberty-associated androgens.¹ The lesion tends to persist indefinitely but has no propensity for malignant transformation.

Becker’s nevus is generally an isolated skin lesion without other anomalies. However, in rare instances, it may be associated with ipsilateral breast hypoplasia or hypoplastic defects of the muscle, skin, or skeleton, which is known as Becker’s nevus syndrome.² Treatment is not medically warranted for an isolated Becker’s nevus but may be pursued for cosmetic reasons. Although treatment is generally discouraged because of variable success, laser hair removal and laser therapy may be pursued to address the hypertrichosis and hyperpigmentation, respectively.
 

What is on the differential?

A café-au-lait macule (CALM) is a light- to dark-brown, oval lesion that commonly presents at birth or in early childhood. CALMs vary widely in size from less than 1.5 cm to more than 20 cm in diameter. They are asymptomatic and grow in proportion to the individual over time.³ Becker’s nevus can be distinguished from CALMs by the development of hypertrichosis, typical location and course, and other skin changes within the nevus.

Postinflammatory hyperpigmentation (PIH) is characterized by asymptomatic, darkened macules or patches that are brown to blue-gray in color. It is one of the most common causes of hyperpigmentation, particularly in skin of color, and can take months to years to resolve. PIH is caused by increased melanin production in response to a cutaneous inflammatory process, such as a drug reaction, allergy, mechanical or thermal injury, infection, phototoxicity, or an underlying skin condition.³ Our patient’s history with the lack of an inciting inflammatory process is more consistent with Becker’s nevus.

Erythema ab igne is a cutaneous reaction to heat that presents as a hyperpigmented patch with a reticular or mottled configuration and superficial venular telangiectasia. The lesion is initially erythematous and progresses to a pale pink to purplish dark-brown color.⁴ Causes include long-term use of a heating pad, laptop, electric blanket, or a hot water bottle. The absence of prolonged heat exposure in our patient’s history does not favor erythema ab igne.

Pigmentary mosaicism is characterized by a distinctive pattern of hyperpigmentation that follows the lines of ectodermal embryologic development, known as the lines of Blaschko.⁵ This condition is also known as linear and whorled nevoid hypermelanosis because of its streaky or swirl-like pattern. Pigmentary mosaicism can be present at birth or appear within the first few weeks of life. It is caused by genetic heterogeneity in neuroectodermal cells, which results in skin with areas of varying colors. Pigmentary mosaicism is unlikely in this case as our patient’s lesion does not follow the lines of Blaschko.
 

Ms. Laborada is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Dr. Eichenfield is the vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital. Ms. Laborada and Dr. Eichenfield have no relevant financial disclosures.

References

1. Atzmony L et al. J Cutan Pathol. 2020;47(8):681-5.

2. Danarti R et al. J Am Acad Dermatol. 2004;51(6):965-9.

3. Paller A and Mancini AJ. “Hurwitz Clinical Pediatric Dermatology: A textbook of skin disorders of childhood and adolescence” 4th ed. Philadelphia: Elsevier Saunders, 2011.

4. Patel DP. JAMA Dermatol. 2017;153(7):685.

5. Kromann AB et al. Orphanet J Rare Dis. 2018;13(1):39.

Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis that typically affects children between 4 months and 2 years of age.¹ Etiology is unknown but the majority of cases are preceded by infections, vaccinations, or certain medications.²

AHEI is a self-limited disease that runs a benign course with spontaneous resolution within days to 3 weeks.³ Classic presentation involves acute onset of fever, purpura, ecchymosis, and inflammatory edema. Edema is often the first sign, and may involve the face, ears, scrotum, or extremities. Hemorrhagic lesions may vary in size but often coalesce and present in a distinctive “cockade” or rosette pattern with scalloped borders. Systemic manifestations are rare, but renal and joint involvement may occur.⁴ Despite the dramatic and sometimes extensive appearance of the dermatologic manifestations, patients with AHEI are usually not in significant distress.

Courtesy Dr. David Schairer

What is on the differential?

Kawasaki disease. Similar to AHEI, patients with Kawasaki disease also may present with facial and extremity edema. However, patients with Kawasaki disease appear sicker, have associated lymphadenopathy, conjunctivitis, and fever longer than 5 days. The lack of elevated inflammatory markers, acute-onset, classic dermatologic lesions, and nontoxic appearance in our patient rule out Kawasaki disease and make AHEI more likely.

Courtesy Dr. David Schairer

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Kleinman is a pediatric dermatology research associate at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Dr. Matiz nor Ms. Kleinman has any relevant financial disclosures.

References

1. Savino F et al. Pediatr Dermatol. 2013;30(6):e149-e152.

2. Carboni E et al. F1000Res. 2019;8:1771. 2019 Oct 17.

3. Fiore E et al. J Am Acad Dermatol. 2008;59(4):684-95.

4. Watanabe T and Sato Y. Pediatr Nephrol. 2007;22(11):1979-81.

5. Cunha DF et al. Autops Case Rep. 2015;5(3):37-41.

Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis that typically affects children between 4 months and 2 years of age.¹ Etiology is unknown but the majority of cases are preceded by infections, vaccinations, or certain medications.²

AHEI is a self-limited disease that runs a benign course with spontaneous resolution within days to 3 weeks.³ Classic presentation involves acute onset of fever, purpura, ecchymosis, and inflammatory edema. Edema is often the first sign, and may involve the face, ears, scrotum, or extremities. Hemorrhagic lesions may vary in size but often coalesce and present in a distinctive “cockade” or rosette pattern with scalloped borders. Systemic manifestations are rare, but renal and joint involvement may occur.⁴ Despite the dramatic and sometimes extensive appearance of the dermatologic manifestations, patients with AHEI are usually not in significant distress.

Courtesy Dr. David Schairer

What is on the differential?

Kawasaki disease. Similar to AHEI, patients with Kawasaki disease also may present with facial and extremity edema. However, patients with Kawasaki disease appear sicker, have associated lymphadenopathy, conjunctivitis, and fever longer than 5 days. The lack of elevated inflammatory markers, acute-onset, classic dermatologic lesions, and nontoxic appearance in our patient rule out Kawasaki disease and make AHEI more likely.

Courtesy Dr. David Schairer

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Kleinman is a pediatric dermatology research associate at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Dr. Matiz nor Ms. Kleinman has any relevant financial disclosures.

References

1. Savino F et al. Pediatr Dermatol. 2013;30(6):e149-e152.

2. Carboni E et al. F1000Res. 2019;8:1771. 2019 Oct 17.

3. Fiore E et al. J Am Acad Dermatol. 2008;59(4):684-95.

4. Watanabe T and Sato Y. Pediatr Nephrol. 2007;22(11):1979-81.

5. Cunha DF et al. Autops Case Rep. 2015;5(3):37-41.

Acute hemorrhagic edema of infancy (AHEI) is a leukocytoclastic vasculitis that typically affects children between 4 months and 2 years of age.¹ Etiology is unknown but the majority of cases are preceded by infections, vaccinations, or certain medications.²

AHEI is a self-limited disease that runs a benign course with spontaneous resolution within days to 3 weeks.³ Classic presentation involves acute onset of fever, purpura, ecchymosis, and inflammatory edema. Edema is often the first sign, and may involve the face, ears, scrotum, or extremities. Hemorrhagic lesions may vary in size but often coalesce and present in a distinctive “cockade” or rosette pattern with scalloped borders. Systemic manifestations are rare, but renal and joint involvement may occur.⁴ Despite the dramatic and sometimes extensive appearance of the dermatologic manifestations, patients with AHEI are usually not in significant distress.

Courtesy Dr. David Schairer

What is on the differential?

Kawasaki disease. Similar to AHEI, patients with Kawasaki disease also may present with facial and extremity edema. However, patients with Kawasaki disease appear sicker, have associated lymphadenopathy, conjunctivitis, and fever longer than 5 days. The lack of elevated inflammatory markers, acute-onset, classic dermatologic lesions, and nontoxic appearance in our patient rule out Kawasaki disease and make AHEI more likely.

Courtesy Dr. David Schairer

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Ms. Kleinman is a pediatric dermatology research associate at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Neither Dr. Matiz nor Ms. Kleinman has any relevant financial disclosures.

References

1. Savino F et al. Pediatr Dermatol. 2013;30(6):e149-e152.

2. Carboni E et al. F1000Res. 2019;8:1771. 2019 Oct 17.

3. Fiore E et al. J Am Acad Dermatol. 2008;59(4):684-95.

4. Watanabe T and Sato Y. Pediatr Nephrol. 2007;22(11):1979-81.

5. Cunha DF et al. Autops Case Rep. 2015;5(3):37-41.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that is becoming more recognized in children. It has a variable presentation, most commonly presenting as painful, recurrent cysts, abscesses, nodules, and/or pustules in classic locations with associated scarring and sinus tract formation.

The majority of patients present with bilateral lesions found most commonly in the axillae and inguinal folds.¹ There are myriad other potential sites of involvement including the inframammary folds, inner thighs, buttocks, and groin.¹ Diagnosis is made based on history and physical exam. There is a standard severity classification scheme called the Hurley score, which stratifies disease severity based on the presence of sinus tracts and extent of disease.¹ HS is associated with comorbid conditions such as obesity, overweight, acne, and inflammatory bowel and joint disease.² This painful, persistent condition is well documented to have a negative impact on quality of life in adult patients, and similar impairment has been found in pediatric patients.^3,4

HS may be increasing in pediatric and adolescent patients, with recent studies showing onset coinciding most commonly with the onset of puberty.^1,2 There is often a period of several years between symptom onset and diagnosis.¹ A recent editorial highlighted the disparities that exist in HS, with disease more common in Black children and limited information about disease prevalence in Hispanic children.⁵
 

What’s the treatment plan?

HS is a difficult disease to treat, with few patients achieving remission and a significant proportion of patients with treatment-refractory disease.¹ There are limited studies of HS treatment in pediatric patients. Topical and systemic antibiotic therapy are mainstays of HS treatment, with tetracyclines and a combination of clindamycin plus rifampin commonly used in adults and children alike. Topical therapies including topical antibiotics and antibacterial solutions are frequently used as adjunctive therapy.⁶ Adalimumab, a tumor necrosis factor receptor blocker, has been Food and Drug Administration approved for HS for ages 12 and up and is currently the only FDA-approved medication for HS in pediatric patients. Our patient was started on 100 mg doxycycline twice daily, with short-dose topical corticosteroids for symptom management of the most inflamed lesions.

What’s on the differential?

Acne conglobata

Acne conglobata is an uncommon, severe variant of acne vulgaris which arise in patients with a history of acne vulgaris and presents with comedones, cysts, abscesses, and scarring with possible drainage of pus. Lesions can present diffusely on the face, back, and body, including in the axillae, groin, and buttocks, and as such can be confused with HS.⁷

However, in contrast with HS, patients with acne conglobata will also develop disease in non–apocrine gland–bearing skin. This patient’s lack of preceding acne and restriction of lesions to the axillae, inguinal folds, and buttocks makes acne conglobata less likely.

Epidermal inclusion cyst

Epidermal inclusion cyst (EIC) is a common cutaneous cyst, presenting as a well-circumscribed nodule(s) with a central punctum. If not excised, lesions can sometimes become infected and painful.⁸ In contrast with HS, EIC presents only uncommonly as multiple lesions arising in different areas, and spontaneous drainage is uncommon. Our patient’s development of multiple draining lesions makes this diagnosis unlikely.

Furunculosis

Furunculosis is a common bacterial infection of the skin, presenting with inflammatory nodules or pustules centered around the hair follicle. Lesions may commonly present at sites of skin trauma and are found most frequently on the extremities.⁹ Though furunculosis lesions may drain pus and can coalesce to form larger “carbuncles,” our patient’s presence of significant scarring and lack of extremity involvement makes HS more likely.

Recurrent MRSA abscesses

Methicillin-resistant Staphylococcus aureus skin and soft-tissue infections are not uncommon in the pediatric population, with presentation of infection ranging from cellulitis to fluid-containing abscesses.¹⁰ Recurrent abscesses may be seen in MRSA infection, however in this patient the presence of draining, scarring lesions in multiple locations typical for HS over time is more consistent with a diagnosis of HS.

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Appiah is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Appiah have no relevant financial disclosures.

References

1. Liy-Wong C et al. JAMA Dermatol. 2021;157(4):385-91.

2. Choi E et al. J Am Acad Dermatol. 2022;86(1):140-7.

3. Machado MO et al. JAMA Dermatol. 2019;155(8):939-45.

4. McAndrew R et al. J Am Acad Dermatol. 2021;84(3):829-30.

5. Kirby JS and Zaenglein AL. JAMA Dermatol. 2021;157(4):379-80.

6. Alikhan A et al. J Am Acad Dermatol. 2019;81(1):91-101.

7. Greydanus DE et al. Dis Mon. 2021;67(4):101103.

8. Weir CB, St. Hilaire NJ. Epidermal Inclusion Cyst, in “StatPearls.” Treasure Island, Fla: StatPearls Publishing, 2021.

9. Atanaskova N and Tomecki KJ. Dermatol Clin. 2010;28(3):479-87.

10. Papastefan ST et al. J Surg Res. 2019;242:70-7.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that is becoming more recognized in children. It has a variable presentation, most commonly presenting as painful, recurrent cysts, abscesses, nodules, and/or pustules in classic locations with associated scarring and sinus tract formation.

The majority of patients present with bilateral lesions found most commonly in the axillae and inguinal folds.¹ There are myriad other potential sites of involvement including the inframammary folds, inner thighs, buttocks, and groin.¹ Diagnosis is made based on history and physical exam. There is a standard severity classification scheme called the Hurley score, which stratifies disease severity based on the presence of sinus tracts and extent of disease.¹ HS is associated with comorbid conditions such as obesity, overweight, acne, and inflammatory bowel and joint disease.² This painful, persistent condition is well documented to have a negative impact on quality of life in adult patients, and similar impairment has been found in pediatric patients.^3,4

HS may be increasing in pediatric and adolescent patients, with recent studies showing onset coinciding most commonly with the onset of puberty.^1,2 There is often a period of several years between symptom onset and diagnosis.¹ A recent editorial highlighted the disparities that exist in HS, with disease more common in Black children and limited information about disease prevalence in Hispanic children.⁵
 

What’s the treatment plan?

HS is a difficult disease to treat, with few patients achieving remission and a significant proportion of patients with treatment-refractory disease.¹ There are limited studies of HS treatment in pediatric patients. Topical and systemic antibiotic therapy are mainstays of HS treatment, with tetracyclines and a combination of clindamycin plus rifampin commonly used in adults and children alike. Topical therapies including topical antibiotics and antibacterial solutions are frequently used as adjunctive therapy.⁶ Adalimumab, a tumor necrosis factor receptor blocker, has been Food and Drug Administration approved for HS for ages 12 and up and is currently the only FDA-approved medication for HS in pediatric patients. Our patient was started on 100 mg doxycycline twice daily, with short-dose topical corticosteroids for symptom management of the most inflamed lesions.

What’s on the differential?

Acne conglobata

Acne conglobata is an uncommon, severe variant of acne vulgaris which arise in patients with a history of acne vulgaris and presents with comedones, cysts, abscesses, and scarring with possible drainage of pus. Lesions can present diffusely on the face, back, and body, including in the axillae, groin, and buttocks, and as such can be confused with HS.⁷

However, in contrast with HS, patients with acne conglobata will also develop disease in non–apocrine gland–bearing skin. This patient’s lack of preceding acne and restriction of lesions to the axillae, inguinal folds, and buttocks makes acne conglobata less likely.

Epidermal inclusion cyst

Epidermal inclusion cyst (EIC) is a common cutaneous cyst, presenting as a well-circumscribed nodule(s) with a central punctum. If not excised, lesions can sometimes become infected and painful.⁸ In contrast with HS, EIC presents only uncommonly as multiple lesions arising in different areas, and spontaneous drainage is uncommon. Our patient’s development of multiple draining lesions makes this diagnosis unlikely.

Furunculosis

Furunculosis is a common bacterial infection of the skin, presenting with inflammatory nodules or pustules centered around the hair follicle. Lesions may commonly present at sites of skin trauma and are found most frequently on the extremities.⁹ Though furunculosis lesions may drain pus and can coalesce to form larger “carbuncles,” our patient’s presence of significant scarring and lack of extremity involvement makes HS more likely.

Recurrent MRSA abscesses

Methicillin-resistant Staphylococcus aureus skin and soft-tissue infections are not uncommon in the pediatric population, with presentation of infection ranging from cellulitis to fluid-containing abscesses.¹⁰ Recurrent abscesses may be seen in MRSA infection, however in this patient the presence of draining, scarring lesions in multiple locations typical for HS over time is more consistent with a diagnosis of HS.

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Appiah is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Appiah have no relevant financial disclosures.

References

1. Liy-Wong C et al. JAMA Dermatol. 2021;157(4):385-91.

2. Choi E et al. J Am Acad Dermatol. 2022;86(1):140-7.

3. Machado MO et al. JAMA Dermatol. 2019;155(8):939-45.

4. McAndrew R et al. J Am Acad Dermatol. 2021;84(3):829-30.

5. Kirby JS and Zaenglein AL. JAMA Dermatol. 2021;157(4):379-80.

6. Alikhan A et al. J Am Acad Dermatol. 2019;81(1):91-101.

7. Greydanus DE et al. Dis Mon. 2021;67(4):101103.

8. Weir CB, St. Hilaire NJ. Epidermal Inclusion Cyst, in “StatPearls.” Treasure Island, Fla: StatPearls Publishing, 2021.

9. Atanaskova N and Tomecki KJ. Dermatol Clin. 2010;28(3):479-87.

10. Papastefan ST et al. J Surg Res. 2019;242:70-7.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that is becoming more recognized in children. It has a variable presentation, most commonly presenting as painful, recurrent cysts, abscesses, nodules, and/or pustules in classic locations with associated scarring and sinus tract formation.

The majority of patients present with bilateral lesions found most commonly in the axillae and inguinal folds.¹ There are myriad other potential sites of involvement including the inframammary folds, inner thighs, buttocks, and groin.¹ Diagnosis is made based on history and physical exam. There is a standard severity classification scheme called the Hurley score, which stratifies disease severity based on the presence of sinus tracts and extent of disease.¹ HS is associated with comorbid conditions such as obesity, overweight, acne, and inflammatory bowel and joint disease.² This painful, persistent condition is well documented to have a negative impact on quality of life in adult patients, and similar impairment has been found in pediatric patients.^3,4

HS may be increasing in pediatric and adolescent patients, with recent studies showing onset coinciding most commonly with the onset of puberty.^1,2 There is often a period of several years between symptom onset and diagnosis.¹ A recent editorial highlighted the disparities that exist in HS, with disease more common in Black children and limited information about disease prevalence in Hispanic children.⁵
 

What’s the treatment plan?

HS is a difficult disease to treat, with few patients achieving remission and a significant proportion of patients with treatment-refractory disease.¹ There are limited studies of HS treatment in pediatric patients. Topical and systemic antibiotic therapy are mainstays of HS treatment, with tetracyclines and a combination of clindamycin plus rifampin commonly used in adults and children alike. Topical therapies including topical antibiotics and antibacterial solutions are frequently used as adjunctive therapy.⁶ Adalimumab, a tumor necrosis factor receptor blocker, has been Food and Drug Administration approved for HS for ages 12 and up and is currently the only FDA-approved medication for HS in pediatric patients. Our patient was started on 100 mg doxycycline twice daily, with short-dose topical corticosteroids for symptom management of the most inflamed lesions.

What’s on the differential?

Acne conglobata

Acne conglobata is an uncommon, severe variant of acne vulgaris which arise in patients with a history of acne vulgaris and presents with comedones, cysts, abscesses, and scarring with possible drainage of pus. Lesions can present diffusely on the face, back, and body, including in the axillae, groin, and buttocks, and as such can be confused with HS.⁷

However, in contrast with HS, patients with acne conglobata will also develop disease in non–apocrine gland–bearing skin. This patient’s lack of preceding acne and restriction of lesions to the axillae, inguinal folds, and buttocks makes acne conglobata less likely.

Epidermal inclusion cyst

Epidermal inclusion cyst (EIC) is a common cutaneous cyst, presenting as a well-circumscribed nodule(s) with a central punctum. If not excised, lesions can sometimes become infected and painful.⁸ In contrast with HS, EIC presents only uncommonly as multiple lesions arising in different areas, and spontaneous drainage is uncommon. Our patient’s development of multiple draining lesions makes this diagnosis unlikely.

Furunculosis

Furunculosis is a common bacterial infection of the skin, presenting with inflammatory nodules or pustules centered around the hair follicle. Lesions may commonly present at sites of skin trauma and are found most frequently on the extremities.⁹ Though furunculosis lesions may drain pus and can coalesce to form larger “carbuncles,” our patient’s presence of significant scarring and lack of extremity involvement makes HS more likely.

Recurrent MRSA abscesses

Methicillin-resistant Staphylococcus aureus skin and soft-tissue infections are not uncommon in the pediatric population, with presentation of infection ranging from cellulitis to fluid-containing abscesses.¹⁰ Recurrent abscesses may be seen in MRSA infection, however in this patient the presence of draining, scarring lesions in multiple locations typical for HS over time is more consistent with a diagnosis of HS.

Dr. Eichenfield is vice chair of the department of dermatology and professor of dermatology and pediatrics at the University of California, San Diego, and Rady Children’s Hospital, San Diego. Ms. Appiah is a pediatric dermatology research associate in the division of pediatric and adolescent dermatology at the University of California, San Diego, and Rady Children’s Hospital. Dr. Eichenfield and Ms. Appiah have no relevant financial disclosures.

References

1. Liy-Wong C et al. JAMA Dermatol. 2021;157(4):385-91.

2. Choi E et al. J Am Acad Dermatol. 2022;86(1):140-7.

3. Machado MO et al. JAMA Dermatol. 2019;155(8):939-45.

4. McAndrew R et al. J Am Acad Dermatol. 2021;84(3):829-30.

5. Kirby JS and Zaenglein AL. JAMA Dermatol. 2021;157(4):379-80.

6. Alikhan A et al. J Am Acad Dermatol. 2019;81(1):91-101.

7. Greydanus DE et al. Dis Mon. 2021;67(4):101103.

8. Weir CB, St. Hilaire NJ. Epidermal Inclusion Cyst, in “StatPearls.” Treasure Island, Fla: StatPearls Publishing, 2021.

9. Atanaskova N and Tomecki KJ. Dermatol Clin. 2010;28(3):479-87.

10. Papastefan ST et al. J Surg Res. 2019;242:70-7.

As the lesion was growing, getting more violaceous and indurated, a biopsy was performed. The biopsy showed multiple discrete lobules of dermal capillaries with slight extension into the superficial subcutis. Capillary lobules demonstrate the “cannonball-like” architecture often associated with tufted angioma, and some lobules showed bulging into adjacent thin-walled vessels. Spindled endothelial cells lining slit-like vessels were present in the mid dermis, although this comprises a minority of the lesion. The majority of the subcutis was uninvolved. The findings are overall most consistent with a tufted angioma.

Kaposiform hemangioendothelioma (KHE) has been considered given the presence of occasional slit-like vascular spaces; however, the lesion is predominantly superficial and therefore the lesion is best classified as tufted angioma. GLUT–1 staining was negative.

At the time of biopsy, blood work was ordered, which showed a normal complete blood count with normal number of platelets, slightly elevated D-dimer, and slightly low fibrinogen. Several repeat blood counts and coagulation tests once a week for a few weeks revealed no changes.

The patient was started on aspirin at a dose of 5 mg/kg per day. After a week on the medication the lesion was starting to get smaller and less red.

Tufted angiomas are a rare type of vascular tumor within the spectrum of kaposiform hemangioendotheliomas. Most cases present within the first year of life; some occur at birth. They usually present as papules, plaques, or erythematous, violaceous indurated nodules on the face, neck, trunk, and extremities. The lesions can also be present with hyperhidrosis and hypertrichosis. Clinically, the lesions will have to be differentiated from other vascular tumors such as infantile hemangiomas, congenital hemangiomas, and Kaposi’s sarcoma, as well as subcutaneous fat necrosis of the newborn, cellulitis, and nonaccidental trauma.

Pathogenesis of tufted angiomas is poorly understood. A recent case report found a somatic mutation on GNA14.This protein regulates Ras activity and modulates endothelial cell permeability and migration in response to FGF2 and VEGFA. The p.205L mutation causes activation of GNA14, which upregulates pERK-MAPK pathway, suggesting MAPK inhibition as a potential target for therapy. Clinically, tufted angioma can present in three patterns: uncomplicated tufted angioma (most common type); tufted angioma without thrombocytopenia but with chronic coagulopathy, as it was seen in our patient; and tufted angioma associated with Kasabach-Merritt phenomenon (KMP). KMP is characterized by thrombocytopenia in association with microangiopathic hemolytic anemia, consumptive coagulopathy, and enlarging vascular tumor. Treatment of uncomplicated tufted angioma will depend on symptomatology, size, and location of the lesion. Smaller lesions in noncosmetically sensitive areas can be treated with surgical excision. Cases that are not amenable to excision can be treated with aspirin. There are also reports of response to topical modalities including tacrolimus and timolol. For complicated cases associated with KMP, sirolimus, systemic corticosteroids, ticlopidine, interferon, or vincristine are recommended. Some lesions may demonstrate spontaneous regression.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Cohen S et al. Dermatol Online J. 2019 Sep 15;25(9):13030/qt6pv254mc.

Lim YH et al. Pediatr Dermatol. 2019 Nov;36(6):963-4.

Prasuna A, Rao PN. Indian Dermatol Online J. 2015;6:266-8.

As the lesion was growing, getting more violaceous and indurated, a biopsy was performed. The biopsy showed multiple discrete lobules of dermal capillaries with slight extension into the superficial subcutis. Capillary lobules demonstrate the “cannonball-like” architecture often associated with tufted angioma, and some lobules showed bulging into adjacent thin-walled vessels. Spindled endothelial cells lining slit-like vessels were present in the mid dermis, although this comprises a minority of the lesion. The majority of the subcutis was uninvolved. The findings are overall most consistent with a tufted angioma.

Kaposiform hemangioendothelioma (KHE) has been considered given the presence of occasional slit-like vascular spaces; however, the lesion is predominantly superficial and therefore the lesion is best classified as tufted angioma. GLUT–1 staining was negative.

At the time of biopsy, blood work was ordered, which showed a normal complete blood count with normal number of platelets, slightly elevated D-dimer, and slightly low fibrinogen. Several repeat blood counts and coagulation tests once a week for a few weeks revealed no changes.

The patient was started on aspirin at a dose of 5 mg/kg per day. After a week on the medication the lesion was starting to get smaller and less red.

Tufted angiomas are a rare type of vascular tumor within the spectrum of kaposiform hemangioendotheliomas. Most cases present within the first year of life; some occur at birth. They usually present as papules, plaques, or erythematous, violaceous indurated nodules on the face, neck, trunk, and extremities. The lesions can also be present with hyperhidrosis and hypertrichosis. Clinically, the lesions will have to be differentiated from other vascular tumors such as infantile hemangiomas, congenital hemangiomas, and Kaposi’s sarcoma, as well as subcutaneous fat necrosis of the newborn, cellulitis, and nonaccidental trauma.

Pathogenesis of tufted angiomas is poorly understood. A recent case report found a somatic mutation on GNA14.This protein regulates Ras activity and modulates endothelial cell permeability and migration in response to FGF2 and VEGFA. The p.205L mutation causes activation of GNA14, which upregulates pERK-MAPK pathway, suggesting MAPK inhibition as a potential target for therapy. Clinically, tufted angioma can present in three patterns: uncomplicated tufted angioma (most common type); tufted angioma without thrombocytopenia but with chronic coagulopathy, as it was seen in our patient; and tufted angioma associated with Kasabach-Merritt phenomenon (KMP). KMP is characterized by thrombocytopenia in association with microangiopathic hemolytic anemia, consumptive coagulopathy, and enlarging vascular tumor. Treatment of uncomplicated tufted angioma will depend on symptomatology, size, and location of the lesion. Smaller lesions in noncosmetically sensitive areas can be treated with surgical excision. Cases that are not amenable to excision can be treated with aspirin. There are also reports of response to topical modalities including tacrolimus and timolol. For complicated cases associated with KMP, sirolimus, systemic corticosteroids, ticlopidine, interferon, or vincristine are recommended. Some lesions may demonstrate spontaneous regression.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Cohen S et al. Dermatol Online J. 2019 Sep 15;25(9):13030/qt6pv254mc.

Lim YH et al. Pediatr Dermatol. 2019 Nov;36(6):963-4.

Prasuna A, Rao PN. Indian Dermatol Online J. 2015;6:266-8.

As the lesion was growing, getting more violaceous and indurated, a biopsy was performed. The biopsy showed multiple discrete lobules of dermal capillaries with slight extension into the superficial subcutis. Capillary lobules demonstrate the “cannonball-like” architecture often associated with tufted angioma, and some lobules showed bulging into adjacent thin-walled vessels. Spindled endothelial cells lining slit-like vessels were present in the mid dermis, although this comprises a minority of the lesion. The majority of the subcutis was uninvolved. The findings are overall most consistent with a tufted angioma.

Kaposiform hemangioendothelioma (KHE) has been considered given the presence of occasional slit-like vascular spaces; however, the lesion is predominantly superficial and therefore the lesion is best classified as tufted angioma. GLUT–1 staining was negative.

At the time of biopsy, blood work was ordered, which showed a normal complete blood count with normal number of platelets, slightly elevated D-dimer, and slightly low fibrinogen. Several repeat blood counts and coagulation tests once a week for a few weeks revealed no changes.

The patient was started on aspirin at a dose of 5 mg/kg per day. After a week on the medication the lesion was starting to get smaller and less red.

Tufted angiomas are a rare type of vascular tumor within the spectrum of kaposiform hemangioendotheliomas. Most cases present within the first year of life; some occur at birth. They usually present as papules, plaques, or erythematous, violaceous indurated nodules on the face, neck, trunk, and extremities. The lesions can also be present with hyperhidrosis and hypertrichosis. Clinically, the lesions will have to be differentiated from other vascular tumors such as infantile hemangiomas, congenital hemangiomas, and Kaposi’s sarcoma, as well as subcutaneous fat necrosis of the newborn, cellulitis, and nonaccidental trauma.

Pathogenesis of tufted angiomas is poorly understood. A recent case report found a somatic mutation on GNA14.This protein regulates Ras activity and modulates endothelial cell permeability and migration in response to FGF2 and VEGFA. The p.205L mutation causes activation of GNA14, which upregulates pERK-MAPK pathway, suggesting MAPK inhibition as a potential target for therapy. Clinically, tufted angioma can present in three patterns: uncomplicated tufted angioma (most common type); tufted angioma without thrombocytopenia but with chronic coagulopathy, as it was seen in our patient; and tufted angioma associated with Kasabach-Merritt phenomenon (KMP). KMP is characterized by thrombocytopenia in association with microangiopathic hemolytic anemia, consumptive coagulopathy, and enlarging vascular tumor. Treatment of uncomplicated tufted angioma will depend on symptomatology, size, and location of the lesion. Smaller lesions in noncosmetically sensitive areas can be treated with surgical excision. Cases that are not amenable to excision can be treated with aspirin. There are also reports of response to topical modalities including tacrolimus and timolol. For complicated cases associated with KMP, sirolimus, systemic corticosteroids, ticlopidine, interferon, or vincristine are recommended. Some lesions may demonstrate spontaneous regression.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.

References

Cohen S et al. Dermatol Online J. 2019 Sep 15;25(9):13030/qt6pv254mc.

Lim YH et al. Pediatr Dermatol. 2019 Nov;36(6):963-4.

Prasuna A, Rao PN. Indian Dermatol Online J. 2015;6:266-8.