Pediatric Dermatology Consult

Numerous morphologies of skin rashes have been described in the setting of COVID-19, including pernio, livedoid rash, exanthem, and vasculitis. This classic constellation of symptoms (palpable purpura on buttocks/legs, abdominal pain, arthralgia, hematuria) is highly consistent with Henoch-Schonlein purpura (HSP). There are now multiple case reports of COVID-19–associated HSP.

HSP is the most common type of childhood systemic vasculitis. It is mediated by immunoglobulin A (IgA) immune complex deposition and has been associated with respiratory tract infections, streptococcal species, parainfluenza virus, and human parvovirus B19, medications, vaccinations, and malignancies. HSP is usually a self-limiting disease, with a course over 4-6 weeks, and can affect multiple organs, including the skin, gastrointestinal tract, joints, and the kidneys. The diagnostic criteria include palpable purpura in the presence of one or more of the following: diffuse abdominal pain, arthritis or arthralgia, any biopsy showing predominant IgA deposition, and renal involvement in the form of hematuria or proteinuria. Renal disease is variable and is the most significant indicator of long-term prognosis. This teenager was treated with oral corticosteroids because of the severe periarticular edema and responded rapidly. His subsequent urine analyses normalized.
 

What is on the differential?

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal, complication of COVID-19 infection that causes inflammation of multiple organs, including the heart, lungs, kidneys, brain, skin, eyes, or the gastrointestinal tract. It commonly affects children around ages 8-9 years. Initial symptoms include fever, rash, red eyes, diarrhea, and vomiting that appear 2-6 weeks post COVID-19 infection. Like HSP, MIS-C can present with edema of the extremities, worsening hand/foot pain, and hematuria; however, the absence of both fever and the pattern of system involvement seen with MIS-C and classic findings in this patient are more consistent with HSP.

Reactive infectious mucocutaneous eruption (RIME) was recently coined to encompass both infection-associated Stevens-Johnson eruptions including Mycoplasma pneumoniae-induced rash and mucositis (MIRM) and mucocutaneous eruptions caused by nonmycoplasma pathogens (including Chlamydia pneumoniae, human parainfluenza virus 2, rhinovirus, adenovirus, enterovirus, human metapneumovirus, influenza B virus, and COVID-19). It is usually seen in male children and adolescents. Prodromal symptoms include cough, fever, and malaise and they precede the prominent feature of mucositis. Our patient’s lack of mucosal involvement is not consistent with RIME.

Perniosis (chilblains) is characterized by localized edematous patches of erythema or cyanosis on exposed extremities, that may be associated with cold exposure. Lesions are usually symmetric and self-limiting, and symptoms can include numbness, tingling, pruritus, burning, or pain. Pernio-like skin lesions have been seen during the COVID-19 pandemic, though many patients have negative testing for infection by PCR and serology. Pernio may also be seen with autoimmune diseases or malignancy.

Meningococcemia is a rare disease caused by infection with gram-negative diplococci bacteria Neisseria meningitidis and spreads through saliva or respiratory secretions. Its clinical presentation can vary widely, from transient fever to fulminant disease. It is characterized by upper respiratory tract infection, fever, and petechial lesions associated with thrombocytopenia and coagulopathy.
 

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. 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. Eichenfield and Ms. Laborada have no relevant financial disclosures.

References

AlGhoozi DA, AlKhayyat HM. BMJ Case Reports CP 2021;14:e239910.

Jacobi M et al. Pediatr Infect Dis J. 2021;40(2):e93-4.

Paller A, Mancini AJ. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 4th ed. Philadelphia (PA): Elsevier Saunders; 2011.

Radia T et al. Paediatr Respir Rev. 2021;38:51-7.

Ramien ML. Clin Exp Dermatol. 2021;46(3):420-9.

Numerous morphologies of skin rashes have been described in the setting of COVID-19, including pernio, livedoid rash, exanthem, and vasculitis. This classic constellation of symptoms (palpable purpura on buttocks/legs, abdominal pain, arthralgia, hematuria) is highly consistent with Henoch-Schonlein purpura (HSP). There are now multiple case reports of COVID-19–associated HSP.

HSP is the most common type of childhood systemic vasculitis. It is mediated by immunoglobulin A (IgA) immune complex deposition and has been associated with respiratory tract infections, streptococcal species, parainfluenza virus, and human parvovirus B19, medications, vaccinations, and malignancies. HSP is usually a self-limiting disease, with a course over 4-6 weeks, and can affect multiple organs, including the skin, gastrointestinal tract, joints, and the kidneys. The diagnostic criteria include palpable purpura in the presence of one or more of the following: diffuse abdominal pain, arthritis or arthralgia, any biopsy showing predominant IgA deposition, and renal involvement in the form of hematuria or proteinuria. Renal disease is variable and is the most significant indicator of long-term prognosis. This teenager was treated with oral corticosteroids because of the severe periarticular edema and responded rapidly. His subsequent urine analyses normalized.
 

What is on the differential?

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal, complication of COVID-19 infection that causes inflammation of multiple organs, including the heart, lungs, kidneys, brain, skin, eyes, or the gastrointestinal tract. It commonly affects children around ages 8-9 years. Initial symptoms include fever, rash, red eyes, diarrhea, and vomiting that appear 2-6 weeks post COVID-19 infection. Like HSP, MIS-C can present with edema of the extremities, worsening hand/foot pain, and hematuria; however, the absence of both fever and the pattern of system involvement seen with MIS-C and classic findings in this patient are more consistent with HSP.

Reactive infectious mucocutaneous eruption (RIME) was recently coined to encompass both infection-associated Stevens-Johnson eruptions including Mycoplasma pneumoniae-induced rash and mucositis (MIRM) and mucocutaneous eruptions caused by nonmycoplasma pathogens (including Chlamydia pneumoniae, human parainfluenza virus 2, rhinovirus, adenovirus, enterovirus, human metapneumovirus, influenza B virus, and COVID-19). It is usually seen in male children and adolescents. Prodromal symptoms include cough, fever, and malaise and they precede the prominent feature of mucositis. Our patient’s lack of mucosal involvement is not consistent with RIME.

Perniosis (chilblains) is characterized by localized edematous patches of erythema or cyanosis on exposed extremities, that may be associated with cold exposure. Lesions are usually symmetric and self-limiting, and symptoms can include numbness, tingling, pruritus, burning, or pain. Pernio-like skin lesions have been seen during the COVID-19 pandemic, though many patients have negative testing for infection by PCR and serology. Pernio may also be seen with autoimmune diseases or malignancy.

Meningococcemia is a rare disease caused by infection with gram-negative diplococci bacteria Neisseria meningitidis and spreads through saliva or respiratory secretions. Its clinical presentation can vary widely, from transient fever to fulminant disease. It is characterized by upper respiratory tract infection, fever, and petechial lesions associated with thrombocytopenia and coagulopathy.
 

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. 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. Eichenfield and Ms. Laborada have no relevant financial disclosures.

References

AlGhoozi DA, AlKhayyat HM. BMJ Case Reports CP 2021;14:e239910.

Jacobi M et al. Pediatr Infect Dis J. 2021;40(2):e93-4.

Paller A, Mancini AJ. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 4th ed. Philadelphia (PA): Elsevier Saunders; 2011.

Radia T et al. Paediatr Respir Rev. 2021;38:51-7.

Ramien ML. Clin Exp Dermatol. 2021;46(3):420-9.

Numerous morphologies of skin rashes have been described in the setting of COVID-19, including pernio, livedoid rash, exanthem, and vasculitis. This classic constellation of symptoms (palpable purpura on buttocks/legs, abdominal pain, arthralgia, hematuria) is highly consistent with Henoch-Schonlein purpura (HSP). There are now multiple case reports of COVID-19–associated HSP.

HSP is the most common type of childhood systemic vasculitis. It is mediated by immunoglobulin A (IgA) immune complex deposition and has been associated with respiratory tract infections, streptococcal species, parainfluenza virus, and human parvovirus B19, medications, vaccinations, and malignancies. HSP is usually a self-limiting disease, with a course over 4-6 weeks, and can affect multiple organs, including the skin, gastrointestinal tract, joints, and the kidneys. The diagnostic criteria include palpable purpura in the presence of one or more of the following: diffuse abdominal pain, arthritis or arthralgia, any biopsy showing predominant IgA deposition, and renal involvement in the form of hematuria or proteinuria. Renal disease is variable and is the most significant indicator of long-term prognosis. This teenager was treated with oral corticosteroids because of the severe periarticular edema and responded rapidly. His subsequent urine analyses normalized.
 

What is on the differential?

Multisystem inflammatory syndrome in children (MIS-C) is a rare, potentially fatal, complication of COVID-19 infection that causes inflammation of multiple organs, including the heart, lungs, kidneys, brain, skin, eyes, or the gastrointestinal tract. It commonly affects children around ages 8-9 years. Initial symptoms include fever, rash, red eyes, diarrhea, and vomiting that appear 2-6 weeks post COVID-19 infection. Like HSP, MIS-C can present with edema of the extremities, worsening hand/foot pain, and hematuria; however, the absence of both fever and the pattern of system involvement seen with MIS-C and classic findings in this patient are more consistent with HSP.

Reactive infectious mucocutaneous eruption (RIME) was recently coined to encompass both infection-associated Stevens-Johnson eruptions including Mycoplasma pneumoniae-induced rash and mucositis (MIRM) and mucocutaneous eruptions caused by nonmycoplasma pathogens (including Chlamydia pneumoniae, human parainfluenza virus 2, rhinovirus, adenovirus, enterovirus, human metapneumovirus, influenza B virus, and COVID-19). It is usually seen in male children and adolescents. Prodromal symptoms include cough, fever, and malaise and they precede the prominent feature of mucositis. Our patient’s lack of mucosal involvement is not consistent with RIME.

Perniosis (chilblains) is characterized by localized edematous patches of erythema or cyanosis on exposed extremities, that may be associated with cold exposure. Lesions are usually symmetric and self-limiting, and symptoms can include numbness, tingling, pruritus, burning, or pain. Pernio-like skin lesions have been seen during the COVID-19 pandemic, though many patients have negative testing for infection by PCR and serology. Pernio may also be seen with autoimmune diseases or malignancy.

Meningococcemia is a rare disease caused by infection with gram-negative diplococci bacteria Neisseria meningitidis and spreads through saliva or respiratory secretions. Its clinical presentation can vary widely, from transient fever to fulminant disease. It is characterized by upper respiratory tract infection, fever, and petechial lesions associated with thrombocytopenia and coagulopathy.
 

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. 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. Eichenfield and Ms. Laborada have no relevant financial disclosures.

References

AlGhoozi DA, AlKhayyat HM. BMJ Case Reports CP 2021;14:e239910.

Jacobi M et al. Pediatr Infect Dis J. 2021;40(2):e93-4.

Paller A, Mancini AJ. Hurwitz clinical pediatric dermatology: A textbook of skin disorders of childhood and adolescence. 4th ed. Philadelphia (PA): Elsevier Saunders; 2011.

Radia T et al. Paediatr Respir Rev. 2021;38:51-7.

Ramien ML. Clin Exp Dermatol. 2021;46(3):420-9.

The Diagnosis: Linear Lichen Planus

The patient was clinically diagnosed with linear lichen planus and was started on betamethasone dipropionate ointment 0.05% applied once daily with improvement in both the pruritus and appearance at 4-month follow-up. A biopsy was deferred based on the parents’ wishes.

Lichen planus is an inflammatory disorder involving the skin and oral mucosa. Cutaneous lichen planus classically presents as flat-topped, violaceous, pruritic, polygonal papules with overlying fine white or grey lines known as Wickham striae.¹ Postinflammatory hyperpigmentation is common, especially in patients with darker skin tones. Expected histologic findings include orthokeratosis, apoptotic keratinocytes, and bandlike lymphocytic infiltration at the dermoepidermal junction.¹

An estimated 5% of cases of cutaneous lichen planus occur in children.² A study of 316 children with lichen planus demonstrated that the classic morphology remained the most common presentation, while the linear variant was present in only 6.9% of pediatric cases.³ Linear lichen planus appears to be more common among children than adults. A study of 36 pediatric cases showed a greater representation of lichen planus in Black children (67% affected vs 21% cohort).²

Cutaneous lichen planus often clears spontaneously in approximately 1 year.⁴ Treatment in children primarily is focused on shortening the time to resolution and relieving pruritus, with topical corticosteroids as firstline therapy.^3,4 Oral corticosteroids have a faster clinical response; greater efficacy; and more effectively prevent residual hyperpigmentation, which is especially relevant in individuals with darker skin.³ Nonetheless, oral corticosteroids are considered a second-line treatment due to their unfavorable side-effect profile. Additional treatment options include oral aromatic retinoids (acitretin) and phototherapy.³

Incontinentia pigmenti is characterized by a defect in the inhibitor of nuclear factor–κB kinase regulatory subunit gamma, IKBKG, gene on the X chromosome. Incontinentia pigmenti usually is lethal in males; in females, it leads to ectodermal dysplasia associated with skin findings in a blaschkoid distribution occurring in 4 stages.⁵ The verrucous stage is preceded by the vesicular stage and expected to occur within the first few months of life, making it unlikely in our 5-year-old patient. Inflammatory linear verrucous epidermal nevus usually occurs in children younger than 5 years and is characterized by psoriasiform papules coalescing into a plaque with substantial scale instead of Wickham striae, as seen in our patient.⁶ Lichen striatus consists of smaller, pink to flesh-colored papules that rarely are pruritic.⁷ It is more common among atopic individuals and is associated with postinflammatory hypopigmentation.⁸ Linear psoriasis presents similarly to inflammatory linear verrucous epidermal nevus, with greater erythema and scale compared to the fine lacy Wickham striae that were seen in our patient.⁸

The Diagnosis: Linear Lichen Planus

The patient was clinically diagnosed with linear lichen planus and was started on betamethasone dipropionate ointment 0.05% applied once daily with improvement in both the pruritus and appearance at 4-month follow-up. A biopsy was deferred based on the parents’ wishes.

Lichen planus is an inflammatory disorder involving the skin and oral mucosa. Cutaneous lichen planus classically presents as flat-topped, violaceous, pruritic, polygonal papules with overlying fine white or grey lines known as Wickham striae.¹ Postinflammatory hyperpigmentation is common, especially in patients with darker skin tones. Expected histologic findings include orthokeratosis, apoptotic keratinocytes, and bandlike lymphocytic infiltration at the dermoepidermal junction.¹

An estimated 5% of cases of cutaneous lichen planus occur in children.² A study of 316 children with lichen planus demonstrated that the classic morphology remained the most common presentation, while the linear variant was present in only 6.9% of pediatric cases.³ Linear lichen planus appears to be more common among children than adults. A study of 36 pediatric cases showed a greater representation of lichen planus in Black children (67% affected vs 21% cohort).²

Cutaneous lichen planus often clears spontaneously in approximately 1 year.⁴ Treatment in children primarily is focused on shortening the time to resolution and relieving pruritus, with topical corticosteroids as firstline therapy.^3,4 Oral corticosteroids have a faster clinical response; greater efficacy; and more effectively prevent residual hyperpigmentation, which is especially relevant in individuals with darker skin.³ Nonetheless, oral corticosteroids are considered a second-line treatment due to their unfavorable side-effect profile. Additional treatment options include oral aromatic retinoids (acitretin) and phototherapy.³

Incontinentia pigmenti is characterized by a defect in the inhibitor of nuclear factor–κB kinase regulatory subunit gamma, IKBKG, gene on the X chromosome. Incontinentia pigmenti usually is lethal in males; in females, it leads to ectodermal dysplasia associated with skin findings in a blaschkoid distribution occurring in 4 stages.⁵ The verrucous stage is preceded by the vesicular stage and expected to occur within the first few months of life, making it unlikely in our 5-year-old patient. Inflammatory linear verrucous epidermal nevus usually occurs in children younger than 5 years and is characterized by psoriasiform papules coalescing into a plaque with substantial scale instead of Wickham striae, as seen in our patient.⁶ Lichen striatus consists of smaller, pink to flesh-colored papules that rarely are pruritic.⁷ It is more common among atopic individuals and is associated with postinflammatory hypopigmentation.⁸ Linear psoriasis presents similarly to inflammatory linear verrucous epidermal nevus, with greater erythema and scale compared to the fine lacy Wickham striae that were seen in our patient.⁸

The Diagnosis: Linear Lichen Planus

The patient was clinically diagnosed with linear lichen planus and was started on betamethasone dipropionate ointment 0.05% applied once daily with improvement in both the pruritus and appearance at 4-month follow-up. A biopsy was deferred based on the parents’ wishes.

Lichen planus is an inflammatory disorder involving the skin and oral mucosa. Cutaneous lichen planus classically presents as flat-topped, violaceous, pruritic, polygonal papules with overlying fine white or grey lines known as Wickham striae.¹ Postinflammatory hyperpigmentation is common, especially in patients with darker skin tones. Expected histologic findings include orthokeratosis, apoptotic keratinocytes, and bandlike lymphocytic infiltration at the dermoepidermal junction.¹

An estimated 5% of cases of cutaneous lichen planus occur in children.² A study of 316 children with lichen planus demonstrated that the classic morphology remained the most common presentation, while the linear variant was present in only 6.9% of pediatric cases.³ Linear lichen planus appears to be more common among children than adults. A study of 36 pediatric cases showed a greater representation of lichen planus in Black children (67% affected vs 21% cohort).²

Cutaneous lichen planus often clears spontaneously in approximately 1 year.⁴ Treatment in children primarily is focused on shortening the time to resolution and relieving pruritus, with topical corticosteroids as firstline therapy.^3,4 Oral corticosteroids have a faster clinical response; greater efficacy; and more effectively prevent residual hyperpigmentation, which is especially relevant in individuals with darker skin.³ Nonetheless, oral corticosteroids are considered a second-line treatment due to their unfavorable side-effect profile. Additional treatment options include oral aromatic retinoids (acitretin) and phototherapy.³

Incontinentia pigmenti is characterized by a defect in the inhibitor of nuclear factor–κB kinase regulatory subunit gamma, IKBKG, gene on the X chromosome. Incontinentia pigmenti usually is lethal in males; in females, it leads to ectodermal dysplasia associated with skin findings in a blaschkoid distribution occurring in 4 stages.⁵ The verrucous stage is preceded by the vesicular stage and expected to occur within the first few months of life, making it unlikely in our 5-year-old patient. Inflammatory linear verrucous epidermal nevus usually occurs in children younger than 5 years and is characterized by psoriasiform papules coalescing into a plaque with substantial scale instead of Wickham striae, as seen in our patient.⁶ Lichen striatus consists of smaller, pink to flesh-colored papules that rarely are pruritic.⁷ It is more common among atopic individuals and is associated with postinflammatory hypopigmentation.⁸ Linear psoriasis presents similarly to inflammatory linear verrucous epidermal nevus, with greater erythema and scale compared to the fine lacy Wickham striae that were seen in our patient.⁸

The Diagnosis: Striated Muscle Hamartoma

Histopathologic evaluation revealed a dome-shaped papule with a center composed of mature striated muscle bundles, vellus hairs, sebaceous lobules, and nerve twigs (Figure) consistent with a diagnosis of striated muscle hamartoma (SMH).

Striated muscle hamartoma was first described in 1986 by Hendrick et al1 with 2 cases in neonates. Biopsies of the lesions taken from the upper lip and sternum showed a characteristic histology consisting of dermal striated muscle fibers and nerve bundles in the central core of the papules associated with a marked number of adnexa. In 1989, the diagnosis of rhabdomyomatous mesenchymal hamartoma was described, which showed similar findings.² Cases reported since these entities were discovered have used the terms striated muscle hamartoma and rhabdomyomatous mesenchymal hamartoma interchangeably.³

Most commonly found on the head and neck, SMH has now been observed in diverse locations including the sternum, hallux, vagina, and oral cavity.^1-15 Many reported cases describe lesions around or in the nose.^4,7,8 Multiple congenital anomalies have been described alongside SMH and may be associated with this entity including amniotic bands, cleft lip and palate, coloboma, and Delleman syndrome.^1,3,4 Almost all of the lesions present as a sessile or pedunculated papule, polyp, nodule, or plaque measuring from 0.3 cm up to 4.9 cm and typically are present since birth.^3,5,15 However, there are a few cases of lesions presenting in adults with no prior history.^5,6,15

Microscopically, SMH is defined by a dermal lesion with a core comprised of mature skeletal muscle admixed with adipose tissue, adnexa, nerve bundles, and fibrovascular tissue.¹ There are other entities that should be considered before making the diagnosis of SMH. Other hamartomas such as accessory tragus, connective tissue nevus, fibrous hamartoma of infancy, and nevus lipomatosis may present similarly; however, these lesions classically lack skeletal muscle. Benign triton tumors, or neuromuscular hamartomas, are rare lesions composed of skeletal muscle and abundant, intimately associated neural tissue. Neuromuscular hamartomas frequently involve large nerves.¹⁶ Rhabdomyomas also should be considered. Adult rhabdomyomas are composed of eosinophilic polygonal cells with granular cytoplasm and occasional cross-striations. Fetal rhabdomyomas have multiple histologic types and are defined by a variable myxoid stroma, eosinophilic spindled cells, and rhabdomyocytes in various stages of maturity. Genital rhabdomyomas histopathologically appear similar to fetal rhabdomyomas but are confined to the genital region. The skeletal muscle present in rhabdomyomas typically is less differentiated.¹⁷ TMature skeletal bundles should be a dominant component of the lesion before diagnosing SMH.

Typically presenting as congenital lesions in the head and neck region, papules with a dermal core of mature skeletal muscle associated with adnexa and nerve twigs should prompt consideration of a diagnosis of SMH or rhabdomyomatous mesenchymal hamartoma. These lesions are benign and usually are cured with complete excision.

The Diagnosis: Striated Muscle Hamartoma

Histopathologic evaluation revealed a dome-shaped papule with a center composed of mature striated muscle bundles, vellus hairs, sebaceous lobules, and nerve twigs (Figure) consistent with a diagnosis of striated muscle hamartoma (SMH).

Striated muscle hamartoma was first described in 1986 by Hendrick et al1 with 2 cases in neonates. Biopsies of the lesions taken from the upper lip and sternum showed a characteristic histology consisting of dermal striated muscle fibers and nerve bundles in the central core of the papules associated with a marked number of adnexa. In 1989, the diagnosis of rhabdomyomatous mesenchymal hamartoma was described, which showed similar findings.² Cases reported since these entities were discovered have used the terms striated muscle hamartoma and rhabdomyomatous mesenchymal hamartoma interchangeably.³

Most commonly found on the head and neck, SMH has now been observed in diverse locations including the sternum, hallux, vagina, and oral cavity.^1-15 Many reported cases describe lesions around or in the nose.^4,7,8 Multiple congenital anomalies have been described alongside SMH and may be associated with this entity including amniotic bands, cleft lip and palate, coloboma, and Delleman syndrome.^1,3,4 Almost all of the lesions present as a sessile or pedunculated papule, polyp, nodule, or plaque measuring from 0.3 cm up to 4.9 cm and typically are present since birth.^3,5,15 However, there are a few cases of lesions presenting in adults with no prior history.^5,6,15

Microscopically, SMH is defined by a dermal lesion with a core comprised of mature skeletal muscle admixed with adipose tissue, adnexa, nerve bundles, and fibrovascular tissue.¹ There are other entities that should be considered before making the diagnosis of SMH. Other hamartomas such as accessory tragus, connective tissue nevus, fibrous hamartoma of infancy, and nevus lipomatosis may present similarly; however, these lesions classically lack skeletal muscle. Benign triton tumors, or neuromuscular hamartomas, are rare lesions composed of skeletal muscle and abundant, intimately associated neural tissue. Neuromuscular hamartomas frequently involve large nerves.¹⁶ Rhabdomyomas also should be considered. Adult rhabdomyomas are composed of eosinophilic polygonal cells with granular cytoplasm and occasional cross-striations. Fetal rhabdomyomas have multiple histologic types and are defined by a variable myxoid stroma, eosinophilic spindled cells, and rhabdomyocytes in various stages of maturity. Genital rhabdomyomas histopathologically appear similar to fetal rhabdomyomas but are confined to the genital region. The skeletal muscle present in rhabdomyomas typically is less differentiated.¹⁷ TMature skeletal bundles should be a dominant component of the lesion before diagnosing SMH.

Typically presenting as congenital lesions in the head and neck region, papules with a dermal core of mature skeletal muscle associated with adnexa and nerve twigs should prompt consideration of a diagnosis of SMH or rhabdomyomatous mesenchymal hamartoma. These lesions are benign and usually are cured with complete excision.

The Diagnosis: Striated Muscle Hamartoma

Histopathologic evaluation revealed a dome-shaped papule with a center composed of mature striated muscle bundles, vellus hairs, sebaceous lobules, and nerve twigs (Figure) consistent with a diagnosis of striated muscle hamartoma (SMH).

Striated muscle hamartoma was first described in 1986 by Hendrick et al1 with 2 cases in neonates. Biopsies of the lesions taken from the upper lip and sternum showed a characteristic histology consisting of dermal striated muscle fibers and nerve bundles in the central core of the papules associated with a marked number of adnexa. In 1989, the diagnosis of rhabdomyomatous mesenchymal hamartoma was described, which showed similar findings.² Cases reported since these entities were discovered have used the terms striated muscle hamartoma and rhabdomyomatous mesenchymal hamartoma interchangeably.³

Most commonly found on the head and neck, SMH has now been observed in diverse locations including the sternum, hallux, vagina, and oral cavity.^1-15 Many reported cases describe lesions around or in the nose.^4,7,8 Multiple congenital anomalies have been described alongside SMH and may be associated with this entity including amniotic bands, cleft lip and palate, coloboma, and Delleman syndrome.^1,3,4 Almost all of the lesions present as a sessile or pedunculated papule, polyp, nodule, or plaque measuring from 0.3 cm up to 4.9 cm and typically are present since birth.^3,5,15 However, there are a few cases of lesions presenting in adults with no prior history.^5,6,15

Microscopically, SMH is defined by a dermal lesion with a core comprised of mature skeletal muscle admixed with adipose tissue, adnexa, nerve bundles, and fibrovascular tissue.¹ There are other entities that should be considered before making the diagnosis of SMH. Other hamartomas such as accessory tragus, connective tissue nevus, fibrous hamartoma of infancy, and nevus lipomatosis may present similarly; however, these lesions classically lack skeletal muscle. Benign triton tumors, or neuromuscular hamartomas, are rare lesions composed of skeletal muscle and abundant, intimately associated neural tissue. Neuromuscular hamartomas frequently involve large nerves.¹⁶ Rhabdomyomas also should be considered. Adult rhabdomyomas are composed of eosinophilic polygonal cells with granular cytoplasm and occasional cross-striations. Fetal rhabdomyomas have multiple histologic types and are defined by a variable myxoid stroma, eosinophilic spindled cells, and rhabdomyocytes in various stages of maturity. Genital rhabdomyomas histopathologically appear similar to fetal rhabdomyomas but are confined to the genital region. The skeletal muscle present in rhabdomyomas typically is less differentiated.¹⁷ TMature skeletal bundles should be a dominant component of the lesion before diagnosing SMH.

Typically presenting as congenital lesions in the head and neck region, papules with a dermal core of mature skeletal muscle associated with adnexa and nerve twigs should prompt consideration of a diagnosis of SMH or rhabdomyomatous mesenchymal hamartoma. These lesions are benign and usually are cured with complete excision.

A biopsy of the lesion was performed which showed an increased number of eccrine glands and blood vessels within the dermis. Some areas showed an increase in adipocytes and smooth muscle bundles. The changes were consistent with eccrine angiomatous hamartoma (EAH).

The boy was referred to vascular laser therapy for treatment of the lesion.

EAH is a rare benign vascular growth characterized by an increased number of mature eccrine glands and blood vessels in the dermis and subcutis. The lesions are mostly present on the extremities, but cases of diffuse congenital lesions and lesions on the face and trunk have also been described. The lesions can be seen at birth or during the first years of life in about half of the cases, and the others tend to occur later in puberty and rarely in adulthood^.1

Clinically, EAH lesions present as red, yellow to brown papules and plaques. Different dermoscopic patterns have been described which include the popcorn pattern that presents as yellow, confluent nodules with popcornlike shapes over a background of erythema, and linear arborizing vessels. The spitzoid pattern are brown globules on a background of erythema and pseudoreticular pigmentation around the globules. The verrucous hemangiomalike pattern has a bluish-white hue, reddish-blue or bluish lacunae, as seen in our patient.^2-4

Most of the lesions are asymptomatic, but in some patients, they can be associated with pain, hyperhidrosis, and sometimes bleeding. Hyperhidrosis has been reported early in the presentation or during puberty or pregnancy. Our patient had started on amphetamines when hyperhidrosis occurred. Hyperhidrosis is a knowns side effect of this type of medication and may have had a role in the increased sweating noted on the hamartoma.

EAH can clinically look like verrucous hemangiomas, angiokeratomas, and vascular malformations, and histopathology may be needed to differentiate between them. Eccrine nevi and EAH can be similar. Hyperhidrosis is an early and predominant component of eccrine nevi, compared with one-third of EAH.

The exact etiology of this lesion is not known. It is thought to be caused by an abnormal differentiation of the epithelium, adnexal structure, and the mesenchyme during organogenesis.³ No other associated conditions have been described with EAH.

EAH are benign lesions that rarely require treatment. If the lesions are symptomatic or because of cosmetic reasons, they can be removed surgically. There are some reports of successful treatment with pulse dual-wavelength sequential 595- and 1064-nm lasers.⁵ Botulinum toxin has also been used in cases of symptomatic hyperhidrosis.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She has no conflicts. Email her at [email protected].

References

1. Smith SD et al. Pediatr Dermatol. 2019 Nov;36(6):909-12.

2. Patterson AT et al. Am J Dermatopathol. 2016;38:413-7.

3. Garcıa-Garcıa SC et al. JAAD Case Rep. 2018;4(2):165-7.

4. Awatef Kelati et al. JAAD Case Rep. 2018;4(8)835-6.

5. Felgueiras J et al. Dermatol Surg. 2015 Mar;41(3):428-30.

A biopsy of the lesion was performed which showed an increased number of eccrine glands and blood vessels within the dermis. Some areas showed an increase in adipocytes and smooth muscle bundles. The changes were consistent with eccrine angiomatous hamartoma (EAH).

The boy was referred to vascular laser therapy for treatment of the lesion.

EAH is a rare benign vascular growth characterized by an increased number of mature eccrine glands and blood vessels in the dermis and subcutis. The lesions are mostly present on the extremities, but cases of diffuse congenital lesions and lesions on the face and trunk have also been described. The lesions can be seen at birth or during the first years of life in about half of the cases, and the others tend to occur later in puberty and rarely in adulthood^.1

Clinically, EAH lesions present as red, yellow to brown papules and plaques. Different dermoscopic patterns have been described which include the popcorn pattern that presents as yellow, confluent nodules with popcornlike shapes over a background of erythema, and linear arborizing vessels. The spitzoid pattern are brown globules on a background of erythema and pseudoreticular pigmentation around the globules. The verrucous hemangiomalike pattern has a bluish-white hue, reddish-blue or bluish lacunae, as seen in our patient.^2-4

Most of the lesions are asymptomatic, but in some patients, they can be associated with pain, hyperhidrosis, and sometimes bleeding. Hyperhidrosis has been reported early in the presentation or during puberty or pregnancy. Our patient had started on amphetamines when hyperhidrosis occurred. Hyperhidrosis is a knowns side effect of this type of medication and may have had a role in the increased sweating noted on the hamartoma.

EAH can clinically look like verrucous hemangiomas, angiokeratomas, and vascular malformations, and histopathology may be needed to differentiate between them. Eccrine nevi and EAH can be similar. Hyperhidrosis is an early and predominant component of eccrine nevi, compared with one-third of EAH.

The exact etiology of this lesion is not known. It is thought to be caused by an abnormal differentiation of the epithelium, adnexal structure, and the mesenchyme during organogenesis.³ No other associated conditions have been described with EAH.

EAH are benign lesions that rarely require treatment. If the lesions are symptomatic or because of cosmetic reasons, they can be removed surgically. There are some reports of successful treatment with pulse dual-wavelength sequential 595- and 1064-nm lasers.⁵ Botulinum toxin has also been used in cases of symptomatic hyperhidrosis.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She has no conflicts. Email her at [email protected].

References

1. Smith SD et al. Pediatr Dermatol. 2019 Nov;36(6):909-12.

2. Patterson AT et al. Am J Dermatopathol. 2016;38:413-7.

3. Garcıa-Garcıa SC et al. JAAD Case Rep. 2018;4(2):165-7.

4. Awatef Kelati et al. JAAD Case Rep. 2018;4(8)835-6.

5. Felgueiras J et al. Dermatol Surg. 2015 Mar;41(3):428-30.

A biopsy of the lesion was performed which showed an increased number of eccrine glands and blood vessels within the dermis. Some areas showed an increase in adipocytes and smooth muscle bundles. The changes were consistent with eccrine angiomatous hamartoma (EAH).

The boy was referred to vascular laser therapy for treatment of the lesion.

EAH is a rare benign vascular growth characterized by an increased number of mature eccrine glands and blood vessels in the dermis and subcutis. The lesions are mostly present on the extremities, but cases of diffuse congenital lesions and lesions on the face and trunk have also been described. The lesions can be seen at birth or during the first years of life in about half of the cases, and the others tend to occur later in puberty and rarely in adulthood^.1

Clinically, EAH lesions present as red, yellow to brown papules and plaques. Different dermoscopic patterns have been described which include the popcorn pattern that presents as yellow, confluent nodules with popcornlike shapes over a background of erythema, and linear arborizing vessels. The spitzoid pattern are brown globules on a background of erythema and pseudoreticular pigmentation around the globules. The verrucous hemangiomalike pattern has a bluish-white hue, reddish-blue or bluish lacunae, as seen in our patient.^2-4

Most of the lesions are asymptomatic, but in some patients, they can be associated with pain, hyperhidrosis, and sometimes bleeding. Hyperhidrosis has been reported early in the presentation or during puberty or pregnancy. Our patient had started on amphetamines when hyperhidrosis occurred. Hyperhidrosis is a knowns side effect of this type of medication and may have had a role in the increased sweating noted on the hamartoma.

EAH can clinically look like verrucous hemangiomas, angiokeratomas, and vascular malformations, and histopathology may be needed to differentiate between them. Eccrine nevi and EAH can be similar. Hyperhidrosis is an early and predominant component of eccrine nevi, compared with one-third of EAH.

The exact etiology of this lesion is not known. It is thought to be caused by an abnormal differentiation of the epithelium, adnexal structure, and the mesenchyme during organogenesis.³ No other associated conditions have been described with EAH.

EAH are benign lesions that rarely require treatment. If the lesions are symptomatic or because of cosmetic reasons, they can be removed surgically. There are some reports of successful treatment with pulse dual-wavelength sequential 595- and 1064-nm lasers.⁵ Botulinum toxin has also been used in cases of symptomatic hyperhidrosis.
 

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She has no conflicts. Email her at [email protected].

References

1. Smith SD et al. Pediatr Dermatol. 2019 Nov;36(6):909-12.

2. Patterson AT et al. Am J Dermatopathol. 2016;38:413-7.

3. Garcıa-Garcıa SC et al. JAAD Case Rep. 2018;4(2):165-7.

4. Awatef Kelati et al. JAAD Case Rep. 2018;4(8)835-6.

5. Felgueiras J et al. Dermatol Surg. 2015 Mar;41(3):428-30.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

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

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

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

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

Juvenile xanthogranuloma (JXG) is a benign disorder presenting as firm, yellow-red skin papules or nodules, usually in infancy or early childhood. It derives its name based on its yellowish color and the histologic finding of lipid-filled histiocytes. In fact, it is a form of non-Langerhans’ cell histiocytosis. It most commonly presents on the head, neck, and trunk, but can arise anywhere on the body as demonstrated by this case. While often pink to reddish early on, the characteristic yellow or orange, brown appearance over time is common, occasionally with overlying telangiectasia, and ranging in size from 1 mm to 2 cm. While typically asymptomatic, it is possible for lesions to itch. JXG is usually self-limiting, and spontaneously resolves over several years. On dermoscopy (with polarized light), it has a characteristic “setting sun” appearance because of its central yellow area surrounded by a reddish periphery.

David Schairer, MD

JXGs have been associated with neurofibromatosis-1 and a “triple association” of NF-1, JXG, and juvenile myelomonocytic leukemia (JMML) has been debated. Many cases are diagnosed on clinical grounds without histologic confirmation, so while the absolute incidence is unknown, they are not uncommon.
 

What is on the differential?

Spitz nevus is a melanocytic lesion which typically presents as a sharply circumscribed, dome-shaped, pink-red or brown papule or nodule, and is composed of large epithelioid and/or spindled cells. These nevi can present with a spectrum of morphology and biologic activity; commonly with benign melanocytic proliferations and a symmetric appearance or, rarely, with atypical tumors or lesions, characterized as Spitzoid melanomas. The yellowish color of JXG is distinct from the appearance of Spitz tumors.

Molluscum contagiosum is a common pox viral infection seen in children that presents with round, flat-topped firm papules on the skin and distinctive whitish centers with or without umbilication. Like JXG, molluscum contagiosum papules may grow over time and cause pruritus. However, this diagnosis is less likely given the absence of other lesions on the skin, lack of known contacts with similar lesions, and yellowish color without a more typical appearance of molluscum.

Dermatofibromas occur in people of all ages, although more commonly between the ages of 20 and 40 and in those with a history of trauma at the lesion. Like JXGs, dermatofibromas tend to be firm, solitary papules or nodules. They usually are hyperpigmented, and classically “dimple when pinched” as they are fixed to the subcutaneous tissue. However, this patient’s age, lack of trauma, and the lesion morphology are not consistent with dermatofibromas.

Like XJGs, mastocytomas commonly present in the first 2 years of life with maculopapular or nodular lesions that itch. However, the history of new-onset itch in recent months as the lesion grew larger and the yellow color on dermoscopy are more consistent with JXG.

Eruptive xanthomas typically appear suddenly as multiple erythematous yellow, dome-shaped papules on the extensor surfaces of the extremities, buttocks, and hands. They are usually present with hypertriglyceridemia and are very rare in young children. The presence of a solitary lesion in a 6-month-old patient without a history of lipid abnormalities favors the diagnosis of XJG.
 

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

References

Hernandez-Martin A et al. J Am Acad Dermatol. 1997 Mar;36(3 Pt 1):355-67.

Prendiville J. Lumps, bumps and hamartomas in “Neonatal and Infant Dermatology,” 3rd ed. (Philadelphia: Elsevier, 2015).

Püttgen KB. Juvenile xanthogranuloma. UpToDate, 2021.

Schaffer JV. Am J Clin Dermatol. 2021 Mar;22(2):205-20.

The Diagnosis: Microcystic Lymphatic Malformation 

The shave biopsy demonstrated numerous thin-walled vascular spaces filled with lymphatic fluid within the dermis (Figure), consistent with a diagnosis of microcystic lymphatic malformation (LM). Lymphatic malformations represent a class of benign vascular lesions consisting of anomalous or dilated lymphatic vessels, which can be broadly categorized as macrocystic (formerly cavernous lymphangioma or cystic hygroma), microcystic (formerly lymphangioma circumscriptum), or mixed.¹ Patients often will present with pruritus, crusting, secondary infection, edema, or oozing.² The superficial blebs of microcystic LMs resemble frog spawn and range in color from clear to pink, brawny, or deep maroon.³ Although the lymphatic vessels involved in microcystic LMs appear disconnected from the major lymphatic circulation,³ systemic fluid overload could plausibly promote lesional swelling and tenderness; we attributed our patient's worsening symptoms to the cumulative ^7.8 L of intravenous fluid he received intraoperatively during his cardiac transplant. The excess fluid allowed communication between lymphatic cisterns and thin-walled vesicles on the skin surface through dilated channels. Overall, LMs represent roughly 26% of pediatric benign vascular tumors and approximately 4% of all vascular tumors.⁴  

Although microcystic LMs may appear especially vascular or verrucous, the differential diagnosis for our patient's LM included condyloma acuminatum,^5,6 condyloma lata,⁷ epidermal nevus, and lymphangiosarcoma. Epidermal nevi are congenital lesions, varying in appearance from velvety to verrucous patches and plaques that often evolve during puberty and become thicker, more verrucous, and hyperpigmented. Keratinocytic epidermal nevus syndromes and other entities such as nevus sebaceous have been associated with somatic mutations affecting proteins in the fibroblast growth factor receptor signaling pathway (eg, FGFR3, HRAS).⁸ Although the clinical appearance alone may be similar, lymphangiosarcoma can be distinguished from LM via biopsy.  

There are several methods to diagnose LM. Duplex sonography is possibly the best noninvasive method to identify the flow between venous valves. Magnetic resonance imaging can detect larger occurrences of LM, and lymphangiography can be utilized to confirm a normal or abnormal lymphatic network.⁴ Treatment options are broad, including surgical excision, laser ablation, and topical sirolimus. Hypertonic saline sclerotherapy can be injected into the afflicted lymphatic channels to decrease inflammation, erythema, and hyperpigmentation without further treatment or major side effects.⁴

However, the benefits of sclerotherapy alone in the treatment of LM often come gradually, and radiofrequency ablation may need to be utilized to achieve more immediate results.² Overall, outcomes are highly variable, but favorable outcomes often can be difficult to obtain due to a high recurrence rate.^2,8 Our patient's symptoms improved during his postoperative recovery, and he declined further intervention.  

The Diagnosis: Microcystic Lymphatic Malformation 

The shave biopsy demonstrated numerous thin-walled vascular spaces filled with lymphatic fluid within the dermis (Figure), consistent with a diagnosis of microcystic lymphatic malformation (LM). Lymphatic malformations represent a class of benign vascular lesions consisting of anomalous or dilated lymphatic vessels, which can be broadly categorized as macrocystic (formerly cavernous lymphangioma or cystic hygroma), microcystic (formerly lymphangioma circumscriptum), or mixed.¹ Patients often will present with pruritus, crusting, secondary infection, edema, or oozing.² The superficial blebs of microcystic LMs resemble frog spawn and range in color from clear to pink, brawny, or deep maroon.³ Although the lymphatic vessels involved in microcystic LMs appear disconnected from the major lymphatic circulation,³ systemic fluid overload could plausibly promote lesional swelling and tenderness; we attributed our patient's worsening symptoms to the cumulative ^7.8 L of intravenous fluid he received intraoperatively during his cardiac transplant. The excess fluid allowed communication between lymphatic cisterns and thin-walled vesicles on the skin surface through dilated channels. Overall, LMs represent roughly 26% of pediatric benign vascular tumors and approximately 4% of all vascular tumors.⁴  

Although microcystic LMs may appear especially vascular or verrucous, the differential diagnosis for our patient's LM included condyloma acuminatum,^5,6 condyloma lata,⁷ epidermal nevus, and lymphangiosarcoma. Epidermal nevi are congenital lesions, varying in appearance from velvety to verrucous patches and plaques that often evolve during puberty and become thicker, more verrucous, and hyperpigmented. Keratinocytic epidermal nevus syndromes and other entities such as nevus sebaceous have been associated with somatic mutations affecting proteins in the fibroblast growth factor receptor signaling pathway (eg, FGFR3, HRAS).⁸ Although the clinical appearance alone may be similar, lymphangiosarcoma can be distinguished from LM via biopsy.  

There are several methods to diagnose LM. Duplex sonography is possibly the best noninvasive method to identify the flow between venous valves. Magnetic resonance imaging can detect larger occurrences of LM, and lymphangiography can be utilized to confirm a normal or abnormal lymphatic network.⁴ Treatment options are broad, including surgical excision, laser ablation, and topical sirolimus. Hypertonic saline sclerotherapy can be injected into the afflicted lymphatic channels to decrease inflammation, erythema, and hyperpigmentation without further treatment or major side effects.⁴

However, the benefits of sclerotherapy alone in the treatment of LM often come gradually, and radiofrequency ablation may need to be utilized to achieve more immediate results.² Overall, outcomes are highly variable, but favorable outcomes often can be difficult to obtain due to a high recurrence rate.^2,8 Our patient's symptoms improved during his postoperative recovery, and he declined further intervention.  

The Diagnosis: Microcystic Lymphatic Malformation 

The shave biopsy demonstrated numerous thin-walled vascular spaces filled with lymphatic fluid within the dermis (Figure), consistent with a diagnosis of microcystic lymphatic malformation (LM). Lymphatic malformations represent a class of benign vascular lesions consisting of anomalous or dilated lymphatic vessels, which can be broadly categorized as macrocystic (formerly cavernous lymphangioma or cystic hygroma), microcystic (formerly lymphangioma circumscriptum), or mixed.¹ Patients often will present with pruritus, crusting, secondary infection, edema, or oozing.² The superficial blebs of microcystic LMs resemble frog spawn and range in color from clear to pink, brawny, or deep maroon.³ Although the lymphatic vessels involved in microcystic LMs appear disconnected from the major lymphatic circulation,³ systemic fluid overload could plausibly promote lesional swelling and tenderness; we attributed our patient's worsening symptoms to the cumulative ^7.8 L of intravenous fluid he received intraoperatively during his cardiac transplant. The excess fluid allowed communication between lymphatic cisterns and thin-walled vesicles on the skin surface through dilated channels. Overall, LMs represent roughly 26% of pediatric benign vascular tumors and approximately 4% of all vascular tumors.⁴  

Although microcystic LMs may appear especially vascular or verrucous, the differential diagnosis for our patient's LM included condyloma acuminatum,^5,6 condyloma lata,⁷ epidermal nevus, and lymphangiosarcoma. Epidermal nevi are congenital lesions, varying in appearance from velvety to verrucous patches and plaques that often evolve during puberty and become thicker, more verrucous, and hyperpigmented. Keratinocytic epidermal nevus syndromes and other entities such as nevus sebaceous have been associated with somatic mutations affecting proteins in the fibroblast growth factor receptor signaling pathway (eg, FGFR3, HRAS).⁸ Although the clinical appearance alone may be similar, lymphangiosarcoma can be distinguished from LM via biopsy.  

There are several methods to diagnose LM. Duplex sonography is possibly the best noninvasive method to identify the flow between venous valves. Magnetic resonance imaging can detect larger occurrences of LM, and lymphangiography can be utilized to confirm a normal or abnormal lymphatic network.⁴ Treatment options are broad, including surgical excision, laser ablation, and topical sirolimus. Hypertonic saline sclerotherapy can be injected into the afflicted lymphatic channels to decrease inflammation, erythema, and hyperpigmentation without further treatment or major side effects.⁴

However, the benefits of sclerotherapy alone in the treatment of LM often come gradually, and radiofrequency ablation may need to be utilized to achieve more immediate results.² Overall, outcomes are highly variable, but favorable outcomes often can be difficult to obtain due to a high recurrence rate.^2,8 Our patient's symptoms improved during his postoperative recovery, and he declined further intervention.  

After the teledermatology consultation, an x-ray was recommended. The x-ray showed an elongated irregular radiopaque mass projecting from the anterior medial aspect of the midshaft of the distal phalanx of the great toe (Picture 3). With these findings, subungual exostosis was suspected, and she was referred to orthopedic surgery for excision of the lesion. Histopathology showed a stack of trabecular bone with a fibrocartilaginous cap, confirming the diagnosis of subungual exostosis.

Courtesy Dr. Puong To, Southern California Medical Group

Subungual exostosis is a benign osteocartilaginous tumor, first described by Dupuytren in 1874. These lesions are rare and are seen mainly in children and young adults. Females appear to be affected more often than males.¹ In a systematic review by DaCambra and colleagues, 55% of the cases occur in patients aged younger than 18 years, and the hallux was the most commonly affected digit, though any finger or toe can be affected.² There are reported case of congenital multiple exostosis delineated to translocation t(X;6)(q22;q13-14).³

The exact cause of these lesions is unknown, but there are multiple theories, which include a reactive process secondary to trauma, infection, or genetic causes. Pathologic examination of the lesions shows an osseous center covered by a fibrocartilaginous cap. There is proliferation of spindle cells that generate cartilage, which later forms trabecular bone.⁴

On physical examination, subungual exostosis appear like a firm, fixed nodule with a hyperkeratotic smooth surface at the distal end of the nail bed, that slowly grows and can distort and lift up the nail. Dermoscopy features of these lesions include vascular ectasia, hyperkeratosis, onycholysis, and ulceration.

The differential diagnosis of subungual growths includes osteochondromas, which can present in a similar way but are rarer. Pathologic examination is usually required to differentiate between both lesions.⁵ In exostoses, bone is formed directly from fibrous tissue, whereas in osteochondromas they derive from enchondral ossification.⁶ The cartilaginous cap of this lesion is what helps to differentiate it in histopathology. In subungual exostosis, the cap is composed of fibrocartilage, while in osteochondromas it is made of hyaline cartilage similar to what is seen in normal growing epiphysis.⁵ Subungual exostosis can be confused with pyogenic granulomas and verruca, and often are treated as such, which delays appropriate surgical management.

Firm, slow-growing tumors in the fingers or toes of children should raise suspicion for underlying bony lesions like subungual exostosis and osteochondromas. X-rays of the lesion should be performed in order to clarify the diagnosis. Referral to orthopedic surgery is needed for definitive surgical management.

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

References

1. Zhang W et al. JAAD Case Rep. 2020 Jun 1;6(8):725-6.

2. DaCambra MP et al. Clin Orthop Relat Res. 2014 Apr;472(4):1251-9.

3. Torlazzi C et al. Int J Cancer. 2006;118:1972-6.

4. Calonje E et al. McKee’s pathology of the skin: With clinical correlations. (4th ed.) Philadelphia: Elsevier/Saunders, 2012.

5. Lee SK et al. Foot Ankle Int. 2007 May;28(5):595-601.

6. Mavrogenis A et al. Orthopedics. 2008 Oct;31(10).

After the teledermatology consultation, an x-ray was recommended. The x-ray showed an elongated irregular radiopaque mass projecting from the anterior medial aspect of the midshaft of the distal phalanx of the great toe (Picture 3). With these findings, subungual exostosis was suspected, and she was referred to orthopedic surgery for excision of the lesion. Histopathology showed a stack of trabecular bone with a fibrocartilaginous cap, confirming the diagnosis of subungual exostosis.

Courtesy Dr. Puong To, Southern California Medical Group

Subungual exostosis is a benign osteocartilaginous tumor, first described by Dupuytren in 1874. These lesions are rare and are seen mainly in children and young adults. Females appear to be affected more often than males.¹ In a systematic review by DaCambra and colleagues, 55% of the cases occur in patients aged younger than 18 years, and the hallux was the most commonly affected digit, though any finger or toe can be affected.² There are reported case of congenital multiple exostosis delineated to translocation t(X;6)(q22;q13-14).³

The exact cause of these lesions is unknown, but there are multiple theories, which include a reactive process secondary to trauma, infection, or genetic causes. Pathologic examination of the lesions shows an osseous center covered by a fibrocartilaginous cap. There is proliferation of spindle cells that generate cartilage, which later forms trabecular bone.⁴

On physical examination, subungual exostosis appear like a firm, fixed nodule with a hyperkeratotic smooth surface at the distal end of the nail bed, that slowly grows and can distort and lift up the nail. Dermoscopy features of these lesions include vascular ectasia, hyperkeratosis, onycholysis, and ulceration.

The differential diagnosis of subungual growths includes osteochondromas, which can present in a similar way but are rarer. Pathologic examination is usually required to differentiate between both lesions.⁵ In exostoses, bone is formed directly from fibrous tissue, whereas in osteochondromas they derive from enchondral ossification.⁶ The cartilaginous cap of this lesion is what helps to differentiate it in histopathology. In subungual exostosis, the cap is composed of fibrocartilage, while in osteochondromas it is made of hyaline cartilage similar to what is seen in normal growing epiphysis.⁵ Subungual exostosis can be confused with pyogenic granulomas and verruca, and often are treated as such, which delays appropriate surgical management.

Firm, slow-growing tumors in the fingers or toes of children should raise suspicion for underlying bony lesions like subungual exostosis and osteochondromas. X-rays of the lesion should be performed in order to clarify the diagnosis. Referral to orthopedic surgery is needed for definitive surgical management.

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

References

1. Zhang W et al. JAAD Case Rep. 2020 Jun 1;6(8):725-6.

2. DaCambra MP et al. Clin Orthop Relat Res. 2014 Apr;472(4):1251-9.

3. Torlazzi C et al. Int J Cancer. 2006;118:1972-6.

4. Calonje E et al. McKee’s pathology of the skin: With clinical correlations. (4th ed.) Philadelphia: Elsevier/Saunders, 2012.

5. Lee SK et al. Foot Ankle Int. 2007 May;28(5):595-601.

6. Mavrogenis A et al. Orthopedics. 2008 Oct;31(10).

After the teledermatology consultation, an x-ray was recommended. The x-ray showed an elongated irregular radiopaque mass projecting from the anterior medial aspect of the midshaft of the distal phalanx of the great toe (Picture 3). With these findings, subungual exostosis was suspected, and she was referred to orthopedic surgery for excision of the lesion. Histopathology showed a stack of trabecular bone with a fibrocartilaginous cap, confirming the diagnosis of subungual exostosis.

Courtesy Dr. Puong To, Southern California Medical Group

Subungual exostosis is a benign osteocartilaginous tumor, first described by Dupuytren in 1874. These lesions are rare and are seen mainly in children and young adults. Females appear to be affected more often than males.¹ In a systematic review by DaCambra and colleagues, 55% of the cases occur in patients aged younger than 18 years, and the hallux was the most commonly affected digit, though any finger or toe can be affected.² There are reported case of congenital multiple exostosis delineated to translocation t(X;6)(q22;q13-14).³

The exact cause of these lesions is unknown, but there are multiple theories, which include a reactive process secondary to trauma, infection, or genetic causes. Pathologic examination of the lesions shows an osseous center covered by a fibrocartilaginous cap. There is proliferation of spindle cells that generate cartilage, which later forms trabecular bone.⁴

On physical examination, subungual exostosis appear like a firm, fixed nodule with a hyperkeratotic smooth surface at the distal end of the nail bed, that slowly grows and can distort and lift up the nail. Dermoscopy features of these lesions include vascular ectasia, hyperkeratosis, onycholysis, and ulceration.

The differential diagnosis of subungual growths includes osteochondromas, which can present in a similar way but are rarer. Pathologic examination is usually required to differentiate between both lesions.⁵ In exostoses, bone is formed directly from fibrous tissue, whereas in osteochondromas they derive from enchondral ossification.⁶ The cartilaginous cap of this lesion is what helps to differentiate it in histopathology. In subungual exostosis, the cap is composed of fibrocartilage, while in osteochondromas it is made of hyaline cartilage similar to what is seen in normal growing epiphysis.⁵ Subungual exostosis can be confused with pyogenic granulomas and verruca, and often are treated as such, which delays appropriate surgical management.

Firm, slow-growing tumors in the fingers or toes of children should raise suspicion for underlying bony lesions like subungual exostosis and osteochondromas. X-rays of the lesion should be performed in order to clarify the diagnosis. Referral to orthopedic surgery is needed for definitive surgical management.

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

References

1. Zhang W et al. JAAD Case Rep. 2020 Jun 1;6(8):725-6.

2. DaCambra MP et al. Clin Orthop Relat Res. 2014 Apr;472(4):1251-9.

3. Torlazzi C et al. Int J Cancer. 2006;118:1972-6.

4. Calonje E et al. McKee’s pathology of the skin: With clinical correlations. (4th ed.) Philadelphia: Elsevier/Saunders, 2012.

5. Lee SK et al. Foot Ankle Int. 2007 May;28(5):595-601.

6. Mavrogenis A et al. Orthopedics. 2008 Oct;31(10).

A potassium hydroxide preparation (KOH) from skin scrapings from the scalp lesions demonstrated no fungal elements. Further laboratory work up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti–Sjögren’s syndrome type B (SSB) antibody but negative anti–Sjögren’s syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Liver function tests were normal. The complete blood count showed mild thrombocytopenia. Given the typical skin lesions and the positive SSB test and associated thrombocytopenia, the baby was diagnosed with neonatal lupus erythematosus.

Because of the diagnosis of neonatal lupus the mother was also tested and was found to have an elevated ANA of 1:640, positive SSB and antiphospholipid antibodies. The mother was healthy and her review of systems was negative for any collagen vascular disease–related symptoms.
 

Discussion

Neonatal lupus erythematosus (NLE) is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjögren’s syndrome antigen A, SSA), or, less commonly, anti-La (Sjögren’s syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these cases, 40% are also associated with maternal anti-SSB.¹ Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or SSB positive mothers develop NLE.

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age.³ Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate,³ though many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, though NLE has been rarely reported in the offspring of mothers with Sjögren’s syndrome, rheumatoid arthritis, and psoriasis.^4,5

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. However, certain genetic relationships have been established. Fetal mutations in tumor necrosis factor–alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations taken together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block.⁶

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to the sun. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale (“raccoon eyes”) should prompt consideration of NLE. However, annular, or discoid lesions are sometimes not present in NLE; telangiectasias, bullae, atrophic divots (“ice-pick scars”) or ulcerations may be seen instead. Lesions in the genital area have been described in fewer than 5% of patients with NLE.

The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and seborrheic dermatitis. Annular erythema of infancy is a rare skin condition characterized by a cyclical eruption of erythematous annular lesions with minimal scaling which resolve spontaneously within a few weeks to months without leaving scaring or pigment changes. There is no treatment needed as the lesions self-resolve.⁷ Acute urticaria can sometimes appear similar to NLE but these are not scaly and also the lesions will disappear within 24-36 hours, compared with NLE lesions, which may take weeks to months to go away. Seborrheic dermatitis is a common skin condition seen in newborns with in the first few weeks of life and can present as scaly annular erythematous plaques on the face, scalp, torso, and the diaper area. Seborrheic dermatitis usually responds well to a combination of an antiyeast cream and a low-potency topical corticosteroid medication.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis. Neonates with cutaneous manifestations of lupus may also have systemic disease. The most common and serious complication is heart block, whose pathophysiology is described above. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported, but is usually mild. Hematologic abnormalities have also been described that include anemia, neutropenia, and thrombocytopenia, which resolve by 9 months of age. Central nervous system involvement may rarely occur. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used, but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE – the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications,⁸ as can the so-called “triple therapy” of plasmapheresis, steroids, and IVIg.⁹

The cutaneous manifestations of NLE are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.

Dr. Matiz is with the department of dermatology, Southern California Permanente Medical Group, San Diego. Mr. Kusari is with the department of dermatology, University of California, San Francisco.

References

1. Moretti D et al. Int J Dermatol. 2014;53(12):1508-12.

2. Buyon JP et al. Nature Clin Prac Rheum. 2009;5(3):139-48.

3. Li Y-Q et al. Int J Rheum Dis. 2015;18(7):761-7.

4. Rivera TL et al. Annals Rheum Dis. 2009;68(6):828-35.

5. Li L et al. Zhonghua er ke za zhi 2011;49(2):146-50.

6. Izmirly PM et al. Clin Rheumatol. 2011;30(12):1641-5.

7. Toledo-Alberola F and Betlloch-Mas I. Actas Dermosifiliogr. 2010 Jul;101(6):473-84.

8. Izmirly PM et al. Circulation. 2012;126(1):76-82.

9. Martinez-Sanchez N et al. Autoimmun Rev. 2015;14(5):423-8.

A potassium hydroxide preparation (KOH) from skin scrapings from the scalp lesions demonstrated no fungal elements. Further laboratory work up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti–Sjögren’s syndrome type B (SSB) antibody but negative anti–Sjögren’s syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Liver function tests were normal. The complete blood count showed mild thrombocytopenia. Given the typical skin lesions and the positive SSB test and associated thrombocytopenia, the baby was diagnosed with neonatal lupus erythematosus.

Because of the diagnosis of neonatal lupus the mother was also tested and was found to have an elevated ANA of 1:640, positive SSB and antiphospholipid antibodies. The mother was healthy and her review of systems was negative for any collagen vascular disease–related symptoms.
 

Discussion

Neonatal lupus erythematosus (NLE) is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjögren’s syndrome antigen A, SSA), or, less commonly, anti-La (Sjögren’s syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these cases, 40% are also associated with maternal anti-SSB.¹ Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or SSB positive mothers develop NLE.

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age.³ Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate,³ though many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, though NLE has been rarely reported in the offspring of mothers with Sjögren’s syndrome, rheumatoid arthritis, and psoriasis.^4,5

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. However, certain genetic relationships have been established. Fetal mutations in tumor necrosis factor–alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations taken together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block.⁶

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to the sun. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale (“raccoon eyes”) should prompt consideration of NLE. However, annular, or discoid lesions are sometimes not present in NLE; telangiectasias, bullae, atrophic divots (“ice-pick scars”) or ulcerations may be seen instead. Lesions in the genital area have been described in fewer than 5% of patients with NLE.

The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and seborrheic dermatitis. Annular erythema of infancy is a rare skin condition characterized by a cyclical eruption of erythematous annular lesions with minimal scaling which resolve spontaneously within a few weeks to months without leaving scaring or pigment changes. There is no treatment needed as the lesions self-resolve.⁷ Acute urticaria can sometimes appear similar to NLE but these are not scaly and also the lesions will disappear within 24-36 hours, compared with NLE lesions, which may take weeks to months to go away. Seborrheic dermatitis is a common skin condition seen in newborns with in the first few weeks of life and can present as scaly annular erythematous plaques on the face, scalp, torso, and the diaper area. Seborrheic dermatitis usually responds well to a combination of an antiyeast cream and a low-potency topical corticosteroid medication.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis. Neonates with cutaneous manifestations of lupus may also have systemic disease. The most common and serious complication is heart block, whose pathophysiology is described above. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported, but is usually mild. Hematologic abnormalities have also been described that include anemia, neutropenia, and thrombocytopenia, which resolve by 9 months of age. Central nervous system involvement may rarely occur. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used, but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE – the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications,⁸ as can the so-called “triple therapy” of plasmapheresis, steroids, and IVIg.⁹

The cutaneous manifestations of NLE are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.

Dr. Matiz is with the department of dermatology, Southern California Permanente Medical Group, San Diego. Mr. Kusari is with the department of dermatology, University of California, San Francisco.

References

1. Moretti D et al. Int J Dermatol. 2014;53(12):1508-12.

2. Buyon JP et al. Nature Clin Prac Rheum. 2009;5(3):139-48.

3. Li Y-Q et al. Int J Rheum Dis. 2015;18(7):761-7.

4. Rivera TL et al. Annals Rheum Dis. 2009;68(6):828-35.

5. Li L et al. Zhonghua er ke za zhi 2011;49(2):146-50.

6. Izmirly PM et al. Clin Rheumatol. 2011;30(12):1641-5.

7. Toledo-Alberola F and Betlloch-Mas I. Actas Dermosifiliogr. 2010 Jul;101(6):473-84.

8. Izmirly PM et al. Circulation. 2012;126(1):76-82.

9. Martinez-Sanchez N et al. Autoimmun Rev. 2015;14(5):423-8.

A potassium hydroxide preparation (KOH) from skin scrapings from the scalp lesions demonstrated no fungal elements. Further laboratory work up revealed a normal blood cell count, normal liver enzymes, an antinuclear antibody (ANA) titer of less than 1:80, a positive anti–Sjögren’s syndrome type B (SSB) antibody but negative anti–Sjögren’s syndrome type A (SSA) antibody and anti-U1RNP antibody. An electrocardiogram revealed no abnormalities. Liver function tests were normal. The complete blood count showed mild thrombocytopenia. Given the typical skin lesions and the positive SSB test and associated thrombocytopenia, the baby was diagnosed with neonatal lupus erythematosus.

Because of the diagnosis of neonatal lupus the mother was also tested and was found to have an elevated ANA of 1:640, positive SSB and antiphospholipid antibodies. The mother was healthy and her review of systems was negative for any collagen vascular disease–related symptoms.
 

Discussion

Neonatal lupus erythematosus (NLE) is a rare form of systemic lupus erythematosus (SLE) believed to be caused by transplacental transfer of anti-Ro (Sjögren’s syndrome antigen A, SSA), or, less commonly, anti-La (Sjögren’s syndrome antigen B, SSB) from mothers who are positive for these antibodies. Approximately 95% of NLE is associated with maternal anti-SSA; of these cases, 40% are also associated with maternal anti-SSB.¹ Only about 2% of children of mothers who have anti-SSA or anti-SSB develop NLE, a finding that has led some researchers to postulate that maternal factors, fetal genetic factors, and environmental factors determine which children of anti-SSA or SSB positive mothers develop NLE.

A recent review found no association between the development of NLE and fetal birth weight, prematurity, or age.³ Over half of mothers of children who develop NLE are asymptomatic at the time of diagnosis of the neonate,³ though many become symptomatic in following years. Of mothers who are symptomatic, SLE and undifferentiated autoimmune syndrome are the most common diagnoses, though NLE has been rarely reported in the offspring of mothers with Sjögren’s syndrome, rheumatoid arthritis, and psoriasis.^4,5

Fetal genetics are not an absolute determinant of development of NLE, as discordance in the development of NLE in twins has been reported. However, certain genetic relationships have been established. Fetal mutations in tumor necrosis factor–alpha appear to increase the likelihood of cutaneous manifestations. Mutations in transforming growth factor beta appear to increase the likelihood of cardiac manifestations, and experiments in cultured mouse cardiocytes have shown anti-SSB antibodies to impair macrophage phagocytosis of apoptotic cells in the developing fetal heart. These observations taken together suggest a fibroblast-mediated response to unphagocytosed cardiocyte debris may account for conduction abnormalities in neonates with NLE-induced heart block.⁶

Cutaneous disease in NLE is possible at birth, but more skin findings develop upon exposure to the sun. Nearly 80% of neonates affected by NLE develop cutaneous manifestations in the first few months of life. The head, neck, and extensor surfaces of the arms are most commonly affected, presumably because they are most likely to be exposed to the sun. Erythematous, annular, or discoid lesions are most common, and periorbital erythema with or without scale (“raccoon eyes”) should prompt consideration of NLE. However, annular, or discoid lesions are sometimes not present in NLE; telangiectasias, bullae, atrophic divots (“ice-pick scars”) or ulcerations may be seen instead. Lesions in the genital area have been described in fewer than 5% of patients with NLE.

The differential diagnosis of annular, scaly lesions in neonates includes annular erythema of infancy, tinea corporis, and seborrheic dermatitis. Annular erythema of infancy is a rare skin condition characterized by a cyclical eruption of erythematous annular lesions with minimal scaling which resolve spontaneously within a few weeks to months without leaving scaring or pigment changes. There is no treatment needed as the lesions self-resolve.⁷ Acute urticaria can sometimes appear similar to NLE but these are not scaly and also the lesions will disappear within 24-36 hours, compared with NLE lesions, which may take weeks to months to go away. Seborrheic dermatitis is a common skin condition seen in newborns with in the first few weeks of life and can present as scaly annular erythematous plaques on the face, scalp, torso, and the diaper area. Seborrheic dermatitis usually responds well to a combination of an antiyeast cream and a low-potency topical corticosteroid medication.

When NLE is suspected, diagnostic testing for lupus antibodies (anti-SSA, anti-SSB, and anti-U1RNP) in both maternal and neonatal serum should be undertaken. The presence of a characteristic rash plus maternal or neonatal antibodies is sufficient to make the diagnosis. If the rash is less characteristic, a biopsy showing an interface dermatitis can help solidify the diagnosis. Neonates with cutaneous manifestations of lupus may also have systemic disease. The most common and serious complication is heart block, whose pathophysiology is described above. Neonates with evidence of first-, second-, or third-degree heart block should be referred to a pediatric cardiologist for careful monitoring and management. Hepatic involvement has been reported, but is usually mild. Hematologic abnormalities have also been described that include anemia, neutropenia, and thrombocytopenia, which resolve by 9 months of age. Central nervous system involvement may rarely occur. The mainstay of treatment for the rash in NLE is diligent sun avoidance and sun protection. Topical corticosteroids may be used, but are not needed as the rash typically resolves by 9 months to 1 year without treatment. Mothers who have one child with NLE should be advised that they are more likely to have another with NLE – the risk is as high as 30%-40% in the second child. Hydroxychloroquine taken during subsequent pregnancies can reduce the incidence of cardiac complications,⁸ as can the so-called “triple therapy” of plasmapheresis, steroids, and IVIg.⁹

The cutaneous manifestations of NLE are usually self-limiting. However, they can serve as important clues that can prompt diagnosis of SLE in the mother, investigation of cardiac complications in the infant, and appropriate preventative care in future pregnancies.

Dr. Matiz is with the department of dermatology, Southern California Permanente Medical Group, San Diego. Mr. Kusari is with the department of dermatology, University of California, San Francisco.

References

1. Moretti D et al. Int J Dermatol. 2014;53(12):1508-12.

2. Buyon JP et al. Nature Clin Prac Rheum. 2009;5(3):139-48.

3. Li Y-Q et al. Int J Rheum Dis. 2015;18(7):761-7.

4. Rivera TL et al. Annals Rheum Dis. 2009;68(6):828-35.

5. Li L et al. Zhonghua er ke za zhi 2011;49(2):146-50.

6. Izmirly PM et al. Clin Rheumatol. 2011;30(12):1641-5.

7. Toledo-Alberola F and Betlloch-Mas I. Actas Dermosifiliogr. 2010 Jul;101(6):473-84.

8. Izmirly PM et al. Circulation. 2012;126(1):76-82.

9. Martinez-Sanchez N et al. Autoimmun Rev. 2015;14(5):423-8.

The Diagnosis: Trichodysplasia Spinulosa 

Trichodysplasia spinulosa has been described in case reports over the last several decades, with its causative virus trichodysplasia spinulosa-associated polyomavirus (TSPyV) identified in 2010 by van der Meijden et al.¹ Trichodysplasia spinulosa-associated polyomavirus is a small, nonenveloped, double-stranded DNA virus in the Polyomaviridae family, among several other known cutaneous polyomaviruses including Merkel cell polyomavirus, human polyomavirus (HPyV) 6, HPyV7, HPyV10, and possibly HPyV13.² The primary target of TSPyV is follicular keratinocytes, and it is believed to cause trichodysplasia spinulosa by primary infection rather than by reactivation. Trichodysplasia spinulosa presents in immunosuppressed patients as a folliculocentric eruption of papules with keratinous spines on the face, often with concurrent alopecia, eventually spreading to the trunk and extremities.³ The diagnosis often is clinical, but a biopsy may be performed for histopathologic confirmation. Alternatively, lesional spicules can be painlessly collected manually and submitted for viral polymerase chain reaction (PCR).⁴ The diagnosis of trichodysplasia spinulosa can be difficult due to similarities with other more common conditions such as keratosis pilaris, milia, filiform warts, or lichen spinulosus.  

Similar to trichodysplasia spinulosa, keratosis pilaris also presents with folliculocentric and often erythematous papules.⁵ Keratosis pilaris most frequently affects the posterior upper arms and thighs but also may affect the cheeks, as seen in trichodysplasia spinulosa. Differentiation between the 2 diagnoses can be made on a clinical basis, as keratosis pilaris lacks the characteristic keratinous spines and often spares the central face and nose, locations that commonly are affected in trichodysplasia spinulosa.³ 

Milia typically appear as white to yellow papules, often on the cheeks, eyelids, nose, and chin.⁶ Given their predilection for the face, milia can appear similarly to trichodysplasia spinulosa. Differentiation can be made clinically, as milia typically are not as numerous as the spiculed papules seen in trichodysplasia spinulosa. Morphologically, milia will present as smooth, dome-shaped papules as opposed to the keratinous spicules seen in trichodysplasia spinulosa. The diagnosis of milia can be confirmed by incision and removal of the white chalky keratin core, a feature absent in trichodysplasia spinulosa.  

Filiform warts are benign epidermal proliferations caused by human papillomavirus infection that manifest as flesh-colored, verrucous, hyperkeratotic papules.⁷ They can appear on virtually any skin surface, including the face, and thus may be mistaken for trichodysplasia spinulosa. Close inspection usually will reveal tiny black dots that represent thrombosed capillaries, a feature lacking in trichodysplasia spinulosa. In long-standing lesions or immunocompromised patients, confluent verrucous plaques may develop.⁸ Diagnosis of filiform warts can be confirmed with biopsy, which will demonstrate a compact stratum corneum, coarse hypergranulosis, and papillomatosis curving inward, while biopsy of a trichodysplasia spinulosa lesion would show polyomavirus infection of the hair follicle and characteristic eosinophilic inclusion bodies.⁹ 

Lichen spinulosus may appear as multiple folliculocentric scaly papules with hairlike horny spines.¹⁰ Lichen spinulosus differs from trichodysplasia spinulosa in that it commonly appears on the neck, abdomen, trochanteric region, arms, elbows, or knees. Lichen spinulosus also classically appears as a concrete cluster of papules, often localized to a certain region, in contrast to trichodysplasia spinulosa, which will be widespread, often spreading over time. Finally, clinical history may help differentiate the 2 entities. Lichen spinulosus most often appears in children and adolescents and often has an indolent course, typically resolving during puberty, while trichodysplasia spinulosa is seen in immunocompromised patients. 

In our patient, the dermatology team made a diagnosis of trichodysplasia spinulosa based on the characteristic clinical presentation, which was confirmed after approximately 10 lesional spicules were removed by tissue forceps and submitted for PCR analysis showing TSPyV (Figure). Two other cases utilized spicule PCR analysis for confirmation of TSPyV.^11,12 This technique may represent a viable option for diagnostic confirmation in pediatric cases. 

Although some articles have examined the molecular and biologic features of trichodysplasia spinulosa, literature on clinical presentation and management is limited to isolated case reports with no comprehensive studies to establish a standardized treatment. Of these reports, oral valganciclovir 900 mg daily, topical retinoids, cidofovir cream 1% to 3%, and decreasing or altering the immunosuppressive regimen all have been noted to provide clinical improvement.^13,14 Other therapies including leflunomide and routine manual extraction of spicules also have shown effectiveness in the treatment of trichodysplasia spinulosa.¹⁵  

In our patient, treatment included decreasing immunosuppression, as she was getting recurrent sinus and upper respiratory infections. Mycophenolate mofetil was discontinued, and the patient was continued solely on tacrolimus therapy. She demonstrated notable improvement after 3 months, with approximately 50% clearance of the eruption. A mutual decision was made at that visit to initiate therapy with compounded cidofovir cream 1% daily to the lesions until the next follow-up visit. Unfortunately, the patient did not return for her scheduled dermatology visits and was lost to long-term follow-up. 

Acknowledgment
We thank Richard C. Wang, MD, PhD (Dallas, Texas), for his dermatologic expertise and assistance in analysis of lesional samples for TSPyV. 

The Diagnosis: Trichodysplasia Spinulosa 

Trichodysplasia spinulosa has been described in case reports over the last several decades, with its causative virus trichodysplasia spinulosa-associated polyomavirus (TSPyV) identified in 2010 by van der Meijden et al.¹ Trichodysplasia spinulosa-associated polyomavirus is a small, nonenveloped, double-stranded DNA virus in the Polyomaviridae family, among several other known cutaneous polyomaviruses including Merkel cell polyomavirus, human polyomavirus (HPyV) 6, HPyV7, HPyV10, and possibly HPyV13.² The primary target of TSPyV is follicular keratinocytes, and it is believed to cause trichodysplasia spinulosa by primary infection rather than by reactivation. Trichodysplasia spinulosa presents in immunosuppressed patients as a folliculocentric eruption of papules with keratinous spines on the face, often with concurrent alopecia, eventually spreading to the trunk and extremities.³ The diagnosis often is clinical, but a biopsy may be performed for histopathologic confirmation. Alternatively, lesional spicules can be painlessly collected manually and submitted for viral polymerase chain reaction (PCR).⁴ The diagnosis of trichodysplasia spinulosa can be difficult due to similarities with other more common conditions such as keratosis pilaris, milia, filiform warts, or lichen spinulosus.  

Similar to trichodysplasia spinulosa, keratosis pilaris also presents with folliculocentric and often erythematous papules.⁵ Keratosis pilaris most frequently affects the posterior upper arms and thighs but also may affect the cheeks, as seen in trichodysplasia spinulosa. Differentiation between the 2 diagnoses can be made on a clinical basis, as keratosis pilaris lacks the characteristic keratinous spines and often spares the central face and nose, locations that commonly are affected in trichodysplasia spinulosa.³ 

Milia typically appear as white to yellow papules, often on the cheeks, eyelids, nose, and chin.⁶ Given their predilection for the face, milia can appear similarly to trichodysplasia spinulosa. Differentiation can be made clinically, as milia typically are not as numerous as the spiculed papules seen in trichodysplasia spinulosa. Morphologically, milia will present as smooth, dome-shaped papules as opposed to the keratinous spicules seen in trichodysplasia spinulosa. The diagnosis of milia can be confirmed by incision and removal of the white chalky keratin core, a feature absent in trichodysplasia spinulosa.  

Filiform warts are benign epidermal proliferations caused by human papillomavirus infection that manifest as flesh-colored, verrucous, hyperkeratotic papules.⁷ They can appear on virtually any skin surface, including the face, and thus may be mistaken for trichodysplasia spinulosa. Close inspection usually will reveal tiny black dots that represent thrombosed capillaries, a feature lacking in trichodysplasia spinulosa. In long-standing lesions or immunocompromised patients, confluent verrucous plaques may develop.⁸ Diagnosis of filiform warts can be confirmed with biopsy, which will demonstrate a compact stratum corneum, coarse hypergranulosis, and papillomatosis curving inward, while biopsy of a trichodysplasia spinulosa lesion would show polyomavirus infection of the hair follicle and characteristic eosinophilic inclusion bodies.⁹ 

Lichen spinulosus may appear as multiple folliculocentric scaly papules with hairlike horny spines.¹⁰ Lichen spinulosus differs from trichodysplasia spinulosa in that it commonly appears on the neck, abdomen, trochanteric region, arms, elbows, or knees. Lichen spinulosus also classically appears as a concrete cluster of papules, often localized to a certain region, in contrast to trichodysplasia spinulosa, which will be widespread, often spreading over time. Finally, clinical history may help differentiate the 2 entities. Lichen spinulosus most often appears in children and adolescents and often has an indolent course, typically resolving during puberty, while trichodysplasia spinulosa is seen in immunocompromised patients. 

In our patient, the dermatology team made a diagnosis of trichodysplasia spinulosa based on the characteristic clinical presentation, which was confirmed after approximately 10 lesional spicules were removed by tissue forceps and submitted for PCR analysis showing TSPyV (Figure). Two other cases utilized spicule PCR analysis for confirmation of TSPyV.^11,12 This technique may represent a viable option for diagnostic confirmation in pediatric cases. 

Although some articles have examined the molecular and biologic features of trichodysplasia spinulosa, literature on clinical presentation and management is limited to isolated case reports with no comprehensive studies to establish a standardized treatment. Of these reports, oral valganciclovir 900 mg daily, topical retinoids, cidofovir cream 1% to 3%, and decreasing or altering the immunosuppressive regimen all have been noted to provide clinical improvement.^13,14 Other therapies including leflunomide and routine manual extraction of spicules also have shown effectiveness in the treatment of trichodysplasia spinulosa.¹⁵  

In our patient, treatment included decreasing immunosuppression, as she was getting recurrent sinus and upper respiratory infections. Mycophenolate mofetil was discontinued, and the patient was continued solely on tacrolimus therapy. She demonstrated notable improvement after 3 months, with approximately 50% clearance of the eruption. A mutual decision was made at that visit to initiate therapy with compounded cidofovir cream 1% daily to the lesions until the next follow-up visit. Unfortunately, the patient did not return for her scheduled dermatology visits and was lost to long-term follow-up. 

Acknowledgment
We thank Richard C. Wang, MD, PhD (Dallas, Texas), for his dermatologic expertise and assistance in analysis of lesional samples for TSPyV. 

The Diagnosis: Trichodysplasia Spinulosa 

Trichodysplasia spinulosa has been described in case reports over the last several decades, with its causative virus trichodysplasia spinulosa-associated polyomavirus (TSPyV) identified in 2010 by van der Meijden et al.¹ Trichodysplasia spinulosa-associated polyomavirus is a small, nonenveloped, double-stranded DNA virus in the Polyomaviridae family, among several other known cutaneous polyomaviruses including Merkel cell polyomavirus, human polyomavirus (HPyV) 6, HPyV7, HPyV10, and possibly HPyV13.² The primary target of TSPyV is follicular keratinocytes, and it is believed to cause trichodysplasia spinulosa by primary infection rather than by reactivation. Trichodysplasia spinulosa presents in immunosuppressed patients as a folliculocentric eruption of papules with keratinous spines on the face, often with concurrent alopecia, eventually spreading to the trunk and extremities.³ The diagnosis often is clinical, but a biopsy may be performed for histopathologic confirmation. Alternatively, lesional spicules can be painlessly collected manually and submitted for viral polymerase chain reaction (PCR).⁴ The diagnosis of trichodysplasia spinulosa can be difficult due to similarities with other more common conditions such as keratosis pilaris, milia, filiform warts, or lichen spinulosus.  

Similar to trichodysplasia spinulosa, keratosis pilaris also presents with folliculocentric and often erythematous papules.⁵ Keratosis pilaris most frequently affects the posterior upper arms and thighs but also may affect the cheeks, as seen in trichodysplasia spinulosa. Differentiation between the 2 diagnoses can be made on a clinical basis, as keratosis pilaris lacks the characteristic keratinous spines and often spares the central face and nose, locations that commonly are affected in trichodysplasia spinulosa.³ 

Milia typically appear as white to yellow papules, often on the cheeks, eyelids, nose, and chin.⁶ Given their predilection for the face, milia can appear similarly to trichodysplasia spinulosa. Differentiation can be made clinically, as milia typically are not as numerous as the spiculed papules seen in trichodysplasia spinulosa. Morphologically, milia will present as smooth, dome-shaped papules as opposed to the keratinous spicules seen in trichodysplasia spinulosa. The diagnosis of milia can be confirmed by incision and removal of the white chalky keratin core, a feature absent in trichodysplasia spinulosa.  

Filiform warts are benign epidermal proliferations caused by human papillomavirus infection that manifest as flesh-colored, verrucous, hyperkeratotic papules.⁷ They can appear on virtually any skin surface, including the face, and thus may be mistaken for trichodysplasia spinulosa. Close inspection usually will reveal tiny black dots that represent thrombosed capillaries, a feature lacking in trichodysplasia spinulosa. In long-standing lesions or immunocompromised patients, confluent verrucous plaques may develop.⁸ Diagnosis of filiform warts can be confirmed with biopsy, which will demonstrate a compact stratum corneum, coarse hypergranulosis, and papillomatosis curving inward, while biopsy of a trichodysplasia spinulosa lesion would show polyomavirus infection of the hair follicle and characteristic eosinophilic inclusion bodies.⁹ 

Lichen spinulosus may appear as multiple folliculocentric scaly papules with hairlike horny spines.¹⁰ Lichen spinulosus differs from trichodysplasia spinulosa in that it commonly appears on the neck, abdomen, trochanteric region, arms, elbows, or knees. Lichen spinulosus also classically appears as a concrete cluster of papules, often localized to a certain region, in contrast to trichodysplasia spinulosa, which will be widespread, often spreading over time. Finally, clinical history may help differentiate the 2 entities. Lichen spinulosus most often appears in children and adolescents and often has an indolent course, typically resolving during puberty, while trichodysplasia spinulosa is seen in immunocompromised patients. 

In our patient, the dermatology team made a diagnosis of trichodysplasia spinulosa based on the characteristic clinical presentation, which was confirmed after approximately 10 lesional spicules were removed by tissue forceps and submitted for PCR analysis showing TSPyV (Figure). Two other cases utilized spicule PCR analysis for confirmation of TSPyV.^11,12 This technique may represent a viable option for diagnostic confirmation in pediatric cases. 

Although some articles have examined the molecular and biologic features of trichodysplasia spinulosa, literature on clinical presentation and management is limited to isolated case reports with no comprehensive studies to establish a standardized treatment. Of these reports, oral valganciclovir 900 mg daily, topical retinoids, cidofovir cream 1% to 3%, and decreasing or altering the immunosuppressive regimen all have been noted to provide clinical improvement.^13,14 Other therapies including leflunomide and routine manual extraction of spicules also have shown effectiveness in the treatment of trichodysplasia spinulosa.¹⁵  

In our patient, treatment included decreasing immunosuppression, as she was getting recurrent sinus and upper respiratory infections. Mycophenolate mofetil was discontinued, and the patient was continued solely on tacrolimus therapy. She demonstrated notable improvement after 3 months, with approximately 50% clearance of the eruption. A mutual decision was made at that visit to initiate therapy with compounded cidofovir cream 1% daily to the lesions until the next follow-up visit. Unfortunately, the patient did not return for her scheduled dermatology visits and was lost to long-term follow-up. 

Acknowledgment
We thank Richard C. Wang, MD, PhD (Dallas, Texas), for his dermatologic expertise and assistance in analysis of lesional samples for TSPyV. 

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft 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. He is MS4 at the University of Rochester, N.Y. 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. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft 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. He is MS4 at the University of Rochester, N.Y. 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. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.

The history of a brownish to pink patch with color change and rapid growth within the first year combined with the exam findings, are suggestive of a tufted angioma, though the findings presented may be nonspecific.

A tufted angioma is a rare vascular tumor of infancy or early childhood, that is present at birth in approximately half of cases. It may initially present as a faint pink to brown plaque, but develops as a firm, red to violaceous nodule or plaque, usually with “lumpiness” or nodularity.^1-3 Lesions usually are infiltrative with indistinct borders. They are named for their histologic appearance, with lobules of capillaries which appear as “tufts” in the dermis and subdermis with “cannonball” appearance, and are considered to be on a spectrum with another vascular tumor called kaposiform hemangioendothelioma (KHE).⁴ These vascular tumors can trigger Kasabach-Merritt syndrome, a disease process in which vascular tumors trap platelets and clotting factors, resulting in a life-threatening thrombocytopenia and consumptive coagulopathy with a high risk of bleeding and high-output heart failure.⁵
 

What’s the differential diagnosis?

The differential diagnosis of tufted angioma includes other potentially large vascular lesions including infantile hemangioma, congenital hemangioma, port-wine birth marks (capillary malformations), hemangioendotheliomas, and rhabdomyosarcomas.

Infantile hemangiomas (IH) are common vascular tumors of infancy seen in 4%-5% of infants that are characterized by a growth and involution phase. Classically, lesions can be absent or minimally evident at birth, becoming noticeable within the first months of life with a rapid growth phase and typical progression to bright red papules, nodules, or plaques. Deeper hemangiomas may appear more skin colored on the surface with a bluish coloration underneath. They are usually more discreet, with relatively defined borders. Diagnosis is typically clinical and many IHs self-resolve, albeit with residual findings including skin atrophy, scarring, and telangiectasia. Observation or topical timolol are first-line treatment options for more superficial lesions while systemic propranolol is the treatment of choice for deeper IHs or those resulting in possible airway or vision compromise.

Congenital hemangiomas (CH) are another type of vascular growth characterized by a solitary erythematous to violaceous plaque or nodule present at birth with overlying telangiectasia. CHs can be subdivided into categories including rapidly involuting (RICH), partially involuting (PICH), and noninvoluting (NICH). Diagnosis is usually clinical and, depending on the subtype, treatment can involve watchful waiting (for RICHs) or more active intervention such as pulse dye laser or surgical resection (for PICHs or NICHs). The growing nature of this patient’s mass makes a diagnosis of CH unlikely.

Port-wine birth mark, also known as nevus flammeus, is a vascular malformation that appears at birth as a nonpalpable irregular erythematous to violaceous macular plaque. Port-wine stains may be isolated birthmarks, or associated with Sturge-Weber syndrome, complex vascular malformations, or soft-tissue overgrowth. Klippel-Trenauny syndrome (KTS) describes capillary-venous malformations with limb overgrowth, with or without lymphatic malformations, and many are associated with somatic mutations in the PIK3CA gene. While KTS could be considered in this patient, the nodular appearance with lumpy texture and rapid growth makes a vascular tumor more likely.

Rhabdomyosarcoma is a malignancy of skeletal muscle lineage and the most common soft tissue tumor in pediatrics. Cutaneous rhabdomyosarcomas present as erythematous nodules, markedly firm, often “fixed” to deep tissue. A rapidly growing atypical, firm tumor of infancy should raise the consideration of rhabdomyosarcoma and imaging and biopsy are appropriate for evaluation.
 

What should the evaluation and management of this patient be?

Initial workup should include a complete blood count with platelet count as well as coagulation studies including D-dimer, fibrinogen, prothrombin time, and activated partial thromboplastin time, to assess for any thrombocytopenia or coagulopathy.⁶ Ultrasound and/or MRI may also be performed to determine lesion extent. While typical MRI findings might be suggestive of a tufted angioma or hemangioendothelioma, biopsy for histologic examination is usually the approach to diagnosis, which will demonstrate stereotypic round lobules of capillaries in a “tufted” distribution.^2,7 Biopsy may be performed by a surgeon or dermatologist but bleeding at time of biopsy needs to be considered before moving forward with the procedure.

Tufted angiomas of early life may regress spontaneously, though lesions with symptoms, with functional significance, or associated with KHE may require therapy. Surgical excision is one option, but it may be difficult to execute given that these lesions often have poorly defined margins.¹ Other treatment choices include but are not limited to aspirin, systemic corticosteroids, vincristine, interferon-alpha, embolization, and sirolimus.⁸ No specific expert-directed consensus guidelines exist for these lesions, and suspicion of this lesion should prompt urgent referral to a pediatric dermatologist. Concern for Kasabach-Merritt syndrome should trigger immediate referral for rapid evaluation and management.

Complete blood count with platelet count and coagulation studies were normal in our patient. This infant underwent biopsy to confirm the diagnosis of tufted angioma and MRI to determine lesion extent. The lesion slowly involuted spontaneously without recurrence.
 

Mr. Haft 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. He is MS4 at the University of Rochester, N.Y. 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. Neither Mr. Haft nor Dr. Eichenfield have any relevant financial disclosures.

References

1. Herron MD et al. Pediatr Dermatol. 2002;19(5):394-401.

2. Jones EW and Orkin M. J Am Acad Dermatol. 1989;20(2 Pt 1):214-25.

3. Wong SN and Tay YK. Pediatr Dermatol. 2002;19(5):388-93.

4. Croteau SE and Gupta D. Semin Cutan Med Surg. 2016;35(3):147-52.

5. Kelly M. Pediatr Clin North Am. 2010;57(5):1085-9.

6. Osio A et al. Arch Dermatol. 2010;146(7):758-63.

7. Padilla RS et al. Am J Dermatopathol. 1987;9(4):292-300.

8. Liu XH et al. Int J Cancer. 2016;139(7):1658-66.