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The Diagnosis: Infantile Transient Smooth Muscle Contraction of the Skin

A diagnosis of infantile transient smooth muscle contraction of the skin (ITSMC) was made based on our patient’s clinical presentation and eliminating the diagnoses in the differential. No treatment ultimately was indicated, as episodes became less frequent over time.

The term infantile transient smooth muscle contraction of the skin was first proposed in 2013 by Torrelo et al,¹ who described 9 newborns with episodic skin rippling occasionally associated with exposure to cold or friction. The authors postulated that ITSMC was the result of a transient contraction of the arrector pili smooth muscle fibers of the skin, secondary to autonomic immaturity, primitive reflexes, or smooth muscle hypersensitivity.¹ Since this first description, ITSMC has remained a rarely reported and poorly understood phenomenon with rare identified cases in the literature.^2,3 Clinical history and examination of infants with intermittent transient skin rippling help to distinguish ITSMC from other diagnoses without the need for biopsy, which is particularly undesirable in the pediatric population.

Congenital smooth muscle hamartoma is a benign proliferation of mature smooth muscle that also can arise from the arrector pili muscles.⁴ In contrast to ITSMC, a hamartoma does not clear; rather, it persists and grows proportionally with the child and is associated with overlying hyperpigmentation and hypertrichosis. The transient nature of ITSMC may be worrisome for mastocytoma; however, this condition presents as erythematous, yellow, red, or brown macules, papules, plaques, or nodules with a positive Darier sign.⁵ Although the differential diagnosis includes the shagreen patch characteristic of tuberous sclerosis, this irregular plaque typically is located on the lower back with overlying peau d’orange skin changes, and our patient lacked other features indicative of this condition.⁶ Becker nevus also remains a consideration in patients with rippled skin, but this entity typically becomes more notable at puberty and is associated with hyperpigmentation and hypertrichosis and is a type of smooth muscle hamartoma.⁴

Our case highlighted the unusual presentation of ITSMC, a condition that can easily go unrecognized, leading to unnecessary referrals and concern. Familiarity with this benign diagnosis is essential to inform prognosis and guide management.

The Diagnosis: Infantile Transient Smooth Muscle Contraction of the Skin

A diagnosis of infantile transient smooth muscle contraction of the skin (ITSMC) was made based on our patient’s clinical presentation and eliminating the diagnoses in the differential. No treatment ultimately was indicated, as episodes became less frequent over time.

The term infantile transient smooth muscle contraction of the skin was first proposed in 2013 by Torrelo et al,¹ who described 9 newborns with episodic skin rippling occasionally associated with exposure to cold or friction. The authors postulated that ITSMC was the result of a transient contraction of the arrector pili smooth muscle fibers of the skin, secondary to autonomic immaturity, primitive reflexes, or smooth muscle hypersensitivity.¹ Since this first description, ITSMC has remained a rarely reported and poorly understood phenomenon with rare identified cases in the literature.^2,3 Clinical history and examination of infants with intermittent transient skin rippling help to distinguish ITSMC from other diagnoses without the need for biopsy, which is particularly undesirable in the pediatric population.

Congenital smooth muscle hamartoma is a benign proliferation of mature smooth muscle that also can arise from the arrector pili muscles.⁴ In contrast to ITSMC, a hamartoma does not clear; rather, it persists and grows proportionally with the child and is associated with overlying hyperpigmentation and hypertrichosis. The transient nature of ITSMC may be worrisome for mastocytoma; however, this condition presents as erythematous, yellow, red, or brown macules, papules, plaques, or nodules with a positive Darier sign.⁵ Although the differential diagnosis includes the shagreen patch characteristic of tuberous sclerosis, this irregular plaque typically is located on the lower back with overlying peau d’orange skin changes, and our patient lacked other features indicative of this condition.⁶ Becker nevus also remains a consideration in patients with rippled skin, but this entity typically becomes more notable at puberty and is associated with hyperpigmentation and hypertrichosis and is a type of smooth muscle hamartoma.⁴

Our case highlighted the unusual presentation of ITSMC, a condition that can easily go unrecognized, leading to unnecessary referrals and concern. Familiarity with this benign diagnosis is essential to inform prognosis and guide management.

The Diagnosis: Infantile Transient Smooth Muscle Contraction of the Skin

A diagnosis of infantile transient smooth muscle contraction of the skin (ITSMC) was made based on our patient’s clinical presentation and eliminating the diagnoses in the differential. No treatment ultimately was indicated, as episodes became less frequent over time.

The term infantile transient smooth muscle contraction of the skin was first proposed in 2013 by Torrelo et al,¹ who described 9 newborns with episodic skin rippling occasionally associated with exposure to cold or friction. The authors postulated that ITSMC was the result of a transient contraction of the arrector pili smooth muscle fibers of the skin, secondary to autonomic immaturity, primitive reflexes, or smooth muscle hypersensitivity.¹ Since this first description, ITSMC has remained a rarely reported and poorly understood phenomenon with rare identified cases in the literature.^2,3 Clinical history and examination of infants with intermittent transient skin rippling help to distinguish ITSMC from other diagnoses without the need for biopsy, which is particularly undesirable in the pediatric population.

Congenital smooth muscle hamartoma is a benign proliferation of mature smooth muscle that also can arise from the arrector pili muscles.⁴ In contrast to ITSMC, a hamartoma does not clear; rather, it persists and grows proportionally with the child and is associated with overlying hyperpigmentation and hypertrichosis. The transient nature of ITSMC may be worrisome for mastocytoma; however, this condition presents as erythematous, yellow, red, or brown macules, papules, plaques, or nodules with a positive Darier sign.⁵ Although the differential diagnosis includes the shagreen patch characteristic of tuberous sclerosis, this irregular plaque typically is located on the lower back with overlying peau d’orange skin changes, and our patient lacked other features indicative of this condition.⁶ Becker nevus also remains a consideration in patients with rippled skin, but this entity typically becomes more notable at puberty and is associated with hyperpigmentation and hypertrichosis and is a type of smooth muscle hamartoma.⁴

Our case highlighted the unusual presentation of ITSMC, a condition that can easily go unrecognized, leading to unnecessary referrals and concern. Familiarity with this benign diagnosis is essential to inform prognosis and guide management.

The Diagnosis: Congenital Cutaneous Langerhans Cell Histiocytosis

Although the infectious workup was positive for herpes simplex virus type 1 and cytomegalovirus antibodies, serologies for the rest of the TORCH (toxoplasmosis, other agents [syphilis, hepatitis B virus], rubella, cytomegalovirus) group of infections, as well as other bacterial, fungal, and viral infections, were negative. A skin biopsy from the right fifth toe showed a dense infiltrate of CD1a+ histiocytic cells with folded or kidney-shaped nuclei mixed with eosinophils, which was consistent with Langerhans cell histiocytosis (LCH) (Figure 1). Skin lesions were treated with hydrocortisone cream 2.5% and progressively faded over a few weeks.

Langerhans cell histiocytosis is a rare disorder with a variable clinical presentation depending on the sites affected and the extent of involvement. It can involve multiple organ systems, most commonly the skeletal system and the skin. Organ involvement is characterized by histiocyte infiltration. Acute disseminated multisystem disease most commonly is seen in children younger than 3 years.¹

Congenital cutaneous LCH presents with variable skin lesions ranging from papules to vesicles, pustules, and ulcers, with onset at birth or in the neonatal period. Various morphologic traits of skin lesions have been described; the most common presentation is multiple red to yellow-brown, crusted papules with accompanying hemorrhage or erosion.¹ Other cases have described an eczematous, seborrheic, diffuse eruption or erosive intertrigo. One case of a child with a solitary necrotic nodule on the scalp has been reported.²

Our patient presented with disseminated, nonblanching, purple to dark red papules and nodules of the skin and oral mucosa, as well as nail dystrophy (Figure 2). However, LCH in a neonate can mimic other causes of congenital papulonodular eruptions. Red-brown papules and nodules with or without crusting in a newborn can be mistaken for erythema toxicum neonatorum, transient neonatal pustular melanosis, congenital leukemia cutis, neonatal erythropoiesis, disseminated neonatal hemangiomatosis, infantile acropustulosis, or congenital TORCH infections such as rubella or syphilis. When LCH presents as vesicles or eroded papules or nodules in a newborn, the differential diagnosis includes incontinentia pigmenti and hereditary epidermolysis bullosa.

Langerhans cell histiocytosis may even present with a classic blueberry muffin rash that can lead clinicians to consider cutaneous metastasis from various hematologic malignancies or the more common TORCH infections. Several diagnostic tests can be performed to clarify the diagnosis, including bacterial and viral cultures and stains, serology, immunohistochemistry, flow cytometry, bone marrow aspiration, or skin biopsy.³ Langerhans cell histiocytosis is diagnosed with a combination of histology, immunohistochemistry, and clinical presentation; however, a skin biopsy is crucial. Tissue should be taken from the most easily accessible yet representative lesion. The characteristic appearance of LCH lesions is described as a dense infiltrate of histiocytic cells mixed with numerous eosinophils in the dermis.¹ Histiocytes usually have folded nuclei and eosinophilic cytoplasm or kidney-shaped nuclei with prominent nucleoli. Positive CD1a and/or CD207 (Langerin) staining of the cells is required for definitive diagnosis.⁴ After diagnosis, it is important to obtain baseline laboratory and radiographic studies to determine the extent of systemic involvement.

Treatment of congenital LCH is tailored to the extent of organ involvement. The dermatologic manifestations resolve without medications in many cases. However, true self-resolving LCH can only be diagnosed retrospectively after a full evaluation for other sites of disease. Disseminated disease can be life-threatening and requires more active management. In cases of skin-limited disease, therapies include topical steroids, nitrogen mustard, or imiquimod; surgical resection of isolated lesions; phototherapy; or systemic therapies such as methotrexate, 6-mercaptopurine, vinblastine/vincristine, cladribine, and/or cytarabine. Symptomatic patients initially are treated with methotrexate and 6-mercaptopurine.⁵ Asymptomatic infants with skin-limited involvement can be managed with topical treatments.

Our patient had skin-limited disease. Abdominal ultrasonography, skeletal survey, and magnetic resonance imaging of the brain revealed no abnormalities. The patient’s family was advised to monitor him for reoccurrence of the skin lesions and to continue close follow-up with hematology and dermatology. Although congenital LCH often is self-resolving, extensive skin involvement increases the risk for internal organ involvement for several years.⁶ These patients require long-term follow-up for potential musculoskeletal, ophthalmologic, endocrine, hepatic, and/or pulmonary disease.

The Diagnosis: Congenital Cutaneous Langerhans Cell Histiocytosis

Although the infectious workup was positive for herpes simplex virus type 1 and cytomegalovirus antibodies, serologies for the rest of the TORCH (toxoplasmosis, other agents [syphilis, hepatitis B virus], rubella, cytomegalovirus) group of infections, as well as other bacterial, fungal, and viral infections, were negative. A skin biopsy from the right fifth toe showed a dense infiltrate of CD1a+ histiocytic cells with folded or kidney-shaped nuclei mixed with eosinophils, which was consistent with Langerhans cell histiocytosis (LCH) (Figure 1). Skin lesions were treated with hydrocortisone cream 2.5% and progressively faded over a few weeks.

Langerhans cell histiocytosis is a rare disorder with a variable clinical presentation depending on the sites affected and the extent of involvement. It can involve multiple organ systems, most commonly the skeletal system and the skin. Organ involvement is characterized by histiocyte infiltration. Acute disseminated multisystem disease most commonly is seen in children younger than 3 years.¹

Congenital cutaneous LCH presents with variable skin lesions ranging from papules to vesicles, pustules, and ulcers, with onset at birth or in the neonatal period. Various morphologic traits of skin lesions have been described; the most common presentation is multiple red to yellow-brown, crusted papules with accompanying hemorrhage or erosion.¹ Other cases have described an eczematous, seborrheic, diffuse eruption or erosive intertrigo. One case of a child with a solitary necrotic nodule on the scalp has been reported.²

Our patient presented with disseminated, nonblanching, purple to dark red papules and nodules of the skin and oral mucosa, as well as nail dystrophy (Figure 2). However, LCH in a neonate can mimic other causes of congenital papulonodular eruptions. Red-brown papules and nodules with or without crusting in a newborn can be mistaken for erythema toxicum neonatorum, transient neonatal pustular melanosis, congenital leukemia cutis, neonatal erythropoiesis, disseminated neonatal hemangiomatosis, infantile acropustulosis, or congenital TORCH infections such as rubella or syphilis. When LCH presents as vesicles or eroded papules or nodules in a newborn, the differential diagnosis includes incontinentia pigmenti and hereditary epidermolysis bullosa.

Langerhans cell histiocytosis may even present with a classic blueberry muffin rash that can lead clinicians to consider cutaneous metastasis from various hematologic malignancies or the more common TORCH infections. Several diagnostic tests can be performed to clarify the diagnosis, including bacterial and viral cultures and stains, serology, immunohistochemistry, flow cytometry, bone marrow aspiration, or skin biopsy.³ Langerhans cell histiocytosis is diagnosed with a combination of histology, immunohistochemistry, and clinical presentation; however, a skin biopsy is crucial. Tissue should be taken from the most easily accessible yet representative lesion. The characteristic appearance of LCH lesions is described as a dense infiltrate of histiocytic cells mixed with numerous eosinophils in the dermis.¹ Histiocytes usually have folded nuclei and eosinophilic cytoplasm or kidney-shaped nuclei with prominent nucleoli. Positive CD1a and/or CD207 (Langerin) staining of the cells is required for definitive diagnosis.⁴ After diagnosis, it is important to obtain baseline laboratory and radiographic studies to determine the extent of systemic involvement.

Treatment of congenital LCH is tailored to the extent of organ involvement. The dermatologic manifestations resolve without medications in many cases. However, true self-resolving LCH can only be diagnosed retrospectively after a full evaluation for other sites of disease. Disseminated disease can be life-threatening and requires more active management. In cases of skin-limited disease, therapies include topical steroids, nitrogen mustard, or imiquimod; surgical resection of isolated lesions; phototherapy; or systemic therapies such as methotrexate, 6-mercaptopurine, vinblastine/vincristine, cladribine, and/or cytarabine. Symptomatic patients initially are treated with methotrexate and 6-mercaptopurine.⁵ Asymptomatic infants with skin-limited involvement can be managed with topical treatments.

Our patient had skin-limited disease. Abdominal ultrasonography, skeletal survey, and magnetic resonance imaging of the brain revealed no abnormalities. The patient’s family was advised to monitor him for reoccurrence of the skin lesions and to continue close follow-up with hematology and dermatology. Although congenital LCH often is self-resolving, extensive skin involvement increases the risk for internal organ involvement for several years.⁶ These patients require long-term follow-up for potential musculoskeletal, ophthalmologic, endocrine, hepatic, and/or pulmonary disease.

The Diagnosis: Congenital Cutaneous Langerhans Cell Histiocytosis

Although the infectious workup was positive for herpes simplex virus type 1 and cytomegalovirus antibodies, serologies for the rest of the TORCH (toxoplasmosis, other agents [syphilis, hepatitis B virus], rubella, cytomegalovirus) group of infections, as well as other bacterial, fungal, and viral infections, were negative. A skin biopsy from the right fifth toe showed a dense infiltrate of CD1a+ histiocytic cells with folded or kidney-shaped nuclei mixed with eosinophils, which was consistent with Langerhans cell histiocytosis (LCH) (Figure 1). Skin lesions were treated with hydrocortisone cream 2.5% and progressively faded over a few weeks.

Langerhans cell histiocytosis is a rare disorder with a variable clinical presentation depending on the sites affected and the extent of involvement. It can involve multiple organ systems, most commonly the skeletal system and the skin. Organ involvement is characterized by histiocyte infiltration. Acute disseminated multisystem disease most commonly is seen in children younger than 3 years.¹

Congenital cutaneous LCH presents with variable skin lesions ranging from papules to vesicles, pustules, and ulcers, with onset at birth or in the neonatal period. Various morphologic traits of skin lesions have been described; the most common presentation is multiple red to yellow-brown, crusted papules with accompanying hemorrhage or erosion.¹ Other cases have described an eczematous, seborrheic, diffuse eruption or erosive intertrigo. One case of a child with a solitary necrotic nodule on the scalp has been reported.²

Our patient presented with disseminated, nonblanching, purple to dark red papules and nodules of the skin and oral mucosa, as well as nail dystrophy (Figure 2). However, LCH in a neonate can mimic other causes of congenital papulonodular eruptions. Red-brown papules and nodules with or without crusting in a newborn can be mistaken for erythema toxicum neonatorum, transient neonatal pustular melanosis, congenital leukemia cutis, neonatal erythropoiesis, disseminated neonatal hemangiomatosis, infantile acropustulosis, or congenital TORCH infections such as rubella or syphilis. When LCH presents as vesicles or eroded papules or nodules in a newborn, the differential diagnosis includes incontinentia pigmenti and hereditary epidermolysis bullosa.

Langerhans cell histiocytosis may even present with a classic blueberry muffin rash that can lead clinicians to consider cutaneous metastasis from various hematologic malignancies or the more common TORCH infections. Several diagnostic tests can be performed to clarify the diagnosis, including bacterial and viral cultures and stains, serology, immunohistochemistry, flow cytometry, bone marrow aspiration, or skin biopsy.³ Langerhans cell histiocytosis is diagnosed with a combination of histology, immunohistochemistry, and clinical presentation; however, a skin biopsy is crucial. Tissue should be taken from the most easily accessible yet representative lesion. The characteristic appearance of LCH lesions is described as a dense infiltrate of histiocytic cells mixed with numerous eosinophils in the dermis.¹ Histiocytes usually have folded nuclei and eosinophilic cytoplasm or kidney-shaped nuclei with prominent nucleoli. Positive CD1a and/or CD207 (Langerin) staining of the cells is required for definitive diagnosis.⁴ After diagnosis, it is important to obtain baseline laboratory and radiographic studies to determine the extent of systemic involvement.

Treatment of congenital LCH is tailored to the extent of organ involvement. The dermatologic manifestations resolve without medications in many cases. However, true self-resolving LCH can only be diagnosed retrospectively after a full evaluation for other sites of disease. Disseminated disease can be life-threatening and requires more active management. In cases of skin-limited disease, therapies include topical steroids, nitrogen mustard, or imiquimod; surgical resection of isolated lesions; phototherapy; or systemic therapies such as methotrexate, 6-mercaptopurine, vinblastine/vincristine, cladribine, and/or cytarabine. Symptomatic patients initially are treated with methotrexate and 6-mercaptopurine.⁵ Asymptomatic infants with skin-limited involvement can be managed with topical treatments.

Our patient had skin-limited disease. Abdominal ultrasonography, skeletal survey, and magnetic resonance imaging of the brain revealed no abnormalities. The patient’s family was advised to monitor him for reoccurrence of the skin lesions and to continue close follow-up with hematology and dermatology. Although congenital LCH often is self-resolving, extensive skin involvement increases the risk for internal organ involvement for several years.⁶ These patients require long-term follow-up for potential musculoskeletal, ophthalmologic, endocrine, hepatic, and/or pulmonary disease.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Flagellate Dermatitis

Upon further questioning by dermatology, the patient noted recent ingestion of shiitake mushrooms, which were not a part of his typical diet. Based on the appearance of the rash in the context of ingesting shiitake mushrooms, our patient was diagnosed with flagellate dermatitis. At 6-week followup, the patient’s rash had resolved spontaneously without further intervention.

Flagellate dermatitis usually appears on the torso as linear whiplike streaks.¹ The eruption often is pruritic and may be preceded by severe pruritus. Flagellate dermatitis also is a well-documented complication of bleomycin sulfate therapy with an incidence rate of 8% to 66%.²

Other chemotherapeutic causes include peplomycin, bendamustine, docetaxel, cisplatin, and trastuzumab.³ Flagellate dermatitis also is seen in some patients with dermatomyositis.⁴ A thorough patient history, including medications and dietary habits, is necessary to differentiate flagellate dermatitis from dermatomyositis.

Flagellate dermatitis, also known as shiitake dermatitis, is observed as erythematous flagellate eruptions involving the trunk or extremities that present within 2 hours to 5 days of handling or consuming undercooked or raw shiitake mushrooms (Lentinula edodes),^5,6 as was observed in our patient. Lentinan is the polysaccharide component of the shiitake species and is destabilized by heat.⁶ Ingestion of polysaccharide is associated with dermatitis, particularly in Japan, China, and Korea; however, the consumption of shiitake mushrooms has increased worldwide, and cases increasingly are reported outside of these typical regions. The rash typically resolves spontaneously; therefore, treatment is supportive. However, more severe symptomatic cases may require courses of topical corticosteroids and antihistamines.⁶

In our case, the differential diagnosis consisted of acute urticaria, cutaneous dermatomyositis, dermatographism, and maculopapular cutaneous mastocytosis. Acute urticaria displays well-circumscribed edematous papules or plaques, and individual lesions last less than 24 hours. Cutaneous dermatomyositis includes additional systemic manifestations such as fatigue, malaise, and myalgia, as well as involvement of the gastrointestinal, respiratory, or cardiac organs. Dermatographism is evoked by stroking or rubbing of the skin, which results in asymptomatic lesions that persist for 15 to 30 minutes. Cases of maculopapular cutaneous mastocytosis more often are seen in children, and the histamine release most often causes gastrointestinal tract symptoms such as nausea, vomiting, and diarrhea, as well as flushing, blushing, pruritus, respiratory difficulty, and malaise.

The Diagnosis: Neonatal Lupus Erythematosus

A review of the medical records of the patient’s mother from her first pregnancy revealed positive anti-Ro/SSA (Sjögren syndrome A) (>8.0 U [reference range <1.0 U]) and anti-La/SSB (Sjögren syndrome B) antibodies (>8.0 U [reference range <1.0 U]), which were reconfirmed during her pregnancy with our patient (the second child). The patient’s older brother was diagnosed with neonatal lupus erythematosus (NLE) 2 years prior at 1 month of age; therefore, the mother took hydroxychloroquine during the pregnancy with the second child to help prevent heart block if the child was diagnosed with NLE. Given the family history, positive antibodies in the mother, and clinical presentation, our patient was diagnosed with NLE. He was referred to a pediatric cardiologist and pediatrician to continue the workup of systemic manifestations of NLE and to rule out the presence of congenital heart block. The rash resolved 6 months after the initial presentation, and he did not develop any systemic manifestations of NLE.

Neonatal lupus erythematosus is a rare acquired autoimmune disorder caused by the placental transfer of anti-Ro/SSA and anti-La/SSB antibodies and less commonly anti-U1 ribonucleoprotein antinuclear autoantibodies.^1,2 Approximately 1% to 2% of mothers with these positive antibodies will have infants affected with NLE.² The annual prevalence of NLE in the United States is approximately 1 in 20,000 live births. Mothers of children with NLE most commonly have clinical Sjögren syndrome; however, anti-Ro/SSA and anti-LA/SSB antibodies may be present in 0.1% to 1.5% of healthy women, and 25% to 60% of women with autoimmune disease may be asymptomatic.¹ As demonstrated in our case, when there is a family history of NLE in an infant from an earlier pregnancy, the risk for NLE increases to 17% to 20% in subsequent pregnancies^1,3 and up to 25% in subsequent pregnancies if the initial child was diagnosed with a congenital heart block in the setting of NLE.¹

Neonatal lupus erythematosus classically presents as annular erythematous macules and plaques with central scaling, telangictasia, atrophy, and pigmentary changes. It may start on the scalp and face and spread caudally.^1,2 Patients may develop these lesions after UV exposure, and 80% of infants may not have dermatologic findings at birth. Importantly, 40% to 60% of mothers may be asymptomatic at the time of presentation of their child’s NLE.¹ The diagnosis can be confirmed via antibody testing in the mother and/or infant. If performed, a punch biopsy shows interface dermatitis, vacuolar degeneration, and possible periadnexal lymphocytic infiltrates on histopathology.^1,2

Management of cutaneous NLE includes sun protection (eg, application of sunscreen) and topical corticosteroids. Most dermatologic manifestations of NLE are transient, resolving after clearance of maternal IgG antibodies in 6 to 9 months; however, some telangiectasia, dyspigmentation, and atrophic scarring may persist.^1-3

Neonatal lupus erythematosus also may have hepatobiliary, cardiac, hematologic, and less commonly neurologic manifestations. Hepatobiliary manifestations usually present as hepatomegaly or asymptomatic elevated transaminases or γ-glutamyl transferase.^1,3 Approximately 10% to 20% of infants with NLE may present with transient anemia and thrombocytopenia.¹ Cardiac manifestations are permanent and may require pacemaker implantation.^1,3 The incidence of a congenital heart block in infants with NLE is 15% to 30%.³ Cardiac NLE most commonly injures the conductive tissue, leading to a congenital atrioventricular block. The development of a congenital heart block develops in the 18th to 24th week of gestation. Manifestations of a more advanced condition can include dilation of the ascending aorta and dilated cardiomyopathy.¹ As such, patients need to be followed by a pediatric cardiologist for monitoring and treatment of any cardiac manifestations.

The overall prognosis of infants affected with NLE varies. Cardiac involvement is associated with a poor prognosis, while isolated cutaneous involvement requires little treatment and portends a favorable prognosis. It is critical for dermatologists to recognize NLE to refer patients to appropriate specialists to investigate and further monitor possible extracutaneous manifestations. With an understanding of the increased risk for a congenital heart block and NLE in subsequent pregnancies, mothers with positive anti-Ro/La antibodies should receive timely counseling and screening. In expectant mothers with suspected autoimmune disease, testing for antinuclear antibodies and SSA and SSB antibodies can be considered, as administration of hydroxychloroquine or prenatal systemic corticosteroids has proven to be effective in preventing a congenital heart block.¹ Our patient was followed by pediatric cardiology and was not found to have a congenital heart block.

The differential diagnosis includes other causes of annular erythema in infants, as NLE can mimic several conditions. Tinea corporis may present as scaly annular plaques with central clearing; however, it rarely is encountered fulminantly in neonates.⁴ Erythema multiforme is a mucocutaneous hypersensitivy reaction distinguished by targetoid morphology.⁵ It is an exceedingly rare diagnosis in neonates; the average pediatric age of onset is 5.6 years.⁶ Erythema multiforme often is associated with an infection, most commonly herpes simplex virus,⁵ and mucosal involvement is common.⁶ Urticaria multiforme (also known as acute annular urticaria) is a benign disease that appears between 2 months to 3 years of age with blanchable urticarial plaques that likely are triggered by viral or bacterial infections, antibiotics, or vaccines.⁶ Specific lesions usually will resolve within 24 hours. Annular erythema of infancy is a benign and asymptomatic gyrate erythema that presents as annular plaques with palpable borders that spread centrifugally in patients younger than 1 year. Notably, lesions should periodically fade and may reappear cyclically for months to years. Evaluation for underlying disease usually is negative.⁶

The Diagnosis: Neonatal Lupus Erythematosus

A review of the medical records of the patient’s mother from her first pregnancy revealed positive anti-Ro/SSA (Sjögren syndrome A) (>8.0 U [reference range <1.0 U]) and anti-La/SSB (Sjögren syndrome B) antibodies (>8.0 U [reference range <1.0 U]), which were reconfirmed during her pregnancy with our patient (the second child). The patient’s older brother was diagnosed with neonatal lupus erythematosus (NLE) 2 years prior at 1 month of age; therefore, the mother took hydroxychloroquine during the pregnancy with the second child to help prevent heart block if the child was diagnosed with NLE. Given the family history, positive antibodies in the mother, and clinical presentation, our patient was diagnosed with NLE. He was referred to a pediatric cardiologist and pediatrician to continue the workup of systemic manifestations of NLE and to rule out the presence of congenital heart block. The rash resolved 6 months after the initial presentation, and he did not develop any systemic manifestations of NLE.

Neonatal lupus erythematosus is a rare acquired autoimmune disorder caused by the placental transfer of anti-Ro/SSA and anti-La/SSB antibodies and less commonly anti-U1 ribonucleoprotein antinuclear autoantibodies.^1,2 Approximately 1% to 2% of mothers with these positive antibodies will have infants affected with NLE.² The annual prevalence of NLE in the United States is approximately 1 in 20,000 live births. Mothers of children with NLE most commonly have clinical Sjögren syndrome; however, anti-Ro/SSA and anti-LA/SSB antibodies may be present in 0.1% to 1.5% of healthy women, and 25% to 60% of women with autoimmune disease may be asymptomatic.¹ As demonstrated in our case, when there is a family history of NLE in an infant from an earlier pregnancy, the risk for NLE increases to 17% to 20% in subsequent pregnancies^1,3 and up to 25% in subsequent pregnancies if the initial child was diagnosed with a congenital heart block in the setting of NLE.¹

Neonatal lupus erythematosus classically presents as annular erythematous macules and plaques with central scaling, telangictasia, atrophy, and pigmentary changes. It may start on the scalp and face and spread caudally.^1,2 Patients may develop these lesions after UV exposure, and 80% of infants may not have dermatologic findings at birth. Importantly, 40% to 60% of mothers may be asymptomatic at the time of presentation of their child’s NLE.¹ The diagnosis can be confirmed via antibody testing in the mother and/or infant. If performed, a punch biopsy shows interface dermatitis, vacuolar degeneration, and possible periadnexal lymphocytic infiltrates on histopathology.^1,2

Management of cutaneous NLE includes sun protection (eg, application of sunscreen) and topical corticosteroids. Most dermatologic manifestations of NLE are transient, resolving after clearance of maternal IgG antibodies in 6 to 9 months; however, some telangiectasia, dyspigmentation, and atrophic scarring may persist.^1-3

Neonatal lupus erythematosus also may have hepatobiliary, cardiac, hematologic, and less commonly neurologic manifestations. Hepatobiliary manifestations usually present as hepatomegaly or asymptomatic elevated transaminases or γ-glutamyl transferase.^1,3 Approximately 10% to 20% of infants with NLE may present with transient anemia and thrombocytopenia.¹ Cardiac manifestations are permanent and may require pacemaker implantation.^1,3 The incidence of a congenital heart block in infants with NLE is 15% to 30%.³ Cardiac NLE most commonly injures the conductive tissue, leading to a congenital atrioventricular block. The development of a congenital heart block develops in the 18th to 24th week of gestation. Manifestations of a more advanced condition can include dilation of the ascending aorta and dilated cardiomyopathy.¹ As such, patients need to be followed by a pediatric cardiologist for monitoring and treatment of any cardiac manifestations.

The overall prognosis of infants affected with NLE varies. Cardiac involvement is associated with a poor prognosis, while isolated cutaneous involvement requires little treatment and portends a favorable prognosis. It is critical for dermatologists to recognize NLE to refer patients to appropriate specialists to investigate and further monitor possible extracutaneous manifestations. With an understanding of the increased risk for a congenital heart block and NLE in subsequent pregnancies, mothers with positive anti-Ro/La antibodies should receive timely counseling and screening. In expectant mothers with suspected autoimmune disease, testing for antinuclear antibodies and SSA and SSB antibodies can be considered, as administration of hydroxychloroquine or prenatal systemic corticosteroids has proven to be effective in preventing a congenital heart block.¹ Our patient was followed by pediatric cardiology and was not found to have a congenital heart block.

The differential diagnosis includes other causes of annular erythema in infants, as NLE can mimic several conditions. Tinea corporis may present as scaly annular plaques with central clearing; however, it rarely is encountered fulminantly in neonates.⁴ Erythema multiforme is a mucocutaneous hypersensitivy reaction distinguished by targetoid morphology.⁵ It is an exceedingly rare diagnosis in neonates; the average pediatric age of onset is 5.6 years.⁶ Erythema multiforme often is associated with an infection, most commonly herpes simplex virus,⁵ and mucosal involvement is common.⁶ Urticaria multiforme (also known as acute annular urticaria) is a benign disease that appears between 2 months to 3 years of age with blanchable urticarial plaques that likely are triggered by viral or bacterial infections, antibiotics, or vaccines.⁶ Specific lesions usually will resolve within 24 hours. Annular erythema of infancy is a benign and asymptomatic gyrate erythema that presents as annular plaques with palpable borders that spread centrifugally in patients younger than 1 year. Notably, lesions should periodically fade and may reappear cyclically for months to years. Evaluation for underlying disease usually is negative.⁶

The Diagnosis: Neonatal Lupus Erythematosus

A review of the medical records of the patient’s mother from her first pregnancy revealed positive anti-Ro/SSA (Sjögren syndrome A) (>8.0 U [reference range <1.0 U]) and anti-La/SSB (Sjögren syndrome B) antibodies (>8.0 U [reference range <1.0 U]), which were reconfirmed during her pregnancy with our patient (the second child). The patient’s older brother was diagnosed with neonatal lupus erythematosus (NLE) 2 years prior at 1 month of age; therefore, the mother took hydroxychloroquine during the pregnancy with the second child to help prevent heart block if the child was diagnosed with NLE. Given the family history, positive antibodies in the mother, and clinical presentation, our patient was diagnosed with NLE. He was referred to a pediatric cardiologist and pediatrician to continue the workup of systemic manifestations of NLE and to rule out the presence of congenital heart block. The rash resolved 6 months after the initial presentation, and he did not develop any systemic manifestations of NLE.

Neonatal lupus erythematosus is a rare acquired autoimmune disorder caused by the placental transfer of anti-Ro/SSA and anti-La/SSB antibodies and less commonly anti-U1 ribonucleoprotein antinuclear autoantibodies.^1,2 Approximately 1% to 2% of mothers with these positive antibodies will have infants affected with NLE.² The annual prevalence of NLE in the United States is approximately 1 in 20,000 live births. Mothers of children with NLE most commonly have clinical Sjögren syndrome; however, anti-Ro/SSA and anti-LA/SSB antibodies may be present in 0.1% to 1.5% of healthy women, and 25% to 60% of women with autoimmune disease may be asymptomatic.¹ As demonstrated in our case, when there is a family history of NLE in an infant from an earlier pregnancy, the risk for NLE increases to 17% to 20% in subsequent pregnancies^1,3 and up to 25% in subsequent pregnancies if the initial child was diagnosed with a congenital heart block in the setting of NLE.¹

Neonatal lupus erythematosus classically presents as annular erythematous macules and plaques with central scaling, telangictasia, atrophy, and pigmentary changes. It may start on the scalp and face and spread caudally.^1,2 Patients may develop these lesions after UV exposure, and 80% of infants may not have dermatologic findings at birth. Importantly, 40% to 60% of mothers may be asymptomatic at the time of presentation of their child’s NLE.¹ The diagnosis can be confirmed via antibody testing in the mother and/or infant. If performed, a punch biopsy shows interface dermatitis, vacuolar degeneration, and possible periadnexal lymphocytic infiltrates on histopathology.^1,2

Management of cutaneous NLE includes sun protection (eg, application of sunscreen) and topical corticosteroids. Most dermatologic manifestations of NLE are transient, resolving after clearance of maternal IgG antibodies in 6 to 9 months; however, some telangiectasia, dyspigmentation, and atrophic scarring may persist.^1-3

Neonatal lupus erythematosus also may have hepatobiliary, cardiac, hematologic, and less commonly neurologic manifestations. Hepatobiliary manifestations usually present as hepatomegaly or asymptomatic elevated transaminases or γ-glutamyl transferase.^1,3 Approximately 10% to 20% of infants with NLE may present with transient anemia and thrombocytopenia.¹ Cardiac manifestations are permanent and may require pacemaker implantation.^1,3 The incidence of a congenital heart block in infants with NLE is 15% to 30%.³ Cardiac NLE most commonly injures the conductive tissue, leading to a congenital atrioventricular block. The development of a congenital heart block develops in the 18th to 24th week of gestation. Manifestations of a more advanced condition can include dilation of the ascending aorta and dilated cardiomyopathy.¹ As such, patients need to be followed by a pediatric cardiologist for monitoring and treatment of any cardiac manifestations.

The overall prognosis of infants affected with NLE varies. Cardiac involvement is associated with a poor prognosis, while isolated cutaneous involvement requires little treatment and portends a favorable prognosis. It is critical for dermatologists to recognize NLE to refer patients to appropriate specialists to investigate and further monitor possible extracutaneous manifestations. With an understanding of the increased risk for a congenital heart block and NLE in subsequent pregnancies, mothers with positive anti-Ro/La antibodies should receive timely counseling and screening. In expectant mothers with suspected autoimmune disease, testing for antinuclear antibodies and SSA and SSB antibodies can be considered, as administration of hydroxychloroquine or prenatal systemic corticosteroids has proven to be effective in preventing a congenital heart block.¹ Our patient was followed by pediatric cardiology and was not found to have a congenital heart block.

The differential diagnosis includes other causes of annular erythema in infants, as NLE can mimic several conditions. Tinea corporis may present as scaly annular plaques with central clearing; however, it rarely is encountered fulminantly in neonates.⁴ Erythema multiforme is a mucocutaneous hypersensitivy reaction distinguished by targetoid morphology.⁵ It is an exceedingly rare diagnosis in neonates; the average pediatric age of onset is 5.6 years.⁶ Erythema multiforme often is associated with an infection, most commonly herpes simplex virus,⁵ and mucosal involvement is common.⁶ Urticaria multiforme (also known as acute annular urticaria) is a benign disease that appears between 2 months to 3 years of age with blanchable urticarial plaques that likely are triggered by viral or bacterial infections, antibiotics, or vaccines.⁶ Specific lesions usually will resolve within 24 hours. Annular erythema of infancy is a benign and asymptomatic gyrate erythema that presents as annular plaques with palpable borders that spread centrifugally in patients younger than 1 year. Notably, lesions should periodically fade and may reappear cyclically for months to years. Evaluation for underlying disease usually is negative.⁶

The Diagnosis: Pretibial Myxedema

Histopathology showed superficial and deep mucin deposition with proliferation of fibroblasts and thin wiry collagen bundles that were consistent with a diagnosis of pretibial myxedema. The patient was treated with clobetasol ointment 0.05% twice daily for 3 months, followed by a trial of pentoxifylline 400 mg 3 times daily for 3 months. After this treatment failed, she was started on rituximab infusions of 1 g biweekly for 1 month, followed by 500 mg at 6 months, with marked improvement after the first 2 doses of 1 g.

Pretibial myxedema is an uncommon cutaneous manifestation of autoimmune thyroid disease, occurring in 1% to 5% of patients with Graves disease. It usually occurs in older adult women on the pretibial regions and less commonly on the upper extremities, face, and areas of prior trauma.^1-3 Although typically asymptomatic, it can be painful and ulcerate.³ The clinical presentation consists of bilateral nonpitting edema with overlying indurated skin as well as flesh-colored, yellow-brown, violaceous, or peau d’orange papules and plaques.^2,3 Lesions develop over months and often have been associated with hyperhidrosis and hypertrichosis.² Many variants have been identified including nodular, plaquelike, diffuse swelling (ie, nonpitting edema), tumor, mixture, polypoid, and elephantiasis; severe cases with acral involvement are termed thyroid acropachy.^1-3 Pathogenesis likely involves the activation of thyrotropin receptors on fibroblasts by the circulating thyrotropin autoantibodies found in Graves disease. Activated fibroblasts upregulate glycosaminoglycan production, which osmotically drives the accumulation of dermal and subdermal fluid.^1,3

This diagnosis should be considered in any patient with pretibial edema or edema in areas of trauma. Graves disease most commonly is diagnosed 1 to 2 years prior to the development of pretibial myxedema; other extrathyroidal manifestations, most commonly ophthalmopathies, almost always are found in patients with pretibial myxedema. If a diagnosis of Graves disease has not been established, thyroid studies, including thyrotropin receptor antibody serum levels, should be obtained. Histopathology showing increased mucin in the dermis and increased fibroblasts can aid in diagnosis.^2,3

The differential diagnosis includes inflammatory dermatoses, such as stasis dermatitis and lipodermatosclerosis. Stasis dermatitis is characterized by lichenified yellowbrown plaques that present on the lower extremities; lipodermatosclerosis then can develop and present as atrophic sclerotic plaques with a champagne bottle–like appearance. Necrobiosis lipoidica demonstrates atrophic, shiny, yellow plaques with telangiectases and ulcerations. Hypertrophic lichen planus presents with hyperkeratotic hyperpigmented plaques on the shins.^1,2 Other diseases of cutaneous mucin deposition, namely scleromyxedema, demonstrate similar physical findings but more commonly are located on the trunk, face, and dorsal hands rather than the lower extremities.^1-3

Treatment of pretibial myxedema is difficult; normalization of thyroid function, weight reduction, and compression stockings can help reduce edema. Medical therapies aim to decrease glycosaminoglycan production by fibroblasts. First-line treatment includes topical steroids under occlusion, and second-line therapies include intralesional steroids, systemic corticosteroids, pentoxifylline, and octreotide.^2,3 Therapies for refractory disease include plasmapheresis, surgical excision, radiotherapy, and intravenous immunoglobulin; more recent studies also endorse the use of isotretinoin, intralesional hyaluronidase, and rituximab.^2,4 Success also has been observed with the insulin growth factor 1 receptor inhibitor teprotumumab in active thyroid eye disease, in which insulin growth factor 1 receptor is overexpressed by fibroblasts. Given the similar pathogenesis of thyroid ophthalmopathy with other extrathyroidal manifestations, teprotumumab is a promising option for refractory cases of pretibial myxedema and has led to disease resolution in several patients.⁴

The Diagnosis: Pretibial Myxedema

Histopathology showed superficial and deep mucin deposition with proliferation of fibroblasts and thin wiry collagen bundles that were consistent with a diagnosis of pretibial myxedema. The patient was treated with clobetasol ointment 0.05% twice daily for 3 months, followed by a trial of pentoxifylline 400 mg 3 times daily for 3 months. After this treatment failed, she was started on rituximab infusions of 1 g biweekly for 1 month, followed by 500 mg at 6 months, with marked improvement after the first 2 doses of 1 g.

Pretibial myxedema is an uncommon cutaneous manifestation of autoimmune thyroid disease, occurring in 1% to 5% of patients with Graves disease. It usually occurs in older adult women on the pretibial regions and less commonly on the upper extremities, face, and areas of prior trauma.^1-3 Although typically asymptomatic, it can be painful and ulcerate.³ The clinical presentation consists of bilateral nonpitting edema with overlying indurated skin as well as flesh-colored, yellow-brown, violaceous, or peau d’orange papules and plaques.^2,3 Lesions develop over months and often have been associated with hyperhidrosis and hypertrichosis.² Many variants have been identified including nodular, plaquelike, diffuse swelling (ie, nonpitting edema), tumor, mixture, polypoid, and elephantiasis; severe cases with acral involvement are termed thyroid acropachy.^1-3 Pathogenesis likely involves the activation of thyrotropin receptors on fibroblasts by the circulating thyrotropin autoantibodies found in Graves disease. Activated fibroblasts upregulate glycosaminoglycan production, which osmotically drives the accumulation of dermal and subdermal fluid.^1,3

This diagnosis should be considered in any patient with pretibial edema or edema in areas of trauma. Graves disease most commonly is diagnosed 1 to 2 years prior to the development of pretibial myxedema; other extrathyroidal manifestations, most commonly ophthalmopathies, almost always are found in patients with pretibial myxedema. If a diagnosis of Graves disease has not been established, thyroid studies, including thyrotropin receptor antibody serum levels, should be obtained. Histopathology showing increased mucin in the dermis and increased fibroblasts can aid in diagnosis.^2,3

The differential diagnosis includes inflammatory dermatoses, such as stasis dermatitis and lipodermatosclerosis. Stasis dermatitis is characterized by lichenified yellowbrown plaques that present on the lower extremities; lipodermatosclerosis then can develop and present as atrophic sclerotic plaques with a champagne bottle–like appearance. Necrobiosis lipoidica demonstrates atrophic, shiny, yellow plaques with telangiectases and ulcerations. Hypertrophic lichen planus presents with hyperkeratotic hyperpigmented plaques on the shins.^1,2 Other diseases of cutaneous mucin deposition, namely scleromyxedema, demonstrate similar physical findings but more commonly are located on the trunk, face, and dorsal hands rather than the lower extremities.^1-3

Treatment of pretibial myxedema is difficult; normalization of thyroid function, weight reduction, and compression stockings can help reduce edema. Medical therapies aim to decrease glycosaminoglycan production by fibroblasts. First-line treatment includes topical steroids under occlusion, and second-line therapies include intralesional steroids, systemic corticosteroids, pentoxifylline, and octreotide.^2,3 Therapies for refractory disease include plasmapheresis, surgical excision, radiotherapy, and intravenous immunoglobulin; more recent studies also endorse the use of isotretinoin, intralesional hyaluronidase, and rituximab.^2,4 Success also has been observed with the insulin growth factor 1 receptor inhibitor teprotumumab in active thyroid eye disease, in which insulin growth factor 1 receptor is overexpressed by fibroblasts. Given the similar pathogenesis of thyroid ophthalmopathy with other extrathyroidal manifestations, teprotumumab is a promising option for refractory cases of pretibial myxedema and has led to disease resolution in several patients.⁴

The Diagnosis: Pretibial Myxedema

Histopathology showed superficial and deep mucin deposition with proliferation of fibroblasts and thin wiry collagen bundles that were consistent with a diagnosis of pretibial myxedema. The patient was treated with clobetasol ointment 0.05% twice daily for 3 months, followed by a trial of pentoxifylline 400 mg 3 times daily for 3 months. After this treatment failed, she was started on rituximab infusions of 1 g biweekly for 1 month, followed by 500 mg at 6 months, with marked improvement after the first 2 doses of 1 g.

Pretibial myxedema is an uncommon cutaneous manifestation of autoimmune thyroid disease, occurring in 1% to 5% of patients with Graves disease. It usually occurs in older adult women on the pretibial regions and less commonly on the upper extremities, face, and areas of prior trauma.^1-3 Although typically asymptomatic, it can be painful and ulcerate.³ The clinical presentation consists of bilateral nonpitting edema with overlying indurated skin as well as flesh-colored, yellow-brown, violaceous, or peau d’orange papules and plaques.^2,3 Lesions develop over months and often have been associated with hyperhidrosis and hypertrichosis.² Many variants have been identified including nodular, plaquelike, diffuse swelling (ie, nonpitting edema), tumor, mixture, polypoid, and elephantiasis; severe cases with acral involvement are termed thyroid acropachy.^1-3 Pathogenesis likely involves the activation of thyrotropin receptors on fibroblasts by the circulating thyrotropin autoantibodies found in Graves disease. Activated fibroblasts upregulate glycosaminoglycan production, which osmotically drives the accumulation of dermal and subdermal fluid.^1,3

This diagnosis should be considered in any patient with pretibial edema or edema in areas of trauma. Graves disease most commonly is diagnosed 1 to 2 years prior to the development of pretibial myxedema; other extrathyroidal manifestations, most commonly ophthalmopathies, almost always are found in patients with pretibial myxedema. If a diagnosis of Graves disease has not been established, thyroid studies, including thyrotropin receptor antibody serum levels, should be obtained. Histopathology showing increased mucin in the dermis and increased fibroblasts can aid in diagnosis.^2,3

The differential diagnosis includes inflammatory dermatoses, such as stasis dermatitis and lipodermatosclerosis. Stasis dermatitis is characterized by lichenified yellowbrown plaques that present on the lower extremities; lipodermatosclerosis then can develop and present as atrophic sclerotic plaques with a champagne bottle–like appearance. Necrobiosis lipoidica demonstrates atrophic, shiny, yellow plaques with telangiectases and ulcerations. Hypertrophic lichen planus presents with hyperkeratotic hyperpigmented plaques on the shins.^1,2 Other diseases of cutaneous mucin deposition, namely scleromyxedema, demonstrate similar physical findings but more commonly are located on the trunk, face, and dorsal hands rather than the lower extremities.^1-3

Treatment of pretibial myxedema is difficult; normalization of thyroid function, weight reduction, and compression stockings can help reduce edema. Medical therapies aim to decrease glycosaminoglycan production by fibroblasts. First-line treatment includes topical steroids under occlusion, and second-line therapies include intralesional steroids, systemic corticosteroids, pentoxifylline, and octreotide.^2,3 Therapies for refractory disease include plasmapheresis, surgical excision, radiotherapy, and intravenous immunoglobulin; more recent studies also endorse the use of isotretinoin, intralesional hyaluronidase, and rituximab.^2,4 Success also has been observed with the insulin growth factor 1 receptor inhibitor teprotumumab in active thyroid eye disease, in which insulin growth factor 1 receptor is overexpressed by fibroblasts. Given the similar pathogenesis of thyroid ophthalmopathy with other extrathyroidal manifestations, teprotumumab is a promising option for refractory cases of pretibial myxedema and has led to disease resolution in several patients.⁴

The Diagnosis: Mycobacterial Infection

Mycobacterium marinum is a waterborne nontuberculous mycobacterium prevailing in salt water, brackish water, and still or streaming fresh water that infects fish and amphibians worldwide.^1,2 Although first described in 1926 as the organism responsible for the demise of fish in an aquarium in Philadelphia, Pennsylvania, it was not until 1954 that the organism was linked to the cause of infection in humans after it was identified in 80 individuals who had utilized the same swimming pool.¹ Due to its ability to secondarily contaminate aquariums, swimming pools, and rivers, this species can give rise to infection in humans, likely though an impaired skin barrier or points of trauma. It commonly is known as swimming pool or fish tank granuloma.^3,4

Infection by M marinum commonly presents with lesions on the upper extremities, particularly the hands, that appear approximately 2 to 3 weeks following exposure to the organism.² Lesions are categorized as superficial (type 1), granulomatous (type 2), or deep (type 3).¹ Superficial lesions usually are solitary and painless; may exhibit purulent secretions; and consist of papulonodular, verrucose, or ulcerated granulomatous inflammation.¹ These lesions may spread in a sporotrichoidlike pattern or in a linear fashion along lymphatic channels, similar to sporotrichosis. Granulomatous lesions present as solitary or numerous granulomas that typically are swollen, tender, and purulent. Deep lesions are the rarest form and primarily are seen in immunocompromised patients, particularly transplant recipients. Infection can lead to arthritis, tenosynovitis, or osteomyelitis.¹

Mycobacterium marinum infection is diagnosed via tissue biopsy for concomitant histopathologic examination and culture from a nonulcerated area close to the lesion.^1,2 If cultures do not grow, polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism analysis can be conducted. These techniques can exclude other potential diagnoses; however, PCR is unable to provide information on antibiotic susceptibility.1 Biopsy of lesions reveals a nonspecific inflammatory type of reaction within the dermis consisting of lymphocytes, polymorphonuclear cells, and histiocytes.^1,4 Additionally, a granulomatous inflammatory infiltrate resembling tuberculoid granuloma, sarcoidlike granuloma, or rheumatoidlike nodules also may be observed.1 With staining, the acid-fast organisms can be viewed within histiocytes, sometimes demonstrating transverse bands.⁴

The preferred treatment of M marinum infection is antibiotic therapy.² It generally is not recommended to obtain in vitro drug sensitivity testing, as mutational resistance to the commonly utilized drugs is minimal. Microbiologic investigation may be warranted in cases of treatment failure or persistently positive cultures over a period of several months.^1,2 Due to its rarity, no clinical trials exist to guide optimal management of M marinum infection, according to a search of ClinicalTrials.gov. Nonetheless, anecdotal evidence of prior cases can direct the selection of antibiotics. Mycobacterium marinum appears to respond to certain tetracyclines, including minocycline followed by doxycycline. Other options include clarithromycin, clarithromycin in combination with rifampin, rifampin in combination with ethambutol, trimethoprimsulfamethoxazole, and ciprofloxacin.^1,2 Surgical debridement or excision may be indicated, especially in an infection involving deep structures, though recurrences have been reported in some individuals following surgery.^2,4 Nonspecific treatment such as hyperthermic or liquid nitrogen local treatment have been used experimentally with positive outcomes; however, experience with this treatment modality is limited.²

Sarcoidosis is an immune-mediated systemic disorder that most commonly affects the lungs and skin. Histopathology shows sarcoidal granulomas with features similar to M marinum infection. The clinical presentation often is described as red-brown macules or papules affecting the face, rarely with overlying scale or ulceration.⁵ Majocchi granuloma is a dermatophyte fungal infection involving the hair follicles. Although application of topical steroids can worsen the involvement, it commonly displays perifollicular pustules,⁶ which were not seen in our patient. Granuloma annulare is a benign granulomatous disorder that will spontaneously resolve, typically within 2 years of onset. It presents as an annular or arcuate red-brown papule or plaque without overlying scale or ulceration,⁷ unlike the lesion seen in our patient. Cutaneous lymphoma is a malignant lymphoproliferative disease most commonly affecting middle-aged White men. The presentation is variable and may include an ulcerated plaque⁸; the lack of systemic symptoms and notable progression over several years in our patient made this a less likely diagnosis.

The Diagnosis: Mycobacterial Infection

Mycobacterium marinum is a waterborne nontuberculous mycobacterium prevailing in salt water, brackish water, and still or streaming fresh water that infects fish and amphibians worldwide.^1,2 Although first described in 1926 as the organism responsible for the demise of fish in an aquarium in Philadelphia, Pennsylvania, it was not until 1954 that the organism was linked to the cause of infection in humans after it was identified in 80 individuals who had utilized the same swimming pool.¹ Due to its ability to secondarily contaminate aquariums, swimming pools, and rivers, this species can give rise to infection in humans, likely though an impaired skin barrier or points of trauma. It commonly is known as swimming pool or fish tank granuloma.^3,4

Infection by M marinum commonly presents with lesions on the upper extremities, particularly the hands, that appear approximately 2 to 3 weeks following exposure to the organism.² Lesions are categorized as superficial (type 1), granulomatous (type 2), or deep (type 3).¹ Superficial lesions usually are solitary and painless; may exhibit purulent secretions; and consist of papulonodular, verrucose, or ulcerated granulomatous inflammation.¹ These lesions may spread in a sporotrichoidlike pattern or in a linear fashion along lymphatic channels, similar to sporotrichosis. Granulomatous lesions present as solitary or numerous granulomas that typically are swollen, tender, and purulent. Deep lesions are the rarest form and primarily are seen in immunocompromised patients, particularly transplant recipients. Infection can lead to arthritis, tenosynovitis, or osteomyelitis.¹

Mycobacterium marinum infection is diagnosed via tissue biopsy for concomitant histopathologic examination and culture from a nonulcerated area close to the lesion.^1,2 If cultures do not grow, polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism analysis can be conducted. These techniques can exclude other potential diagnoses; however, PCR is unable to provide information on antibiotic susceptibility.1 Biopsy of lesions reveals a nonspecific inflammatory type of reaction within the dermis consisting of lymphocytes, polymorphonuclear cells, and histiocytes.^1,4 Additionally, a granulomatous inflammatory infiltrate resembling tuberculoid granuloma, sarcoidlike granuloma, or rheumatoidlike nodules also may be observed.1 With staining, the acid-fast organisms can be viewed within histiocytes, sometimes demonstrating transverse bands.⁴

The preferred treatment of M marinum infection is antibiotic therapy.² It generally is not recommended to obtain in vitro drug sensitivity testing, as mutational resistance to the commonly utilized drugs is minimal. Microbiologic investigation may be warranted in cases of treatment failure or persistently positive cultures over a period of several months.^1,2 Due to its rarity, no clinical trials exist to guide optimal management of M marinum infection, according to a search of ClinicalTrials.gov. Nonetheless, anecdotal evidence of prior cases can direct the selection of antibiotics. Mycobacterium marinum appears to respond to certain tetracyclines, including minocycline followed by doxycycline. Other options include clarithromycin, clarithromycin in combination with rifampin, rifampin in combination with ethambutol, trimethoprimsulfamethoxazole, and ciprofloxacin.^1,2 Surgical debridement or excision may be indicated, especially in an infection involving deep structures, though recurrences have been reported in some individuals following surgery.^2,4 Nonspecific treatment such as hyperthermic or liquid nitrogen local treatment have been used experimentally with positive outcomes; however, experience with this treatment modality is limited.²

Sarcoidosis is an immune-mediated systemic disorder that most commonly affects the lungs and skin. Histopathology shows sarcoidal granulomas with features similar to M marinum infection. The clinical presentation often is described as red-brown macules or papules affecting the face, rarely with overlying scale or ulceration.⁵ Majocchi granuloma is a dermatophyte fungal infection involving the hair follicles. Although application of topical steroids can worsen the involvement, it commonly displays perifollicular pustules,⁶ which were not seen in our patient. Granuloma annulare is a benign granulomatous disorder that will spontaneously resolve, typically within 2 years of onset. It presents as an annular or arcuate red-brown papule or plaque without overlying scale or ulceration,⁷ unlike the lesion seen in our patient. Cutaneous lymphoma is a malignant lymphoproliferative disease most commonly affecting middle-aged White men. The presentation is variable and may include an ulcerated plaque⁸; the lack of systemic symptoms and notable progression over several years in our patient made this a less likely diagnosis.

The Diagnosis: Mycobacterial Infection

Mycobacterium marinum is a waterborne nontuberculous mycobacterium prevailing in salt water, brackish water, and still or streaming fresh water that infects fish and amphibians worldwide.^1,2 Although first described in 1926 as the organism responsible for the demise of fish in an aquarium in Philadelphia, Pennsylvania, it was not until 1954 that the organism was linked to the cause of infection in humans after it was identified in 80 individuals who had utilized the same swimming pool.¹ Due to its ability to secondarily contaminate aquariums, swimming pools, and rivers, this species can give rise to infection in humans, likely though an impaired skin barrier or points of trauma. It commonly is known as swimming pool or fish tank granuloma.^3,4

Infection by M marinum commonly presents with lesions on the upper extremities, particularly the hands, that appear approximately 2 to 3 weeks following exposure to the organism.² Lesions are categorized as superficial (type 1), granulomatous (type 2), or deep (type 3).¹ Superficial lesions usually are solitary and painless; may exhibit purulent secretions; and consist of papulonodular, verrucose, or ulcerated granulomatous inflammation.¹ These lesions may spread in a sporotrichoidlike pattern or in a linear fashion along lymphatic channels, similar to sporotrichosis. Granulomatous lesions present as solitary or numerous granulomas that typically are swollen, tender, and purulent. Deep lesions are the rarest form and primarily are seen in immunocompromised patients, particularly transplant recipients. Infection can lead to arthritis, tenosynovitis, or osteomyelitis.¹

Mycobacterium marinum infection is diagnosed via tissue biopsy for concomitant histopathologic examination and culture from a nonulcerated area close to the lesion.^1,2 If cultures do not grow, polymerase chain reaction (PCR) or PCR restriction fragment length polymorphism analysis can be conducted. These techniques can exclude other potential diagnoses; however, PCR is unable to provide information on antibiotic susceptibility.1 Biopsy of lesions reveals a nonspecific inflammatory type of reaction within the dermis consisting of lymphocytes, polymorphonuclear cells, and histiocytes.^1,4 Additionally, a granulomatous inflammatory infiltrate resembling tuberculoid granuloma, sarcoidlike granuloma, or rheumatoidlike nodules also may be observed.1 With staining, the acid-fast organisms can be viewed within histiocytes, sometimes demonstrating transverse bands.⁴

The preferred treatment of M marinum infection is antibiotic therapy.² It generally is not recommended to obtain in vitro drug sensitivity testing, as mutational resistance to the commonly utilized drugs is minimal. Microbiologic investigation may be warranted in cases of treatment failure or persistently positive cultures over a period of several months.^1,2 Due to its rarity, no clinical trials exist to guide optimal management of M marinum infection, according to a search of ClinicalTrials.gov. Nonetheless, anecdotal evidence of prior cases can direct the selection of antibiotics. Mycobacterium marinum appears to respond to certain tetracyclines, including minocycline followed by doxycycline. Other options include clarithromycin, clarithromycin in combination with rifampin, rifampin in combination with ethambutol, trimethoprimsulfamethoxazole, and ciprofloxacin.^1,2 Surgical debridement or excision may be indicated, especially in an infection involving deep structures, though recurrences have been reported in some individuals following surgery.^2,4 Nonspecific treatment such as hyperthermic or liquid nitrogen local treatment have been used experimentally with positive outcomes; however, experience with this treatment modality is limited.²

Sarcoidosis is an immune-mediated systemic disorder that most commonly affects the lungs and skin. Histopathology shows sarcoidal granulomas with features similar to M marinum infection. The clinical presentation often is described as red-brown macules or papules affecting the face, rarely with overlying scale or ulceration.⁵ Majocchi granuloma is a dermatophyte fungal infection involving the hair follicles. Although application of topical steroids can worsen the involvement, it commonly displays perifollicular pustules,⁶ which were not seen in our patient. Granuloma annulare is a benign granulomatous disorder that will spontaneously resolve, typically within 2 years of onset. It presents as an annular or arcuate red-brown papule or plaque without overlying scale or ulceration,⁷ unlike the lesion seen in our patient. Cutaneous lymphoma is a malignant lymphoproliferative disease most commonly affecting middle-aged White men. The presentation is variable and may include an ulcerated plaque⁸; the lack of systemic symptoms and notable progression over several years in our patient made this a less likely diagnosis.

The Diagnosis: Majocchi Granuloma

Histopathology showed rare follicular-based organisms highlighted by periodic acid–Schiff staining. This finding along with her use of clobetasol ointment on the hands led to a diagnosis of Majocchi granuloma in our patient. Clobetasol and crisaborole ointments were discontinued, and she was started on oral terbinafine 250 mg daily for 4 weeks, which resulted in resolution of the rash.

Majocchi granuloma (also known as nodular granulomatous perifolliculitis) is a perifollicular granulomatous process caused by a dermatophyte infection of the hair follicles. Trichophyton rubrum is the most commonly implicated organism, followed by Trichophyton mentagrophytes and Epidermophyton floccosum, which also cause tinea corporis and tinea pedis.¹ This condition most commonly occurs in women aged 20 to 35 years. Risk factors include trauma, occlusion of the hair follicles, immunosuppression, and use of potent topical corticosteroids in patients with tinea.^2,3 Immunocompetent patients present with perifollicular papules or pustules with erythematous scaly plaques on the extremities, while immunocompromised patients may have subcutaneous nodules or abscesses on any hair-bearing parts of the body.³

Majocchi granuloma is considered a dermal fungal infection in which the disruption of hair follicles from occlusion or trauma allows fungal organisms and keratinaceous material substrates to be introduced into the dermis. The differential diagnosis is based on the types of presenting lesions. The papules of Majocchi granuloma can resemble folliculitis, acne, or insect bites, while nodules can resemble erythema nodosum or furunculosis.⁴ Plaques, such as those seen in our patient, can mimic cellulitis and allergic or irritant contact dermatitis.⁴ Additionally, the plaques may appear annular or figurate, which may resemble erythema gyratum repens or erythema annulare centrifugum.

The diagnosis of Majocchi granuloma often requires fungal culture and biopsy because a potassium hydroxide preparation is unable to distinguish between superficial and invasive dermatophytes.³ Histopathology will show perifollicular granulomatous inflammation. Fungal elements can be detected with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining of the hairs and hair follicles as well as dermal infiltrates.⁴

Topical corticosteroids should be discontinued. Systemic antifungals are the treatment of choice for Majocchi granuloma, as topical antifungals are not effective against deep fungal infections. Although there are no standard guidelines on duration or dosage, recommended regimens in immunocompetent patients include terbinafine 250 mg/d for 4 weeks; itraconazole pulse therapy consisting of 200 mg twice daily for 1 week with 2 weeks off therapy, then repeat the cycle for a total of 2 to 3 pulses; and griseofulvin 500 mg twice daily for 8 to 12 weeks (Table).³ For immunocompromised patients, combination therapy with more than one antifungal may be necessary.

The Diagnosis: Majocchi Granuloma

Histopathology showed rare follicular-based organisms highlighted by periodic acid–Schiff staining. This finding along with her use of clobetasol ointment on the hands led to a diagnosis of Majocchi granuloma in our patient. Clobetasol and crisaborole ointments were discontinued, and she was started on oral terbinafine 250 mg daily for 4 weeks, which resulted in resolution of the rash.

Majocchi granuloma (also known as nodular granulomatous perifolliculitis) is a perifollicular granulomatous process caused by a dermatophyte infection of the hair follicles. Trichophyton rubrum is the most commonly implicated organism, followed by Trichophyton mentagrophytes and Epidermophyton floccosum, which also cause tinea corporis and tinea pedis.¹ This condition most commonly occurs in women aged 20 to 35 years. Risk factors include trauma, occlusion of the hair follicles, immunosuppression, and use of potent topical corticosteroids in patients with tinea.^2,3 Immunocompetent patients present with perifollicular papules or pustules with erythematous scaly plaques on the extremities, while immunocompromised patients may have subcutaneous nodules or abscesses on any hair-bearing parts of the body.³

Majocchi granuloma is considered a dermal fungal infection in which the disruption of hair follicles from occlusion or trauma allows fungal organisms and keratinaceous material substrates to be introduced into the dermis. The differential diagnosis is based on the types of presenting lesions. The papules of Majocchi granuloma can resemble folliculitis, acne, or insect bites, while nodules can resemble erythema nodosum or furunculosis.⁴ Plaques, such as those seen in our patient, can mimic cellulitis and allergic or irritant contact dermatitis.⁴ Additionally, the plaques may appear annular or figurate, which may resemble erythema gyratum repens or erythema annulare centrifugum.

The diagnosis of Majocchi granuloma often requires fungal culture and biopsy because a potassium hydroxide preparation is unable to distinguish between superficial and invasive dermatophytes.³ Histopathology will show perifollicular granulomatous inflammation. Fungal elements can be detected with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining of the hairs and hair follicles as well as dermal infiltrates.⁴

Topical corticosteroids should be discontinued. Systemic antifungals are the treatment of choice for Majocchi granuloma, as topical antifungals are not effective against deep fungal infections. Although there are no standard guidelines on duration or dosage, recommended regimens in immunocompetent patients include terbinafine 250 mg/d for 4 weeks; itraconazole pulse therapy consisting of 200 mg twice daily for 1 week with 2 weeks off therapy, then repeat the cycle for a total of 2 to 3 pulses; and griseofulvin 500 mg twice daily for 8 to 12 weeks (Table).³ For immunocompromised patients, combination therapy with more than one antifungal may be necessary.

The Diagnosis: Majocchi Granuloma

Histopathology showed rare follicular-based organisms highlighted by periodic acid–Schiff staining. This finding along with her use of clobetasol ointment on the hands led to a diagnosis of Majocchi granuloma in our patient. Clobetasol and crisaborole ointments were discontinued, and she was started on oral terbinafine 250 mg daily for 4 weeks, which resulted in resolution of the rash.

Majocchi granuloma (also known as nodular granulomatous perifolliculitis) is a perifollicular granulomatous process caused by a dermatophyte infection of the hair follicles. Trichophyton rubrum is the most commonly implicated organism, followed by Trichophyton mentagrophytes and Epidermophyton floccosum, which also cause tinea corporis and tinea pedis.¹ This condition most commonly occurs in women aged 20 to 35 years. Risk factors include trauma, occlusion of the hair follicles, immunosuppression, and use of potent topical corticosteroids in patients with tinea.^2,3 Immunocompetent patients present with perifollicular papules or pustules with erythematous scaly plaques on the extremities, while immunocompromised patients may have subcutaneous nodules or abscesses on any hair-bearing parts of the body.³

Majocchi granuloma is considered a dermal fungal infection in which the disruption of hair follicles from occlusion or trauma allows fungal organisms and keratinaceous material substrates to be introduced into the dermis. The differential diagnosis is based on the types of presenting lesions. The papules of Majocchi granuloma can resemble folliculitis, acne, or insect bites, while nodules can resemble erythema nodosum or furunculosis.⁴ Plaques, such as those seen in our patient, can mimic cellulitis and allergic or irritant contact dermatitis.⁴ Additionally, the plaques may appear annular or figurate, which may resemble erythema gyratum repens or erythema annulare centrifugum.

The diagnosis of Majocchi granuloma often requires fungal culture and biopsy because a potassium hydroxide preparation is unable to distinguish between superficial and invasive dermatophytes.³ Histopathology will show perifollicular granulomatous inflammation. Fungal elements can be detected with periodic acid–Schiff or Grocott-Gomori methenamine-silver staining of the hairs and hair follicles as well as dermal infiltrates.⁴

Topical corticosteroids should be discontinued. Systemic antifungals are the treatment of choice for Majocchi granuloma, as topical antifungals are not effective against deep fungal infections. Although there are no standard guidelines on duration or dosage, recommended regimens in immunocompetent patients include terbinafine 250 mg/d for 4 weeks; itraconazole pulse therapy consisting of 200 mg twice daily for 1 week with 2 weeks off therapy, then repeat the cycle for a total of 2 to 3 pulses; and griseofulvin 500 mg twice daily for 8 to 12 weeks (Table).³ For immunocompromised patients, combination therapy with more than one antifungal may be necessary.

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Scrotal Calcinosis

Scrotal calcinosis is a rare benign disease that results from the deposition of calcium, magnesium, phosphate, and carbonate within the dermis and subcutaneous layer of the skin in the absence of underlying systemic disease or serum calcium and phosphorus abnormalities.^1,2 Lesions usually are asymptomatic but can be mildly painful or pruritic. They usually present in childhood or early adulthood as yellow-white firm nodules ranging in size from a few millimeters to a few centimeters that increase in size and number over time. Additionally, lesions can ulcerate and discharge a chalklike exudative material. Although benign in nature, the quality-of-life impact in patients with this condition can be substantial, specifically regarding cosmesis, which may cause patients to feel embarrassed and even avoid sexual activity. This condition rarely has been associated with infection.¹

Our patient elected to undergo surgical excision under local anesthesia, and the lesions were sent for histopathologic examination. His postoperative course was unremarkable, and he was pleased with the cosmetic result of the surgery (Figure 1). Histopathology revealed calcified deposits that appeared as intradermal basophilic nodules lacking an epithelial lining (Figure 2), consistent with the diagnosis of scrotal calcinosis.² No recurrence of the lesions was documented over the course of 18 months.

The pathogenesis of this condition is not clear. Most research supports scrotal calcinosis resulting from dystrophic calcification of epidermal inclusion cysts.³ There have been cases of scrotal calcinosis coinciding with epidermal inclusion cysts of the scrotum in varying stages of inflammation (some intact and some ruptured).² Some research also suggests dystrophic calcification of eccrine epithelial cysts and degenerated dartos muscle as the origin of scrotal calcinosis.³

The differential diagnosis for this case included calcified steatocystoma multiplex, eruptive xanthomas, nodular scabies, and epidermal inclusion cysts. Steatocystoma multiplex can be inherited in an autosomal-dominant fashion or can develop sporadically with mutations in the KRT17 gene.⁴ It is characterized by multiple sebum-filled, cystic lesions of the pilosebaceous unit that may become calcified. Calcified lesions appear as yellow, firm, irregularly shaped papules or nodules ranging from a few millimeters to centimeters in size. Cysts can develop anywhere on the body with a predilection for the chest, upper extremities, axillae, trunk, groin, and scrotum.⁴ Histologically, our patient’s lesions were not associated with the pilosebaceous unit. Additionally, our patient denied a family history of similar skin lesions, which made calcified steatocystoma multiplex an unlikely diagnosis.

Eruptive xanthomas result from localized deposition of lipids within the dermis, typically in the setting of dyslipidemia or poorly controlled diabetes mellitus. They commonly appear on the extremities or buttocks as pruritic crops of yellow-red papules or nodules that are a few millimeters in size. Although our patient has a history of hyperlipidemia, his lesions differed substantially from eruptive xanthomas in clinical presentation.

Nodular scabies is a manifestation of classic scabies that presents with intensely pruritic erythematous papules and nodules that are a few millimeters in size and commonly occur on the axillae, groin, and genitalia. Our patient’s skin lesions were not pruritic and differed in appearance from nodular scabies.

Although research indicates scrotal calcinosis may result from dystrophic calcification of epidermal inclusion cysts,² the latter present as dome-shaped, flesh-colored nodules with central pores representing the opening of hair follicles. Our patient lacked characteristic findings of epidermal inclusion cysts on histology.

The preferred treatment for scrotal calcinosis is surgical excision, which improves the aesthetic appearance, relieves itch, and removes ulcerative lesions.⁵ Additionally, surgical excision provides histological diagnostic confirmation. Recurrence with incomplete excision is possible; therefore, all lesions should be completely excised to reduce the risk for recurrence.³

The Diagnosis: Extragenital Lichen Sclerosus et Atrophicus

A punch biopsy of the lesion revealed epidermal hyperkeratosis, atrophy, follicular plugs with basal vacuolar degeneration, and homogenous dense fibrosis in the papillary dermis with a dense lymphocytic infiltrate beneath the fibrosis (Figure 1). Dermoscopic examination was remarkable for a distinctive rainbow pattern. Clinical, histopathologic, and dermoscopic findings led to the diagnosis of extragenital lichen sclerosus et atrophicus (LSEA). A potent corticosteroid cream was prescribed twice daily for 2 months, after which the lesions completely resolved. At 2-year follow-up, a relapse was not observed (Figure 2).

Lichen sclerosus et atrophicus is an inflammatory dermatosis that clinically presents as atrophic or hypertrophic plaques that may show pigmentation changes with anogenital and extragenital involvement. It is common among females and predominantly occurs in prepubescent girls and postmenopausal women. The exact etiology is unclear; however, it is hypothesized to occur secondary to autoimmunity with an underlying genetic predisposition. Local trauma, hormonal influences, and infections are other suspected etiologic factors. Genital lesions often lead to itching, pain, and dyspareunia, whereas extragenital lesions predominantly are asymptomatic. When symptomatic, itching usually is the main concern. Unlike genital LSEA, extragenital lesions are not associated with squamous cell carcinoma development. Reported dermoscopic features of LSEA are white structureless areas with scaling, comedolike openings, follicular plugs, white shiny streaks, blue-gray peppering, pigment network, and red-purple globules.¹ In our case, the dermoscopic finding of a rainbow pattern in LSEA is rare.² Although the mechanism behind this appearance unclear, it can be the result of the birefringence effect—local variations in refractive index—influenced by the direction of structures within the dermis such as collagen. In this case, there was diffuse and dense homogenous fibrosis in the superficial dermis that corresponded to dermoscopic white polygonal clods.

Extragenital LSEA commonly is located on the neck, shoulders, wrists, and upper trunk and manifests clinically as whitish papules coalescing into scarlike plaques. Of all patients who have LSEA, 20% have extragenital lesions, and most of these lesions are seen in patients who also have genital LSEA. Approximately 6% of all LSEA patients have extragenital LSEA without genital involvement.³

For experienced dermatologists, clinical symptoms and lesion characteristics usually are sufficient for diagnosis; however, a differential diagnosis of atypical lesions and isolated extragenital presentations such as morphea, lichen simplex chronicus, lichen planus, and vitiligo requires the correlation of clinical findings with histopathology and dermoscopy. Morphea, known as localized scleroderma, is an idiopathic inflammatory skin disease with sclerotic changes. It manifests as inflammatory plaques that vary in color from red to purple. If there is moderate sclerosis in the center of this plaque, the color progressively fades to white, leaving a purplish ring around the edges. Dermoscopic features of morphea are reported as areas of erythema; red-focused vessels of linear, irregular, or dotted morphology; white fibrotic beams; and pigmentary structures.² Lichen simplex chronicus is characterized by single or multiple dry and patchy skin lesions that are intensely pruritic. It commonly occurs on the neck, scalp, extremities, genital areas, and buttocks. Scratching the lesions leads to scarring, thickening of the skin, and increased frequency of itching. Histopathology of lichen simplex chronicus most frequently demonstrates a thickening of the epidermis and papillary dermis, irregularly elongated rete ridges, and fibroplasia with stellate or multinucleated fibroblasts completed by perivascular lymphocytic inflammation.⁴ Lichen planus presents with pruritic, polygonal, purple papules and/or plaques that can present in a variety of clinical forms, including atrophic and hypertrophic lichen planus.⁵ Lichen planus was an unlikely diagnosis for our patient due to the presence of patchy scarlike lesions and dermoscopic features that are well described in patients with LSEA. Lichen sclerosus et atrophicus presents with hypopigmented and/or hyperpigmented patches and plaques, distinguishing itself from vitiligo, which has flat lesions.

Topical steroids are the first-line therapeutic agents in the treatment of LSEA.6 Despite frequent use in this setting, common side effects such as localized scarring and atrophic degenerations have led to debate about their use. In our patient, the lesions resolved almost completely in 2 months, and no relapse was observed in the following 2 years. In the setting of topical steroid resistance, topical calcineurin inhibitors, UVA/UVB phototherapy, and topical tacrolimus can be used for treatment.⁶

The diagnosis of isolated extragenital LSEA may be a clinical challenge and generally requires further workup. When evaluating extragenital lesions, dermatologists should keep in mind extragenital LSEA as a differential diagnosis in the presence of a dermoscopic rainbow pattern arranged over white polygonal clods.

The Diagnosis: Extragenital Lichen Sclerosus et Atrophicus

A punch biopsy of the lesion revealed epidermal hyperkeratosis, atrophy, follicular plugs with basal vacuolar degeneration, and homogenous dense fibrosis in the papillary dermis with a dense lymphocytic infiltrate beneath the fibrosis (Figure 1). Dermoscopic examination was remarkable for a distinctive rainbow pattern. Clinical, histopathologic, and dermoscopic findings led to the diagnosis of extragenital lichen sclerosus et atrophicus (LSEA). A potent corticosteroid cream was prescribed twice daily for 2 months, after which the lesions completely resolved. At 2-year follow-up, a relapse was not observed (Figure 2).

Lichen sclerosus et atrophicus is an inflammatory dermatosis that clinically presents as atrophic or hypertrophic plaques that may show pigmentation changes with anogenital and extragenital involvement. It is common among females and predominantly occurs in prepubescent girls and postmenopausal women. The exact etiology is unclear; however, it is hypothesized to occur secondary to autoimmunity with an underlying genetic predisposition. Local trauma, hormonal influences, and infections are other suspected etiologic factors. Genital lesions often lead to itching, pain, and dyspareunia, whereas extragenital lesions predominantly are asymptomatic. When symptomatic, itching usually is the main concern. Unlike genital LSEA, extragenital lesions are not associated with squamous cell carcinoma development. Reported dermoscopic features of LSEA are white structureless areas with scaling, comedolike openings, follicular plugs, white shiny streaks, blue-gray peppering, pigment network, and red-purple globules.¹ In our case, the dermoscopic finding of a rainbow pattern in LSEA is rare.² Although the mechanism behind this appearance unclear, it can be the result of the birefringence effect—local variations in refractive index—influenced by the direction of structures within the dermis such as collagen. In this case, there was diffuse and dense homogenous fibrosis in the superficial dermis that corresponded to dermoscopic white polygonal clods.

Extragenital LSEA commonly is located on the neck, shoulders, wrists, and upper trunk and manifests clinically as whitish papules coalescing into scarlike plaques. Of all patients who have LSEA, 20% have extragenital lesions, and most of these lesions are seen in patients who also have genital LSEA. Approximately 6% of all LSEA patients have extragenital LSEA without genital involvement.³

For experienced dermatologists, clinical symptoms and lesion characteristics usually are sufficient for diagnosis; however, a differential diagnosis of atypical lesions and isolated extragenital presentations such as morphea, lichen simplex chronicus, lichen planus, and vitiligo requires the correlation of clinical findings with histopathology and dermoscopy. Morphea, known as localized scleroderma, is an idiopathic inflammatory skin disease with sclerotic changes. It manifests as inflammatory plaques that vary in color from red to purple. If there is moderate sclerosis in the center of this plaque, the color progressively fades to white, leaving a purplish ring around the edges. Dermoscopic features of morphea are reported as areas of erythema; red-focused vessels of linear, irregular, or dotted morphology; white fibrotic beams; and pigmentary structures.² Lichen simplex chronicus is characterized by single or multiple dry and patchy skin lesions that are intensely pruritic. It commonly occurs on the neck, scalp, extremities, genital areas, and buttocks. Scratching the lesions leads to scarring, thickening of the skin, and increased frequency of itching. Histopathology of lichen simplex chronicus most frequently demonstrates a thickening of the epidermis and papillary dermis, irregularly elongated rete ridges, and fibroplasia with stellate or multinucleated fibroblasts completed by perivascular lymphocytic inflammation.⁴ Lichen planus presents with pruritic, polygonal, purple papules and/or plaques that can present in a variety of clinical forms, including atrophic and hypertrophic lichen planus.⁵ Lichen planus was an unlikely diagnosis for our patient due to the presence of patchy scarlike lesions and dermoscopic features that are well described in patients with LSEA. Lichen sclerosus et atrophicus presents with hypopigmented and/or hyperpigmented patches and plaques, distinguishing itself from vitiligo, which has flat lesions.

Topical steroids are the first-line therapeutic agents in the treatment of LSEA.6 Despite frequent use in this setting, common side effects such as localized scarring and atrophic degenerations have led to debate about their use. In our patient, the lesions resolved almost completely in 2 months, and no relapse was observed in the following 2 years. In the setting of topical steroid resistance, topical calcineurin inhibitors, UVA/UVB phototherapy, and topical tacrolimus can be used for treatment.⁶

The diagnosis of isolated extragenital LSEA may be a clinical challenge and generally requires further workup. When evaluating extragenital lesions, dermatologists should keep in mind extragenital LSEA as a differential diagnosis in the presence of a dermoscopic rainbow pattern arranged over white polygonal clods.

The Diagnosis: Extragenital Lichen Sclerosus et Atrophicus

A punch biopsy of the lesion revealed epidermal hyperkeratosis, atrophy, follicular plugs with basal vacuolar degeneration, and homogenous dense fibrosis in the papillary dermis with a dense lymphocytic infiltrate beneath the fibrosis (Figure 1). Dermoscopic examination was remarkable for a distinctive rainbow pattern. Clinical, histopathologic, and dermoscopic findings led to the diagnosis of extragenital lichen sclerosus et atrophicus (LSEA). A potent corticosteroid cream was prescribed twice daily for 2 months, after which the lesions completely resolved. At 2-year follow-up, a relapse was not observed (Figure 2).

Lichen sclerosus et atrophicus is an inflammatory dermatosis that clinically presents as atrophic or hypertrophic plaques that may show pigmentation changes with anogenital and extragenital involvement. It is common among females and predominantly occurs in prepubescent girls and postmenopausal women. The exact etiology is unclear; however, it is hypothesized to occur secondary to autoimmunity with an underlying genetic predisposition. Local trauma, hormonal influences, and infections are other suspected etiologic factors. Genital lesions often lead to itching, pain, and dyspareunia, whereas extragenital lesions predominantly are asymptomatic. When symptomatic, itching usually is the main concern. Unlike genital LSEA, extragenital lesions are not associated with squamous cell carcinoma development. Reported dermoscopic features of LSEA are white structureless areas with scaling, comedolike openings, follicular plugs, white shiny streaks, blue-gray peppering, pigment network, and red-purple globules.¹ In our case, the dermoscopic finding of a rainbow pattern in LSEA is rare.² Although the mechanism behind this appearance unclear, it can be the result of the birefringence effect—local variations in refractive index—influenced by the direction of structures within the dermis such as collagen. In this case, there was diffuse and dense homogenous fibrosis in the superficial dermis that corresponded to dermoscopic white polygonal clods.

Extragenital LSEA commonly is located on the neck, shoulders, wrists, and upper trunk and manifests clinically as whitish papules coalescing into scarlike plaques. Of all patients who have LSEA, 20% have extragenital lesions, and most of these lesions are seen in patients who also have genital LSEA. Approximately 6% of all LSEA patients have extragenital LSEA without genital involvement.³

For experienced dermatologists, clinical symptoms and lesion characteristics usually are sufficient for diagnosis; however, a differential diagnosis of atypical lesions and isolated extragenital presentations such as morphea, lichen simplex chronicus, lichen planus, and vitiligo requires the correlation of clinical findings with histopathology and dermoscopy. Morphea, known as localized scleroderma, is an idiopathic inflammatory skin disease with sclerotic changes. It manifests as inflammatory plaques that vary in color from red to purple. If there is moderate sclerosis in the center of this plaque, the color progressively fades to white, leaving a purplish ring around the edges. Dermoscopic features of morphea are reported as areas of erythema; red-focused vessels of linear, irregular, or dotted morphology; white fibrotic beams; and pigmentary structures.² Lichen simplex chronicus is characterized by single or multiple dry and patchy skin lesions that are intensely pruritic. It commonly occurs on the neck, scalp, extremities, genital areas, and buttocks. Scratching the lesions leads to scarring, thickening of the skin, and increased frequency of itching. Histopathology of lichen simplex chronicus most frequently demonstrates a thickening of the epidermis and papillary dermis, irregularly elongated rete ridges, and fibroplasia with stellate or multinucleated fibroblasts completed by perivascular lymphocytic inflammation.⁴ Lichen planus presents with pruritic, polygonal, purple papules and/or plaques that can present in a variety of clinical forms, including atrophic and hypertrophic lichen planus.⁵ Lichen planus was an unlikely diagnosis for our patient due to the presence of patchy scarlike lesions and dermoscopic features that are well described in patients with LSEA. Lichen sclerosus et atrophicus presents with hypopigmented and/or hyperpigmented patches and plaques, distinguishing itself from vitiligo, which has flat lesions.

Topical steroids are the first-line therapeutic agents in the treatment of LSEA.6 Despite frequent use in this setting, common side effects such as localized scarring and atrophic degenerations have led to debate about their use. In our patient, the lesions resolved almost completely in 2 months, and no relapse was observed in the following 2 years. In the setting of topical steroid resistance, topical calcineurin inhibitors, UVA/UVB phototherapy, and topical tacrolimus can be used for treatment.⁶

The diagnosis of isolated extragenital LSEA may be a clinical challenge and generally requires further workup. When evaluating extragenital lesions, dermatologists should keep in mind extragenital LSEA as a differential diagnosis in the presence of a dermoscopic rainbow pattern arranged over white polygonal clods.

The Diagnosis: Mpox (Monkeypox)

Tests for active herpes simplex virus (HHV), gonorrhea, chlamydia, HIV, and syphilis were negative. Swabs from the penile lesion demonstrated positivity for the West African clade of mpox (monkeypox) virus (MPXV) by polymerase chain reaction. The patient was treated supportively without the addition of antiviral therapy, and he experienced a complete recovery.

Mpox virus was first isolated in 1958 in a research facility and was named after the laboratory animals that were housed there. The first human documentation of the disease occurred in 1970, and it was first documented in the United States in 2003 in an infection that was traced to a shipment of small mammals from Ghana to Texas.¹ The disease has always been endemic to Africa; however, the incidence has been increasing.² A new MPXV outbreak was reported in many countries in early 2022, including the United States.¹

The MPXV is a double-stranded DNA virus of the genus Orthopoxvirus, and 2 genetic clades have been identified: clade I (formerly the Central African clade) and clade II (formerly the West African clade). The virus has the capability to infect many mammals; however, its host remains unidentified.¹ The exact mechanism of transmission from infected animals to humans largely is unknown; however, direct or indirect contact with infected animals likely is responsible. Human-to-human transmission can occur by many mechanisms including contact with large respiratory droplets, bodily fluids, and contaminated surfaces. The incubation period is 5 to 21 days, and the symptoms last 2 to 5 weeks.¹

The clinical manifestations of MPXV during the most recent outbreak differ from prior outbreaks. Patients are more likely to experience minimal to no systemic symptoms, and cutaneous lesions can be few and localized to a focal area, especially on the face and in the anogenital region,³ similar to the presentation in our patient (Figure 1). Cutaneous lesions of the most recent MPXV outbreak also include painless ulcerations similar to syphilitic chancres and lesions that are in various stages of healing.³ Lesions often begin as pseudopustules, which are firm white papules with or without a necrotic center that resemble pustules; unlike true pustules, there is no identifiable purulent material within it. Bacterial superinfection of the lesions is not uncommon.⁴ Over time, a secondary pustular eruption resembling folliculitis also may occur,4 as noted in our patient (Figure 2).

Although we did not have a biopsy to support the diagnosis of associated erythema multiforme (EM) in our patient, features supportive of this diagnosis included the classic clinical appearance of typical, well-defined, targetoid plaques with 3 distinct zones (Figure 3); the association with a known infection; the distribution on the arms with truncal sparing; and self-limited lesions. More than 90% of EM cases are associated with infection, with HHV representing the most common culprit⁵; therefore, the relationship with a different virus is not an unreasonable suggestion. Additionally, there have been rare reports of EM in association with MPXV.⁴

Histopathology of MPXV may have distinctive features. Lesions often demonstrate keratinocytic necrosis and basal layer vacuolization with an associated superficial and deep perivascular lymphohistiocytic infiltrate. When the morphology of the lesion is vesicular, histopathology reveals spongiosis and ballooning degeneration with epidermal necrosis. Viral inclusion bodies within keratinocytes may be identified.¹ Death rates from MPXV has been reported from 1% to 11%, with increased mortality among high-risk populations including children and immunocompromised individuals. Treatment of the disease largely consists of supportive care and management of any associated complications including bacterial infection, pneumonia, and encephalitis.¹

The differential diagnosis of MPXV includes other ulcerative lesions that can occur on the genital skin. Fixed drug eruptions often present on the penis,⁶ but there was no identifiable inciting drug in our patient. Herpes simplex virus infection was very high on the differential given our patient’s history of recurrent infections and association with a targetoid rash, but HHV type 1 and HHV type 2 testing of the lesion was negative. A syphilitic chancre also may present with the nontender genital ulceration⁷ that was seen in our patient, but serology did not support this diagnosis. Cutaneous Crohn disease also may manifest with genital ulceration even before a diagnosis of Crohn disease is made, but these lesions often present as linear knife-cut ulcerations of the anogenital region.⁸

Our case further supports a clinical presentation that diverges from the more traditional cases of MPXV. Additionally, associated EM may be a clue to infection, especially in cases of negative HHV and other sexually transmitted infection testing.

The Diagnosis: Mpox (Monkeypox)

Tests for active herpes simplex virus (HHV), gonorrhea, chlamydia, HIV, and syphilis were negative. Swabs from the penile lesion demonstrated positivity for the West African clade of mpox (monkeypox) virus (MPXV) by polymerase chain reaction. The patient was treated supportively without the addition of antiviral therapy, and he experienced a complete recovery.

Mpox virus was first isolated in 1958 in a research facility and was named after the laboratory animals that were housed there. The first human documentation of the disease occurred in 1970, and it was first documented in the United States in 2003 in an infection that was traced to a shipment of small mammals from Ghana to Texas.¹ The disease has always been endemic to Africa; however, the incidence has been increasing.² A new MPXV outbreak was reported in many countries in early 2022, including the United States.¹

The MPXV is a double-stranded DNA virus of the genus Orthopoxvirus, and 2 genetic clades have been identified: clade I (formerly the Central African clade) and clade II (formerly the West African clade). The virus has the capability to infect many mammals; however, its host remains unidentified.¹ The exact mechanism of transmission from infected animals to humans largely is unknown; however, direct or indirect contact with infected animals likely is responsible. Human-to-human transmission can occur by many mechanisms including contact with large respiratory droplets, bodily fluids, and contaminated surfaces. The incubation period is 5 to 21 days, and the symptoms last 2 to 5 weeks.¹

The clinical manifestations of MPXV during the most recent outbreak differ from prior outbreaks. Patients are more likely to experience minimal to no systemic symptoms, and cutaneous lesions can be few and localized to a focal area, especially on the face and in the anogenital region,³ similar to the presentation in our patient (Figure 1). Cutaneous lesions of the most recent MPXV outbreak also include painless ulcerations similar to syphilitic chancres and lesions that are in various stages of healing.³ Lesions often begin as pseudopustules, which are firm white papules with or without a necrotic center that resemble pustules; unlike true pustules, there is no identifiable purulent material within it. Bacterial superinfection of the lesions is not uncommon.⁴ Over time, a secondary pustular eruption resembling folliculitis also may occur,4 as noted in our patient (Figure 2).

Although we did not have a biopsy to support the diagnosis of associated erythema multiforme (EM) in our patient, features supportive of this diagnosis included the classic clinical appearance of typical, well-defined, targetoid plaques with 3 distinct zones (Figure 3); the association with a known infection; the distribution on the arms with truncal sparing; and self-limited lesions. More than 90% of EM cases are associated with infection, with HHV representing the most common culprit⁵; therefore, the relationship with a different virus is not an unreasonable suggestion. Additionally, there have been rare reports of EM in association with MPXV.⁴

Histopathology of MPXV may have distinctive features. Lesions often demonstrate keratinocytic necrosis and basal layer vacuolization with an associated superficial and deep perivascular lymphohistiocytic infiltrate. When the morphology of the lesion is vesicular, histopathology reveals spongiosis and ballooning degeneration with epidermal necrosis. Viral inclusion bodies within keratinocytes may be identified.¹ Death rates from MPXV has been reported from 1% to 11%, with increased mortality among high-risk populations including children and immunocompromised individuals. Treatment of the disease largely consists of supportive care and management of any associated complications including bacterial infection, pneumonia, and encephalitis.¹

The differential diagnosis of MPXV includes other ulcerative lesions that can occur on the genital skin. Fixed drug eruptions often present on the penis,⁶ but there was no identifiable inciting drug in our patient. Herpes simplex virus infection was very high on the differential given our patient’s history of recurrent infections and association with a targetoid rash, but HHV type 1 and HHV type 2 testing of the lesion was negative. A syphilitic chancre also may present with the nontender genital ulceration⁷ that was seen in our patient, but serology did not support this diagnosis. Cutaneous Crohn disease also may manifest with genital ulceration even before a diagnosis of Crohn disease is made, but these lesions often present as linear knife-cut ulcerations of the anogenital region.⁸

Our case further supports a clinical presentation that diverges from the more traditional cases of MPXV. Additionally, associated EM may be a clue to infection, especially in cases of negative HHV and other sexually transmitted infection testing.

The Diagnosis: Mpox (Monkeypox)

Tests for active herpes simplex virus (HHV), gonorrhea, chlamydia, HIV, and syphilis were negative. Swabs from the penile lesion demonstrated positivity for the West African clade of mpox (monkeypox) virus (MPXV) by polymerase chain reaction. The patient was treated supportively without the addition of antiviral therapy, and he experienced a complete recovery.

Mpox virus was first isolated in 1958 in a research facility and was named after the laboratory animals that were housed there. The first human documentation of the disease occurred in 1970, and it was first documented in the United States in 2003 in an infection that was traced to a shipment of small mammals from Ghana to Texas.¹ The disease has always been endemic to Africa; however, the incidence has been increasing.² A new MPXV outbreak was reported in many countries in early 2022, including the United States.¹

The MPXV is a double-stranded DNA virus of the genus Orthopoxvirus, and 2 genetic clades have been identified: clade I (formerly the Central African clade) and clade II (formerly the West African clade). The virus has the capability to infect many mammals; however, its host remains unidentified.¹ The exact mechanism of transmission from infected animals to humans largely is unknown; however, direct or indirect contact with infected animals likely is responsible. Human-to-human transmission can occur by many mechanisms including contact with large respiratory droplets, bodily fluids, and contaminated surfaces. The incubation period is 5 to 21 days, and the symptoms last 2 to 5 weeks.¹

The clinical manifestations of MPXV during the most recent outbreak differ from prior outbreaks. Patients are more likely to experience minimal to no systemic symptoms, and cutaneous lesions can be few and localized to a focal area, especially on the face and in the anogenital region,³ similar to the presentation in our patient (Figure 1). Cutaneous lesions of the most recent MPXV outbreak also include painless ulcerations similar to syphilitic chancres and lesions that are in various stages of healing.³ Lesions often begin as pseudopustules, which are firm white papules with or without a necrotic center that resemble pustules; unlike true pustules, there is no identifiable purulent material within it. Bacterial superinfection of the lesions is not uncommon.⁴ Over time, a secondary pustular eruption resembling folliculitis also may occur,4 as noted in our patient (Figure 2).

Although we did not have a biopsy to support the diagnosis of associated erythema multiforme (EM) in our patient, features supportive of this diagnosis included the classic clinical appearance of typical, well-defined, targetoid plaques with 3 distinct zones (Figure 3); the association with a known infection; the distribution on the arms with truncal sparing; and self-limited lesions. More than 90% of EM cases are associated with infection, with HHV representing the most common culprit⁵; therefore, the relationship with a different virus is not an unreasonable suggestion. Additionally, there have been rare reports of EM in association with MPXV.⁴

Histopathology of MPXV may have distinctive features. Lesions often demonstrate keratinocytic necrosis and basal layer vacuolization with an associated superficial and deep perivascular lymphohistiocytic infiltrate. When the morphology of the lesion is vesicular, histopathology reveals spongiosis and ballooning degeneration with epidermal necrosis. Viral inclusion bodies within keratinocytes may be identified.¹ Death rates from MPXV has been reported from 1% to 11%, with increased mortality among high-risk populations including children and immunocompromised individuals. Treatment of the disease largely consists of supportive care and management of any associated complications including bacterial infection, pneumonia, and encephalitis.¹

The differential diagnosis of MPXV includes other ulcerative lesions that can occur on the genital skin. Fixed drug eruptions often present on the penis,⁶ but there was no identifiable inciting drug in our patient. Herpes simplex virus infection was very high on the differential given our patient’s history of recurrent infections and association with a targetoid rash, but HHV type 1 and HHV type 2 testing of the lesion was negative. A syphilitic chancre also may present with the nontender genital ulceration⁷ that was seen in our patient, but serology did not support this diagnosis. Cutaneous Crohn disease also may manifest with genital ulceration even before a diagnosis of Crohn disease is made, but these lesions often present as linear knife-cut ulcerations of the anogenital region.⁸

Our case further supports a clinical presentation that diverges from the more traditional cases of MPXV. Additionally, associated EM may be a clue to infection, especially in cases of negative HHV and other sexually transmitted infection testing.