Photo Challenge

The Diagnosis: Linear Lichen Planus

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

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

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

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

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

The Diagnosis: Linear Lichen Planus

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

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

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

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

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

The Diagnosis: Linear Lichen Planus

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

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

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

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

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

The Diagnosis: Calcinosis Cutis Due to Systemic Sclerosis Sine Scleroderma

Laboratory evaluation was notable for high titers of antinuclear antibodies (>1/320; reference range, 0–1/80) and positive anticentromere antibodies. There were no other relevant laboratory findings; phosphocalcic metabolism was within normal limits, and urinary sediment was normal. Biopsy of the edge of the ulcer revealed basophilic material compatible with calcium deposits. In a 3D volume rendering reconstruction from the lower limb scanner, grouped calcifications were observed in subcutaneous cellular tissue near the ulcer (Figure). The patient had a restrictive ventilatory pattern observed in a pulmonary function test. An esophageal motility study was normal.

The patient was diagnosed with systemic sclerosis sine scleroderma (ssSSc) type II because she met the 4 criteria established by Poormoghim et al¹ : (1) Raynaud phenomenon or a peripheral vascular equivalent (ie, digital pitting scars, digital-tip ulcers, digital-tip gangrene, abnormal nail fold capillaries); (2) positive antinuclear antibodies; (3) distal esophageal hypomotility, small bowel hypomotility, pulmonary interstitial fibrosis, primary pulmonary arterial hypertension (without fibrosis), cardiac involvement typical of scleroderma, or renal failure; and (4) no other defined connective tissue or other disease as a cause of the prior conditions.

Systemic sclerosis is a chronic disease characterized by progressive fibrosis of the skin and other internal organs—especially the lungs, kidneys, digestive tract, and heart—as well as generalized vascular dysfunction. Cutaneous induration is its hallmark; however, up to 10% of affected patients have ssSSc.² This entity is characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. There are 3 types of ssSSc depending on the grade of skin involvement. Type I is characterized by the lack of any typical cutaneous stigmata of the disease. Type II is without sclerodactyly but can coexist with other cutaneous findings such as calcifications, telangiectases, or pitting scars. Type III is characterized clinically by internal organ involvement, typical of systemic sclerosis, that has appeared before skin changes.²

An abnormal deposit of calcium in the cutaneous and subcutaneous tissue is called calcinosis cutis. There are 5 subtypes of calcinosis cutis: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Dystrophic skin calcifications may appear in patients with connective tissue diseases such as dermatomyositis or systemic sclerosis.³ Up to 25% of patients with systemic sclerosis can develop calcinosis cutis due to local tissue damage, with normal phosphocalcic metabolism.³

Calcinosis cutis is more common in patients with systemic sclerosis and positive anticentromere antibodies.⁴ The calcifications usually are located in areas that are subject to repeated trauma, such as the fingers or arms, though other locations have been described such as cervical, paraspinal, or on the hips.^5,6 Our patient developed calcifications on both legs, which represent atypical areas for this process.

Dermatomyositis also can present with calcinosis cutis. There are 4 patterns of calcification: superficial nodulelike calcified masses; deep calcified masses; deep sheetlike calcifications within the fascial planes; and a rare, diffuse, superficial lacy and reticular calcification that involves almost the entire body surface area.⁷ Patients with calcinosis cutis secondary to dermatomyositis usually develop proximal muscle weakness, high titers of creatine kinase, heliotrope rash, or interstitial lung disease with specific antibodies.

Calciphylaxis is a serious disorder involving the calcification of dermal and subcutaneous arterioles and capillaries. It presents with painful cutaneous areas of necrosis.

Venous ulcers also can present with secondary dystrophic calcification due to local tissue damage. These patients usually have cutaneous signs of chronic venous insufficiency. Our patient denied prior trauma to the area; therefore, a traumatic ulcer with secondary calcification was ruled out.

The most concerning complication of calcinosis cutis is the development of ulcers, which occurred in 154 of 316 calcinoses (48.7%) in patients with systemic sclerosis and secondary calcifications.⁸ These ulcers can cause disabling pain or become superinfected, as in our patient.

There currently is no drug capable of removing dystrophic calcifications, but diltiazem, minocycline, or colchicine can reduce their size and prevent their progression. In the event of neurologic compromise or intractable pain, the treatment of choice is surgical removal of the calcification.⁹ Curettage, intralesional sodium thiosulfate, and intravenous sodium thiosulfate also have been suggested as therapeutic options.¹⁰ Antibiotic treatment was carried out in our patient, which controlled the superinfection of the ulcers. Diltiazem also was started, with stabilization of the calcium deposits without a reduction in their size.

There are few studies evaluating the presence of nondigital ulcers in patients with systemic sclerosis. Shanmugam et al¹¹ calculated a 4% (N=249) prevalence of ulcers in the lower limbs of systemic sclerosis patients. In a study by Bohelay et al¹² of 45 patients, the estimated prevalence of lower limb ulcers was 12.8%, and the etiologies consisted of 22 cases of venous insufficiency (49%), 21 cases of ischemic causes (47%), and 2 cases of other causes (4%).

We present the case of a woman with ssSSc who developed dystrophic calcinosis cutis in atypical areas with secondary ulceration and superinfection. The skin usually plays a key role in the diagnosis of systemic sclerosis, as sclerodactyly and the characteristic generalized skin induration stand out in affected individuals. Although our patient was diagnosed with ssSSc, her skin manifestations also were crucial for the diagnosis, as she had ulcers on the lower limbs.

The Diagnosis: Calcinosis Cutis Due to Systemic Sclerosis Sine Scleroderma

Laboratory evaluation was notable for high titers of antinuclear antibodies (>1/320; reference range, 0–1/80) and positive anticentromere antibodies. There were no other relevant laboratory findings; phosphocalcic metabolism was within normal limits, and urinary sediment was normal. Biopsy of the edge of the ulcer revealed basophilic material compatible with calcium deposits. In a 3D volume rendering reconstruction from the lower limb scanner, grouped calcifications were observed in subcutaneous cellular tissue near the ulcer (Figure). The patient had a restrictive ventilatory pattern observed in a pulmonary function test. An esophageal motility study was normal.

The patient was diagnosed with systemic sclerosis sine scleroderma (ssSSc) type II because she met the 4 criteria established by Poormoghim et al¹ : (1) Raynaud phenomenon or a peripheral vascular equivalent (ie, digital pitting scars, digital-tip ulcers, digital-tip gangrene, abnormal nail fold capillaries); (2) positive antinuclear antibodies; (3) distal esophageal hypomotility, small bowel hypomotility, pulmonary interstitial fibrosis, primary pulmonary arterial hypertension (without fibrosis), cardiac involvement typical of scleroderma, or renal failure; and (4) no other defined connective tissue or other disease as a cause of the prior conditions.

Systemic sclerosis is a chronic disease characterized by progressive fibrosis of the skin and other internal organs—especially the lungs, kidneys, digestive tract, and heart—as well as generalized vascular dysfunction. Cutaneous induration is its hallmark; however, up to 10% of affected patients have ssSSc.² This entity is characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. There are 3 types of ssSSc depending on the grade of skin involvement. Type I is characterized by the lack of any typical cutaneous stigmata of the disease. Type II is without sclerodactyly but can coexist with other cutaneous findings such as calcifications, telangiectases, or pitting scars. Type III is characterized clinically by internal organ involvement, typical of systemic sclerosis, that has appeared before skin changes.²

An abnormal deposit of calcium in the cutaneous and subcutaneous tissue is called calcinosis cutis. There are 5 subtypes of calcinosis cutis: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Dystrophic skin calcifications may appear in patients with connective tissue diseases such as dermatomyositis or systemic sclerosis.³ Up to 25% of patients with systemic sclerosis can develop calcinosis cutis due to local tissue damage, with normal phosphocalcic metabolism.³

Calcinosis cutis is more common in patients with systemic sclerosis and positive anticentromere antibodies.⁴ The calcifications usually are located in areas that are subject to repeated trauma, such as the fingers or arms, though other locations have been described such as cervical, paraspinal, or on the hips.^5,6 Our patient developed calcifications on both legs, which represent atypical areas for this process.

Dermatomyositis also can present with calcinosis cutis. There are 4 patterns of calcification: superficial nodulelike calcified masses; deep calcified masses; deep sheetlike calcifications within the fascial planes; and a rare, diffuse, superficial lacy and reticular calcification that involves almost the entire body surface area.⁷ Patients with calcinosis cutis secondary to dermatomyositis usually develop proximal muscle weakness, high titers of creatine kinase, heliotrope rash, or interstitial lung disease with specific antibodies.

Calciphylaxis is a serious disorder involving the calcification of dermal and subcutaneous arterioles and capillaries. It presents with painful cutaneous areas of necrosis.

Venous ulcers also can present with secondary dystrophic calcification due to local tissue damage. These patients usually have cutaneous signs of chronic venous insufficiency. Our patient denied prior trauma to the area; therefore, a traumatic ulcer with secondary calcification was ruled out.

The most concerning complication of calcinosis cutis is the development of ulcers, which occurred in 154 of 316 calcinoses (48.7%) in patients with systemic sclerosis and secondary calcifications.⁸ These ulcers can cause disabling pain or become superinfected, as in our patient.

There currently is no drug capable of removing dystrophic calcifications, but diltiazem, minocycline, or colchicine can reduce their size and prevent their progression. In the event of neurologic compromise or intractable pain, the treatment of choice is surgical removal of the calcification.⁹ Curettage, intralesional sodium thiosulfate, and intravenous sodium thiosulfate also have been suggested as therapeutic options.¹⁰ Antibiotic treatment was carried out in our patient, which controlled the superinfection of the ulcers. Diltiazem also was started, with stabilization of the calcium deposits without a reduction in their size.

There are few studies evaluating the presence of nondigital ulcers in patients with systemic sclerosis. Shanmugam et al¹¹ calculated a 4% (N=249) prevalence of ulcers in the lower limbs of systemic sclerosis patients. In a study by Bohelay et al¹² of 45 patients, the estimated prevalence of lower limb ulcers was 12.8%, and the etiologies consisted of 22 cases of venous insufficiency (49%), 21 cases of ischemic causes (47%), and 2 cases of other causes (4%).

We present the case of a woman with ssSSc who developed dystrophic calcinosis cutis in atypical areas with secondary ulceration and superinfection. The skin usually plays a key role in the diagnosis of systemic sclerosis, as sclerodactyly and the characteristic generalized skin induration stand out in affected individuals. Although our patient was diagnosed with ssSSc, her skin manifestations also were crucial for the diagnosis, as she had ulcers on the lower limbs.

The Diagnosis: Calcinosis Cutis Due to Systemic Sclerosis Sine Scleroderma

Laboratory evaluation was notable for high titers of antinuclear antibodies (>1/320; reference range, 0–1/80) and positive anticentromere antibodies. There were no other relevant laboratory findings; phosphocalcic metabolism was within normal limits, and urinary sediment was normal. Biopsy of the edge of the ulcer revealed basophilic material compatible with calcium deposits. In a 3D volume rendering reconstruction from the lower limb scanner, grouped calcifications were observed in subcutaneous cellular tissue near the ulcer (Figure). The patient had a restrictive ventilatory pattern observed in a pulmonary function test. An esophageal motility study was normal.

The patient was diagnosed with systemic sclerosis sine scleroderma (ssSSc) type II because she met the 4 criteria established by Poormoghim et al¹ : (1) Raynaud phenomenon or a peripheral vascular equivalent (ie, digital pitting scars, digital-tip ulcers, digital-tip gangrene, abnormal nail fold capillaries); (2) positive antinuclear antibodies; (3) distal esophageal hypomotility, small bowel hypomotility, pulmonary interstitial fibrosis, primary pulmonary arterial hypertension (without fibrosis), cardiac involvement typical of scleroderma, or renal failure; and (4) no other defined connective tissue or other disease as a cause of the prior conditions.

Systemic sclerosis is a chronic disease characterized by progressive fibrosis of the skin and other internal organs—especially the lungs, kidneys, digestive tract, and heart—as well as generalized vascular dysfunction. Cutaneous induration is its hallmark; however, up to 10% of affected patients have ssSSc.² This entity is characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. There are 3 types of ssSSc depending on the grade of skin involvement. Type I is characterized by the lack of any typical cutaneous stigmata of the disease. Type II is without sclerodactyly but can coexist with other cutaneous findings such as calcifications, telangiectases, or pitting scars. Type III is characterized clinically by internal organ involvement, typical of systemic sclerosis, that has appeared before skin changes.²

An abnormal deposit of calcium in the cutaneous and subcutaneous tissue is called calcinosis cutis. There are 5 subtypes of calcinosis cutis: dystrophic, metastatic, idiopathic, iatrogenic, and calciphylaxis. Dystrophic skin calcifications may appear in patients with connective tissue diseases such as dermatomyositis or systemic sclerosis.³ Up to 25% of patients with systemic sclerosis can develop calcinosis cutis due to local tissue damage, with normal phosphocalcic metabolism.³

Calcinosis cutis is more common in patients with systemic sclerosis and positive anticentromere antibodies.⁴ The calcifications usually are located in areas that are subject to repeated trauma, such as the fingers or arms, though other locations have been described such as cervical, paraspinal, or on the hips.^5,6 Our patient developed calcifications on both legs, which represent atypical areas for this process.

Dermatomyositis also can present with calcinosis cutis. There are 4 patterns of calcification: superficial nodulelike calcified masses; deep calcified masses; deep sheetlike calcifications within the fascial planes; and a rare, diffuse, superficial lacy and reticular calcification that involves almost the entire body surface area.⁷ Patients with calcinosis cutis secondary to dermatomyositis usually develop proximal muscle weakness, high titers of creatine kinase, heliotrope rash, or interstitial lung disease with specific antibodies.

Calciphylaxis is a serious disorder involving the calcification of dermal and subcutaneous arterioles and capillaries. It presents with painful cutaneous areas of necrosis.

Venous ulcers also can present with secondary dystrophic calcification due to local tissue damage. These patients usually have cutaneous signs of chronic venous insufficiency. Our patient denied prior trauma to the area; therefore, a traumatic ulcer with secondary calcification was ruled out.

The most concerning complication of calcinosis cutis is the development of ulcers, which occurred in 154 of 316 calcinoses (48.7%) in patients with systemic sclerosis and secondary calcifications.⁸ These ulcers can cause disabling pain or become superinfected, as in our patient.

There currently is no drug capable of removing dystrophic calcifications, but diltiazem, minocycline, or colchicine can reduce their size and prevent their progression. In the event of neurologic compromise or intractable pain, the treatment of choice is surgical removal of the calcification.⁹ Curettage, intralesional sodium thiosulfate, and intravenous sodium thiosulfate also have been suggested as therapeutic options.¹⁰ Antibiotic treatment was carried out in our patient, which controlled the superinfection of the ulcers. Diltiazem also was started, with stabilization of the calcium deposits without a reduction in their size.

There are few studies evaluating the presence of nondigital ulcers in patients with systemic sclerosis. Shanmugam et al¹¹ calculated a 4% (N=249) prevalence of ulcers in the lower limbs of systemic sclerosis patients. In a study by Bohelay et al¹² of 45 patients, the estimated prevalence of lower limb ulcers was 12.8%, and the etiologies consisted of 22 cases of venous insufficiency (49%), 21 cases of ischemic causes (47%), and 2 cases of other causes (4%).

We present the case of a woman with ssSSc who developed dystrophic calcinosis cutis in atypical areas with secondary ulceration and superinfection. The skin usually plays a key role in the diagnosis of systemic sclerosis, as sclerodactyly and the characteristic generalized skin induration stand out in affected individuals. Although our patient was diagnosed with ssSSc, her skin manifestations also were crucial for the diagnosis, as she had ulcers on the lower limbs.

The Diagnosis: Striated Muscle Hamartoma

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

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

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

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

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

The Diagnosis: Striated Muscle Hamartoma

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

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

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

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

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

The Diagnosis: Striated Muscle Hamartoma

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

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

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

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

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

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Ecthyma Gangrenosum

Histopathology revealed basophilic bacterial rods around necrotic vessels with thrombosis and edema (Figure). Blood and tissue cultures grew Pseudomonas aeruginosa. Based on the histopathology and clinical presentation, a diagnosis of P aeruginosa–associated ecthyma gangrenosum (EG) was made. The patient’s symptoms resolved with intravenous cefepime, and he later was transitioned to oral levofloxacin for outpatient treatment.

Ecthyma gangrenosum is an uncommon cutaneous manifestation of bacteremia that most commonly occurs secondary to P aeruginosa in immunocompromised patients, particularly patients with severe neutropenia in the setting of recent chemotherapy.^1,2 Ecthyma gangrenosum can occur anywhere on the body, predominantly in moist areas such as the axillae and groin; the arms and legs, such as in our patient, as well as the trunk and face also may be involved.³ Other causes of EG skin lesions include methicillin-resistant Staphylococcus aureus, Citrobacter freundii, Escherichia coli, fungi such as Candida, and viruses such as herpes simplex virus.^2,4-6 Common predisposing conditions associated with EG include neutropenia, leukemia, HIV, diabetes mellitus, extensive burn wounds, and a history of immunosuppressive medications. It also has been known to occur in otherwise healthy, immunocompetent individuals with no difference in clinical manifestation.²

The diagnosis is clinicopathologic, with initial evaluation including blood and wound cultures as well as a complete blood cell count once EG is suspected. An excisional or punch biopsy is performed for confirmation, showing many gram-negative, rod-shaped bacteria in cases of pseudomonal EG.⁷ Histopathology is characterized by bacterial perivascular invasion that then leads to secondary arteriole thrombosis, tissue edema, and separation of the epidermis.^7,8 Resultant ischemic necrosis results in the classic macroscopic appearance of an erythematous macule that rapidly progresses into a central necrotic lesion surrounded by an erythematous or violaceous halo after undergoing a hemorrhagic bullous stage.1,9 A Wood lamp can be used to expedite the diagnosis, as Pseudomonas bacteria excretes a pigment (pyoverdine) that fluoresces yellowish green.¹⁰

Ecthyma gangrenosum can be classified as a primary skin lesion that may or may not be followed by bacteremia or as a lesion secondary to pseudomonal bacteremia.¹¹ Bacteremia has been reported in half of cases, with hematogenous metastasis of the infection, likely in manifestations with multiple bilateral lesions.² Our patient’s presentation of a single lesion revealed a positive blood culture result. Lesions also can develop by direct inoculation of the epidermis causing local destruction of the surrounding tissue. The nonbacteremic form of EG has been associated with a lower mortality rate of around 15% compared to patients with bacteremia ranging from 38% to 96%.¹² The presence of neutropenia is the most important prognostic factor for mortality at the time of diagnosis.¹³

Prompt empiric therapy should be initiated after obtaining wound and blood cultures in those with infection until the causative organism and its susceptibility are identified. Pseudomonal infections account for 4% of all cases of hospital-acquired bacteremia and are the third leading cause of gram-negative bloodstream infection.⁷ Initial broad-spectrum antibiotics include antipseudomonal β-lactams (piperacillin-tazobactam), cephalosporins (cefepime), fluoroquinolones (levofloxacin), and carbapenems (imipenem).^1,7 Medical therapy alone may be sufficient without requiring extensive surgical debridement to remove necrotic tissue in some patients. Surgical debridement usually is warranted for lesions larger than 10 cm in diameter.³ Our patient was treated with intravenous cefepime with resolution and was followed with outpatient oral levofloxacin as appropriate. A high index of suspicion should be maintained for relapsing pseudomonal EG infection among patients with AIDS, as the reported recurrence rate is 57%.¹⁴

Clinically, the differential diagnosis of EG presenting in immunocompromised patients or individuals with underlying malignancy includes pyoderma gangrenosum, papulonecrotic tuberculid, and leukemia cutis. An erythematous rash with central necrosis presenting in a patient with systemic symptoms is pathognomonic for erythema migrans and should be considered as a diagnostic possibility in areas endemic for Lyme disease in the United States, including the northeastern, mid-Atlantic, and north-central regions.¹⁵ A thorough history, physical examination, basic laboratory studies, and histopathology are critical to differentiate between these entities with similar macroscopic features. Pyoderma gangrenosum histologically manifests as a noninfectious, deep, suppurative folliculitis with leukocytoclastic vasculitis in 40% of cases.¹⁶ Although papulonecrotic tuberculid can present with dermal necrosis resulting from a hypersensitivity reaction to antigenic components of mycobacteria, there typically are granulomatous infiltrates present and a lack of observed organisms on histopathology.¹⁷ Although leukemia cutis infrequently occurs in patients diagnosed with leukemia, its salient features on pathology are nodular or diffuse infiltrates of leukemic cells in the dermis and subcutis with a high nuclear-to-cytoplasmic ratio, often with prominent nucleoli.¹⁸ Lyme disease can present in various ways; however, cutaneous involvement in the primary lesion is histologically characterized by a perivascular lymphohistiocytic infiltrate containing plasma cells at the periphery of the expanding annular lesion and eosinophils present at the center.¹⁹

The Diagnosis: Acquired Acrodermatitis Enteropathica

A punch biopsy of an elevated scaly border of the rash on the thigh revealed parakeratosis, absence of the granular layer, and epidermal pallor with psoriasiform and spongiotic dermatitis (Figure). Serum zinc levels were 60.1 μg/dL (reference range, 75.0–120.0 μg/dL), suggestive of a nutritional deficiency dermatitis. Laboratory and histopathologic findings were most consistent with a diagnosis of acquired acrodermatitis enteropathica (AE).

Acrodermatitis enteropathica has been associated with Roux-en-Y gastric bypass and alcohol use disorder working synergistically to cause malabsorption and malnutrition, respectively.¹ Zinc functions in the structural integrity, wound healing, and anti-inflammatory properties of the skin. There is a 17.3% risk for hypozincemia worldwide; in developed nations there is an estimated 3% to 10% occurrence rate.² Acrodermatitis enteropathica can be classified as either acquired or hereditary. Both classically present as a triad of acral dermatitis, diarrhea, and alopecia, though the complete triad is seen in 20% of cases.^3,4

Hereditary AE is an autosomal-recessive disorder presenting in infancy that results in the loss of a zinc transporter. In contrast, acquired AE occurs later in life and usually is seen in patients who have decreased intake, malabsorption, or excessive loss of zinc.⁴ Acrodermatitis enteropathica is observed in individuals with conditions such as anorexia nervosa, pancreatic insufficiency, celiac disease, Crohn disease, or gastric bypass surgery (as in our case) and alcohol recidivism. In early disease, AE often presents with angular cheilitis and paronychia, but if left untreated, it can progress to mental status changes, hypogonadism, and depression.4 Acrodermatitis enteropathica presents as erythematous, erosive, scaly plaques or a papulosquamous psoriasiform rash with well-demarcated borders typically involving the orificial, acral, and intertriginous areas of the body.^1,4

Acrodermatitis enteropathica belongs to a family of deficiency dermatoses that includes pellagra, necrolytic acral erythema (NAE), and necrolytic migratory erythema (NME).⁵ It is important to distinguish AE from NAE, as they can present similarly with well-defined and tender psoriasiform lesions peripherally. Histologically, NAE mimics AE with psoriasiform hyperplasia with parakeratosis.⁶ Necrolytic acral erythema characteristically is associated with active hepatitis C infection, which was absent in our patient.⁷

Similar to AE, NME affects the perineal and intertriginous surfaces.⁸ However, necrolytic migratory erythema has cutaneous manifestations in up to 70% of patients with glucagonoma syndrome, which classically presents as a triad of NME, weight loss, and diabetes mellitus.⁵ Laboratory studies show marked hyperglucagonemia, and imaging reveals enteropancreatic neoplasia. Necrolytic migratory erythema will rapidly resolve once the glucagonoma has been surgically removed.⁵ Bazex syndrome, or acrokeratosis paraneoplastica, is a paraneoplastic skin disease that is linked to underlying aerodigestive tract malignancies.

Bazex syndrome clinically is characterized by hyperkeratotic and psoriasiform lesions favoring the ears, nails, and nose.⁹

Psoriasis vulgaris is a common chronic inflammatory skin condition that usually presents as well-demarcated plaques with silvery scale and observed pinpoint bleeding when layers of scale are removed (Auspitz sign). Lesions typically are found on the extensor surfaces of the body in addition to the neck, feet, hands, and trunk. Treatment of psoriasis vulgaris ranges from topical steroids for mild cases to systemic biologics for moderate to severe circumstances.¹⁰ In our patient, topical triamcinolone offered little relief.

Acrodermatitis enteropathica displays clinical and histologic characteristics analogous to many deficiency dermatoses and may represent a spectrum of disease. Because the clinicopathologic findings are nonspecific, it is critical to obtain a comprehensive history and maintain a high index of suspicion in patients with risk factors for malnutrition. The treatment for AE is supplemental oral zinc usually initiated at 0.5 to 1 mg/kg daily in children and 30 to 45 mg daily in adults.³ Our patient initially was prescribed oral zinc supplementation; however, at 1-month follow-up, the rash had not improved. Failure of zinc monotherapy supports a multifactorial nutritional deficiency, which necessitated comprehensive nutritional appraisal and supplementation in our patient. Due to the steatorrhea, fecal pancreatic elastase levels were evaluated and were less than 15 μg/g (reference range, ≥201 μg/g), confirming pancreatic exocrine insufficiency, a known complication of Roux-en-Y gastric bypass.¹¹ Pancrelipase 500 U/kg per meal was added in addition to zinc oxide 40% paste to apply to the rash twice daily, with more frequent applications to the anogenital regions after bowel movements. The patient had substantial clinical improvement after 2 months.

The Diagnosis: Acquired Acrodermatitis Enteropathica

A punch biopsy of an elevated scaly border of the rash on the thigh revealed parakeratosis, absence of the granular layer, and epidermal pallor with psoriasiform and spongiotic dermatitis (Figure). Serum zinc levels were 60.1 μg/dL (reference range, 75.0–120.0 μg/dL), suggestive of a nutritional deficiency dermatitis. Laboratory and histopathologic findings were most consistent with a diagnosis of acquired acrodermatitis enteropathica (AE).

Acrodermatitis enteropathica has been associated with Roux-en-Y gastric bypass and alcohol use disorder working synergistically to cause malabsorption and malnutrition, respectively.¹ Zinc functions in the structural integrity, wound healing, and anti-inflammatory properties of the skin. There is a 17.3% risk for hypozincemia worldwide; in developed nations there is an estimated 3% to 10% occurrence rate.² Acrodermatitis enteropathica can be classified as either acquired or hereditary. Both classically present as a triad of acral dermatitis, diarrhea, and alopecia, though the complete triad is seen in 20% of cases.^3,4

Hereditary AE is an autosomal-recessive disorder presenting in infancy that results in the loss of a zinc transporter. In contrast, acquired AE occurs later in life and usually is seen in patients who have decreased intake, malabsorption, or excessive loss of zinc.⁴ Acrodermatitis enteropathica is observed in individuals with conditions such as anorexia nervosa, pancreatic insufficiency, celiac disease, Crohn disease, or gastric bypass surgery (as in our case) and alcohol recidivism. In early disease, AE often presents with angular cheilitis and paronychia, but if left untreated, it can progress to mental status changes, hypogonadism, and depression.4 Acrodermatitis enteropathica presents as erythematous, erosive, scaly plaques or a papulosquamous psoriasiform rash with well-demarcated borders typically involving the orificial, acral, and intertriginous areas of the body.^1,4

Acrodermatitis enteropathica belongs to a family of deficiency dermatoses that includes pellagra, necrolytic acral erythema (NAE), and necrolytic migratory erythema (NME).⁵ It is important to distinguish AE from NAE, as they can present similarly with well-defined and tender psoriasiform lesions peripherally. Histologically, NAE mimics AE with psoriasiform hyperplasia with parakeratosis.⁶ Necrolytic acral erythema characteristically is associated with active hepatitis C infection, which was absent in our patient.⁷

Similar to AE, NME affects the perineal and intertriginous surfaces.⁸ However, necrolytic migratory erythema has cutaneous manifestations in up to 70% of patients with glucagonoma syndrome, which classically presents as a triad of NME, weight loss, and diabetes mellitus.⁵ Laboratory studies show marked hyperglucagonemia, and imaging reveals enteropancreatic neoplasia. Necrolytic migratory erythema will rapidly resolve once the glucagonoma has been surgically removed.⁵ Bazex syndrome, or acrokeratosis paraneoplastica, is a paraneoplastic skin disease that is linked to underlying aerodigestive tract malignancies.

Bazex syndrome clinically is characterized by hyperkeratotic and psoriasiform lesions favoring the ears, nails, and nose.⁹

Psoriasis vulgaris is a common chronic inflammatory skin condition that usually presents as well-demarcated plaques with silvery scale and observed pinpoint bleeding when layers of scale are removed (Auspitz sign). Lesions typically are found on the extensor surfaces of the body in addition to the neck, feet, hands, and trunk. Treatment of psoriasis vulgaris ranges from topical steroids for mild cases to systemic biologics for moderate to severe circumstances.¹⁰ In our patient, topical triamcinolone offered little relief.

Acrodermatitis enteropathica displays clinical and histologic characteristics analogous to many deficiency dermatoses and may represent a spectrum of disease. Because the clinicopathologic findings are nonspecific, it is critical to obtain a comprehensive history and maintain a high index of suspicion in patients with risk factors for malnutrition. The treatment for AE is supplemental oral zinc usually initiated at 0.5 to 1 mg/kg daily in children and 30 to 45 mg daily in adults.³ Our patient initially was prescribed oral zinc supplementation; however, at 1-month follow-up, the rash had not improved. Failure of zinc monotherapy supports a multifactorial nutritional deficiency, which necessitated comprehensive nutritional appraisal and supplementation in our patient. Due to the steatorrhea, fecal pancreatic elastase levels were evaluated and were less than 15 μg/g (reference range, ≥201 μg/g), confirming pancreatic exocrine insufficiency, a known complication of Roux-en-Y gastric bypass.¹¹ Pancrelipase 500 U/kg per meal was added in addition to zinc oxide 40% paste to apply to the rash twice daily, with more frequent applications to the anogenital regions after bowel movements. The patient had substantial clinical improvement after 2 months.

The Diagnosis: Acquired Acrodermatitis Enteropathica

A punch biopsy of an elevated scaly border of the rash on the thigh revealed parakeratosis, absence of the granular layer, and epidermal pallor with psoriasiform and spongiotic dermatitis (Figure). Serum zinc levels were 60.1 μg/dL (reference range, 75.0–120.0 μg/dL), suggestive of a nutritional deficiency dermatitis. Laboratory and histopathologic findings were most consistent with a diagnosis of acquired acrodermatitis enteropathica (AE).

Acrodermatitis enteropathica has been associated with Roux-en-Y gastric bypass and alcohol use disorder working synergistically to cause malabsorption and malnutrition, respectively.¹ Zinc functions in the structural integrity, wound healing, and anti-inflammatory properties of the skin. There is a 17.3% risk for hypozincemia worldwide; in developed nations there is an estimated 3% to 10% occurrence rate.² Acrodermatitis enteropathica can be classified as either acquired or hereditary. Both classically present as a triad of acral dermatitis, diarrhea, and alopecia, though the complete triad is seen in 20% of cases.^3,4

Hereditary AE is an autosomal-recessive disorder presenting in infancy that results in the loss of a zinc transporter. In contrast, acquired AE occurs later in life and usually is seen in patients who have decreased intake, malabsorption, or excessive loss of zinc.⁴ Acrodermatitis enteropathica is observed in individuals with conditions such as anorexia nervosa, pancreatic insufficiency, celiac disease, Crohn disease, or gastric bypass surgery (as in our case) and alcohol recidivism. In early disease, AE often presents with angular cheilitis and paronychia, but if left untreated, it can progress to mental status changes, hypogonadism, and depression.4 Acrodermatitis enteropathica presents as erythematous, erosive, scaly plaques or a papulosquamous psoriasiform rash with well-demarcated borders typically involving the orificial, acral, and intertriginous areas of the body.^1,4

Acrodermatitis enteropathica belongs to a family of deficiency dermatoses that includes pellagra, necrolytic acral erythema (NAE), and necrolytic migratory erythema (NME).⁵ It is important to distinguish AE from NAE, as they can present similarly with well-defined and tender psoriasiform lesions peripherally. Histologically, NAE mimics AE with psoriasiform hyperplasia with parakeratosis.⁶ Necrolytic acral erythema characteristically is associated with active hepatitis C infection, which was absent in our patient.⁷

Similar to AE, NME affects the perineal and intertriginous surfaces.⁸ However, necrolytic migratory erythema has cutaneous manifestations in up to 70% of patients with glucagonoma syndrome, which classically presents as a triad of NME, weight loss, and diabetes mellitus.⁵ Laboratory studies show marked hyperglucagonemia, and imaging reveals enteropancreatic neoplasia. Necrolytic migratory erythema will rapidly resolve once the glucagonoma has been surgically removed.⁵ Bazex syndrome, or acrokeratosis paraneoplastica, is a paraneoplastic skin disease that is linked to underlying aerodigestive tract malignancies.

Bazex syndrome clinically is characterized by hyperkeratotic and psoriasiform lesions favoring the ears, nails, and nose.⁹

Psoriasis vulgaris is a common chronic inflammatory skin condition that usually presents as well-demarcated plaques with silvery scale and observed pinpoint bleeding when layers of scale are removed (Auspitz sign). Lesions typically are found on the extensor surfaces of the body in addition to the neck, feet, hands, and trunk. Treatment of psoriasis vulgaris ranges from topical steroids for mild cases to systemic biologics for moderate to severe circumstances.¹⁰ In our patient, topical triamcinolone offered little relief.

Acrodermatitis enteropathica displays clinical and histologic characteristics analogous to many deficiency dermatoses and may represent a spectrum of disease. Because the clinicopathologic findings are nonspecific, it is critical to obtain a comprehensive history and maintain a high index of suspicion in patients with risk factors for malnutrition. The treatment for AE is supplemental oral zinc usually initiated at 0.5 to 1 mg/kg daily in children and 30 to 45 mg daily in adults.³ Our patient initially was prescribed oral zinc supplementation; however, at 1-month follow-up, the rash had not improved. Failure of zinc monotherapy supports a multifactorial nutritional deficiency, which necessitated comprehensive nutritional appraisal and supplementation in our patient. Due to the steatorrhea, fecal pancreatic elastase levels were evaluated and were less than 15 μg/g (reference range, ≥201 μg/g), confirming pancreatic exocrine insufficiency, a known complication of Roux-en-Y gastric bypass.¹¹ Pancrelipase 500 U/kg per meal was added in addition to zinc oxide 40% paste to apply to the rash twice daily, with more frequent applications to the anogenital regions after bowel movements. The patient had substantial clinical improvement after 2 months.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Drug-Induced Hyperpigmentation

Additional history provided by the patient’s caretaker elucidated an extensive list of medications including chlorpromazine and minocycline, among several others. The caretaker revealed that the patient began treatment for acne vulgaris 2 years prior; despite the acne resolving, therapy was not discontinued. The blue-gray and brown pigmentation on our patient’s shins likely was attributed to a medication he was taking.

Both chlorpromazine and minocycline, among many other medications, are known to cause abnormal pigmentation of the skin.¹ Minocycline is a tetracycline antibiotic prescribed for acne and other inflammatory cutaneous conditions. It is highly lipophilic, allowing it to reach high drug concentrations in the skin and nail unit.² Patients taking minocycline long term and at high doses are at greatest risk for pigment deposition.^3,4

Minocycline-induced hyperpigmentation is classified into 3 types. Type I describes blue-black deposition of pigment in acne scars and areas of inflammation, typically on facial skin.^1,5 Histologically, type I stains positive for Perls Prussian blue, indicating an increased deposition of iron as hemosiderin,¹ which likely occurs because minocycline is thought to play a role in defective clearance of hemosiderin from the dermis of injured tissue.⁵ Type II hyperpigmentation presents as bluegray pigment on the lower legs and occasionally the arms.^6,7 Type II stains positive for both Perls Prussian blue and Fontana-Masson, demonstrating hemosiderin and melanin, respectively.⁶ The third form of hyperpigmentation results in diffuse, dark brown to gray pigmentation with a predilection for sun-exposed areas.⁸ Histology of type III shows increased pigment in the basal portion of the epidermis and brown-black pigment in macrophages of the dermis. Type III stains positive for Fontana-Masson and negative for Perls Prussian blue. The etiology of hyperpigmentation has been suspected to be caused by minocycline stimulating melanin production and/or deposition of minocycline-melanin complexes in dermal macrophages after a certain drug level; this largely is seen in patients receiving 100 to 200 mg daily as early as 1 year into treatment.⁸

Chlorpromazine is a typical antipsychotic that causes abnormal skin pigmentation in sun-exposed areas due to increased melanogenesis.⁹ Similar to type III minocyclineinduced hyperpigmentation, a histologic specimen may stain positive for Fontana-Masson yet negative for Perls Prussian blue. Lal et al10 demonstrated complete resolution of abnormal skin pigmentation within 5 years after stopping chlorpromazine. In contrast, minocyclineinduced hyperpigmentation may be permanent in some cases. There is substantial clinical and histologic overlap for drug-induced hyperpigmentation etiologies; it would behoove the clinician to focus on the most common locations affected and the generalized coloration.

Treatment of minocycline-induced hyperpigmentation includes the use of Q-switched lasers, specifically Q-switched ruby and Q-switched alexandrite.¹¹ The use of the Q-switched Nd:YAG laser appears to be ineffective at clearing minocycline-induced pigmentation.^7,11 In our patient, minocycline was discontinued immediately. Due to the patient’s critical condition, he deferred all other therapy. Erythema dyschromicum perstans, also referred to as ashy dermatosis, is an idiopathic form of hyperpigmentation.¹² Lesions start as blue-gray to ashy gray macules, occasionally surrounded by a slightly erythematous, raised border.

Erythema dyschromicum perstans typically presents on the trunk, face, and arms of patients with Fitzpatrick skin types III and IV; it is considered a variant of lichen planus actinicus.¹² Histologically, erythema dyschromicum perstans may mimic lichen planus pigmentosus (LPP); however, subtle differences exist to distinguish the 2 conditions. Erythema dyschromicum perstans demonstrates a mild lichenoid infiltrate, focal basal vacuolization at the dermoepidermal junction, and melanophage deposition.¹³ In contrast, LPP demonstrates pigmentary incontinence and a more severe inflammatory infiltrate. A perifollicular infiltrate and fibrosis also can be seen in LPP, which may explain the frontal fibrosing alopecia that often precedes LPP.¹³

Addison disease, also known as primary adrenal insufficiency, can cause diffuse hyperpigmentation in the skin, mucosae, and nail beds. The pigmentation is prominent in regions of naturally increased pigmentation, such as the flexural surfaces and intertriginous areas.¹⁴ Patients with adrenal insufficiency will have accompanying weight loss, hypotension, and fatigue, among other symptoms related to deficiency of cortisol and aldosterone. Skin biopsy shows acanthosis, hyperkeratosis, focal parakeratosis, spongiosis, superficial perivascular lymphocytic infiltrate, basal melanin deposition, and superficial dermal macrophages.¹⁵

Confluent and reticulated papillomatosis is an uncommon dermatosis that presents with multiple hyperpigmented macules and papules that coalesce to form patches and plaques centrally with reticulation in the periphery.¹⁶ Confluent and reticulated papillomatosis commonly presents on the upper trunk, axillae, and neck, though involvement can include flexural surfaces as well as the lower trunk and legs.^16,17 Biopsy demonstrates undulating hyperkeratosis, papillomatosis, acanthosis, and negative fungal staining.¹⁶

Pretibial myxedema most commonly is associated with Graves disease and presents as well-defined thickening and induration with overlying pink or purple-brown papules in the pretibial region.¹⁸ An acral surface and mucin deposition within the entire dermis may be appreciated on histology with staining for colloidal iron or Alcian blue.

The Diagnosis: Nodular Hidradenoma

A biopsy of the nodule showed a large, fungating, well-circumscribed, multilobulated neoplasm composed of primarily monotonous eosinophilic cells in a background of keloidal stroma (Figure). There was a minority population of small, monotonous, clear cells within the lobules, and no glandular structures were noted. Neither cytological nor architectural atypia were evident. MART-1/Melan-A and S-100 stains were negative, consistent with a diagnosis of benign nodular hidradenoma.

Nodular hidradenoma (also known as acrospiroma, solid-cystic hidradenoma, clear cell hidradenoma, and eccrine sweat gland adenoma) is a benign adnexal tumor of the apocrine or eccrine glands.^1,2 Nodular hidradenoma can arise at any cutaneous site but most commonly arises on the head and anterior portion of the trunk and rarely on the extremities.² It presents as a solitary nodular, cystic, or pedunculated mass that can reach up to several centimeters in diameter.^2,3 Nodular hidradenoma more commonly affects women compared to men with a ratio of 1.7 to 1 and commonly presents between the third and fifth decades of life, with an average age at presentation of 37.2 years.^2,4 There can be associated skin changes, including smoothening, thickening, ulceration, and bluish discoloration. Dermoscopy commonly shows a pinkish homogenous area that extends throughout the entire lesion. This homogenous area less commonly can be bluish, brownish, or pink-blue. Most nodular hidradenomas also can exhibit vascularization, with arborizing telangiectases, polymorphous atypical vessels, and linear irregular vessels being most common; however, this is not specific to nodular hidradenoma.3 Occasionally, tumors can drain serous or hemorrhagic fluid. Nodular hidradenoma commonly is a slow-growing tumor.⁵ Rapid increase in tumor size can be indicative of malignant transformation, hemorrhage into the tumor, or trauma to the area.²

Histologically, nodular hidradenoma consists of a circumscribed, nonencapsulated, multilobular tumor commonly found in the dermis and sometimes extending into the subcutaneous tissue. There usually is no epidermal attachment, and the overlying epidermis largely is normal. The tumor consists of large multilobulated areas of epithelial cells, tubular lamina, and large cystic areas filled with homogenous eosinophilic material.¹ It notably is composed of 2 epithelial cell types: (1) fusiform cells with elongated vesicular nuclei and basophilic cytoplasm, and (2) large polygonal cells with round eccentric nuclei and eosinophilic, periodic acid–Schiff–positive cytoplasm that washes away during fixation, giving the appearance of clear cells.⁵ Both types of cells are small, monotonous, and void of mitosis or dyskeratosis. Although there can be ducts with apocrine secretion present within the lobulated tumor, they are not consistently found. Due to the varying features that are neither mandatory nor consistent to arrive at this diagnosis, some dermatopathologists view the term hidradenoma as a catch-all term that includes several different types of benign sweat gland tumors. Some authors divide the terminology into apocrine hidradenoma and eccrine hidradenoma based on whether the tumor is composed of solely clear mucinous cells, or poroid and cuticular cells, respectively.

Although nodular hidradenoma classically is a benign tumor, total surgical excision is recommended due to the rare risk for malignant transformation. Rarely, longstanding hidradenomas can metastasize to lymph nodes, bone, or viscera; in these instances, metastatic hidradenoma has a 5-year survival rate of 30%. Recurrence may occur in tumors that are inadequately excised, and the rate of recurrence is estimated to be approximately 10% of surgically excised tumors.⁵ However, utilization of Mohs micrographic surgery for excision of nodular hidradenoma is associated with a reduced recurrence rate.⁶

Keloids present as painful, sometimes pruritic, raised scars that extend beyond the boundary of the initial injury, commonly arising on the shoulder, upper arm, and chest. Histopathology reveals nodules of thick hyalinized collagen bundles, keloidal collagen with mucinous ground substance, and few fibroblasts.⁷

Metastatic renal cell carcinoma to the skin most commonly presents on the face and scalp as a nodular, rapidly growing, round to oval lesion that is flesh colored to reddish purple in a patient with history of renal cell carcinoma.⁸ Histopathology shows clusters of atypical, nucleated clear cells surrounded by chicken wire vasculature.^8,9

Verruca vulgaris is caused by human papillomavirus and most commonly occurs on the hands and feet. It presents as a pink to white, sessile lesion with a verrucous surface and exophytic growths. Histopathology shows acanthosis; hypergranulosis; exophytic projections with a fibrovascular core; inward cupping of the rete ridges; and koilocytes, which are cells with an eccentric, raisinlike nucleus and vacuolated cytoplasm in the granular layer of the epidermis.¹⁰

Similar to nodular hidradenoma, nodular melanoma most commonly presents on the head and neck as a symmetric, elevated, amelanotic nodule, but in contrast to nodular hidradenoma, it typically is confined to a smaller diameter.¹¹ Histologically, it is characterized by sheets of atypical, commonly epithelioid melanocytes with a lack of maturation and brisk mitotic activity extending through the epidermis and dermis with lateral extension limited to less than 3 rete ridges.¹²

The Diagnosis: Nodular Hidradenoma

A biopsy of the nodule showed a large, fungating, well-circumscribed, multilobulated neoplasm composed of primarily monotonous eosinophilic cells in a background of keloidal stroma (Figure). There was a minority population of small, monotonous, clear cells within the lobules, and no glandular structures were noted. Neither cytological nor architectural atypia were evident. MART-1/Melan-A and S-100 stains were negative, consistent with a diagnosis of benign nodular hidradenoma.

Nodular hidradenoma (also known as acrospiroma, solid-cystic hidradenoma, clear cell hidradenoma, and eccrine sweat gland adenoma) is a benign adnexal tumor of the apocrine or eccrine glands.^1,2 Nodular hidradenoma can arise at any cutaneous site but most commonly arises on the head and anterior portion of the trunk and rarely on the extremities.² It presents as a solitary nodular, cystic, or pedunculated mass that can reach up to several centimeters in diameter.^2,3 Nodular hidradenoma more commonly affects women compared to men with a ratio of 1.7 to 1 and commonly presents between the third and fifth decades of life, with an average age at presentation of 37.2 years.^2,4 There can be associated skin changes, including smoothening, thickening, ulceration, and bluish discoloration. Dermoscopy commonly shows a pinkish homogenous area that extends throughout the entire lesion. This homogenous area less commonly can be bluish, brownish, or pink-blue. Most nodular hidradenomas also can exhibit vascularization, with arborizing telangiectases, polymorphous atypical vessels, and linear irregular vessels being most common; however, this is not specific to nodular hidradenoma.3 Occasionally, tumors can drain serous or hemorrhagic fluid. Nodular hidradenoma commonly is a slow-growing tumor.⁵ Rapid increase in tumor size can be indicative of malignant transformation, hemorrhage into the tumor, or trauma to the area.²

Histologically, nodular hidradenoma consists of a circumscribed, nonencapsulated, multilobular tumor commonly found in the dermis and sometimes extending into the subcutaneous tissue. There usually is no epidermal attachment, and the overlying epidermis largely is normal. The tumor consists of large multilobulated areas of epithelial cells, tubular lamina, and large cystic areas filled with homogenous eosinophilic material.¹ It notably is composed of 2 epithelial cell types: (1) fusiform cells with elongated vesicular nuclei and basophilic cytoplasm, and (2) large polygonal cells with round eccentric nuclei and eosinophilic, periodic acid–Schiff–positive cytoplasm that washes away during fixation, giving the appearance of clear cells.⁵ Both types of cells are small, monotonous, and void of mitosis or dyskeratosis. Although there can be ducts with apocrine secretion present within the lobulated tumor, they are not consistently found. Due to the varying features that are neither mandatory nor consistent to arrive at this diagnosis, some dermatopathologists view the term hidradenoma as a catch-all term that includes several different types of benign sweat gland tumors. Some authors divide the terminology into apocrine hidradenoma and eccrine hidradenoma based on whether the tumor is composed of solely clear mucinous cells, or poroid and cuticular cells, respectively.

Although nodular hidradenoma classically is a benign tumor, total surgical excision is recommended due to the rare risk for malignant transformation. Rarely, longstanding hidradenomas can metastasize to lymph nodes, bone, or viscera; in these instances, metastatic hidradenoma has a 5-year survival rate of 30%. Recurrence may occur in tumors that are inadequately excised, and the rate of recurrence is estimated to be approximately 10% of surgically excised tumors.⁵ However, utilization of Mohs micrographic surgery for excision of nodular hidradenoma is associated with a reduced recurrence rate.⁶

Keloids present as painful, sometimes pruritic, raised scars that extend beyond the boundary of the initial injury, commonly arising on the shoulder, upper arm, and chest. Histopathology reveals nodules of thick hyalinized collagen bundles, keloidal collagen with mucinous ground substance, and few fibroblasts.⁷

Metastatic renal cell carcinoma to the skin most commonly presents on the face and scalp as a nodular, rapidly growing, round to oval lesion that is flesh colored to reddish purple in a patient with history of renal cell carcinoma.⁸ Histopathology shows clusters of atypical, nucleated clear cells surrounded by chicken wire vasculature.^8,9

Verruca vulgaris is caused by human papillomavirus and most commonly occurs on the hands and feet. It presents as a pink to white, sessile lesion with a verrucous surface and exophytic growths. Histopathology shows acanthosis; hypergranulosis; exophytic projections with a fibrovascular core; inward cupping of the rete ridges; and koilocytes, which are cells with an eccentric, raisinlike nucleus and vacuolated cytoplasm in the granular layer of the epidermis.¹⁰

Similar to nodular hidradenoma, nodular melanoma most commonly presents on the head and neck as a symmetric, elevated, amelanotic nodule, but in contrast to nodular hidradenoma, it typically is confined to a smaller diameter.¹¹ Histologically, it is characterized by sheets of atypical, commonly epithelioid melanocytes with a lack of maturation and brisk mitotic activity extending through the epidermis and dermis with lateral extension limited to less than 3 rete ridges.¹²

The Diagnosis: Nodular Hidradenoma

A biopsy of the nodule showed a large, fungating, well-circumscribed, multilobulated neoplasm composed of primarily monotonous eosinophilic cells in a background of keloidal stroma (Figure). There was a minority population of small, monotonous, clear cells within the lobules, and no glandular structures were noted. Neither cytological nor architectural atypia were evident. MART-1/Melan-A and S-100 stains were negative, consistent with a diagnosis of benign nodular hidradenoma.

Nodular hidradenoma (also known as acrospiroma, solid-cystic hidradenoma, clear cell hidradenoma, and eccrine sweat gland adenoma) is a benign adnexal tumor of the apocrine or eccrine glands.^1,2 Nodular hidradenoma can arise at any cutaneous site but most commonly arises on the head and anterior portion of the trunk and rarely on the extremities.² It presents as a solitary nodular, cystic, or pedunculated mass that can reach up to several centimeters in diameter.^2,3 Nodular hidradenoma more commonly affects women compared to men with a ratio of 1.7 to 1 and commonly presents between the third and fifth decades of life, with an average age at presentation of 37.2 years.^2,4 There can be associated skin changes, including smoothening, thickening, ulceration, and bluish discoloration. Dermoscopy commonly shows a pinkish homogenous area that extends throughout the entire lesion. This homogenous area less commonly can be bluish, brownish, or pink-blue. Most nodular hidradenomas also can exhibit vascularization, with arborizing telangiectases, polymorphous atypical vessels, and linear irregular vessels being most common; however, this is not specific to nodular hidradenoma.3 Occasionally, tumors can drain serous or hemorrhagic fluid. Nodular hidradenoma commonly is a slow-growing tumor.⁵ Rapid increase in tumor size can be indicative of malignant transformation, hemorrhage into the tumor, or trauma to the area.²

Histologically, nodular hidradenoma consists of a circumscribed, nonencapsulated, multilobular tumor commonly found in the dermis and sometimes extending into the subcutaneous tissue. There usually is no epidermal attachment, and the overlying epidermis largely is normal. The tumor consists of large multilobulated areas of epithelial cells, tubular lamina, and large cystic areas filled with homogenous eosinophilic material.¹ It notably is composed of 2 epithelial cell types: (1) fusiform cells with elongated vesicular nuclei and basophilic cytoplasm, and (2) large polygonal cells with round eccentric nuclei and eosinophilic, periodic acid–Schiff–positive cytoplasm that washes away during fixation, giving the appearance of clear cells.⁵ Both types of cells are small, monotonous, and void of mitosis or dyskeratosis. Although there can be ducts with apocrine secretion present within the lobulated tumor, they are not consistently found. Due to the varying features that are neither mandatory nor consistent to arrive at this diagnosis, some dermatopathologists view the term hidradenoma as a catch-all term that includes several different types of benign sweat gland tumors. Some authors divide the terminology into apocrine hidradenoma and eccrine hidradenoma based on whether the tumor is composed of solely clear mucinous cells, or poroid and cuticular cells, respectively.

Although nodular hidradenoma classically is a benign tumor, total surgical excision is recommended due to the rare risk for malignant transformation. Rarely, longstanding hidradenomas can metastasize to lymph nodes, bone, or viscera; in these instances, metastatic hidradenoma has a 5-year survival rate of 30%. Recurrence may occur in tumors that are inadequately excised, and the rate of recurrence is estimated to be approximately 10% of surgically excised tumors.⁵ However, utilization of Mohs micrographic surgery for excision of nodular hidradenoma is associated with a reduced recurrence rate.⁶

Keloids present as painful, sometimes pruritic, raised scars that extend beyond the boundary of the initial injury, commonly arising on the shoulder, upper arm, and chest. Histopathology reveals nodules of thick hyalinized collagen bundles, keloidal collagen with mucinous ground substance, and few fibroblasts.⁷

Metastatic renal cell carcinoma to the skin most commonly presents on the face and scalp as a nodular, rapidly growing, round to oval lesion that is flesh colored to reddish purple in a patient with history of renal cell carcinoma.⁸ Histopathology shows clusters of atypical, nucleated clear cells surrounded by chicken wire vasculature.^8,9

Verruca vulgaris is caused by human papillomavirus and most commonly occurs on the hands and feet. It presents as a pink to white, sessile lesion with a verrucous surface and exophytic growths. Histopathology shows acanthosis; hypergranulosis; exophytic projections with a fibrovascular core; inward cupping of the rete ridges; and koilocytes, which are cells with an eccentric, raisinlike nucleus and vacuolated cytoplasm in the granular layer of the epidermis.¹⁰

Similar to nodular hidradenoma, nodular melanoma most commonly presents on the head and neck as a symmetric, elevated, amelanotic nodule, but in contrast to nodular hidradenoma, it typically is confined to a smaller diameter.¹¹ Histologically, it is characterized by sheets of atypical, commonly epithelioid melanocytes with a lack of maturation and brisk mitotic activity extending through the epidermis and dermis with lateral extension limited to less than 3 rete ridges.¹²

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Dermatitis Neglecta

A punch biopsy of the abdomen revealed hyperkeratosis and mild papillomatosis (Figure), which can be seen in dermatitis neglecta (DN) and acanthosis nigricans (AN) as well as confluent and reticulated papillomatosis (CARP). Due to the patient’s history of mood and psychotic disorders, collateral information was obtained from the patient’s family, who reported that the patient had a depressed mood in the last few months and was not showering or caring for herself during this period. There was no additional personal or family history of skin disease. Clinical and histopathologic findings led to a diagnosis of DN. Following recommendations for daily cleansing with soap and water along with topical ammonium lactate, near-complete resolution of the rash was achieved in 3 weeks.

Dermatitis neglecta, or unwashed dermatosis, is a skin condition that occurs secondary to poor hygiene, which was first reported in 1995 by Poskitt et al.¹ Avoidance of washing in affected areas can be due to physical disability, pain after injury, neurological deficit, or psychologically induced fear or neglect. Sebum, sweat, corneocytes, and bacteria combine into compact adherent crusts of dirt, which appear as hyperkeratotic plaques with cornflakelike scale.^2,3 Despite its innate simplicity, DN is a diagnostic challenge, as it clinically and histologically mimics other dermatoses including AN, terra firmaforme dermatosis, and CARP.^2,4 Ultimately, the diagnosis of DN can be made when a history of poor hygiene is probable or elicited, and lesions can be removed with soap and water. Treatment of DN includes daily cleansing with soap and water; however, resistant lesions or extensive disease may require keratolytic agents, as in our patient.^2-4 In contrast, terra firma-forme dermatosis, which may look similar, is not due to poor hygiene, and the lesions typically are resistant to soap and water, classically requiring isopropyl alcohol for removal. Overall, maintained awareness of DN is imperative, as early diagnosis can avoid unnecessary biopsies and more complex treatment measures as well as facilitate coordination of care when additional medical or psychiatric concerns are present.

Although the diagnoses of DN and terra firma-forme dermatosis can be distinguished based on the patient’s clinical history and response to simple cleansing measures alone, the alternate diagnoses can be excluded based on different clinical distributions and response to other treatment modalities but sometimes may require clinicopathologic correlation for definitive diagnosis. Our patient had a biopsy diagnosis of psoriasiform dermatitis from an outside provider, but neither her clinical disease nor repeated histopathologic findings supported a diagnosis of psoriasis or other classic psoriasiform dermatoses such as contact dermatitis, dermatophyte/ candidal infection, seborrheic dermatitis, pityriasis rubra pilaris, pityriasis rosea, scabies, or syphilis.

It is imperative to exclude alternative diagnoses because they can have systemic implications and can misguide treatment, as was done initially with our patient. Psoriasis vulgaris in its classic form is a chronic inflammatory skin disease that manifests as sharply demarcated, erythematous plaques with overlying thick silvery scale; it has the additional histologic findings of neutrophilic spongiform pustules in the epidermis, tortuous blood vessels in the papillary dermis, and neutrophils and parakeratosis in the stratum corneum. In its benign form, AN is associated with endocrinopathies, most commonly obesity and insulin-resistant diabetes mellitus, and presents as hyperkeratotic, velvety, hyperpigmented plaques typically limited to the neck and axillae. Malignant AN spontaneously arises in association with systemic malignancy and can be extensive and generalized.⁵ Treatment of AN primarily focuses on resolution of the underlying systemic disease; however, cosmetic treatment with topical or oral retinoids may hasten resolution of cutaneous disease.⁶ Confluent and reticulated papillomatosis is characterized by reticulated hyperkeratotic plaques with a common distribution over the central and upper trunk. Unlike DN and AN, which may occur at any age, CARP typically is seen in adolescents and young adults.⁷ There is no evidence-based gold standard for the management of CARP; however, the successful use of various antibiotics, antifungals, and retinoids—alone or in combination—has been reported.⁸ Overall, compared to the other entities in the differential diagnosis, DN easily can be prevented with consistent use of soap and water and may be underreported given the asymptomatic nature of the disease and the typical patient population.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Recurrent Cutaneous T-Cell Lymphoma

The skin biopsy revealed alternating orthokeratosis and parakeratosis with mild to moderate spongiosis and intraepidermal vesiculation as well as individual and nested atypical mononuclear cells with moderately enlarged hyperchromatic nuclei in the epidermis. There was a superficial interstitial lymphocytic infiltrate with occasional enlarged cells (Figure, A and B), and atypical cells in the epidermis and dermis stained with antibodies against CD3 and CD4 (Figure, C and D) but not against CD20 or CD8. These histopathologic findings were consistent with cutaneous T-cell lymphoma (CTCL), mycosis fungoides (MF) type. Additional application of bexarotene gel on days the patient received narrowband UVB was recommended with noted improvement of the skin.

Cutaneous T-cell lymphomas are a heterogenous group of diseases with monoclonal proliferation of T lymphocytes that largely are confined to the skin at the time of diagnosis.¹ The incidence of CTCL rose steadily for more than 25 years, with an annual age-adjusted incidence of 6.4 to 9.6 cases per million individuals in the United States from 1973 to 2002.² Mycosis fungoides is the most common classification of CTCL. It usually is characterized by patches or plaques of scaly erythema or poikiloderma; however, it also can present with annular, arcuate, concentrative, annular and linear morphologies. Mycosis fungoides tumor cells typically express a mature memory T helper cell phenotype of CD3+, CD4+, and CD8−, but there are different variants that have been discovered.³ Mycosis fungoides distributed in a spiral pattern is a distinctly unusual manifestation. Mechanisms of such dynamic morphologies are unknown but may represent an interplay between malignant cell proliferation and lost immune responses in temporospatial relationships.

The presence of keratotic gyrate lesions on acral surfaces should raise the possibility of pagetoid reticulosis. However, our patient had a history of MF involving areas of the body beyond the extremities, making this diagnosis less likely. Pagetoid reticulosis is categorized as an MF variant under the current World Health Organization– European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas.⁴ Pagetoid reticulosis clinically presents as a solitary psoriasiform or hyperkeratotic patch or plaque that affects the distal extremities. Variable immunophenotypes have been shown in pagetoid reticulosis, such as CD4−/CD8+ and CD4−/CD8−, while classic MF typically shows CD4+/CD8−, as in our case.⁵

Tinea pedis is a superficial fungal infection usually caused by anthropophilic dermatophytes, with Trichophyton rubrum being the most common organism. Four common clinical presentations of tinea pedis have been identified: interdigital, moccasin, vesicular, and acute ulcerative. Clinical presentation ranges from macerations, ulcerations, and erosions in the toe web spaces to dry hyperkeratotic scaling and fissures on the plantar foot.⁶ Tinea pedis primarily affects the plantar and interdigital spaces, sparing the dorsal foot and ankle. Treatment is recommended to alleviate symptoms and limit the spread of infection; topical antifungals for 4 weeks is the treatment of choice. However, recurrence is common, and maintenance therapy often is indicated. Oral antifungals or a combination of both topical and oral medications may be needed in certain cases.⁷

Erythema annulare centrifugum (EAC) is a rare dermatologic disease described as erythematous or urticarial papules that can enlarge centrifugally to form annular lesions that clear centrally. Thought to be a hypersensitivity reaction to an underlying condition, EAC has been associated with fungal infections, various cutaneous diseases, and even internal malignancies. Clinically, EAC can be divided into 2 forms: deep and superficial. Deep gyrate erythema is characterized by a firm indurated border with rare scaling and pruritus that histologically shows perivascular lymphocytic infiltration in the upper and deep dermis. Superficial gyrate erythema has minimally elevated lesions with an indistinct border and trailing scales and pruritus; histopathologic findings present a dense, perivascular, lymphocytic infiltration restricted to the upper dermis.⁸ Therapy for EAC is directed at relieving symptoms and treating the underlying condition if there is one associated.

Granuloma annulare (GA) is a common skin disorder classically characterized by ringed erythematous plaques, though many variants have been identified. Localized GA is the most common variant and presents with pink-red, nonscaly, annular patches or plaques, typically affecting the hands and feet. Generalized GA is characterized as diffuse annular patches or plaques classically affecting the trunk and extremities. Histology is notable for mucin with a palisading or interstitial pattern of granulomatous inflammation, which was not evident in our patient.⁹ Topical or intralesional corticosteroids are the first-line treatment of localized GA; however, localized GA generally is self-limited, and treatment often is not necessary. Treatment with cryosurgery, laser therapy, and topical dapsone and tacrolimus also has been described, but evidence of the efficacy of these agents is limited. For generalized GA, phototherapy currently is the most reliable therapy. Systemic therapies include antimalarials, fumaric acid esters, biologics, antimicrobials, and isotretinoin.¹⁰

Erythema gyratum repens (EGR) is a rare dermatologic disease described as erythematous concentric bands arranged in parallel rings that can be annular, figurate, or gyrate, with a fine scale trailing the leading edge. Histopathologic features of EGR are nonspecific but are characterized by a perivascular, superficial, mononuclear dermatitis. Diagnosis is based on its characteristic clinical presentation. Although EGR commonly is associated with internal malignancies such as bronchial carcinoma, it also may be associated with benign conditions.¹¹ Improvement often is seen with successful therapy of the underlying associated malignancy.¹²

Treatment of MF is based on tumor-node-metastasisblood classification, prognostic factors, and clinical stage at the time of diagnosis. Early-stage MF (IA–IIA) commonly is treated with skin-directed therapies such as topical corticosteroids, topical mechlorethamine, topical retinoids, UV phototherapy, and localized radiotherapy. In late stages (IIB–IV), systemic therapy is indicated and includes systemic retinoids, interferon alfa, chemotherapy, monoclonal antibodies, and psoralen plus UVA.¹³ In many cases, patients may require combination therapy to achieve remission or better control of their condition, as in our patient.

The Diagnosis: Microcystic Lymphatic Malformation 

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

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

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

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

The Diagnosis: Microcystic Lymphatic Malformation 

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

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

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

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

The Diagnosis: Microcystic Lymphatic Malformation 

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

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

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

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