Photo Challenge

The Diagnosis: PELVIS Syndrome

Infantile hemangiomas (IHs) are present in up to 10% of infants by 1 year of age and are most commonly located on the face and upper extremities. Less than 10% of IHs develop in the perineum.¹ Perineal IHs are benign tumors of the vascular endothelium that present as plaques and commonly are accompanied by painful ulcerations. Ulceration is more common in the diaper area secondary to irritation from urine, stool, and friction.² Although most IHs are benign isolated findings, facial IHs have been associated with several syndromes including Sturge-Weber and PHACE (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies and coarctation of the aorta, and eye and endocrine abnormalities) syndromes.³ Researchers also have identified an association between lumbosacral IHs and spinal dysraphism (tethered spinal cord).⁴

A smaller number of studies have investigated congenital anomalies related to perineal IH,^1,5 specifically PELVIS syndrome. The acronym PELVIS has been used to describe a syndrome of congenital malformations including perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag.¹ An alternative description of similar findings is LUMBAR (lower body hemangioma and other cutaneous defects; urogenital anomalies, ulceration; myelopathy; bony deformities; anorectal malformations, arterial anomalies; and renal anomalies).⁵ Researchers have suggested that both of these acronyms describe the same syndrome, and it is common for the syndrome to be incomplete.⁶ One study (N=11) found that perineal hemangiomas are most commonly associated with anal malformations (8 patients), followed by urinary tract abnormalities (7 patients) and malformation of the external genitalia (7 patients). A skin tag was present in 5 patients.¹ The pathogenesis of PELVIS syndrome is unknown.

When an infant presents with a perineal hemangioma and physical examination suggests PELVIS syndrome, imaging should be performed to evaluate for other anomalies. Before 4 months of age, ultrasound should be utilized to investigate the presence of reno-genitourinary or spinal malformations. Magnetic resonance imaging is the preferred imaging modality in children older than 4 months.⁷ Management of PELVIS syndrome requires a multidisciplinary approach and early recognition of the full extent of congenital malformations. Pediatric dermatologists, urologists, endocrinologists, and neonatologists have a role in its diagnosis and treatment.

The Diagnosis: PELVIS Syndrome

Infantile hemangiomas (IHs) are present in up to 10% of infants by 1 year of age and are most commonly located on the face and upper extremities. Less than 10% of IHs develop in the perineum.¹ Perineal IHs are benign tumors of the vascular endothelium that present as plaques and commonly are accompanied by painful ulcerations. Ulceration is more common in the diaper area secondary to irritation from urine, stool, and friction.² Although most IHs are benign isolated findings, facial IHs have been associated with several syndromes including Sturge-Weber and PHACE (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies and coarctation of the aorta, and eye and endocrine abnormalities) syndromes.³ Researchers also have identified an association between lumbosacral IHs and spinal dysraphism (tethered spinal cord).⁴

A smaller number of studies have investigated congenital anomalies related to perineal IH,^1,5 specifically PELVIS syndrome. The acronym PELVIS has been used to describe a syndrome of congenital malformations including perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag.¹ An alternative description of similar findings is LUMBAR (lower body hemangioma and other cutaneous defects; urogenital anomalies, ulceration; myelopathy; bony deformities; anorectal malformations, arterial anomalies; and renal anomalies).⁵ Researchers have suggested that both of these acronyms describe the same syndrome, and it is common for the syndrome to be incomplete.⁶ One study (N=11) found that perineal hemangiomas are most commonly associated with anal malformations (8 patients), followed by urinary tract abnormalities (7 patients) and malformation of the external genitalia (7 patients). A skin tag was present in 5 patients.¹ The pathogenesis of PELVIS syndrome is unknown.

When an infant presents with a perineal hemangioma and physical examination suggests PELVIS syndrome, imaging should be performed to evaluate for other anomalies. Before 4 months of age, ultrasound should be utilized to investigate the presence of reno-genitourinary or spinal malformations. Magnetic resonance imaging is the preferred imaging modality in children older than 4 months.⁷ Management of PELVIS syndrome requires a multidisciplinary approach and early recognition of the full extent of congenital malformations. Pediatric dermatologists, urologists, endocrinologists, and neonatologists have a role in its diagnosis and treatment.

The Diagnosis: PELVIS Syndrome

Infantile hemangiomas (IHs) are present in up to 10% of infants by 1 year of age and are most commonly located on the face and upper extremities. Less than 10% of IHs develop in the perineum.¹ Perineal IHs are benign tumors of the vascular endothelium that present as plaques and commonly are accompanied by painful ulcerations. Ulceration is more common in the diaper area secondary to irritation from urine, stool, and friction.² Although most IHs are benign isolated findings, facial IHs have been associated with several syndromes including Sturge-Weber and PHACE (posterior fossa brain malformations, hemangiomas, arterial anomalies, cardiac anomalies and coarctation of the aorta, and eye and endocrine abnormalities) syndromes.³ Researchers also have identified an association between lumbosacral IHs and spinal dysraphism (tethered spinal cord).⁴

A smaller number of studies have investigated congenital anomalies related to perineal IH,^1,5 specifically PELVIS syndrome. The acronym PELVIS has been used to describe a syndrome of congenital malformations including perineal hemangioma, external genital malformations, lipomyelomeningocele, vesicorenal abnormalities, imperforate anus, and skin tag.¹ An alternative description of similar findings is LUMBAR (lower body hemangioma and other cutaneous defects; urogenital anomalies, ulceration; myelopathy; bony deformities; anorectal malformations, arterial anomalies; and renal anomalies).⁵ Researchers have suggested that both of these acronyms describe the same syndrome, and it is common for the syndrome to be incomplete.⁶ One study (N=11) found that perineal hemangiomas are most commonly associated with anal malformations (8 patients), followed by urinary tract abnormalities (7 patients) and malformation of the external genitalia (7 patients). A skin tag was present in 5 patients.¹ The pathogenesis of PELVIS syndrome is unknown.

When an infant presents with a perineal hemangioma and physical examination suggests PELVIS syndrome, imaging should be performed to evaluate for other anomalies. Before 4 months of age, ultrasound should be utilized to investigate the presence of reno-genitourinary or spinal malformations. Magnetic resonance imaging is the preferred imaging modality in children older than 4 months.⁷ Management of PELVIS syndrome requires a multidisciplinary approach and early recognition of the full extent of congenital malformations. Pediatric dermatologists, urologists, endocrinologists, and neonatologists have a role in its diagnosis and treatment.

The Diagnosis: Cutaneous Mastocytoma

Physical examination revealed a 58×51-mm hyperpigmented plaque with central pink coloration and scale on the right side of the back as well as a 39×33-mm pink plaque with a hyperpigmented border on the left side of the flank (Figure 1). At follow-up 2 weeks later, the patient's parents reported that blisters formed within both of the plaques. The blisters ruptured a few hours after forming and drained clear fluid with scant blood. Both plaques contained erosions from the ruptured bullae but remained the same size with no surrounding erythema or warmth. A 4-mm punch biopsy was performed of intact skin from the back lesion (Figure 2A). Histologic examination revealed a cellular infiltrate of monotonous bland cells that completely filled the dermis without epidermal involvement, along with occasional intermixed eosinophils. The morphology of these infiltrating cells was compatible with mast cells confirmed by strongly positive Leder staining (Figure 2B).

Mastocytosis encompasses a rare group of disorders characterized by abnormal mast cell accumulation or mast cell mediator release in various tissues. These disorders can be classified as either systemic mastocytosis with mast cell infiltration into bone marrow or other extracutaneous organs, or cutaneous mastocytosis with disease limited to the skin.¹ Mutations involving activation of the c-Kit receptor in stimulating mast cell growth and development have been implicated in both systemic and cutaneous forms of the disease.^2,3

Cutaneous mastocytosis is most often diagnosed in childhood and typically is characterized by spontaneous regression before puberty in a majority of cases.^1,4 Under the World Health Organization classification system, cutaneous mastocytosis can be further subdivided into 3 disorders (listed in order of most to least common): urticaria pigmentosa (also known as maculopapular cutaneous mastocytosis) with typical, plaque, and nodular forms; cutaneous mastocytoma (as seen in this patient); and diffuse cutaneous mastocytosis.⁵ Compared to the widespread distribution of small macules and papules in urticaria pigmentosa, the cutaneous mastocytoma subtype presents with 1 to 6 brown to orange-yellow plaques or nodules measuring more than 1 cm in diameter. Cutaneous mastocytoma typically presents in infancy and is located most commonly on the trunk and extremities, though it may be found on the face or scalp. The plaques of mastocytoma often have well-defined margins, and these lesions may become bullous or demonstrate Darier sign of urtication and erythema on physical stimulation. Patients most commonly experience pruritus from mast cell degranulation and rarely exhibit systemic symptoms of mast cell mediator release; however, generalized flushing, hypotension, headaches, and gastrointestinal symptoms may occur, particularly if the lesion is vigorously rubbed.^6,7 Conditions in the differential include aplasia cutis congenita, connective tissue nevus, epidermal nevus, and epidermolysis bullosa. They should not elicit a blister if rubbed, except for epidermolysis bullosa, which can easily be differentiated based on histology.

The workup for cutaneous mastocytosis in the pediatric population may include a biopsy of lesional skin, though in many cases the characteristic cutaneous manifestations are sufficient to make a diagnosis. Histologically, biopsy results often reveal abundant diffuse dermal infiltration of mast cells, which are characterized by their large pink granular cytoplasm and round dense central nuclei. In pediatric patients, mast cells typically are restricted to the dermis, and there is a low risk for hematologic abnormalities, thereby precluding the need for bone marrow examination in the absence of organomegaly or notable peripheral blood abnormalities such as severe cytopenia.^5,6

Management of cutaneous mastocytosis consists of avoidance of mast cell degranulation triggers and symptomatic treatment of histamine release. Triggers include certain medications (eg, narcotic analgesics, aspirin, nonsteroidal anti-inflammatory drugs, iodinated contrast agents, antibiotics, muscle relaxants), mechanical irritation, insect stings, spicy foods, stress, or extreme temperature changes.⁸ Symptomatic treatment can be achieved through topical corticosteroid or oral antihistamine use. Along with decreasing pruritus, topical corticosteroids also may be helpful in decreasing time to spontaneous resolution and healing.⁷ The patient in this case was treated with desonide ointment 0.05% daily to both lesions as well as mupirocin ointment 2% as needed for erosions. These treatments helped reduce the patient's symptoms, but her lesions persisted over a follow-up period of 4 months.

The Diagnosis: Cutaneous Mastocytoma

Physical examination revealed a 58×51-mm hyperpigmented plaque with central pink coloration and scale on the right side of the back as well as a 39×33-mm pink plaque with a hyperpigmented border on the left side of the flank (Figure 1). At follow-up 2 weeks later, the patient's parents reported that blisters formed within both of the plaques. The blisters ruptured a few hours after forming and drained clear fluid with scant blood. Both plaques contained erosions from the ruptured bullae but remained the same size with no surrounding erythema or warmth. A 4-mm punch biopsy was performed of intact skin from the back lesion (Figure 2A). Histologic examination revealed a cellular infiltrate of monotonous bland cells that completely filled the dermis without epidermal involvement, along with occasional intermixed eosinophils. The morphology of these infiltrating cells was compatible with mast cells confirmed by strongly positive Leder staining (Figure 2B).

Mastocytosis encompasses a rare group of disorders characterized by abnormal mast cell accumulation or mast cell mediator release in various tissues. These disorders can be classified as either systemic mastocytosis with mast cell infiltration into bone marrow or other extracutaneous organs, or cutaneous mastocytosis with disease limited to the skin.¹ Mutations involving activation of the c-Kit receptor in stimulating mast cell growth and development have been implicated in both systemic and cutaneous forms of the disease.^2,3

Cutaneous mastocytosis is most often diagnosed in childhood and typically is characterized by spontaneous regression before puberty in a majority of cases.^1,4 Under the World Health Organization classification system, cutaneous mastocytosis can be further subdivided into 3 disorders (listed in order of most to least common): urticaria pigmentosa (also known as maculopapular cutaneous mastocytosis) with typical, plaque, and nodular forms; cutaneous mastocytoma (as seen in this patient); and diffuse cutaneous mastocytosis.⁵ Compared to the widespread distribution of small macules and papules in urticaria pigmentosa, the cutaneous mastocytoma subtype presents with 1 to 6 brown to orange-yellow plaques or nodules measuring more than 1 cm in diameter. Cutaneous mastocytoma typically presents in infancy and is located most commonly on the trunk and extremities, though it may be found on the face or scalp. The plaques of mastocytoma often have well-defined margins, and these lesions may become bullous or demonstrate Darier sign of urtication and erythema on physical stimulation. Patients most commonly experience pruritus from mast cell degranulation and rarely exhibit systemic symptoms of mast cell mediator release; however, generalized flushing, hypotension, headaches, and gastrointestinal symptoms may occur, particularly if the lesion is vigorously rubbed.^6,7 Conditions in the differential include aplasia cutis congenita, connective tissue nevus, epidermal nevus, and epidermolysis bullosa. They should not elicit a blister if rubbed, except for epidermolysis bullosa, which can easily be differentiated based on histology.

The workup for cutaneous mastocytosis in the pediatric population may include a biopsy of lesional skin, though in many cases the characteristic cutaneous manifestations are sufficient to make a diagnosis. Histologically, biopsy results often reveal abundant diffuse dermal infiltration of mast cells, which are characterized by their large pink granular cytoplasm and round dense central nuclei. In pediatric patients, mast cells typically are restricted to the dermis, and there is a low risk for hematologic abnormalities, thereby precluding the need for bone marrow examination in the absence of organomegaly or notable peripheral blood abnormalities such as severe cytopenia.^5,6

Management of cutaneous mastocytosis consists of avoidance of mast cell degranulation triggers and symptomatic treatment of histamine release. Triggers include certain medications (eg, narcotic analgesics, aspirin, nonsteroidal anti-inflammatory drugs, iodinated contrast agents, antibiotics, muscle relaxants), mechanical irritation, insect stings, spicy foods, stress, or extreme temperature changes.⁸ Symptomatic treatment can be achieved through topical corticosteroid or oral antihistamine use. Along with decreasing pruritus, topical corticosteroids also may be helpful in decreasing time to spontaneous resolution and healing.⁷ The patient in this case was treated with desonide ointment 0.05% daily to both lesions as well as mupirocin ointment 2% as needed for erosions. These treatments helped reduce the patient's symptoms, but her lesions persisted over a follow-up period of 4 months.

The Diagnosis: Cutaneous Mastocytoma

Physical examination revealed a 58×51-mm hyperpigmented plaque with central pink coloration and scale on the right side of the back as well as a 39×33-mm pink plaque with a hyperpigmented border on the left side of the flank (Figure 1). At follow-up 2 weeks later, the patient's parents reported that blisters formed within both of the plaques. The blisters ruptured a few hours after forming and drained clear fluid with scant blood. Both plaques contained erosions from the ruptured bullae but remained the same size with no surrounding erythema or warmth. A 4-mm punch biopsy was performed of intact skin from the back lesion (Figure 2A). Histologic examination revealed a cellular infiltrate of monotonous bland cells that completely filled the dermis without epidermal involvement, along with occasional intermixed eosinophils. The morphology of these infiltrating cells was compatible with mast cells confirmed by strongly positive Leder staining (Figure 2B).

Mastocytosis encompasses a rare group of disorders characterized by abnormal mast cell accumulation or mast cell mediator release in various tissues. These disorders can be classified as either systemic mastocytosis with mast cell infiltration into bone marrow or other extracutaneous organs, or cutaneous mastocytosis with disease limited to the skin.¹ Mutations involving activation of the c-Kit receptor in stimulating mast cell growth and development have been implicated in both systemic and cutaneous forms of the disease.^2,3

Cutaneous mastocytosis is most often diagnosed in childhood and typically is characterized by spontaneous regression before puberty in a majority of cases.^1,4 Under the World Health Organization classification system, cutaneous mastocytosis can be further subdivided into 3 disorders (listed in order of most to least common): urticaria pigmentosa (also known as maculopapular cutaneous mastocytosis) with typical, plaque, and nodular forms; cutaneous mastocytoma (as seen in this patient); and diffuse cutaneous mastocytosis.⁵ Compared to the widespread distribution of small macules and papules in urticaria pigmentosa, the cutaneous mastocytoma subtype presents with 1 to 6 brown to orange-yellow plaques or nodules measuring more than 1 cm in diameter. Cutaneous mastocytoma typically presents in infancy and is located most commonly on the trunk and extremities, though it may be found on the face or scalp. The plaques of mastocytoma often have well-defined margins, and these lesions may become bullous or demonstrate Darier sign of urtication and erythema on physical stimulation. Patients most commonly experience pruritus from mast cell degranulation and rarely exhibit systemic symptoms of mast cell mediator release; however, generalized flushing, hypotension, headaches, and gastrointestinal symptoms may occur, particularly if the lesion is vigorously rubbed.^6,7 Conditions in the differential include aplasia cutis congenita, connective tissue nevus, epidermal nevus, and epidermolysis bullosa. They should not elicit a blister if rubbed, except for epidermolysis bullosa, which can easily be differentiated based on histology.

The workup for cutaneous mastocytosis in the pediatric population may include a biopsy of lesional skin, though in many cases the characteristic cutaneous manifestations are sufficient to make a diagnosis. Histologically, biopsy results often reveal abundant diffuse dermal infiltration of mast cells, which are characterized by their large pink granular cytoplasm and round dense central nuclei. In pediatric patients, mast cells typically are restricted to the dermis, and there is a low risk for hematologic abnormalities, thereby precluding the need for bone marrow examination in the absence of organomegaly or notable peripheral blood abnormalities such as severe cytopenia.^5,6

Management of cutaneous mastocytosis consists of avoidance of mast cell degranulation triggers and symptomatic treatment of histamine release. Triggers include certain medications (eg, narcotic analgesics, aspirin, nonsteroidal anti-inflammatory drugs, iodinated contrast agents, antibiotics, muscle relaxants), mechanical irritation, insect stings, spicy foods, stress, or extreme temperature changes.⁸ Symptomatic treatment can be achieved through topical corticosteroid or oral antihistamine use. Along with decreasing pruritus, topical corticosteroids also may be helpful in decreasing time to spontaneous resolution and healing.⁷ The patient in this case was treated with desonide ointment 0.05% daily to both lesions as well as mupirocin ointment 2% as needed for erosions. These treatments helped reduce the patient's symptoms, but her lesions persisted over a follow-up period of 4 months.

The Diagnosis: Erythema Dyschromicum Perstans

Erythema dyschromicum perstans (EDP), also referred to as ashy dermatosis, was first described by Ramirez¹ in 1957 who labeled the patients los cenicientos (the ashen ones). It preferentially affects women in the second decade of life; however, patients of all ages can be affected, with reported cases occurring in children as young as 2 years of age.² Most patients have Fitzpatrick skin type IV, mainly Amerindian, Hispanic South Asian, and Southwest Asian; however, there are cases reported worldwide.³ A genetic predisposition is proposed, as major histocompatibility complex genes associated with HLA-DR4⁎0407 are frequent in Mexican patients with ashy dermatosis and in the Amerindian population.⁴

The etiology of EDP is unknown. Various contributing factors have been reported including alimentary, occupational, and climatic factors,^5,6 yet none have been conclusively demonstrated. High expression of CD36 (thrombospondin receptor not found in normal skin) in spinous and granular layers, CD94 (cytotoxic cell marker) in the basal cell layer and in the inflammatory dermal infiltrate,⁷ and focal keratinocytic expression of intercellular adhesion molecule I (CD54) in the active lesions of EDP, as well as the absence of these findings in normal skin, suggests an immunologic role in the development of the disease.⁸

Erythema dyschromicum perstans presents clinically with blue-gray hyperpigmented macules varying in size and shape and developing symmetrically in both sun-exposed and sun-protected areas of the face, neck, trunk, arms, and sometimes the dorsal hands (Figures 1 and 2). Notable sparing of the palms, soles, scalp, and mucous membranes occurs.

Occasionally, in the early active stage of the disease, elevated erythematous borders are noted surrounding the hyperpigmented macules. Eventually a hypopigmented halo develops after a prolonged duration of disease.⁹ The eruption typically is chronic and asymptomatic, though some cases may be pruritic.¹⁰

Histopathologically, the early lesions of EDP with an erythematous active border reveal lichenoid dermatitis with basal vacuolar change and occasional Civatte bodies. A mild to moderate perivascular lymphohistiocytic infiltrate admixed with melanophages can be seen in the papillary dermis (Figure 3). In older lesions, the inflammatory infiltrate is sparse, and pigment incontinence consistent with postinflammatory pigmentation is prominent, though melanophages extending deep into the reticular dermis may aid in distinguishing EDP from other causes of postinflammatory pigment alteration.^7,11

Erythema dyschromicum perstans and lichen planus pigmentosus (LPP) may be indistinguishable histopathologically and may both be variants of lichen planus actinicus. Lichen planus pigmentosus often differs from EDP in that it presents with brown-black macules and patches often on the face and flexural areas. A subset of cases of LPP also may have mucous membrane involvement. The erythematous border that characterizes the active lesion of EDP is characteristically absent in LPP. In addition, pruritus often is reported with LPP. Direct immunofluorescence is not a beneficial tool in distinguishing the entities.¹²

Other differential diagnoses of predominantly facial hyperpigmentation include a lichenoid drug eruption; drug-induced hyperpigmentation (deposition disorder); postinflammatory hyperpigmentation following atopic dermatitis; contact dermatitis or photosensitivity reaction; early pinta; and cutaneous findings of systemic diseases manifesting with diffuse hyperpigmentation such as lupus erythematosus, dermatomyositis, hemochromatosis, and Addison disease. A detailed history including medication use, thorough clinical examination, and careful histopathologic evaluation will help distinguish these conditions.

Chrysiasis is a rare bluish to slate gray discoloration of the skin that predominantly occurs in sun-exposed areas. It is caused by chronic use of gold salts, which have been used to treat rheumatoid arthritis. UV light may contribute to induce the uptake of gold and subsequently stimulate tyrosinase activity.¹³ Histologic features of chrysiasis include dermal and perivascular gold deposition within the macrophages and endothelial cells as well as extracellular granules. It demonstrates an orange-red birefringence on fluorescent microscopy.^14,15

Minocycline-induced hyperpigmentation is a well-recognized side effect of this drug. It is dose dependent and appears as a blue-black pigmentation that most frequently affects the shins, ankles, and arms.¹⁶ Three distinct types were documented: abnormal discoloration of the skin that has been linked to deposition of pigmented metabolites of minocycline producing blue-black pigmentation at the site of scarring or prior inflammation (type 1); blue-gray pigmentation affecting normal skin, mainly the legs (type 2); and elevated levels of melanin on the sun-exposed areas producing dirty skin syndrome (type 3).^17,18

Topical and systemic corticosteroids, UV light therapy, oral dapsone, griseofulvin, retinoids, and clofazimine are reported as treatment options for ashy dermatosis, though results typically are disappointing.⁷

The Diagnosis: Erythema Dyschromicum Perstans

Erythema dyschromicum perstans (EDP), also referred to as ashy dermatosis, was first described by Ramirez¹ in 1957 who labeled the patients los cenicientos (the ashen ones). It preferentially affects women in the second decade of life; however, patients of all ages can be affected, with reported cases occurring in children as young as 2 years of age.² Most patients have Fitzpatrick skin type IV, mainly Amerindian, Hispanic South Asian, and Southwest Asian; however, there are cases reported worldwide.³ A genetic predisposition is proposed, as major histocompatibility complex genes associated with HLA-DR4⁎0407 are frequent in Mexican patients with ashy dermatosis and in the Amerindian population.⁴

The etiology of EDP is unknown. Various contributing factors have been reported including alimentary, occupational, and climatic factors,^5,6 yet none have been conclusively demonstrated. High expression of CD36 (thrombospondin receptor not found in normal skin) in spinous and granular layers, CD94 (cytotoxic cell marker) in the basal cell layer and in the inflammatory dermal infiltrate,⁷ and focal keratinocytic expression of intercellular adhesion molecule I (CD54) in the active lesions of EDP, as well as the absence of these findings in normal skin, suggests an immunologic role in the development of the disease.⁸

Erythema dyschromicum perstans presents clinically with blue-gray hyperpigmented macules varying in size and shape and developing symmetrically in both sun-exposed and sun-protected areas of the face, neck, trunk, arms, and sometimes the dorsal hands (Figures 1 and 2). Notable sparing of the palms, soles, scalp, and mucous membranes occurs.

Occasionally, in the early active stage of the disease, elevated erythematous borders are noted surrounding the hyperpigmented macules. Eventually a hypopigmented halo develops after a prolonged duration of disease.⁹ The eruption typically is chronic and asymptomatic, though some cases may be pruritic.¹⁰

Histopathologically, the early lesions of EDP with an erythematous active border reveal lichenoid dermatitis with basal vacuolar change and occasional Civatte bodies. A mild to moderate perivascular lymphohistiocytic infiltrate admixed with melanophages can be seen in the papillary dermis (Figure 3). In older lesions, the inflammatory infiltrate is sparse, and pigment incontinence consistent with postinflammatory pigmentation is prominent, though melanophages extending deep into the reticular dermis may aid in distinguishing EDP from other causes of postinflammatory pigment alteration.^7,11

Erythema dyschromicum perstans and lichen planus pigmentosus (LPP) may be indistinguishable histopathologically and may both be variants of lichen planus actinicus. Lichen planus pigmentosus often differs from EDP in that it presents with brown-black macules and patches often on the face and flexural areas. A subset of cases of LPP also may have mucous membrane involvement. The erythematous border that characterizes the active lesion of EDP is characteristically absent in LPP. In addition, pruritus often is reported with LPP. Direct immunofluorescence is not a beneficial tool in distinguishing the entities.¹²

Other differential diagnoses of predominantly facial hyperpigmentation include a lichenoid drug eruption; drug-induced hyperpigmentation (deposition disorder); postinflammatory hyperpigmentation following atopic dermatitis; contact dermatitis or photosensitivity reaction; early pinta; and cutaneous findings of systemic diseases manifesting with diffuse hyperpigmentation such as lupus erythematosus, dermatomyositis, hemochromatosis, and Addison disease. A detailed history including medication use, thorough clinical examination, and careful histopathologic evaluation will help distinguish these conditions.

Chrysiasis is a rare bluish to slate gray discoloration of the skin that predominantly occurs in sun-exposed areas. It is caused by chronic use of gold salts, which have been used to treat rheumatoid arthritis. UV light may contribute to induce the uptake of gold and subsequently stimulate tyrosinase activity.¹³ Histologic features of chrysiasis include dermal and perivascular gold deposition within the macrophages and endothelial cells as well as extracellular granules. It demonstrates an orange-red birefringence on fluorescent microscopy.^14,15

Minocycline-induced hyperpigmentation is a well-recognized side effect of this drug. It is dose dependent and appears as a blue-black pigmentation that most frequently affects the shins, ankles, and arms.¹⁶ Three distinct types were documented: abnormal discoloration of the skin that has been linked to deposition of pigmented metabolites of minocycline producing blue-black pigmentation at the site of scarring or prior inflammation (type 1); blue-gray pigmentation affecting normal skin, mainly the legs (type 2); and elevated levels of melanin on the sun-exposed areas producing dirty skin syndrome (type 3).^17,18

Topical and systemic corticosteroids, UV light therapy, oral dapsone, griseofulvin, retinoids, and clofazimine are reported as treatment options for ashy dermatosis, though results typically are disappointing.⁷

The Diagnosis: Erythema Dyschromicum Perstans

Erythema dyschromicum perstans (EDP), also referred to as ashy dermatosis, was first described by Ramirez¹ in 1957 who labeled the patients los cenicientos (the ashen ones). It preferentially affects women in the second decade of life; however, patients of all ages can be affected, with reported cases occurring in children as young as 2 years of age.² Most patients have Fitzpatrick skin type IV, mainly Amerindian, Hispanic South Asian, and Southwest Asian; however, there are cases reported worldwide.³ A genetic predisposition is proposed, as major histocompatibility complex genes associated with HLA-DR4⁎0407 are frequent in Mexican patients with ashy dermatosis and in the Amerindian population.⁴

The etiology of EDP is unknown. Various contributing factors have been reported including alimentary, occupational, and climatic factors,^5,6 yet none have been conclusively demonstrated. High expression of CD36 (thrombospondin receptor not found in normal skin) in spinous and granular layers, CD94 (cytotoxic cell marker) in the basal cell layer and in the inflammatory dermal infiltrate,⁷ and focal keratinocytic expression of intercellular adhesion molecule I (CD54) in the active lesions of EDP, as well as the absence of these findings in normal skin, suggests an immunologic role in the development of the disease.⁸

Erythema dyschromicum perstans presents clinically with blue-gray hyperpigmented macules varying in size and shape and developing symmetrically in both sun-exposed and sun-protected areas of the face, neck, trunk, arms, and sometimes the dorsal hands (Figures 1 and 2). Notable sparing of the palms, soles, scalp, and mucous membranes occurs.

Occasionally, in the early active stage of the disease, elevated erythematous borders are noted surrounding the hyperpigmented macules. Eventually a hypopigmented halo develops after a prolonged duration of disease.⁹ The eruption typically is chronic and asymptomatic, though some cases may be pruritic.¹⁰

Histopathologically, the early lesions of EDP with an erythematous active border reveal lichenoid dermatitis with basal vacuolar change and occasional Civatte bodies. A mild to moderate perivascular lymphohistiocytic infiltrate admixed with melanophages can be seen in the papillary dermis (Figure 3). In older lesions, the inflammatory infiltrate is sparse, and pigment incontinence consistent with postinflammatory pigmentation is prominent, though melanophages extending deep into the reticular dermis may aid in distinguishing EDP from other causes of postinflammatory pigment alteration.^7,11

Erythema dyschromicum perstans and lichen planus pigmentosus (LPP) may be indistinguishable histopathologically and may both be variants of lichen planus actinicus. Lichen planus pigmentosus often differs from EDP in that it presents with brown-black macules and patches often on the face and flexural areas. A subset of cases of LPP also may have mucous membrane involvement. The erythematous border that characterizes the active lesion of EDP is characteristically absent in LPP. In addition, pruritus often is reported with LPP. Direct immunofluorescence is not a beneficial tool in distinguishing the entities.¹²

Other differential diagnoses of predominantly facial hyperpigmentation include a lichenoid drug eruption; drug-induced hyperpigmentation (deposition disorder); postinflammatory hyperpigmentation following atopic dermatitis; contact dermatitis or photosensitivity reaction; early pinta; and cutaneous findings of systemic diseases manifesting with diffuse hyperpigmentation such as lupus erythematosus, dermatomyositis, hemochromatosis, and Addison disease. A detailed history including medication use, thorough clinical examination, and careful histopathologic evaluation will help distinguish these conditions.

Chrysiasis is a rare bluish to slate gray discoloration of the skin that predominantly occurs in sun-exposed areas. It is caused by chronic use of gold salts, which have been used to treat rheumatoid arthritis. UV light may contribute to induce the uptake of gold and subsequently stimulate tyrosinase activity.¹³ Histologic features of chrysiasis include dermal and perivascular gold deposition within the macrophages and endothelial cells as well as extracellular granules. It demonstrates an orange-red birefringence on fluorescent microscopy.^14,15

Minocycline-induced hyperpigmentation is a well-recognized side effect of this drug. It is dose dependent and appears as a blue-black pigmentation that most frequently affects the shins, ankles, and arms.¹⁶ Three distinct types were documented: abnormal discoloration of the skin that has been linked to deposition of pigmented metabolites of minocycline producing blue-black pigmentation at the site of scarring or prior inflammation (type 1); blue-gray pigmentation affecting normal skin, mainly the legs (type 2); and elevated levels of melanin on the sun-exposed areas producing dirty skin syndrome (type 3).^17,18

Topical and systemic corticosteroids, UV light therapy, oral dapsone, griseofulvin, retinoids, and clofazimine are reported as treatment options for ashy dermatosis, though results typically are disappointing.⁷

The Diagnosis: Hypertrophic Lupus Erythematosus

Physical examination at initial presentation revealed well-demarcated, 2- to 3-cm plaques with scale distributed most extensively on the elbows and shins with lesser involvement of the chest and abdomen. After treatment with topical steroids, adalimumab, methotrexate, and narrowband UVB phototherapy, new annular, erythematous, and edematous lesions began to appear on the chest and abdomen (Figure 1). These new lesions appeared less hyperkeratotic than the older ones.

Biopsy of a hyperkeratotic lesion from the patient's arm revealed marked hyperkeratosis, parakeratosis, epidermal hyperplasia, focal vacuolar change, solar elastosis, and transepidermal elastotic elimination (Figure 2A). A second biopsy performed on a newer chest lesion revealed interface changes, degeneration of the basal layer, follicular plugging, and dermal mucin (Figure 2B). Serology revealed an antinuclear antibody (ANA) titer of 1:1280 (reference range, <1:40 dilution) and hemoglobin of 11.5 g/dL (reference range, 14.0-17.5 g/dL). On the basis of clinical, histologic, and serologic findings, hypertrophic lupus erythematosus (LE) was diagnosed. The patient was treated with oral prednisone, which resulted in rapid improvement.

Hypertrophic LE is a rare subset of chronic cutaneous lupus first described by Behcet¹ in 1942. Lesions are identified as verrucous keratotic plaques with a characteristic erythematous indurated border.² Patients predominantly are middle-aged women with lesions distributed on sun-exposed areas. Most often, hypertrophic LE is seen in association with the classic lesions of discoid LE; however, patients may present exclusively with the cutaneous manifestations of hypertrophic LE. More rarely, as seen in this case, hypertrophic LE may present in conjunction with systemic features.³ The diagnosis of systemic LE requires 4 of the following criteria be fulfilled: malar rash; discoid rash; photosensitivity; oral ulcers; arthritis; cardiopulmonary serositis; renal involvement; positive ANA titer; and neurologic, hematologic, or immunologic disorders.⁴ Our patient qualified for discoid rash, photosensitivity, cardiopulmonary involvement with mitral valve defects and pulmonary pleuritis, hematologic disorder (anemia), and a positive ANA titer. Furthermore, in patients with only cutaneous discoid LE, serology generally reveals negative or low-titer ANA and negative anti-Ro antibodies.⁵

Hypertrophic LE is characterized histologically by irregular epidermal hyperplasia in association with features of classic cutaneous LE. Distinctive features of cutaneous LE include interface changes, follicular plugging, dermal mucin, and angiocentric lymphocytic inflammation.⁶ Notably, additional biopsies of the less hyperkeratotic lesions on our patient's chest and abdomen were performed, which revealed classic cutaneous LE features (Figure 2B).

Hypertrophic LE has 2 histological variants: lichen planus-like and keratoacanthoma (KA)-like patterns. Most cases are described as lichen planus-like, with a dense bandlike infiltrate in association with irregular epidermal hyperplasia, vacuolar interface changes, and reactive squamous atypia.⁵ In contrast, the less common KA-like lesions consist of a keratinous center with vigorous squamous epithelial proliferation.⁶

Clinically, hypertrophic LE may resemble hypertrophic psoriasis, lichen planus, KA, or squamous cell carcinoma (SCC). Due to the presence of pseudocarcinomatous hyperplasia, the histopathologic differential includes hypertrophic lichen planus, SCC, KA, and deep fungal infections. However, these other diseases lack the classic features of cutaneous LE, which include interface changes, follicular plugging, dermal mucin, and perivascular lymphocytic inflammation. Additionally, transepidermal elastotic elimination (Figure 2A) helps distinguish hypertrophic LE from other diagnoses.⁷ One of the most important tasks is distinguishing hypertrophic LE from SCC. Hypertrophic LE does not typically display eosinophil infiltrates, which differentiates it from SCC and KA. Additionally, studies report that CD123 positivity can be useful.⁶ Positive plasmacytoid dendritic cells are abundant at the dermoepidermal junction in hypertrophic LE, while only single or rare clusters of CD123⁺ cells are seen in SCC.⁸ Also, SCC has been found to arise in long-standing cutaneous LE lesions including both discoid and hypertrophic LE. Therefore, clinical and sometimes histological follow-up is required.

Hypertrophic LE often is challenging to treat and frequently is resistant to antimalarial drugs. The primary goals of treatment involve reducing inflammatory infiltrate and minimizing hyperkeratinization. Topical corticosteroids and calcineurin inhibitors often are inadequate as monotherapy due to reduced penetrance through the thick lesions; however, intralesional corticosteroids may be beneficial in patients with localized disease.⁹ Unfortunately, topical or intralesional treatments are impractical in patients with extensive lesions, as seen in our patient, in which case systemic corticosteroids can be beneficial.

Topical retinoids also have been found to be highly effective.¹⁰ Specifically, retinoids such as acitretin and isotretinoin, in some cases combined with antimalarial drugs, are effective in reducing the keratinization of these lesions. Successful treatment also has been reported with ustekinumab, thalidomide, mycophenolate mofetil, and pulsed dye laser.¹¹ As in other types of cutaneous LE, hyperkeratotic LE is photosensitive; avoidance of prolonged sun exposure should be advised.⁸

The Diagnosis: Hypertrophic Lupus Erythematosus

Physical examination at initial presentation revealed well-demarcated, 2- to 3-cm plaques with scale distributed most extensively on the elbows and shins with lesser involvement of the chest and abdomen. After treatment with topical steroids, adalimumab, methotrexate, and narrowband UVB phototherapy, new annular, erythematous, and edematous lesions began to appear on the chest and abdomen (Figure 1). These new lesions appeared less hyperkeratotic than the older ones.

Biopsy of a hyperkeratotic lesion from the patient's arm revealed marked hyperkeratosis, parakeratosis, epidermal hyperplasia, focal vacuolar change, solar elastosis, and transepidermal elastotic elimination (Figure 2A). A second biopsy performed on a newer chest lesion revealed interface changes, degeneration of the basal layer, follicular plugging, and dermal mucin (Figure 2B). Serology revealed an antinuclear antibody (ANA) titer of 1:1280 (reference range, <1:40 dilution) and hemoglobin of 11.5 g/dL (reference range, 14.0-17.5 g/dL). On the basis of clinical, histologic, and serologic findings, hypertrophic lupus erythematosus (LE) was diagnosed. The patient was treated with oral prednisone, which resulted in rapid improvement.

Hypertrophic LE is a rare subset of chronic cutaneous lupus first described by Behcet¹ in 1942. Lesions are identified as verrucous keratotic plaques with a characteristic erythematous indurated border.² Patients predominantly are middle-aged women with lesions distributed on sun-exposed areas. Most often, hypertrophic LE is seen in association with the classic lesions of discoid LE; however, patients may present exclusively with the cutaneous manifestations of hypertrophic LE. More rarely, as seen in this case, hypertrophic LE may present in conjunction with systemic features.³ The diagnosis of systemic LE requires 4 of the following criteria be fulfilled: malar rash; discoid rash; photosensitivity; oral ulcers; arthritis; cardiopulmonary serositis; renal involvement; positive ANA titer; and neurologic, hematologic, or immunologic disorders.⁴ Our patient qualified for discoid rash, photosensitivity, cardiopulmonary involvement with mitral valve defects and pulmonary pleuritis, hematologic disorder (anemia), and a positive ANA titer. Furthermore, in patients with only cutaneous discoid LE, serology generally reveals negative or low-titer ANA and negative anti-Ro antibodies.⁵

Hypertrophic LE is characterized histologically by irregular epidermal hyperplasia in association with features of classic cutaneous LE. Distinctive features of cutaneous LE include interface changes, follicular plugging, dermal mucin, and angiocentric lymphocytic inflammation.⁶ Notably, additional biopsies of the less hyperkeratotic lesions on our patient's chest and abdomen were performed, which revealed classic cutaneous LE features (Figure 2B).

Hypertrophic LE has 2 histological variants: lichen planus-like and keratoacanthoma (KA)-like patterns. Most cases are described as lichen planus-like, with a dense bandlike infiltrate in association with irregular epidermal hyperplasia, vacuolar interface changes, and reactive squamous atypia.⁵ In contrast, the less common KA-like lesions consist of a keratinous center with vigorous squamous epithelial proliferation.⁶

Clinically, hypertrophic LE may resemble hypertrophic psoriasis, lichen planus, KA, or squamous cell carcinoma (SCC). Due to the presence of pseudocarcinomatous hyperplasia, the histopathologic differential includes hypertrophic lichen planus, SCC, KA, and deep fungal infections. However, these other diseases lack the classic features of cutaneous LE, which include interface changes, follicular plugging, dermal mucin, and perivascular lymphocytic inflammation. Additionally, transepidermal elastotic elimination (Figure 2A) helps distinguish hypertrophic LE from other diagnoses.⁷ One of the most important tasks is distinguishing hypertrophic LE from SCC. Hypertrophic LE does not typically display eosinophil infiltrates, which differentiates it from SCC and KA. Additionally, studies report that CD123 positivity can be useful.⁶ Positive plasmacytoid dendritic cells are abundant at the dermoepidermal junction in hypertrophic LE, while only single or rare clusters of CD123⁺ cells are seen in SCC.⁸ Also, SCC has been found to arise in long-standing cutaneous LE lesions including both discoid and hypertrophic LE. Therefore, clinical and sometimes histological follow-up is required.

Hypertrophic LE often is challenging to treat and frequently is resistant to antimalarial drugs. The primary goals of treatment involve reducing inflammatory infiltrate and minimizing hyperkeratinization. Topical corticosteroids and calcineurin inhibitors often are inadequate as monotherapy due to reduced penetrance through the thick lesions; however, intralesional corticosteroids may be beneficial in patients with localized disease.⁹ Unfortunately, topical or intralesional treatments are impractical in patients with extensive lesions, as seen in our patient, in which case systemic corticosteroids can be beneficial.

Topical retinoids also have been found to be highly effective.¹⁰ Specifically, retinoids such as acitretin and isotretinoin, in some cases combined with antimalarial drugs, are effective in reducing the keratinization of these lesions. Successful treatment also has been reported with ustekinumab, thalidomide, mycophenolate mofetil, and pulsed dye laser.¹¹ As in other types of cutaneous LE, hyperkeratotic LE is photosensitive; avoidance of prolonged sun exposure should be advised.⁸

The Diagnosis: Hypertrophic Lupus Erythematosus

Physical examination at initial presentation revealed well-demarcated, 2- to 3-cm plaques with scale distributed most extensively on the elbows and shins with lesser involvement of the chest and abdomen. After treatment with topical steroids, adalimumab, methotrexate, and narrowband UVB phototherapy, new annular, erythematous, and edematous lesions began to appear on the chest and abdomen (Figure 1). These new lesions appeared less hyperkeratotic than the older ones.

Biopsy of a hyperkeratotic lesion from the patient's arm revealed marked hyperkeratosis, parakeratosis, epidermal hyperplasia, focal vacuolar change, solar elastosis, and transepidermal elastotic elimination (Figure 2A). A second biopsy performed on a newer chest lesion revealed interface changes, degeneration of the basal layer, follicular plugging, and dermal mucin (Figure 2B). Serology revealed an antinuclear antibody (ANA) titer of 1:1280 (reference range, <1:40 dilution) and hemoglobin of 11.5 g/dL (reference range, 14.0-17.5 g/dL). On the basis of clinical, histologic, and serologic findings, hypertrophic lupus erythematosus (LE) was diagnosed. The patient was treated with oral prednisone, which resulted in rapid improvement.

Hypertrophic LE is a rare subset of chronic cutaneous lupus first described by Behcet¹ in 1942. Lesions are identified as verrucous keratotic plaques with a characteristic erythematous indurated border.² Patients predominantly are middle-aged women with lesions distributed on sun-exposed areas. Most often, hypertrophic LE is seen in association with the classic lesions of discoid LE; however, patients may present exclusively with the cutaneous manifestations of hypertrophic LE. More rarely, as seen in this case, hypertrophic LE may present in conjunction with systemic features.³ The diagnosis of systemic LE requires 4 of the following criteria be fulfilled: malar rash; discoid rash; photosensitivity; oral ulcers; arthritis; cardiopulmonary serositis; renal involvement; positive ANA titer; and neurologic, hematologic, or immunologic disorders.⁴ Our patient qualified for discoid rash, photosensitivity, cardiopulmonary involvement with mitral valve defects and pulmonary pleuritis, hematologic disorder (anemia), and a positive ANA titer. Furthermore, in patients with only cutaneous discoid LE, serology generally reveals negative or low-titer ANA and negative anti-Ro antibodies.⁵

Hypertrophic LE is characterized histologically by irregular epidermal hyperplasia in association with features of classic cutaneous LE. Distinctive features of cutaneous LE include interface changes, follicular plugging, dermal mucin, and angiocentric lymphocytic inflammation.⁶ Notably, additional biopsies of the less hyperkeratotic lesions on our patient's chest and abdomen were performed, which revealed classic cutaneous LE features (Figure 2B).

Hypertrophic LE has 2 histological variants: lichen planus-like and keratoacanthoma (KA)-like patterns. Most cases are described as lichen planus-like, with a dense bandlike infiltrate in association with irregular epidermal hyperplasia, vacuolar interface changes, and reactive squamous atypia.⁵ In contrast, the less common KA-like lesions consist of a keratinous center with vigorous squamous epithelial proliferation.⁶

Clinically, hypertrophic LE may resemble hypertrophic psoriasis, lichen planus, KA, or squamous cell carcinoma (SCC). Due to the presence of pseudocarcinomatous hyperplasia, the histopathologic differential includes hypertrophic lichen planus, SCC, KA, and deep fungal infections. However, these other diseases lack the classic features of cutaneous LE, which include interface changes, follicular plugging, dermal mucin, and perivascular lymphocytic inflammation. Additionally, transepidermal elastotic elimination (Figure 2A) helps distinguish hypertrophic LE from other diagnoses.⁷ One of the most important tasks is distinguishing hypertrophic LE from SCC. Hypertrophic LE does not typically display eosinophil infiltrates, which differentiates it from SCC and KA. Additionally, studies report that CD123 positivity can be useful.⁶ Positive plasmacytoid dendritic cells are abundant at the dermoepidermal junction in hypertrophic LE, while only single or rare clusters of CD123⁺ cells are seen in SCC.⁸ Also, SCC has been found to arise in long-standing cutaneous LE lesions including both discoid and hypertrophic LE. Therefore, clinical and sometimes histological follow-up is required.

Hypertrophic LE often is challenging to treat and frequently is resistant to antimalarial drugs. The primary goals of treatment involve reducing inflammatory infiltrate and minimizing hyperkeratinization. Topical corticosteroids and calcineurin inhibitors often are inadequate as monotherapy due to reduced penetrance through the thick lesions; however, intralesional corticosteroids may be beneficial in patients with localized disease.⁹ Unfortunately, topical or intralesional treatments are impractical in patients with extensive lesions, as seen in our patient, in which case systemic corticosteroids can be beneficial.

Topical retinoids also have been found to be highly effective.¹⁰ Specifically, retinoids such as acitretin and isotretinoin, in some cases combined with antimalarial drugs, are effective in reducing the keratinization of these lesions. Successful treatment also has been reported with ustekinumab, thalidomide, mycophenolate mofetil, and pulsed dye laser.¹¹ As in other types of cutaneous LE, hyperkeratotic LE is photosensitive; avoidance of prolonged sun exposure should be advised.⁸

The Diagnosis: Verrucous Hemangioma

Verrucous hemangioma (VH) is a rare vascular anomaly that has not been definitively delineated as a malformation or a tumor, as it has features of both. Verrucous hemangioma presents at birth as a compressible soft mass with a red violaceous hue favoring the legs.^1,2 Over time VH will develop a warty, friable, and keratotic surface that can begin to evolve as early as 6 months or as late as 34 years of age.³ Verrucous hemangioma does not involute and tends to grow proportionally with the patient. Thus, VH classically has been considered a vascular malformation.

On histopathology VH shows collections of uniform, thin-walled vessels with a multilamellated basement membrane throughout the dermis, similar to an infantile hemangioma (IH). These lesions extend deep into the subcutaneous tissue and often involve the underlying fascia. The papillary dermis has large ectatic vessels, while the epidermis displays verrucous hyperkeratosis, papillomatosis, and irregular acanthosis without viral change (Figure).^4,5 The superficial component can resemble an angiokeratoma; however, VH is differentiated by a deeper component that is often larger in size and has a more protracted clinical course.

Similar to IH, immunohistochemical studies have shown that VH expresses Wilms tumor 1 and glucose transporter 1 but is negative for D2-40.⁴ These findings suggest that VH is a vascular tumor rather than a vascular malformation, as was previously reported.⁶ Additional research has shown that the immunohistochemical staining profile of VH is nearly identical to IH, which has led to postulation that VH may be of placental mesodermal origin, as has been hypothesized for IH.⁵

Due to its deep infiltration and tendency for recurrence, VH is most effectively treated with wide local excision.^3,6-8 Preoperative planning with magnetic resonance imaging may be indicated. Although laser monotherapy and other local destructive therapies have been largely unsuccessful, postsurgical laser therapy with CO2 lasers as well as dual pulsed dye laser and Nd:YAG laser have shown promise in preventing recurrence.³

The Diagnosis: Verrucous Hemangioma

Verrucous hemangioma (VH) is a rare vascular anomaly that has not been definitively delineated as a malformation or a tumor, as it has features of both. Verrucous hemangioma presents at birth as a compressible soft mass with a red violaceous hue favoring the legs.^1,2 Over time VH will develop a warty, friable, and keratotic surface that can begin to evolve as early as 6 months or as late as 34 years of age.³ Verrucous hemangioma does not involute and tends to grow proportionally with the patient. Thus, VH classically has been considered a vascular malformation.

On histopathology VH shows collections of uniform, thin-walled vessels with a multilamellated basement membrane throughout the dermis, similar to an infantile hemangioma (IH). These lesions extend deep into the subcutaneous tissue and often involve the underlying fascia. The papillary dermis has large ectatic vessels, while the epidermis displays verrucous hyperkeratosis, papillomatosis, and irregular acanthosis without viral change (Figure).^4,5 The superficial component can resemble an angiokeratoma; however, VH is differentiated by a deeper component that is often larger in size and has a more protracted clinical course.

Similar to IH, immunohistochemical studies have shown that VH expresses Wilms tumor 1 and glucose transporter 1 but is negative for D2-40.⁴ These findings suggest that VH is a vascular tumor rather than a vascular malformation, as was previously reported.⁶ Additional research has shown that the immunohistochemical staining profile of VH is nearly identical to IH, which has led to postulation that VH may be of placental mesodermal origin, as has been hypothesized for IH.⁵

Due to its deep infiltration and tendency for recurrence, VH is most effectively treated with wide local excision.^3,6-8 Preoperative planning with magnetic resonance imaging may be indicated. Although laser monotherapy and other local destructive therapies have been largely unsuccessful, postsurgical laser therapy with CO2 lasers as well as dual pulsed dye laser and Nd:YAG laser have shown promise in preventing recurrence.³

The Diagnosis: Verrucous Hemangioma

Verrucous hemangioma (VH) is a rare vascular anomaly that has not been definitively delineated as a malformation or a tumor, as it has features of both. Verrucous hemangioma presents at birth as a compressible soft mass with a red violaceous hue favoring the legs.^1,2 Over time VH will develop a warty, friable, and keratotic surface that can begin to evolve as early as 6 months or as late as 34 years of age.³ Verrucous hemangioma does not involute and tends to grow proportionally with the patient. Thus, VH classically has been considered a vascular malformation.

On histopathology VH shows collections of uniform, thin-walled vessels with a multilamellated basement membrane throughout the dermis, similar to an infantile hemangioma (IH). These lesions extend deep into the subcutaneous tissue and often involve the underlying fascia. The papillary dermis has large ectatic vessels, while the epidermis displays verrucous hyperkeratosis, papillomatosis, and irregular acanthosis without viral change (Figure).^4,5 The superficial component can resemble an angiokeratoma; however, VH is differentiated by a deeper component that is often larger in size and has a more protracted clinical course.

Similar to IH, immunohistochemical studies have shown that VH expresses Wilms tumor 1 and glucose transporter 1 but is negative for D2-40.⁴ These findings suggest that VH is a vascular tumor rather than a vascular malformation, as was previously reported.⁶ Additional research has shown that the immunohistochemical staining profile of VH is nearly identical to IH, which has led to postulation that VH may be of placental mesodermal origin, as has been hypothesized for IH.⁵

Due to its deep infiltration and tendency for recurrence, VH is most effectively treated with wide local excision.^3,6-8 Preoperative planning with magnetic resonance imaging may be indicated. Although laser monotherapy and other local destructive therapies have been largely unsuccessful, postsurgical laser therapy with CO2 lasers as well as dual pulsed dye laser and Nd:YAG laser have shown promise in preventing recurrence.³

The Diagnosis: Cutaneous Protothecosis

A 4-mm punch biopsy of the plaque on the right forearm was performed. The biopsy showed chronic inflammation with prominent histiocytes, foreign body giant cells, plasma cells, and abundant eosinophils (Figure 1). Grocott-Gomori methenamine-silver stain demonstrated abundant soccer ball-like or floretlike sporangia that were 3 to 11 μm, consistent with a diagnosis of protothecosis (Figure 2).

Cutaneous protothecosis is an infection caused by chlorophyll-lacking algae of the genus Prototheca.¹ It is ubiquitous in nature and can be isolated from various reservoirs such as trees, grass, water, and food sources.² Protothecosis is present worldwide and in the United States; it is most prevalent in the Southeast. Prototheca species are rare but often endemic in cattle and can cause bovine mastitis and enteritis.³ However, they are rare opportunistic infections in humans.

The pathogenesis of cutaneous protothecosis is largely unknown.⁴ However, most infections are thought to be caused by traumatic inoculation into subcutaneous tissues.^1,2 The majority of cases occur in patients older than 30 years. To date, approximately 160 cases have been reported in the literature worldwide.⁵ There are 3 main species of Prototheca, but almost all human infections are caused by Prototheca wickerhamii.² Clinically, most patients with protothecosis present with cutaneous findings, but olecranon bursitis and systemic forms also have been reported.¹

Risk factors for protothecosis include immunosuppression, most often due to steroids, in addition to malignancies, diabetes mellitus, and certain occupations.¹ The presentation can be variable from papules and plaques to even herpetiform appearances.⁴ Protothecosis usually affects the skin and soft tissues of exposed areas such as the extremities or the face.⁶ Diagnosis largely is made on detection of characteristic floretlike sporangia with a prominent cell wall on histopathological examination. Prototheca wickerhamii specifically produces a morula form of sporangia with endospores arranged symmetrically, giving it a characteristic soccer ball appearance.²

Treatment of protothecosis is difficult and remains controversial.¹ There are no established protothecosis treatment protocols or guidelines due to the small number of cases.⁷ In vitro studies have demonstrated sensitivity to amphotericin B and various azoles as well as a wide range of antibiotics.¹ Olecranon bursitis and small skin lesions can be treated by surgical excision. All other Prototheca infections require systemic treatment with azoles or  intravenous amphotericin B for immunocompromised patients or those with disseminated disease.⁵ However, failure to respond to medical management often occurs, requiring surgical excision.^1,6

Our patient was treated with a 3-month course of voriconazole but therapy failed and the plaque continued to expand. The patient underwent a wide excision that was repaired with a partial-thickness skin graft. Rebiopsy of the papule adjacent to the skin graft showed no further recurrence.

In conclusion, protothecosis generally is not clinically suspected and patients are subjected to various treatments without adequate results. A definitive diagnosis easily can be established with a skin biopsy, which can direct timely and appropriate treatment.

The Diagnosis: Cutaneous Protothecosis

A 4-mm punch biopsy of the plaque on the right forearm was performed. The biopsy showed chronic inflammation with prominent histiocytes, foreign body giant cells, plasma cells, and abundant eosinophils (Figure 1). Grocott-Gomori methenamine-silver stain demonstrated abundant soccer ball-like or floretlike sporangia that were 3 to 11 μm, consistent with a diagnosis of protothecosis (Figure 2).

Cutaneous protothecosis is an infection caused by chlorophyll-lacking algae of the genus Prototheca.¹ It is ubiquitous in nature and can be isolated from various reservoirs such as trees, grass, water, and food sources.² Protothecosis is present worldwide and in the United States; it is most prevalent in the Southeast. Prototheca species are rare but often endemic in cattle and can cause bovine mastitis and enteritis.³ However, they are rare opportunistic infections in humans.

The pathogenesis of cutaneous protothecosis is largely unknown.⁴ However, most infections are thought to be caused by traumatic inoculation into subcutaneous tissues.^1,2 The majority of cases occur in patients older than 30 years. To date, approximately 160 cases have been reported in the literature worldwide.⁵ There are 3 main species of Prototheca, but almost all human infections are caused by Prototheca wickerhamii.² Clinically, most patients with protothecosis present with cutaneous findings, but olecranon bursitis and systemic forms also have been reported.¹

Risk factors for protothecosis include immunosuppression, most often due to steroids, in addition to malignancies, diabetes mellitus, and certain occupations.¹ The presentation can be variable from papules and plaques to even herpetiform appearances.⁴ Protothecosis usually affects the skin and soft tissues of exposed areas such as the extremities or the face.⁶ Diagnosis largely is made on detection of characteristic floretlike sporangia with a prominent cell wall on histopathological examination. Prototheca wickerhamii specifically produces a morula form of sporangia with endospores arranged symmetrically, giving it a characteristic soccer ball appearance.²

Treatment of protothecosis is difficult and remains controversial.¹ There are no established protothecosis treatment protocols or guidelines due to the small number of cases.⁷ In vitro studies have demonstrated sensitivity to amphotericin B and various azoles as well as a wide range of antibiotics.¹ Olecranon bursitis and small skin lesions can be treated by surgical excision. All other Prototheca infections require systemic treatment with azoles or  intravenous amphotericin B for immunocompromised patients or those with disseminated disease.⁵ However, failure to respond to medical management often occurs, requiring surgical excision.^1,6

Our patient was treated with a 3-month course of voriconazole but therapy failed and the plaque continued to expand. The patient underwent a wide excision that was repaired with a partial-thickness skin graft. Rebiopsy of the papule adjacent to the skin graft showed no further recurrence.

In conclusion, protothecosis generally is not clinically suspected and patients are subjected to various treatments without adequate results. A definitive diagnosis easily can be established with a skin biopsy, which can direct timely and appropriate treatment.

The Diagnosis: Cutaneous Protothecosis

A 4-mm punch biopsy of the plaque on the right forearm was performed. The biopsy showed chronic inflammation with prominent histiocytes, foreign body giant cells, plasma cells, and abundant eosinophils (Figure 1). Grocott-Gomori methenamine-silver stain demonstrated abundant soccer ball-like or floretlike sporangia that were 3 to 11 μm, consistent with a diagnosis of protothecosis (Figure 2).

Cutaneous protothecosis is an infection caused by chlorophyll-lacking algae of the genus Prototheca.¹ It is ubiquitous in nature and can be isolated from various reservoirs such as trees, grass, water, and food sources.² Protothecosis is present worldwide and in the United States; it is most prevalent in the Southeast. Prototheca species are rare but often endemic in cattle and can cause bovine mastitis and enteritis.³ However, they are rare opportunistic infections in humans.

The pathogenesis of cutaneous protothecosis is largely unknown.⁴ However, most infections are thought to be caused by traumatic inoculation into subcutaneous tissues.^1,2 The majority of cases occur in patients older than 30 years. To date, approximately 160 cases have been reported in the literature worldwide.⁵ There are 3 main species of Prototheca, but almost all human infections are caused by Prototheca wickerhamii.² Clinically, most patients with protothecosis present with cutaneous findings, but olecranon bursitis and systemic forms also have been reported.¹

Risk factors for protothecosis include immunosuppression, most often due to steroids, in addition to malignancies, diabetes mellitus, and certain occupations.¹ The presentation can be variable from papules and plaques to even herpetiform appearances.⁴ Protothecosis usually affects the skin and soft tissues of exposed areas such as the extremities or the face.⁶ Diagnosis largely is made on detection of characteristic floretlike sporangia with a prominent cell wall on histopathological examination. Prototheca wickerhamii specifically produces a morula form of sporangia with endospores arranged symmetrically, giving it a characteristic soccer ball appearance.²

Treatment of protothecosis is difficult and remains controversial.¹ There are no established protothecosis treatment protocols or guidelines due to the small number of cases.⁷ In vitro studies have demonstrated sensitivity to amphotericin B and various azoles as well as a wide range of antibiotics.¹ Olecranon bursitis and small skin lesions can be treated by surgical excision. All other Prototheca infections require systemic treatment with azoles or  intravenous amphotericin B for immunocompromised patients or those with disseminated disease.⁵ However, failure to respond to medical management often occurs, requiring surgical excision.^1,6

Our patient was treated with a 3-month course of voriconazole but therapy failed and the plaque continued to expand. The patient underwent a wide excision that was repaired with a partial-thickness skin graft. Rebiopsy of the papule adjacent to the skin graft showed no further recurrence.

In conclusion, protothecosis generally is not clinically suspected and patients are subjected to various treatments without adequate results. A definitive diagnosis easily can be established with a skin biopsy, which can direct timely and appropriate treatment.

The Diagnosis: Xanthoma Disseminatum

Genital examination revealed approximately 1.5×3-cm soft, yellow-pink plaques extending from the bilateral inguinal folds to the proximal medial thighs (Figure 1). There was no mucosal, axillary, extensor extremity, or palmoplantar involvement. Histopathologic examination of a biopsy from a plaque on the left side of the lower abdomen revealed sheets of foamy histiocytes distributed throughout a fibrotic dermis. Both mononucleated and multinucleated histiocytes were present, including many Touton giant cells (Figure 2). A patchy infiltrate of lymphocytes and rare eosinophils also was noted. The histiocytes labeled with factor XIIIa but not with S-100. Laboratory tests were performed with the following pertinent findings: low-density lipoprotein, 150 mg/dL (reference range, <130 mg/dL); high-density lipoprotein, 30 mg/dL (reference range, >40 mg/dL). Total cholesterol and triglyceride levels were within reference range, and complete blood cell count and basic metabolic panel were normal.

Xanthoma disseminatum (XD)(also known as Montgomery syndrome) is a rare, nonfamilial, normolipemic non-Langerhans cell histiocytosis characterized by extensive lipid deposition in the skin, mucous membranes, and internal organs. The pathogenesis of XD is poorly understood, but it may represent a macrophage-mediated reactive process triggered by superantigens.¹

Xanthoma disseminatum most commonly affects males aged 5 to 25 years.² Clinically, it is characterized by red-brown to yellowish papules and plaques symmetrically distributed over the eyelids, trunk, face, and proximal extremities. There is a predilection for involvement of flexural and intertriginous surfaces and tendency for extension along Langer lines. Extracutaneous involvement can be a notable cause of morbidity and mortality, underscoring the importance of distinguishing XD from other clinically similar xanthomatoses. Mucous membrane involvement occurs in 40% to 60% of patients.³ The oropharynx, larynx, and corneal and conjunctival membranes are most commonly affected, resulting in dysphagia, dysphonia or dyspnea, and visual impairment, respectively. Symptoms of internal organ involvement can be manifold, including pain or limited mobility secondary to osteolytic bone lesions or muscle or synovial membrane involvement, as well as seizures, strabismus, and cerebellar ataxia due to central nervous system lesions.^2-4 Approximately 40% of patients develop diabetes insipidus secondary to involvement of the pituitary meninges.³

The differential diagnosis of XD includes juvenile xanthogranuloma, papular xanthomas, eruptive xanthomas, generalized eruptive histiocytosis, progressive nodular histiocytosis, multicentric reticulohistiocytosis, eruptive syringomas, sarcoidosis, and Langerhans cell histiocytosis; the latter should be considered, especially when there is concomitant diabetes insipidus.⁵ Laboratory studies typically are unremarkable. Although the majority of patients are normolipemic, rates of hyperlipemia within this group are comparable to the general population, occasionally rendering it difficult for the clinician to distinguish XD from hyperlipemic xanthomatoses. As such, diagnosis and differentiation from other xanthomatous processes rests on clinicopathological correlation. Histopathology reveals dermal collections of histiocytes, some with foamy cytoplasm, that range in appearance from spindled to scalloped to Touton-like. Early histopathology demonstrates scalloped macrophages with few foamy cells; a mixture of foamy cells, scalloped cells, inflammatory cells, and Touton and foreign body giant cells is characteristic of late lesions. Immunohistochemistry stains positive for non-Langerhans cell surface markers CD68 and factor XIIIa. Electron microscopy demonstrates dense and myeloid bodies, cholesterol crystals, and lipid vacuoles.⁵

Three subtypes of XD have been described based on the distinct clinical courses that have been observed in patients: a common, persistent, cutaneous form; a self-limited form with spontaneous resolution; and a progressive subtype with internal organ involvement. No consistently efficacious therapies have been identified, but isolated case reports attest to the efficacy of various agents, including azathioprine, clofibrate, cyclophosphamide, glucocorticoids, chlorambucil, and combination or monotherapy with lipid-lowering agents.^3,5,6 Surgical resection, cryotherapy, radiotherapy, and CO2 laser therapy may offer some temporary benefit but do not alter the typically relapsing course of the disease.^7,8 Remission and long-term control of lesions was reported with use of 2-chlorodeoxyadenosine, a purine nucleoside analogue, for 5 of 8 patients in a case series.³

The Diagnosis: Xanthoma Disseminatum

Genital examination revealed approximately 1.5×3-cm soft, yellow-pink plaques extending from the bilateral inguinal folds to the proximal medial thighs (Figure 1). There was no mucosal, axillary, extensor extremity, or palmoplantar involvement. Histopathologic examination of a biopsy from a plaque on the left side of the lower abdomen revealed sheets of foamy histiocytes distributed throughout a fibrotic dermis. Both mononucleated and multinucleated histiocytes were present, including many Touton giant cells (Figure 2). A patchy infiltrate of lymphocytes and rare eosinophils also was noted. The histiocytes labeled with factor XIIIa but not with S-100. Laboratory tests were performed with the following pertinent findings: low-density lipoprotein, 150 mg/dL (reference range, <130 mg/dL); high-density lipoprotein, 30 mg/dL (reference range, >40 mg/dL). Total cholesterol and triglyceride levels were within reference range, and complete blood cell count and basic metabolic panel were normal.

Xanthoma disseminatum (XD)(also known as Montgomery syndrome) is a rare, nonfamilial, normolipemic non-Langerhans cell histiocytosis characterized by extensive lipid deposition in the skin, mucous membranes, and internal organs. The pathogenesis of XD is poorly understood, but it may represent a macrophage-mediated reactive process triggered by superantigens.¹

Xanthoma disseminatum most commonly affects males aged 5 to 25 years.² Clinically, it is characterized by red-brown to yellowish papules and plaques symmetrically distributed over the eyelids, trunk, face, and proximal extremities. There is a predilection for involvement of flexural and intertriginous surfaces and tendency for extension along Langer lines. Extracutaneous involvement can be a notable cause of morbidity and mortality, underscoring the importance of distinguishing XD from other clinically similar xanthomatoses. Mucous membrane involvement occurs in 40% to 60% of patients.³ The oropharynx, larynx, and corneal and conjunctival membranes are most commonly affected, resulting in dysphagia, dysphonia or dyspnea, and visual impairment, respectively. Symptoms of internal organ involvement can be manifold, including pain or limited mobility secondary to osteolytic bone lesions or muscle or synovial membrane involvement, as well as seizures, strabismus, and cerebellar ataxia due to central nervous system lesions.^2-4 Approximately 40% of patients develop diabetes insipidus secondary to involvement of the pituitary meninges.³

The differential diagnosis of XD includes juvenile xanthogranuloma, papular xanthomas, eruptive xanthomas, generalized eruptive histiocytosis, progressive nodular histiocytosis, multicentric reticulohistiocytosis, eruptive syringomas, sarcoidosis, and Langerhans cell histiocytosis; the latter should be considered, especially when there is concomitant diabetes insipidus.⁵ Laboratory studies typically are unremarkable. Although the majority of patients are normolipemic, rates of hyperlipemia within this group are comparable to the general population, occasionally rendering it difficult for the clinician to distinguish XD from hyperlipemic xanthomatoses. As such, diagnosis and differentiation from other xanthomatous processes rests on clinicopathological correlation. Histopathology reveals dermal collections of histiocytes, some with foamy cytoplasm, that range in appearance from spindled to scalloped to Touton-like. Early histopathology demonstrates scalloped macrophages with few foamy cells; a mixture of foamy cells, scalloped cells, inflammatory cells, and Touton and foreign body giant cells is characteristic of late lesions. Immunohistochemistry stains positive for non-Langerhans cell surface markers CD68 and factor XIIIa. Electron microscopy demonstrates dense and myeloid bodies, cholesterol crystals, and lipid vacuoles.⁵

Three subtypes of XD have been described based on the distinct clinical courses that have been observed in patients: a common, persistent, cutaneous form; a self-limited form with spontaneous resolution; and a progressive subtype with internal organ involvement. No consistently efficacious therapies have been identified, but isolated case reports attest to the efficacy of various agents, including azathioprine, clofibrate, cyclophosphamide, glucocorticoids, chlorambucil, and combination or monotherapy with lipid-lowering agents.^3,5,6 Surgical resection, cryotherapy, radiotherapy, and CO2 laser therapy may offer some temporary benefit but do not alter the typically relapsing course of the disease.^7,8 Remission and long-term control of lesions was reported with use of 2-chlorodeoxyadenosine, a purine nucleoside analogue, for 5 of 8 patients in a case series.³

The Diagnosis: Xanthoma Disseminatum

Genital examination revealed approximately 1.5×3-cm soft, yellow-pink plaques extending from the bilateral inguinal folds to the proximal medial thighs (Figure 1). There was no mucosal, axillary, extensor extremity, or palmoplantar involvement. Histopathologic examination of a biopsy from a plaque on the left side of the lower abdomen revealed sheets of foamy histiocytes distributed throughout a fibrotic dermis. Both mononucleated and multinucleated histiocytes were present, including many Touton giant cells (Figure 2). A patchy infiltrate of lymphocytes and rare eosinophils also was noted. The histiocytes labeled with factor XIIIa but not with S-100. Laboratory tests were performed with the following pertinent findings: low-density lipoprotein, 150 mg/dL (reference range, <130 mg/dL); high-density lipoprotein, 30 mg/dL (reference range, >40 mg/dL). Total cholesterol and triglyceride levels were within reference range, and complete blood cell count and basic metabolic panel were normal.

Xanthoma disseminatum (XD)(also known as Montgomery syndrome) is a rare, nonfamilial, normolipemic non-Langerhans cell histiocytosis characterized by extensive lipid deposition in the skin, mucous membranes, and internal organs. The pathogenesis of XD is poorly understood, but it may represent a macrophage-mediated reactive process triggered by superantigens.¹

Xanthoma disseminatum most commonly affects males aged 5 to 25 years.² Clinically, it is characterized by red-brown to yellowish papules and plaques symmetrically distributed over the eyelids, trunk, face, and proximal extremities. There is a predilection for involvement of flexural and intertriginous surfaces and tendency for extension along Langer lines. Extracutaneous involvement can be a notable cause of morbidity and mortality, underscoring the importance of distinguishing XD from other clinically similar xanthomatoses. Mucous membrane involvement occurs in 40% to 60% of patients.³ The oropharynx, larynx, and corneal and conjunctival membranes are most commonly affected, resulting in dysphagia, dysphonia or dyspnea, and visual impairment, respectively. Symptoms of internal organ involvement can be manifold, including pain or limited mobility secondary to osteolytic bone lesions or muscle or synovial membrane involvement, as well as seizures, strabismus, and cerebellar ataxia due to central nervous system lesions.^2-4 Approximately 40% of patients develop diabetes insipidus secondary to involvement of the pituitary meninges.³

The differential diagnosis of XD includes juvenile xanthogranuloma, papular xanthomas, eruptive xanthomas, generalized eruptive histiocytosis, progressive nodular histiocytosis, multicentric reticulohistiocytosis, eruptive syringomas, sarcoidosis, and Langerhans cell histiocytosis; the latter should be considered, especially when there is concomitant diabetes insipidus.⁵ Laboratory studies typically are unremarkable. Although the majority of patients are normolipemic, rates of hyperlipemia within this group are comparable to the general population, occasionally rendering it difficult for the clinician to distinguish XD from hyperlipemic xanthomatoses. As such, diagnosis and differentiation from other xanthomatous processes rests on clinicopathological correlation. Histopathology reveals dermal collections of histiocytes, some with foamy cytoplasm, that range in appearance from spindled to scalloped to Touton-like. Early histopathology demonstrates scalloped macrophages with few foamy cells; a mixture of foamy cells, scalloped cells, inflammatory cells, and Touton and foreign body giant cells is characteristic of late lesions. Immunohistochemistry stains positive for non-Langerhans cell surface markers CD68 and factor XIIIa. Electron microscopy demonstrates dense and myeloid bodies, cholesterol crystals, and lipid vacuoles.⁵

Three subtypes of XD have been described based on the distinct clinical courses that have been observed in patients: a common, persistent, cutaneous form; a self-limited form with spontaneous resolution; and a progressive subtype with internal organ involvement. No consistently efficacious therapies have been identified, but isolated case reports attest to the efficacy of various agents, including azathioprine, clofibrate, cyclophosphamide, glucocorticoids, chlorambucil, and combination or monotherapy with lipid-lowering agents.^3,5,6 Surgical resection, cryotherapy, radiotherapy, and CO2 laser therapy may offer some temporary benefit but do not alter the typically relapsing course of the disease.^7,8 Remission and long-term control of lesions was reported with use of 2-chlorodeoxyadenosine, a purine nucleoside analogue, for 5 of 8 patients in a case series.³

The Diagnosis: Persistent Still Disease

At the time of presentation, the patient had not taken systemic medications for a year. Laboratory studies revealed leukocytosis with neutrophilia and a serum ferritin level of 5493 ng/mL (reference range, 15-200 ng/mL). Rheumatoid factor and antinuclear antibody serologies were within reference range. Microbiologic workup was negative. Lymph node and bone marrow biopsies were negative for a lymphoproliferative disorder. Skin biopsies were performed on the back and forearm. Histologic evaluation revealed orthokeratosis, slight acanthosis, and dyskeratosis confined to the upper layers of the epidermis without evidence of interface dermatitis. There was a mixed perivascular infiltrate composed of lymphocytes and neutrophils with no attendant vasculitic change (Figure).

The patient was discharged on prednisone and seen for outpatient follow-up weeks later. Six weeks later, the cutaneous eruption remained unchanged. The patient was unable to start other systemic medications due to lack of insurance and ineligibility for the local patient-assistance program; he was subsequently lost to follow-up. 

Adult-onset Still disease is a rare, systemic, inflammatory condition with a broad spectrum of clinical presentations.^1-3 Still disease affects all age groups, and children with Still disease (<16 years) usually have a concurrent diagnosis of juvenile idiopathic arthritis (formerly known as juvenile rheumatoid arthritis).^1,2,4 Still disease preferentially affects adolescents and adults aged 16 to 35 years, with more than 75% of new cases occurring in this age range.¹ Worldwide, the incidence and prevalence of Still disease is disputed with no conclusive rates established.^1,3

Still disease is characterized by 4 cardinal signs: high spiking fevers (temperature, ≥39°C); leukocytosis with a predominance of neutrophils (≥10,000 cells/mm³ with ≥80% neutrophils); arthralgia or arthritis; and an evanescent, nonpruritic, salmon-colored morbilliform eruption of the skin, typically on the trunk or extremities.² Histologic evaluation of the classic Still disease eruption displays perivascular inflammation of the superficial dermis with infiltration by lymphocytes and histiocytes.³

In 1992, major and minor diagnostic criteria were established for adult-onset Still disease. For diagnosis, patients must meet 5 criteria, including 2 major criteria.⁵ Major criteria include arthralgia or arthritis present for more than 2 weeks, fever (temperature, >39°C) for at least 1 week, the classic Still disease morbilliform eruption (ie, salmon colored, evanescent, morbilliform), and leukocytosis with more than 80% neutrophils. Minor criteria include sore throat, lymphadenopathy and/or splenomegaly, negative rheumatoid factor and antinuclear antibody serologies, and abnormal liver function (defined as elevated transaminases).⁵ Although not included in the diagnostic criteria, there have been reports of elevated serum ferritin levels in patients with Still disease, a finding that potentially is useful in distinguishing between active and inactive rheumatic conditions.^6,7

Several case reports have described persistent Still disease, a subtype of Still disease in which patients present with brown-red, persistent, pruritic macules, papules, and plaques that are widespread and oddly shaped.^8,9 Histologically, this subtype is characterized by necrotic keratinocytes in the epidermis and dermal perivascular inflammation composed of neutrophils and lymphocytes.¹⁰ This histology differs from classic Still disease in that the latter typically does not have superficial epidermal dyskeratosis. Our case is consistent with reports of persistent Still disease.

Although the etiology of Still disease remains to be elucidated, HLA-B17, -B18, -B35, and -DR2 have been associated with the disease.³ Furthermore, helper T cell T_H1, IL-2, IFN-γ, and tumor necrosis factor α have been implicated in disease pathology, enabling the use of newer targeted pharmacologic therapies. Canakinumab, an IL-1β inhibitor, has been found to improve arthritis, fever, and rash in patients with Still disease.¹¹ These findings are particularly encouraging for patients who have not experienced improvement with traditional antirheumatic drugs, such as our patient who was not steroid responsive.³

Although a salmon-colored, evanescent, morbilliform eruption in the context of other systemic signs and symptoms readily evokes consideration of Still disease, the less common fixed cutaneous eruption seen in our case may evade accurate diagnosis. Our case aims to increase awareness of this unusual and rare subtype of the cutaneous eruption of Still disease, as a timely diagnosis may prevent potentially life-threatening sequelae including cardiopulmonary disease and respiratory failure.^3,5,9

The Diagnosis: Persistent Still Disease

At the time of presentation, the patient had not taken systemic medications for a year. Laboratory studies revealed leukocytosis with neutrophilia and a serum ferritin level of 5493 ng/mL (reference range, 15-200 ng/mL). Rheumatoid factor and antinuclear antibody serologies were within reference range. Microbiologic workup was negative. Lymph node and bone marrow biopsies were negative for a lymphoproliferative disorder. Skin biopsies were performed on the back and forearm. Histologic evaluation revealed orthokeratosis, slight acanthosis, and dyskeratosis confined to the upper layers of the epidermis without evidence of interface dermatitis. There was a mixed perivascular infiltrate composed of lymphocytes and neutrophils with no attendant vasculitic change (Figure).

The patient was discharged on prednisone and seen for outpatient follow-up weeks later. Six weeks later, the cutaneous eruption remained unchanged. The patient was unable to start other systemic medications due to lack of insurance and ineligibility for the local patient-assistance program; he was subsequently lost to follow-up. 

Adult-onset Still disease is a rare, systemic, inflammatory condition with a broad spectrum of clinical presentations.^1-3 Still disease affects all age groups, and children with Still disease (<16 years) usually have a concurrent diagnosis of juvenile idiopathic arthritis (formerly known as juvenile rheumatoid arthritis).^1,2,4 Still disease preferentially affects adolescents and adults aged 16 to 35 years, with more than 75% of new cases occurring in this age range.¹ Worldwide, the incidence and prevalence of Still disease is disputed with no conclusive rates established.^1,3

Still disease is characterized by 4 cardinal signs: high spiking fevers (temperature, ≥39°C); leukocytosis with a predominance of neutrophils (≥10,000 cells/mm³ with ≥80% neutrophils); arthralgia or arthritis; and an evanescent, nonpruritic, salmon-colored morbilliform eruption of the skin, typically on the trunk or extremities.² Histologic evaluation of the classic Still disease eruption displays perivascular inflammation of the superficial dermis with infiltration by lymphocytes and histiocytes.³

In 1992, major and minor diagnostic criteria were established for adult-onset Still disease. For diagnosis, patients must meet 5 criteria, including 2 major criteria.⁵ Major criteria include arthralgia or arthritis present for more than 2 weeks, fever (temperature, >39°C) for at least 1 week, the classic Still disease morbilliform eruption (ie, salmon colored, evanescent, morbilliform), and leukocytosis with more than 80% neutrophils. Minor criteria include sore throat, lymphadenopathy and/or splenomegaly, negative rheumatoid factor and antinuclear antibody serologies, and abnormal liver function (defined as elevated transaminases).⁵ Although not included in the diagnostic criteria, there have been reports of elevated serum ferritin levels in patients with Still disease, a finding that potentially is useful in distinguishing between active and inactive rheumatic conditions.^6,7

Several case reports have described persistent Still disease, a subtype of Still disease in which patients present with brown-red, persistent, pruritic macules, papules, and plaques that are widespread and oddly shaped.^8,9 Histologically, this subtype is characterized by necrotic keratinocytes in the epidermis and dermal perivascular inflammation composed of neutrophils and lymphocytes.¹⁰ This histology differs from classic Still disease in that the latter typically does not have superficial epidermal dyskeratosis. Our case is consistent with reports of persistent Still disease.

Although the etiology of Still disease remains to be elucidated, HLA-B17, -B18, -B35, and -DR2 have been associated with the disease.³ Furthermore, helper T cell T_H1, IL-2, IFN-γ, and tumor necrosis factor α have been implicated in disease pathology, enabling the use of newer targeted pharmacologic therapies. Canakinumab, an IL-1β inhibitor, has been found to improve arthritis, fever, and rash in patients with Still disease.¹¹ These findings are particularly encouraging for patients who have not experienced improvement with traditional antirheumatic drugs, such as our patient who was not steroid responsive.³

Although a salmon-colored, evanescent, morbilliform eruption in the context of other systemic signs and symptoms readily evokes consideration of Still disease, the less common fixed cutaneous eruption seen in our case may evade accurate diagnosis. Our case aims to increase awareness of this unusual and rare subtype of the cutaneous eruption of Still disease, as a timely diagnosis may prevent potentially life-threatening sequelae including cardiopulmonary disease and respiratory failure.^3,5,9

The Diagnosis: Persistent Still Disease

At the time of presentation, the patient had not taken systemic medications for a year. Laboratory studies revealed leukocytosis with neutrophilia and a serum ferritin level of 5493 ng/mL (reference range, 15-200 ng/mL). Rheumatoid factor and antinuclear antibody serologies were within reference range. Microbiologic workup was negative. Lymph node and bone marrow biopsies were negative for a lymphoproliferative disorder. Skin biopsies were performed on the back and forearm. Histologic evaluation revealed orthokeratosis, slight acanthosis, and dyskeratosis confined to the upper layers of the epidermis without evidence of interface dermatitis. There was a mixed perivascular infiltrate composed of lymphocytes and neutrophils with no attendant vasculitic change (Figure).

The patient was discharged on prednisone and seen for outpatient follow-up weeks later. Six weeks later, the cutaneous eruption remained unchanged. The patient was unable to start other systemic medications due to lack of insurance and ineligibility for the local patient-assistance program; he was subsequently lost to follow-up. 

Adult-onset Still disease is a rare, systemic, inflammatory condition with a broad spectrum of clinical presentations.^1-3 Still disease affects all age groups, and children with Still disease (<16 years) usually have a concurrent diagnosis of juvenile idiopathic arthritis (formerly known as juvenile rheumatoid arthritis).^1,2,4 Still disease preferentially affects adolescents and adults aged 16 to 35 years, with more than 75% of new cases occurring in this age range.¹ Worldwide, the incidence and prevalence of Still disease is disputed with no conclusive rates established.^1,3

Still disease is characterized by 4 cardinal signs: high spiking fevers (temperature, ≥39°C); leukocytosis with a predominance of neutrophils (≥10,000 cells/mm³ with ≥80% neutrophils); arthralgia or arthritis; and an evanescent, nonpruritic, salmon-colored morbilliform eruption of the skin, typically on the trunk or extremities.² Histologic evaluation of the classic Still disease eruption displays perivascular inflammation of the superficial dermis with infiltration by lymphocytes and histiocytes.³

In 1992, major and minor diagnostic criteria were established for adult-onset Still disease. For diagnosis, patients must meet 5 criteria, including 2 major criteria.⁵ Major criteria include arthralgia or arthritis present for more than 2 weeks, fever (temperature, >39°C) for at least 1 week, the classic Still disease morbilliform eruption (ie, salmon colored, evanescent, morbilliform), and leukocytosis with more than 80% neutrophils. Minor criteria include sore throat, lymphadenopathy and/or splenomegaly, negative rheumatoid factor and antinuclear antibody serologies, and abnormal liver function (defined as elevated transaminases).⁵ Although not included in the diagnostic criteria, there have been reports of elevated serum ferritin levels in patients with Still disease, a finding that potentially is useful in distinguishing between active and inactive rheumatic conditions.^6,7

Several case reports have described persistent Still disease, a subtype of Still disease in which patients present with brown-red, persistent, pruritic macules, papules, and plaques that are widespread and oddly shaped.^8,9 Histologically, this subtype is characterized by necrotic keratinocytes in the epidermis and dermal perivascular inflammation composed of neutrophils and lymphocytes.¹⁰ This histology differs from classic Still disease in that the latter typically does not have superficial epidermal dyskeratosis. Our case is consistent with reports of persistent Still disease.

Although the etiology of Still disease remains to be elucidated, HLA-B17, -B18, -B35, and -DR2 have been associated with the disease.³ Furthermore, helper T cell T_H1, IL-2, IFN-γ, and tumor necrosis factor α have been implicated in disease pathology, enabling the use of newer targeted pharmacologic therapies. Canakinumab, an IL-1β inhibitor, has been found to improve arthritis, fever, and rash in patients with Still disease.¹¹ These findings are particularly encouraging for patients who have not experienced improvement with traditional antirheumatic drugs, such as our patient who was not steroid responsive.³

Although a salmon-colored, evanescent, morbilliform eruption in the context of other systemic signs and symptoms readily evokes consideration of Still disease, the less common fixed cutaneous eruption seen in our case may evade accurate diagnosis. Our case aims to increase awareness of this unusual and rare subtype of the cutaneous eruption of Still disease, as a timely diagnosis may prevent potentially life-threatening sequelae including cardiopulmonary disease and respiratory failure.^3,5,9

The Diagnosis: Allergic Contact Dermatitis

An allergic contact dermatitis (ACD) to acrylates was suspected and 4 patches were applied to the forearm (the North American Standard Series of the North American Contact Dermatitis Group). The patches were 2-hydroxyethyl methacrylate (2-HEMA) 2.0% permissible exposure limit (peL), ethyl acrylate 0.1% peL, tosylamide formaldehyde resin 10.0% peL, and methyl methacrylate 2.0% peL. A reading at 72 hours was performed and showed a positive reaction to hydroxyethyl methacrylate, ethyl acrylate, and methyl methacrylate, and a negative patch test to tosylamide formaldehyde resin (nail polish)(Figure). The patient was diagnosed with an allergic contact hypersensitivity to the aforementioned acrylates and instructed to avoid artificial nails and acrylate glues. She also was started on oral biotin supplements. On 6-month follow-up the patient had regrowth of all 10 fingernails without brittleness or splitting. She was able to use nail polishes but avoided all acrylic artificial nails and acrylate-containing personal care products.

Acrylate Allergy and Artificial Nails

Acrylates are plastic materials formed by polymerization of acrylic or methacrylic acid monomers and have been cited as a major cause of occupational and nonoccupational contact dermatitis. Contact dermatitis to acrylates in artificial nails was first reported in the 1950s.^1,2 Products containing 100% methyl methacrylate monomers in acrylic nails were banned by the US Food and Drug Administration in the early 1970s after receiving a number of complaints.³ However, no regulation prohibits the use of methyl methacrylate monomer in cosmetic products, and various methacrylate and acrylate monomers remain widely used.⁴ With a growing popularity in artificial nails, it is expected the number of sensitized persons will increase.

Acrylate allergy from sculptured nails concern self-curing resins made from a polymer powder and a liquid monomer solution. Advantages of new UV-cured products include the lack of unpleasant smell and simplified modeling. They also do not require an irritant, such as methacrylic acid, as a bonding agent. Instead, 2-HEMA and 2-hydroxypropyl methacrylate are added. These photobonded nails colloquially are called gel nails (acid free) as opposed to acrylic nails (using methacrylic acid as a primer). It is important to note that the esters of acrylic acid but not the acid itself sensitize patients, and sensitization is not caused by the uncured gel or the monomer solution but by the remaining monomers in the cured plastic nail and the dust filings that are produced during the finishing process.

Clinical Presentation

Symptoms of an ACD to nail acrylates include pruritus and fingertip dermatitis along with nail plate dystrophy. There may be pruritus at the nail base, with subsequent dryness, thickening, and onycholysis. The brittle nails may become split, discolored, and develop paronychia. Inadvertent contact with glue monomers or other acrylate-containing substances may cause eczematous lesions at distant sites. Avoidance of the allergen often results in complete restoration of the normal nail and fingertip within months.

Sensitization

Acrylates and methacrylates are ubiquitous materials used for both industrial and commercial applications. Due to their widespread industrial use, contact allergies to acrylates including 2-HEMA, 2-hydroxypropyl methacrylate, and triethyleneglycol diacrylate (TREGDA) are common. Cross-reaction of these compounds has been observed and is postulated to be due to reaction of the (meth)acrylate carboxyethyl group with the receptors of antigen-presenting cells.⁵ As a result, an individual with an acrylate allergy sensitized to one allergen often is allergic to its similar compounds and cross-reactors and must avoid the assortment of compounds containing these ingredients, which is important for individuals with occupational sensitization to a particular acrylate who is subsequently susceptible to other acrylate-containing compounds triggering allergic reactions when reexposure occurs in different settings.

Allergens and Occupational Exposure

Acrylates in cosmetic nail products are a source of ACD for not only the customer but also the manicurist.⁶ The most frequently cited sources of ACD in beauticians are acrylate chemicals.⁷ However, acrylate compounds are an occupational hazard for a number of other specialists, including dentists and dental technicians, histology technicians, and individuals in the printing industry.^8,9 Other individuals may be sensitized to acrylates through their inclusion in adhesives, dental bonding agents, hearing aids, electrocardiogram electrodes, artificial bone cement, and a myriad of other medical and nonmedical applications.^4,10-12 For workers who cannot avoid occupational exposure to these allergens, polyvinyl alcohol and multilayer laminate gloves are recommended, as natural rubber latex gloves do not always provide adequate protection from many of these agents.¹⁰

Testing for Suspected Acrylate Allergy

Cross-reactivity among acrylates is widely considered in the literature but remains enigmatic and is an important consideration with regard to routine patch test screening.¹³ In the case of an acrylate allergy to nail products, using 2-HEMA and ethylene glycol dimethacrylate is effective in detecting sensitization by photobonded nails and in patients sensitized by powder liquid products.¹⁴ One study showed a patch test panel including 2-HEMA, ethylene glycol dimethacrylate, and TREGDA was effective in identifying the majority of individuals with an allergy to acrylates in nail products and nail technicians.¹⁵ Another study has shown the most commonly positive testing allergens to be HEMA, ethyl acrylate, and methyl methacrylate.¹⁶ If one is patch testing only one chemical, it appears 2-HEMA is preferred.¹⁷ However, broader panels of screening allergens are necessary to achieve an accurate diagnosis. Furthermore, different panels of test allergens have been shown to vary in their ability to detect an acrylate allergy in different occupational exposures.¹² 

The time to patch test read also is important. A standard read at 72 hours is warranted; however, one study showed if only one read at day 3 was done without a subsequent day 7 read, then 25% of TREGDA and 50% of 2-HEMA allergies would have been missed in patients with occupational acrylate allergy.¹⁵ Other studies have reported late-appearing and long-lasting test reactions when testing for an acrylate allergy.^18,19 Clinicians should be cognizant that an acrylate allergy may be present even if initial screening is negative but the history and clinical picture are suggestive.

The Diagnosis: Allergic Contact Dermatitis

An allergic contact dermatitis (ACD) to acrylates was suspected and 4 patches were applied to the forearm (the North American Standard Series of the North American Contact Dermatitis Group). The patches were 2-hydroxyethyl methacrylate (2-HEMA) 2.0% permissible exposure limit (peL), ethyl acrylate 0.1% peL, tosylamide formaldehyde resin 10.0% peL, and methyl methacrylate 2.0% peL. A reading at 72 hours was performed and showed a positive reaction to hydroxyethyl methacrylate, ethyl acrylate, and methyl methacrylate, and a negative patch test to tosylamide formaldehyde resin (nail polish)(Figure). The patient was diagnosed with an allergic contact hypersensitivity to the aforementioned acrylates and instructed to avoid artificial nails and acrylate glues. She also was started on oral biotin supplements. On 6-month follow-up the patient had regrowth of all 10 fingernails without brittleness or splitting. She was able to use nail polishes but avoided all acrylic artificial nails and acrylate-containing personal care products.

Acrylate Allergy and Artificial Nails

Acrylates are plastic materials formed by polymerization of acrylic or methacrylic acid monomers and have been cited as a major cause of occupational and nonoccupational contact dermatitis. Contact dermatitis to acrylates in artificial nails was first reported in the 1950s.^1,2 Products containing 100% methyl methacrylate monomers in acrylic nails were banned by the US Food and Drug Administration in the early 1970s after receiving a number of complaints.³ However, no regulation prohibits the use of methyl methacrylate monomer in cosmetic products, and various methacrylate and acrylate monomers remain widely used.⁴ With a growing popularity in artificial nails, it is expected the number of sensitized persons will increase.

Acrylate allergy from sculptured nails concern self-curing resins made from a polymer powder and a liquid monomer solution. Advantages of new UV-cured products include the lack of unpleasant smell and simplified modeling. They also do not require an irritant, such as methacrylic acid, as a bonding agent. Instead, 2-HEMA and 2-hydroxypropyl methacrylate are added. These photobonded nails colloquially are called gel nails (acid free) as opposed to acrylic nails (using methacrylic acid as a primer). It is important to note that the esters of acrylic acid but not the acid itself sensitize patients, and sensitization is not caused by the uncured gel or the monomer solution but by the remaining monomers in the cured plastic nail and the dust filings that are produced during the finishing process.

Clinical Presentation

Symptoms of an ACD to nail acrylates include pruritus and fingertip dermatitis along with nail plate dystrophy. There may be pruritus at the nail base, with subsequent dryness, thickening, and onycholysis. The brittle nails may become split, discolored, and develop paronychia. Inadvertent contact with glue monomers or other acrylate-containing substances may cause eczematous lesions at distant sites. Avoidance of the allergen often results in complete restoration of the normal nail and fingertip within months.

Sensitization

Acrylates and methacrylates are ubiquitous materials used for both industrial and commercial applications. Due to their widespread industrial use, contact allergies to acrylates including 2-HEMA, 2-hydroxypropyl methacrylate, and triethyleneglycol diacrylate (TREGDA) are common. Cross-reaction of these compounds has been observed and is postulated to be due to reaction of the (meth)acrylate carboxyethyl group with the receptors of antigen-presenting cells.⁵ As a result, an individual with an acrylate allergy sensitized to one allergen often is allergic to its similar compounds and cross-reactors and must avoid the assortment of compounds containing these ingredients, which is important for individuals with occupational sensitization to a particular acrylate who is subsequently susceptible to other acrylate-containing compounds triggering allergic reactions when reexposure occurs in different settings.

Allergens and Occupational Exposure

Acrylates in cosmetic nail products are a source of ACD for not only the customer but also the manicurist.⁶ The most frequently cited sources of ACD in beauticians are acrylate chemicals.⁷ However, acrylate compounds are an occupational hazard for a number of other specialists, including dentists and dental technicians, histology technicians, and individuals in the printing industry.^8,9 Other individuals may be sensitized to acrylates through their inclusion in adhesives, dental bonding agents, hearing aids, electrocardiogram electrodes, artificial bone cement, and a myriad of other medical and nonmedical applications.^4,10-12 For workers who cannot avoid occupational exposure to these allergens, polyvinyl alcohol and multilayer laminate gloves are recommended, as natural rubber latex gloves do not always provide adequate protection from many of these agents.¹⁰

Testing for Suspected Acrylate Allergy

Cross-reactivity among acrylates is widely considered in the literature but remains enigmatic and is an important consideration with regard to routine patch test screening.¹³ In the case of an acrylate allergy to nail products, using 2-HEMA and ethylene glycol dimethacrylate is effective in detecting sensitization by photobonded nails and in patients sensitized by powder liquid products.¹⁴ One study showed a patch test panel including 2-HEMA, ethylene glycol dimethacrylate, and TREGDA was effective in identifying the majority of individuals with an allergy to acrylates in nail products and nail technicians.¹⁵ Another study has shown the most commonly positive testing allergens to be HEMA, ethyl acrylate, and methyl methacrylate.¹⁶ If one is patch testing only one chemical, it appears 2-HEMA is preferred.¹⁷ However, broader panels of screening allergens are necessary to achieve an accurate diagnosis. Furthermore, different panels of test allergens have been shown to vary in their ability to detect an acrylate allergy in different occupational exposures.¹² 

The time to patch test read also is important. A standard read at 72 hours is warranted; however, one study showed if only one read at day 3 was done without a subsequent day 7 read, then 25% of TREGDA and 50% of 2-HEMA allergies would have been missed in patients with occupational acrylate allergy.¹⁵ Other studies have reported late-appearing and long-lasting test reactions when testing for an acrylate allergy.^18,19 Clinicians should be cognizant that an acrylate allergy may be present even if initial screening is negative but the history and clinical picture are suggestive.

The Diagnosis: Allergic Contact Dermatitis

An allergic contact dermatitis (ACD) to acrylates was suspected and 4 patches were applied to the forearm (the North American Standard Series of the North American Contact Dermatitis Group). The patches were 2-hydroxyethyl methacrylate (2-HEMA) 2.0% permissible exposure limit (peL), ethyl acrylate 0.1% peL, tosylamide formaldehyde resin 10.0% peL, and methyl methacrylate 2.0% peL. A reading at 72 hours was performed and showed a positive reaction to hydroxyethyl methacrylate, ethyl acrylate, and methyl methacrylate, and a negative patch test to tosylamide formaldehyde resin (nail polish)(Figure). The patient was diagnosed with an allergic contact hypersensitivity to the aforementioned acrylates and instructed to avoid artificial nails and acrylate glues. She also was started on oral biotin supplements. On 6-month follow-up the patient had regrowth of all 10 fingernails without brittleness or splitting. She was able to use nail polishes but avoided all acrylic artificial nails and acrylate-containing personal care products.

Acrylate Allergy and Artificial Nails

Acrylates are plastic materials formed by polymerization of acrylic or methacrylic acid monomers and have been cited as a major cause of occupational and nonoccupational contact dermatitis. Contact dermatitis to acrylates in artificial nails was first reported in the 1950s.^1,2 Products containing 100% methyl methacrylate monomers in acrylic nails were banned by the US Food and Drug Administration in the early 1970s after receiving a number of complaints.³ However, no regulation prohibits the use of methyl methacrylate monomer in cosmetic products, and various methacrylate and acrylate monomers remain widely used.⁴ With a growing popularity in artificial nails, it is expected the number of sensitized persons will increase.

Acrylate allergy from sculptured nails concern self-curing resins made from a polymer powder and a liquid monomer solution. Advantages of new UV-cured products include the lack of unpleasant smell and simplified modeling. They also do not require an irritant, such as methacrylic acid, as a bonding agent. Instead, 2-HEMA and 2-hydroxypropyl methacrylate are added. These photobonded nails colloquially are called gel nails (acid free) as opposed to acrylic nails (using methacrylic acid as a primer). It is important to note that the esters of acrylic acid but not the acid itself sensitize patients, and sensitization is not caused by the uncured gel or the monomer solution but by the remaining monomers in the cured plastic nail and the dust filings that are produced during the finishing process.

Clinical Presentation

Symptoms of an ACD to nail acrylates include pruritus and fingertip dermatitis along with nail plate dystrophy. There may be pruritus at the nail base, with subsequent dryness, thickening, and onycholysis. The brittle nails may become split, discolored, and develop paronychia. Inadvertent contact with glue monomers or other acrylate-containing substances may cause eczematous lesions at distant sites. Avoidance of the allergen often results in complete restoration of the normal nail and fingertip within months.

Sensitization

Acrylates and methacrylates are ubiquitous materials used for both industrial and commercial applications. Due to their widespread industrial use, contact allergies to acrylates including 2-HEMA, 2-hydroxypropyl methacrylate, and triethyleneglycol diacrylate (TREGDA) are common. Cross-reaction of these compounds has been observed and is postulated to be due to reaction of the (meth)acrylate carboxyethyl group with the receptors of antigen-presenting cells.⁵ As a result, an individual with an acrylate allergy sensitized to one allergen often is allergic to its similar compounds and cross-reactors and must avoid the assortment of compounds containing these ingredients, which is important for individuals with occupational sensitization to a particular acrylate who is subsequently susceptible to other acrylate-containing compounds triggering allergic reactions when reexposure occurs in different settings.

Allergens and Occupational Exposure

Acrylates in cosmetic nail products are a source of ACD for not only the customer but also the manicurist.⁶ The most frequently cited sources of ACD in beauticians are acrylate chemicals.⁷ However, acrylate compounds are an occupational hazard for a number of other specialists, including dentists and dental technicians, histology technicians, and individuals in the printing industry.^8,9 Other individuals may be sensitized to acrylates through their inclusion in adhesives, dental bonding agents, hearing aids, electrocardiogram electrodes, artificial bone cement, and a myriad of other medical and nonmedical applications.^4,10-12 For workers who cannot avoid occupational exposure to these allergens, polyvinyl alcohol and multilayer laminate gloves are recommended, as natural rubber latex gloves do not always provide adequate protection from many of these agents.¹⁰

Testing for Suspected Acrylate Allergy

Cross-reactivity among acrylates is widely considered in the literature but remains enigmatic and is an important consideration with regard to routine patch test screening.¹³ In the case of an acrylate allergy to nail products, using 2-HEMA and ethylene glycol dimethacrylate is effective in detecting sensitization by photobonded nails and in patients sensitized by powder liquid products.¹⁴ One study showed a patch test panel including 2-HEMA, ethylene glycol dimethacrylate, and TREGDA was effective in identifying the majority of individuals with an allergy to acrylates in nail products and nail technicians.¹⁵ Another study has shown the most commonly positive testing allergens to be HEMA, ethyl acrylate, and methyl methacrylate.¹⁶ If one is patch testing only one chemical, it appears 2-HEMA is preferred.¹⁷ However, broader panels of screening allergens are necessary to achieve an accurate diagnosis. Furthermore, different panels of test allergens have been shown to vary in their ability to detect an acrylate allergy in different occupational exposures.¹² 

The time to patch test read also is important. A standard read at 72 hours is warranted; however, one study showed if only one read at day 3 was done without a subsequent day 7 read, then 25% of TREGDA and 50% of 2-HEMA allergies would have been missed in patients with occupational acrylate allergy.¹⁵ Other studies have reported late-appearing and long-lasting test reactions when testing for an acrylate allergy.^18,19 Clinicians should be cognizant that an acrylate allergy may be present even if initial screening is negative but the history and clinical picture are suggestive.

The Diagnosis: Pemphigus Vegetans

Pemphigus vegetans is a rare variant of pemphigus vulgaris. Clinically, pemphigus vegetans is characterized by vegetative lesions over the flexures, but any area of the skin may be involved. There have been case reports involving the scalp,^1,2 mouth,³ and foot.⁴ There are 2 clinical subtypes: the Neumann type and the Hallopeau type.⁵ The Hallopeau type is relatively benign, requires lower doses of systemic corticosteroids, and has a prolonged remission, while the Neumann type necessitates higher doses of systemic corticosteroids and often presents with relapses and remissions.

The diagnosis of pemphigus vegetans is based on clinical suspicion and confirmed by histological examination and immunological findings. The diagnosis may be difficult, as its presentation varies and histopathological findings may resemble other conditions.

Systemic corticosteroids are the well-established drug of choice for treating pemphigus vegetans to induce remission and maintain healing before cautiously tapering down the dosage approximately 50% every 2 weeks.⁶ Adjuvant drugs used in conjunction with steroids for steroid-sparing purpose include azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, and cyclosporine.⁶ Pulsed intravenous steroids,⁷ intravenous immunoglobulins,⁸ pulsed dexamethasone cyclophosphamide,⁹ and extracorporeal photopheresis¹⁰ are given for severe and recalcitrant disease.

Laboratory investigations of our patient showed a normal complete blood cell count and a normal renal and liver profile. Herpes simplex virus serology was positive for type 1 and type 2 IgM and IgG. Urethral swab was dry and negative for gonorrhea. Serology for chlamydia, toxoplasma, amoebiasis, and leishmaniasis was negative. Human immunodeficiency virus serology, hepatitis screening, rapid plasma reagin, Treponema pallidum hemagglutination, rheumatoid factor, and antinuclear antibody all were negative. The patient was given a course of oral acyclovir 400 mg 3 times daily and empirical treatment with oral doxycycline 100 mg twice daily for a week with no clinical response.

Two biopsies from the perianal ulcers showed inflamed squamous papillomata with no Donovan bodies. A third biopsy from an intact blister showed acantholytic cells in the suprabasal bullae with eosinophilic and lymphocytic infiltrates at the upper dermis. Direct immunofluorescence demonstrated intercellular C3 and IgG deposits.

The patient was started on oral prednisolone at 1 mg/kg daily and oral azathioprine 50 mg daily with resolution of the perianal, penile, and oral ulcers (Figures 1 and 2). He achieved good suppression of further eruption. At the patient's most recent follow-up (2.5 years after the initial presentation), he was in remission and was currently taking oral azathioprine 100 mg once daily and no oral corticosteroids.

The Diagnosis: Pemphigus Vegetans

Pemphigus vegetans is a rare variant of pemphigus vulgaris. Clinically, pemphigus vegetans is characterized by vegetative lesions over the flexures, but any area of the skin may be involved. There have been case reports involving the scalp,^1,2 mouth,³ and foot.⁴ There are 2 clinical subtypes: the Neumann type and the Hallopeau type.⁵ The Hallopeau type is relatively benign, requires lower doses of systemic corticosteroids, and has a prolonged remission, while the Neumann type necessitates higher doses of systemic corticosteroids and often presents with relapses and remissions.

The diagnosis of pemphigus vegetans is based on clinical suspicion and confirmed by histological examination and immunological findings. The diagnosis may be difficult, as its presentation varies and histopathological findings may resemble other conditions.

Systemic corticosteroids are the well-established drug of choice for treating pemphigus vegetans to induce remission and maintain healing before cautiously tapering down the dosage approximately 50% every 2 weeks.⁶ Adjuvant drugs used in conjunction with steroids for steroid-sparing purpose include azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, and cyclosporine.⁶ Pulsed intravenous steroids,⁷ intravenous immunoglobulins,⁸ pulsed dexamethasone cyclophosphamide,⁹ and extracorporeal photopheresis¹⁰ are given for severe and recalcitrant disease.

Laboratory investigations of our patient showed a normal complete blood cell count and a normal renal and liver profile. Herpes simplex virus serology was positive for type 1 and type 2 IgM and IgG. Urethral swab was dry and negative for gonorrhea. Serology for chlamydia, toxoplasma, amoebiasis, and leishmaniasis was negative. Human immunodeficiency virus serology, hepatitis screening, rapid plasma reagin, Treponema pallidum hemagglutination, rheumatoid factor, and antinuclear antibody all were negative. The patient was given a course of oral acyclovir 400 mg 3 times daily and empirical treatment with oral doxycycline 100 mg twice daily for a week with no clinical response.

Two biopsies from the perianal ulcers showed inflamed squamous papillomata with no Donovan bodies. A third biopsy from an intact blister showed acantholytic cells in the suprabasal bullae with eosinophilic and lymphocytic infiltrates at the upper dermis. Direct immunofluorescence demonstrated intercellular C3 and IgG deposits.

The patient was started on oral prednisolone at 1 mg/kg daily and oral azathioprine 50 mg daily with resolution of the perianal, penile, and oral ulcers (Figures 1 and 2). He achieved good suppression of further eruption. At the patient's most recent follow-up (2.5 years after the initial presentation), he was in remission and was currently taking oral azathioprine 100 mg once daily and no oral corticosteroids.

The Diagnosis: Pemphigus Vegetans

Pemphigus vegetans is a rare variant of pemphigus vulgaris. Clinically, pemphigus vegetans is characterized by vegetative lesions over the flexures, but any area of the skin may be involved. There have been case reports involving the scalp,^1,2 mouth,³ and foot.⁴ There are 2 clinical subtypes: the Neumann type and the Hallopeau type.⁵ The Hallopeau type is relatively benign, requires lower doses of systemic corticosteroids, and has a prolonged remission, while the Neumann type necessitates higher doses of systemic corticosteroids and often presents with relapses and remissions.

The diagnosis of pemphigus vegetans is based on clinical suspicion and confirmed by histological examination and immunological findings. The diagnosis may be difficult, as its presentation varies and histopathological findings may resemble other conditions.

Systemic corticosteroids are the well-established drug of choice for treating pemphigus vegetans to induce remission and maintain healing before cautiously tapering down the dosage approximately 50% every 2 weeks.⁶ Adjuvant drugs used in conjunction with steroids for steroid-sparing purpose include azathioprine, cyclophosphamide, mycophenolate mofetil, methotrexate, and cyclosporine.⁶ Pulsed intravenous steroids,⁷ intravenous immunoglobulins,⁸ pulsed dexamethasone cyclophosphamide,⁹ and extracorporeal photopheresis¹⁰ are given for severe and recalcitrant disease.

Laboratory investigations of our patient showed a normal complete blood cell count and a normal renal and liver profile. Herpes simplex virus serology was positive for type 1 and type 2 IgM and IgG. Urethral swab was dry and negative for gonorrhea. Serology for chlamydia, toxoplasma, amoebiasis, and leishmaniasis was negative. Human immunodeficiency virus serology, hepatitis screening, rapid plasma reagin, Treponema pallidum hemagglutination, rheumatoid factor, and antinuclear antibody all were negative. The patient was given a course of oral acyclovir 400 mg 3 times daily and empirical treatment with oral doxycycline 100 mg twice daily for a week with no clinical response.

Two biopsies from the perianal ulcers showed inflamed squamous papillomata with no Donovan bodies. A third biopsy from an intact blister showed acantholytic cells in the suprabasal bullae with eosinophilic and lymphocytic infiltrates at the upper dermis. Direct immunofluorescence demonstrated intercellular C3 and IgG deposits.

The patient was started on oral prednisolone at 1 mg/kg daily and oral azathioprine 50 mg daily with resolution of the perianal, penile, and oral ulcers (Figures 1 and 2). He achieved good suppression of further eruption. At the patient's most recent follow-up (2.5 years after the initial presentation), he was in remission and was currently taking oral azathioprine 100 mg once daily and no oral corticosteroids.