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The Diagnosis: Black-Spot Poison Ivy

Due to the detailed account of the patient's history including acuity of current presentation, history of recent activities, travel history, and recent exposures, as well as a thorough skin examination, a diagnosis of black-spot poison ivy was made. In this case, the linear distribution of the lesions with overlying black pigment that could not be removed (Figures 1 and 2) provided important clues to diagnosis.

Poison ivy is an allergic contact dermatitis that affects an estimated 25 to 40 million Americans annually who are exposed to its resin. Poison ivy is a plant from the Toxicodendron genus, and an estimated 85% of the North American population report sensitivity to these plants, of which poison ivy (Toxicodendron radicans) is the most common.¹ Other related plants include poison sumac and poison oak. Poison ivy and other Toxicodendron plants produce urushiol, the oleoresin responsible for one of the most common allergic contact dermatitides in the United States.² Black-spot poison ivy is an uncommon presentation following exposure to urushiol or oleoresin,³ as sufficient concentration of urushiol on the skin rarely is achieved.^3,4 This plant's resin oxidizes and turns coal black when exposed to air.⁵ Contact with enough of this oleoresin will produce black-spot poison ivy.⁶ Patients with sufficient concentrations of oleoresin on their skin to cause this black oxidation usually have similar black spots on their clothing.⁷ Interestingly, some Toxicodendron species, such as the Japanese lacquer tree, Toxicodendron vernicifluum, have a black lacquer sap that was historically used as ink.⁸ This ink was used on Chinese and Japanese jars and has caused contact dermatitis hundreds of years after they were created.⁷

Poison ivy is characterized by a generalized, pruritic, erythematous rash with vesicles and papules in a linear distribution.⁹ Black-spot poison ivy presents the same with the addition of black lacquer-like macules with surrounding erythema.¹⁰ The skin lesions usually appear on exposed areas 24 to 48 hours after contact.¹¹ Histology of black-spot poison ivy lesions should reveal yellow material in the stratum corneum with epidermal necrosis, in addition to classic features of acute allergic contact dermatitis.³ Interestingly, because these lesions occur with the first exposure to poison ivy, a patient may not develop the typical itchy eczematous eruption characteristic of poison ivy dermatitis. Differential diagnosis includes superficial purpura; exogenous pigment such as marker, ink, or tattoo pigment; tinea nigra; purpuric allergic contact dermatitis to resins or dyes; arthropod assault; irritant contact dermatitis; and infectious and noninfectious vasculitis.¹¹

Similar to poison ivy, treatment of black-spot poison ivy involves oral and topical steroids combined with antihistamines if the patient continues to experience pruritus.^6,12 It was recommended to our patient to apply cool compresses with water or Burow solution to alleviate itching and promote drying of the lesions. Calamine lotion can provide similar outcomes.¹³ Once the oleoresin is oxidized and bound to skin, the black spots cannot be removed with soap, water, or alcohol. The black spots gradually desquamate 1 to 2 weeks after formation without scarring,¹¹ and patients do not require further monitoring.¹ Patients should clean or discard clothing and evaluate for possible sources of poison ivy exposure. Because this type of poison ivy dermatitis is rare, most health care workers likely have never seen black-spot poison ivy, and it is an important diagnosis to consider.¹³

The Diagnosis: Black-Spot Poison Ivy

Due to the detailed account of the patient's history including acuity of current presentation, history of recent activities, travel history, and recent exposures, as well as a thorough skin examination, a diagnosis of black-spot poison ivy was made. In this case, the linear distribution of the lesions with overlying black pigment that could not be removed (Figures 1 and 2) provided important clues to diagnosis.

Poison ivy is an allergic contact dermatitis that affects an estimated 25 to 40 million Americans annually who are exposed to its resin. Poison ivy is a plant from the Toxicodendron genus, and an estimated 85% of the North American population report sensitivity to these plants, of which poison ivy (Toxicodendron radicans) is the most common.¹ Other related plants include poison sumac and poison oak. Poison ivy and other Toxicodendron plants produce urushiol, the oleoresin responsible for one of the most common allergic contact dermatitides in the United States.² Black-spot poison ivy is an uncommon presentation following exposure to urushiol or oleoresin,³ as sufficient concentration of urushiol on the skin rarely is achieved.^3,4 This plant's resin oxidizes and turns coal black when exposed to air.⁵ Contact with enough of this oleoresin will produce black-spot poison ivy.⁶ Patients with sufficient concentrations of oleoresin on their skin to cause this black oxidation usually have similar black spots on their clothing.⁷ Interestingly, some Toxicodendron species, such as the Japanese lacquer tree, Toxicodendron vernicifluum, have a black lacquer sap that was historically used as ink.⁸ This ink was used on Chinese and Japanese jars and has caused contact dermatitis hundreds of years after they were created.⁷

Poison ivy is characterized by a generalized, pruritic, erythematous rash with vesicles and papules in a linear distribution.⁹ Black-spot poison ivy presents the same with the addition of black lacquer-like macules with surrounding erythema.¹⁰ The skin lesions usually appear on exposed areas 24 to 48 hours after contact.¹¹ Histology of black-spot poison ivy lesions should reveal yellow material in the stratum corneum with epidermal necrosis, in addition to classic features of acute allergic contact dermatitis.³ Interestingly, because these lesions occur with the first exposure to poison ivy, a patient may not develop the typical itchy eczematous eruption characteristic of poison ivy dermatitis. Differential diagnosis includes superficial purpura; exogenous pigment such as marker, ink, or tattoo pigment; tinea nigra; purpuric allergic contact dermatitis to resins or dyes; arthropod assault; irritant contact dermatitis; and infectious and noninfectious vasculitis.¹¹

Similar to poison ivy, treatment of black-spot poison ivy involves oral and topical steroids combined with antihistamines if the patient continues to experience pruritus.^6,12 It was recommended to our patient to apply cool compresses with water or Burow solution to alleviate itching and promote drying of the lesions. Calamine lotion can provide similar outcomes.¹³ Once the oleoresin is oxidized and bound to skin, the black spots cannot be removed with soap, water, or alcohol. The black spots gradually desquamate 1 to 2 weeks after formation without scarring,¹¹ and patients do not require further monitoring.¹ Patients should clean or discard clothing and evaluate for possible sources of poison ivy exposure. Because this type of poison ivy dermatitis is rare, most health care workers likely have never seen black-spot poison ivy, and it is an important diagnosis to consider.¹³

The Diagnosis: Black-Spot Poison Ivy

Due to the detailed account of the patient's history including acuity of current presentation, history of recent activities, travel history, and recent exposures, as well as a thorough skin examination, a diagnosis of black-spot poison ivy was made. In this case, the linear distribution of the lesions with overlying black pigment that could not be removed (Figures 1 and 2) provided important clues to diagnosis.

Poison ivy is an allergic contact dermatitis that affects an estimated 25 to 40 million Americans annually who are exposed to its resin. Poison ivy is a plant from the Toxicodendron genus, and an estimated 85% of the North American population report sensitivity to these plants, of which poison ivy (Toxicodendron radicans) is the most common.¹ Other related plants include poison sumac and poison oak. Poison ivy and other Toxicodendron plants produce urushiol, the oleoresin responsible for one of the most common allergic contact dermatitides in the United States.² Black-spot poison ivy is an uncommon presentation following exposure to urushiol or oleoresin,³ as sufficient concentration of urushiol on the skin rarely is achieved.^3,4 This plant's resin oxidizes and turns coal black when exposed to air.⁵ Contact with enough of this oleoresin will produce black-spot poison ivy.⁶ Patients with sufficient concentrations of oleoresin on their skin to cause this black oxidation usually have similar black spots on their clothing.⁷ Interestingly, some Toxicodendron species, such as the Japanese lacquer tree, Toxicodendron vernicifluum, have a black lacquer sap that was historically used as ink.⁸ This ink was used on Chinese and Japanese jars and has caused contact dermatitis hundreds of years after they were created.⁷

Poison ivy is characterized by a generalized, pruritic, erythematous rash with vesicles and papules in a linear distribution.⁹ Black-spot poison ivy presents the same with the addition of black lacquer-like macules with surrounding erythema.¹⁰ The skin lesions usually appear on exposed areas 24 to 48 hours after contact.¹¹ Histology of black-spot poison ivy lesions should reveal yellow material in the stratum corneum with epidermal necrosis, in addition to classic features of acute allergic contact dermatitis.³ Interestingly, because these lesions occur with the first exposure to poison ivy, a patient may not develop the typical itchy eczematous eruption characteristic of poison ivy dermatitis. Differential diagnosis includes superficial purpura; exogenous pigment such as marker, ink, or tattoo pigment; tinea nigra; purpuric allergic contact dermatitis to resins or dyes; arthropod assault; irritant contact dermatitis; and infectious and noninfectious vasculitis.¹¹

Similar to poison ivy, treatment of black-spot poison ivy involves oral and topical steroids combined with antihistamines if the patient continues to experience pruritus.^6,12 It was recommended to our patient to apply cool compresses with water or Burow solution to alleviate itching and promote drying of the lesions. Calamine lotion can provide similar outcomes.¹³ Once the oleoresin is oxidized and bound to skin, the black spots cannot be removed with soap, water, or alcohol. The black spots gradually desquamate 1 to 2 weeks after formation without scarring,¹¹ and patients do not require further monitoring.¹ Patients should clean or discard clothing and evaluate for possible sources of poison ivy exposure. Because this type of poison ivy dermatitis is rare, most health care workers likely have never seen black-spot poison ivy, and it is an important diagnosis to consider.¹³

The Diagnosis: Acute Generalized Exanthematous Pustulosis

Histopathology demonstrated spongiosis with subcorneal pustules and an overlying basket-weave pattern stratum corneum. There was mild papillary dermal edema with scattered dermal neutrophils and rare eosinophils (Figure). The patient's clinical presentation and histopathology were consistent with acute generalized exanthematous pustulosis (AGEP). The inciting agent in this case was the contrast medium iopamidol. The patient was treated with a short course of prednisone, triamcinolone cream, diphenhydramine, and acetaminophen. Within 1 week the pustules and erythema had resolved.

Acute generalized exanthematous pustulosis is an uncommon T cell-mediated cutaneous reaction characterized by widespread progressive erythema with numerous nonfollicular pinpoint pustules. The patient usually is well appearing; however, he/she often will have concurrent fever and facial edema. Mucous membranes rarely are involved. Laboratory results typically are notable only for leukocytosis with neutrophilia.

The pustular eruption typically occurs within 1 to 2 days after exposure to an inciting agent¹; however, this latent period can range from 1 hour to nearly 4 weeks in some studies.² Systemic medications are the cause in approximately 90% of cases, with antibiotics being the most common category. Frequently implicated medications include β-lactams, macrolides, quinolones, sulfonamides, proton pump inhibitors, hydroxychloroquine, terbinafine, nonsteroidal anti-inflammatory drugs, diltiazem, ketoconazole, and fluconazole. Acute generalized exanthematous pustulosis also has been rarely reported following contact with mercury, viral and bacterial infections, and spider bites.³

Iodinated contrast agents have long been known to cause immediate and delayed adverse cutaneous reactions. However, one consensus study indicated that these reactions occur in only 0.05% to 0.10% of patients.⁴ Although rare, iodinated contrast media (eg, iopamidol, iohexol, ioversol, iodixanol, iomeprol, iobitridol, iopromide) have been reported as a cause of AGEP. A PubMed search of articles indexed for MEDLINE using the terms acute generalized exanthematous pustulosis, contrast, iodine, and iodinated revealed 10 adult cases reported in 6 articles in the English-language literature.^1,5-9 The most recent articles focus on methods to identify the causative agent. If the etiology of the reaction is unclear, patch or intradermal testing can help to confirm the causative agent. These tests also can help determine similar agents to which the patient may cross-react.^4,5

It can be difficult to differentiate AGEP from other cutaneous drug reactions and other nonfollicular pustular conditions. Drug-induced hypersensitivity syndrome typically presents with facial edema and a morbilliform rash. Although it can present with pustules, the latent period is longer (2-6 weeks), and there frequently are signs of multiorgan involvement including hepatic dysfunction, eosinophilia, atypical lymphocytosis, and lymphadenopathy. Patients with generalized pustular psoriasis often have a history of plaque psoriasis; the pustules are more concentrated in flexural sites; the eruption is gradual in onset; and histologically there tends to be features of psoriasis including parakeratosis, Munro microabscesses, and dilated blood vessels.¹⁰ Subcorneal pustular dermatosis also is more concentrated in flexural sites and frequently has an annular or serpiginous configuration. The onset also is gradual, and it follows a more chronic course than AGEP. Exfoliative erythroderma presents with widespread erythema and superficial desquamating scale. It often occurs in association with systemic symptoms and can be the result of a drug reaction or underlying inflammatory dermatosis such as psoriasis, mycosis fungoides, or pityriasis rubra pilaris.

Acute generalized exanthematous pustulosis usually resolves spontaneously within 2 weeks and is associated with a superficial desquamation as it clears. Appropriate treatment includes discontinuing the offending agent; monitoring for systemic involvement; and treating the patient's symptoms with antihistamines, analgesics, topical steroids, and emollients. In more severe or persistent cases, treatment with systemic steroids and tumor necrosis factor α inhibitors has been attempted, though their efficacy remains unclear. We report a case of iopamidol-induced AGEP that highlights the importance of eliciting a history of contrast exposure from a patient with suspected AGEP.

The Diagnosis: Acute Generalized Exanthematous Pustulosis

Histopathology demonstrated spongiosis with subcorneal pustules and an overlying basket-weave pattern stratum corneum. There was mild papillary dermal edema with scattered dermal neutrophils and rare eosinophils (Figure). The patient's clinical presentation and histopathology were consistent with acute generalized exanthematous pustulosis (AGEP). The inciting agent in this case was the contrast medium iopamidol. The patient was treated with a short course of prednisone, triamcinolone cream, diphenhydramine, and acetaminophen. Within 1 week the pustules and erythema had resolved.

Acute generalized exanthematous pustulosis is an uncommon T cell-mediated cutaneous reaction characterized by widespread progressive erythema with numerous nonfollicular pinpoint pustules. The patient usually is well appearing; however, he/she often will have concurrent fever and facial edema. Mucous membranes rarely are involved. Laboratory results typically are notable only for leukocytosis with neutrophilia.

The pustular eruption typically occurs within 1 to 2 days after exposure to an inciting agent¹; however, this latent period can range from 1 hour to nearly 4 weeks in some studies.² Systemic medications are the cause in approximately 90% of cases, with antibiotics being the most common category. Frequently implicated medications include β-lactams, macrolides, quinolones, sulfonamides, proton pump inhibitors, hydroxychloroquine, terbinafine, nonsteroidal anti-inflammatory drugs, diltiazem, ketoconazole, and fluconazole. Acute generalized exanthematous pustulosis also has been rarely reported following contact with mercury, viral and bacterial infections, and spider bites.³

Iodinated contrast agents have long been known to cause immediate and delayed adverse cutaneous reactions. However, one consensus study indicated that these reactions occur in only 0.05% to 0.10% of patients.⁴ Although rare, iodinated contrast media (eg, iopamidol, iohexol, ioversol, iodixanol, iomeprol, iobitridol, iopromide) have been reported as a cause of AGEP. A PubMed search of articles indexed for MEDLINE using the terms acute generalized exanthematous pustulosis, contrast, iodine, and iodinated revealed 10 adult cases reported in 6 articles in the English-language literature.^1,5-9 The most recent articles focus on methods to identify the causative agent. If the etiology of the reaction is unclear, patch or intradermal testing can help to confirm the causative agent. These tests also can help determine similar agents to which the patient may cross-react.^4,5

It can be difficult to differentiate AGEP from other cutaneous drug reactions and other nonfollicular pustular conditions. Drug-induced hypersensitivity syndrome typically presents with facial edema and a morbilliform rash. Although it can present with pustules, the latent period is longer (2-6 weeks), and there frequently are signs of multiorgan involvement including hepatic dysfunction, eosinophilia, atypical lymphocytosis, and lymphadenopathy. Patients with generalized pustular psoriasis often have a history of plaque psoriasis; the pustules are more concentrated in flexural sites; the eruption is gradual in onset; and histologically there tends to be features of psoriasis including parakeratosis, Munro microabscesses, and dilated blood vessels.¹⁰ Subcorneal pustular dermatosis also is more concentrated in flexural sites and frequently has an annular or serpiginous configuration. The onset also is gradual, and it follows a more chronic course than AGEP. Exfoliative erythroderma presents with widespread erythema and superficial desquamating scale. It often occurs in association with systemic symptoms and can be the result of a drug reaction or underlying inflammatory dermatosis such as psoriasis, mycosis fungoides, or pityriasis rubra pilaris.

Acute generalized exanthematous pustulosis usually resolves spontaneously within 2 weeks and is associated with a superficial desquamation as it clears. Appropriate treatment includes discontinuing the offending agent; monitoring for systemic involvement; and treating the patient's symptoms with antihistamines, analgesics, topical steroids, and emollients. In more severe or persistent cases, treatment with systemic steroids and tumor necrosis factor α inhibitors has been attempted, though their efficacy remains unclear. We report a case of iopamidol-induced AGEP that highlights the importance of eliciting a history of contrast exposure from a patient with suspected AGEP.

The Diagnosis: Acute Generalized Exanthematous Pustulosis

Histopathology demonstrated spongiosis with subcorneal pustules and an overlying basket-weave pattern stratum corneum. There was mild papillary dermal edema with scattered dermal neutrophils and rare eosinophils (Figure). The patient's clinical presentation and histopathology were consistent with acute generalized exanthematous pustulosis (AGEP). The inciting agent in this case was the contrast medium iopamidol. The patient was treated with a short course of prednisone, triamcinolone cream, diphenhydramine, and acetaminophen. Within 1 week the pustules and erythema had resolved.

Acute generalized exanthematous pustulosis is an uncommon T cell-mediated cutaneous reaction characterized by widespread progressive erythema with numerous nonfollicular pinpoint pustules. The patient usually is well appearing; however, he/she often will have concurrent fever and facial edema. Mucous membranes rarely are involved. Laboratory results typically are notable only for leukocytosis with neutrophilia.

The pustular eruption typically occurs within 1 to 2 days after exposure to an inciting agent¹; however, this latent period can range from 1 hour to nearly 4 weeks in some studies.² Systemic medications are the cause in approximately 90% of cases, with antibiotics being the most common category. Frequently implicated medications include β-lactams, macrolides, quinolones, sulfonamides, proton pump inhibitors, hydroxychloroquine, terbinafine, nonsteroidal anti-inflammatory drugs, diltiazem, ketoconazole, and fluconazole. Acute generalized exanthematous pustulosis also has been rarely reported following contact with mercury, viral and bacterial infections, and spider bites.³

Iodinated contrast agents have long been known to cause immediate and delayed adverse cutaneous reactions. However, one consensus study indicated that these reactions occur in only 0.05% to 0.10% of patients.⁴ Although rare, iodinated contrast media (eg, iopamidol, iohexol, ioversol, iodixanol, iomeprol, iobitridol, iopromide) have been reported as a cause of AGEP. A PubMed search of articles indexed for MEDLINE using the terms acute generalized exanthematous pustulosis, contrast, iodine, and iodinated revealed 10 adult cases reported in 6 articles in the English-language literature.^1,5-9 The most recent articles focus on methods to identify the causative agent. If the etiology of the reaction is unclear, patch or intradermal testing can help to confirm the causative agent. These tests also can help determine similar agents to which the patient may cross-react.^4,5

It can be difficult to differentiate AGEP from other cutaneous drug reactions and other nonfollicular pustular conditions. Drug-induced hypersensitivity syndrome typically presents with facial edema and a morbilliform rash. Although it can present with pustules, the latent period is longer (2-6 weeks), and there frequently are signs of multiorgan involvement including hepatic dysfunction, eosinophilia, atypical lymphocytosis, and lymphadenopathy. Patients with generalized pustular psoriasis often have a history of plaque psoriasis; the pustules are more concentrated in flexural sites; the eruption is gradual in onset; and histologically there tends to be features of psoriasis including parakeratosis, Munro microabscesses, and dilated blood vessels.¹⁰ Subcorneal pustular dermatosis also is more concentrated in flexural sites and frequently has an annular or serpiginous configuration. The onset also is gradual, and it follows a more chronic course than AGEP. Exfoliative erythroderma presents with widespread erythema and superficial desquamating scale. It often occurs in association with systemic symptoms and can be the result of a drug reaction or underlying inflammatory dermatosis such as psoriasis, mycosis fungoides, or pityriasis rubra pilaris.

Acute generalized exanthematous pustulosis usually resolves spontaneously within 2 weeks and is associated with a superficial desquamation as it clears. Appropriate treatment includes discontinuing the offending agent; monitoring for systemic involvement; and treating the patient's symptoms with antihistamines, analgesics, topical steroids, and emollients. In more severe or persistent cases, treatment with systemic steroids and tumor necrosis factor α inhibitors has been attempted, though their efficacy remains unclear. We report a case of iopamidol-induced AGEP that highlights the importance of eliciting a history of contrast exposure from a patient with suspected AGEP.

The Diagnosis: Self-healing Langerhans Cell Histiocytosis

Histopathologic examination showed an infiltrate of mononuclear cells with indented nuclei admixed with a variable dermal inflammatory infiltrate. Immunohistochemistry demonstrated cells that were strongly positive for CD1a (Figure, A) and langerin (Figure, B) antigens as well as S-100 protein (Figure, C), which was consistent with Langerhans cell histiocytosis (LCH).

Histiocytoses are a heterogeneous group of disorders in which the infiltrating cells belong to the mononuclear phagocyte system.^1,2 Langerhans cell histiocytosis is the most common dendritic cell-related histiocytosis, occurring in approximately 5 per 1 million children annually, giving it an incidence comparable to pediatric Hodgkin lymphoma and acute myeloid leukemia.^1,2

Historically, there has been much debate about the pathogenesis of the disease.² Until recently it was unknown whether LCH was primarily a neoplastic or an inflammatory disorder. Although the condition initially was thought to have a reactive etiology,¹ more recent evidence suggests a clonal neoplastic process. Langerhans cell histiocytosis lesions are clonal and display malignancy-associated mechanisms such as immune evasion. Genome sequencing has revealed several mutations in precursor myeloid cells that result in the common downstream hyperactivation of the mitogen-activated protein kinase signaling pathway that regulates cell proliferation and differentiation.¹

Langerhans cell histiocytosis displays a wide spectrum of clinical phenotypes, which historically were subclassified as eosinophilic granulomas (localized lesions in bone), Hand-Schüller-Christian disease (multiple organ involvement with the classic triad of skull defects, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (visceral lesions involving multiple organs).³ However, in 1997 the Reclassification Working Group of the Histiocyte Society redefined LCH as single-system single site (SS-s) LCH, single-system multisite LCH, and multisystem LCH.⁴

In SS-s LCH, the most common site is bone (82%), followed by the skin (12%).⁵ Skin SS-s LCH classically presents as multiple skin lesions at birth without systemic manifestations; the lesions spontaneously involute within a few months.⁶ Less commonly, skin SS-s LCH can present as a single lesion. Berger et al⁷ described 4 neonates with unilesional skin SS-s LCH. Since then, more than 30 cases have been reported in the literature,⁸ and we report herein another unilesional self-healing LCH.

The morphology of skin lesions in self-healing LCH is highly variable, with the most common being multiple erythematous crusted papules (50%), followed by eczematous scaly lesions resembling seborrheic dermatitis in intertriginous areas (37.5%).^3,6 Unilesional self-healing LCH typically presents as an ulcerated or crusted nodule or papule on the trunk. This variability results in a large differential diagnosis. Self-healing LCH is easily mistaken for infectious processes including neonatal herpes simplex and varicella-zoster virus infection.⁹ Often, the dermatology department is consulted to rule out LCH when the asymptomatic neonate does not respond to parenteral acyclovir.

Less commonly, the magenta-colored papulonodules of self-healing LCH can mimic blueberry muffin rash and mandate a workup for intrauterine infections, especially cytomegalovirus, rubella, and blood dyscrasia.¹⁰ Other noninfectious processes in the differential of self-healing LCH include congenital infantile hemangioma, neonatal lupus erythematosus, seborrheic dermatitis (cradle cap), pyogenic granuloma, and psoriasis.^3,10 Definitive diagnosis requires histopathology.

Because unilesional self-healing LCH has an excellent prognosis and usually resolves on its own, therapy is unnecessary.^3,8 One large retrospective study (N=146) found that of all patients with skin lesions, 56% were managed with biopsy only.⁵ Other options include watchful waiting and topical corticosteroids. If the skin lesions are large, ulcerated, and/or painful, alkylating antitumor agents have been used. For extensive cutaneous disease, systemic corticosteroids combined with chemotherapy and psoralen plus UVA can be effective.⁶

The primary concern in the management of self-healing LCH is that the solitary skin lesion may be the harbinger of an aggressive disorder that can progress to systemic disease.⁵ Moreover, recurrent visceral or disseminated disease may occur months to years after resolution of solitary skin lesions.⁹ Studies have shown that localized and disseminated disease cannot be differentiated on the basis of clinical findings, histology, immunohistochemistry, or biomarkers.^3,11 As a result, an evaluation for systemic disease should be performed at the time of diagnosis for cutaneous LCH.^3,9 Minimum baseline studies recommended by the Writing Group of the Histiocyte Society include a complete blood cell count, liver function tests, coagulation studies, chest radiography, skeletal surveys, and urine osmolality testing.¹² Periodic clinical follow-up is recommended for all variants of LCH.⁹

Our case was diagnosed as self-healing LCH based on histologic findings. No treatment was required, and at 3-month follow-up the infant was asymptomatic without recurrence and was meeting all developmental milestones.

The Diagnosis: Self-healing Langerhans Cell Histiocytosis

Histopathologic examination showed an infiltrate of mononuclear cells with indented nuclei admixed with a variable dermal inflammatory infiltrate. Immunohistochemistry demonstrated cells that were strongly positive for CD1a (Figure, A) and langerin (Figure, B) antigens as well as S-100 protein (Figure, C), which was consistent with Langerhans cell histiocytosis (LCH).

Histiocytoses are a heterogeneous group of disorders in which the infiltrating cells belong to the mononuclear phagocyte system.^1,2 Langerhans cell histiocytosis is the most common dendritic cell-related histiocytosis, occurring in approximately 5 per 1 million children annually, giving it an incidence comparable to pediatric Hodgkin lymphoma and acute myeloid leukemia.^1,2

Historically, there has been much debate about the pathogenesis of the disease.² Until recently it was unknown whether LCH was primarily a neoplastic or an inflammatory disorder. Although the condition initially was thought to have a reactive etiology,¹ more recent evidence suggests a clonal neoplastic process. Langerhans cell histiocytosis lesions are clonal and display malignancy-associated mechanisms such as immune evasion. Genome sequencing has revealed several mutations in precursor myeloid cells that result in the common downstream hyperactivation of the mitogen-activated protein kinase signaling pathway that regulates cell proliferation and differentiation.¹

Langerhans cell histiocytosis displays a wide spectrum of clinical phenotypes, which historically were subclassified as eosinophilic granulomas (localized lesions in bone), Hand-Schüller-Christian disease (multiple organ involvement with the classic triad of skull defects, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (visceral lesions involving multiple organs).³ However, in 1997 the Reclassification Working Group of the Histiocyte Society redefined LCH as single-system single site (SS-s) LCH, single-system multisite LCH, and multisystem LCH.⁴

In SS-s LCH, the most common site is bone (82%), followed by the skin (12%).⁵ Skin SS-s LCH classically presents as multiple skin lesions at birth without systemic manifestations; the lesions spontaneously involute within a few months.⁶ Less commonly, skin SS-s LCH can present as a single lesion. Berger et al⁷ described 4 neonates with unilesional skin SS-s LCH. Since then, more than 30 cases have been reported in the literature,⁸ and we report herein another unilesional self-healing LCH.

The morphology of skin lesions in self-healing LCH is highly variable, with the most common being multiple erythematous crusted papules (50%), followed by eczematous scaly lesions resembling seborrheic dermatitis in intertriginous areas (37.5%).^3,6 Unilesional self-healing LCH typically presents as an ulcerated or crusted nodule or papule on the trunk. This variability results in a large differential diagnosis. Self-healing LCH is easily mistaken for infectious processes including neonatal herpes simplex and varicella-zoster virus infection.⁹ Often, the dermatology department is consulted to rule out LCH when the asymptomatic neonate does not respond to parenteral acyclovir.

Less commonly, the magenta-colored papulonodules of self-healing LCH can mimic blueberry muffin rash and mandate a workup for intrauterine infections, especially cytomegalovirus, rubella, and blood dyscrasia.¹⁰ Other noninfectious processes in the differential of self-healing LCH include congenital infantile hemangioma, neonatal lupus erythematosus, seborrheic dermatitis (cradle cap), pyogenic granuloma, and psoriasis.^3,10 Definitive diagnosis requires histopathology.

Because unilesional self-healing LCH has an excellent prognosis and usually resolves on its own, therapy is unnecessary.^3,8 One large retrospective study (N=146) found that of all patients with skin lesions, 56% were managed with biopsy only.⁵ Other options include watchful waiting and topical corticosteroids. If the skin lesions are large, ulcerated, and/or painful, alkylating antitumor agents have been used. For extensive cutaneous disease, systemic corticosteroids combined with chemotherapy and psoralen plus UVA can be effective.⁶

The primary concern in the management of self-healing LCH is that the solitary skin lesion may be the harbinger of an aggressive disorder that can progress to systemic disease.⁵ Moreover, recurrent visceral or disseminated disease may occur months to years after resolution of solitary skin lesions.⁹ Studies have shown that localized and disseminated disease cannot be differentiated on the basis of clinical findings, histology, immunohistochemistry, or biomarkers.^3,11 As a result, an evaluation for systemic disease should be performed at the time of diagnosis for cutaneous LCH.^3,9 Minimum baseline studies recommended by the Writing Group of the Histiocyte Society include a complete blood cell count, liver function tests, coagulation studies, chest radiography, skeletal surveys, and urine osmolality testing.¹² Periodic clinical follow-up is recommended for all variants of LCH.⁹

Our case was diagnosed as self-healing LCH based on histologic findings. No treatment was required, and at 3-month follow-up the infant was asymptomatic without recurrence and was meeting all developmental milestones.

The Diagnosis: Self-healing Langerhans Cell Histiocytosis

Histopathologic examination showed an infiltrate of mononuclear cells with indented nuclei admixed with a variable dermal inflammatory infiltrate. Immunohistochemistry demonstrated cells that were strongly positive for CD1a (Figure, A) and langerin (Figure, B) antigens as well as S-100 protein (Figure, C), which was consistent with Langerhans cell histiocytosis (LCH).

Histiocytoses are a heterogeneous group of disorders in which the infiltrating cells belong to the mononuclear phagocyte system.^1,2 Langerhans cell histiocytosis is the most common dendritic cell-related histiocytosis, occurring in approximately 5 per 1 million children annually, giving it an incidence comparable to pediatric Hodgkin lymphoma and acute myeloid leukemia.^1,2

Historically, there has been much debate about the pathogenesis of the disease.² Until recently it was unknown whether LCH was primarily a neoplastic or an inflammatory disorder. Although the condition initially was thought to have a reactive etiology,¹ more recent evidence suggests a clonal neoplastic process. Langerhans cell histiocytosis lesions are clonal and display malignancy-associated mechanisms such as immune evasion. Genome sequencing has revealed several mutations in precursor myeloid cells that result in the common downstream hyperactivation of the mitogen-activated protein kinase signaling pathway that regulates cell proliferation and differentiation.¹

Langerhans cell histiocytosis displays a wide spectrum of clinical phenotypes, which historically were subclassified as eosinophilic granulomas (localized lesions in bone), Hand-Schüller-Christian disease (multiple organ involvement with the classic triad of skull defects, diabetes insipidus, and exophthalmos), and Letterer-Siwe disease (visceral lesions involving multiple organs).³ However, in 1997 the Reclassification Working Group of the Histiocyte Society redefined LCH as single-system single site (SS-s) LCH, single-system multisite LCH, and multisystem LCH.⁴

In SS-s LCH, the most common site is bone (82%), followed by the skin (12%).⁵ Skin SS-s LCH classically presents as multiple skin lesions at birth without systemic manifestations; the lesions spontaneously involute within a few months.⁶ Less commonly, skin SS-s LCH can present as a single lesion. Berger et al⁷ described 4 neonates with unilesional skin SS-s LCH. Since then, more than 30 cases have been reported in the literature,⁸ and we report herein another unilesional self-healing LCH.

The morphology of skin lesions in self-healing LCH is highly variable, with the most common being multiple erythematous crusted papules (50%), followed by eczematous scaly lesions resembling seborrheic dermatitis in intertriginous areas (37.5%).^3,6 Unilesional self-healing LCH typically presents as an ulcerated or crusted nodule or papule on the trunk. This variability results in a large differential diagnosis. Self-healing LCH is easily mistaken for infectious processes including neonatal herpes simplex and varicella-zoster virus infection.⁹ Often, the dermatology department is consulted to rule out LCH when the asymptomatic neonate does not respond to parenteral acyclovir.

Less commonly, the magenta-colored papulonodules of self-healing LCH can mimic blueberry muffin rash and mandate a workup for intrauterine infections, especially cytomegalovirus, rubella, and blood dyscrasia.¹⁰ Other noninfectious processes in the differential of self-healing LCH include congenital infantile hemangioma, neonatal lupus erythematosus, seborrheic dermatitis (cradle cap), pyogenic granuloma, and psoriasis.^3,10 Definitive diagnosis requires histopathology.

Because unilesional self-healing LCH has an excellent prognosis and usually resolves on its own, therapy is unnecessary.^3,8 One large retrospective study (N=146) found that of all patients with skin lesions, 56% were managed with biopsy only.⁵ Other options include watchful waiting and topical corticosteroids. If the skin lesions are large, ulcerated, and/or painful, alkylating antitumor agents have been used. For extensive cutaneous disease, systemic corticosteroids combined with chemotherapy and psoralen plus UVA can be effective.⁶

The primary concern in the management of self-healing LCH is that the solitary skin lesion may be the harbinger of an aggressive disorder that can progress to systemic disease.⁵ Moreover, recurrent visceral or disseminated disease may occur months to years after resolution of solitary skin lesions.⁹ Studies have shown that localized and disseminated disease cannot be differentiated on the basis of clinical findings, histology, immunohistochemistry, or biomarkers.^3,11 As a result, an evaluation for systemic disease should be performed at the time of diagnosis for cutaneous LCH.^3,9 Minimum baseline studies recommended by the Writing Group of the Histiocyte Society include a complete blood cell count, liver function tests, coagulation studies, chest radiography, skeletal surveys, and urine osmolality testing.¹² Periodic clinical follow-up is recommended for all variants of LCH.⁹

Our case was diagnosed as self-healing LCH based on histologic findings. No treatment was required, and at 3-month follow-up the infant was asymptomatic without recurrence and was meeting all developmental milestones.

The Diagnosis: Pediculosis Pubis

Dermoscopy of the pubic hair demonstrated a louse clutching multiple shafts of hairs (Figure) as well as scattered nits, confirming the presence of Phthirus pubis and diagnosis of pediculosis pubis. The key clinical diagnostic feature in this case was severe itching of the pubic area, with visible nits present on pubic hairs. Itching and infestation also can involve other hair-bearing areas such as the chest, legs, and axillae. The patient was treated with permethrin cream 5% applied to the pubic area and chest. Symptoms and infestation were resolved at 1-week follow-up.

Pediculosis pubis is an infestation of pubic hairs by the pubic (crab) louse P pubis, which feeds on host blood. Other body areas covered with dense hair also may be involved; 60% of patients are infested in at least 2 different sites.¹ Pediculosis pubis is most commonly sexually transmitted through direct contact.² Worldwide prevalence has been estimated at approximately 2% of the adult population, and a survey of 817 US college students in 2009 indicated a lifetime prevalence of 1.3%.³ The prevalence is slightly higher in men, highest in men who have sex with men, and rare in individuals with shaved pubic hair.¹ The most common symptom is pruritus of the genital area. Infested patients also may develop asymptomatic bluish gray macules (maculae ceruleae) secondary to hemosiderin deposition from louse bites.⁴

The diagnosis of pediculosis pubis is made by identification of P pubis, either by examination with the naked eye or confirmation with dermoscopy or microscopy. Although the 0.8- to 1.2-mm lice are visible to the naked eye, they can be difficult to see if not filled with blood, and nits on the hairs can be mistaken for white piedra (fungal infection of the hair shafts) or trichomycosis pubis (bacterial infection of the hair shafts).⁴ Scabies and tinea cruris do not present with attachments to the hairs. Scabies may present with papules and burrows and tinea cruris with scaly erythematous plaques. Small numbers of lice and nits may be missed by the naked eye or a traditional magnifying glass.⁵ The use of dermoscopy allows for fast and accurate identification of the characteristic lice and nits, even in these more challenging cases.⁵ Accurate diagnosis is important, as approximately 31% of infested patients have other concurrent sexually transmitted infections that warrant screening.⁶

The Centers for Disease Control and Prevention recommends first-line treatment with permethrin cream (1% or 5%) or pyrethrin with piperonyl butoxide applied to all affected areas and washed off after 10 minutes.⁷ Patients should be reevaluated after 1 week if symptoms persist and re-treated if lice are found on examination.^7,8 Malathion lotion 0.5% (applied and washed off after 8-12 hours) or oral ivermectin (250 µg/kg, repeated after 2 weeks) may be used for alternative therapies or cases of permethrin or pyrethrin resistance.⁷ Ivermectin also is effective for involvement of eyelashes where topical insecticides should not be used.⁹ Sexual partners should be treated to prevent repeat transmission.^7,8 Bedding and clothing can be decontaminated by machine wash on hot cycle or isolating from body contact for 72 hours.⁷ Patients also should be screened for other sexually transmitted infections, including human immunodeficiency virus.⁶

The Diagnosis: Pediculosis Pubis

Dermoscopy of the pubic hair demonstrated a louse clutching multiple shafts of hairs (Figure) as well as scattered nits, confirming the presence of Phthirus pubis and diagnosis of pediculosis pubis. The key clinical diagnostic feature in this case was severe itching of the pubic area, with visible nits present on pubic hairs. Itching and infestation also can involve other hair-bearing areas such as the chest, legs, and axillae. The patient was treated with permethrin cream 5% applied to the pubic area and chest. Symptoms and infestation were resolved at 1-week follow-up.

Pediculosis pubis is an infestation of pubic hairs by the pubic (crab) louse P pubis, which feeds on host blood. Other body areas covered with dense hair also may be involved; 60% of patients are infested in at least 2 different sites.¹ Pediculosis pubis is most commonly sexually transmitted through direct contact.² Worldwide prevalence has been estimated at approximately 2% of the adult population, and a survey of 817 US college students in 2009 indicated a lifetime prevalence of 1.3%.³ The prevalence is slightly higher in men, highest in men who have sex with men, and rare in individuals with shaved pubic hair.¹ The most common symptom is pruritus of the genital area. Infested patients also may develop asymptomatic bluish gray macules (maculae ceruleae) secondary to hemosiderin deposition from louse bites.⁴

The diagnosis of pediculosis pubis is made by identification of P pubis, either by examination with the naked eye or confirmation with dermoscopy or microscopy. Although the 0.8- to 1.2-mm lice are visible to the naked eye, they can be difficult to see if not filled with blood, and nits on the hairs can be mistaken for white piedra (fungal infection of the hair shafts) or trichomycosis pubis (bacterial infection of the hair shafts).⁴ Scabies and tinea cruris do not present with attachments to the hairs. Scabies may present with papules and burrows and tinea cruris with scaly erythematous plaques. Small numbers of lice and nits may be missed by the naked eye or a traditional magnifying glass.⁵ The use of dermoscopy allows for fast and accurate identification of the characteristic lice and nits, even in these more challenging cases.⁵ Accurate diagnosis is important, as approximately 31% of infested patients have other concurrent sexually transmitted infections that warrant screening.⁶

The Centers for Disease Control and Prevention recommends first-line treatment with permethrin cream (1% or 5%) or pyrethrin with piperonyl butoxide applied to all affected areas and washed off after 10 minutes.⁷ Patients should be reevaluated after 1 week if symptoms persist and re-treated if lice are found on examination.^7,8 Malathion lotion 0.5% (applied and washed off after 8-12 hours) or oral ivermectin (250 µg/kg, repeated after 2 weeks) may be used for alternative therapies or cases of permethrin or pyrethrin resistance.⁷ Ivermectin also is effective for involvement of eyelashes where topical insecticides should not be used.⁹ Sexual partners should be treated to prevent repeat transmission.^7,8 Bedding and clothing can be decontaminated by machine wash on hot cycle or isolating from body contact for 72 hours.⁷ Patients also should be screened for other sexually transmitted infections, including human immunodeficiency virus.⁶

The Diagnosis: Pediculosis Pubis

Dermoscopy of the pubic hair demonstrated a louse clutching multiple shafts of hairs (Figure) as well as scattered nits, confirming the presence of Phthirus pubis and diagnosis of pediculosis pubis. The key clinical diagnostic feature in this case was severe itching of the pubic area, with visible nits present on pubic hairs. Itching and infestation also can involve other hair-bearing areas such as the chest, legs, and axillae. The patient was treated with permethrin cream 5% applied to the pubic area and chest. Symptoms and infestation were resolved at 1-week follow-up.

Pediculosis pubis is an infestation of pubic hairs by the pubic (crab) louse P pubis, which feeds on host blood. Other body areas covered with dense hair also may be involved; 60% of patients are infested in at least 2 different sites.¹ Pediculosis pubis is most commonly sexually transmitted through direct contact.² Worldwide prevalence has been estimated at approximately 2% of the adult population, and a survey of 817 US college students in 2009 indicated a lifetime prevalence of 1.3%.³ The prevalence is slightly higher in men, highest in men who have sex with men, and rare in individuals with shaved pubic hair.¹ The most common symptom is pruritus of the genital area. Infested patients also may develop asymptomatic bluish gray macules (maculae ceruleae) secondary to hemosiderin deposition from louse bites.⁴

The diagnosis of pediculosis pubis is made by identification of P pubis, either by examination with the naked eye or confirmation with dermoscopy or microscopy. Although the 0.8- to 1.2-mm lice are visible to the naked eye, they can be difficult to see if not filled with blood, and nits on the hairs can be mistaken for white piedra (fungal infection of the hair shafts) or trichomycosis pubis (bacterial infection of the hair shafts).⁴ Scabies and tinea cruris do not present with attachments to the hairs. Scabies may present with papules and burrows and tinea cruris with scaly erythematous plaques. Small numbers of lice and nits may be missed by the naked eye or a traditional magnifying glass.⁵ The use of dermoscopy allows for fast and accurate identification of the characteristic lice and nits, even in these more challenging cases.⁵ Accurate diagnosis is important, as approximately 31% of infested patients have other concurrent sexually transmitted infections that warrant screening.⁶

The Centers for Disease Control and Prevention recommends first-line treatment with permethrin cream (1% or 5%) or pyrethrin with piperonyl butoxide applied to all affected areas and washed off after 10 minutes.⁷ Patients should be reevaluated after 1 week if symptoms persist and re-treated if lice are found on examination.^7,8 Malathion lotion 0.5% (applied and washed off after 8-12 hours) or oral ivermectin (250 µg/kg, repeated after 2 weeks) may be used for alternative therapies or cases of permethrin or pyrethrin resistance.⁷ Ivermectin also is effective for involvement of eyelashes where topical insecticides should not be used.⁹ Sexual partners should be treated to prevent repeat transmission.^7,8 Bedding and clothing can be decontaminated by machine wash on hot cycle or isolating from body contact for 72 hours.⁷ Patients also should be screened for other sexually transmitted infections, including human immunodeficiency virus.⁶

The Diagnosis: Pemphigus Vegetans

A punch biopsy was taken from the verrucous plaque, and microscopic examination demonstrated prominent epidermal hyperplasia with intraepidermal eosinophilic microabscesses and a superficial dermatitis with abundant eosinophils (Figure 1A). Suprabasal acantholytic cleft formation was noted in a focal area (Figure 1B). Another punch biopsy was performed from the perilesional skin for direct immunofluorescence examination, which revealed intercellular deposits of IgG and C3 throughout the lower half of the epidermis (Figure 1C). Indirect immunofluorescence performed on monkey esophagus substrate showed circulating intercellular IgG antibodies in all the titers of up to 1/160 and an elevated level of IgG antidesmoglein 3 (anti-Dsg3) antibody (enzyme-linked immunosorbent assay index value, >200 RU/mL [reference range, <20 RU/mL]).

Because there was a solitary lesion, the decision was made to perform local treatment. One intralesional triamcinolone acetonide injection (20 mg/mL) resulted in remarkable flattening of the lesion (Figure 2). Subsequently, treatment was continued with clobetasol propionate ointment 3 times weekly for 1 month. During a follow-up period of 2 years, no signs of local relapse or new lesions elsewhere were noted, and the patient continued to be on long-term longitudinal evaluation.

Pemphigus vegetans (PV) is an uncommon variant of pemphigus, typically manifesting with vegetating erosions and plaques localized to the intertriginous areas of the body. Local factors such as semiocclusion, maceration, and/or bacterial or fungal colonization have been hypothesized to account for the distinctive localization and vegetation of the lesions.^1,2 Traditionally, 2 clinical subtypes of PV have been described: (1) Hallopeau type presenting with pustules that later evolve into vegetating plaques, and (2) Neumann type that initially manifests as vesicles and bullae with a more disseminated distribution, transforming into hypertrophic masses with erosions.^1-5 However, this distinction may not always be clear, and patients with features of both forms have been reported.^2,5

At present, our case would best be regarded as a localized form of PV presenting with a solitary lesion. It may progress to more disseminated disease or remain localized during its course; the literature contains reports exemplifying both possibilities. In a large retrospective study from Tunisia encompassing almost 3 decades, the majority of the patients initially presented with unifocal involvement; however, the disease eventually became multifocal in almost all patients during the study period, emphasizing the need for long-term follow-up.² There also are reports of PV confined to a single anatomic site, such as the scalp, sole, or vulva, that remained localized for years.^2,4,6,7 Involvement of the oral mucosa is an important finding of PV and the presenting concern in approximately three-quarters of patients.² Interestingly, the oral mucosa was not involved in our patient despite the high titer of anti-Dsg3 antibody, which suggests the need for the presence of other factors for clinical expression of the disease.

Although PV is considered a vegetating clinicomorphologic variant of pemphigus vulgaris, PV is histopathologically distinguished from pemphigus vulgaris by the presence of epidermal hyperplasia and intraepidermal eosinophilic microabscesses. Importantly, the epidermis displays signs of exuberant proliferation such as pseudoepitheliomatous hyperplasia and/or papillomatosis of a varying degree.^1,2,5 Of note, suprabasal acantholysis is usually overshadowed by the changes in PV and presents only focally, as in our patient. The most common autoantibody profile is IgG targeting Dsg3; however, a spectrum of other autoantibodies has been identified, such as IgG antidesmocollin 3, IgA anti-Dsg3, and IgG anti-Dsg1.^8,9

The most important differential diagnosis of PV is pyodermatitis-pyostomatitis vegetans. These 2 entities share many clinical and histopathological features; however, direct immunofluorescence is helpfulfor differentiation because it generally is negative in pyodermatitis-pyostomatitis vegetans.^2,10 Furthermore, there is a well-established association between pyodermatitis-pyostomatitis vegetans and inflammatory bowel disorders, whereas PV has anecdotally been linked to malignancy, human immunodeficiency virus infection, and heroin abuse.^1,2,10 Our patient was seronegative for human immunodeficiency virus and denied weight loss or loss of appetite. For those cases of PV involving a single anatomic site, the differential diagnosis is broader and encompasses dermatoses such as verrucae, syphilitic chancre, condylomata lata, granuloma inguinale, herpes simplex virus infection, and Kaposi sarcoma.

Treatment of PV is similar to pemphigus vulgaris and consists of a combination of systemic corticosteroids and steroid-sparing agents.^1,5 On the other hand, more limited presentations of PV may be suitable for intralesional treatment with triamcinolone acetonide, thus avoiding potential adverse effects of systemic therapy.^1,2 In our case with localized involvement, a favorable response was obtained with intralesional triamcinolone acetonide, and we plan to utilize systemic corticosteroids if the disease becomes generalized during follow-up.

The Diagnosis: Pemphigus Vegetans

A punch biopsy was taken from the verrucous plaque, and microscopic examination demonstrated prominent epidermal hyperplasia with intraepidermal eosinophilic microabscesses and a superficial dermatitis with abundant eosinophils (Figure 1A). Suprabasal acantholytic cleft formation was noted in a focal area (Figure 1B). Another punch biopsy was performed from the perilesional skin for direct immunofluorescence examination, which revealed intercellular deposits of IgG and C3 throughout the lower half of the epidermis (Figure 1C). Indirect immunofluorescence performed on monkey esophagus substrate showed circulating intercellular IgG antibodies in all the titers of up to 1/160 and an elevated level of IgG antidesmoglein 3 (anti-Dsg3) antibody (enzyme-linked immunosorbent assay index value, >200 RU/mL [reference range, <20 RU/mL]).

Because there was a solitary lesion, the decision was made to perform local treatment. One intralesional triamcinolone acetonide injection (20 mg/mL) resulted in remarkable flattening of the lesion (Figure 2). Subsequently, treatment was continued with clobetasol propionate ointment 3 times weekly for 1 month. During a follow-up period of 2 years, no signs of local relapse or new lesions elsewhere were noted, and the patient continued to be on long-term longitudinal evaluation.

Pemphigus vegetans (PV) is an uncommon variant of pemphigus, typically manifesting with vegetating erosions and plaques localized to the intertriginous areas of the body. Local factors such as semiocclusion, maceration, and/or bacterial or fungal colonization have been hypothesized to account for the distinctive localization and vegetation of the lesions.^1,2 Traditionally, 2 clinical subtypes of PV have been described: (1) Hallopeau type presenting with pustules that later evolve into vegetating plaques, and (2) Neumann type that initially manifests as vesicles and bullae with a more disseminated distribution, transforming into hypertrophic masses with erosions.^1-5 However, this distinction may not always be clear, and patients with features of both forms have been reported.^2,5

At present, our case would best be regarded as a localized form of PV presenting with a solitary lesion. It may progress to more disseminated disease or remain localized during its course; the literature contains reports exemplifying both possibilities. In a large retrospective study from Tunisia encompassing almost 3 decades, the majority of the patients initially presented with unifocal involvement; however, the disease eventually became multifocal in almost all patients during the study period, emphasizing the need for long-term follow-up.² There also are reports of PV confined to a single anatomic site, such as the scalp, sole, or vulva, that remained localized for years.^2,4,6,7 Involvement of the oral mucosa is an important finding of PV and the presenting concern in approximately three-quarters of patients.² Interestingly, the oral mucosa was not involved in our patient despite the high titer of anti-Dsg3 antibody, which suggests the need for the presence of other factors for clinical expression of the disease.

Although PV is considered a vegetating clinicomorphologic variant of pemphigus vulgaris, PV is histopathologically distinguished from pemphigus vulgaris by the presence of epidermal hyperplasia and intraepidermal eosinophilic microabscesses. Importantly, the epidermis displays signs of exuberant proliferation such as pseudoepitheliomatous hyperplasia and/or papillomatosis of a varying degree.^1,2,5 Of note, suprabasal acantholysis is usually overshadowed by the changes in PV and presents only focally, as in our patient. The most common autoantibody profile is IgG targeting Dsg3; however, a spectrum of other autoantibodies has been identified, such as IgG antidesmocollin 3, IgA anti-Dsg3, and IgG anti-Dsg1.^8,9

The most important differential diagnosis of PV is pyodermatitis-pyostomatitis vegetans. These 2 entities share many clinical and histopathological features; however, direct immunofluorescence is helpfulfor differentiation because it generally is negative in pyodermatitis-pyostomatitis vegetans.^2,10 Furthermore, there is a well-established association between pyodermatitis-pyostomatitis vegetans and inflammatory bowel disorders, whereas PV has anecdotally been linked to malignancy, human immunodeficiency virus infection, and heroin abuse.^1,2,10 Our patient was seronegative for human immunodeficiency virus and denied weight loss or loss of appetite. For those cases of PV involving a single anatomic site, the differential diagnosis is broader and encompasses dermatoses such as verrucae, syphilitic chancre, condylomata lata, granuloma inguinale, herpes simplex virus infection, and Kaposi sarcoma.

Treatment of PV is similar to pemphigus vulgaris and consists of a combination of systemic corticosteroids and steroid-sparing agents.^1,5 On the other hand, more limited presentations of PV may be suitable for intralesional treatment with triamcinolone acetonide, thus avoiding potential adverse effects of systemic therapy.^1,2 In our case with localized involvement, a favorable response was obtained with intralesional triamcinolone acetonide, and we plan to utilize systemic corticosteroids if the disease becomes generalized during follow-up.

The Diagnosis: Pemphigus Vegetans

A punch biopsy was taken from the verrucous plaque, and microscopic examination demonstrated prominent epidermal hyperplasia with intraepidermal eosinophilic microabscesses and a superficial dermatitis with abundant eosinophils (Figure 1A). Suprabasal acantholytic cleft formation was noted in a focal area (Figure 1B). Another punch biopsy was performed from the perilesional skin for direct immunofluorescence examination, which revealed intercellular deposits of IgG and C3 throughout the lower half of the epidermis (Figure 1C). Indirect immunofluorescence performed on monkey esophagus substrate showed circulating intercellular IgG antibodies in all the titers of up to 1/160 and an elevated level of IgG antidesmoglein 3 (anti-Dsg3) antibody (enzyme-linked immunosorbent assay index value, >200 RU/mL [reference range, <20 RU/mL]).

Because there was a solitary lesion, the decision was made to perform local treatment. One intralesional triamcinolone acetonide injection (20 mg/mL) resulted in remarkable flattening of the lesion (Figure 2). Subsequently, treatment was continued with clobetasol propionate ointment 3 times weekly for 1 month. During a follow-up period of 2 years, no signs of local relapse or new lesions elsewhere were noted, and the patient continued to be on long-term longitudinal evaluation.

Pemphigus vegetans (PV) is an uncommon variant of pemphigus, typically manifesting with vegetating erosions and plaques localized to the intertriginous areas of the body. Local factors such as semiocclusion, maceration, and/or bacterial or fungal colonization have been hypothesized to account for the distinctive localization and vegetation of the lesions.^1,2 Traditionally, 2 clinical subtypes of PV have been described: (1) Hallopeau type presenting with pustules that later evolve into vegetating plaques, and (2) Neumann type that initially manifests as vesicles and bullae with a more disseminated distribution, transforming into hypertrophic masses with erosions.^1-5 However, this distinction may not always be clear, and patients with features of both forms have been reported.^2,5

At present, our case would best be regarded as a localized form of PV presenting with a solitary lesion. It may progress to more disseminated disease or remain localized during its course; the literature contains reports exemplifying both possibilities. In a large retrospective study from Tunisia encompassing almost 3 decades, the majority of the patients initially presented with unifocal involvement; however, the disease eventually became multifocal in almost all patients during the study period, emphasizing the need for long-term follow-up.² There also are reports of PV confined to a single anatomic site, such as the scalp, sole, or vulva, that remained localized for years.^2,4,6,7 Involvement of the oral mucosa is an important finding of PV and the presenting concern in approximately three-quarters of patients.² Interestingly, the oral mucosa was not involved in our patient despite the high titer of anti-Dsg3 antibody, which suggests the need for the presence of other factors for clinical expression of the disease.

Although PV is considered a vegetating clinicomorphologic variant of pemphigus vulgaris, PV is histopathologically distinguished from pemphigus vulgaris by the presence of epidermal hyperplasia and intraepidermal eosinophilic microabscesses. Importantly, the epidermis displays signs of exuberant proliferation such as pseudoepitheliomatous hyperplasia and/or papillomatosis of a varying degree.^1,2,5 Of note, suprabasal acantholysis is usually overshadowed by the changes in PV and presents only focally, as in our patient. The most common autoantibody profile is IgG targeting Dsg3; however, a spectrum of other autoantibodies has been identified, such as IgG antidesmocollin 3, IgA anti-Dsg3, and IgG anti-Dsg1.^8,9

The most important differential diagnosis of PV is pyodermatitis-pyostomatitis vegetans. These 2 entities share many clinical and histopathological features; however, direct immunofluorescence is helpfulfor differentiation because it generally is negative in pyodermatitis-pyostomatitis vegetans.^2,10 Furthermore, there is a well-established association between pyodermatitis-pyostomatitis vegetans and inflammatory bowel disorders, whereas PV has anecdotally been linked to malignancy, human immunodeficiency virus infection, and heroin abuse.^1,2,10 Our patient was seronegative for human immunodeficiency virus and denied weight loss or loss of appetite. For those cases of PV involving a single anatomic site, the differential diagnosis is broader and encompasses dermatoses such as verrucae, syphilitic chancre, condylomata lata, granuloma inguinale, herpes simplex virus infection, and Kaposi sarcoma.

Treatment of PV is similar to pemphigus vulgaris and consists of a combination of systemic corticosteroids and steroid-sparing agents.^1,5 On the other hand, more limited presentations of PV may be suitable for intralesional treatment with triamcinolone acetonide, thus avoiding potential adverse effects of systemic therapy.^1,2 In our case with localized involvement, a favorable response was obtained with intralesional triamcinolone acetonide, and we plan to utilize systemic corticosteroids if the disease becomes generalized during follow-up.

The Diagnosis: Trichotillomania

A scalp punch biopsy revealed pigmented hair casts, an increase in catagen and telogen follicles, and a lack of perifollicular inflammation (Figure). Based on the clinical and histopathological findings, a diagnosis of trichotillomania (TTM) was established.

Trichotillomania is a hairpulling disorder with notable dermatologic and psychiatric overlap. Although previously considered an impulse control disorder, the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) reclassified it within obsessive-compulsive and related disorders, which also include body dysmorphic disorder and excoriation (skin-picking) disorder. Diagnostic criteria for TTM include the following: the patient must have recurrent pulling out of his/her hair resulting in hair loss despite repeated attempts to stop; underlying medical conditions and other psychiatric diagnoses must be excluded; and the patient must experience distress or impairment in social, occupational, or other areas of functioning from the hairpulling.¹ Trichotillomania mainly occurs in children and young adults, with a lifetime prevalence of approximately 1% to 2%.² The coexistence of a mood or anxiety disorder is common, as seen in our patient.

The diagnosis of TTM requires strong clinical suspicion because patients and their parents/guardians usually deny hairpulling. The main clinical differential diagnosis often is alopecia areata (AA) because both conditions can present as well-defined patches of nonscarring hair loss. Trichoscopy provides an invaluable noninvasive diagnostic tool that can be particularly useful in pediatric patients who may be reluctant to have a scalp biopsy. There are many overlapping trichoscopic findings of TTM and AA, including yellow dots, black dots, broken hairs, coiled hairs, and exclamation mark hairs.³ More specific trichoscopy findings for TTM include flame hairs (wavy proximal hair residue), V-sign (2 shafts within 1 follicle broken at the same length), and tulip hairs (dark, tulip-shaped ends of broken hairs).⁴ Hair breakage of varying lengths and trichoptilosis (split ends) can be better visualized using trichoscopy and support a diagnosis of TTM over AA.

Androgenetic alopecia (female pattern hair loss) presents with gradual thinning around the part line of the frontal and parietal scalp with trichoscopy showing miniaturization of hairs and decreased follicle density. The moth-eaten-like appearance of alopecia due to secondary syphilis may mimic alopecia areata clinically, but serologic testing can confirm the diagnosis of syphilis. Telogen effluvium does not have the trichoscopic features that are seen in TTM and is clinically distinguished by hair shedding and a positive hair pull test.

Biopsy can provide objective yet nonspecific support for the diagnosis, demonstrating trichomalacia, pigmented hair casts, empty follicles, and an increase in catagen hairs with a lack of inflammation. Normal and damaged hair follicles may be seen in close proximity, and hemorrhage may be seen secondary to trauma. Pigmented hair casts are not specific to TTM and are present in other traumatic hair disorders, such as traction alopecia; therefore, clinical correlation is essential for diagnosis.

Habit reversal training is the most effective treatment of TTM and involves 3 major components: awareness training with self-monitoring, stimulus control, and competing response procedures.⁵ Although numerous pharmacotherapies have been reported as effective treatments for TTM, a 2013 Cochrane review of 8 randomized controlled trials concluded that no medication has demonstrated reliable efficacy. Reported therapies included selective serotonin reuptake inhibitors, naltrexone, olanzapine, N-acetylcysteine, and clomipramine.⁶

The Diagnosis: Trichotillomania

A scalp punch biopsy revealed pigmented hair casts, an increase in catagen and telogen follicles, and a lack of perifollicular inflammation (Figure). Based on the clinical and histopathological findings, a diagnosis of trichotillomania (TTM) was established.

Trichotillomania is a hairpulling disorder with notable dermatologic and psychiatric overlap. Although previously considered an impulse control disorder, the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) reclassified it within obsessive-compulsive and related disorders, which also include body dysmorphic disorder and excoriation (skin-picking) disorder. Diagnostic criteria for TTM include the following: the patient must have recurrent pulling out of his/her hair resulting in hair loss despite repeated attempts to stop; underlying medical conditions and other psychiatric diagnoses must be excluded; and the patient must experience distress or impairment in social, occupational, or other areas of functioning from the hairpulling.¹ Trichotillomania mainly occurs in children and young adults, with a lifetime prevalence of approximately 1% to 2%.² The coexistence of a mood or anxiety disorder is common, as seen in our patient.

The diagnosis of TTM requires strong clinical suspicion because patients and their parents/guardians usually deny hairpulling. The main clinical differential diagnosis often is alopecia areata (AA) because both conditions can present as well-defined patches of nonscarring hair loss. Trichoscopy provides an invaluable noninvasive diagnostic tool that can be particularly useful in pediatric patients who may be reluctant to have a scalp biopsy. There are many overlapping trichoscopic findings of TTM and AA, including yellow dots, black dots, broken hairs, coiled hairs, and exclamation mark hairs.³ More specific trichoscopy findings for TTM include flame hairs (wavy proximal hair residue), V-sign (2 shafts within 1 follicle broken at the same length), and tulip hairs (dark, tulip-shaped ends of broken hairs).⁴ Hair breakage of varying lengths and trichoptilosis (split ends) can be better visualized using trichoscopy and support a diagnosis of TTM over AA.

Androgenetic alopecia (female pattern hair loss) presents with gradual thinning around the part line of the frontal and parietal scalp with trichoscopy showing miniaturization of hairs and decreased follicle density. The moth-eaten-like appearance of alopecia due to secondary syphilis may mimic alopecia areata clinically, but serologic testing can confirm the diagnosis of syphilis. Telogen effluvium does not have the trichoscopic features that are seen in TTM and is clinically distinguished by hair shedding and a positive hair pull test.

Biopsy can provide objective yet nonspecific support for the diagnosis, demonstrating trichomalacia, pigmented hair casts, empty follicles, and an increase in catagen hairs with a lack of inflammation. Normal and damaged hair follicles may be seen in close proximity, and hemorrhage may be seen secondary to trauma. Pigmented hair casts are not specific to TTM and are present in other traumatic hair disorders, such as traction alopecia; therefore, clinical correlation is essential for diagnosis.

Habit reversal training is the most effective treatment of TTM and involves 3 major components: awareness training with self-monitoring, stimulus control, and competing response procedures.⁵ Although numerous pharmacotherapies have been reported as effective treatments for TTM, a 2013 Cochrane review of 8 randomized controlled trials concluded that no medication has demonstrated reliable efficacy. Reported therapies included selective serotonin reuptake inhibitors, naltrexone, olanzapine, N-acetylcysteine, and clomipramine.⁶

The Diagnosis: Trichotillomania

A scalp punch biopsy revealed pigmented hair casts, an increase in catagen and telogen follicles, and a lack of perifollicular inflammation (Figure). Based on the clinical and histopathological findings, a diagnosis of trichotillomania (TTM) was established.

Trichotillomania is a hairpulling disorder with notable dermatologic and psychiatric overlap. Although previously considered an impulse control disorder, the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) reclassified it within obsessive-compulsive and related disorders, which also include body dysmorphic disorder and excoriation (skin-picking) disorder. Diagnostic criteria for TTM include the following: the patient must have recurrent pulling out of his/her hair resulting in hair loss despite repeated attempts to stop; underlying medical conditions and other psychiatric diagnoses must be excluded; and the patient must experience distress or impairment in social, occupational, or other areas of functioning from the hairpulling.¹ Trichotillomania mainly occurs in children and young adults, with a lifetime prevalence of approximately 1% to 2%.² The coexistence of a mood or anxiety disorder is common, as seen in our patient.

The diagnosis of TTM requires strong clinical suspicion because patients and their parents/guardians usually deny hairpulling. The main clinical differential diagnosis often is alopecia areata (AA) because both conditions can present as well-defined patches of nonscarring hair loss. Trichoscopy provides an invaluable noninvasive diagnostic tool that can be particularly useful in pediatric patients who may be reluctant to have a scalp biopsy. There are many overlapping trichoscopic findings of TTM and AA, including yellow dots, black dots, broken hairs, coiled hairs, and exclamation mark hairs.³ More specific trichoscopy findings for TTM include flame hairs (wavy proximal hair residue), V-sign (2 shafts within 1 follicle broken at the same length), and tulip hairs (dark, tulip-shaped ends of broken hairs).⁴ Hair breakage of varying lengths and trichoptilosis (split ends) can be better visualized using trichoscopy and support a diagnosis of TTM over AA.

Androgenetic alopecia (female pattern hair loss) presents with gradual thinning around the part line of the frontal and parietal scalp with trichoscopy showing miniaturization of hairs and decreased follicle density. The moth-eaten-like appearance of alopecia due to secondary syphilis may mimic alopecia areata clinically, but serologic testing can confirm the diagnosis of syphilis. Telogen effluvium does not have the trichoscopic features that are seen in TTM and is clinically distinguished by hair shedding and a positive hair pull test.

Biopsy can provide objective yet nonspecific support for the diagnosis, demonstrating trichomalacia, pigmented hair casts, empty follicles, and an increase in catagen hairs with a lack of inflammation. Normal and damaged hair follicles may be seen in close proximity, and hemorrhage may be seen secondary to trauma. Pigmented hair casts are not specific to TTM and are present in other traumatic hair disorders, such as traction alopecia; therefore, clinical correlation is essential for diagnosis.

Habit reversal training is the most effective treatment of TTM and involves 3 major components: awareness training with self-monitoring, stimulus control, and competing response procedures.⁵ Although numerous pharmacotherapies have been reported as effective treatments for TTM, a 2013 Cochrane review of 8 randomized controlled trials concluded that no medication has demonstrated reliable efficacy. Reported therapies included selective serotonin reuptake inhibitors, naltrexone, olanzapine, N-acetylcysteine, and clomipramine.⁶

The Diagnosis: Terra Firma-Forme Dermatosis

Terra firma-forme dermatosis (TFFD), also known as Duncan dirty dermatosis, is an idiopathic benign cutaneous condition that is easily misdiagnosed or mismanaged. In 1987, Duncan et al1 first described the condition in children who had mothers that lamented over dirty skin spots that could not be washed off. The term terra firma translates in Latin to solid ground, which describes the characteristic dirtlike appearance of these lesions.

Terra firma-forme dermatosis most commonly affects children and young adults, though it can present in patients of any age without any known predisposing risk factors.^1-4 The lesions have a predilection for the face, neck, shoulders, trunk, and ankles. Terra firma-forme dermatosis has no association with bathing and hygiene habits, and most patients describe unsuccessful removal of the lesions, even after vigorous scrubbing with soaps and detergents at home. The lesions are asymptomatic, and many patients present to dermatology for cosmetic concerns.^1-8

The etiology of TFFD is not well understood and is considered a retention hyperkeratosis. Duncan et al¹ postulated that TFFD is the result of partial or improper maturation of keratinocytes leading to keratinocyte and melanin retention. Hematoxylin and eosin stains demonstrate lamellar hyperkeratosis of the stratum corneum without parakeratosis as well as keratin pearls scattered throughout. Mild acanthosis and papillomatosis also have been reported.^1,5-7 Fontana-Masson stain shows excess melanin in these lesions, extending from the basal layer to the stratum corneum. Fungal and bacterial stains as well as cultures often have no notable findings.^1,7 Similarly, histopathologic examination of our patient's biopsy with hematoxylin and eosin stain revealed hyperorthokeratosis with scattered naked vellus hair shafts and incidental yeast forms (Figure 1).

The differential diagnosis for TFFD may include pityriasis versicolor, confluent and reticulated papillomatosis, acanthosis nigricans, ichthyosis, malignant melanoma, and seborrheic keratosis. All of these diagnoses can be ruled out by the easy removal of the lesions with isopropyl alcohol 70%, which was performed on our patient by scrubbing the lesions with soaked gauze (Figure 2). Indeed, removal with isopropyl alcohol 70% is both the therapeutic and diagnostic procedure for TFFD.^1-8 Of note, dermatitis neglecta is histologically and clinically identical to TFFD, albeit with a history of uncleanly habits or exposure to dirty environments.

The diagnosis of TFFD often is discovered incidentally as physicians wipe the area with alcohol to prepare for biopsy.¹ Occasionally, vigorous scrubbing is needed to completely remove the lesions, and without this effort the lesions may be easily mistaken for another cutaneous process.³ Failure to consider TFFD as a diagnosis has led to unnecessary endocrine workups and invasive biopsies.⁴ Therefore, physicians should have early clinical suspicion of TFFD and be aware of the bedside diagnostic procedure using isopropyl alcohol.

The Diagnosis: Terra Firma-Forme Dermatosis

Terra firma-forme dermatosis (TFFD), also known as Duncan dirty dermatosis, is an idiopathic benign cutaneous condition that is easily misdiagnosed or mismanaged. In 1987, Duncan et al1 first described the condition in children who had mothers that lamented over dirty skin spots that could not be washed off. The term terra firma translates in Latin to solid ground, which describes the characteristic dirtlike appearance of these lesions.

Terra firma-forme dermatosis most commonly affects children and young adults, though it can present in patients of any age without any known predisposing risk factors.^1-4 The lesions have a predilection for the face, neck, shoulders, trunk, and ankles. Terra firma-forme dermatosis has no association with bathing and hygiene habits, and most patients describe unsuccessful removal of the lesions, even after vigorous scrubbing with soaps and detergents at home. The lesions are asymptomatic, and many patients present to dermatology for cosmetic concerns.^1-8

The etiology of TFFD is not well understood and is considered a retention hyperkeratosis. Duncan et al¹ postulated that TFFD is the result of partial or improper maturation of keratinocytes leading to keratinocyte and melanin retention. Hematoxylin and eosin stains demonstrate lamellar hyperkeratosis of the stratum corneum without parakeratosis as well as keratin pearls scattered throughout. Mild acanthosis and papillomatosis also have been reported.^1,5-7 Fontana-Masson stain shows excess melanin in these lesions, extending from the basal layer to the stratum corneum. Fungal and bacterial stains as well as cultures often have no notable findings.^1,7 Similarly, histopathologic examination of our patient's biopsy with hematoxylin and eosin stain revealed hyperorthokeratosis with scattered naked vellus hair shafts and incidental yeast forms (Figure 1).

The differential diagnosis for TFFD may include pityriasis versicolor, confluent and reticulated papillomatosis, acanthosis nigricans, ichthyosis, malignant melanoma, and seborrheic keratosis. All of these diagnoses can be ruled out by the easy removal of the lesions with isopropyl alcohol 70%, which was performed on our patient by scrubbing the lesions with soaked gauze (Figure 2). Indeed, removal with isopropyl alcohol 70% is both the therapeutic and diagnostic procedure for TFFD.^1-8 Of note, dermatitis neglecta is histologically and clinically identical to TFFD, albeit with a history of uncleanly habits or exposure to dirty environments.

The diagnosis of TFFD often is discovered incidentally as physicians wipe the area with alcohol to prepare for biopsy.¹ Occasionally, vigorous scrubbing is needed to completely remove the lesions, and without this effort the lesions may be easily mistaken for another cutaneous process.³ Failure to consider TFFD as a diagnosis has led to unnecessary endocrine workups and invasive biopsies.⁴ Therefore, physicians should have early clinical suspicion of TFFD and be aware of the bedside diagnostic procedure using isopropyl alcohol.

The Diagnosis: Terra Firma-Forme Dermatosis

Terra firma-forme dermatosis (TFFD), also known as Duncan dirty dermatosis, is an idiopathic benign cutaneous condition that is easily misdiagnosed or mismanaged. In 1987, Duncan et al1 first described the condition in children who had mothers that lamented over dirty skin spots that could not be washed off. The term terra firma translates in Latin to solid ground, which describes the characteristic dirtlike appearance of these lesions.

Terra firma-forme dermatosis most commonly affects children and young adults, though it can present in patients of any age without any known predisposing risk factors.^1-4 The lesions have a predilection for the face, neck, shoulders, trunk, and ankles. Terra firma-forme dermatosis has no association with bathing and hygiene habits, and most patients describe unsuccessful removal of the lesions, even after vigorous scrubbing with soaps and detergents at home. The lesions are asymptomatic, and many patients present to dermatology for cosmetic concerns.^1-8

The etiology of TFFD is not well understood and is considered a retention hyperkeratosis. Duncan et al¹ postulated that TFFD is the result of partial or improper maturation of keratinocytes leading to keratinocyte and melanin retention. Hematoxylin and eosin stains demonstrate lamellar hyperkeratosis of the stratum corneum without parakeratosis as well as keratin pearls scattered throughout. Mild acanthosis and papillomatosis also have been reported.^1,5-7 Fontana-Masson stain shows excess melanin in these lesions, extending from the basal layer to the stratum corneum. Fungal and bacterial stains as well as cultures often have no notable findings.^1,7 Similarly, histopathologic examination of our patient's biopsy with hematoxylin and eosin stain revealed hyperorthokeratosis with scattered naked vellus hair shafts and incidental yeast forms (Figure 1).

The differential diagnosis for TFFD may include pityriasis versicolor, confluent and reticulated papillomatosis, acanthosis nigricans, ichthyosis, malignant melanoma, and seborrheic keratosis. All of these diagnoses can be ruled out by the easy removal of the lesions with isopropyl alcohol 70%, which was performed on our patient by scrubbing the lesions with soaked gauze (Figure 2). Indeed, removal with isopropyl alcohol 70% is both the therapeutic and diagnostic procedure for TFFD.^1-8 Of note, dermatitis neglecta is histologically and clinically identical to TFFD, albeit with a history of uncleanly habits or exposure to dirty environments.

The diagnosis of TFFD often is discovered incidentally as physicians wipe the area with alcohol to prepare for biopsy.¹ Occasionally, vigorous scrubbing is needed to completely remove the lesions, and without this effort the lesions may be easily mistaken for another cutaneous process.³ Failure to consider TFFD as a diagnosis has led to unnecessary endocrine workups and invasive biopsies.⁴ Therefore, physicians should have early clinical suspicion of TFFD and be aware of the bedside diagnostic procedure using isopropyl alcohol.

The Diagnosis: Chromomycosis

Skin scrapings revealed brownish sclerotic bodies. A review of the skin biopsy performed 4 years prior showed florid pseudoepitheliomatous hyperplasia overlying dense mixed inflammatory infiltrates of predominantly granulomatous microabscesses in the dermis. Numerous sclerotic bodies were evident within multinucleated giant cells and scattered among epidermal and dermal microabscesses (Figure). Few atypical basal keratinocytes were noted, but frank pleomorphism and aberrant mitosis was absent.

Chromomycosis is a chronic subcutaneous fungal infection caused by pigmented (dematiaceous) fungi growing in soil, decaying vegetables, and rotting wood. Infection usually occurs via traumatic inoculation from splinters and thorns. Some of the agents responsible include Fonsecaea pedrosoi, Cladophialophora carrionii, and Phialophora verrucosa.¹

Diverse cutaneous manifestations have been observed with 5 different clinical forms: nodules, verrucous hyperkeratotic plaques, cicatricial lesions with central sparing, scaly plaques, and tumoral (cauliflowerlike) lesions.² Of these clinical presentations, verrucous hyperkeratotic plaques are the most common, as seen in our patient. However, this presentation is not exclusive to chromomycosis because many conditions appear similarly, including sporotrichosis, nontuberculous mycobacterial infection, tuberculosis verrucosa cutis, and squamous cell carcinoma (SCC). The presence of small ulcerations may appear as the black dots seen on the plaques of chromomycosis, distinguishing chromomycosis from other conditions. Although this feature may be a fundamental clue for diagnosis, it should be emphasized that in many occasions, clinical differences between chromomycosis and its differentials are subtle. A study involving 9 patients with chromomycosis reported that only 1 was given the initial diagnosis of mycosis. Six patients initially were diagnosed with cutaneous malignancies, 1 patient with viral warts, and another patient with ganglion.³ Therefore, unless there is a high index of suspicion, these conditions may easily be mistaken for others by clinicians who are unfamiliar with their presentations, particularly in the setting of a busy clinic.

Chromomycosis routinely is diagnosed based on histologic examination and culture. Apart from sclerotic bodies, other histopathologic features include an inflammatory infiltrate characterized by neutrophilic microabscesses, multinucleated cells, fibrosis, acanthosis, papillomatosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia (PEH).² Pseudoepitheliomatous hyperplasia is an exaggerated proliferation of the epidermis, usually secondary to chronic inflammatory skin conditions.⁴ Because most verrucous lesions are thought to be neoplastic and carcinomas more commonly are seen and expected in dermatopathology, PEH can sometimes be mistaken for SCC. At times, the squamous epithelium of PEH can appear infiltrative, giving the illusion of well-differentiated SCC.⁵ However, absence of marked cellular atypia and abnormal mitotic activity should suggest otherwise. Thorough scrutiny for a concomitant infective process is necessary to avoid the overdiagnosis of SCC. Special stains for infectious agents such as periodic acid-Schiff and Grocott-Gomori methenamine-silver for fungal spores and Ziehl-Neelsen for acid-fast bacilli may reveal infectious organisms. Multilevel sections of deeper levels also may be essential to uncover sparse organisms.⁶

There is no standard treatment of chromomycosis. Some treatment options are available based on few open clinical studies and expert opinions. Systemic antifungals such as itraconazole or terbinafine most commonly are used with 15% to 80% cure rates.⁷ In invasive refractory cases, a combination of itraconazole and terbinafine has been employed as salvage therapy. Recently, the use of newer azoles such as posaconazole is favored due to its expanded-spectrum profile along with better pharmacodynamics and pharmacokinetic profile versus itraconazole. Physical methods such as cryotherapy, heat therapy, laser therapy, and photodynamic therapy frequently are practiced in conjunction with systemic antifungal therapy.⁸ Surgical procedures such as photocoagulation, Mohs micrographic surgery, and curettage sometimes are recommended for smaller well-defined lesions. Amputation, however, is rarely ever indicated, as there rarely is deep tissue involvement.²

Our case highlights the importance of clinicopathologic correlation in diagnosing squamous epithelial lesions. A high index of clinical suspicion and a wider list of differential diagnoses of verrucous plaques are necessary to minimize pitfalls in diagnosing lesions with squamous proliferation and therefore reduces the need for unnecessary interventions.

The Diagnosis: Chromomycosis

Skin scrapings revealed brownish sclerotic bodies. A review of the skin biopsy performed 4 years prior showed florid pseudoepitheliomatous hyperplasia overlying dense mixed inflammatory infiltrates of predominantly granulomatous microabscesses in the dermis. Numerous sclerotic bodies were evident within multinucleated giant cells and scattered among epidermal and dermal microabscesses (Figure). Few atypical basal keratinocytes were noted, but frank pleomorphism and aberrant mitosis was absent.

Chromomycosis is a chronic subcutaneous fungal infection caused by pigmented (dematiaceous) fungi growing in soil, decaying vegetables, and rotting wood. Infection usually occurs via traumatic inoculation from splinters and thorns. Some of the agents responsible include Fonsecaea pedrosoi, Cladophialophora carrionii, and Phialophora verrucosa.¹

Diverse cutaneous manifestations have been observed with 5 different clinical forms: nodules, verrucous hyperkeratotic plaques, cicatricial lesions with central sparing, scaly plaques, and tumoral (cauliflowerlike) lesions.² Of these clinical presentations, verrucous hyperkeratotic plaques are the most common, as seen in our patient. However, this presentation is not exclusive to chromomycosis because many conditions appear similarly, including sporotrichosis, nontuberculous mycobacterial infection, tuberculosis verrucosa cutis, and squamous cell carcinoma (SCC). The presence of small ulcerations may appear as the black dots seen on the plaques of chromomycosis, distinguishing chromomycosis from other conditions. Although this feature may be a fundamental clue for diagnosis, it should be emphasized that in many occasions, clinical differences between chromomycosis and its differentials are subtle. A study involving 9 patients with chromomycosis reported that only 1 was given the initial diagnosis of mycosis. Six patients initially were diagnosed with cutaneous malignancies, 1 patient with viral warts, and another patient with ganglion.³ Therefore, unless there is a high index of suspicion, these conditions may easily be mistaken for others by clinicians who are unfamiliar with their presentations, particularly in the setting of a busy clinic.

Chromomycosis routinely is diagnosed based on histologic examination and culture. Apart from sclerotic bodies, other histopathologic features include an inflammatory infiltrate characterized by neutrophilic microabscesses, multinucleated cells, fibrosis, acanthosis, papillomatosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia (PEH).² Pseudoepitheliomatous hyperplasia is an exaggerated proliferation of the epidermis, usually secondary to chronic inflammatory skin conditions.⁴ Because most verrucous lesions are thought to be neoplastic and carcinomas more commonly are seen and expected in dermatopathology, PEH can sometimes be mistaken for SCC. At times, the squamous epithelium of PEH can appear infiltrative, giving the illusion of well-differentiated SCC.⁵ However, absence of marked cellular atypia and abnormal mitotic activity should suggest otherwise. Thorough scrutiny for a concomitant infective process is necessary to avoid the overdiagnosis of SCC. Special stains for infectious agents such as periodic acid-Schiff and Grocott-Gomori methenamine-silver for fungal spores and Ziehl-Neelsen for acid-fast bacilli may reveal infectious organisms. Multilevel sections of deeper levels also may be essential to uncover sparse organisms.⁶

There is no standard treatment of chromomycosis. Some treatment options are available based on few open clinical studies and expert opinions. Systemic antifungals such as itraconazole or terbinafine most commonly are used with 15% to 80% cure rates.⁷ In invasive refractory cases, a combination of itraconazole and terbinafine has been employed as salvage therapy. Recently, the use of newer azoles such as posaconazole is favored due to its expanded-spectrum profile along with better pharmacodynamics and pharmacokinetic profile versus itraconazole. Physical methods such as cryotherapy, heat therapy, laser therapy, and photodynamic therapy frequently are practiced in conjunction with systemic antifungal therapy.⁸ Surgical procedures such as photocoagulation, Mohs micrographic surgery, and curettage sometimes are recommended for smaller well-defined lesions. Amputation, however, is rarely ever indicated, as there rarely is deep tissue involvement.²

Our case highlights the importance of clinicopathologic correlation in diagnosing squamous epithelial lesions. A high index of clinical suspicion and a wider list of differential diagnoses of verrucous plaques are necessary to minimize pitfalls in diagnosing lesions with squamous proliferation and therefore reduces the need for unnecessary interventions.

The Diagnosis: Chromomycosis

Skin scrapings revealed brownish sclerotic bodies. A review of the skin biopsy performed 4 years prior showed florid pseudoepitheliomatous hyperplasia overlying dense mixed inflammatory infiltrates of predominantly granulomatous microabscesses in the dermis. Numerous sclerotic bodies were evident within multinucleated giant cells and scattered among epidermal and dermal microabscesses (Figure). Few atypical basal keratinocytes were noted, but frank pleomorphism and aberrant mitosis was absent.

Chromomycosis is a chronic subcutaneous fungal infection caused by pigmented (dematiaceous) fungi growing in soil, decaying vegetables, and rotting wood. Infection usually occurs via traumatic inoculation from splinters and thorns. Some of the agents responsible include Fonsecaea pedrosoi, Cladophialophora carrionii, and Phialophora verrucosa.¹

Diverse cutaneous manifestations have been observed with 5 different clinical forms: nodules, verrucous hyperkeratotic plaques, cicatricial lesions with central sparing, scaly plaques, and tumoral (cauliflowerlike) lesions.² Of these clinical presentations, verrucous hyperkeratotic plaques are the most common, as seen in our patient. However, this presentation is not exclusive to chromomycosis because many conditions appear similarly, including sporotrichosis, nontuberculous mycobacterial infection, tuberculosis verrucosa cutis, and squamous cell carcinoma (SCC). The presence of small ulcerations may appear as the black dots seen on the plaques of chromomycosis, distinguishing chromomycosis from other conditions. Although this feature may be a fundamental clue for diagnosis, it should be emphasized that in many occasions, clinical differences between chromomycosis and its differentials are subtle. A study involving 9 patients with chromomycosis reported that only 1 was given the initial diagnosis of mycosis. Six patients initially were diagnosed with cutaneous malignancies, 1 patient with viral warts, and another patient with ganglion.³ Therefore, unless there is a high index of suspicion, these conditions may easily be mistaken for others by clinicians who are unfamiliar with their presentations, particularly in the setting of a busy clinic.

Chromomycosis routinely is diagnosed based on histologic examination and culture. Apart from sclerotic bodies, other histopathologic features include an inflammatory infiltrate characterized by neutrophilic microabscesses, multinucleated cells, fibrosis, acanthosis, papillomatosis, hyperkeratosis, and pseudoepitheliomatous hyperplasia (PEH).² Pseudoepitheliomatous hyperplasia is an exaggerated proliferation of the epidermis, usually secondary to chronic inflammatory skin conditions.⁴ Because most verrucous lesions are thought to be neoplastic and carcinomas more commonly are seen and expected in dermatopathology, PEH can sometimes be mistaken for SCC. At times, the squamous epithelium of PEH can appear infiltrative, giving the illusion of well-differentiated SCC.⁵ However, absence of marked cellular atypia and abnormal mitotic activity should suggest otherwise. Thorough scrutiny for a concomitant infective process is necessary to avoid the overdiagnosis of SCC. Special stains for infectious agents such as periodic acid-Schiff and Grocott-Gomori methenamine-silver for fungal spores and Ziehl-Neelsen for acid-fast bacilli may reveal infectious organisms. Multilevel sections of deeper levels also may be essential to uncover sparse organisms.⁶

There is no standard treatment of chromomycosis. Some treatment options are available based on few open clinical studies and expert opinions. Systemic antifungals such as itraconazole or terbinafine most commonly are used with 15% to 80% cure rates.⁷ In invasive refractory cases, a combination of itraconazole and terbinafine has been employed as salvage therapy. Recently, the use of newer azoles such as posaconazole is favored due to its expanded-spectrum profile along with better pharmacodynamics and pharmacokinetic profile versus itraconazole. Physical methods such as cryotherapy, heat therapy, laser therapy, and photodynamic therapy frequently are practiced in conjunction with systemic antifungal therapy.⁸ Surgical procedures such as photocoagulation, Mohs micrographic surgery, and curettage sometimes are recommended for smaller well-defined lesions. Amputation, however, is rarely ever indicated, as there rarely is deep tissue involvement.²

Our case highlights the importance of clinicopathologic correlation in diagnosing squamous epithelial lesions. A high index of clinical suspicion and a wider list of differential diagnoses of verrucous plaques are necessary to minimize pitfalls in diagnosing lesions with squamous proliferation and therefore reduces the need for unnecessary interventions.

The Diagnosis: Herpes Simplex Virus Infection

Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.

Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.¹ Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.² This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.^1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.⁶ Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.^7-10

Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.

Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.^1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.^3,5,6,11

The Diagnosis: Herpes Simplex Virus Infection

Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.

Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.¹ Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.² This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.^1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.⁶ Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.^7-10

Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.

Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.^1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.^3,5,6,11

The Diagnosis: Herpes Simplex Virus Infection

Viral culture of the ulcer was positive for herpes simplex virus type 2 (HHV-2). Bacterial culture grew enteric flora. The patient was started on intravenous acyclovir 5 mg/kg every 8 hours for 7 days and then transitioned to oral acyclovir for chronic suppressive therapy. One month later, there was near-complete reepithelialization with 2 remaining 1-cm shallow ulcers. The verrucous lesions had dried up and were flaking off (Figure). At 6-month follow-up, the ulcers and verrucous lesions had completely resolved.

Herpes simplex virus type 2 is the most common cause of genital and perianal ulcers in immunocompromised individuals.¹ Patients classically present with painful grouped vesicles followed by painful superficial ulcers that may rapidly progress to extensive confluent ulceration. A hypertrophic variant of genital herpes characterized by anogenital verrucous lesions, similar to condyloma acuminata, also can be seen in immunocompromised individuals.² This form has almost exclusively been observed in patients with human immunodeficiency virus and may occur in isolation or together with the ulcerative form.^1-5 A case of vegetative HHV infection of the genital area in a patient with common variable immunodeficiency has been reported.⁶ Verrucous lesions of the mouth secondary to HHV have been observed in Hodgkin lymphoma, acute myelogenous leukemia, and individuals on immunosuppressive medications.^7-10

Perianal involvement of Crohn disease typically presents with fistulas, ulcers, abscesses, strictures, and skin tags in some cases. Invasive squamous cell carcinoma may arise within a chronic ulcer of the anogenital area or may itself manifest as an ulcer or anal fissure. Perianal ulcerative skin tuberculosis has been reported in the literature as a rare manifestation of extrapulmonary tuberculosis and should be considered in a patient with an appropriate clinical history. Pyoderma gangrenosum classically pre-sents as a large ulcer with irregular rolled borders, though a rare variant of vegetative pyoderma gangrenosum may manifest as a nodular or verrucous plaque.

Studies to diagnose HHV include viral cell culture, HHV polymerase chain reaction testing, HHV serology, and direct fluorescent antibody testing. Skin biopsy may be necessary to rule out underlying malignancy. Treatment of perianal HHV infection includes acyclovir, valacyclovir, or famciclovir.^1,5,6 Hypertrophic lesions often are refractory to first-line antiviral therapy and may require surgical resection or treatment with alternative medications such as imiquimod, a topical immunomodulator.^3,5,6,11

The Diagnosis: Hailey-Hailey Disease (Benign Familial Chronic Pemphigus)

Our patient had a long-standing history of Hailey-Hailey disease, as confirmed by multiple prior skin biopsies at outside institutions as well as our affiliated site. He began treatment with oral doxycycline 50 mg twice daily for 2 weeks, triamcinolone cream 0.1% twice daily to the affected region, and aluminum acetate solution soaks and chlorhexidine wash daily along with petroleum jelly, which resulted in good control of the disease. The differential diagnosis of eroded plaques, particularly in the axillary, crural, and inframammary folds, is broad and includes candidiasis, inverse psoriasis, contact dermatitis, dermatophyte infection, pemphigus vegetans or foliaceus, and granular parakeratosis.

Hailey-Hailey disease is a genetic disorder with a prevalence of 1 in 50,000 individuals. Most patients develop symptoms during the second or third decades of life.1 Hailey-Hailey disease exhibits an autosomal-dominant pattern of inheritance secondary to mutation in the human ATP2C1 gene, which codes for the ATPase secretory pathway of the Ca²⁺ transporting pump type 1 (SPCA1) localized in the Golgi apparatus.² Altered SPCA1 protein reduces concentration of Ca²⁺ within the Golgi lumen, which in turn impairs the processing of junctional proteins needed for normal cell-to-cell adhesion.¹

Clinically, Hailey-Hailey disease is characterized by vesicular or erosive plaques that have a predilection for intertriginous areas of the body.¹ The primary lesions often are flaccid vesicles that easily rupture, leaving behind crusted erosions that spread peripherally. The lesions also can appear as macerated plaques resembling torn tissue paper, as in our case. Friction, heat, and sweat exacerbate the disease. Complications occur from secondary bacterial, fungal, and viral colonization. Malodor and vegetations can indicate bacterial or fungal infections and can lead to persistence of skin lesions. Herpes simplex virus infections can exacerbate preexisting lesions.³ Hailey-Hailey disease of the anogenital region also can be complicated by infection with oncogenic strains of human papillomavirus and lead to cutaneous squamous cell carcinoma.⁴

Hailey-Hailey disease histologically appears as suprabasal and intraepidermal keratinocyte acantholysis,⁵ which typically is widespread in the epidermis, with large areas of dyscohesion with a dilapidated brick wall-like appearance.¹ In more chronic lesions, epidermal hyperplasia, parakeratosis, and focal crusts may be observed. A moderate perivascular lymphocytic infiltrate can be observed in the superficial dermis. Direct immunofluorescence typically is negative.

Topical corticosteroids and antimicrobials are first-line therapies that often only provide temporary suppression. When the disease is refractory to topical therapies, intralesional corticosteroids may be attempted. There is no strong evidence to support the use of systemic therapy, aside from antimicrobial agents (eg, doxycycline) for the use of superinfections. In severe cases, immunomodulating therapies such as prednisone, cyclosporine, methotrexate, dapsone, alefacept, and oral retinoids may be effective.^6-8 Surgical therapy also can be considered for recalcitrant disease, including wide excision and grafting, though these techniques can be associated with morbidity.⁹

Superficial ablative techniques including dermabrasion, laser therapy with CO₂ and erbium-doped YAG, photodynamic therapy, and electron beam radiation have been shown to be effective modalities in severe cases.^5,9-11 It has been hypothesized that keratinocytes expressing the molecular defect are ablated, while the surrounding normal adnexal epithelium can regenerate normal epithelium. It also is thought that dermal fibrosis leads to better support of the diseased epidermis and decreases the risk for ulceration and fissuring.⁹

The Diagnosis: Hailey-Hailey Disease (Benign Familial Chronic Pemphigus)

Our patient had a long-standing history of Hailey-Hailey disease, as confirmed by multiple prior skin biopsies at outside institutions as well as our affiliated site. He began treatment with oral doxycycline 50 mg twice daily for 2 weeks, triamcinolone cream 0.1% twice daily to the affected region, and aluminum acetate solution soaks and chlorhexidine wash daily along with petroleum jelly, which resulted in good control of the disease. The differential diagnosis of eroded plaques, particularly in the axillary, crural, and inframammary folds, is broad and includes candidiasis, inverse psoriasis, contact dermatitis, dermatophyte infection, pemphigus vegetans or foliaceus, and granular parakeratosis.

Hailey-Hailey disease is a genetic disorder with a prevalence of 1 in 50,000 individuals. Most patients develop symptoms during the second or third decades of life.1 Hailey-Hailey disease exhibits an autosomal-dominant pattern of inheritance secondary to mutation in the human ATP2C1 gene, which codes for the ATPase secretory pathway of the Ca²⁺ transporting pump type 1 (SPCA1) localized in the Golgi apparatus.² Altered SPCA1 protein reduces concentration of Ca²⁺ within the Golgi lumen, which in turn impairs the processing of junctional proteins needed for normal cell-to-cell adhesion.¹

Clinically, Hailey-Hailey disease is characterized by vesicular or erosive plaques that have a predilection for intertriginous areas of the body.¹ The primary lesions often are flaccid vesicles that easily rupture, leaving behind crusted erosions that spread peripherally. The lesions also can appear as macerated plaques resembling torn tissue paper, as in our case. Friction, heat, and sweat exacerbate the disease. Complications occur from secondary bacterial, fungal, and viral colonization. Malodor and vegetations can indicate bacterial or fungal infections and can lead to persistence of skin lesions. Herpes simplex virus infections can exacerbate preexisting lesions.³ Hailey-Hailey disease of the anogenital region also can be complicated by infection with oncogenic strains of human papillomavirus and lead to cutaneous squamous cell carcinoma.⁴

Hailey-Hailey disease histologically appears as suprabasal and intraepidermal keratinocyte acantholysis,⁵ which typically is widespread in the epidermis, with large areas of dyscohesion with a dilapidated brick wall-like appearance.¹ In more chronic lesions, epidermal hyperplasia, parakeratosis, and focal crusts may be observed. A moderate perivascular lymphocytic infiltrate can be observed in the superficial dermis. Direct immunofluorescence typically is negative.

Topical corticosteroids and antimicrobials are first-line therapies that often only provide temporary suppression. When the disease is refractory to topical therapies, intralesional corticosteroids may be attempted. There is no strong evidence to support the use of systemic therapy, aside from antimicrobial agents (eg, doxycycline) for the use of superinfections. In severe cases, immunomodulating therapies such as prednisone, cyclosporine, methotrexate, dapsone, alefacept, and oral retinoids may be effective.^6-8 Surgical therapy also can be considered for recalcitrant disease, including wide excision and grafting, though these techniques can be associated with morbidity.⁹

Superficial ablative techniques including dermabrasion, laser therapy with CO₂ and erbium-doped YAG, photodynamic therapy, and electron beam radiation have been shown to be effective modalities in severe cases.^5,9-11 It has been hypothesized that keratinocytes expressing the molecular defect are ablated, while the surrounding normal adnexal epithelium can regenerate normal epithelium. It also is thought that dermal fibrosis leads to better support of the diseased epidermis and decreases the risk for ulceration and fissuring.⁹

The Diagnosis: Hailey-Hailey Disease (Benign Familial Chronic Pemphigus)

Our patient had a long-standing history of Hailey-Hailey disease, as confirmed by multiple prior skin biopsies at outside institutions as well as our affiliated site. He began treatment with oral doxycycline 50 mg twice daily for 2 weeks, triamcinolone cream 0.1% twice daily to the affected region, and aluminum acetate solution soaks and chlorhexidine wash daily along with petroleum jelly, which resulted in good control of the disease. The differential diagnosis of eroded plaques, particularly in the axillary, crural, and inframammary folds, is broad and includes candidiasis, inverse psoriasis, contact dermatitis, dermatophyte infection, pemphigus vegetans or foliaceus, and granular parakeratosis.

Hailey-Hailey disease is a genetic disorder with a prevalence of 1 in 50,000 individuals. Most patients develop symptoms during the second or third decades of life.1 Hailey-Hailey disease exhibits an autosomal-dominant pattern of inheritance secondary to mutation in the human ATP2C1 gene, which codes for the ATPase secretory pathway of the Ca²⁺ transporting pump type 1 (SPCA1) localized in the Golgi apparatus.² Altered SPCA1 protein reduces concentration of Ca²⁺ within the Golgi lumen, which in turn impairs the processing of junctional proteins needed for normal cell-to-cell adhesion.¹

Clinically, Hailey-Hailey disease is characterized by vesicular or erosive plaques that have a predilection for intertriginous areas of the body.¹ The primary lesions often are flaccid vesicles that easily rupture, leaving behind crusted erosions that spread peripherally. The lesions also can appear as macerated plaques resembling torn tissue paper, as in our case. Friction, heat, and sweat exacerbate the disease. Complications occur from secondary bacterial, fungal, and viral colonization. Malodor and vegetations can indicate bacterial or fungal infections and can lead to persistence of skin lesions. Herpes simplex virus infections can exacerbate preexisting lesions.³ Hailey-Hailey disease of the anogenital region also can be complicated by infection with oncogenic strains of human papillomavirus and lead to cutaneous squamous cell carcinoma.⁴

Hailey-Hailey disease histologically appears as suprabasal and intraepidermal keratinocyte acantholysis,⁵ which typically is widespread in the epidermis, with large areas of dyscohesion with a dilapidated brick wall-like appearance.¹ In more chronic lesions, epidermal hyperplasia, parakeratosis, and focal crusts may be observed. A moderate perivascular lymphocytic infiltrate can be observed in the superficial dermis. Direct immunofluorescence typically is negative.

Topical corticosteroids and antimicrobials are first-line therapies that often only provide temporary suppression. When the disease is refractory to topical therapies, intralesional corticosteroids may be attempted. There is no strong evidence to support the use of systemic therapy, aside from antimicrobial agents (eg, doxycycline) for the use of superinfections. In severe cases, immunomodulating therapies such as prednisone, cyclosporine, methotrexate, dapsone, alefacept, and oral retinoids may be effective.^6-8 Surgical therapy also can be considered for recalcitrant disease, including wide excision and grafting, though these techniques can be associated with morbidity.⁹

Superficial ablative techniques including dermabrasion, laser therapy with CO₂ and erbium-doped YAG, photodynamic therapy, and electron beam radiation have been shown to be effective modalities in severe cases.^5,9-11 It has been hypothesized that keratinocytes expressing the molecular defect are ablated, while the surrounding normal adnexal epithelium can regenerate normal epithelium. It also is thought that dermal fibrosis leads to better support of the diseased epidermis and decreases the risk for ulceration and fissuring.⁹