Jonathan Madden, MD

A 36-year-old African-American man presented to our clinic for evaluation of a chronic “rash” on his trunk, arms, and legs that had been present for 3 years. Empiric therapy for tinea corporis, nummular eczema, and confluent and reticulated papillomatosis had failed to improve his lesions.

Physical examination revealed a widespread skin eruption consisting of well-demarcated, hyperpigmented, scaly patches and plaques distributed throughout the patient’s trunk and extremities. Initial biopsies of the skin lesions (performed at an outside institution prior to current presentation) were nondiagnostic.

Over the next several months, the patient developed numerous cutaneous nodules and tumors within the background of his persistent patches and plaques (FIGURE). These nodules and tumors intermittently disappeared and recurred, seemingly independent of therapies including psoralen and ultraviolet A phototherapy (PUVA), interferon, and methotrexate.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Repeat biopsies ultimately confirmed a diagnosis of mycosis fungoides (MF), a primary cutaneous non-Hodgkin lymphoma of T-cell origin.

Lymphomas occurring in the skin without evidence of disease in other areas of the body at the time of diagnosis are referred to as primary cutaneous lymphomas. They are broadly divided by their cell of origin into cutaneous T-cell and cutaneous B-cell lymphomas. Differentiating primary cutaneous lymphoma from systemic lymphomas with secondary skin involvement is an important distinction, as primary cutaneous lymphomas have different clinical courses and prognoses and require different treatments.¹

One literature review found that 25 unique dermatoses can be mimicked clinically by mycosis fungoides.

MF is the most common type of cutaneous T-cell lymphoma (CTCL), yet it remains an uncommon diagnosis as cutaneous lymphomas comprise only 3.9% of all non-Hodgkin lymphomas.² The CD30+ transformed variant identified in this patient is a rare subtype of MF that is associated with increased morbidity and mortality.³ Other types of CTCL include primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, and adult T-cell leukemia/lymphoma, all of which can resemble MF clinically and are diagnosed by histopathology.

A nonspecific presentation

Patients with MF typically present with a complaint of chronic, slowly progressive skin lesions of various sizes and morphologies including scaly patches, plaques, and tumors, often in skin distributions that are not directly exposed to the sun (often referred to as a “bathing suit” distribution).⁴ Pruritus typically accompanies these skin lesions, and alopecia and poikiloderma are common findings. Patients with more advanced cases may present with generalized erythroderma. This finding should raise concern for progression to Sézary syndrome, a more aggressive type of CTCL that manifests with leukemic involvement of malignant T-cells matching the T-cell clones found in the skin.²

Alopecia is a common manifestation of MF that can be clinically indistinguishable from alopecia areata.⁵ While isolated alopecia is unlikely to be a consequence of MF, alopecia in the setting of widespread patches and plaques should raise suspicion for a diagnosis of MF.

Continue to: Diagnostic dilemma

This case illustrates the diagnostic dilemma posed by MF due to its propensity to mimic more benign skin disorders, both clinically and histologically.² One literature review of MF cases in which the diagnosis was not suspected clinically but was eventually confirmed histopathologically found that 25 unique dermatoses can be mimicked clinically by MF.⁶ The more common conditions that MF can be mistaken for are discussed below. In light of the diagnostic challenge posed by this multitude of morphologic presentations, referral to Dermatology for histopathologic evaluation is a reasonable next step when empiric treatment fails to improve symptoms of these common skin disorders.

Chronic atopic dermatitis (eczema) is characterized by dry skin and severe pruritis, usually associated with lichenified plaques and a history of atopic disease. The pruritic, scaly plaques typical of MF may be misdiagnosed as eczema; however, a distribution involving the “bathing suit” area is more suggestive of MF. Patients with atopic dermatitis are more likely to display a flexural distribution.²

Tinea corporis typically presents as annular, erythematous, pruritic, scaly patches or plaques that are similar to the scaling lesions of MF. Tinea corporis can be distinguished from MF via potassium hydroxide preparation of skin scrapings from an active lesion, which should demonstrate the segmented hyphae characteristic of this infection. If lesions of this type fail to respond to topical antifungal therapy, a skin biopsy may be warranted for further evaluation.

Nummular eczema, like tinea corporis, presents with round, coin-shaped patches that are highly pruritic and can be difficult to distinguish from the pruritic patches of MF. Unlike MF, however, nummular eczema typically is observed in patients with diffusely dry skin⁷; the lack of this finding should prompt consideration of alternative diagnoses, including MF.

Psoriasis classically presents with symmetrically distributed, well-demarcated plaques with prominent scaling that are usually asymptomatic, but may be associated with pruritis. Psoriatic plaques may be difficult to distinguish clinically from the plaques of MF, but their distribution may offer clues; psoriasis typically follows an extensor surface distribution, whereas MF is more commonly identified in a “bathing suit” or generalized distribution.⁴

Continue to: Tx based on disease extent, impact on quality of life

Staging of MF is the primary determinant of treatment and involves evaluation of skin, lymph node, viscera, and blood involvement. Early-stage MF has a favorable prognosis and can be effectively managed with skin-directed treatments. These include topical corticosteroids, topical nitrogen mustard agents, topical retinoids, and phototherapy (PUVA).⁸ Total skin electron beam therapy has been proven effective in the treatment of refractory and extensive MF, and local radiation therapy also is an effective treatment for isolated cutaneous tumors. Prolonged complete remissions of early-stage MF have been achieved using skin-directed treatments.⁸

In contrast, advanced MF often is treatment refractory and carries a poor prognosis. Systemic treatments such as interferon therapy, oral retinoids, extracorporeal photopheresis, and chemotherapy are added in patients with advanced disease after skin-directed therapy fails to adequately control tumor burden.

Our patient initially was treated with PUVA as well as 6 million U of interferon alfa-2B 3 times weekly, which he eventually elected to discontinue after 8 months because he wanted to father a child. His disease became more widespread after discontinuing these treatments despite interim therapy with clobetasol ointment .05%. His larger nodules and tumors were intermittently treated with local radiation with good response. Methotrexate 15 mg weekly was initiated following his decline after discontinuing PUVA and interferon treatment. Treatment with methotrexate resulted in an overall decrease in his tumor burden and several months of clinical stability.

Early stage mycosis fungoides has a favorable prognosis and can be effectively managed with skin-directed treatments. Advanced MF often is treatment refractory and has a poor prognosis.

Approximately 6 months after initiating methotrexate, his condition notably worsened. He developed generalized erythroderma, systemic symptoms including fever, chills, and unintentional 9.07-kg weight loss, in addition to new findings of palmoplantar keratoderma and nail dystrophy. In light of this systemic progression and concern for developing Sézary syndrome, extracorporeal photopheresis, bexarotene (an oral retinoid) 75 mg twice daily, and interferon alfa-2B 5 million U 3 times weekly were initiated. His condition continued to decline despite these therapies, culminating in a hospital admission for sepsis.

The patient recovered, and his regimen was changed to PUVA 3 times weekly in addition to treatment with intravenous brentuximab 1.8 mg/kg, a monoclonal antibody that targets CD30 receptors. Unfortunately, his condition continued to decline on this treatment regimen, which was subsequently abandoned in favor of chemotherapy with gemcitabine 1980 mg/250 mL normal saline. The patient was improving clinically with each cycle of gemcitabine and the plan was to transition him to extracorporeal photopheresis and bexarotene for maintenance therapy; however, the patient succumbed to his disease and passed away at the age of 37.

CORRESPONDENCE
Jonathan Banta, MD, PSC 103, Box 3613, APO, AE 09603 jonathan.c.banta.mil@mail.mil

A 36-year-old African-American man presented to our clinic for evaluation of a chronic “rash” on his trunk, arms, and legs that had been present for 3 years. Empiric therapy for tinea corporis, nummular eczema, and confluent and reticulated papillomatosis had failed to improve his lesions.

Physical examination revealed a widespread skin eruption consisting of well-demarcated, hyperpigmented, scaly patches and plaques distributed throughout the patient’s trunk and extremities. Initial biopsies of the skin lesions (performed at an outside institution prior to current presentation) were nondiagnostic.

Over the next several months, the patient developed numerous cutaneous nodules and tumors within the background of his persistent patches and plaques (FIGURE). These nodules and tumors intermittently disappeared and recurred, seemingly independent of therapies including psoralen and ultraviolet A phototherapy (PUVA), interferon, and methotrexate.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Repeat biopsies ultimately confirmed a diagnosis of mycosis fungoides (MF), a primary cutaneous non-Hodgkin lymphoma of T-cell origin.

Lymphomas occurring in the skin without evidence of disease in other areas of the body at the time of diagnosis are referred to as primary cutaneous lymphomas. They are broadly divided by their cell of origin into cutaneous T-cell and cutaneous B-cell lymphomas. Differentiating primary cutaneous lymphoma from systemic lymphomas with secondary skin involvement is an important distinction, as primary cutaneous lymphomas have different clinical courses and prognoses and require different treatments.¹

One literature review found that 25 unique dermatoses can be mimicked clinically by mycosis fungoides.

MF is the most common type of cutaneous T-cell lymphoma (CTCL), yet it remains an uncommon diagnosis as cutaneous lymphomas comprise only 3.9% of all non-Hodgkin lymphomas.² The CD30+ transformed variant identified in this patient is a rare subtype of MF that is associated with increased morbidity and mortality.³ Other types of CTCL include primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, and adult T-cell leukemia/lymphoma, all of which can resemble MF clinically and are diagnosed by histopathology.

A nonspecific presentation

Patients with MF typically present with a complaint of chronic, slowly progressive skin lesions of various sizes and morphologies including scaly patches, plaques, and tumors, often in skin distributions that are not directly exposed to the sun (often referred to as a “bathing suit” distribution).⁴ Pruritus typically accompanies these skin lesions, and alopecia and poikiloderma are common findings. Patients with more advanced cases may present with generalized erythroderma. This finding should raise concern for progression to Sézary syndrome, a more aggressive type of CTCL that manifests with leukemic involvement of malignant T-cells matching the T-cell clones found in the skin.²

Alopecia is a common manifestation of MF that can be clinically indistinguishable from alopecia areata.⁵ While isolated alopecia is unlikely to be a consequence of MF, alopecia in the setting of widespread patches and plaques should raise suspicion for a diagnosis of MF.

Continue to: Diagnostic dilemma

This case illustrates the diagnostic dilemma posed by MF due to its propensity to mimic more benign skin disorders, both clinically and histologically.² One literature review of MF cases in which the diagnosis was not suspected clinically but was eventually confirmed histopathologically found that 25 unique dermatoses can be mimicked clinically by MF.⁶ The more common conditions that MF can be mistaken for are discussed below. In light of the diagnostic challenge posed by this multitude of morphologic presentations, referral to Dermatology for histopathologic evaluation is a reasonable next step when empiric treatment fails to improve symptoms of these common skin disorders.

Chronic atopic dermatitis (eczema) is characterized by dry skin and severe pruritis, usually associated with lichenified plaques and a history of atopic disease. The pruritic, scaly plaques typical of MF may be misdiagnosed as eczema; however, a distribution involving the “bathing suit” area is more suggestive of MF. Patients with atopic dermatitis are more likely to display a flexural distribution.²

Tinea corporis typically presents as annular, erythematous, pruritic, scaly patches or plaques that are similar to the scaling lesions of MF. Tinea corporis can be distinguished from MF via potassium hydroxide preparation of skin scrapings from an active lesion, which should demonstrate the segmented hyphae characteristic of this infection. If lesions of this type fail to respond to topical antifungal therapy, a skin biopsy may be warranted for further evaluation.

Nummular eczema, like tinea corporis, presents with round, coin-shaped patches that are highly pruritic and can be difficult to distinguish from the pruritic patches of MF. Unlike MF, however, nummular eczema typically is observed in patients with diffusely dry skin⁷; the lack of this finding should prompt consideration of alternative diagnoses, including MF.

Psoriasis classically presents with symmetrically distributed, well-demarcated plaques with prominent scaling that are usually asymptomatic, but may be associated with pruritis. Psoriatic plaques may be difficult to distinguish clinically from the plaques of MF, but their distribution may offer clues; psoriasis typically follows an extensor surface distribution, whereas MF is more commonly identified in a “bathing suit” or generalized distribution.⁴

Continue to: Tx based on disease extent, impact on quality of life

Staging of MF is the primary determinant of treatment and involves evaluation of skin, lymph node, viscera, and blood involvement. Early-stage MF has a favorable prognosis and can be effectively managed with skin-directed treatments. These include topical corticosteroids, topical nitrogen mustard agents, topical retinoids, and phototherapy (PUVA).⁸ Total skin electron beam therapy has been proven effective in the treatment of refractory and extensive MF, and local radiation therapy also is an effective treatment for isolated cutaneous tumors. Prolonged complete remissions of early-stage MF have been achieved using skin-directed treatments.⁸

In contrast, advanced MF often is treatment refractory and carries a poor prognosis. Systemic treatments such as interferon therapy, oral retinoids, extracorporeal photopheresis, and chemotherapy are added in patients with advanced disease after skin-directed therapy fails to adequately control tumor burden.

Our patient initially was treated with PUVA as well as 6 million U of interferon alfa-2B 3 times weekly, which he eventually elected to discontinue after 8 months because he wanted to father a child. His disease became more widespread after discontinuing these treatments despite interim therapy with clobetasol ointment .05%. His larger nodules and tumors were intermittently treated with local radiation with good response. Methotrexate 15 mg weekly was initiated following his decline after discontinuing PUVA and interferon treatment. Treatment with methotrexate resulted in an overall decrease in his tumor burden and several months of clinical stability.

Early stage mycosis fungoides has a favorable prognosis and can be effectively managed with skin-directed treatments. Advanced MF often is treatment refractory and has a poor prognosis.

Approximately 6 months after initiating methotrexate, his condition notably worsened. He developed generalized erythroderma, systemic symptoms including fever, chills, and unintentional 9.07-kg weight loss, in addition to new findings of palmoplantar keratoderma and nail dystrophy. In light of this systemic progression and concern for developing Sézary syndrome, extracorporeal photopheresis, bexarotene (an oral retinoid) 75 mg twice daily, and interferon alfa-2B 5 million U 3 times weekly were initiated. His condition continued to decline despite these therapies, culminating in a hospital admission for sepsis.

The patient recovered, and his regimen was changed to PUVA 3 times weekly in addition to treatment with intravenous brentuximab 1.8 mg/kg, a monoclonal antibody that targets CD30 receptors. Unfortunately, his condition continued to decline on this treatment regimen, which was subsequently abandoned in favor of chemotherapy with gemcitabine 1980 mg/250 mL normal saline. The patient was improving clinically with each cycle of gemcitabine and the plan was to transition him to extracorporeal photopheresis and bexarotene for maintenance therapy; however, the patient succumbed to his disease and passed away at the age of 37.

CORRESPONDENCE
Jonathan Banta, MD, PSC 103, Box 3613, APO, AE 09603 jonathan.c.banta.mil@mail.mil

A 36-year-old African-American man presented to our clinic for evaluation of a chronic “rash” on his trunk, arms, and legs that had been present for 3 years. Empiric therapy for tinea corporis, nummular eczema, and confluent and reticulated papillomatosis had failed to improve his lesions.

Physical examination revealed a widespread skin eruption consisting of well-demarcated, hyperpigmented, scaly patches and plaques distributed throughout the patient’s trunk and extremities. Initial biopsies of the skin lesions (performed at an outside institution prior to current presentation) were nondiagnostic.

Over the next several months, the patient developed numerous cutaneous nodules and tumors within the background of his persistent patches and plaques (FIGURE). These nodules and tumors intermittently disappeared and recurred, seemingly independent of therapies including psoralen and ultraviolet A phototherapy (PUVA), interferon, and methotrexate.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Repeat biopsies ultimately confirmed a diagnosis of mycosis fungoides (MF), a primary cutaneous non-Hodgkin lymphoma of T-cell origin.

Lymphomas occurring in the skin without evidence of disease in other areas of the body at the time of diagnosis are referred to as primary cutaneous lymphomas. They are broadly divided by their cell of origin into cutaneous T-cell and cutaneous B-cell lymphomas. Differentiating primary cutaneous lymphoma from systemic lymphomas with secondary skin involvement is an important distinction, as primary cutaneous lymphomas have different clinical courses and prognoses and require different treatments.¹

One literature review found that 25 unique dermatoses can be mimicked clinically by mycosis fungoides.

MF is the most common type of cutaneous T-cell lymphoma (CTCL), yet it remains an uncommon diagnosis as cutaneous lymphomas comprise only 3.9% of all non-Hodgkin lymphomas.² The CD30+ transformed variant identified in this patient is a rare subtype of MF that is associated with increased morbidity and mortality.³ Other types of CTCL include primary cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, and adult T-cell leukemia/lymphoma, all of which can resemble MF clinically and are diagnosed by histopathology.

A nonspecific presentation

Patients with MF typically present with a complaint of chronic, slowly progressive skin lesions of various sizes and morphologies including scaly patches, plaques, and tumors, often in skin distributions that are not directly exposed to the sun (often referred to as a “bathing suit” distribution).⁴ Pruritus typically accompanies these skin lesions, and alopecia and poikiloderma are common findings. Patients with more advanced cases may present with generalized erythroderma. This finding should raise concern for progression to Sézary syndrome, a more aggressive type of CTCL that manifests with leukemic involvement of malignant T-cells matching the T-cell clones found in the skin.²

Alopecia is a common manifestation of MF that can be clinically indistinguishable from alopecia areata.⁵ While isolated alopecia is unlikely to be a consequence of MF, alopecia in the setting of widespread patches and plaques should raise suspicion for a diagnosis of MF.

Continue to: Diagnostic dilemma

This case illustrates the diagnostic dilemma posed by MF due to its propensity to mimic more benign skin disorders, both clinically and histologically.² One literature review of MF cases in which the diagnosis was not suspected clinically but was eventually confirmed histopathologically found that 25 unique dermatoses can be mimicked clinically by MF.⁶ The more common conditions that MF can be mistaken for are discussed below. In light of the diagnostic challenge posed by this multitude of morphologic presentations, referral to Dermatology for histopathologic evaluation is a reasonable next step when empiric treatment fails to improve symptoms of these common skin disorders.

Chronic atopic dermatitis (eczema) is characterized by dry skin and severe pruritis, usually associated with lichenified plaques and a history of atopic disease. The pruritic, scaly plaques typical of MF may be misdiagnosed as eczema; however, a distribution involving the “bathing suit” area is more suggestive of MF. Patients with atopic dermatitis are more likely to display a flexural distribution.²

Tinea corporis typically presents as annular, erythematous, pruritic, scaly patches or plaques that are similar to the scaling lesions of MF. Tinea corporis can be distinguished from MF via potassium hydroxide preparation of skin scrapings from an active lesion, which should demonstrate the segmented hyphae characteristic of this infection. If lesions of this type fail to respond to topical antifungal therapy, a skin biopsy may be warranted for further evaluation.

Nummular eczema, like tinea corporis, presents with round, coin-shaped patches that are highly pruritic and can be difficult to distinguish from the pruritic patches of MF. Unlike MF, however, nummular eczema typically is observed in patients with diffusely dry skin⁷; the lack of this finding should prompt consideration of alternative diagnoses, including MF.

Psoriasis classically presents with symmetrically distributed, well-demarcated plaques with prominent scaling that are usually asymptomatic, but may be associated with pruritis. Psoriatic plaques may be difficult to distinguish clinically from the plaques of MF, but their distribution may offer clues; psoriasis typically follows an extensor surface distribution, whereas MF is more commonly identified in a “bathing suit” or generalized distribution.⁴

Continue to: Tx based on disease extent, impact on quality of life

Staging of MF is the primary determinant of treatment and involves evaluation of skin, lymph node, viscera, and blood involvement. Early-stage MF has a favorable prognosis and can be effectively managed with skin-directed treatments. These include topical corticosteroids, topical nitrogen mustard agents, topical retinoids, and phototherapy (PUVA).⁸ Total skin electron beam therapy has been proven effective in the treatment of refractory and extensive MF, and local radiation therapy also is an effective treatment for isolated cutaneous tumors. Prolonged complete remissions of early-stage MF have been achieved using skin-directed treatments.⁸

In contrast, advanced MF often is treatment refractory and carries a poor prognosis. Systemic treatments such as interferon therapy, oral retinoids, extracorporeal photopheresis, and chemotherapy are added in patients with advanced disease after skin-directed therapy fails to adequately control tumor burden.

Our patient initially was treated with PUVA as well as 6 million U of interferon alfa-2B 3 times weekly, which he eventually elected to discontinue after 8 months because he wanted to father a child. His disease became more widespread after discontinuing these treatments despite interim therapy with clobetasol ointment .05%. His larger nodules and tumors were intermittently treated with local radiation with good response. Methotrexate 15 mg weekly was initiated following his decline after discontinuing PUVA and interferon treatment. Treatment with methotrexate resulted in an overall decrease in his tumor burden and several months of clinical stability.

Early stage mycosis fungoides has a favorable prognosis and can be effectively managed with skin-directed treatments. Advanced MF often is treatment refractory and has a poor prognosis.

Approximately 6 months after initiating methotrexate, his condition notably worsened. He developed generalized erythroderma, systemic symptoms including fever, chills, and unintentional 9.07-kg weight loss, in addition to new findings of palmoplantar keratoderma and nail dystrophy. In light of this systemic progression and concern for developing Sézary syndrome, extracorporeal photopheresis, bexarotene (an oral retinoid) 75 mg twice daily, and interferon alfa-2B 5 million U 3 times weekly were initiated. His condition continued to decline despite these therapies, culminating in a hospital admission for sepsis.

The patient recovered, and his regimen was changed to PUVA 3 times weekly in addition to treatment with intravenous brentuximab 1.8 mg/kg, a monoclonal antibody that targets CD30 receptors. Unfortunately, his condition continued to decline on this treatment regimen, which was subsequently abandoned in favor of chemotherapy with gemcitabine 1980 mg/250 mL normal saline. The patient was improving clinically with each cycle of gemcitabine and the plan was to transition him to extracorporeal photopheresis and bexarotene for maintenance therapy; however, the patient succumbed to his disease and passed away at the age of 37.

CORRESPONDENCE
Jonathan Banta, MD, PSC 103, Box 3613, APO, AE 09603 jonathan.c.banta.mil@mail.mil

A 22-year-old Caucasian man with a history of atopic dermatitis (AD) was referred to our dermatology clinic for evaluation of a diffuse facial rash that had been present for the previous 7 days. The rash initially presented as erythema on the right malar cheek that rapidly spread to the entire face. Initially diagnosed as impetigo, empiric treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg PO BID for 7 days), dicloxacillin (500 mg PO BID for 6 days), cephalexin (500 mg TID for 5 days), and mupirocin (2% topical cream applied TID for 6 days) failed to improve the patient’s symptoms. He reported mild pain associated with facial movements.

The patient had a history of similar (but more limited) rashes, which he described as “recurrent impetigo,” that began during his career as a high school and collegiate wrestler. These rashes were different from the rashes he described as his history of AD, which consisted of pruritic and erythematous skin in his antecubital and popliteal fossae. He denied any history of herpes simplex virus (HSV) infection.

A physical examination revealed numerous monomorphic, 1- to 3-mm, punched-out erosions and ulcers with overlying yellow-brown crust encompassing the patient’s entire face and portions of his anterior neck. Several clustered vesicles on erythematous bases also were noted (FIGUREs 1A and 1B). We used a Dermablade to unroof some of the vesicles and sent the scrapings to the lab for Tzanck, direct fluorescent antibody assay (DFA), and HSV polymerase chain reaction (PCR) testing.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Eczema herpeticum secondary to herpes gladiatorum

The patient’s laboratory results came back and the Tzanck preparation was positive for multinucleated giant cells, and both the DFA and HSV PCR were positive for HSV infection. This, paired with the widely disseminated rash observed on examination and the patient’s history of AD, was consistent with a diagnosis of eczema herpeticum (EH).

Rather than primary impetigo, the patient’s self-described history of recurrent rashes was felt to represent a history of HSV outbreaks. Given his denial of prior oral or genital HSV infection, as well as the coincident onset of these outbreaks during his career as a competitive wrestler, the most likely primary infection source was direct contact with another HSV-infected wrestler.

Herpes gladiatorum refers to a primary cutaneous HSV infection contracted by an athlete through direct skin-to-skin contact with another athlete.¹ It is common in contact sports, such as rugby and wrestling, and particularly common at organized wrestling camps, where mass outbreaks are a frequent occurrence.² Herpes gladiatorum is so common at these camps that many recommend prophylactic valacyclovir treatment for all participants to mitigate the risk of contracting HSV. In a 2016 review, Anderson et al concluded that prophylactic valacyclovir treatment at a 28-day high school wrestling camp effectively reduced outbreak incidence by 89.5%.²

Prophylactic valacyclovir treatment at a 28-day high school wrestling camp reduced outbreak incidence of herpes gladiatorum by 89.5%.

The lesions of herpes gladiatorum are classically limited in distribution and reflective of the areas of direct contact with infected skin, most commonly the face, neck, and arms. Our patient’s history of more limited outbreaks on his face was consistent with this typical presentation. His current outbreak, however, had become much more widely disseminated, which led to the diagnosis of EH secondary to herpes gladiatorum.

Eczema herpeticum: Pathogenesis and diagnosis

Also known as Kaposi’s varicelliform eruption, EH is a rapid, widespread cutaneous dissemination of HSV infection in areas of dermatitis or skin barrier disruption, most commonly caused by HSV-1 infection.³ It is classically associated with AD, but also can occur in patients with impaired epidermal barrier function due to other conditions, such as burns, pemphigus vulgaris, mycosis fungoides, and Darier disease.⁴ It occurs in <3% of patients with AD and is more commonly observed in infants and children with AD than adults.⁵

Continue to: Clinically, the most common manifestations are discrete..

Clinically, the most common manifestations are discrete, monomorphic, 2- to 3-mm, punched-out erosions with hemorrhagic crusts; intact vesicles are less commonly observed.⁴ Involved skin is typically painful and may be pruritic. Clinical diagnosis should be confirmed by laboratory evaluation, typically Tzanck preparation, DFA, and/or HSV PCR.

Complications and the importance of rapid treatment

The most common complication of EH is bacterial superinfection (impetigo), usually by Staphylococcus aureus or group A streptococci. Signs of bacterial superinfection include weeping lesions, pustules, honey-colored/golden crusting, worsening of existing dermatitis, and failure to respond to antiviral treatment. Topical mupirocin 2% cream is generally effective for controlling limited infection. However, systemic antibiotics (cephalosporins or penicillinase-resistant penicillins) may be necessary to control widespread disease.⁴ Clinical improvement should be observed within a single course of an appropriate antibiotic.

In contrast to impetigo, less common but more serious complications of EH can be life threatening. Systemic dissemination of disease is of particular importance in vulnerable populations such as pediatric and immunocompromised patients. Meningoencephalitis, secondary bacteremia, and herpes keratitis can all develop secondary to EH and incur significant morbidity and mortality.¹

Fever, malaise, lymphadenopathy, or eye pain should prompt immediate consideration of inpatient evaluation and treatment for these potentially deadly or debilitating complications. All patients with EH distributed near the eyes should be referred to ophthalmology to rule out ocular involvement.

A diagnosis of eczema herpeticum requires immediate treatment with oral or intravenous antiviral medication.

Immediately treat with antivirals

Due to the potential complications discussed above, a diagnosis of EH necessitates immediate treatment with oral or intravenous antiviral medication. Acyclovir, valacyclovir, or famciclovir may be used, with typical treatment courses ranging from 10 to 14 days or until all mucocutaneous lesions are healed.⁴ Although typically reserved for patients with recurrent genital herpes resulting in 6 or more outbreaks annually, chronic suppressive therapy also may be considered for patients with EH who suffer from frequent or severe recurrent outbreaks.

Continue to: Our patient

Our patient. Given his otherwise excellent health and the absence of symptoms of potentially serious complications, our patient was treated as an outpatient with a 10-day course of valacyclovir 1000 mg PO BID. He was additionally prescribed a 7-day course of cephalexin 500 mg PO TID for coverage of bacterial superinfection. He responded well to treatment.

Ten days after his initial presentation to our clinic, his erosions and vesicles had completely cleared, and the associated erythema had significantly improved (FIGURE 2). Given the severity of his presentation and his history of 2 to 3 outbreaks annually, he opted to continue prophylactic valacyclovir (500 mg/d) for long-term suppression.

CORRESPONDENCE
Jonathan Madden, MD, 221 3rd Street West, JBSA-Randolph, TX 78150, jonathan.f.madden.mil@mail.mil

A 22-year-old Caucasian man with a history of atopic dermatitis (AD) was referred to our dermatology clinic for evaluation of a diffuse facial rash that had been present for the previous 7 days. The rash initially presented as erythema on the right malar cheek that rapidly spread to the entire face. Initially diagnosed as impetigo, empiric treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg PO BID for 7 days), dicloxacillin (500 mg PO BID for 6 days), cephalexin (500 mg TID for 5 days), and mupirocin (2% topical cream applied TID for 6 days) failed to improve the patient’s symptoms. He reported mild pain associated with facial movements.

The patient had a history of similar (but more limited) rashes, which he described as “recurrent impetigo,” that began during his career as a high school and collegiate wrestler. These rashes were different from the rashes he described as his history of AD, which consisted of pruritic and erythematous skin in his antecubital and popliteal fossae. He denied any history of herpes simplex virus (HSV) infection.

A physical examination revealed numerous monomorphic, 1- to 3-mm, punched-out erosions and ulcers with overlying yellow-brown crust encompassing the patient’s entire face and portions of his anterior neck. Several clustered vesicles on erythematous bases also were noted (FIGUREs 1A and 1B). We used a Dermablade to unroof some of the vesicles and sent the scrapings to the lab for Tzanck, direct fluorescent antibody assay (DFA), and HSV polymerase chain reaction (PCR) testing.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Eczema herpeticum secondary to herpes gladiatorum

The patient’s laboratory results came back and the Tzanck preparation was positive for multinucleated giant cells, and both the DFA and HSV PCR were positive for HSV infection. This, paired with the widely disseminated rash observed on examination and the patient’s history of AD, was consistent with a diagnosis of eczema herpeticum (EH).

Rather than primary impetigo, the patient’s self-described history of recurrent rashes was felt to represent a history of HSV outbreaks. Given his denial of prior oral or genital HSV infection, as well as the coincident onset of these outbreaks during his career as a competitive wrestler, the most likely primary infection source was direct contact with another HSV-infected wrestler.

Herpes gladiatorum refers to a primary cutaneous HSV infection contracted by an athlete through direct skin-to-skin contact with another athlete.¹ It is common in contact sports, such as rugby and wrestling, and particularly common at organized wrestling camps, where mass outbreaks are a frequent occurrence.² Herpes gladiatorum is so common at these camps that many recommend prophylactic valacyclovir treatment for all participants to mitigate the risk of contracting HSV. In a 2016 review, Anderson et al concluded that prophylactic valacyclovir treatment at a 28-day high school wrestling camp effectively reduced outbreak incidence by 89.5%.²

Prophylactic valacyclovir treatment at a 28-day high school wrestling camp reduced outbreak incidence of herpes gladiatorum by 89.5%.

The lesions of herpes gladiatorum are classically limited in distribution and reflective of the areas of direct contact with infected skin, most commonly the face, neck, and arms. Our patient’s history of more limited outbreaks on his face was consistent with this typical presentation. His current outbreak, however, had become much more widely disseminated, which led to the diagnosis of EH secondary to herpes gladiatorum.

Eczema herpeticum: Pathogenesis and diagnosis

Also known as Kaposi’s varicelliform eruption, EH is a rapid, widespread cutaneous dissemination of HSV infection in areas of dermatitis or skin barrier disruption, most commonly caused by HSV-1 infection.³ It is classically associated with AD, but also can occur in patients with impaired epidermal barrier function due to other conditions, such as burns, pemphigus vulgaris, mycosis fungoides, and Darier disease.⁴ It occurs in <3% of patients with AD and is more commonly observed in infants and children with AD than adults.⁵

Continue to: Clinically, the most common manifestations are discrete..

Clinically, the most common manifestations are discrete, monomorphic, 2- to 3-mm, punched-out erosions with hemorrhagic crusts; intact vesicles are less commonly observed.⁴ Involved skin is typically painful and may be pruritic. Clinical diagnosis should be confirmed by laboratory evaluation, typically Tzanck preparation, DFA, and/or HSV PCR.

Complications and the importance of rapid treatment

The most common complication of EH is bacterial superinfection (impetigo), usually by Staphylococcus aureus or group A streptococci. Signs of bacterial superinfection include weeping lesions, pustules, honey-colored/golden crusting, worsening of existing dermatitis, and failure to respond to antiviral treatment. Topical mupirocin 2% cream is generally effective for controlling limited infection. However, systemic antibiotics (cephalosporins or penicillinase-resistant penicillins) may be necessary to control widespread disease.⁴ Clinical improvement should be observed within a single course of an appropriate antibiotic.

In contrast to impetigo, less common but more serious complications of EH can be life threatening. Systemic dissemination of disease is of particular importance in vulnerable populations such as pediatric and immunocompromised patients. Meningoencephalitis, secondary bacteremia, and herpes keratitis can all develop secondary to EH and incur significant morbidity and mortality.¹

Fever, malaise, lymphadenopathy, or eye pain should prompt immediate consideration of inpatient evaluation and treatment for these potentially deadly or debilitating complications. All patients with EH distributed near the eyes should be referred to ophthalmology to rule out ocular involvement.

A diagnosis of eczema herpeticum requires immediate treatment with oral or intravenous antiviral medication.

Immediately treat with antivirals

Due to the potential complications discussed above, a diagnosis of EH necessitates immediate treatment with oral or intravenous antiviral medication. Acyclovir, valacyclovir, or famciclovir may be used, with typical treatment courses ranging from 10 to 14 days or until all mucocutaneous lesions are healed.⁴ Although typically reserved for patients with recurrent genital herpes resulting in 6 or more outbreaks annually, chronic suppressive therapy also may be considered for patients with EH who suffer from frequent or severe recurrent outbreaks.

Continue to: Our patient

Our patient. Given his otherwise excellent health and the absence of symptoms of potentially serious complications, our patient was treated as an outpatient with a 10-day course of valacyclovir 1000 mg PO BID. He was additionally prescribed a 7-day course of cephalexin 500 mg PO TID for coverage of bacterial superinfection. He responded well to treatment.

Ten days after his initial presentation to our clinic, his erosions and vesicles had completely cleared, and the associated erythema had significantly improved (FIGURE 2). Given the severity of his presentation and his history of 2 to 3 outbreaks annually, he opted to continue prophylactic valacyclovir (500 mg/d) for long-term suppression.

CORRESPONDENCE
Jonathan Madden, MD, 221 3rd Street West, JBSA-Randolph, TX 78150, jonathan.f.madden.mil@mail.mil

A 22-year-old Caucasian man with a history of atopic dermatitis (AD) was referred to our dermatology clinic for evaluation of a diffuse facial rash that had been present for the previous 7 days. The rash initially presented as erythema on the right malar cheek that rapidly spread to the entire face. Initially diagnosed as impetigo, empiric treatment with sulfamethoxazole/trimethoprim (800 mg/160 mg PO BID for 7 days), dicloxacillin (500 mg PO BID for 6 days), cephalexin (500 mg TID for 5 days), and mupirocin (2% topical cream applied TID for 6 days) failed to improve the patient’s symptoms. He reported mild pain associated with facial movements.

The patient had a history of similar (but more limited) rashes, which he described as “recurrent impetigo,” that began during his career as a high school and collegiate wrestler. These rashes were different from the rashes he described as his history of AD, which consisted of pruritic and erythematous skin in his antecubital and popliteal fossae. He denied any history of herpes simplex virus (HSV) infection.

A physical examination revealed numerous monomorphic, 1- to 3-mm, punched-out erosions and ulcers with overlying yellow-brown crust encompassing the patient’s entire face and portions of his anterior neck. Several clustered vesicles on erythematous bases also were noted (FIGUREs 1A and 1B). We used a Dermablade to unroof some of the vesicles and sent the scrapings to the lab for Tzanck, direct fluorescent antibody assay (DFA), and HSV polymerase chain reaction (PCR) testing.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Diagnosis: Eczema herpeticum secondary to herpes gladiatorum

The patient’s laboratory results came back and the Tzanck preparation was positive for multinucleated giant cells, and both the DFA and HSV PCR were positive for HSV infection. This, paired with the widely disseminated rash observed on examination and the patient’s history of AD, was consistent with a diagnosis of eczema herpeticum (EH).

Rather than primary impetigo, the patient’s self-described history of recurrent rashes was felt to represent a history of HSV outbreaks. Given his denial of prior oral or genital HSV infection, as well as the coincident onset of these outbreaks during his career as a competitive wrestler, the most likely primary infection source was direct contact with another HSV-infected wrestler.

Herpes gladiatorum refers to a primary cutaneous HSV infection contracted by an athlete through direct skin-to-skin contact with another athlete.¹ It is common in contact sports, such as rugby and wrestling, and particularly common at organized wrestling camps, where mass outbreaks are a frequent occurrence.² Herpes gladiatorum is so common at these camps that many recommend prophylactic valacyclovir treatment for all participants to mitigate the risk of contracting HSV. In a 2016 review, Anderson et al concluded that prophylactic valacyclovir treatment at a 28-day high school wrestling camp effectively reduced outbreak incidence by 89.5%.²

Prophylactic valacyclovir treatment at a 28-day high school wrestling camp reduced outbreak incidence of herpes gladiatorum by 89.5%.

The lesions of herpes gladiatorum are classically limited in distribution and reflective of the areas of direct contact with infected skin, most commonly the face, neck, and arms. Our patient’s history of more limited outbreaks on his face was consistent with this typical presentation. His current outbreak, however, had become much more widely disseminated, which led to the diagnosis of EH secondary to herpes gladiatorum.

Eczema herpeticum: Pathogenesis and diagnosis

Also known as Kaposi’s varicelliform eruption, EH is a rapid, widespread cutaneous dissemination of HSV infection in areas of dermatitis or skin barrier disruption, most commonly caused by HSV-1 infection.³ It is classically associated with AD, but also can occur in patients with impaired epidermal barrier function due to other conditions, such as burns, pemphigus vulgaris, mycosis fungoides, and Darier disease.⁴ It occurs in <3% of patients with AD and is more commonly observed in infants and children with AD than adults.⁵

Continue to: Clinically, the most common manifestations are discrete..

Clinically, the most common manifestations are discrete, monomorphic, 2- to 3-mm, punched-out erosions with hemorrhagic crusts; intact vesicles are less commonly observed.⁴ Involved skin is typically painful and may be pruritic. Clinical diagnosis should be confirmed by laboratory evaluation, typically Tzanck preparation, DFA, and/or HSV PCR.

Complications and the importance of rapid treatment

The most common complication of EH is bacterial superinfection (impetigo), usually by Staphylococcus aureus or group A streptococci. Signs of bacterial superinfection include weeping lesions, pustules, honey-colored/golden crusting, worsening of existing dermatitis, and failure to respond to antiviral treatment. Topical mupirocin 2% cream is generally effective for controlling limited infection. However, systemic antibiotics (cephalosporins or penicillinase-resistant penicillins) may be necessary to control widespread disease.⁴ Clinical improvement should be observed within a single course of an appropriate antibiotic.

In contrast to impetigo, less common but more serious complications of EH can be life threatening. Systemic dissemination of disease is of particular importance in vulnerable populations such as pediatric and immunocompromised patients. Meningoencephalitis, secondary bacteremia, and herpes keratitis can all develop secondary to EH and incur significant morbidity and mortality.¹

Fever, malaise, lymphadenopathy, or eye pain should prompt immediate consideration of inpatient evaluation and treatment for these potentially deadly or debilitating complications. All patients with EH distributed near the eyes should be referred to ophthalmology to rule out ocular involvement.

A diagnosis of eczema herpeticum requires immediate treatment with oral or intravenous antiviral medication.

Immediately treat with antivirals

Due to the potential complications discussed above, a diagnosis of EH necessitates immediate treatment with oral or intravenous antiviral medication. Acyclovir, valacyclovir, or famciclovir may be used, with typical treatment courses ranging from 10 to 14 days or until all mucocutaneous lesions are healed.⁴ Although typically reserved for patients with recurrent genital herpes resulting in 6 or more outbreaks annually, chronic suppressive therapy also may be considered for patients with EH who suffer from frequent or severe recurrent outbreaks.

Continue to: Our patient

Our patient. Given his otherwise excellent health and the absence of symptoms of potentially serious complications, our patient was treated as an outpatient with a 10-day course of valacyclovir 1000 mg PO BID. He was additionally prescribed a 7-day course of cephalexin 500 mg PO TID for coverage of bacterial superinfection. He responded well to treatment.

Ten days after his initial presentation to our clinic, his erosions and vesicles had completely cleared, and the associated erythema had significantly improved (FIGURE 2). Given the severity of his presentation and his history of 2 to 3 outbreaks annually, he opted to continue prophylactic valacyclovir (500 mg/d) for long-term suppression.

CORRESPONDENCE
Jonathan Madden, MD, 221 3rd Street West, JBSA-Randolph, TX 78150, jonathan.f.madden.mil@mail.mil