Darier Disease Presenting with Recurrent Kaposi Varicelliform Eruption in a 10-year-old Boy with Seborrheic Dermatitis.

Abstract

We present a case of a 10-year-old boy with a longstanding history of seborrheic dermatitis (SD) referred to the Allergy and Immunology Department for recurrent Kaposi varicelliform eruption (KVE) secondary to herpes simplex 1 (HSV-1) infection and possible primary immunodeficiency. The patient was the second child of non-consanguineous parents, with an older, healthy brother. Family history was negative for primary immunodeficiency and skin disorders. The patient's skin problems began in infancy when he was diagnosed and treated by a dermatologist for SD. From preschool age, he was under the care of a pediatric neurologist and a defectologist for a sensory processing disorder. For the last two years, the patient had been receiving chlorpromazine therapy for aggressive behavior. The first episode of KVE was diagnosed at the age of six, following potent topical corticosteroid therapy for SD and sun exposure, another known risk factor for HSV infection. After the third KVE episode, prophylaxis with oral acyclovir was initiated. The skin changes were treated with topical steroids and oral antibiotics during disease flares, with poor clinical response. On presentation, the patient was in good general health, adipose, and of unremarkable somatic status, except for numerous symmetrical yellowish-brown keratotic papules and plaques on the forehead, cheeks, and the lateral side of the neck (Figure 1). The nail plate had multiple red and white longitudinal streaks and V-shaped notches on the distal free end of the nail plate (Figure 2). The allergy tests revealed increased total immunoglobulin E (IgE) and sensitization to ragweed. Immunological workup showed normal immunoglobulins and good specific immunity (good vaccine response and normal humoral response to HSV-1) but a decreased number of T- cells (CD3+ 1020/µL (1320-3300), CD3+CD8+ 281/µL (390-1100) with normal T-cell response after antigen stimulation. The diagnosis of Darier disease (DD) was confirmed based on medical history, clinical findings and histological finding of focal suprabasal acantholysis and dyskeratosis (Figure 3). Low-dose oral retinoid therapy was initiated with modest clinical response after 6 months of therapy. In the light of recent publication (1), we initiated intravenous immunoglobulin (IVIG) substitution (400 mg/kg every month) with excellent clinical response. After 4 months, the patient's skin improved in terms of reduced inflammation, scab healing, and reduced itching. Acyclovir prophylaxis was continued. The patient had no new episodes of KVE during follow-up. Kaposi's varicelliform eruption (KVE) or eczema herpeticum occurs in a chronic inflammatory skin disease such as atopic dermatitis (AD), SD, Hailey-Hailey disease, allergic contact dermatitis, psoriasis, and DD (2). It is considered a dermatologic emergency due to its high mortality rate if misdiagnosed or left untreated (3). DD is a rare autosomal dominant genodermatosis of variable expressivity caused by mutations in the ATP2A2 gene, which encodes a sarco/endoplasmic reticulum calcium ATPase (SERCA2) highly expressed in keratinocytes (4). The onset of the disease usually occurs between the ages of 6 and 20 years. There are several clinical variants of DD: hypertrophic, verrucous, vesicular-bullous (dyshidrotic), erosive, and predominantly intertriginous forms (4). The fact that skin lesions occurred in infancy and a negative family history for skin diseases could be the reason our patient was initially misdiagnosed with seborrheic dermatitis. Due to the variable expressivity of the disease, it is impossible to exclude the diagnosis in other family members, and genetic testing of the patient and family members is therefore planned. A co-occurrence of neuropsychiatric abnormalities such as epilepsy, mental impairment, and mood disorders have been reported in patients with Darier disease, and these disorders were also present in our patient (5), indicating a correct diagnosis. Patients with DD have a high propensity for severe viral, bacterial, and fungal skin infection, probably due to local disruption of the skin barrier function or as the result of an underlying defect in general host defence (6). The occurrence of KVE in patients with DD is rare (7) and possibly caused by a disturbances in cell-mediated immunity (8). Despite abnormal findings in cellular immunity in some patients with DD, no consistent or specific abnormalities of the immune system have yet been demonstrated (6). Our patient had a decreased number of cytotoxic T-cells with normal T-cell response after antigen stimulation (in contrast with the findings of Jegasothy et al. (6)) and normal humoral response to HSV-1 infection. Recurrent KVE in our patient could be related to immune system dysfunction as an additional risk factor, along with impaired skin barrier. The excellent clinical response to IVIG speaks in favor of the role of antibody immune response in preserving the skin barrier. Occurrence of KVE in patients with mild DD (as in the case of our patient) and in some patients immediately preceding clinical skin manifestations of disease, argues very strongly against the second supposition. The severity of DD is variable and has a chronic course with frequent exacerbations and remissions. Known exacerbating triggers are: heat, sweat, sun exposure, friction, medication, and infection (9,10). The disease is chronic, and management is focused on the improvement of the skin appearance, relief of symptoms (e.g., irritation, pruritus, and malodor), and prevention or treatment of secondary infections. Topical (emollients, corticosteroids, retinoids, 5-fluorouracil, tacrolimus, pimecrolimus), physical (excision, electrodessication, dermabrasion, ablative laser, photodynamic therapy), and systemic (oral antibiotics, antiviral drugs, antimicrobial prophylaxis, vitamin A, retinoids) therapies are among the treatment options, all of which are of limited effect (2,11,12). IVIG substitution could be beneficial in some patients with Darier disease (1). In conclusion, this case highlights the association of DD with impaired cellular immunity and indicates the importance of proper diagnosis due to adequate management and avoidance of possible fatal outcomes. However, whether a subtle abnormality of T-cells in DD predisposes the patient to KVE remains unclear. Possible underlying mechanisms should be investigated further.