A Case of Segmental Darier Disease

Darier disease (DD), also known as Darier-White disease, follicular keratosis, or dyskeratosis follicularis, is an uncommon autosomal dominant genodermatosis with complete penetrance and variable expressivity. This disorder is caused by mutations in the ATP2A2 gene and affects the skin, nails, and mucous membranes (1,2). A 40-year-old woman, without comorbidities, presented with pruritic, unilateral skin lesions on the trunk since she was 37 years old. Lesions had remained stable since onset, with physical examination revealing tiny scattered erythematous to light brown keratotic papules beginning at the patient's abdominal midline, extending over her left flank and onto her back (Figure 1, a, b). No other lesions were observed, and family history was negative. Skin punch biopsy revealed parakeratotic and acanthotic epidermis with foci of suprabasilar acantholysis and corps ronds in the stratum spinosum (Figure 2, a, b, c). Based on these findings, the patient was diagnosed with segmental DD - localized form type 1. DD usually develops between the ages of 6 and 20 and is characterized by keratotic, red to brown, sometimes yellowish, crusted, pruritic papules in a seborrheic distribution (3,4). Nail abnormalities, alternating red and/or white longitudinal bands, fragility, and subungual keratosis can be present. Mucosal whitish papules and palmoplantar keratotic papules are also frequently observed. Insufficient function of the ATP2A2 gene that encodes for the sarco/endoplasmic reticulum Ca2+ ATPase type 2 (SERCA2) leads to calcium dyshomeostasis, loss of cellular adhesion, and characteristic histological findings of acantholysis and dyskeratosis. The main pathological finding is the presence of two types of dyskeratotic cells, "corps ronds", present in the Malpighian layer, and "grains", mostly located in the stratum corneum (1). Approximately 10% of cases present as the localized form of disease, with two phenotypes of segmental DD having been observed. The more common, type 1, is characterized by a unilateral distribution along Blaschko's lines with normal surrounding skin, whereas the type 2 variant presents with generalized disease and localized areas of increased severity. Although generalized DD is associated with nail and mucosal involvement, as well as positive family history, these findings are rarely seen in localized forms (1). Family members with identical ATP2A2 mutations may have notable differences in clinical manifestations of the disease (5). DD is usually a chronic disease with reccurent exacerbations. Exacerbating factors include sun exposure, heat, sweat, and occlusion (2). Infection is a common complication (1). Associated conditions include neuropsychiatric abnormalities and squamous cell carcinoma (6,7). Increased risk of heart failure has also been observed (8). Type 1 segmental DD may be clinically and histologically hard to distinguish from acantholytic dyskeratotic epidermal nevus (ADEN). Age of onset plays an important role in differentiation, as ADEN is often congenital (3). However, some studies suggest ADEN is a localized form of DD (1). Other differential diagnoses include herpes zoster, lichen striatus, lichen planus (4), severe seborrheic dermatitis, and Grover disease. Our patient was treated with a topical retinoid, for the first two weeks in combination with a topical corticosteroid. She was advised on the use of proper daily skincare with antimicrobial cleansers and emollients, as well as behavioral measures such as avoiding triggering factors and wearing light clothing, resulting in substantial clinical improvement (Figure 1, c, d) and amelioration of pruritus. Other treatment options include salicylic and lactic acid as well as topical 5-fluorouracil, while oral retinoids are reserved for more severe disease (1-3). Doxycycline and pulsed dye laser have also been reported to be effective (2,9). One in vitro study showed that COX-2 inhibitors may reinstitute the dysregulated ATP2A2 gene (4). In summary, DD is a rare keratinization disorder that can present in a generalized or localized pattern. Although uncommon, segmental DD should be included in the differential diagnosis of dermatoses that follow Blaschko's lines. Treatment options include various topical and oral treatments, depending on disease severity.