Segmental type 1 Darier disease: a case series highlighting late-onset disease.

Darier disease (DD), also known as dyskeratosis follicularis, keratosis follicularis or Darier–White disease, is a genodermatosis with autosomal inheritance. It is characterized by multiple, red-to-brown, crusted, follicular and nonfollicular hyperkeratotic papules preferentially affecting the scalp, face, neck, trunk and acral extremities. Skin lesions are exacerbated by ultraviolet radiation exposure, heat, occlusion, sweating and, interestingly, administration of lithium. DD affects men and women equally, with an estimated prevalence of 1 per 36 000–100 000. Most patients first develop lesions during the second decade of life. The pathogenesis of DD is related to mutations in the reticulum Ca ATPase gene (ATP2A2) on chromosome 12q23–24.1. Symmetrical distribution of skin lesions is typically seen in individuals with a germline mutation. However, mosaicism can occur in DD via postzygotic mutations. A de novo mutation in an otherwise normal embryo will result in type 1 mosaicism: a strikingly linear array of lesions following the lines of Blaschko. We present several notable cases. Patient 1 (index case). A 69-year-old woman presented with a 10-month history of a pruritic skin eruption initially limited to the right flank. Triamcinolone 0 1% cream had provided some improvement. Three months later she noticed development of additional lesions, involving the right side of the chest, right thigh and then the right side of the back. Her family history was unremarkable. Examination showed multiple coalescing, brown to erythematous, umbilicated papules with mildly crusted centres and striking predilection for the right side of the body in a blaschkoid distribution . Skin biopsy from the right abdomen showed focal acantholytic dyskeratosis. The diagnosis of segmental type 1 DD was rendered, and treatment with topical retinoids was instituted with resolution of most lesions, with mild residual hyperpigmentation. To uncover additional cases of segmental type 1 DD, a retrospective review was conducted of the clinical and histopathological features of patients with segmental or mosaic type 1 DD who were evaluated at the Mayo Clinic between 1 January 1997 and 28 October 2013. We queried our institutional electronic database (clinical notes and final pathology diagnosis) for this period using the keywords ‘Darier disease’, ‘Darier–White disease’, ‘dyskeratosis follicularis’ and ‘keratosis follicularis’. Age, sex, symptoms, duration, precipitating or aggravating factors, differential diagnosis, previous diagnosis, previous treatments, family history and complications were recorded. The study was approved by the institutional review board. The diagnosis of segmental DD was based on clinical findings and histopathological examination, taking into account the broad differential diagnosis of acantholytic dyskeratosis, including Grover disease and Hailey–Hailey disease. The association of segmental (blaschkoid) acantholytic dyskeratosis in a seborrhoeic distribution is restricted to segmental DD. Confirmatory genetic testing was not performed. We identified 45 patients with DD, including six who had segmental type 1 DD. The patients’ characteristics are presented in Table 1. Clinical findings and treatment recommendations are described below. Histopathological examination in all patients showed acantholytic dyskeratosis (corps ronds and grains). Patient 2. A 33-year-old woman presented with a 4-year history of persistent, slightly pruritic ‘bumps’. Examination showed slightly hyperpigmented, minimally scaly papules scattered about the volar and dorsal aspects of the left forearm, with extension to the left axilla, as well as several hundred papules, scattered individually and coalescing into plaques, on the posterior aspect of the left shoulder. Treatment with topical tretinoin was recommended. Patient 3. A 38-year-old man presented with a recurrent asymptomatic eruption of the right chest, flank and back for three consecutive years. Examination showed multiple confluent, erythematous, slightly crusted, keratotic 1–2-mm papules in a linear array on the right chest and right flank, extending onto the right back. Treatment with a lactic acid-based lotion was initiated. Patient 4. A 38-year-old woman presented with an 8-year history of somewhat pruritic erythematous papules,