Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome.

BACKGROUND: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome (APECED; OMIM 240300) is a rare autosomal recessive disorder defined by a variable combination of endocrine failure, chronic mucocutaneous candidiasis (CMC), and dystrophy of the dental enamel and nails. APECED is caused by mutations in the autoimmune regulator gene (AIRE). Alopecia areata (AA) and vitiligo are diseases with autoimmune pathogeneses, and have been recognized as part of the APECED complex. There are rare reports of other cutaneous manifestations.

OBJECTIVES: We sought to delineate the dermatological features of APECED in an Irish case series with emphasis on timing of their appearance and association with disease severity. Furthermore, we looked for evidence of genotype: phenotype correlation. Finally, we wanted to determine if the ectodermal changes described represent a primary ectodermal dysplasia or whether the ectodermal manifestations are secondary phenomena.

METHODS: Irish patients with APECED were invited to attend a multidisciplinary clinic (Dermatology, Endocrinology, Dentistry and Ophthalmology) held in Our Lady's Hospital for Sick Children, Dublin. Clinical data were compiled from case notes and questionnaires. All patients had a detailed cutaneous examination. Blood samples were obtained for mutational analysis.

RESULTS: Eighteen patients (seven males and 11 females) from 15 families were interviewed and examined. The mean age at diagnosis was 6 years (range 8 months-18 years). All patients had evidence of CMC, 13 (72%) had candidal onychomycosis or paronychia, six (33%) had AA and two had vitiligo. In the case of two patients the diagnosis was made on recognition of dermatological manifestations and confirmed by mutational analysis. Both patients developed Addison's disease on follow-up. CMC was an early feature, often predating diagnosis (10 of 18). AA and vitiligo presented later, and may reflect more severe disease in these cases. There was no correlation between the AIRE mutations identified on mutational analysis and the clinical presentation. We found no evidence of an isolated nail dystrophy or features consistent with a primary ectodermal dysplasia.

CONCLUSIONS: APECED is a rare but complex and potentially life-threatening autoimmune disease. CMC is a common and early feature; diagnosis at this stage may pre-empt life-threatening endocrinological crises. It is important for dermatologists to be aware of this association as they are likely to be the earliest clinicians who encounter these children. AA and vitiligo in our series occurred in the setting of established disease. The term "ectodermal dystrophy" is misleading as the ectodermal features described in our series and in the literature are most likely to be secondary phenomena.