Chronic mucocutaneous candidiasis (CMC) is the “signature” infection of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), a primary immunodeficiency disorder caused by mutations in autoimmune regulator (AIRE) that manifests with CMC and autoimmunity in endocrine and non-endocrine organs. Although widely recognized in Europe, APECED is less defined in patients from the Western Hemisphere. No study has examined clinical, microbiological, and treatment characteristics of CMC in American APECED thus far.
We enrolled 35 consecutive American APECED patients (33 from the US) and collected information on the presence of CMC, site(s) involved, AIRE mutations, and treatment. All patients had cultures of mucosal sites with Candida speciation by MALDI-TOF.
Among all patients, 30 (86%) had CMC; no genotype-phenotype correlation was noted for CMC and specific AIRE mutations. The median age of onset of CMC in affected patients was 1 year (mean, 4.4 years; range, 0.5-26 years), with CMC and urticarial eruption being the most common initial manifestations among all patients. Among the 30 CMC patients, all (100%) had oral candidiasis, while 18 (60%), 12 (40%) and 6 (20%) had esophageal, nail and skin candidiasis, respectively. Twelve of 17 women with CMC (71%) had vaginal candidiasis. Among cultured Candida strains, 74% were C. albicans, 26% were C. glabrata, while mixed C. albicans-C. glabrata isolation was noted in 2 patients. No oral or esophageal carcinomas were seen. Several topical and systemic antifungals were used to treat CMC over time including fluconazole (77%), voriconazole (7%), posaconazole (3%), ketoconazole (17%), miconazole (3%), micafungin (7%), gentian violet (7%), nystatin (20%), and orally formulated amphotericin B (13%). The majority of patients (83%) responded to a first-line therapy, while the remaining patients required multiple different regimens. Eleven patients (37%) required continuous treatment to prevent frequent CMC recurrences, while the remaining patients only required treatment sporadically.
CMC is a common early manifestation of American APECED patients. Oral, esophageal and vaginal candidiasis caused by C. albicans predominate, and patients require variable intensity and duration of antifungal therapy to sustain remission.
A. Bondici, None
S. R. Rose, None
M. S. Lionakis, Viamet Pharmaceuticals: Collaborator , Research support
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