Chronic mucocutaneous candidiasis

Chronic mucocutaneous candidiasis (CMC) is a group of rare primary immunodeficiency disorders characterized by persistent or recurrent infections of the skin, nails, and mucous membranes caused by Candida species, most commonly Candida albicans. The condition results from a selective deficiency in T-cell-mediated immunity against Candida and, in some forms, other fungi. CMC can occur as an isolated condition or as part of broader syndromes, including autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED/APS-1) caused by mutations in the AIRE gene, or as autosomal dominant CMC caused by gain-of-function mutations in STAT1. Other genetic causes include mutations in STAT3, IL17F, IL17RA, IL17RC, and ACT1/TRAF3IP2, reflecting the critical role of the IL-17 pathway in antifungal defense. The disease primarily affects the skin, nails, and mucosal surfaces including the oral cavity, esophagus, and genital tract. Patients typically present with persistent oral thrush (white plaques on the tongue and buccal mucosa), chronic nail dystrophy (thickened, discolored, and deformed nails), and skin lesions that can become thickened and crusted. In some forms, patients may also develop autoimmune manifestations such as hypothyroidism, adrenal insufficiency, or type 1 diabetes, particularly in APECED. Patients with STAT1 gain-of-function mutations may additionally be susceptible to viral and bacterial infections and may develop autoimmune cytopenias, cerebral aneurysms, or squamous cell carcinoma of the esophagus or oral cavity as complications of chronic infection. Treatment of CMC involves long-term antifungal therapy, most commonly with azole antifungals such as fluconazole or itraconazole. Refractory cases may require newer agents such as voriconazole or posaconazole. Management of associated autoimmune conditions requires appropriate hormone replacement or immunomodulatory therapy. For severe cases, particularly those with STAT1 gain-of-function mutations, JAK inhibitors (such as ruxolitinib) have shown promise as targeted therapies. Hematopoietic stem cell transplantation has been considered in severe, life-threatening cases, though outcomes vary depending on the underlying genetic defect.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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