Chronic mucocutaneous candidiasis, recurrent herpetic infections and suppurative eyelid infections in a patient carrying a novel gain-of-function mutation in the STAT1 DNA-binding domain

Chronic mucocutaneous candidiasis (CMCC) is characterized by noninvasive persistent Candida infections. Gain-of-function mutations in signal transducer and activator of transcription 1 (STAT1) cause impaired STAT1 dephosphorylation, diminished IL-17-producing T-cells, and CMCC. We report on a 17-year-old boy with CMCC. At 7 years of age he developed mucocutaneous candidiasis. At 8 years he suffered from severe varicella infection and since 11 he experienced recurrent herpetic infections involving genitals and limbs, recurrent abscesses and suppurative eyelid infections. Familial history was negative. The physical examination revealed oral thrush, onichomycosis, suppurative eyelid infection (figure), furunculosis and parodontitis. Azole-sensitive Candida Albicans grew from oral lesions, nails and esophageal mucosa cultures. Prophylactic treatment with fluconazole resulted in a decrease of frequency and severity of fungal infections. Laboratory evaluation revealed normal white blood cell, T- and B-lymphocyte counts, T-lymphocyte proliferation, Ig and IgG subclasses serum levels and responses to vaccines. HIV serology was negative and IgE levels were persistently elevated (684 KU/L). Transitional (8.2%), mature (79.8%) and memory (12%) B cell levels were normal. Memory B cells mostly included IgM and only few switched cells (88 and 12%, respectively). CD4 and CD8 naïve and memory T cells were normal. IL-17-producing T-cell numbers were 0%. Toll like receptor stimulation resulted in high levels of IL-10, IL1 beta, TNF alpha, IFN-gamma, IL-6 and IL-8. Full-length sequencing of STAT1 genomic DNA identified a T387A heterozygous mutations in the DNA-binding domain, not identified in the unaffected parents. This mutation has not been previously reported.