Mutations in signal transducer and activator of transcription 1 (STAT1) cause a broad spectrum of infection susceptibility: severe viral and bacterial infections, nontuberculous mycobacterial disease, and chronic mucocutaneous candidiasis (CMC). CMC is most often associated with hypermorphic mutations that lead to impaired responses to interferon gamma and diminished numbers of IL-17 producing T cells. Herein, we report a case of severe chronic fungal granuloma and mucocutaneous candidiasis due to gain of function mutation inSTAT1.
Sequencing of STAT1 was performed on PCR amplified DNA.
A 24-year-old woman developed a large fungating mass involving the right hand over 10 months, ultimately compromising movement and function. Biopsies yielded Trichophyton tonsurans. She had persistent scaly lesions on her trunk, extremities, and dorsal surfaces of the feet that failed treatment with topical antifungals. Recurrent oral thrush, onychomycosis, and tinea corporis occurred. Immunologic evaluation revealed normal immunoglobulin levels (IgG 2800 mg/dl, IgA 339 mg/dl, IgM 168 mg/dl) with protective vaccine titers. DHR was normal. T cell subsets (CD3 2329 cells/μl, CD4 1138 cells/μl, CD8 1106 cells/μl) were normal as were lymphocyte mitogen responses. Lymphocyte stimulation to tetanus and Candida were suboptimal. A missense mutation was found within the DNA binding domain of STAT1, c.1057G>A, p.E353K.
Defects in STAT1 are an increasingly recognized cause of mucocutaneous fungal susceptibility. This is the first case to our knowledge of severe fungal granuloma caused by a gain of function STAT1 mutation.
- AAAAI 2014 (70th)