Abstract
IntroductionSTAT3 dominant negative disease (STAT3 DN) is characterized by elevated IgE, recurrent skin and lung infections, skeletal, connective tissue, and vascular abnormalities. Early genetic diagnosis, especially with familial disease, allows for early intervention, which may impact natural history through minimizing infectious complications. MethodsWe retrospectively reviewed medical records of 18 STAT3 DN pediatric patients born after 2007, when STAT3 genetic testing was available. Clinical features, laboratory results, infections and treatments were compared between those with STAT3 DN family history and probands. ResultsOur cohort included 8 patients with STAT3 DN diagnosed by family history (median age 9 years; range 4–14) and 10 probands (median age 13 years, range 5–14). For those with family history, one was diagnosed in utero, six by 6 months of age, and one at 2 years. Probands were diagnosed at a median age of 2 years (range 1–6 years). STAT3 mutation domains were similar between groups. Those with family history started antiseptic washes at a mean of 2.4 months and prophylactic antibiotics at 0.4 years, whereas probands initiated antiseptics at 4.5 years and prophylactic antibiotics at 3 years. Compared to probands, patients with STAT3 DN diagnosed by family history had significantly (p < 0.05) reduced rates of hospitalizations (mean 0.6 vs 6.2 times), bacterial pneumonias (13% vs 90%), >4 skin abscesses (25% vs 90%), other serious infections (0% vs 40%), recurrent ear infections and/or tympanostomy tube placement (0% vs 60%), and severe eczema (13% vs 60%). Significant differences were not seen in parenchymal lung abnormalities (13% vs 50%, p = 0.09) and non-immunologic features, such as fractures and joint hyperextensibility. Mean peak serum IgE and absolute eosinophil counts (AEC) were comparable (IgE 6,865 vs 13,317 IU/mL; AEC 1,023 vs 1,182 cells/uL in family history vs probands). Those with family history received less advanced therapies than probands, specifically immunoglobulin replacement (13% vs 60%), antifungals (25% vs 60%), and lung surgery (0% vs 40%). One proband received bone marrow transplantation. ConclusionEarly diagnosis and intervention positively impacts disease course and management with markedly reduced rates of infectious complications, which may decrease future morbidity and mortality in this vulnerable patient population.
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