Title: Hypereosinophilia as a Novel Presenting Feature of STAT1 Gain-of-Function Mutation.
Abstract: We aim to expand the clinical and immunologic phenotype of STAT1 gain-of-function to include early onset peripheral hypereosinophilia. We present a case of a 12 month-old female who presented with 3 weeks of intermittent fevers, hypereosinophilia and diffuse rash. We performed a completed history and physical examination. We obtained serum immunoglobulins, cytokines, lymphocyte immunophenotyping, NK cell function, STAT1 dephosphorylation by flow cytometry and genetic testing. We obtained skin, liver, duodenal, lymph node and bone marrow biopsies. The patient was previously non-atopic. The initial eosinophil count was 7.41cells K/mcL. She had IgG of 943 mg/dL, IgM of 120 mg/dL, IgA of 175 mg/dL and IgE of 2 IU/ml. Lymphocyte phenotyping revealed an absolute T cell count of 3,428, CD4 count of 1,403, CD8 count of 1,403, with 71% CD4+ CD45RA+ cells, and 1.2% CD4-CD8-TCRa/b+ cells, NK cell count of 600, and absolute B lymphocyte count of 2,360. Cytokine panel showed elevated sIL2R, IFN-gamma, IL1, IL8 and IL7. CXCL9 was elevated at 124,354pg/ml. NK cell function analysis was normal. Skin biopsy revealed non-specific lymphocytic dermatitis. Bone marrow and lymph node biopsies were unremarkable. Liver biopsy showed steatosis and mixed portal inflammatory infiltrate with scattered eosinophils. Intestinal biopsies revealed duodenal mucosa with villous blunting and diffuse intraepithelial lymphocytes. The patient failed Anakinra, but responded to systemic glucocorticoids and was eventually started on Ruxolitinib. Genetic testing revealed a heterozygous variant in STAT1 c.1169 T>C (p.Met390Thr). STAT1 dephosphorylation by flow cytometry was delayed. Early onset hypereosinophilia can be a presenting feature of STAT1 gain-of-function.