• Monica Tsai, Timothy J Thauland, Alden Y Huang, Chantana Bun, Sean Fitzwater, Paul Krogstad, Emilie D Douine, Stanley F Nelson, Hane Lee, Maria I Garcia-Lloret, and Manish J Butte.
• From the Divisions of Immunology, Allergy, and Rheumatology (M.T., T.J.T., C.B., M.I.G.-L., M.J.B.) and Infectious Diseases (S.F., P.K.), Department of Pediatrics, the Department of Human Genetics (E.D.D., S.F.N., H.L.), the Department of Pathology and Laboratory Medicine (H.L.), and the California Center for Rare Diseases, Institute for Precision Health (A.Y.H., S.F.N., M.J.B.), University of California, Los Angeles, Los Angeles.
• N. Engl. J. Med. 2020 Jun 11; 382 (24): 2337-2343.

AbstractWe describe a case of life-threatening disseminated coccidioidomycosis in a previously healthy child. Like most patients with disseminated coccidioidomycosis, this child had no genomic evidence of any known, rare immune disease. However, comprehensive immunologic testing showed exaggerated production of interleukin-4 and reduced production of interferon-γ. Supplementation of antifungal agents with interferon-γ treatment slowed disease progression, and the addition of interleukin-4 and interleukin-13 blockade with dupilumab resulted in rapid resolution of the patient's clinical symptoms. This report shows that blocking of type 2 immune responses can treat infection. This immunomodulatory approach could be used to enhance immune clearance of refractory fungal, mycobacterial, and viral infections. (Supported by the Jeffrey Modell Foundation and the National Institutes of Health.).Copyright © 2020 Massachusetts Medical Society.

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