Disseminated Coccidioidomycosis Treated with Interferon-gamma and Dupilumab

Disseminated coccidioidomycosis that was unresponsive to antifungal antibiotics developed in a child later found to have defective interleukin-12 signaling. Addition of interferon-gamma and dupilumab, an antibody to block the interleukin-4 and interleukin-13 receptor, led to resolution of lesions in the skeleton, lungs, soft tissues, and nodes. We 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-gamma. Supplementation of antifungal agents with interferon-gamma 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.)