A systematic literature review of CVID reveals pervasive detrimental noninfectious manifestations.

Noninfectious manifestations of common variable immunodeficiency (CVID) are not formally summarized. We performed a systematic literature review to generate a comprehensive reference for the field. Splenomegaly was the most reported manifestation across 53 publications, occurring in a median of 35.2% of patients. Frequently reported digestive system manifestations included diarrhea (median 27.8%; 21 publications), hepato(spleno)megaly (median, 21.0%; 19 publications), portal hypertension (median 21.0%; 3 publications), nodular lymphoid hyperplasia (median, 17.0%; 9 publications), and enteropathy (median, 16.0%; 34 publications). Other notable manifestations included interstitial lung disease (median, 8.7%; 32 publications) and autoimmune cytopenias (median 18.0%; 21 publications). Steroids and rituximab were the most frequently reported treatments. Numerous manifestations significantly adversely affected survival, including lymphoma, granulomatous lymphocytic interstitial lung disease, splenomegaly, and liver diseases. These comprehensive data document the pervasiveness and negative impact of noninfectious manifestations in CVID and support a call to action to develop novel therapeutics.