Chronic granulomatous disease (CGD) is characterized by defective neutrophil oxidative burst activity with subsequent susceptibility to catalase-positive organisms, invasive fungal infections, in addition to inflammatory bowel disease (IBD)-like enteropathy. Autoimmune and inflammatory complications have also been less commonly described. Autosomal recessive CGD due to NCF1 is challenging to assess genetically through commercial IEI panels due to the presence of pseudogenes.
We describe a patient with presumed NCF1 CGD with a common variable immunodeficiency (CVID)-like pattern of hypogammaglobulinemia, immune thrombocytopenia (ITP), and recurrent sinopulmonary infections.
The patient was found to have pancytopenia, splenomegaly, and mildly elevated IgG with low IgA on initial investigations at age 7. He was subsequently treated for suspected leishmaniasis with amphotericin B. CGD was later diagnosed after hospitalization with an empyema and cutaneous Serratia infection. He was found to have an NCF1 mutation on genetic testing. He was prescribed trimethoprim-sulfamethoxazole and itraconazole for prophylaxis. Years later, he developed chronic ITP treated with intermittent rituximab throughout his teenage years. He was referred six years after his last rituximab treatment for hypogammaglobulinemia and CGD.
The neutrophil oxidative burst assay was very low at 3.1% activation. IgG level at age 7 was reportedly 1,600 mg/dL. In 2020, one year post-rituximab, this was low at 361. In 2025, repeat IgG level was found to be 116 mg/dL with an IgA <5 mg/dL. Invitae genetic testing demonstrated a pathogenic large deletion encompassing exons 21–34 in DUOX2.
Hypogammaglobulinemia is an unexpected finding in CGD. The patient’s previous low IgA and ITP preceding rituximab raises the question of a previous evolving CVID. However, rituximab use makes it impossible to differentiate this from post-rituximab persistent hypogammaglobulinemia.
