Use of Interferon Gamma in Female Carriers of X-linked Chronic Granulomatous Disease

Abstract

IntroductionChronic granulomatous disease (CGD) is characterized by increased frequency and severity of certain infections, autoimmune disease, and hyperinflammation. Heterozygous female carriers of X-linked CGD may experience similar symptoms. Guidance for management of female carriers is limited. We describe the use of interferon gamma (IFNγ) in X-linked CGD carriers. MethodsA multi-center retrospective chart review identified 4 carriers of X-linked CGD who received prophylaxis with IFNγ. Results of dihydrorhodamine (DHR) assay, infections and autoinflammatory features were documented and adverse events (AE) related to IFNγ were recorded. ResultsFour females (mean age 40 [range 0.5–71] years) received IFNγ (75–100 µg 3 times per week via subcutaneous injection) for a mean duration of 43 (range 16–63) months. Infections prior to the start of IFNγ included sepsis/bacteremia, pneumonia, skin and soft tissue infection, osteomyelitis, and gastroenteritis with CGD-associated pathogens including Serratia marscescens, Burkholderia cepacia, Nocardia spp, and methicillin-resistant Staphylococcus aureus (MRSA). Inflammatory complications (some in more than one subject) included dermatologic (pyoderma gangrenosum [n = 1], unspecified dermatitis [n = 2]), rheumatologic (arthritis [n = 1], Raynaud's syndrome [n = 1]), and gastrointestinal (inflammatory diarrhea [n = 1], Barrett's esophagus [n = 1]). Each carrier exhibited two populations of neutrophil oxidative burst. The populations expressing DHR were as follows: 0.08, 1, 3, and 10.8 +DHR%. Antibacterial prophylaxis was administered in all 4 subjects, and antifungal prophylaxis in 3 subjects. Pre-medications were not administered, and AE associated with IFNγ were mild or moderate in 3 of 4 subjects (one subject had no AE) and did not result in any treatment discontinuations. One patient discontinued prophylaxis with IFNγ after correction of CGD following hematopoietic stem cell transplant. The average length of follow-up since starting IFNγ was 38 months. While on IFNγ therapy, one patient developed atypical mycobacterial and cytomegalovirus pneumonia and MRSA chronic osteomyelitis thought related to poor compliance, while another developed Serratia olecranon abscess/. None developed autoimmune/inflammatory disease while on therapy. ConclusionsThis is the first report to our knowledge of IFNγ use for prophylaxis in carriers of X-linked CGD. IFNγ was well tolerated, and should be considered for prophylaxis in female carriers with very low neutrophil oxidative burst or frequent or severe CGD-associated infections.