X-linked chronic granulomatous disease (XLCGD) is a rare inborn error of immunity (IEI) associated with infections, inflammation, and autoimmunity. Female carriers of XLCGD experience similar symptoms due to skewed X-chromosome inactivation (lyonization). National registries for IEI currently do not capture XLCGD carriers, creating deficiencies in understanding prevalence, clinical manifestations, complications, management, and long-term outcomes. We developed a patient survey to collect clinical and laboratory data to address these current gaps.
Thirteen XLCGD carriers were recruited to complete a REDCap® survey. Data collected included demographics, clinical symptoms, infections, autoimmune conditions, laboratory details, family history, and treatment, including antimicrobial and immunomodulatory medications. Dihydrorhodamine (DHR), used to assess neutrophil function, was collected when available.
Symptoms were reported in 11 of 13 (84%) participants. The median age was 54.0 (range: 22-78) years. In those symptomatic, the age of symptom onset was median 13.8 years (range: 0.4-52) and duration of symptoms averaged 39 (range: 24.9-52.3) years. The most common symptoms were infection in 11 of 13 (84%), including pneumonia (n = 5), skin abscess (n = 7), cellulitis (n = 3), organ abscess (n = 1), lymphadenitis (n = 2), and urinary tract infections (n = 7). Serratia marcescens (n = 1), Staphylococcus aureus (n = 1), and Prevotella species (n = 1) were isolated from skin abscesses. Five (41%) participants received infection prophylaxis, including trimethoprim-sulfamethoxazole (n = 5), itraconazole (n = 3), and interferon gamma-1b (n = 1). One subject declined interferon gamma-1b due to insurance concerns. Autoimmunity was noted in 9 of 13 (69%) participants, including inflammatory bowel disease and photosensitive rash (both present in 25% of patients), and less commonly oral ulcers, rheumatoid and psoriatic arthritis, uveitis, celiac disease, pyoderma gangrenosum, lupus, Raynaud phenomenon, and autoimmune thyroid disease. The median DHR, available in 4 patients, was 9% (range: 6-33.5%) in those with infections (n = 3) and 52% in the asymptomatic participant.
To our knowledge, this is the first national patient registry for XLCGD carriers. The majority of XLCGD carriers were symptomatic, had a long duration of symptoms, and had a high symptom burden including infections and autoimmunity. A lower DHR percentile was associated with increased infections. Management often included antimicrobial prophylaxis. Recruitment is ongoing, and a larger cohort size is needed to expand these findings.
