A Late Diagnosis of Chronic Granulomatous Disease

A 49-year-old man presented for immunologic evaluation due to recurrent infections since childhood. He had frequent staphylococcal skin infections related to minor skin trauma, including forceps used during delivery, but no abscesses requiring drainage. He was first hospitalized as a teenager with lymphadenitis and pneumonia. At 21 years, he had spontaneous splenic rupture requiring splenectomy. At age 25, he was hospitalized with pulmonary nocardiosis. At age 30, he was hospitalized with pulmonary aspergillosis for the first time. By the time of presentation, he had five episodes of pulmonary aspergillosis and one episode of cutaneous aspergillosis, each treated with prolonged courses of antifungals. He had not received antimicrobial prophylaxis outside these treatment courses. He continued to have bacterial pneumonias, cellulitis, and onychomycosis throughout adulthood. In his early 40s, he developed a chronic cough and dyspnea. A lung biopsy demonstrated noncaseating granulomas, favored to be hypersensitivity pneumonitis. His symptoms were controlled with mycophenolate monotherapy for two years until he stopped taking it and subsequently required chronic corticosteroids. Given the recurrent Aspergillus infections, a neutrophil oxidative burst was sent and found to be 7%, raising concern for chronic granulomatous disease (CGD). He had no family history of immunodeficiency. Further immunologic evaluation revealed normal quantitative immunoglobulins with protective levels of tetanus, diphtheria, and pneumococcal titers, and normal lymphocyte subsets. Repeat neutrophil oxidative burst was 1.3% with a normal control. Genetic testing for inborn errors of immunity was negative, including CGD-associated genes CYBB, CYBA, NCF2, and NCF4. Daily antifungal and antistaphylococcal prophylaxis were started. This case highlights a late diagnosis of CGD in the 5th decade of life. His infectious pattern was relatively mild until his 20s, when he began to have recurrent pulmonary infections with catalase-positive organisms, possibly due to some residual NADPH oxidase function. The mean age of diagnosis for X-linked CGD is 3 years, while the autosomal recessive form is diagnosed at a mean age of 7.8 years. Interestingly, initial genetic testing for this patient was negative, despite his phenotype being consistent with CGD and repeatedly abnormal oxidative burst. Additional testing, including NCF1, is being sent to further evaluate for a monogenic cause.