Autopsies in Chronic Granulomatous Disease: A 35-Year Perspective

We performed a single-center retrospective analysis of chronic granulomatous disease (CGD) autopsy reports to better understand causes of death, end-organ damage, and disease pathophysiology. Forty-four autopsies of CGD patients, including one X-linked female carrier, were performed from February 1990 to June 2025. These cases represent approximately 60% of the CGD deaths over 35 years. There was an increase in age at death over this time, despite a heavy burden of infections. The immediate cause of death was infection n = 30 (68%); Aspergillus species (33%) was the most frequent pathogen. One death was associated with SARS-CoV-2. An aggressive new Aspergillus species, Aspergillus tanneri, and an unidentified Burkholderia species were identified in this cohort.Noninfectious causes of death in 14 patients were associated to accident (1), respiratory failure (2), renal failure (2), surgical complications (1), post-transplant complications (2), cardiovascular complications (2), cerebral infarction (1), Transfusion-Related Acute Lung Injury (TRALI), a serious complication of blood transfusions where the recipient experiences acute lung injury in one case, and one death attributed to metastatic pancreatic ductal adenocarcinoma.A substantial portion had characteristic pigmented-laden macrophages in multiple organs, with a high concentration in the brain parenchyma. Atherosclerotic manifestations were present in a third of the cases. One patient, p22phox, had minimal atherosclerosis manifestations early in life (19 yrs). Lungs and hearts were significantly heavier when compared to norms. Livers were not significantly larger, although there was evidence of underlying inflammatory disease. Periportal inflammation was noted in 19 patients (46%), and nodular regenerative hyperplasia (NRH) was found in 7 (16%). Kidneys were small overall (atrophic), which may be related to drug exposure, specifically amphotericin B. Glomerulosclerosis or chronic renal compromise was found in 17 patients (41%), two of whom were children. Among those with glomerulosclerosis, one had never received amphotericin B. This pathology review shows pigment-laden macrophages across multiple organs not previously recognized, including the brain parenchyma. This is the largest autopsy series known in this population, underscoring the increased survival over time. With fungal infections being the most common cause of death, this emphasizes the importance of antifungal development and definitive cure in this disease.