Sarcoidosis in Chronic Granulomatous Disease

In addition to increased susceptibility to infections in patients with chronic granulomatous disease (CGD), a higher incidence of sterile inflammatory disorders in these patients has been noted. However, sarcoidosis has not been reported previously in CGD. In this report, we describe two patients who have CGD and a disorder consistent with sarcoidosis on the basis of unequivocal clinical-radiographic presentations, their responses to treatment, and serum angiotensin-converting enzyme levels. Serum angiotensin-converting enzyme levels were measured in 26 other patients with CGD to establish an appropriate reference range. A possible relationship between CGD and sarcoidosis is discussed. C HRONIC GRANULOMATOUS DISEASE (CGD) is a rare primary immunodeficiency with an incidence of 1 in 200 000 to 250 000 live births.1 Mutations in any 1 of the 4 genes (CYBB, CYBA, NCF-1, or NCF-2) encoding the subunits (gp91 phox , p22 phox , p47 phox , and p67 phox , respectively) of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex result in defective production of microbicidal reactive oxidant species.2 Patients with CGD therefore are more susceptible to recurrent suppurative infections. Granulomas, typically caseating, in the setting of infections are a hallmark of CGD. The mechanism for granuloma formation remains unclear and may be related to factors such as increased susceptibility to infections and poor clearance of microorganisms. In addition, a significant subset of patients with CGD have noninfectious inflammatory problems that are often autoimmune in character. The reason for this association is poorly understood. Sarcoidosis, a multiorgan granulomatous disease, occurs at a frequency of 1 to 50 per 100 000 individuals with a cause that remains unknown despite its first description 100 years ago.3 The pathognomonic finding of sarcoidosis is noncaseating epithelioid granulomas, although necrosis is occasionally seen.4 Clinically,