Considerations in the Diagnosis of Chronic Granulomatous Disease

Abstract

Chronic granulomatous disease (CGD) is a rare primary immunodeficiency that is caused by defects in the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The disease presents in most patients initially with infection, especially of the lymph nodes, lung, liver, bone, and skin. Patients with CGD are susceptible to a narrow spectrum of pathogens, and Staphylococcus aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia species, and Aspergillus species are the most common organisms implicated in North America. Granuloma formation, most frequently in the gastrointestinal and genitourinary systems, is a common complication of CGD and can be seen even before diagnosis. An increased incidence of autoimmune disease has also been described in patients with CGD and X-linked female carriers. In patients who present with signs and symptoms consistent with CGD, a flow cytometric dihydrorhodamine neutrophil respiratory burst assay is a quick and cost-effective way to evaluate NADPH oxidase function. The purpose of this review is to highlight considerations for and challenges in the diagnosis of CGD.

Figure 1.

Assessment of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase function by flow cytometry using the dihydrorhodamine (DHR) assay. (A) Normal neutrophil respiratory burst showing a complete shift in fluorescence after stimulation. (B) X-linked chronic granulomatous disease (CGD) (gp91^phox) histogram showing no significant change in neutrophil fluorescence after stimulation. (C) Autosomal recessive CGD (p47^phox) histogram showing a proportion of unchanged stimulated neutrophils overlapping with the background fluorescence and some neutrophils with significantly reduced fluorescence. (D) X-linked female carrier status histogram with a pattern of 2 peaks reflecting the 2 populations of abnormal and normal neutrophils that result from X-chromosome inactivation. The dashed line indicates the background fluorescence of unstimulated neutrophils, and the green histogram indicates neutrophil fluorescence after phorbol myristate acetate stimulation. Adapted with permission from reference .