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Chronic granulomatous disease: Pathogenesis, clinical manifestations, and diagnosis

Sergio D Rosenzweig, MD
Steven M Holland, MD
Section Editor
Jordan S Orange, MD, PhD
Deputy Editor
Elizabeth TePas, MD, MS


Chronic granulomatous disease (CGD) is a genetically heterogeneous condition characterized by recurrent, life-threatening bacterial and fungal infections and granuloma formation. CGD is caused by defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, which constitutes the phagocyte oxidase (phox). These genetic defects result in the inability of phagocytes (neutrophils, monocytes, and macrophages) to destroy certain microbes. The diagnosis is made by neutrophil function testing, and then the exact defect is determined by genotyping.

Infections in patients with CGD are generally caused by catalase-positive micro-organisms (most bacterial and all fungal pathogens are catalase positive), but catalase is neither necessary nor sufficient for pathogenicity in CGD. The frequent sites of infection are lung, skin, lymph nodes, and liver. The formation of granulomata is especially problematic in the gastrointestinal and genitourinary tracts. Other inflammatory manifestations are seen as well.

This topic will review the pathogenesis, clinical manifestations, and diagnosis of CGD. The treatment and prognosis of CGD, as well as an overview of primary disorders of phagocyte function, are discussed separately. (See "Chronic granulomatous disease: Treatment and prognosis" and "Primary disorders of phagocytic function: An overview".)


The frequency of CGD in the United States is approximately 1:200,000 live births [1]. The disease primarily affects males as most mutations are X linked. Rates are almost identical across ethnic and racial groups, with approximately one-third of the X-linked mutations occurring de novo. However, in cultures in which consanguineous marriage is common, the autosomal recessive forms of CGD are more common than X-linked forms, and overall incidence rates may be higher [2].

CGD may present at any time from infancy to late adulthood, but the majority of patients are diagnosed as toddlers and children before the age of five years. In several series, the median age at diagnosis was 2.5 to 3 years of age [3-6]. A growing number of patients are diagnosed in later childhood or adulthood. This is due in part to recognition of milder cases of autosomal recessive CGD, as well as delayed diagnosis in some patients. Diagnosis may be delayed because of potent antimicrobials that inadvertently treat many CGD-associated infections, postponing diagnosis until more severe infections indicate CGD as the underlying cause. X-linked CGD tends to have an earlier onset and be more severe than the most common autosomal recessive form, p47phox deficiency [1].

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Literature review current through: Nov 2017. | This topic last updated: Mar 01, 2017.
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