Actinomyces in chronic granulomatous disease: an emerging and unanticipated pathogen

Abstract

Background: Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system that causes defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections, mostly by catalase-producing organisms. We report for the first time, to our knowledge, chronic infections with Actinomyces species in 10 patients with CGD. Actinomycosis is a chronic granulomatous condition that commonly manifests as cervicofacial, pulmonary, or abdominal disease, caused by slowly progressive infection with oral and gastrointestinal commensal Actinomyces species. Treatment of actinomycosis is usually simple in immunocompetent individuals, requiring long-term, high-dose intravenous penicillin, but is more complicated in those with CGD because of delayed diagnosis and an increased risk of chronic invasive or debilitating disease.

Methods: Actinomyces was identified by culture, staining, 16S ribosomal DNA polymerase chain reaction, and/or a complement fixation test in 10 patients with CGD.

Results: All 10 patients presented with a history of fever and elevated inflammatory signs without evident focus. Diagnosis was delayed and clinical course severe and protracted despite high-dose intravenous antibiotic therapy and/or surgery. These results suggest an unrecognized and unanticipated susceptibility to weakly pathogenic Actinomyces species in patients with CGD because these are catalase-negative organisms previously thought to be nonpathogenic in CGD.

Conclusions: Actinomycosis should be vigorously sought and promptly treated in patients with CGD presenting with uncommon and prolonged clinical signs of infection. Actinomycosis is a catalase-negative infection important to consider in CGD.

Figure 1

A, Radiologic signs of abdominal actinomycosis on a computed tomographic (CT) scan (patient 6). Abdominal ultrasonography revealed segmentary portal hypertension and perigastric and esophageal varices (not shown); CT scan showed splenomegaly and thrombosis of the splenic vein (extension delimited by white stars), multiple mesenteric lymph nodes (black arrow), gastric wall thickening (white arrow), and a peripancreatic mass (white arrowhead). B, Histologic analysis of abdominal actinomycosis (patient 6). Liver histologic analysis after liver puncture in patient 6 showed extensive parenchymal necrosis and multiple abscesses with filamentous gram-positive bacteria within the granule surrounded by neutrophil “clubbing” cells typical for actinomycosis (original magnification, x10 and x100; Gram stain on the left and Grocott stain on the right).

Figure 2

Radiologic signs of pulmonary actinomycosis (patient 10). A, High-resolution computed tomographic (CT) scan showing (1) focal consolidation, mediastinal and hilar lymph node enlargement, pleural effusion, and granulomatous lesions with partial calcification and (2) diffuse interstitial infiltration from the age of 7 years on. B, Representative positron emission tomographic–CT scan confirming infectious foci with active inflammation (encircled).