Immune deficiencies, infection, and systemic immune disorders
Inflammatory manifestations in a single-center cohort of patients with chronic granulomatous disease

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Background

Chronic granulomatous disease (CGD) is a rare phagocytic disorder that results in not only infections but also potentially severe inflammatory manifestations that can be difficult to diagnose and treat.

Objective

To describe inflammatory manifestations in a single-center cohort of patients with CGD.

Methods

Medical records of patients treated at Necker-Enfants Malades Hospital (Paris, France) between 1968 and 2009 and registered at the French National Reference Center for Primary Immunodeficiencies (CEREDIH) were retrospectively reviewed.

Results

In a study population of 98 patients, a total of 221 inflammatory episodes were recorded in 68 individuals (69.4%). The incidence rate of inflammatory episodes was 0.15 per person-year (0.18 in patients with X-linked [XL] CGD and 0.08 in patients with autosomal-recessive [AR] CGD). The most commonly affected organs were the gastrointestinal tract (in 88.2% of the patients), lungs (26.4%), the urogenital tract (17.6%), and eyes (8.8%). Inflammation at other sites (the skin, central nervous system, and tympanum) and autoimmune manifestations (lupus, arthritis, etc) were recorded in 19.1% and 10.3% of the patients, respectively. Granuloma was found in 50% of the 44 histological analyses reviewed. The risk of inflammatory episodes was 2-fold higher in patients with XL-CGD than in patients with AR-CGD (relative risk, 2.22; 95% CI, 1.43-3.46).

Conclusions

Patients with XL-CGD have a higher risk of developing inflammatory episodes than do patients with AR-CGD. Although the most commonly affected organ is the gastrointestinal tract, other sites can be involved, making the management of patients with CGD a complex, multidisciplinary task.

Section snippets

Methods

In accordance with French regulatory requirements, informed consent was obtained from patients and/or parents on registration in the French National Center for Primary Immunodeficiencies registry (CEREDIH).38 In this context, we carried out a retrospective analysis of the medical records of patients with CGD referred to Necker-Enfants Malades Hospital, Paris, between April 1968 and June 2009. CGD was defined as the presence of a characteristic mutation and/or the absence of (or a strong

Characteristics of the study population

The final study population comprised 98 patients (from 85 kindreds). Of these, 70 (71.4%) had XL-CGD, 20 (20.4%) had AR-CGD, and 8 (8.1%) had CGD of unknown inheritance (see Table I). Within the AR-CGD group, defects in p47phox were the most prevalent (50%), followed by defects in p22phox (30%) and p67phox (20%). There were no significant differences between the XL and AR subgroups in terms of age at diagnosis, at disease onset, and at first episode and the duration of follow-up. In contrast,

Discussion

Although infections in CGD have been studied in depth over the last few decades, data on inflammatory complications are less abundant. Our retrospective study of a large, single-center cohort of patients provides an overview of these manifestations. We found a higher prevalence of inflammatory manifestations (69.4%) than reported in the literature.7, 34, 36 Moreover, 85% of our patients had experienced their first inflammatory episode by the age of 20 years. Our cohort is similar to other large

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  • Cited by (0)

    This study was funded by the French Ministry of Health and received additional support from the French Association of Patients with Primary Immunodeficiencies (IRIS: Immuno-déficience primitive-recherche-information-soutien). The Centre de Référence des Déficits Immunitaires Héréditaires (CEREDIH) received unrestricted educational grants from LFB, CSL Behring, Baxter Biosciences, GSK, Pfizer, Octapharma, and Orphan-Europe.

    Disclosure of conflicts of interest: The authors declare that they have no relevant conflicts of interest.

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