Chronic Granulomatous Disease

Abstract

Background:Chronic granulomatous disease (CGD) is an uncommon primary immunodeficiency that can be inherited in an X-linked (XL) or an autosomal recessive (AR) manner. We reviewed our large, single-center US experience with CGD.Methods:We reviewed 27 patients at Ann & Robert H. Lurie Children’s Hospital of Chicago from March 1985 to November 2013. Fisher exact test was used to compare differences in categorical variables, and Student t test was used to compare means for continuous variables. Serious infections were defined as those requiring intravenous antibiotics or hospitalization.Results:There were 23 males and 4 females; 19 were XL and 8 were AR. The average age at diagnosis was 3.0 years; 2.1 years for XL and 5.3 years for AR inheritance (P = 0.02). There were 128 serious infections. The most frequent infectious agents were Staphylococcus aureus (n = 13), Serratia (n = 11), Klebsiella (n = 7), Aspergillus (n = 6) and Burkholderia (n = 4). The most common serious infections were pneumonia (n = 38), abscess (n = 32) and lymphadenitis (n = 29). Thirteen patients had granulomatous complications. Five patients were below the 5th percentile for height and 4 were below the 5th percentile for weight. Average length of follow-up after diagnosis was 10.1 years. Twenty-four patients were compliant and maintained on interferon-γ, trimethoprim-sulfamethoxazole and an azole. The serious infection rate was 0.62 per patient-year. Twenty-three patients are alive (1 was lost to follow-up).Conclusions:We present a large, single-center US experience with CGD. Twenty-three of 27 patients are alive after 3276 patient-months of follow-up (1 has been lost to follow-up), and our serious infection rate was 0.62 per patient-year.

Interferon γ-1b in chronic granulomatous disease and severe malignant osteopetrosis: a guide to its use in the USA

“…Interferon c-1b has also been used to treat patients with CGD in the clinical practice setting [33][34][35][36][37]. For example, in a retrospective review of 26 patients with CGD in a single US hospital, 24 patients were receiving treatment with interferon c-1b and prophylactic antibacterials [37].…”

“…After a mean follow-up of 9.8 years from time of diagnosis (equivalent to 3159 patient-months), 23 patients were alive without having undergone haematopoietic stem cell transplantation (HSCT). The rate of serious infections was 0.35 per patientyear, with pneumonia/lung abscess, liver abscess and brain abscess being the most commonly reported serious infections (31, 12 and 2 cases, respectively) [37].…”

“…For example, in a retrospective review of 26 patients with CGD in a single US hospital, 24 patients were receiving treatment with interferon c-1b and prophylactic antibacterials [37]. After a mean follow-up of 9.8 years from time of diagnosis (equivalent to 3159 patient-months), 23 patients were alive without having undergone haematopoietic stem cell transplantation (HSCT).…”

Genetic Susceptibility to Fungal Infections: What is in the Genes?

“…It was initially thought that CGD had an X-linked (XL) pattern of inheritance, but later autosomal recessive (AR) forms of the disease were also recognized. Both forms involve primarily defects in the NADPH oxidase in either its membrane-associated (XL form) or cytosolic (AR form) components [35]. The sex-linked gene encodes for the gp 91 protein.…”

Multiplexed Proteomic Analysis for Diagnosis and Screening of Five Primary Immunodeficiency Disorders From Dried Blood Spots

“…In this study, we expanded the multiplexed proteomic diagnostic panel to screen DBS for five molecularly defined PIDDs using eight signature peptide biomarkers. The current set of targeted PIDDs includes ADA deficiency (ADA) (39,40), Dedicator of cytokinesis 8 (DOCK8) deficiency (6,41), X-Linked Chronic Granulomatous disease (XL-CGD) (42,43), Wiskott-Aldrich Syndrome (WAS) (44,45), and X-Linked Agammaglobulinemia (XLA) (46,47). These specific PIDDs were chosen because they are strong candidates for newborn screening when accounting for the Wilson and Jungner criteria for selecting candidate diseases (48).…”