Common Severe Infections in Chronic Granulomatous Disease

Published on Apr 15, 2015in Clinical Infectious Diseases8.313
· DOI :10.1093/CID/CIU1154
Beatriz E. Marciano22
Estimated H-index: 22
(NIH: National Institutes of Health),
Christine Spalding12
Estimated H-index: 12
(NIH: National Institutes of Health)
+ 26 AuthorsSteven M. Holland114
Estimated H-index: 114
(NIH: National Institutes of Health)
Sources
Abstract
Background. Chronic granulomatous disease (CGD) is due to defective nicotinamide adenine dinucleotide phosphate oxidase activity and characterized by recurrent infections with a limited spectrum of bacteria and fungi as well as inflammatory complications. To understand the impact of common severe infections in CGD, we examined the records of 268 patients followed at a single center over 4 decades. Methods. All patients had confirmed diagnoses of CGD, and genotype was determined where possible. Medical records were excerpted into a standard format. Microbiologic analyses were restricted to Staphylococcus, Burkholderia, Serratia, Nocardia, and Aspergillus. Results. Aspergillus incidence was estimated at 2.6 cases per 100 patient-years; Burkholderia, 1.06 per 100 patient-years; Nocardia, 0.81 per 100 patient-years; Serratia, 0.98 per 100 patient-years, and severe Staphylococcus infection, 1.44 per 100 patient-years. Lung infection occurred in 87% of patients, whereas liver abscess occurred in 32%. Aspergillus incidence was 55% in the lower superoxide-producing quartiles (quartiles 1 and 2) but only 41% in the higher quartiles (rate ratio, <0.0001). Aspergillus and Serratia were somewhat more common in lower superoxide producing gp91phox deficiency. The median age at death has increased from 15.53 years before 1990 to 28.12 years in the last decade. Fungal infection carried a higher risk of mortality than bacterial infection and was the most common cause of death (55%).Gastrointestinal complications were not associated with either infection or mortality. Conclusions. Fungal infections remain a major determinant of survival in CGD. X-linked patients generally had more severe disease, and this was generally in those with lower residual superoxide production. Survival in CGD has increased over the years, but infections are still major causes of morbidity and mortality.
Download
📖 Papers frequently viewed together
1,408 Citations
488 Citations
371 Citations
References34
Newest
#1Eda Kepenekli (Marmara University)H-Index: 3
#2Ahmet Soysal (Marmara University)H-Index: 17
Last. Mustafa Bakir (Marmara University)H-Index: 21
view all 6 authors...
Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Among primary immunodefiencies, chronic granulomatous disease (CGD) has the highest prevalence of invasive fungal diseases. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients. In patients whose aspergillosis is refractory to voriconazole, therapeutic options include changing class of antifungal, for example using an amphotericin B formulation, an ec...
3 CitationsSource
#1Jennifer W. Leiding (USF: University of South Florida)H-Index: 11
#2Beatriz E. Marciano (NIH: National Institutes of Health)H-Index: 22
Last. Steven M. Holland (NIH: National Institutes of Health)H-Index: 114
view all 6 authors...
Chronic granulomatous disease is a rare immunodeficiency due to defects in the phagocyte NADPH oxidase. The X-linked form (gp91 phox deficiency) accounts for about 70 % of cases; autosomal recessive p47 phox deficiency accounts for about 25 % of cases. We identified a 10 % incidence of diabetes in p47 phox deficient CGD, but none in X-linked CGD. Renal and cardiovascular diseases were also higher in p47 phox deficiency. p47 phox deficient CGD has non-infectious morbidities distinct from those in...
18 CitationsSource
Chronic granulomatous disease (CGD) was first described in the 1950s and has become a paradigm for genetic neutrophil diseases. It is characterized by recurrent infections with a narrow spectrum of bacteria and fungi as well as a common set of inflammatory complications most notably including inflammatory bowel disease. Over the last half century major advances in management have profoundly altered the major clinical issues and the life expectancy of CGD. With X-linked and autosomal recessive fo...
260 CitationsSource
#1Emilia Liana Falcone (NIH: National Institutes of Health)H-Index: 2
#1E. Liana Falcone (NIH: National Institutes of Health)H-Index: 9
Last. Steven M HollandH-Index: 1
view all 2 authors...
PURPOSE OF REVIEW: Invasive fungal infections (IFIs) remain a major cause of death in patients with chronic granulomatous disease (CGD). We discuss the new insights into the pathogenesis, diagnosis, prevention, and management of invasive fungal infections in patients with CGD. RECENT FINDINGS: CGD has the highest prevalence of IFIs among the immunodeficiencies. Infections typically involve the lung, and the most commonly isolated pathogen is Aspergillus spp. However, IFIs due to rare opportunist...
57 CitationsSource
#1Shahindokht Bassiri-Jahromi (Pasteur Institute of Iran)H-Index: 8
#2Aida Doostkam (Shiraz University)H-Index: 4
Last. A. Doostkam (NCSE: National Center for Science Education)H-Index: 1
view all 2 authors...
Summary Objective Fungal infection presents a serious risk to individuals with compromised immune systems. Chronic granulomatous disease is a primary immunodeficiency with X-linked or autosomal recessive inheritance. Patients with CGD are predisposed to bacterial and fungal infections. The aim of this study was to determine the incidence of fungal infections, identify the most common fungal pathogens, and determine the risk factors associated with fungal infections and mortality in patients with...
13 CitationsSource
#1Sophie Blumental (Necker-Enfants Malades Hospital)H-Index: 9
#2Richard Mouy (Necker-Enfants Malades Hospital)H-Index: 22
Last. Alain Fischer (Paris V: Paris Descartes University)H-Index: 159
view all 9 authors...
Background. Invasive fungal infection (IFI) represents a life-threatening condition for patients with chronic granulomatous disease (CGD) and causes one-third of deaths in this population. This study offers a descriptive review of invasive mold infection (mIFI) in children with CGD over an extended period of time. Methods. In a cohort of patients with CGD registered in the French National database for Primary Immunodeficiency, we performed a retrospective review of proven mIFI episodes (European...
88 CitationsSource
#1Marieke E. B. Welzen (Radboud University Nijmegen Medical Centre)H-Index: 6
Last. Adilia WarrisH-Index: 44
view all 9 authors...
Posaconazole (PSZ) may be an attractive alternative for antifungal prophylaxis in children with chronic granulomatous disease. Experience with PSZ in pediatric patients is limited, and no specific dose recommendations exist. A twice daily dosing algorithm based on allometric scaling (body-weight based) for PSZ results in adequate exposure and appears to be safe in children with chronic granulomatous disease.
38 CitationsSource
#1Fatemeh Fattahi (Tehran University of Medical Sciences)H-Index: 20
#2Mohsen Badalzadeh (Tehran University of Medical Sciences)H-Index: 7
Last. Mostafa Moin (Tehran University of Medical Sciences)H-Index: 31
view all 22 authors...
Background Chronic granulomatous disease (CGD) is a rare immunodeficiency due to a genetic defect in one of the NADPH-oxidase components. We studied CGD inheritance forms (autosomal recessive (AR) or X-linked (XL)) and AR-CGD subtypes in Iran.
76 CitationsSource
#1Elizabeth M. Kang (NIH: National Institutes of Health)H-Index: 27
#2B.E. Marciano (NIH: National Institutes of Health)H-Index: 2
Last. Harry L. Malech (NIH: National Institutes of Health)H-Index: 99
view all 6 authors...
Chronic granulomatous disease (CGD) still causes significant morbidity and mortality. The difficulty in considering high-risk yet curative treatments, such as allogeneic bone marrow transplantation, lies in the unpredictable courses of both CGD and bone marrow transplantation in different patients. Some patients with CGD can have frequent infections, granulomatous or autoimmune disorders necessitating immunosuppressive therapy, or both but also experience long periods of relative good health. Ho...
148 CitationsSource
#1Julien Beauté (Necker-Enfants Malades Hospital)H-Index: 7
#2Gaelle ObengaH-Index: 4
Last. Olivier LortholaryH-Index: 93
view all 15 authors...
Background:Chronic granulomatous disease (CGD) is a rare inherited phagocytic disorder resulting in an increased susceptibility to infections including invasive fungal diseases (IFDs) and inflammatory complications. This study is aimed at assessing the incidence, prevalence, and outcome of IFDs amon
82 CitationsSource
Cited By202
Newest
#1Hsin-Hui Yu (NTU: National Taiwan University)H-Index: 21
#2Yao-Hsu Yang (NTU: National Taiwan University)H-Index: 41
Last. Bor-Luen Chiang (NTU: National Taiwan University)H-Index: 73
view all 3 authors...
Chronic granulomatous disease (CGD) is a primary immunodeficiency of phagocyte function due to defective NADPH oxidase (phox). Compared with the common types of CYBB/gp91phox, NCF1/p47phox, and CYBA/p22phox deficiency, NCF4/p40phox deficiency is a mild and atypical form of CGD without invasive bacterial or fungal infections. It can be diagnosed using serum-opsonized E.coli as a stimulus in dihydrorhodamine (DHR) assay. Patients with CYBC1/Eros deficiency, a new and rare form of CGD, present as l...
11 CitationsSource
#1Anna-Lena Neehus (University of Paris)H-Index: 5
#1Anna-Lena Neehus (French Institute of Health and Medical Research)
Last. Engin Altundag (OMU: Ondokuz Mayıs University)H-Index: 2
view all 35 authors...
Patients with autosomal recessive protein kinase C δ (PKCδ) deficiency suffer from childhood-onset autoimmunity, including systemic lupus erythematosus. They also suffer from recurrent infections that overlap with those seen in patients with chronic granulomatous disease (CGD), a disease caused by defects of the phagocyte NADPH oxidase and a lack of reactive oxygen species (ROS) production. We studied an international cohort of 17 PKCδ-deficient patients and found that their EBV-B cells and mono...
Source
Chronic granulomatous disease (CGD) is a rare inherited immunodeficiency disorder, characterized by susceptibility to recurrent infections, including hepatic abscess. These abscesses are typically resistant to antibiotics and surgical procedures. Here, we describe an infant with CGD and liver abscesses that was successfully treated with corticosteroids and antibiotics. A 19-day-old neonate was admitted after presenting with malaise, fever, poor feeding, abdominal distension, and hepatomegaly. Ro...
Source
The innate immune system is the host's first line of defense against pathogens. Toll-like receptors (TLRs) are pattern recognition receptors that mediate recognition of pathogen-associated molecular patterns. TLRs also activate signaling transduction pathways involved in host defense, inflammation, development, and the production of inflammatory cytokines. Innate immunodeficiencies associated with defective TLR signaling include mutations in NEMO, IKBA, MyD88, and IRAK4. Other innate immune defe...
Source
#1Rodrigo Prieto-Bermejo (University of Salamanca)H-Index: 5
#2Marta Romo-González (University of Salamanca)H-Index: 3
Last. Angel Hernández-Hernández (University of Salamanca)H-Index: 17
view all 0 authors...
Haematopoiesis is a paradigm of cell differentiation because of the wide variety and overwhelming number of mature blood cells produced daily. Under stress conditions, the organism must adapt to a boosted demand for blood cells. Chronic granulomatous disease (CGD) is a genetic disease caused by inactivating mutations that affect the phagocyte oxidase. Besides a defective innate immune system, CGD patients suffer from recurrent hyper-inflammation episodes, circumstances upon which they must face ...
Source
#1Dae‐goon Yoo (WashU: Washington University in St. Louis)H-Index: 1
#2Luana Chiquetto Paracatu (WashU: Washington University in St. Louis)H-Index: 3
Last. Mary C. Dinauer (WashU: Washington University in St. Louis)H-Index: 84
view all 5 authors...
Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by genetic defects in leukocyte NADPH oxidase, which has both microbicidal and immunomodulatory roles. Hence, CGD is characterized by recurrent bacterial and fungal infections as well as aberrant inflammation. Fungal cell walls induce neutrophilic inflammation in CGD; yet, underlying mechanisms are incompletely understood. This study investigated the receptors and signaling pathways driving aberrant proinflammatory cytokine...
Source
#1A. Launay (NIH: National Institutes of Health)
#2C.-J. Wu (NIH: National Institutes of Health)
Last. John P. Dekker (NIH: National Institutes of Health)H-Index: 19
view all 6 authors...
Zoonotic transfer of animal pathogens to human hosts can generate novel agents, but the genetic events following such host jumps are not well studied. Here we characterize the mechanisms driving adaptive evolution of the emerging zoonotic pathogen Bordetella hinzii in a patient with interleukin-12 receptor β1 deficiency. Genomic sequencing of 24 B. hinzii isolates cultured from blood and stool over 45 months revealed a clonal lineage that had undergone extensive within-host genetic and phenotypi...
Source
#1Cindy Staerck (University of Western Brittany)
#2Hajar Yaakoub (University of Western Brittany)
Last. Yves Delneste (University of Nantes)H-Index: 55
view all 12 authors...
Scedosporium species are common fungal pathogens in patients with cystic fibrosis (CF). To colonize the CF lungs, fungi must cope with the host immune response, especially the reactive oxygen species (ROS) released by phagocytic cells. To this aim, pathogens have developed various antioxidant systems, including superoxide dismutases (SODs) which constitute the first-line protection against oxidative stress. Interestingly, one of the S. apiospermum SOD-encoding genes (SODD gene) exhibits a glycos...
Source
#1Kunal Chopra (University of Manchester)H-Index: 1
#2Folkmanaite M (University of Manchester)
Last. Enrique Amaya (University of Manchester)H-Index: 36
view all 8 authors...
Sustained elevated levels of reactive oxygen species (ROS) have been shown to be essential for whole body, appendage and organ regeneration in various organisms, including planarians, Hydra, zebrafish, axolotl, Xenopus, geckos and mice. In the majority of cases these roles have been shown via the use of NADPH oxidase pharmacological inhibitors, which generally target all NAPDH oxidases (NOXes). To identify the specific NOX or NOXes essential for ROS production during adult fin regeneration in ze...
Source
Background null Pulmonary invasive aspergillosis is a frequent and life-threatening complication for patients with chronic granulomatous disease (CGD). Despite combined treatment with several groups of antifungal agents, conservative treatment of invasive aspergillosis often remains refractory. Pulmonary invasive aspergillosis is often treated by surgical resection of consolidated lobes or segments, donor granulocyte transfusions and allogeneic hematopoietic stem cell transplantation (HSCT). The...
Source