scholarly journals Adult-diagnosed Chronic Granulomatous Disease: The Need to Increase Awareness

2021 ◽  
Author(s):  
Joseph Baxter ◽  
Derek Smith ◽  
Charles Webb
Keyword(s):  
Chronic Granulomatous Disease ◽  
Lupus Erythematosus ◽  
Fungal Infections ◽  
Genetic Disorder ◽  
Immunosuppressive Drugs ◽  
Granulomatous Disease ◽  
Multiple Systems ◽  
Life Saving ◽  
Life Threatening ◽  
History Of

ABSTRACT Chronic granulomatous disease is genetic disorder characterized by the inability of phagocytes to produce sufficient oxidative burst needed to kill intracellular organisms. Patients have recurrent, life-threatening infections involving multiple systems including the lungs, skin, lymph nodes, and liver. The majority of patients with chronic granulomatous disease are diagnosed in childhood although some may present in adulthood due to a milder phenotype. Unfortunately, these patients may also present with concomitant autoimmune diseases. We describe a 48-year-old woman with a history of immune thrombocytopenia and systemic lupus erythematosus on immunosuppressive therapy. She developed subsequent bacterial and fungal infections initially attributed to immunosuppressive drugs. Further evaluation revealed the diagnosis of chronic granulomatous disease. We review the diagnosis and treatment of chronic granulomatous disease in hopes to increase awareness of this disease in adulthood in order to initiate potential life-saving prophylactic antibiotics.

scholarly journals The p47phox mouse knock-out model of chronic granulomatous disease.

1995 ◽  
Vol 182 (3) ◽  
pp. 751-758 ◽  
Author(s):  
S H Jackson ◽  
J I Gallin ◽  
S M Holland
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Fungal Infections ◽  
Critical Role ◽  
Granulomatous Inflammation ◽  
Mammalian Host ◽  
Granulomatous Disease ◽  
Knock Out ◽  
Phagocyte Nadph Oxidase ◽  
Life Threatening

Chronic granulomatous disease (CGD) is caused by a congenital defect in phagocyte reduced nicotinamide dinucleotide phosphate (NADPH) oxidase production of superoxide and related species. It is characterized by recurrent life-threatening bacterial and fungal infections and tissue granuloma formation. We have created a mouse model of CGD by targeted disruption of p47phox, one of the genes in which mutations cause human CGD. Identical to the case in human CGD, leukocytes from p47phox-/- mice produced no superoxide and killed staphylococci ineffectively. p47phox-/- mice developed lethal infections and granulomatous inflammation similar to those encountered in human CGD patients. This model mirrors human CGD and confirms a critical role for the phagocyte NADPH oxidase in mammalian host defense.

scholarly journals An Uncommon Feature of Chronic Granulomatous Disease in a Neonate

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Razieh Afrough ◽  
Sayyed Shahabeddin Mohseni ◽  
Setareh Sagheb
Keyword(s):  
Mortality Rate ◽  
Chronic Granulomatous Disease ◽  
High Mortality ◽  
Neonatal Period ◽  
Fungal Infections ◽  
Granuloma Formation ◽  
Granulomatous Disease ◽  
Life Threatening

Chronic Granulomatous Disease (CGD) represents recurrent life-threatening bacterial and fungal infections and granuloma formation with a high mortality rate. CGD’s sign and symptoms usually appear in infancy and children before the age of five; therefore, its presentation in neonatal period with some uncommon features may be easily overlooked. Here we describe a case of CGD in a 24-day-old boy, presenting with a diffuse purulent vesiculopustular rash and multiple osteomyelitis.

scholarly journals Case Report: Secondary Hemophagocytic Lymphohistiocytosis With Disseminated Infection in Chronic Granulomatous Disease—A Serious Cause of Mortality

2020 ◽  
Vol 11 ◽  
Author(s):  
Jacqueline D. Squire ◽  
Stephanie N. Vazquez ◽  
Angela Chan ◽  
Michele E. Smith ◽  
Deepak Chellapandian ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Chronic Granulomatous Disease ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Fungal Infections ◽  
Primary Immune Deficiency ◽  
Granulomatous Disease ◽  
Simultaneous Treatment ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Life Threatening

Chronic granulomatous disease (CGD) is a primary immune deficiency due to defects in phagocyte respiratory burst leading to severe and life-threatening infections. Patients with CGD also suffer from disorders of inflammation and immune dysregulation including colitis and granulomatous lung disease, among others. Additionally, patients with CGD may be at increased risk of systemic inflammatory disorders such as hemophagocytic lymphohistiocytosis (HLH). The presentation of HLH often overlaps with symptoms of systemic inflammatory response syndrome (SIRS) or sepsis and therefore can be difficult to identify, especially in patients with a primary immune deficiency in which incidence of infection is increased. Thorough evaluation and empiric treatment for bacterial and fungal infections is necessary as HLH in CGD is almost always secondary to infection. Simultaneous treatment of infection with anti-microbials and inflammation with immunosuppression may be needed to blunt the hyperinflammatory response in secondary HLH. Herein, we present a series of X-linked CGD patients who developed HLH secondary to or with concurrent disseminated CGD-related infection. In two patients, CGD was a known diagnosis prior to development of HLH and in the other two CGD was diagnosed as part of the evaluation for HLH. Concurrent infection and HLH were fatal in three; one case was successfully treated, ultimately receiving hematopoietic stem cell transplantation. The current literature on presentation, diagnosis, and treatment of HLH in CGD is reviewed.

Reconstitution of bactericidal activity in chronic granulomatous disease cells by glucose-oxidase–containing liposomes

Blood ◽  
2001 ◽  
Vol 98 (10) ◽  
pp. 3097-3105 ◽  
Author(s):  
Claudia E. Gerber ◽  
Gernot Bruchelt ◽  
Ulrike B. Falk ◽  
Andrea Kimpfler ◽  
Oliver Hauschild ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Glucose Oxidase ◽  
Whole Blood ◽  
Fungal Infections ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Confocal Laser ◽  
Granulomatous Disease ◽  
Life Threatening

Abstract Chronic granulomatous disease (CGD) is an inherited primary immunodeficiency characterized by phagocytes devoid of a functioning nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. The failure of CGD phagocytes to produce reactive oxygen species (ROS) results in a marked increase in the susceptibility of affected patients to life-threatening bacterial and fungal infections. This study investigated whether loading of CGD phagocytes with glucose oxidase (GO)–containing liposomes (GOLs) could restore cellular production of bactericidal ROS (eg, H2O2 and HOCl) in vitro. Results indicate that GO encapsulated in liposomes enabled NADPH oxidase-deficient phagocytes to use H2O2 for the production of highly bactericidal HOCl. The intracellular colocalization of bacteria and liposomes (or liposome-derived ferritin) was demonstrated by confocal laser microscopy and electron microscopy. After uptake of GOLs (approximately 0.2 U/mL at 1 mM total lipid concentration, size approximately 180 nm), CGD granulocytes produced HOCl levels comparable to those of normal phagocytes. Remarkably, after treatment with GOLs, CGD phagocytes killed Staphylococcus aureus as efficiently as normal granulocytes. Moreover, treated cells retained sufficient motility toward chemotactic stimuli as measured by chemotaxis assay. Side effects were evaluated by measuring the H2O2 concentrations and the production of methemoglobin in whole blood. These studies revealed that H2O2 produced by GOLs was degraded immediately by the antioxidative capacity of whole blood. Elevated methemoglobin levels were observed only after application of extremely high amounts of GOLs (2 U/mL). In summary, the application of negatively charged GOLs might provide a novel effective approach in the treatment of patients with CGD at high risk for life-threatening infections.

scholarly journals Lupus Erythematosus and Chronic Granulomatous Disease: Report of Four Iranian Patients with AR-CGD and One XL-CGD

2019 ◽  
Author(s):  
Marzieh Maddah ◽  
Mohammad Reza Fazlollahi ◽  
Reza Shiari ◽  
Farhad Shahram ◽  
Setareh Mamishi ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Chronic Granulomatous Disease ◽  
Lupus Erythematosus ◽  
Genetic Disorder ◽  
Clinical Signs ◽  
Signs And Symptoms ◽  
Granulomatous Disease ◽  
Clinical Signs And Symptoms ◽  
Bacteria And Fungi

Chronic granulomatous disease (CGD) is a rare genetic disorder of neutrophil activity, resulting in increased rate of recurrent infections with catalase–positive bacteria and fungi, as well as various autoimmune diseases such as sarcoidosis, rheumatoid arthritis, and discoid and/or systemic lupus erythematosus. Few reports have reported lupus erythematosus (LE) in patients with X–linked CGD (XL-CGD) and carriers, and very few in autosomal recessive CGD (AR-CGD). Here, we present 5 patients with CGD developing LE at different ages to emphasize on the importance of appropriate follow–up and treatment in patients with CGD with clinical signs and symptoms of autoimmune diseases and even in those with negative serologic results.

scholarly journals Xanthine Oxidase Contributes to Host Defense against Burkholderia cepacia in the p47phox−/− Mouse Model of Chronic Granulomatous Disease

2000 ◽  
Vol 68 (4) ◽  
pp. 2374-2378 ◽  
Author(s):  
Brahm H. Segal ◽  
Nobuaki Sakamoto ◽  
Mayur Patel ◽  
Kosei Maemura ◽  
Andrew S. Klein ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chronic Granulomatous Disease ◽  
Xanthine Oxidase ◽  
Host Defense ◽  
Burkholderia Cepacia ◽  
Fungal Infections ◽  
Granulomatous Disease ◽  
Life Threatening ◽  
Reactive Oxidant ◽  
Reactive Oxidants

ABSTRACT Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase in which phagocytes are defective in generating superoxide and downstream microbicidal reactive oxidants, leading to recurrent life-threatening bacterial and fungal infections. Xanthine oxidase (XO) is another enzyme known to produce superoxide in many tissues. Using the p47 phox−/− mouse model of CGD, we evaluated the residual antibacterial activity of XO. Clearance of Burkholderia cepacia, a major pathogen in CGD, was reduced in p47 phox−/− mice compared to that in wild-type mice and was further inhibited in p47 phox−/− mice by pretreatment with the specific XO inhibitor allopurinol. Hepatic B. cepaciaburden was similar in the two genotypes, but allopurinol significantly reduced net hepatic killing and killing efficiency only in p47 phox−/− mice. Clearance and killing of intravenous Escherichia coli was intact in p47 phox−/− mice and was unaffected by pretreatment with allopurinol. In CGD, XO may contribute to host defense against a subset of reactive oxidant-sensitive pathogens.

NORMAL GRANULOCYTE INFUSION THERAPY FOR ASPERGILLOSIS IN CHRONIC GRANULOMATOUS DISEASE

PEDIATRICS ◽  
1973 ◽  
Vol 51 (2) ◽  
pp. 230-233
Author(s):  
Andrew A. Raubitschek ◽  
Alan S. Levin ◽  
Daniel P. Stites ◽  
Edward B. Shaw ◽  
H. Hugh Fudenberg
Keyword(s):  
Adverse Effects ◽  
Chronic Granulomatous Disease ◽  
Blood Cells ◽  
White Blood Cells ◽  
Infusion Therapy ◽  
Granulomatous Disease ◽  
Transient Improvement ◽  
Life Threatening ◽  
Granulocyte Function

An 8-year-old boy with chronic granulomatous disease (CGD) was admitted in moribund condition with aspergillus pneumonia. Because of the gravity of the situation, normal granulocyte infusions were used as adjuncts to the more conventional antimicrobial therapy. White blood cells, derived from a total of 58 units of whole blood obtained by leukophoresis of the father, were given in two separate doses. The first dose, totaling 2.8 x 1010 granulocytes, was coincident with significant improvement, and the second, totaling 3.0 x 1010 granulocytes, was coincident with the onset of clinical improvement and interim recovery. Transient improvement in in vitro granulocyte function was noted in cells taken from the patient's blood immediately after infusion. No adverse effects of the infusions were noted in either the patient or the donor. Although it is impossible to divorce the therapeutic effect of the granulocyte infusions from the more conventional therapy, we conclude that normal granulocyte infusions can be considered a valid adjunct in children with CGD who are suffering from a life-threatening infection.

Topics in Chronic Granulomatous Disease

PEDIATRICS ◽  
1991 ◽  
Vol 88 (1) ◽  
pp. 183-185
Author(s):  
SHIGENOBU UMEKI
Keyword(s):  
Nadph Oxidase ◽  
Chronic Granulomatous Disease ◽  
Host Defense ◽  
Superoxide Anion ◽  
Fungal Infections ◽  
Regulatory Elements ◽  
Granulomatous Disease ◽  
Phagocytic Cells ◽  
Oxidase System ◽  
Membrane Bound

To the Editor.— Such phagocytic cells as neutrophils and macrophages are crucial elements in the host defense against bacterial [See table in the PDF file] and fungal infections. Microbicidal activity depends to a large extent on NADPH oxidase system, which can be activated by stimuli (bacteria, fungi) and which generates the superoxide anion and other highly reactive forms of reduced oxygen.1,2 The neutrophil NADPH oxidase system is composed functionally of membrane-bound catalytic components (which consist of at least two constituents, the low potential cytochrome b5583-5 and flavoprotein5) and soluble cytosolic components6,7 which participate as either catalytic or regulatory elements.

scholarly journals Clinical observation of Сhronic granulomatous disease in a 6-year-old child

2020 ◽  
Vol 19 (4) ◽  
pp. 69-72
Author(s):  
G. A. Kharchenko ◽  
O. G. Kimirilova
Keyword(s):  
Chronic Granulomatous Disease ◽  
Clinical Observation ◽  
Fungal Infections ◽  
Genetic Defect ◽  
Clinical Manifestations ◽  
Hereditary Disease ◽  
Laboratory Method ◽  
Granulomatous Disease ◽  
Hematopoietic Stem ◽  
Nbt Test

Chronic granulomatous disease (CGD) is a hereditary disease caused by a genetic defect of violations of oxygen — dependent mechanisms of phagocytosis. Clinical manifestations of the disease are recurrent bacterial or fungal infections of the skin, hepatic abscesses, pneumonia, osteomyelitis, sepsis, meningitis et al. Most available laboratory method for the diagnosis of CGD is the test of histochemical nitro blue tetrazolium recovery (NBT-test). Allogeneic hematopoietic stem cell transplantation is considered a radical treatment for chronic granulomatous disease. The article presents a clinical observation of the manifestation of chronic granulomatous disease with an unfavorable outcome in a child aged 6 years.

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