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1.
Kathmandu Univ Med J (KUMJ) ; 17(65): 77-79, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31734685

RESUMO

We report two cases of cutaneous leishmaniasis in natives of central region of Nepal. The first patient in our series, an adult female, presented with a small nodule on the philtrum of upper lip and the second case, a male child, presented with two crusted plaques on forehead. The final diagnosis was based on histopathological findings; however, species characterization was not possible because of its unavailability in the country. These patients responded well to the treatment with Miltefosine (First case) and Fluconazole (second case). Moreover, these cases sparks a question about the origin of diseases in this region and calls for further research in future to find out the cause and prevalence of this disease in Nepal. This case report also emphasizes to consider cutaneous leishmaniasis as differential diagnosis for granulomatous presentations in our context.


Assuntos
Leishmaniose Cutânea/diagnóstico , Adulto , Antifúngicos/uso terapêutico , Antiprotozoários/uso terapêutico , Criança , Diagnóstico Diferencial , Feminino , Fluconazol/uso terapêutico , Doença Granulomatosa Crônica/diagnóstico , Humanos , Masculino , Nepal/epidemiologia , Fosforilcolina/análogos & derivados , Fosforilcolina/uso terapêutico
2.
Iran J Allergy Asthma Immunol ; 18(4): 447-451, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31522453

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocytic NADPH oxidase, causing a complete lack or significant decrease in the production of microbicidal reactive oxygen metabolites. It mainly affects male children; however, there are scarce reports of adult females diagnosed with X-linked-CGD attributed to an extremely skewed X-chromosome inactivation. This condition is characterized by severe and recurrent infections that usually develop after childhood. In clinical practice, physicians who usually confront these patients should suspect this entity and differentiate it from a secondary immunodeficiency. Here, we report a 38-year-old Mexican female with juvenile-onset X linked-CGD, caused by a de novo mutation and extremely skewed X-inactivation, whose clinical features were similar to those in patients with classic X-linked-CDG.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Heterozigoto , Fenótipo , Inativação do Cromossomo X , Adolescente , Biomarcadores , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Avaliação de Sintomas
3.
Iran J Allergy Asthma Immunol ; 18(4): 452-458, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31522454

RESUMO

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.


Assuntos
Genes Recessivos , Genes Ligados ao Cromossomo X , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Adolescente , Alelos , Biomarcadores , Biópsia , Criança , Suscetibilidade a Doenças , Feminino , Genótipo , Humanos , Irã (Geográfico) , Masculino , Fenótipo , Adulto Jovem
4.
Methods Mol Biol ; 1982: 3-16, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172463

RESUMO

Neutrophils serve as the circulating cells that respond early and figure prominently in human host defense to infection and in inflammation in other settings. Optimal oxidant-dependent antimicrobial activity by neutrophils relies on the ability of stimulated phagocytes to utilize a multicomponent NADPH oxidase to generate oxidants. The frequent, severe, and often fatal infections experienced by individuals with chronic granulomatous disease (CGD), an inherited disorder in which one of the NADPH oxidase components is absent or dysfunctional, underscore the link between a functional phagocyte NADPH oxidase and robust host protection against microbial infection.The history of the discovery and characterization of the normal neutrophil NADPH oxidase and the saga of recognizing CGD and its underlying causes together illustrate how the observations of astute clinicians and imaginative basic scientists synergize to forge new understanding of both basic cell biology and pathogenesis of human disease.In this chapter, we review the events in the stepwise evolution of our understanding of the phagocyte NADPH oxidase, both in the context of normal human neutrophil function and in the setting of CGD. The phagocyte oxidase complex employs a heterodimeric transmembrane protein composed of gp91phox and p22phox to relay electrons from NADPH to molecular oxygen, while other cofactors contribute to localization and regulation of the activity of the assembled oxidase. The b-type cytochrome gp91phox, also known as NOX2, serves as the catalytic component of this multicomponent enzyme complex. Although many of the features of the composition and regulation of the phagocyte oxidase may apply as well to NOX2 expressed in non-phagocytes and to other members of the NOX protein family, exceptions exist and pose special challenges to investigators exploring the biology of NADPH oxidases.


Assuntos
Doença Granulomatosa Crônica/etiologia , Doença Granulomatosa Crônica/metabolismo , NADPH Oxidases/metabolismo , Fagócitos/imunologia , Fagócitos/metabolismo , Animais , Biomarcadores , Grupo dos Citocromos b/genética , Grupo dos Citocromos b/metabolismo , Citoplasma/imunologia , Citoplasma/metabolismo , Gerenciamento Clínico , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/terapia , Humanos , NADPH Oxidases/genética , Neutrófilos/imunologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Oxirredução , Fagócitos/patologia , Papel do Médico , Explosão Respiratória , Transdução de Sinais
5.
Methods Mol Biol ; 1982: 531-542, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172494

RESUMO

Chronic granulomatous disease is a clinical condition that stems from inactivating mutations in NOX2 and its auxiliary proteins. Together, these proteins form the phagocyte NADPH oxidase enzyme that generates superoxide. Superoxide (O2c-) and its reduced product hydrogen peroxide (H2O2) give rise to several additional reactive oxygen species (ROS), which together are necessary for adequate killing of pathogens. Thus, CGD patients, with a phagocyte NADPH oxidase that is not properly functioning, suffer from recurrent, life-threatening infections with certain bacteria, fungi, and yeasts. Here, I give a short survey of the genetic mutations that underlie CGD, the effect of these mutations on the activity of the leukocyte NADPH oxidase, the clinical symptoms of CGD patients, and the treatment options for these patients.


Assuntos
Doença Granulomatosa Crônica/etiologia , Doença Granulomatosa Crônica/metabolismo , Biomarcadores , Terapia Combinada , Gerenciamento Clínico , Ativação Enzimática , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/terapia , Humanos , Peróxido de Hidrogênio/metabolismo , Mutação , NADPH Oxidases/química , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Fagócitos/imunologia , Fagócitos/metabolismo , Fenótipo , Ligação Proteica , Espécies Reativas de Oxigênio/metabolismo , Avaliação de Sintomas , Resultado do Tratamento
6.
Methods Mol Biol ; 1982: 543-571, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31172495

RESUMO

Chronic granulomatous disease (CGD) is a rare genetic immunodeficiency associated with recurrent bacterial infections, granulomas, and increased mortality. It is characterized by the inability of phagocytes (neutrophils, monocytes, etc.) to generate reactive oxygen species (ROS), a major component of the microbicidal repertoire of phagocytes. Diagnosis of patients with CGD is commonly based on the assessment of ROS production by neutrophils. Multiple assays to assess ROS production are described-a flow cytometric dihydrorhodamine assay and a histochemical nitroblue tetrazolium assay, both of which can be used to visualize ROS production in individual cells, and two quantitative assays-O2˙- reduction of ferricytochrome c and a ROS-dependent, luminol-enhanced chemiluminescence assay that will quantitate the response of a population of cells. In addition, two approaches to identify the defective phox protein defect are described-standard immunoblotting and flow cytometry of neutrophils stained with phox-specific antibodies. When determining the status of a patient, several assays should be used to assess ROS production and identify the protein defect. The results of these assays should agree and can be used to develop a comprehensive package, which includes confirmation of a diagnosis of CGD, identification of the specific protein target for genetic sequencing, and an indication of the prognosis for the patient.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , Bioensaio , Biomarcadores , Citometria de Fluxo , Doença Granulomatosa Crônica/etiologia , Doença Granulomatosa Crônica/metabolismo , Humanos , Técnicas de Diagnóstico Molecular , NADPH Oxidases/química , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Fagócitos/imunologia , Fagócitos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
7.
Rev Alerg Mex ; 66(2): 232-245, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31200421

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency syndrome which is characterized by increased susceptibility to severe fungal and bacterial infections. CGD is the result of the lack of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase enzyme in the patient's phagocytes to produce superoxide. It is characterized by recurrent infections with a narrow spectrum of bacteria and fungi, as well as a common set of inflammatory complications, including inflammatory bowel disease. The most frequently found pathogens are Staphylococcus aureus, species of Aspergillus, species of Klebsiella, Burkholderia cepacia, Serratia marcescens and species of Salmonella. Long term antibiotic prophylaxis has helped fight infections associated with chronic granulomatous disease, while the steady progress in bone marrow transplants and the possibility of gene therapy are defined as permanent treatment options.


Assuntos
Doença Granulomatosa Crônica , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/terapia , Humanos
8.
Curr Med Sci ; 39(2): 343-348, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016508

RESUMO

Since X-linked chronic granulomatosis disease (X-CGD) exhibits no specific clinical symptoms at an early stage, early diagnosis is difficult and depends predominantly on neonatal screening. Therefore, the aim of this study was to explore routine biomarkers for X-CGD in children and provide clues for early diagnosis. The cases of 10 children with X-CGD diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from 2013 to 2016 and 122 Chinese children with X-CGD reported in the literature were summarized. Serum biomarkers and clinical symptoms at acute infection were organized. A total of 132 children with X-CGD were enrolled in this study. For 55.8% of the patients, the diagnosis was delayed more than one year after the onset of the first symptoms because no typical clinical symptoms manifested. Children with X-CGD at an acute infection stage showed three recurrent signs in terms of serum biomarkers: (1) the total number of white blood cells (especially N%) was increased significantly, accompanied by anemia in some cases; (2) C-reactive protein (CRP) levels were increased significantly; and (3) most of the patients exhibited very high serum IgG levels (>12 g/L). Diagnosis of X-CGD at an early age is difficult because of its nonspecific clinical features. Our study suggested children with X-CGD suffering acute infection show increases in three typical serum biomarkers, which can provide clues for early diagnosis.


Assuntos
Biomarcadores/sangue , Doença Granulomatosa Crônica/sangue , Doença Granulomatosa Crônica/diagnóstico , Proteína C-Reativa/metabolismo , Pré-Escolar , Doença Crônica , Diagnóstico Precoce , Feminino , Humanos , Imunoglobulina G/sangue , Lactente , Leucócitos/fisiologia , Masculino
11.
Pediatr Allergy Immunol ; 30(3): 378-386, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30716179

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a rare disease in China, and very little large-scale studies have been conducted to date. We aimed to investigate the clinical and genetic features of CGD in Chinese pediatric patients. METHODS: Pediatric patients with CGD from Beijing Children's Hospital, Capital Medical University, China, were enrolled from January 2006 to December 2016. RESULTS: A total of 159 pediatric patients with CGD were enrolled. The median age of clinical onset was 1.4 months, and 73% (116/159) had clinical onset symptoms before the 1 year of age. The most common site of invasion was the lungs. The lymph nodes, liver, and skin were more frequently invaded in X-linked (XL) CGD patients than in autosomal recessive (AR) CGD patients (P < 0.05). Approximately 64% (92/144) of the pediatric patients suffered from abnormal response to BCG vaccination. The most frequent pathogens were Aspergillus and Mycobacterium tuberculosis. Gene analysis indicated that 132 cases (89%, 132/147) harbored CYBB pathogenic variants, 7 (5%, 7/147) carried CYBA pathogenic variants, 4 (3%, 4/147) had NCF1 pathogenic variants, and 4 (3%, 4/147) had NCF2 pathogenic variants. The overall mortality rate in this study was 43%, particularly the patients were males, with CYBB mutant and did not receive HSCT treatment. CONCLUSIONS: Chronic granulomatous disease is a rare disease affecting Chinese children; however, it is often diagnosed at a later age, and thus, the mortality rate is relatively high. The prevalence and the severity of disease in XL-CGD are higher than AR-CGD.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , NADPH Oxidases/genética , Adolescente , Anti-Infecciosos/uso terapêutico , Grupo com Ancestrais do Continente Asiático/genética , Criança , Pré-Escolar , China , Feminino , Testes Genéticos/métodos , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Retrospectivos
12.
Blood Adv ; 3(2): 136-147, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30651282

RESUMO

Mutations in NCF1 (p47phox) cause autosomal recessive chronic granulomatous disease (CGD) with abnormal dihydrorhodamine (DHR) assay and absent p47phox protein. Genetic identification of NCF1 mutations is complicated by adjacent highly conserved (>98%) pseudogenes (NCF1B and NCF1C). NCF1 has GTGT at the start of exon 2, whereas the pseudogenes each delete 1 GT (ΔGT). In p47phox CGD, the most common mutation is ΔGT in NCF1 (c.75_76delGT; p.Tyr26fsX26). Sequence homology between NCF1 and its pseudogenes precludes reliable use of standard Sanger sequencing for NCF1 mutations and for confirming carrier status. We first established by flow cytometry that neutrophils from p47phox CGD patients had negligible p47phox expression, whereas those from p47phox CGD carriers had ∼60% of normal p47phox expression, independent of the specific mutation in NCF1 We developed a droplet digital polymerase chain reaction (ddPCR) with 2 distinct probes, recognizing either the wild-type GTGT sequence or the ΔGT sequence. A second ddPCR established copy number by comparison with the single-copy telomerase reverse transcriptase gene, TERT We showed that 84% of p47phox CGD patients were homozygous for ΔGT NCF1 The ddPCR assay also enabled determination of carrier status of relatives. Furthermore, only 79.2% of normal volunteers had 2 copies of GTGT per 6 total (NCF1/NCF1B/NCF1C) copies, designated 2/6; 14.7% had 3/6, and 1.6% had 4/6 GTGT copies. In summary, flow cytometry for p47phox expression quickly identifies patients and carriers of p47phox CGD, and genomic ddPCR identifies patients and carriers of ΔGT NCF1, the most common mutation in p47phox CGD.


Assuntos
Predisposição Genética para Doença , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , NADPH Oxidases/deficiência , Biomarcadores , Mapeamento Cromossômico , Variações do Número de Cópias de DNA , Feminino , Citometria de Fluxo , Expressão Gênica , Estudos de Associação Genética , Loci Gênicos , Genótipo , Doença Granulomatosa Crônica/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , NADPH Oxidases/genética , NADPH Oxidases/metabolismo , Neutrófilos/imunologia , Neutrófilos/metabolismo , Linhagem , Espécies Reativas de Oxigênio/metabolismo
14.
Arch. argent. pediatr ; 116(6): 744-748, dic. 2018. ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-973689

RESUMO

La enfermedad granulomatosa crónica es una inmunodeficiencia primaria infrecuente, debida a un defecto en la actividad microbicida de los fagocitos, originada por mutaciones en los genes que codifican alguna de las subunidades del complejo enzimático nicotinamida adenina dinucleótido fosfato oxidasa. La incidencia estimada es 1 en 250 000 recién nacidos vivos. Puede presentarse desde la infancia hasta la adultez, por lo general, en menores de 2 años. Las infecciones bacterianas y fúngicas, en conjunto con las lesiones granulomatosas, son las manifestaciones más habituales de la enfermedad. Los microorganismos aislados más frecuentemente son Aspergillus spp., Staphylococcus aureus, Serratia marcescens, Nocardia spp. Se reporta el caso clínico de un varón de 1 año de vida en el que se diagnosticó enfermedad granulomatosa crónica a partir de infecciones múltiples que ocurrieron simultáneamente: aspergilosis pulmonar invasiva, osteomielitis por Serratia marcescens y granuloma cervical por Enterobacter cloacae.


Chronic granulomatous disease is an uncommon primary immunodeficiency due to a defect of the killing activity of phagocytes, caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system. The incidence is 1 in 250 000 live births. It can occur from infancy to adulthood, usually in children under 2 years. Bacterial and fungal infections in association with granuloma lesions are the most common manifestations of the disease. Aspergillus species, Staphylococcus aureus, Serratia marcescens, Nocardia species are the most common microorganisms isolated. We describe here a case of a 1-year-old boy with chronic granulomatous disease and invasive pulmonary aspergillosis, Serratia marcescens osteomyelitis and Enterobacter cloacae cervical granuloma.


Assuntos
Humanos , Masculino , Lactente , Infecções por Serratia/diagnóstico , Infecções por Enterobacteriaceae/diagnóstico , Aspergilose Pulmonar/diagnóstico , Doença Granulomatosa Crônica/diagnóstico , Osteomielite/diagnóstico , Osteomielite/metabolismo , Serratia marcescens/isolamento & purificação , Infecções por Serratia/microbiologia , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Doença Granulomatosa Crônica/microbiologia
15.
J Clin Immunol ; 38(8): 898-916, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30470980

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is characterized by mutation in any one of the five genes coding NADPH oxidase components that leads to functional abnormality preventing the killing of phagocytosed microbes by affecting the progression of a respiratory burst. CGD patients have an increased susceptibility to infections by opportunistic and pathogenic organisms. Though initial diagnosis of CGD using a nitroblue tetrazolium (NBT) test or dihydrorhodamine (DHR) test is relatively easy, molecular diagnosis is challenging due to involvement of multiple genes, presence of pseudogenes, large deletions, and GC-rich regions, among other factors. The strategies for molecular diagnosis vary depending on the affected gene and the mutation pattern prevalent in the target population. There is a paucity of molecular data related to CGD for Indian population. METHOD: This report includes data for a large cohort of CGD patients (n = 90) from India, describing the diagnostic approach, mutation spectrum, and novel mutations identified. We have used mosaicism in mothers and the expression pattern of different NADPH components by flow cytometry as a screening tool to identify the underlying affected gene. The techniques like Sanger sequencing, next-generation sequencing (NGS), and Genescan analysis were used for further molecular analysis. RESULT: Of the total molecularly characterized patients (n = 90), 56% of the patients had a mutation in the NCF1 gene, 30% had mutation in the CYBB gene, and 7% each had mutation in the CYBA and NCF2 genes. Among the patients with NCF1 gene mutation, 82% of the patients had 2-bp deletion (DelGT) mutations in the NCF1 gene. In our cohort, 41 different mutations including 9 novel mutations in the CYBB gene and 2 novel mutations each in the NCF2, CYBA, and NCF1 genes were identified. CONCLUSION: Substantial number of the patients lack NCF1 gene on both the alleles. This is often missed by advanced molecular techniques like Sanger sequencing and NGS due to the presence of pseudogenes and requires a simple Genescan method for confirmation. Thus, the diagnostic approach may depend on the prevalence of affected genes in respective population. This study identifies potential gene targets with the help of flow cytometric analysis of NADPH oxidase components to design an algorithm for diagnosis of CGD in India. In Indian population, the Genescan method should be preferred as the primary molecular test to rule out NCF1 gene mutations prior to Sanger sequencing and NGS.


Assuntos
Doença Granulomatosa Crônica/diagnóstico , Mutação/genética , NADPH Oxidase 2/genética , NADPH Oxidases/genética , NADP/metabolismo , Patologia Molecular/métodos , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Feminino , Citometria de Fluxo , Doença Granulomatosa Crônica/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Índia , Lactente , Masculino , Nitroazul de Tetrazólio , Adulto Jovem
16.
Z Gastroenterol ; 56(12): 1507-1512, 2018 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30466133

RESUMO

BACKGROUND: Chronic granulomatous disease is a rare disease with a prevalence of approximately 150 cases in Germany. An intestinal manifestation that mimics chronic inflammatory bowel disease (IBD) has only been described in a few cases. As a result of a deficient superoxide-synthesis, frequent and recurrent infections caused by rare pathogens have been described. We present the case of a 28-year old patient who has been diagnosed with IBD at the age of 2 years. He showed recurrent liver abscesses and the picture of a chronic IBD. METHODS: Clinical and laboratory data was obtained and endoscopic, radiologic and histologic examinations, tests for granulocytic functions as well as a genetic analysis were performed. Literature of the PubMed database and recent literature were analyzed. CASE: Under immunosuppressive therapy, with TNF -blocker Adalimumab followed by therapy with integrin-receptor antagonist Vedolizumab, the patient developed recurrent abscesses of the liver. Those were the result of infection with a sensitive Staphylococcus aureus strain. Colonoscopy showed stenosis of the rectum and some inflammatory activity. Intestinal symptoms were unresponsive to all therapies for IBD. Furthermore, there was a presence of active acne and recurrent liver abscesses due to bacteria not typical for intestinal infections. Consequently, we considered a granulocyte dysfunction as the underlying cause. Diagnosis of a chronic granulomatous disease was confirmed by flow cytometry and oxidative burst test. Genetic analysis showed a homozygote mutation of the p47phox (NCF1) gene located on chromosome 7, which represents the most common autosomal recessive form with 20 - 25 % of cases. RESULTS: In light of recent literature, this case report shows that chronic granulomatous disease should be considered as a differential diagnosis to therapy refractory IBD. This is the case, especially in young patients, when recurrent bacterial lesions caused by intestine-atypical pathogens appear.


Assuntos
Doença Granulomatosa Crônica , Doenças Inflamatórias Intestinais , Intestinos , Adulto , Idade de Início , Diagnóstico Diferencial , Alemanha , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Intestinos/microbiologia , Masculino
17.
BMC Infect Dis ; 18(1): 552, 2018 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-30409207

RESUMO

BACKGROUND: Genetic mutations that reduce intracellular superoxide production by granulocytes causes chronic granulomatous disease (CGD). These patients suffer from frequent and severe bacterial and fungal infections throughout their early life. Diagnosis is usually made in the first 2 years of life but is sometimes only diagnosed when the patient is an adult although they may have suffered from symptoms since childhood. CASE PRESENTATION: A 26-year-old man was referred with weight loss, fever, hepatosplenomegaly and coughing. He had previously been diagnosed with lymphadenopathy in the neck at age 8 and prescribed anti-tuberculosis treatment. A chest radiograph revealed extensive right-sided consolidation along with smaller foci of consolidation in the left lung. On admission to hospital he had respiratory problems with fever. Laboratory investigations including dihydrorhodamine-123 (DHR) tests and mutational analysis indicated CGD. Stimulation of his isolated peripheral blood neutrophils (PMN) with phorbol 12-myristate 13-acetate (PMA) produced low, subnormal levels of reactive oxygen species (ROS). Aspergillus terreus was isolated from bronchoalveolar lavage (BAL) fluid and sequenced. CONCLUSIONS: We describe, for the first time, the presence of pulmonary A. terreus infection in an adult autosomal CGD patient on long-term corticosteroid treatment. The combination of the molecular characterization of the inherited CGD and the sequencing of fungal DNA has allowed the identification of the disease-causing agent and the optimal treatment to be given as a consequence.


Assuntos
Aspergillus/isolamento & purificação , Doença Granulomatosa Crônica/diagnóstico , Infecções Respiratórias/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Aspergillus/genética , Sequência de Bases , Líquido da Lavagem Broncoalveolar/microbiologia , Análise Mutacional de DNA , DNA Fúngico/química , DNA Fúngico/isolamento & purificação , DNA Fúngico/metabolismo , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/tratamento farmacológico , Humanos , Pulmão/diagnóstico por imagem , Masculino , Neutrófilos/citologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Infecções Respiratórias/complicações , Infecções Respiratórias/microbiologia , Rodaminas/análise , Acetato de Tetradecanoilforbol/farmacologia , Tomografia Computadorizada por Raios X
18.
Arch Argent Pediatr ; 116(6): e744-e748, 2018 12 01.
Artigo em Espanhol | MEDLINE | ID: mdl-30457728

RESUMO

Chronic granulomatous disease is an uncommon primary immunodeficiency due to a defect of the killing activity of phagocytes, caused by mutations in any of the genes encoding subunits of the superoxide-generating phagocyte NADPH oxidase system. The incidence is 1 in 250 000 live births. It can occur from infancy to adulthood, usually in children under 2 years. Bacterial and fungal infections in association with granuloma lesions are the most common manifestations of the disease. Aspergillus species, Staphylococcus aureus, Serratia marcescens, Nocardia species are the most common microorganisms isolated. We describe here a case of a 1-year-old boy with chronic granulomatous disease and invasive pulmonary aspergillosis, Serratia marcescens osteomyelitis and Enterobacter cloacae cervical granuloma.


Assuntos
Infecções por Enterobacteriaceae/diagnóstico , Doença Granulomatosa Crônica/diagnóstico , Aspergilose Pulmonar/diagnóstico , Infecções por Serratia/diagnóstico , Enterobacter cloacae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Doença Granulomatosa Crônica/microbiologia , Humanos , Lactente , Masculino , Osteomielite/diagnóstico , Osteomielite/metabolismo , Infecções por Serratia/microbiologia , Serratia marcescens/isolamento & purificação
19.
Indian J Pathol Microbiol ; 61(4): 557-560, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30303148

RESUMO

Chronic granulomatous disease (CGD) is a life threatening inherited disorder with varied clinical presentations often characterized by recurrent bacterial and fungal infections along with widespread granulomatous tissue response. The disease results from phagocytic defects characterized by deficiencies in oxidative burst of neutrophils. Nitroblue tetrazolium reduction test (NBT) and Dihydrorhodamine (DHR) with PMA stimulation by flow cytometry are quick, simple, sensitive and specific laboratory tests that help establish early and reliable diagnosis of CGD with an overall improvement in survival and disease prognosis. We report a case of 2-year old child who presented with small bone osteomyelitis involving bilateral feet and was later diagnosed to have autosomal recessive CGD due to mutation in NCF1 gene.


Assuntos
Doença Granulomatosa Crônica/complicações , Osteomielite/etiologia , Pré-Escolar , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Humanos , Masculino , Mutação , NADPH Oxidases/genética
20.
J Pak Med Assoc ; 68(9): 1387-1390, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30317271

RESUMO

Chronic granulomatous disease (CGD) is the most common of the primary immunodeficiency in children. It is caused by single gene defect resulting in dysfunctional nicotinamide adenine dineucleotide phosphate (NADPH) oxidase complex causing recurrent bacterial and fungal infections. Here we present the case of a 9 year old boy who was a known case of CGD since three years of age. He presented with recent history of fever, left sided pain in the scapular region and difficulty in breathing. Chest imaging revealed developing left upper lobe consolidation and erosion of the 3rd posterior rib. The child underwent video assisted thoracoscopic surgery (VATS) and biopsy of the lesion. Histopathology revealed fungal hyphae which were confirmed to be Aspergillus nidulans on staining. He was successfully treated with voriconazole therapy. We will also review the literature on fungal osteomyelitis in CGD patients.


Assuntos
Aspergilose , Aspergillus nidulans/isolamento & purificação , Doença Granulomatosa Crônica , Pneumopatias , Osteomielite , Voriconazol/administração & dosagem , Antifúngicos/administração & dosagem , Aspergilose/diagnóstico , Aspergilose/fisiopatologia , Aspergilose/terapia , Biópsia/métodos , Criança , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/fisiopatologia , Humanos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias/microbiologia , Pneumopatias/fisiopatologia , Pneumopatias/terapia , Masculino , Osteomielite/diagnóstico , Osteomielite/microbiologia , Osteomielite/fisiopatologia , Osteomielite/terapia , Costelas/diagnóstico por imagem , Costelas/patologia , Cirurgia Torácica Vídeoassistida/métodos , Resultado do Tratamento
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