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1.
J Clin Immunol ; 39(8): 762-775, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31456102

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is the most common phagocyte defect disease. Here, we describe 114 CGD patients in our center and report a rare female infant with XL-CGD to provide a better understanding of diagnosis, treatment, and prenatal diagnosis of CGD. METHOD: Patients were diagnosed by DHR-1,2,3 flow cytometry assays and gene analysis. X chromosome inactivation analysis and gp91phox protein test were used for a female infant with XL-CGD. RESULTS: XL-CGD accounts for the majority of cases in China and results in higher susceptibility to some infections than AR-CGD. The DHR assay can help diagnose CGD quickly, and atypical results should be combined with clinical manifestations, genetic analysis, and regular follow-up. For prenatal diagnosis, both gDNA and cDNA genotypes of amniotic fluid cells should be identified, and cord blood DHR assays should be performed to identify female XL-CGD patients.


Assuntos
Testes Genéticos/estatística & dados numéricos , Doença Granulomatosa Crônica/diagnóstico , Diagnóstico Pré-Natal/estatística & dados numéricos , Inativação do Cromossomo X/genética , Líquido Amniótico/citologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Citometria de Fluxo/estatística & dados numéricos , Seguimentos , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Humanos , Lactente , Masculino , NADPH Oxidase 2/genética , Rodaminas/química
2.
Scand J Immunol ; 89(2): e12737, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30506560

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by susceptibility to bacterial and fungal infections resulting from the inadequacy of phagocytic leucocytes to produce reactive oxygen radicals. CGD is a genetically heterogeneous disease with an X-linked recessive (XR-CGD) form caused by mutations in the CYBB (OMIM #300481) gene encoding the gp91(phox) protein, and an autosomal recessive (AR-CGD) form caused by mutations in the CYBA (OMIM #608508), NCF1 (OMIM #608512), NCF2 (OMIM #608515) and NCF4 (OMIM #601488) genes encoding p22(phox), p47(phox), p67(phox) and p40(phox), respectively. The genetic mutation of one of the cytosolic p47phox/p67phox proteins and membrane-bound gp91phox/p22phox proteins, which constitutes the NADPH oxidase enzyme complex, causes the disease. In this study, we evaluated the clinical, laboratory and genetic findings and the prognostic effects of molecular inheritance of our 24 CGD cases (14 XR, 10 autosomal recessive-AR). Consanguinity (three XR and all AR cases) showed statistically significant relationship with the type of hereditary inheritance (P < 0.001). 83% patients had an infection since early infancy. The mean age of initiation of symptoms was earlier in XR cases, and 78% patients had respiratory tract infections. Bone marrow transplantation was performed in five XR cases (two ex) and four AR (one ex) cases. Three of nine XR and two of six AR cases deceased on medical follow-up. In countries especially with high consanguinity rates, the early diagnosis for appropriate prophylactic treatment of CGD is quietly important to avoid from recurrent severe infections, early death and fatal complications of late transplantation.


Assuntos
Consanguinidade , Doença Granulomatosa Crônica/imunologia , NADPH Oxidases/metabolismo , Adolescente , Idade de Início , Transplante de Medula Óssea , Criança , Pré-Escolar , Feminino , Seguimentos , Genes Recessivos/genética , Genes Ligados ao Cromossomo X/genética , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Humanos , Masculino , Mutação/genética , NADPH Oxidase 2/genética , Espécies Reativas de Oxigênio/metabolismo , Estudos Retrospectivos , Resultado do Tratamento , Turquia/epidemiologia
4.
J Pediatric Infect Dis Soc ; 7(suppl_1): S2-S5, 2018 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-29746675

RESUMO

Chronic Granulomatous Disease is one of the classic primary immunodeficiencies of childhood. While the incidence and severity of bacterial and fungal infections have been greatly reduced in this patient population, much remains to be learned about the pathophysiology of the disease, particularly for autoinflammatory manifestations. In this review, we examine the epidemiology, pathophysiology, and genetic basis for CGD.


Assuntos
Doença Granulomatosa Crônica , Mutação , Criança , Feminino , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/fisiopatologia , Humanos , Masculino , NADPH Oxidases/fisiologia
5.
J Clin Immunol ; 38(3): 260-272, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29560547

RESUMO

PURPOSE: Clinical diagnosis and treatment for chronic granulomatous disease (CGD) have advanced greatly in recent years. However, CGD patients in China have unique clinical features and infection spectrums, which are challenging to their caretakers. Here, we summarized the clinical characteristics, genetic features, treatment, and prognosis of CGD in a single center in Shanghai. METHODS: One hundred sixty-nine CGD patients were recruited between January 2004 and May 2017 based on clinical diagnosis. Electronic medical charts were reviewed to collect clinical data. RESULTS: Among the 169 patients recruited, CYBB mutations were identified in 150 cases, whereas CYBA mutations were identified in 7 cases, NCF1 in 5, and NCF2 in 7. The medium age at onset was 1 month (interquartile range 1-3). The medium age at diagnosis was 8 months (interquartile range 3-19). The most common infection sites were the lung (95.9%), lymph node (58.5%), skin (45.4%), intestinal (43.1%), and perianal (38.5%). Bacillus Calmette-Guérin (BCG) infections were common (59.2%). In addition, other non-infectious complications were also common, including anemia (55.4%) and impaired liver functions (34.6%). Thirty-one patients received stem cell transplantation. By the end of this study, 83/131 patients survived. CONCLUSIONS: Similar to other non-consanguineous populations, X-linked CGD accounted for the majority of the cases in China. However, BCG infections were a clinical challenge unique to China. In addition, severe infections were the major cause of death and the overall mortality was still high in China.


Assuntos
Doença Granulomatosa Crônica/complicações , Mycobacterium bovis/imunologia , Tuberculose/etiologia , Tuberculose/prevenção & controle , Vacinação , Anti-Infecciosos/uso terapêutico , Medicamentos Biossimilares , Pré-Escolar , China/epidemiologia , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/etiologia , Feminino , Testes Genéticos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/etiologia , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Avaliação de Sintomas , Tuberculose/diagnóstico , Tuberculose/epidemiologia
6.
J Clin Immunol ; 38(2): 193-203, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29411231

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is an innate immune deficiency disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex that impair the synthesis of oxygen radicals, thus rendering patients susceptible to recurrent infections and excessive hyperinflammatory responses. The most common autosomal recessive form of CGD is p47phox deficiency, which is often clinically milder than the more common X-linked recessive form. Here, we report data on genetics, clinical and biochemical findings in 17 CGD patients of Kavkazi origin with the nonsense mutation c.579G>A in the NCF1 gene, leading to p47phox deficiency. METHODS: Diagnosis was based on detailed clinical evaluation, respiratory burst activity by cytochrome c reduction and dihydrorhodamine-1,2,3 (DHR) assay by flow cytometry, expression of p47phox by immunoblotting and molecular confirmation by DNA sequence analysis. RESULTS: Twelve male and five female patients with median age at onset of 2.5 years (range 1 day to 9 years) were included in the study. The present cohort displays an encouraging 88% overall long-term survival, with median follow-up of 17 years. Clinical manifestations varied from mild to severe expression of the disease. Correlation between genotype and phenotype is unpredictable, although the Kavkazi patients were more severely affected than other patients with p47phox deficiency. CONCLUSIONS: Kavkazi CGD patients harbor a common genetic mutation that is associated with a heterogeneous clinical phenotype. Early diagnosis and proper clinical management in an experienced phagocytic leukocyte center is imperative to ensure favorable patient outcome. New treatment strategies are ongoing, but results are not yet conclusive.


Assuntos
Variação Biológica da População , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Mutação , NADPH Oxidases/genética , Fenótipo , Idade de Início , Biomarcadores , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Recém-Nascido , Israel/epidemiologia , Masculino
7.
J Biopharm Stat ; 28(3): 518-533, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28544854

RESUMO

Five algorithms are described for imputing partially observed recurrent events modeled by a negative binomial process, or more generally by a mixed Poisson process when the mean function for the recurrent events is continuous over time. We also discuss how to perform the imputation when the mean function of the event process has jump discontinuities. The validity of these algorithms is assessed by simulations. These imputation algorithms are potentially very useful in the implementation of pattern mixture models, which have been popularly used as sensitivity analysis under the non-ignorability assumption in clinical trials. A chronic granulomatous disease trial is analyzed for illustrative purposes.


Assuntos
Algoritmos , Ensaios Clínicos como Assunto/métodos , Doença Granulomatosa Crônica/terapia , Distribuição Binomial , Ensaios Clínicos como Assunto/estatística & dados numéricos , Interpretação Estatística de Dados , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Humanos , Distribuição de Poisson
8.
PET Clin ; 13(1): 19-31, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29157383

RESUMO

Pulmonary tuberculosis infects one-third of world's population and is responsible for the high mortality and morbidity in developing countries. The presence of a high number of macrophages and lymphocytes in active tuberculosis granulomas is associated with high uptake of 18F-fluoro-2-deoxy-d-glucose on PET imaging mimicking lung cancer. In many cases, radiological features of pulmonary tuberculosis are undistinguishable from lung cancer, which makes the diagnosis difficult. Clinical history and computed tomographic (CT) findings on a hybrid PET/CT are as important as findings on a PET in the diagnosis of lung cancer.


Assuntos
Fluordesoxiglucose F18 , Doença Granulomatosa Crônica/epidemiologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/epidemiologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/métodos , Tuberculose/epidemiologia , Comorbidade , Humanos , Pulmão/diagnóstico por imagem , Prevalência , Compostos Radiofarmacêuticos
10.
Turk J Haematol ; 34(4): 345-349, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28404538

RESUMO

Hematopoietic stem cell transplantation is a promising curative therapy for many combined primary immunodeficiencies and phagocytic disorders. We retrospectively reviewed pediatric cases of patients diagnosed with primary immunodeficiencies and scheduled for hematopoietic stem cell transplantation. We identified 22 patients (median age, 6 months; age range, 1 month to 10 years) with various diagnoses who received hematopoietic stem cell transplantation. The patient diagnoses included severe combined immunodeficiency (n=11), Chediak-Higashi syndrome (n=2), leukocyte adhesion deficiency (n=2), MHC class 2 deficiency (n=2), chronic granulomatous syndrome (n=2), hemophagocytic lymphohistiocytosis (n=1), Wiskott-Aldrich syndrome (n=1), and Omenn syndrome (n=1). Of the 22 patients, 7 received human leukocyte antigen-matched related hematopoietic stem cell transplantation, 12 received haploidentical hematopoietic stem cell transplantation, and 2 received matched unrelated hematopoietic stem cell transplantation. The results showed that 5 patients had graft failure. Fourteen patients survived, yielding an overall survival rate of 67%. Screening newborn infants for primary immunodeficiency diseases may result in timely administration of hematopoietic stem cell transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes de Imunodeficiência/terapia , Síndrome de Chediak-Higashi/epidemiologia , Síndrome de Chediak-Higashi/terapia , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/epidemiologia , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/terapia , Humanos , Síndromes de Imunodeficiência/epidemiologia , Lactente , Síndrome da Aderência Leucocítica Deficitária/epidemiologia , Síndrome da Aderência Leucocítica Deficitária/terapia , Linfo-Histiocitose Hemofagocítica/epidemiologia , Linfo-Histiocitose Hemofagocítica/terapia , Masculino , Imunodeficiência Combinada Severa/epidemiologia , Imunodeficiência Combinada Severa/terapia , Análise de Sobrevida , Turquia/epidemiologia , Síndrome de Wiskott-Aldrich/epidemiologia , Síndrome de Wiskott-Aldrich/terapia
11.
Clin Infect Dis ; 64(6): 767-775, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28362954

RESUMO

Background: Although prognosis of Chronic Granulomatous Disease (CGD) has greatly improved, few studies have focused on its long-term outcome. We studied the clinical course and sequelae of CGD patients diagnosed before age 16, at various adult time points. Method: Cross-sectional French nationwide retrospective study of patients screened through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry. Results: Eighty CGD patients (71 males [88.7%], 59 X-linked [73.7%], median age 23.9 years [minimum, 16.6; maximum, 59.9]) were included, Median ages at diagnosis and last follow-up were 2.52 and 23.9 years, respectively. Seven patients underwent hematopoietic stem cell transplantation. A total of 553 infections requiring hospitalization occurred in 2017 patient-years. The most common site of infection was pulmonary (31%). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the commonest pathogens. A total of 224 inflammatory episodes occurred in 71 patients, mainly digestive (50%). Their characteristics as well as their annual frequency did not vary before and after age 16. Main sequelae were a small adult height and weight and mild chronic restrictive respiratory failure. At age 16, only 53% of patients were in high school. After age 30 years, 9/13 patients were working. Ten patients died during adulthood. Conclusions: Adult CGD patients displayed similar characteristics and rates of severe infections and inflammatory episodes that those of childhood. The high rate of handicap has become a matter of medical and social consideration. Careful follow-up in centers of expertise is strongly recommended and an extended indication of curative treatment by HSCT should be considered.


Assuntos
Doença Granulomatosa Crônica/epidemiologia , Adolescente , Fatores Etários , Antibioticoprofilaxia , Autoimunidade , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/prevenção & controle , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Estudos Transversais , Feminino , França/epidemiologia , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , Micoses/tratamento farmacológico , Micoses/epidemiologia , Micoses/etiologia , Micoses/prevenção & controle , Fenótipo , Vigilância da População , Sistema de Registros , Estudos Retrospectivos , Análise de Sobrevida , Avaliação de Sintomas
12.
J Clin Immunol ; 37(3): 319-328, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28332028

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is an inherited phagocytic disorder characterized by recurrent infections with usually catalase-positive organisms. Infections in CGD from developing countries are expected to be different from those in the Western countries. We report the profile of infections in children diagnosed with CGD from a tertiary care center in North India. METHODOLOGY: Case records of children diagnosed with CGD at Pediatric Immunodeficiency Clinic, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India, from August 1993 to April 2016 (23 years) were analyzed. RESULTS: Thirty-eight children were diagnosed to have CGD. Median follow-up of patients was 2 years (interquartile range 0.75, 6.0). Staphylococcus aureus and Pseudomonas spp. were the two most common causative bacteria isolated. Aspergillus was the most common fungus isolated. The most common organ involved was the lung (94.7%). Liver abscesses were identified in 5 patients (13.2%), and 20 (52.6%) patients had lymphadenitis. Infections with Pseudomonas spp. were high in our cohort (15.7%) compared to the other studies. Infections with some unusual organisms (e.g., Fusarium dimerium and Chryseobacterium gleum) were also seen in our cohort. Children with X-linked CGD presented earlier and also had a greater number of infections as compared to autosomal recessive CGD. CONCLUSIONS: Various socioeconomic factors coupled with the lack of awareness and paucity of readily available diagnostic facilities for primary immunodeficiencies accounted for a late clinical presentation with severe infections and increased mortality (28.9%) in our cohort. However, mortality was similar in X-linked and autosomal recessive CGD as was the number of fungal infections. The incidence of infections and mortality was significantly lower after initiation of antibacterial and antifungal prophylaxis.


Assuntos
Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/epidemiologia , Infecções/epidemiologia , Infecções/etiologia , Idade de Início , Anti-Infecciosos/uso terapêutico , Antibioticoprofilaxia , Pré-Escolar , Coinfecção , Análise Mutacional de DNA , Feminino , Seguimentos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/etiologia , Humanos , Imunofenotipagem , Índia/epidemiologia , Lactente , Controle de Infecções , Infecções/diagnóstico , Infecções/tratamento farmacológico , Masculino , Mortalidade , Mutação , Fenótipo , Centros de Atenção Terciária
14.
J Immunol Res ; 2017: 8745254, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28251166

RESUMO

Chronic Granulomatous Disease (CGD) is a rare inherited primary immunodeficiency, which is characterized by recurrent infections due to defective phagocyte NADPH oxidase enzyme. Nowadays, little is known about Chinese CGD patients. Here we report 48 CGD patients in our single center study, which is the largest cohort study from Mainland China. The ratio of male to female was 11 : 1. The mean onset age was 0.29 years old, and 52% patients had an onset within the 1st month of life. The mean diagnosis age was 2.24 years old. 11 patients (23%) had died with an average age of 2.91 years old. 13 patients (28%) had positive family histories. The most prevalent infectious sites were the lungs (77%), followed by gastrointestinal tract (54%), lymph nodes (50%), and skin (46%). In addition, septicopyemia, thrush, and hepatosplenomegaly were also commonly observed, accounting for 23%, 23%, and 40% of the cases. Lesions due to BCG vaccination occurred in more than half of the patients. X-linked CGD due to CYBB gene mutations accounted for 75% of the cases, and 11 of them were novel mutations. Autosomal recessive inheritance accounted for 6% patients, including 1 patient with CYBA, 1 with NCF1, and 1 with NCF2 gene mutations.


Assuntos
Doença Granulomatosa Crônica/genética , Doença Granulomatosa Crônica/fisiopatologia , Mutação , Adolescente , Adulto , Idoso , Vacina BCG/efeitos adversos , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Feminino , Trato Gastrointestinal/microbiologia , Testes Genéticos , Doença Granulomatosa Crônica/congênito , Doença Granulomatosa Crônica/epidemiologia , Humanos , Síndromes de Imunodeficiência/genética , Lactente , Pulmão/microbiologia , Linfonodos/microbiologia , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , NADPH Oxidase 2 , NADPH Oxidases/genética , Pele/microbiologia , Adulto Jovem
15.
Injury ; 47(11): 2484-2489, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27670281

RESUMO

Many previous reports have indicated that atypical femur fractures (AFFs) are associated with the administration of bisphosphonates (BPs). A number of risk factors and hypotheses regarding the pathogenesis of AFFs have been reported to date. The purpose of the present study was to identify the factors associated with AFFs in Japanese individuals and to elucidate the association between bone metabolism and AFFs by evaluating bone turnover markers (BTMs). We prospectively reviewed all patients with femur fractures and identified the patients with AFFs and typical femur fractures (TFFs). We collected the demographic and clinical data that were relevant to the present study, namely age, gender, affected side, affected site, concomitant medical history, and comorbid conditions, and measured the levels of BTMs within 24h after trauma. Welch's test and Fisher's exact probability test were used for the statistical analyses. A total of 338 patients, including 10 patients with AFFs and 328 patients with TFFs, were analyzed under the inclusion criteria. The use of BPs (p<0.001) and collagen disease and chronic granulomatous disease (CD/CGD) (p=0.025) were more frequently observed in patients with AFFs than in patients with TFFs, while the levels of BTMs, including N-terminal propeptides of type 1 procollagen (P1NP), isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) and undercarboxylated osteocalcin (ucOC) were significantly lower in patients with AFFs than in patients with TFFs. Furthermore, the level of TRACP-5b was found to be significantly lower in patients with atypical subtrochanteric fractures than in atypical diaphyseal fractures (p=0.025). Moreover, the levels of P1NP (p=0.016) and TRACP-5b (p=0.015) were found to be significantly lower in patients with AFFs than in patients with TFFs in a subgroup analysis of BPs users. The use of BPs was considered to be a factor associated with AFFs. Our comparison of the BTMs in patients with AFFs and TFFs indicated that the severe suppression of bone turnover was associated with the pathogenesis of AFFs. The extent of the influence of suppressed turnover on the pathogenesis of AFFs may differ depending on the fracture site.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea , Doenças do Colágeno/patologia , Difosfonatos/efeitos adversos , Fraturas do Fêmur/patologia , Consolidação da Fratura/fisiologia , Doença Granulomatosa Crônica/patologia , Osteoporose/patologia , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático , Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Doenças do Colágeno/sangue , Doenças do Colágeno/epidemiologia , Comorbidade , Estudos Transversais , Feminino , Fraturas do Fêmur/sangue , Fraturas do Fêmur/epidemiologia , Doença Granulomatosa Crônica/sangue , Doença Granulomatosa Crônica/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fragmentos de Peptídeos , Pró-Colágeno , Estudos Prospectivos , Fatores de Risco , Fosfatase Ácida Resistente a Tartarato
16.
J Clin Immunol ; 36(8): 764-773, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27582173

RESUMO

An abnormal regulation of immune responses leads to autoimmune and inflammatory manifestations in patients with primary immunodeficiencies (PIDs). The objective of our study was to evaluate the frequency of non-infectious and non-malignant manifestations in a large cohort of patients included in the Slovenian national PID registry and to assess the time of manifestation onset with respect to the time of PID diagnosis. Medical records of registered patients were reviewed. Data on autoimmunity, lymphoproliferation, autoinflammation, allergies, PID diagnosis, and underlying genetic defects were collected and analyzed. The time of each manifestation onset was determined and compared with the time of PID diagnosis. As of May 2015, 247 patients with 50 different PIDs were registered in the Slovenian national PID registry (147 males, 100 females; mean age 20 years). Mean disease duration was 14 years; 78 % of patients were younger than 18 years; and 22 % of patients were adults. Diagnosis of PID was genetically confirmed in 51 % of patients. Non-infectious and non-malignant manifestations were present in 69/235 (29 %) patients, including autoimmune manifestations in 52/235 (22 %), lymphoproliferative/granulomatous in 28/235 (12 %), autoinflammatory in 12/247 (5 %), and allergic manifestations in 10/235 (4 %) of all registered patients. Autoimmune manifestations were present in all patients whose PIDs were classified as diseases of immune dysregulation, 47 % of patients with chronic granulomatous disease, and 38 % of patients with predominantly antibody immune deficiencies. A high prevalence of non-infectious and non-malignant manifestations among patients in the Slovenian national PID registry suggests common genetic factors of autoimmunity, inflammation, and immunodeficiency. Patients with PID should be routinely screened for autoimmune and inflammatory manifestations at the time of PID diagnosis and during the long-term follow up.


Assuntos
Autoimunidade/imunologia , Síndromes de Imunodeficiência/epidemiologia , Síndromes de Imunodeficiência/imunologia , Inflamação/epidemiologia , Inflamação/imunologia , Adulto , Feminino , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/imunologia , Humanos , Masculino , Prevalência , Sistema de Registros , Estudos Retrospectivos , Eslovênia/epidemiologia , Adulto Jovem
17.
J Allergy Clin Immunol ; 138(1): 241-248.e3, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26936803

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency caused by inborn errors of the phagocyte nicotinamide adenine dinucleotide phosphate oxidase complex. From the first year of life onward, most affected patients display multiple, severe, and recurrent infections caused by bacteria and fungi. Mycobacterial infections have also been reported in some patients. OBJECTIVE: Our objective was to assess the effect of mycobacterial disease in patients with CGD. METHODS: We analyzed retrospectively the clinical features of mycobacterial disease in 71 patients with CGD. Tuberculosis and BCG disease were diagnosed on the basis of microbiological, pathological, and/or clinical criteria. RESULTS: Thirty-one (44%) patients had tuberculosis, and 53 (75%) presented with adverse effects of BCG vaccination; 13 (18%) had both tuberculosis and BCG infections. None of these patients displayed clinical disease caused by environmental mycobacteria, Mycobacterium leprae, or Mycobacterium ulcerans. Most patients (76%) also had other pyogenic and fungal infections, but 24% presented solely with mycobacterial disease. Most patients presented a single localized episode of mycobacterial disease (37%), but recurrence (18%), disseminated disease (27%), and even death (18%) were also observed. One common feature in these patients was an early age at presentation for BCG disease. Mycobacterial disease was the first clinical manifestation of CGD in 60% of these patients. CONCLUSION: Mycobacterial disease is relatively common in patients with CGD living in countries in which tuberculosis is endemic, BCG vaccine is mandatory, or both. Adverse reactions to BCG and severe forms of tuberculosis should lead to a suspicion of CGD. BCG vaccine is contraindicated in patients with CGD.


Assuntos
Doença Granulomatosa Crônica/complicações , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/etiologia , Vacina BCG/administração & dosagem , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/etiologia , Infecções Bacterianas/mortalidade , Criança , Pré-Escolar , Feminino , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/mortalidade , Doença Granulomatosa Crônica/terapia , Humanos , Lactente , Masculino , Infecções por Mycobacterium/epidemiologia , Infecções por Mycobacterium/mortalidade , Micoses/diagnóstico , Micoses/epidemiologia , Micoses/etiologia , Micoses/mortalidade , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , Tuberculose/diagnóstico , Tuberculose/etiologia
18.
Pediatr Blood Cancer ; 62(12): 2101-7, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26185101

RESUMO

AIM: We analyzed data from 71 patients with chronic granulomatous disease (CGD) with a confirmed genetic diagnosis, registered in the online Latin American Society of Primary Immunodeficiencies (LASID) database. RESULTS: Latin American CGD patients presented with recurrent and severe infections caused by several organisms. The mean age at disease onset was 23.9 months, and the mean age at CGD diagnosis was 52.7 months. Recurrent pneumonia was the most frequent clinical condition (76.8%), followed by lymphadenopathy (59.4%), granulomata (49.3%), skin infections (42%), chronic diarrhea (41.9%), otitis (29%), sepsis (23.2%), abscesses (21.7%), recurrent urinary tract infection (20.3%), and osteomyelitis (15.9%). Adverse reactions to bacillus Calmette-Guérin (BCG) vaccination were identified in 30% of the studied Latin American CGD cases. The genetic diagnoses of the 71 patients revealed 53 patients from 47 families with heterogeneous mutations in the CYBB gene (five novel mutations: p.W361G, p.C282X, p.W483R, p.R226X, and p.Q93X), 16 patients with the common deletion c.75_76 del.GT in exon 2 of NCF1 gene, and two patients with mutations in the CYBA gene. CONCLUSION: The majority of Latin American CGD patients carry a hemizygous mutation in the CYBB gene. They also presented a wide range of clinical manifestations most frequently bacterial and fungal infections of the respiratory tract, skin, and lymph nodes. Thirty percent of the Latin American CGD patients presented adverse reactions to BCG, indicating that this vaccine should be avoided in these patients.


Assuntos
Doença Granulomatosa Crônica , Glicoproteínas de Membrana/genética , Mutação , NADPH Oxidases/genética , Sistema de Registros , Abscesso/epidemiologia , Abscesso/etiologia , Abscesso/genética , Adolescente , Idade de Início , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/etiologia , Diarreia/genética , Feminino , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/genética , Hispano-Americanos , Humanos , Lactente , Recém-Nascido , Doenças Linfáticas/epidemiologia , Doenças Linfáticas/etiologia , Doenças Linfáticas/genética , Masculino , NADPH Oxidase 2 , Osteomielite/epidemiologia , Osteomielite/etiologia , Osteomielite/genética , Otite/epidemiologia , Otite/etiologia , Otite/genética , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia/genética , Sepse/epidemiologia , Sepse/etiologia , Sepse/genética , Dermatopatias/epidemiologia , Dermatopatias/etiologia , Dermatopatias/genética , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Infecções Urinárias/genética
19.
PLoS One ; 10(6): e0128153, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26083865

RESUMO

OBJECTIVE: To observe the incidence of reversed halo sign in different pulmonary diseases and the pathological correspondence of reversed halo sign. METHODS: Retrospectively studied the high resolution computer tomography scans of all the patients who were admitted in our department with abnormal pulmonary imaging, from 1st of January 2011 to 31st of December 2013, and all the cases with reversed halo sign on the high resolution computer tomography were collected. Clinical data such as pathological findings and confirmed diagnosis of the patients with reversed halo sign on the high resolution computer tomography scan were collected and summarized. RESULTS: Of 1546 abnormal High resolution computer tomography scans 108 had a reverse halo sign present, including 108 cases were observed with reversed halo sign in the high resolution computer tomography, including 40 cases of pulmonary tuberculosis, 43 cases of cryptogenic organizing pneumonia, 16 cases of lung cancer, 7 cases of sarcoidosis, and 1 case of pulmonary cryptococcosis, 1 case of granulomatosis with polyangiitis. Reversed halo sign had a higher incidence in granulomatous diseases (16.28%) compared with non-granulomatous diseases (9.97%). CONCLUSIONS: Reversed halo sign is relatively non specific; it can be observed in different lung diseases, and different phases of diseases; reversed halo sign is more commonly found in granulomatous diseases compared with non-granulomatous diseases, and is most commonly observed in pulmonary tuberculosis among the granulomatous diseases, and in cryptogenic organizing pneumonia among the non-granulomatous diseases.


Assuntos
Pneumopatias/diagnóstico , Adulto , Idoso , Feminino , Doença Granulomatosa Crônica/diagnóstico por imagem , Doença Granulomatosa Crônica/epidemiologia , Humanos , Incidência , Pulmão/diagnóstico por imagem , Pneumopatias/diagnóstico por imagem , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Allergol. immunopatol ; 43(3): 279-285, mayo-jun. 2015. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-136335

RESUMO

BACKGROUND: Chronic granulomatous disease (CGD) is an inherited disease that results from a defect in the phagocytic cells of the immune system. It is caused by defects in one of the major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. The clinical presentations of CGD patients are heterogeneous. OBJECTIVES: This is the first report from Egypt discussing clinical and laboratory data of twenty-nine patients (from 26 families) with CGD from a single tertiary referral centre. RESULTS: There were twenty male and nine female patients. The consanguinity rate was 76% (19/25). Their age of diagnosis ranged from 2 to 168 months with a mean of 52.8 months ± 49.6 SD. The most common manifestations were abscesses in 79.3% (deep organ abscesses in 37.9% of patients), followed by pneumonia in 75.8% and gastrointestinal symptoms in 27.5%. Rare but fatal complications were also reported among patients as one patient developed haemophagocytic lymphohistiocytosis (HLH) syndrome. Although X linked-CGD universally constitutes the most common pattern of inheritance; only 6 of our patients 6/25 (24%) belonged to this group with a Stimulation Index (SI) of 1-5, and confirmed by carrier pattern of their mothers. Mothers were not available for testing in four male children. Nineteen patients (76%) had autosomal recessive patterns; ten males and nine females patients based on having abnormal SI, positive history of consanguinity and their mothers showing normal SI. CONCLUSION: Increasing the awareness of physicians about symptoms of CGD may lead to earlier diagnosis of the disease, thus enhancing proper management and better quality of life


No disponible


Assuntos
Humanos , Masculino , Feminino , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/prevenção & controle , NADP/imunologia , Imunofenotipagem/métodos , Imunofenotipagem , Estudos de Coortes , Egito/epidemiologia , Citometria de Fluxo/métodos , Citometria de Fluxo/tendências , Citometria de Fluxo , Infecções/complicações , Infecções/imunologia , Rodamina 123
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