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1.
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
2.
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
3.
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
4.
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
5.
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 , Infecção/epidemiologia , Infecção/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 , Infecção/diagnóstico , Infecção/tratamento farmacológico , Controle de Infecções , Masculino , Mortalidade , Mutação , Fenótipo , Centros de Atenção Terciária
6.
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
7.
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
8.
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
9.
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
10.
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
11.
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
12.
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 (AU)


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 , Infecção/complicações , Infecção/imunologia , Rodamina 123
13.
Chest ; 147(2): e48-e51, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25644916

RESUMO

A 60-year-old asymptomatic woman was referred to our hospital because of an abnormal chest roentgenogram during a routine medical checkup. The patient had no history of memorable infectious diseases, except a liver abscess caused by Serratia marcescens at age 46 years. Her son was diagnosed with chronic granulomatous disease at the age of 1 year. She had never smoked cigarettes and drank only occasionally.


Assuntos
Infecções Assintomáticas , Doença Granulomatosa Crônica/epidemiologia , Aspergilose Pulmonar/diagnóstico , Aspergilose Pulmonar/epidemiologia , Antifúngicos/administração & dosagem , Antígenos de Fungos/análise , Comorbidade , Feminino , Doença Granulomatosa Crônica/genética , Humanos , Abscesso Hepático , Linfonodos/microbiologia , Doenças Linfáticas , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , NADPH Oxidase 2 , NADPH Oxidases/genética , Neutrófilos/fisiologia , Tomografia Computadorizada por Raios X , Voriconazol/administração & dosagem
14.
J Cutan Med Surg ; 18(6): 397-404, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25348761

RESUMO

BACKGROUND: Mucocutaneous manifestations of inflammatory bowel diseases are relatively common; the mean incidence is around 10% at the time of diagnosis. However, during follow-up, an increased variety of skin lesions, granulomatous cutaneous disease, reactive skin eruptions, nutritional defiencies, and other associated conditions may develop. OBJECTIVE: The objective of this study was to evaluate the prevalence of the mucocutaneous manifestations and their association with gender, duration of disease, arthritis, location of the bowel disease, and disease activity. METHODS: Fifty-six patients with ulcerative colitis (UC) and 36 patients with Crohn disease (CD) who were in follow-up in the Istanbul Medeniyet University Göztepe Training and Research Hospital Department of Gastroenterology were included in the study. Whole-body dermatologic examinations were performed for all patients, and patient files were evaluated for mucocutaneous manifestations. RESULTS: Of the 92 patients, 49 (53.26%) presented with at least one mucocutaneous manifestation (58.9% of patients with UC and 44.4% of patients with CD). Of these, 38 (41.3%) had at least one reactive skin eruption. Aphthous stomatitis was noted in 33 patients (35.86%) and became the most common mucocutaneous manifestation. Granulomatous cutaneous diseases were detected in 18 patients (19.57%), and none of the patients had a nutritional deficiency-associated skin condition. Only 3 patients (3.26%) had erythema nodosum and 2 patients (2.17%) had pyoderma gangrenosum. CONCLUSIONS: We found that mucocutaneous manifestations of inflammatory bowel diseases are more common than thought and are more common in UC than in CD. No association was detected between mucocutaneous manifestions and gender, duration of disease, arthritis, location of the bowel disease, and activity of the disease.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Doença Granulomatosa Crônica/epidemiologia , Dermatopatias/epidemiologia , Estomatite Aftosa/epidemiologia , Adulto , Idoso , Eritema Nodoso/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Pioderma Gangrenoso/epidemiologia , Fatores Sexuais , Turquia/epidemiologia , Adulto Jovem
15.
Circulation ; 130(23): 2031-9, 2014 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-25239440

RESUMO

BACKGROUND: Patients with chronic granulomatous disease (CGD) experience immunodeficiency because of defects in the phagocyte NADPH oxidase and the concomitant reduction in reactive oxygen intermediates. This may result in a reduction in atherosclerotic injury. METHODS AND RESULTS: We prospectively assessed the prevalence of cardiovascular risk factors, biomarkers of inflammation and neutrophil activation, and the presence of magnetic resonance imaging and computed tomography quantified subclinical atherosclerosis in the carotid and coronary arteries of 41 patients with CGD and 25 healthy controls in the same age range. Univariable and multivariable associations among risk factors, inflammatory markers, and atherosclerosis burden were assessed. Patients with CGD had significant elevations in traditional risk factors and inflammatory markers compared with control subjects, including hypertension, high-sensitivity C-reactive protein, oxidized low-density lipoprotein, and low high-density lipoprotein. Despite this, patients with CGD had a 22% lower internal carotid artery wall volume compared with control subjects (361.3±76.4 mm(3) versus 463.5±104.7 mm(3); P<0.001). This difference was comparable in p47(phox)- and gp91(phox)-deficient subtypes of CGD and independent of risk factors in multivariate regression analysis. In contrast, the prevalence of coronary arterial calcification was similar between patients with CGD and control subjects (14.6%, CGD; 6.3%, controls; P=0.39). CONCLUSIONS: The observation by magnetic resonance imaging and computerized tomography of reduced carotid but not coronary artery atherosclerosis in patients with CGD despite the high prevalence of traditional risk factors raises questions about the role of NADPH oxidase in the pathogenesis of clinically significant atherosclerosis. Additional high-resolution studies in multiple vascular beds are required to address the therapeutic potential of NADPH oxidase inhibition in cardiovascular diseases. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01063309.


Assuntos
Doenças das Artérias Carótidas , Doença da Artéria Coronariana , Doença Granulomatosa Crônica , Glicoproteínas de Membrana/imunologia , NADPH Oxidases/deficiência , Adulto , Doenças das Artérias Carótidas/epidemiologia , Doenças das Artérias Carótidas/imunologia , Doenças das Artérias Carótidas/patologia , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Estudos Transversais , Feminino , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/genética , NADPH Oxidases/imunologia , NADPH Oxidases/metabolismo , Fagócitos/imunologia , Prevalência , Fatores de Risco , Calcificação Vascular/epidemiologia , Calcificação Vascular/imunologia , Calcificação Vascular/patologia , Adulto Jovem
17.
J Clin Immunol ; 34(6): 633-41, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24943880

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is an inherited disorder, with phagocytes failing to produce antimicrobial superoxide due to deficient NADPH oxidase activity. Mutations in the gene encoding CYBB are responsible for the majority of the CGD cases. To date, there have been no reports on large samples of children with CGD in China. Therefore, in this study, we described the clinical and molecular features of 38 suspected CGD patients from 36 unrelated Chinese families. METHODS: Clinical diagnosis was performed using dihydrorhodamine assays detected by flow cytometry. Molecular analysis was used to identify underlying CGD-causative genes. RESULTS: The mean age of onset in our 38 patients was 3.4 months, while the mean age at diagnosis was 31.7 months. Apart from recurrent pneumonia and abscesses, tuberculosis (TB) and Bacille Calmette-Guerin (BCG) infections were notable features in our cohort. Overall, 17 cases died and patient 1 did not participate in the follow-up period . In total, we identified 29 different CYBB gene mutations in 31 patients. We found NCF1 and CYBA mutations in 3 and 2 patients, respectively. In addition, we identified 31 carriers and prenatally diagnosed 4 CGD and 4 healthy fetuses. CONCLUSIONS: The results of our study demonstrate that children with BCG infections or recurrent TB infections should have immune function screening tests performed. Moreover, newborns with family histories of primary immunodeficiency diseases should avoid of BCG vaccination. Molecular analysis is an important tool for identifying patients, carriers, and high-risk CGD fetuses.


Assuntos
Doença Granulomatosa Crônica/epidemiologia , Glicoproteínas de Membrana/metabolismo , NADPH Oxidases/metabolismo , Tuberculose Pulmonar/epidemiologia , Idade de Início , Criança , Pré-Escolar , China , Análise Mutacional de DNA , Feminino , Seguimentos , Doença Granulomatosa Crônica/diagnóstico , Humanos , Lactente , Recém-Nascido , Masculino , Glicoproteínas de Membrana/genética , Mutação/genética , NADPH Oxidase 2 , NADPH Oxidases/genética , Gravidez , Risco , Tuberculose Pulmonar/diagnóstico
18.
J Clin Immunol ; 34(1): 58-67, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24276928

RESUMO

Chronic granulomatous disease (CGD) results from an inherited defect in the phagocytic cells of the immune system. It is a genetically heterogenous disease caused by defects in one of the five major subunits of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. There is a paucity of data from India on CGD. We herein describe the clinical features in 17 children with CGD from a single tertiary referral center in India. A detailed analysis of the clinical features, laboratory investigations and outcome of 17 children 7 with X-linked (XL) and 10 with autosomal recessive (AR) form was performed. Diagnosis of CGD was based on an abnormal granulocyte oxidative burst evaluated by either Nitroblue Tetrazolium (NBT) test or flow cytometry based Dihyrorhodamine 123 assay or both. The molecular diagnosis was confirmed by genetic mutation analysis in 13 cases. The mean age at diagnosis and the age at onset of symptoms was significantly lower in children diagnosed with XL- CGD compared those with AR disease. Mutations were detected in CYBB gene in 6 patients with XL-CGD and NCF-1 gene mutations were observed in 7 cases of AR- CGD. The course and outcome of the disease was much worse in children diagnosed with X-linked form of disease compared to AR forms of the disease; 4/7 (57%) children with X-CGD were dead at the time of data analysis. This is one of the largest series on chronic granulomatous disease from any developing country.


Assuntos
Doença Granulomatosa Crônica/epidemiologia , Centros de Atenção Terciária , Idade de Início , Causas de Morte , Criança , Pré-Escolar , Feminino , Seguimentos , Doença Granulomatosa Crônica/complicações , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/genética , Mortalidade Hospitalar , Humanos , Índia , Lactente , Recém-Nascido , Infecção/etiologia , Infecção/microbiologia , Masculino , Mutação , Prognóstico
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