RESUMO
INTRODUCTION: Chronic mucocutaneous candidiasis (CMC) is characterized by susceptibility to chronic or recurrent infections with yeasts of the genus Candida affecting the skin, nails and mucous membranes. We describe a Moroccan patient presenting CMC with heterozygous STAT1 gain-of-function (GOF) mutation. PATIENTS AND METHODS: A 5-year-old boy with no consanguinity presented recurrent episodes of oral thrush, chronic nail candidiasis and herpetic gingivostomatitis from the age of 8 months. He also had mycobacterial adenitis secondary to BCG vaccination and atypical rosacea. Genetic analysis revealed GOF mutation of the STAT1 gene. DISCUSSION: CMC was diagnosed in our patient despite poor clinical features. Sequencing of the genome revealed STAT1GOF mutation. This mutation affects production of IL-17, an important cytokine in mucocutaneous defense against Candida. The association with mycobacterial adenitis is rare and continues to be poorly understood. The presence of atypical rosacea in this setting is suggestive of this entity. Antifungal therapy and prevention of complications are necessary to reduce the morbidity and mortality associated with this condition. CONCLUSION: CMC due to STAT1GOF mutation is characterized by a broad clinical spectrum and should be considered in all cases of chronic or recurrent fungal infection, whether or not associated with other infections.
Assuntos
Candidíase Mucocutânea Crônica/genética , Mutação com Ganho de Função , Fator de Transcrição STAT1/genética , Adjuvantes Imunológicos/efeitos adversos , Vacina BCG/efeitos adversos , Candidíase Mucocutânea Crônica/complicações , Candidíase Bucal/complicações , Calázio/complicações , Pré-Escolar , Doença Crônica , Doenças da Gengiva/virologia , Humanos , Linfadenite/microbiologia , Masculino , Infecções por Mycobacterium/complicações , Onicomicose/complicações , Estomatite Herpética/complicaçõesRESUMO
PURPOSE: Primary immunodeficiencies (PIDs) are a large group of diseases characterized by susceptibility to infections. We provide the first comprehensive report on PIDs in Morocco, the epidemiological, clinical, etiological and outcome features which have never before been described. METHODS: A national registry was established in 2008, grouping together data for PID patients diagnosed since 1998. RESULTS: In total, 421 patients were diagnosed between 1998 and 2012. Parental consanguinity was common (recorded for 43.2 % of patients) and the median time to diagnosis was 2.0 years. Overall, 27.4 % of patients were considered to have well defined syndromes with immunodeficiency (48 cases of hyper-IgE syndrome and 40 of ataxia-telangiectasia); 22.7 % had predominantly antibody deficiencies (29 cases of agammaglobulinemia and 24 of CVID); 20.6 % had combined immunodeficiencies (37 cases of SCID and 26 of MHC II deficiencies) and 17.5 % had phagocyte disorders (14 cases of SCN and 10 of CGD). The principal clinical signs were lower respiratory tract infections (60.8 %), skin infections (33.5 %) and candidiasis (26.1 %). Mortality reached 28.8 %, and only ten patients underwent bone marrow transplantation. We analyzed the impact on mortality of residence, family history, parental consanguinity, date of diagnosis and time to diagnosis, but only date of diagnosis had a significant effect. CONCLUSIONS: The observed prevalence of PID was 0.81/100,000 inhabitants, suggesting considerable underdiagnosis and a need to increase awareness of these conditions in Morocco. The distribution of PIDs was different from that reported in Western countries, with a particularly high proportion of SCID, MHC II deficiencies, hyper-IgE syndrome and autosomal recessive agammaglobulinemia. However, we have now organized a national network, which should improve diagnosis rates in remote regions.
Assuntos
Síndromes de Imunodeficiência/diagnóstico , Síndromes de Imunodeficiência/epidemiologia , Sistema de Registros , Adolescente , Adulto , Transplante de Medula Óssea , Criança , Pré-Escolar , Consanguinidade , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Síndromes de Imunodeficiência/classificação , Síndromes de Imunodeficiência/terapia , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Marrocos/epidemiologia , PrevalênciaRESUMO
Mucocutaneous fungal infections are common and usually occur in the presence of certain risk factors. However, these infections can occur in patients with no known risk factors. This indicates the presence of an underlying genetic susceptibility to fungi reflecting an innate or adaptive immune deficiency. In this review, we highlight genetic factors that predispose to mucocutaneous fungal infections specially candidiasis and dermatophytosis.
Assuntos
Candidíase Mucocutânea Crônica , Síndromes de Imunodeficiência , Micoses , Candidíase Mucocutânea Crônica/epidemiologia , Candidíase Mucocutânea Crônica/genética , Predisposição Genética para Doença , HumanosRESUMO
INTRODUCTION: Type I diabetes (T1D) is an autoimmune disease with a prediabetic, asymptomatic period characterized by the selective destruction of insulin-producing ß cells. During the pre-clinical phase, various auto-antibodies are generated against several beta cell antigens such as anti glutamate acid decarboxylase (Anti-GAD), anti tyrosine phosphatase (Anti-IA2). Today, the coupled detection of Anti-IA2 with that of Anti-GAD proves its great importance in the diagnosis and prediction of type 1 diabetes. The combined positivity for both antibodies has a specificity and a positive predictive value of 100%. OBJECTIVES: In this work, we evaluate the diagnostic value of anti-GAD and anti-IA2 antibodies in a series based on 78 Moroccan subjects initially under 16, suspected T1D. RESULTS AND DISCUSSION: Our series consists mainly of 74% of newly diagnosed patients for T1D and 26% of confirmed diagnostic patients, of whom 52% are females. The mean age of diagnosis is 7 ± 4 years, the mean of HbA1c at the time of diagnosis is 11.63 ± 2.16%, and the percentage of family history in our series is 69%. The proportion of positive results for anti-IA2 antibodies and anti-GAD antibodies are, respectively, 76.92% and 62.82%, and 52.56% of patients are positive for both auto-antibodies. This study confirms that anti-GAD and anti-IA2 auto-antibodies assays can detect patients early and the autoantibodies can persist several years after diagnosis of type 1 diabetes. CONCLUSION: This study confirmed the diagnosis and classification of T1D (type 1A) in 87.18% of patients, and we reported that the prevalence of anti-GAD and anti-IA2 is higher in girls than in boys.
Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Glutamato Descarboxilase/imunologia , Proteínas Tirosina Fosfatases/imunologia , Adolescente , Autoanticorpos , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Adulto JovemRESUMO
A 12-year-old daughter of consanguineous Moroccan parents was diagnosed with cyclic neutropenia, based on a combination of recurrent gingivostomatitis, a fluctuating neutrophil count, and several episodes of severe neutropenia. No ELA2 gene mutations were found. At age 19 years she presented with edema of the limbs, proteinuria and renal failure. Renal amyloidosis AA was diagnosed by biopsy. Gene mutations associated with family Mediterranean fever (FMF) were sought, and a homozygous mutation (M694V) was found in the MFEV gene. This is the novel finding of FMF that masqueraded as cyclic neutropenia.
Assuntos
Febre Familiar do Mediterrâneo/diagnóstico , Febre Familiar do Mediterrâneo/genética , Febre Familiar do Mediterrâneo/fisiopatologia , Neutropenia/patologia , Adulto , Amiloidose/genética , Criança , Doença Crônica , Proteínas do Citoesqueleto/genética , Análise Mutacional de DNA , Diagnóstico Diferencial , Feminino , Febre/genética , Humanos , Nefropatias/genética , Mutação , Pirina , Estomatite Herpética/genéticaRESUMO
The Bacille Calmette-Guérin (BCG) vaccine is used extensively worldwide, and more than 100 million children are vaccinated each year. This is a live vaccine that protects against severe tuberculosis in children. However, BCG complications, specific to the BCG vaccine, do occur, although the epidemiology differs from one country to another. Nevertheless, these complications are considered to be rare and range from benign local BCGitis to BCGosis, a potentially lethal disseminated disease. Etiologies of BCGitis/BCGosis can be related to the vaccine itself (technical errors, vaccinal strain) or to the patient. Indeed, it is well established that some immunodeficiencies, primary or acquired, can expose the patient to BCG disease. The diagnosis of a BCG disease lies on clinical examination and laboratory results. Recent advances in molecular biology help to distinguish BCG disease from other mycobacterial infections, especially from tuberculosis. When BCG complications have been confirmed, the underlying defect should be investigated, particularly if other features of immunodeficiency are reported, such as recurrent infection, failure to thrive, etc. Prognosis largely depends on the immune status, but also on the management of the BCG disease. Although the therapeutic protocols are still controversial, there are more and more publications on the diagnosis and management guidelines of the disease.
Assuntos
Vacina BCG/efeitos adversos , Inflamação/microbiologia , Criança , Humanos , Inflamação/diagnóstico , Osteomielite/microbiologiaRESUMO
SETTING: The utility of interferon-gamma release assays (IGRAs), such as the QuantiFERON-TB Gold In-Tube (QFT-GIT) test, in diagnosing active tuberculosis (TB) in children is unclear and depends on the epidemiological setting. OBJECTIVE: To evaluate the performance of QFT-GIT for TB diagnosis in children living in Morocco, an intermediate TB incidence country with high bacille Calmette-Gurin vaccination coverage. DESIGN: We prospectively recruited 109 Moroccan children hospitalised for clinically suspected TB, all of whom were tested using QFT-GIT. RESULTS: For 81 of the 109 children, the final diagnosis was TB. The remaining 28 children did not have TB. QFT-GIT had a sensitivity of 66% (95%CI 5277) for the diagnosis of TB, and a specificity of 100% (95%CI 88100). The tuberculin skin test (TST) had lower sensitivity, at 46% (95%CI 3360), and its concordance with QFT-GIT was limited (69%). Combining QFT-GIT and TST results increased sensitivity to 83% (95%CI 6992). CONCLUSION: In epidemiological settings such as those found in Morocco, QFT-GIT is more sensitive than the TST for active TB diagnosis in children. Combining the TST and QFT-GIT would be useful for the diagnosis of active TB in children, in combination with clinical, radiological and laboratory data.
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Testes de Liberação de Interferon-gama , Teste Tuberculínico , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Adolescente , Vacina BCG/administração & dosagem , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Marrocos/epidemiologia , Estudos Prospectivos , Sensibilidade e Especificidade , Tuberculose/prevenção & controle , VacinaçãoRESUMO
SETTING: Tuberculosis spondylodiscitis (TS), or Pott's disease, an extra-pulmonary form of tuberculosis (TB), is rare and difficult to diagnose in children. Some cases of severe TB in children were recently explained by inborn errors of immunity affecting the interleukin-12/interferon-gamma (IL-12/IFN-γ) axis. OBJECTIVE: To analyse clinical data on Moroccan children with TS, and to perform immunological and genetic explorations of the IL-12/IFN-γ axis. DESIGN: We studied nine children with TS diagnosed between 2012 and 2014. We investigated the IL-12/IFN-γ circuit by both whole-blood assays and sequencing of the coding regions of 14 core genes of this pathway. RESULTS: A diagnosis of TS was based on a combination of clinical, biological, histological and radiological data. QuantiFERON(®)-TB Gold In-Tube results were positive in 75% of patients. Whole-blood assays showed normal IL-12 and IFN-γ production in all but one patient, who displayed impaired decreased response to IL-12. No candidate disease-causing mutations were detected in the exonic regions of the 14 genes. CONCLUSIONS: TS diagnosis in children remains challenging, and is based largely on imaging. Further investigations of TS in children are required to determine the role of genetic defects in pathways that may or may not be related to the IL-12/IFN-γ axis.
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Interferon gama/sangue , Interleucina-12/sangue , Tuberculose da Coluna Vertebral/imunologia , Adolescente , Criança , Pré-Escolar , Tratamento Farmacológico , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Marrocos , Mycobacterium tuberculosis , Estudos Prospectivos , Tomografia Computadorizada por Raios X , Teste TuberculínicoRESUMO
UNLABELLED: Non-typhoidal Salmonella (NTS) infections are a major cause of infantile death in developing countries. OBJECTIVE: The aim of this study was to determine the epidemiologic and therapeutic data, as well as the evolution of NTS in Morocco. METHOD: This retrospective study was made on 41 patients hospitalized for NTS between 1994 and 2002 in the Casablanca University Hospital Pediatric ward. RESULTS: Twenty cases of digestive salmonellosis were diagnosed, 16 cases of septicemia, and 10 cases of meningitis. Ten patients were hospitalized after an outbreak of resistant Salmonella typhimurium in a nursery. Fifty percent of the patients were less than 3 months of age. The three patients between 1 and 3 years of age presented with primary immunodeficiency. Fever, vomiting, and diarrhea were noted in 97% of the cases. The stools were watery in 89% and severe dehydration in 55% of the cases. Salmonella strains were identified in blood in 25 cases, from stools in 10 cases, and from CSF in nine cases. The following Salmonella serotypes were identified: S. typhimurium (53.6%), S. enteritidis (44%), and S. agona (2.4%). Resistance to antibiotics was noted, especially for Salmonella typhimurium (34%) in the nursery outbreak. The evolution was favorable in 80%, but two children with meningitis developed severe neurological sequels, and six hypotrophic infants under 3 years of age died after septicemia.
Assuntos
Infecções por Salmonella/epidemiologia , Salmonella enteritidis/isolamento & purificação , Salmonella typhimurium/isolamento & purificação , Criança , Creches/estatística & dados numéricos , Pré-Escolar , Comorbidade , Diarreia Infantil/epidemiologia , Diarreia Infantil/microbiologia , Surtos de Doenças , Farmacorresistência Bacteriana Múltipla , Insuficiência de Crescimento/epidemiologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Síndromes de Imunodeficiência/epidemiologia , Lactente , Pacientes Internados , Masculino , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/microbiologia , Marrocos/epidemiologia , Estudos Retrospectivos , Infecções por Salmonella/microbiologia , Salmonella enteritidis/efeitos dos fármacos , Salmonella typhimurium/efeitos dos fármacos , Estações do Ano , Sepse/epidemiologia , Sepse/microbiologia , Sepse/mortalidade , População UrbanaRESUMO
IL-12 receptor ß1 deficiency (IL-12Rß1) predisposes patients to mycobacteria and Salmonella infections. We report a case of IL-12Rß1 deficiency with a fatal multi-resistant Salmonella enteritidis infection. This boy was born after from a consanguineous marriage, and diagnosed as having a IL-12Rß1 deficiency since the age of 3 months. He presented with recurrent Salmonella enteritidis essentially digestive localization, complicated by purulent pericarditis at the same germ at the age of two and a half years. At the age of 3, a colonic infiltration due to a Salmonella enteritidis resistant to antibiotics, was complicated by acute intussusception, and the child died. The IL-12Rß1 deficiency is considered as having a good prognosis, in contrast to what happened in our patient. We review therapeutic issues in these patients.
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Doenças do Colo/microbiologia , Intussuscepção/microbiologia , Pericardite/microbiologia , Infecções por Salmonella/complicações , Salmonella enteritidis , Doença Aguda , Pré-Escolar , Humanos , Masculino , Supuração/microbiologiaRESUMO
Ataxia-telangiectasia (AT) is a rare autosomal recessive disease, affecting neurologic and immune system. Numerous mutations are described in the ATM gene in several populations. However, in Morocco, few data are available concerning this condition. Our main goal is to determine clinical, immunological, and molecular presentation of Moroccan patients with AT. We screened 27 patients, out of 22 unrelated families, for ATM gene mutations. All our patients showed ataxia, ocular telangiectasia, and immunodeficiency, as well as elevated serum alphafetoprotein levels. Mean age at diagnosis was 5.51 years, and consanguinity rate was 81.8 %. Mean age at onset was 2.02 years, and mean time to diagnosis was 3.68 years. We found 14 different mutations in 19 unrelated families, of which 7 were not reported. Our results showed that c.5644C>T mutation was the most common in our series. However, further studies are required to demonstrate a founder effects on ATM gene in Moroccan patients, who showed mutational heterogeneity otherwise. Our data indicate that direct sequencing of coding exons is sufficient for a high detection rate in ATM in Moroccan population.