RESUMO
BACKGROUND: WHIM syndrome corresponds to an inborn error of innate and intrinsic immunity, characterized by: warts (Warts), Hypogammaglobulinemia, Infections and Myelocathexis, for its acronym in English. CASE REPORT: 4-year-old male, with severe neutropenia and B-cell lymphopenia from birth, without severe infections or warts; the panel genetic sequencing study of primary immunodeficiencies with the CXCR4 c.1000C>T (p.Arg334*) variant, which is associated with WHIM syndrome. CONCLUSIONS: The diagnosis of severe neutropenia from birth should include the search for inborn errors of immunity, through genetic sequencing studies, especially in asymptomatic or oligosymptomatic patients.
ANTECEDENTES: El síndrome WHIM corresponde a un error innato de la inmunidad innata e intrínseca, caracterizada por verrugas (Warts), hipogammaglobulinemia, infecciones y mielocatexis, por sus siglas en inglés. REPORTE DE CASO: Paciente masculino de 4 años, con neutropenia severa y linfopenia de células B desde el nacimiento, sin infecciones severas ni verrugas. El estudio de secuenciación genética informó la variante CXCR4 c.1000C>T (p.Arg334*), relacionada con el síndrome de WHIM. CONCLUSIÓN: El diagnóstico de neutropenia severa desde el nacimiento debe incluir la búsqueda de errores innatos de la inmunidad, mediante estudios de secuenciación genética, especialmente en pacientes asintomáticos u oligosintomáticos.
Assuntos
Agamaglobulinemia , Síndromes de Imunodeficiência , Neutropenia , Doenças da Imunodeficiência Primária , Verrugas , Masculino , Humanos , Pré-Escolar , Doenças da Imunodeficiência Primária/diagnóstico , Verrugas/diagnóstico , Verrugas/etiologia , Agamaglobulinemia/diagnóstico , Neutropenia/complicações , Neutropenia/diagnóstico , Neutropenia/genética , Síndromes de Imunodeficiência/diagnósticoRESUMO
Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 109/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, Neutropenia congénita de tipo IV: reporte de un caso Congenital neutropenia type IV: case report a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.
La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 109/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.
Assuntos
Glucosefosfato Desidrogenase , Neutropenia , Síndrome Congênita de Insuficiência da Medula Óssea/diagnóstico , Glucosefosfato Desidrogenase/genética , Fator Estimulador de Colônias de Granulócitos/genética , Humanos , Mutação , Neutropenia/congênito , Neutropenia/diagnóstico , Neutropenia/genéticaRESUMO
La neutropenia congénita grave (NCG) es una entidad heterogénea cuya característica común es un recuento absoluto de neutrófilos inferior a 0,5 x 10 9/l. Presenta gran heterogeneidad genética, las mutaciones más frecuentes son las del gen de la elastasa 2 (ELA 2). El tratamiento de primera elección es la administración de factor estimulador de colonias de granulocitos. Los pacientes con NCG presentan infecciones graves en etapas tempranas de la vida. Se presenta una paciente con NCG asociada a fenotipo peculiar con facies triangular, retromicrognatia, patrón venoso prominente en miembros inferiores, comunicación interauricular y mal progreso ponderal, en quien se diagnosticó déficit de la enzima glucosa 6 fosfato deshidrogenasa, subunidad catalítica 3 (G6PC3). A pesar de lo infrecuente de esta mutación como causa de NCG (2 %), su conocimiento cobra importancia porque la coexistencia del fenotipo característico con una NCG orienta en la solicitud del estudio genético que permite arribar al diagnóstico.
Severe congenital neutropenia (SCN) is a heterogeneous disease whose more common feature is an absolute neutrophil count less than 0.5 x 10 9/l. It presents great genetic heterogeneity. Autosomal dominant inherited mutations of the elastase 2 gene (ELA2) represent the most common etiology. The first choice treatment is the administration of granulocyte colony stimulating factor. Patients with SCN develop severe infections early in life. We present a patient who associated SCN to a peculiar phenotype, characterized by triangular facies, retromicrognathia, prominent venous pattern in the lower limbs, atrial septal defect and poor weight progress, in whom a deficiency of the enzyme glucose 6 phosphate dehydrogenase, a catalytic subunit 3 (G6PC3), was diagnosed. Despite the infrequency of this mutation as the origin of SCN (2%), its knowledge becomes important because the coexistence of the characteristic phenotype and SCN guides the request for the genetic study that allows reaching the diagnosis.
Assuntos
Humanos , Feminino , Lactente , Glucosefosfato Desidrogenase/genética , Neutropenia/congênito , Neutropenia/diagnóstico , Neutropenia/genética , Fator Estimulador de Colônias de Granulócitos/genética , Síndrome Congênita de Insuficiência da Medula Óssea/diagnóstico , MutaçãoRESUMO
BACKGROUND: Mutations along PSTPIP1 gene are associated to two specific conditions, PAPA syndrome and PAMI syndrome, both autoinflammatory disorders associated to disturbances in cytoskeleton formation. Immunological aspects of PAMI syndrome has not yet been reported neither the clinical impact on therapeutical decisions. METHODS: Clinical data of patients records were retrospectively accessed. Genomic DNA were extracted and sequenced following standard procedures. Peripheral lymphocytes were quantified in T, B e FOXP3 phenotypes. RESULTS: We describe two related patients with PAMI syndrome harboring the usual E250K mutation. Anti-IL1 therapy could partially control the disease in the index patient. A broad spectrum of immunological effects as well as an aberrant expression of FOXP3 could be observed. CONCLUSIONS: Here we report two related brazilian patients with PAMI syndromes harboring the E250K mutation in PSTPIP1, their immunological aspects and the therapeutical response to canakinumab.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Anemia , Anticorpos Monoclonais Humanizados/administração & dosagem , Proteínas do Citoesqueleto/genética , Doenças Hereditárias Autoinflamatórias , Interleucina-1beta , Neutropenia , Adulto , Anemia/diagnóstico , Anemia/etiologia , Transfusão de Sangue/métodos , Proteína C-Reativa/análise , Pré-Escolar , Feminino , Doenças Hereditárias Autoinflamatórias/sangue , Doenças Hereditárias Autoinflamatórias/genética , Doenças Hereditárias Autoinflamatórias/fisiopatologia , Doenças Hereditárias Autoinflamatórias/terapia , Humanos , Testes Imunológicos/métodos , Imunofenotipagem/métodos , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/imunologia , Monitorização Imunológica/métodos , Mutação , Neutropenia/diagnóstico , Neutropenia/etiologia , Esteroides/administração & dosagem , Exacerbação dos Sintomas , Resultado do TratamentoRESUMO
Neonatal alloimmune neutropenia (NAIN) is caused by maternal alloimmunisation to fetal human neutrophil antigens (HNAs). This study investigated maternal HNA/HLA alloantibodies involved with NAIN and identified the frequency of NAIN in Brazilian neonates. Neonatal neutropenia (neutrophil count < 1.5 × 109 /L) was investigated in samples from 10,000 unselected neonates, resulting in 88 neutropenic newborns (NBs) and their 83 mothers. Genotyping was performed by PCR-SSP (HNA-1/-4) and PCR-RFLP (HNA-3/-5). Serologic studies were performed by GAT (granulocyte agglutination test), Flow-WIFT (white blood cells immunofluorescence test) and LABScreen-Multi-HNA-Kit (OneLambda®) (LSM). Neonatal neutropenia was identified in 88/10,000 (0·9%) NBs. Genotyping revealed 60·2% maternal-fetal HNA incompatibilities (31·8% for HNA-1; 14·8% for HNA-3; 15·9% for HNA-4; 21·6% for HNA-5). Serologic studies revealed 37·3% of mothers with positive results with at least one technique. The detected anti-HNA specificities were confirmed in eight positive cases related to HNA-1/-3 systems. In cases with maternal-fetal HNA-4/-5 incompatibility, no specific neutrophil alloantibodies were found but anti-HLA I/II were present. Anti-HNA-2 was not identified. This is a large Brazilian study which involved the investigation of antibodies against all five HNA systems in neutropenia cases and showed a frequency of NAIN in 8/10,000 neonates. Among the HNA antibodies identified, we highlight the anti-HNA-1d and anti-HNA-3b, antibodies unusual in alloimmunised women, and rarely related to NAIN cases.
Assuntos
Doenças do Recém-Nascido/diagnóstico , Neutropenia/diagnóstico , Brasil/epidemiologia , Feminino , Genótipo , Humanos , Recém-Nascido , Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/epidemiologia , Doenças do Recém-Nascido/genética , Isoanticorpos/sangue , Isoanticorpos/genética , Isoanticorpos/imunologia , Contagem de Leucócitos , Masculino , Neutropenia/sangue , Neutropenia/epidemiologia , Neutropenia/genética , Neutrófilos/imunologiaAssuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Neutropenia/virologia , Pneumonia Viral/diagnóstico , COVID-19 , Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Neutropenia/diagnóstico , Neutropenia/terapia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/terapia , SARS-CoV-2 , Índice de Gravidade de DoençaRESUMO
OBJECTIVES: To assess risk factors for multidrug-resistant Pseudomonas aeruginosa (MDR-PA) infection in neutropenic patients. METHODS: Single-centre retrospective analysis of consecutive bloodstream infection (BSI) episodes (2004-2017, Barcelona). Two multivariate regression models were used at BSI diagnosis and P. aeruginosa detection. Significant predictors were used to establish rules for stratifying patients according to MDR-PA BSI risk. RESULTS: Of 661 Gram-negative BSI episodes, 190 (28.7%) were caused by P. aeruginosa (70 MDR-PA). Independent factors associated with MDR-PA among Gram-negative organisms were haematological malignancy (OR 3.30; 95% CI 1.15-9.50), pulmonary source of infection (OR 7.85; 95% CI 3.32-18.56), nosocomial-acquired BSI (OR 3.52; 95% CI 1.74-7.09), previous antipseudomonal cephalosporin (OR 13.66; 95% CI 6.64-28.10) and piperacillin/tazobactam (OR 2.42; 95% CI 1.04-5.63), and BSI occurring during ceftriaxone (OR 4.27; 95% CI 1.15-15.83). Once P. aeruginosa was identified as the BSI aetiological pathogen, nosocomial acquisition (OR 7.13; 95% CI 2.87-17.67), haematological malignancy (OR 3.44; 95% CI 1.07-10.98), previous antipseudomonal cephalosporin (OR 3.82; 95% CI 1.42-10.22) and quinolones (OR 3.97; 95% CI 1.37-11.48), corticosteroids (OR 2.92; 95% CI 1.15-7.40), and BSI occurring during quinolone (OR 4.88; 95% CI 1.58-15.05) and ß-lactam other than ertapenem (OR 4.51; 95% CI 1.45-14.04) were independently associated with MDR-PA. Per regression coefficients, 1 point was assigned to each parameter, except for nosocomial-acquired BSI (3 points). In the second analysis, a score >3 points identified 60 (86.3%) out of 70 individuals with MDR-PA BSI and discarded 100 (84.2%) out of 120 with non-MDR-PA BSI. CONCLUSIONS: A simple score based on demographic and clinical factors allows stratification of individuals with bacteraemia according to their risk of MDR-PA BSI, and may help facilitate the use of rapid MDR-detection tools and improve early antibiotic appropriateness.
Assuntos
Farmacorresistência Bacteriana Múltipla , Neutropenia/complicações , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/etiologia , Pseudomonas aeruginosa/efeitos dos fármacos , Adulto , Idoso , Área Sob a Curva , Biomarcadores , Feminino , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Neutropenia/diagnóstico , Neutropenia/epidemiologia , Razão de Chances , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/epidemiologia , Fatores de Risco , Sensibilidade e Especificidade , Espanha/epidemiologiaRESUMO
Here, we describe an invasive infection due to Trichosporon coremiiforme in an HIV positive patient with neutropenia. The strain was first erroneously identified as Trichosporon asahii by conventional methods, but correctly identified by mass spectrometry using matrix-assisted laser desorption/ionization time-of-flight technology (MALDI-TOF MS) and ribosomal DNA sequencing. The infection was successfully resolved after antifungal treatment with amphotericin B and fluconazole. This case report is a contribution to the study of T. coremiiforme infections and reinforces its relevance as a species capable of causing invasive human infection in immunocompromised patients and also contributes to the study of its susceptibility profile against antifungal drugs.
Assuntos
Infecções Relacionadas a Cateter/diagnóstico , Infecções por HIV/complicações , Neutropenia/complicações , Tricosporonose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/sangue , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Anfotericina B/administração & dosagem , Antituberculosos/administração & dosagem , Bacteriemia/diagnóstico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Infecções Relacionadas a Cateter/complicações , Infecções Relacionadas a Cateter/tratamento farmacológico , Infecções Relacionadas a Cateter/microbiologia , Cateteres Venosos Centrais/efeitos adversos , Cateteres Venosos Centrais/microbiologia , Quimioterapia Combinada , Feminino , Fluconazol/administração & dosagem , HIV , Infecções por HIV/diagnóstico , Infecções por HIV/microbiologia , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Neutropenia/diagnóstico , Neutropenia/microbiologia , Neutropenia/virologia , Trichosporon/isolamento & purificação , Tricosporonose/tratamento farmacológico , Tricosporonose/etiologia , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologiaRESUMO
Estudo descritivo retrospectivo realizado no Instituto Nacional do Câncer José Alencar Gomes da Silva, HCI-Rio de Janeiro, Brasil, (INCA-HCI-RJ), no qual foram avaliadas infecções relacionadas aos acessos venosos para tratamento oncológico, nos setores Onco-Hematológicos pediátricos. A infecção representa uma importante complicação em pacientes oncológicos em tratamento. Devido ao tratamento oncológico que envolve: procedimentos cirúrgicos muitas vezes mutilantes, tratamento com quimioterápicos que ocasionam períodos de imunossupressão e neutropenia, e tratamento radioterápico com radiação e lise celular. O uso de dispositivos venosos associados a períodos de imunossupressão pode levar a infecção da corrente sanguínea e outras complicações (por exemplo trombose). No presente estudo foram investigados aspectos clínico-epidemiológicos das infecções e da susceptibilidade antimicrobiana em amostras clínicas obtidas de processos infecciosos associados ao uso de cateteres venosos de longa permanência no tratamento oncológico em pacientes do Hospital do Câncer José de Alencar Gomes da Silva, HCI/INCA, Rio de Janeiro Brasil. Foram avaliadas: a) prevalência das espécies diversas relacionadas aos quadros infecciosos identificados nestes pacientes oncológicos; b) prevalência de casos de complicações e outras infecções invasivas relacionadas ao uso de cateteres de longa permanência; c) perfis de susceptibilidade a antimicrobianos e ocorrência de multirresistência. O desenvolvimento deste projeto de pesquisa possibilitou a observação análise e validação da evolução dos processos envolvidos nos quadros de infecções nosocomiais em pacientes oncológicos pediátricos na prevenção de complicações que envolvem todo o sistema de saúde, além de contribuir na escolha de antimicrobianos e estratégias terapêuticas mais efetivas para o tratamento de infecções em cateteres por espécies multirresistentes de Corynebacterium.
Retrospective descriptive study conducted at the National Cancer Institute José Alencar Gomes da Silva, INCA / HCI-Rio de Janeiro, Brazil, (INCA-HCI-RJ). Infection represents an important complication in cancer patients. This group is more prone to infections due to the cancer treatment that involves: surgical procedures often mutilating, treatment with chemotherapy that cause periods of immunosuppression even with neutropenia, and radiotherapy treatment with radiation and cell lysis. The vascular devices associated with these periods can lead to bloodstream infection besides others complication as thrombosis. The number of reports of infections in hospitalized cancer patients increases morbidity and mortality rates. In the present study clinical and epidemiological aspects of infections were identified and antimicrobial susceptibility were investigated in clinical exams and samples from blood patients and venous catheter in children oncological patients at the José de Alencar Gomes da Silva, HCI / INCA, Rio de Janeiro Brazil. It was possible evaluate a) prevalence of various species infections in cancer patients; b) prevalence of cases of complications and other invasive infections related to the use of long-term catheters; c) antimicrobial susceptibility profiles and occurrence of multidrug resistance. The development of this research project in nosocomial infections in pediatric cancer patients was enabled analysis and validation of some process involved to prevent vascular complications that involve entire health system. In addition to contributing to the choice of antimicrobials and the most effective therapeutic strategies for the treatment of multi-resistant Corynebacterium sp.