RESUMO
BACKGROUND: Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy. OBJECTIVE: We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families. METHODS: We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency. RESULTS: Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells. CONCLUSION: Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.
Assuntos
Eczema , Eosinofilia , Infecções por Vírus Epstein-Barr , Vasculite , Humanos , Proteína 2 Relacionada a Actina , Actinas , Insuficiência de Crescimento , Herpesvirus Humano 4 , Imunoglobulina A , Imunoglobulina E , Reinfecção , Proteína 3 Relacionada a Actina/metabolismoRESUMO
Introduction: The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals. Objective: We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology. Methods: After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells. Results: We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis. Discussion: NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.
Assuntos
Infecções por Vírus Epstein-Barr , Linfo-Histiocitose Hemofagocítica , Adolescente , Criança , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Feminino , Haploinsuficiência , Herpesvirus Humano 4 , Humanos , Masculino , Fatores de Transcrição/genéticaRESUMO
BACKGROUND: Information on anaphylaxis among recipients of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains scarce. OBJECTIVE: To identify the observed incidence of anaphylaxis in recipients of different anti-SARS-CoV-2 vaccines. METHODS: A nationwide observational study among recipients of 61,414,803 doses of seven different anti-SARS-CoV-2 vaccines, describing the incidence and characteristics of adult patients (age ≥ 18 years) who developed anaphylaxis as an adverse event following immunization (AEFI) against SARS-CoV-2 vaccines between December 24, 2020, and October 15, 2021, in Mexico. RESULTS: Sixty-six patients developed anaphylaxis as an AEFI, for an overall observed incidence of 1.07 cases per 1,000,000 (95% CI 0.84-1.37) administered doses. Eighty-six percent of the patients were female, consistent with previous reports of AEFI to COVID-19 vaccines. mRNA-based vaccine recipients had the highest frequency of anaphylaxis, followed by adenovirus-vectored vaccines and inactivated virus recipients, with an observed incidence of 2.5, 0.7, and 0.2 cases per 1,000,000 doses administered, respectively. Only 46% of the patients received correct treatment with epinephrine as the first-line treatment through the appropriate route and dose. We detected one case of anaphylactic reaction-related death occurring 5 min following immunization with ChAdOx1 nCov-19 for a mortality rate of 1.5% among those who developed this AEFI. CONCLUSIONS: In our population, anaphylactic reactions were infrequent. Our study provides further evidence supporting the security of these newly developed vaccines.
Assuntos
Anafilaxia , Vacinas contra COVID-19 , COVID-19 , Adolescente , Adulto , Feminino , Humanos , Masculino , Anafilaxia/induzido quimicamente , Anafilaxia/epidemiologia , ChAdOx1 nCoV-19/efeitos adversos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , SARS-CoV-2 , México/epidemiologiaRESUMO
Griscelli syndrome (GS) is a rare autosomal recessive disease with characteristic pigment distribution, and there are currently 3 types according to the underlying genetic defect and clinical features. We present the case of a girl born from consanguineous parents who presented with predominant neurologic symptoms, silvery hair and granulomatous skin lesions. Cerebral magnetic resonance revealed diffuse white matter lesions, and central nervous system (CNS) lymphocytic infiltration was suspected. The patient underwent haematopoietic stem cell transplantation with graft failure and autologous reconstitution. She developed elevated liver enzyme with a cholestatic pattern. Multiple liver biopsies revealed centrilobular cholestasis and unspecific portal inflammation that improved with immunomodulatory treatment. She was revealed to have an impaired cytotoxicity in NK cells and a decreased expression of RAB27A. However, no variants were found in the gene. All types of GS present with pigment dilution and irregular pigment clumps that can be seen through light microscopy in hair and skin biopsy. Dermic granulomas and immunodeficiency with infectious and HLH predisposition have been described in GS type 2 (GS2). Neurologic alterations might be seen in GS type 1 (GS1) and GS type 2 (GS2), due to different mechanisms. GS1 presents with neurologic impairment secondary to myosin Va role in neuronal development and synapsis. Meanwhile, GS2 can present with neurologic impairment secondary to SNC HLH. Clinical features and cytotoxicity might aid in differentiating GS1 and GS2, especially since treatment differs.
Assuntos
Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/terapia , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/terapia , Piebaldismo/diagnóstico , Piebaldismo/terapia , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/terapia , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/terapia , Biomarcadores , Biópsia , Gerenciamento Clínico , Suscetibilidade a Doenças/imunologia , Predisposição Genética para Doença , Perda Auditiva Neurossensorial/etiologia , Humanos , Linfo-Histiocitose Hemofagocítica/etiologia , Mutação , Fenótipo , Piebaldismo/etiologia , Transtornos da Pigmentação/etiologia , Doenças da Imunodeficiência Primária/etiologia , PrognósticoAssuntos
Complexo 2-3 de Proteínas Relacionadas à Actina/deficiência , COVID-19/complicações , Síndromes de Imunodeficiência/complicações , Complexo 2-3 de Proteínas Relacionadas à Actina/genética , Anti-Infecciosos/uso terapêutico , COVID-19/genética , COVID-19/terapia , Hospitalização , Humanos , Síndromes de Imunodeficiência/terapia , Lactente , Masculino , SARS-CoV-2 , Resultado do TratamentoRESUMO
BACKGROUND: Kawasaki disease (KD) is an acute systemic vasculitis that predominantly affects patients younger than 5 years. In the absence of an available, affordable diagnostic test, detailed clinical history and physical examination are still fundamental to make a diagnosis. METHODS: We present five representative cases with KD-like presentations: systemic onset juvenile idiopathic arthritis, mycoplasma-induced rash and mucositis, staphylococcal scalded skin syndrome, BCGosis, and the recently described multisystemic inflammatory syndrome in children (MIS-C) associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) virus. RESULTS: Rash, fever, and laboratory markers of inflammation can be present in several childhood diseases that may mimic KD. CONCLUSION: The term 'Kawasaki syndrome' instead of 'Kawasaki disease' may be more appropriate. Physicians should consider an alternative diagnosis that may mimic KD, particularly considering MIS-C during the present pandemic, as an aggressive diagnostic and therapeutic approach is needed.
Assuntos
COVID-19 , Síndrome de Linfonodos Mucocutâneos , Criança , Humanos , Síndrome de Linfonodos Mucocutâneos/diagnóstico , RNA Viral , SARS-CoV-2 , Síndrome de Resposta Inflamatória SistêmicaRESUMO
A high proportion of patients on hemodialysis persist with low hemoglobin levels despite receiving treatment with erythropoiesis-stimulating agents. A registered nurse-driven renal anemia protocol was designed and implemented by a team in a pediatric hemodialysis unit. We compared proportion of patients achieving the target hemoglobin (Hgb) and transferrin saturation (TSAT) before and after the implementation of the protocol. There was an increase in patients achieving the target Hgb and TSAT range, with an increase in the Hgb concentration. There were no differences in the proportion of patients with left ventricular hypertrophy, erythropoiesis-stimulating agents or intravenous iron dose, transfusion rates, or hospitalization rates. The implementation of a nurse-driven anemia protocol in a pediatric hemodialysis unit increased the proportion of patients achieving target Hgb and TSAT range without a rise in medication doses.
Assuntos
Anemia/enfermagem , Protocolos Clínicos , Nefropatias/enfermagem , Enfermagem Pediátrica/organização & administração , Diálise Renal/enfermagem , Criança , Hemoglobinas/administração & dosagem , Humanos , Pesquisa em Avaliação de Enfermagem , Transferrinas/administração & dosagemRESUMO
Major histocompatibility complex class II deficiency is a rare case of PID. Specific recommendations for hematopoietic stem cell transplant, the only curative treatment option, are still lacking. This meta-analysis aims to identify the factors associated with better prognosis in these patients. Thirteen articles reporting 63 patients with major histocompatibility complex class II deficiency that underwent hematopoietic stem cell transplant were included. The median age for hematopoietic stem cell transplant was 18 months. The most common source of transplant was bone marrow, with alternative sources as umbilical cord blood emerging during recent years. The highest proportion of engraftment was seen with umbilical cord. Engraftment was higher in patients with matched donors, with better overall survival in patients with reduced-intensity conditioning. Graft-vs-host disease developed in 65% of the patients, with grades I-II being the most frequently encountered. There was a higher mortality in patients with myeloablative conditioning and no engraftment. There was an inverse correlation between survival and stage of graft-vs-host disease. The main cause of mortality was infectious disease, mostly secondary to viral infections. Ideally, matched grafts should be used, and reduced-intensity conditioning should be considered to reduce early post-transplant complications. GVHD and viral prophylaxis are fundamental.