RESUMO
PURPOSE: Chronic granulomatous disease (CGD) is an inherited immunodeficiency caused by pathogenic variants of genes encoding the enzyme complex NADPH oxidase. In countries where tuberculosis (TB) is endemic and the Bacillus Calmette-Guérin (BCG) vaccine is routinely administered, mycobacteria are major disease-causing pathogens in CGD. However, information on the clinical evolution and treatment of mycobacterial diseases in patients with CGD is limited. The present study describes the adverse reactions to BCG and TB in Mexican patients with CGD. METHODS: Patients with CGD who were evaluated at the Immunodeficiency Laboratory of the National Institute of Pediatrics between 2013 and 2024 were included. Medical records were reviewed to determine the clinical course and treatment of adverse reactions to BCG and TB disease. RESULTS: A total of 79 patients with CGD were included in this study. Adverse reactions to BCG were reported in 55 (72%) of 76 patients who received the vaccine. Tuberculosis was diagnosed in 19 (24%) patients. Relapse was documented in three (10%) of 31 patients with BGC-osis and six (32%) of 19 patients with TB, despite antituberculosis treatment. There was no difference in the frequency of BCG and TB disease between patients with pathogenic variants of the X-linked CYBB gene versus recessive variants. CONCLUSIONS: This report highlights the importance of considering TB in endemic areas and BCG complications in children with CGD to enable appropriate diagnostic and therapeutic approaches to improve prognosis and reduce the risk of relapse.
Assuntos
Vacina BCG , Doença Granulomatosa Crônica , NADPH Oxidase 2 , Tuberculose , Humanos , Doença Granulomatosa Crônica/diagnóstico , Doença Granulomatosa Crônica/epidemiologia , Doença Granulomatosa Crônica/complicações , Vacina BCG/efeitos adversos , Masculino , Feminino , Criança , Tuberculose/epidemiologia , Tuberculose/imunologia , Pré-Escolar , Lactente , Adolescente , NADPH Oxidase 2/genética , Estudos de Coortes , Mycobacterium bovis , México/epidemiologia , Antituberculosos/uso terapêutico , NADPH Oxidases/genéticaRESUMO
Mendelian Susceptibility to Mycobacterial Disease describes a spectrum of inherited defects, of which complete deficiency of the interleukin-12 receptor ß subunit 1 (IL-12Rß1) is the most common cause. This condition results in a predisposition to severe disease caused by mycobacteria. We report a case of disseminated multidrug-resistant tuberculosis with extensive central nervous system affection with SARS-CoV-2 co-infection, in a 4-year-old child with IL-12Rß1 complete deficiency.
Assuntos
COVID-19 , Coinfecção , Tuberculose Resistente a Múltiplos Medicamentos , Pré-Escolar , Humanos , Predisposição Genética para Doença , SARS-CoV-2 , Receptores de Interleucina-12RESUMO
Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.