Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico.

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.

[Prevalence of persistent hypogammaglobulinemia in patients with autoimmune rheumatic disease who received treatment with Rituximab in a national medical center in Mexico]. / Prevalencia de hipogammaglobulinemia persistente en pacientes con enfermedad autoinmune que reciben rituximab en un centro de referencia nacional en México.

OBJECTIVE: To describe the prevalence of persistent hypogammaglobulinemia in patients receiving Rituximab as a treatment for autoimmune rheumatological diseases. METHODS: A transversal, retrospective and unicentric study, carried out in patients with autoimmune rheumatic diseases who were admitted to the Rheumatology service of the Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Mexico City, to receive treatment with rituximab between January 2013 and January 2018. Descriptive and inferential statistics of serum levels of immunoglobulins, clinical-demographic characteristics, diagnosis, and treatment received were performed. RESULTS: from 262 patients with autoimmune rheumatological disease who received treatment with Rituximab; We identified 8 patients with persistent hypogammaglobulinemia (6 women and 2 men), this is a prevalence of 3.1%. No associated factors with the development of hypogammaglobulinemia were identified. CONCLUSIONS: Until now, no associated prognostic or predictive factors have been identified with persistent hypogammaglobulinemia. Additional prospective studies are required to understand more precisely the implications of persistent hypogammaglobulinemia in patients with autoimmune diseases.

OBJECTIVO: Determinar la prevalencia de hipogammaglobulinemia persistente en pacientes con enfermedades reumatológicas autoinmunes que reciben rituximab. MÉTODOS: Estudio trasversal, retrospectivo y unicéntrico, emprendido en pacientes con enfermedades reumatológicas autoinmunes, que acudieron a la Consulta externa del servicio de Reumatología del Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Ciudad de México, entre enero de 2013 y enero de 2018, para recibir tratamiento con rituximab. El análisis de los datos se efectuó con estadística descriptiva e inferencial, para la evaluación de las concentraciones séricas de inmunoglobulinas, características clínico demográficas, diagnóstico y tratamiento. RESULTADOS: Estudio trasversal, retrospectivo y unicéntrico, emprendido en pacientes con enfermedades reumatológicas autoinmunes, que acudieron a la Consulta externa del servicio de Reumatología del Hospital de Especialidades Dr. Antonio Fraga Mouret, Centro Médico Nacional La Raza, Ciudad de México, entre enero de 2013 y enero de 2018, para recibir tratamiento con rituximab. El análisis de los datos se efectuó con estadística descriptiva e inferencial, para la evaluación de las concentraciones séricas de inmunoglobulinas, características clínico demográficas, diagnóstico y tratamiento. CONCLUSIONES: Hasta el momento no se han identificado factores asociados, pronósticos o predictivos, con hipogammaglobulinemia persistente. Se requieren estudios prospectivos adicionales para conocer con mayor precisión las implicaciones de la hipogammaglobulinemia persistente en pacientes con enfermedades autoinmunes.

[The diagnostic approach to difficult-to-treat asthma and severe asthma]. / Abordaje diagnóstico del asma difícil de tratar y asma grave.

Difficult-to-treat asthma refers to asthma that is not controlled despite high or medium doses of inhaled steroids or in which high doses of treatment are required to maintain an adequate control of the symptoms and to reduce the risk of exacerbations. An inadequate technique to use the inhaler, poor adherence to treatment, smoking, comorbidities, or an incorrect diagnosis should be considered. In severe asthma, despite adherence to treatment with optimized maximum doses and the management of factors that could contribute, multiple medications in maximum doses are required to have an adequate therapeutic control or this is not achieved. The approach to these patients involves a meticulous process due to the multiple factors that can influence poor asthma control and that can lead to a misclassification of the disease when, in reality, the patient can be presenting different comorbidities whose treatment could decrease the severity of asthma symptoms and modify the prognosis. The objective of this document is to make the approach to patients with difficult-to-treat asthma and severe asthma known, as well as the most frequent comorbidities. A search was made in PubMed with the purpose of identifying the main pathologies that may be present in patients and, based on what is described in the literature, to propose a diagnostic approach. 100 studies were comprised in this review, including clinical guidelines such as GINA, GEMA, and ERS/ATS.

El asma difícil de tratar es la que no se controla a pesar de las dosis altas o medias de esteroides inhalados o la que requiere altas porciones para mantener un control adecuado de los síntomas y reducir el riesgo de exacerbaciones. Se deben tener en cuenta las fallas en la técnica del uso del inhalador, la pobre adherencia al tratamiento, el tabaquismo, las comorbilidades o el diagnóstico incorrecto. En el asma grave, a pesar de la adherencia al tratamiento con dosis optimizadas y el manejo de los factores contribuyentes, se requieren múltiples medicamentos en dosis máximas para tener un adecuado control, si no es así este no se logra. La dirección de estos pacientes implica un proceso minucioso, dados los múltiples factores que pueden influir en el mal control del asma y que pueden llevar a una inadecuada clasificación de la enfermedad, cuando en realidad puedan estar cursando con diferentes comorbilidades cuyo tratamiento puede disminuir la severidad de los síntomas del asma y modificar el pronóstico. El objetivo de esta investigación es dar a conocer el manejo de los pacientes con asma difícil de tratar y asma grave, así como las comorbilidades más frecuentes. Se realizó una búsqueda en Pubmed con el propósito de identificar las principales patologías que puedan estar presentes y, con base en la literatura, proponer un abordaje diagnóstico. Se incluyeron 100 estudios, incluidas las guías clínicas GINA, GEMA y ERS/ATS.

[Disseminated infection caused by the bacillus Calmette-Guérin vaccine and SARS-CoV-2 coinfection in a patient with IL-12 receptor ß1 subunit deficiency]. / Infección diseminada por vacuna con bacilo de Calmette-Guérin y coinfección por SARS-CoV-2 en paciente con deficiencia de la subunidad ß1 del receptor de IL-12.

BACKGROUND: Inborn errors of immunity manifest with a greater susceptibility to infections, autoimmunity, autoinflammatory diseases, allergies, or malignancies. One of these is the mendelian susceptibility to mycobacterial disease. The most frequent etiology is the complete autosomal recessive deficiency of the ß1 subunit of the interleukin 12 receptor. CASE REPORT: A female patient who, by the age of six months, started with a nodular lesion in the right shoulder and ipsilateral axillary adenitis after the bacillus Calmette-Guérin vaccine was applied. Later, she developed a cutaneous fistula in the anterior thorax, the inframammary region, and chronic recidivant suppurative lymphadenitis. A disseminated infection caused by Mycobacterium bovis was diagnosed, therefore, individualized pharmacological treatment was required due to failure with the primary treatment. The patient was diagnosed with deficiency in the ß1 subunit of the interleukin 12 receptor at age six. During her last hospitalization, she presented fever, cough, and tachypnea, and SARS-CoV-2 was detected by quantitative polymerase chain reaction. The patient has had a favorable evolution. CONCLUSION: In patients with disseminated infections caused by bacillus Calmette-Guérin vaccination or by environmental mycobacteria, there should be suspicion of an inborn error of immunity and the patient should be referred to a third level hospital for an early immunological assessment.

Antecedentes: Los errores innatos de la inmunidad se manifiestan con una mayor susceptibilidad a infecciones, autoinmunidad, enfermedades autoinflamatorias, alergia o malignidad. Uno de estos es la susceptibilidad mendeliana a infecciones micobacterianas. La etiología más frecuente es la deficiencia completa autosómica recesiva de la subunidad ß1 del receptor de interleucina 12. Caso clínico: Paciente que comenzó a los seis meses de edad con una lesión nodular en hombro derecho y adenitis axilar ipsolateral posterior a la vacuna con bacilo de Calmette-Guérin. Posteriormente desarrolló una fistula cutánea en tórax anterior, región inframamaria y linfadenitis supurativa crónica recidivante. Se diagnosticó infección diseminada por Mycobacterium bovis, por lo que requirió tratamiento farmacológico individualizado debido al fracaso con el tratamiento primario. La paciente fue diagnosticada con deficiencia de la subunidad ß1 del receptor de interleucina 12 a los seis años. Durante su última hospitalización presentó fiebre, tos y taquipnea, detectándose SARS-CoV-2 por reacción en cadena de la polimerasa cuantitativa. La paciente evolucionó favorablemente. Conclusión: En los pacientes con infecciones diseminadas por la vacuna con bacilo de Calmette-Guérin o micobacterias ambientales, debe sospecharse un error innato de la inmunidad y derivarlos a tercer nivel de atención para la evaluación inmunológica temprana.

[Rhinosinusitis and its impact on the quality of life in patients with common variable immunodeficiency]. / Rinosinusitis y su impacto en la calidad de vida en pacientes con inmunodeficiencia común variable.

BACKGROUND: Common variable immunodeficiency (CVID) is characterized by a derangement in IgG, IgM and IgA antibody production in respiratory and gastrointestinal infections, caused mainly by encapsulated bacteria. Rhinosinusitis is related to both morbidity and quality of life impairment in patients with CVID. In this article we describe the prevalence of rhinosinusitis, its localization by CT scan and the perception of disability determined by the Rhinosinusitis Disability Index (RSDI) score in a group of CVID patients. OBJETIVE: To show the frequency of rhinosinusitis and its impact on quality of life in patients with CVID. METHODS: We included 14 CVID patients. Rhinosinusitis was diagnosed according to the criteria of the European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS 2007). Patients answered the RSDI questionnaire. An axial, coronal and saggital slices of a CT scan of the paranasal sinuses were performed to all patients. RESULTS: In our patientsí sample, ten of them were women. Average age was 34 years (+/-11). Eight patients (57%) had rhinosinusitis at sampling moment, 6 of them (75%) had a chronic evolution and 2 (25%) had chronic rhinosinusitis with periods of acuteness. Maxillar sinuses were the most affected, followed by the ethmoidal sinuses. Five patients were asymptomatic but had CT scan images compatible with rhinosinusitis. The most impaired RSDI domains were the physical and the functional ones. CONCLUSIONS: A Little over half of our group of patients with CVID presented rhinosinusitis, which was corroborated by MDCT. The majority of cases had a chronic evolution. The association between CVID and rhinosinusitis has a negative impact on the quality of life of patients.