[Variabilidad del patrón de sensibilidad alérgica en adultos mayores].

Objective: Describe the pattern of allergic sensitivity in elderly. Methods: Elderly (>60 years old) with a diagnosis of allergic respiratory disease in whom sensitivity was identified by pricking with ALK-abello extracts (Port Washington, NY, United States) were included. The results were analyzed using descriptive statistics and compared with a series of young adults in a 3:1 ratio. Association analyzes were performed with c2 test using SPSSv.21 software (SPSS software, IBM, NY, USA). Results: 17 elderlies, predominantly women were identified (70%) with an average age of 64 years, 52% suffered from asthma and 47% allergic rhinitis, 82% were predominantly intradomiciliary polysensitive (82%), the most frequent being Dermatophagoides pteronyssinus (50%), decreasing to < 18% (p<0.01) to various species (Ligustrum vulgare, Salsola kali, Periplaneta americana, Canis familiaris, Juniperus sp and Fraxinus sp). Interestingly, AM were more sensitive to mites compared to young adults (p<0.01/OR= 8.92). This may be because the reactivity of the skin may decrease with age. Conclusions: The main allergic sensitivity that can be identified by conventional techniques in elderly is Dermatophagoides pteronyssinusm, up to 50%.

Objetivo: Describir el patrón de sensibilidad alérgica en adultos mayores. Métodos: Se incluyeron AM (>60 años) con diagnóstico de enfermedad respiratoria alérgica en quienes se identificó la sensibilidad mediante prick con extrac- tos ALK-abello (Port Washington, NY, Estados Unidos). Los resultados se analizaron mediante estadística descriptiva y se compararon con una serie de adultos jóvenes en relación 3:1. Los análisis de asociación se realizaron con prueba de c2 usando el software SPSSv.21 (SPSS software, IBM, NY, EUA). Resultados: Se identificaron 17 AM, predominantes mujeres (70%) edad promedio de 64 años, 52% padecían asma y 47% rinitis alérgica, 82% eran polisensibles predominantemente intradomiciliares (82%), el más frecuente Dermatophagoides pteronyssinus (50%), disminuyendo a < 18% (p<0.01) a diversas especies (Ligus- trum vulgare, Salsola kali, Periplaneta americana, Canis familiaris, Juniperus sp y Fraxinus sp). Interesantemente, los AM fueron más sensibles a ácaros en compara- ción con adultos jóvenes (p<0.01/OR= 8.92). Esto se puede deber a que la reactividad de la piel pudiera disminuir con la edad. Conclusiones: La principal sensibilidad alérgica que puede ser identificada por técnicas convencionales en adultos mayores es el Dermatophagoides pteronys- sinusm, hasta en un 50%.

Lung Function and Asthma Clinical Control in N-ERD Patients, Three-Year Follow-Up in the Context of Real-World Evidence.

Purpose: To describe the lung function and clinical control of asthma in patients with N-ERD during three years of medical follow-up using GINA guidelines. Methods: We evaluated 75 N-ERD and 68 asthma patients (AG). Clinical control, lung function, and asthma treatment were evaluated according to GINA-2014. We compared all variables at baseline and one, two, and three years after treatment. Results: At baseline, the N-ERD group had better basal lung function (LF) than the AG group (p<0.01), and the AG group used higher doses of inhaled corticosteroids than the N-ERD group (52.4% vs 30.5%, p=0.01) and short-term oral corticosteroid (OCS) use (52.4% vs 30.5%, p<0.01). Instead, N-ERD patients needed more use of leukotriene receptor antagonists (LTRA) (29.3% vs 5.9%, p<0.01). This group had better clinical control than the AG group (62.1% vs 34.1%, p<0.01). During the medical follow-up, the LF of the N-ERD group remained at normal values; however, these parameters improved in AG from one year (p<0.01). Likewise, there was a diminished use of high doses of ICS (52.4% vs 33%, p<0.05) and short-term OCS (67.6% vs 20.6%, p<0.01) in asthma patients. However, N-ERD patients still needed more use of LTRAs (p<0.02) during the study. In this context, one-third of N-ERD patients had to use a combination of two drugs to maintain this control. From the second year on, clinical control of asthma was similar in both groups (p>0.05). Conclusion: According to GINA guidelines, only one-third of patients with N-ERD can gradually achieve adequate lung function and good asthma control with a high ICS dosage. Only a very small portion of patients will require the continued use of a second medication as an LTRA to keep their asthma under control.

[DRESS syndrome induced by anti-TB drugs]. / Síndrome de DRESS inducido por fármacos antituberculosos.

OBJETIVE: To describe the phenotype of DRESS syndrome induced by antituberculosis drugs. METHODS: Descriptive study, withdrawn from the review of the records of patients with DRESS syndrome, identified in the interconsultation of the Department of Research in Immunogenetics and Allergy, of the Insti-tuto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, among 2014 and 2020. Frequency analysis was performed. The associations between biomarkers and latency are calculated with the χ2 test and log-rank, and the evaluation of the change in the biomarkers with the Wilcoxon test. The value of p < 0.05 is considered statistically significant. For data analysis, the SPSS v.21 program was obtained. RESULTS: 15 patients were identified; represented by 0.02% of total cases treated in the Department for so-meimmuno-allergic condition (15/7052); the main symptomatology were: rash (100%), eosinophilia (93%), fe-ver (80%), adenomegaly (60%), kidney damage (40%), liver damage (33%), and latency of 21 days. Liver damage was associated with prolonged latency (p = 0.02). After treatment, the total levels of eosinophils (p < 0.001) and liver and kidney biomarkers (p < 0.04) decreased. DRESS syndrome induced by antituberculosis drugs is not associated with the number of drugs prescribed or with the pattern of resistance of Mycobacterium tuberculosis. CONCLUSIONS: DRESS syndrome induced by antituberculosis drugs is an atypical clinical reaction, similar to other types of DRESS syndrome that respond favorably to systemic corticosteroids.

OBJETIVO: Describir el fenotipo del síndrome de DRESS inducido por fármacos antituberculosos. MÉTODOS: Estudio descriptivo efectuado a partir de la revisión de los expedientes de pacientes con síndrome de DRESS, identificados en la interconsulta del Departamento de Investigación en Inmunogénetica y Alergia, del Instituto Nacional de Enfermedades Respiratorias (INER) Ismael Cosío Villegas, entre 2014 y 2020. Se realizó análisis de frecuencias. Las asociaciones entre biomarcadores y latencia se calcularon con la prueba de χ2 y log-rank, y la evaluación del cambio en los biomarcadores con la prueba de Wilcoxon. Se consideró esta-dísticamente significativo el valor de p < 0.05. Para el análisis de los datos se utilizó el programa SPSS v.21. RESULTADOS: Se identificaron 15 pacientes, que representaron el 0.2% de los casos atendidos en el Departa-mento por algún padecimiento inmuno-alérgico (15/7052); las principales manifestaciones fueron: exantema (100%), eosinofilia (93%), fiebre (80%), adenomegalia (60%), daño renal (40%), daño hepático (33%) y latencia de 21 días. El daño hepático se asoció con latencia prolongada (p = 0.02). Posterior al tratamiento disminu-yeron las concentraciones totales de eosinófilos (p < 0.001) y biomarcadores hepáticos y renales (p < 0.04). El síndrome de DRESS inducido por fármacos antituberculosos no se asoció con la cantidad de fármacos prescritos ni con el patrón de resistencia de Mycobacterium tuberculosis. CONCLUSIONES: El síndrome de DRESS inducido por fármacos antituberculosos es una reacción clínica atípica, similar a otros tipos de síndrome de DRESS que responden favorablemente a corticosteroides sisté-micos.

Biologic Therapies for Asthma and Allergic Disease: Past, Present, and Future.

The discovery of the mechanism underlying allergic disease, mouse models of asthma, and bronchoscopy studies provided initial insights into the role of Th2-type cytokines, including interlukin (IL)-4, IL-5 and IL-13, which became the target of monoclonal antibody therapy. Omalizumab, Benralizumab, Mepolizumab, Reslizumab, and Tezepelumab have been approved. These biologicals have been shown to be good alternative therapies to corticosteroids, particularly in severe asthma management, where they can improve the quality of life of many patients. Given the success in asthma, these drugs have been used in other diseases with type 2 inflammation, including chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis, and chronic urticaria. Like the Th2-type cytokines, chemokines have also been the target of novel monoclonal therapies. However, they have not proved successful to date. In this review, targeted therapy is addressed from its inception to future applications in allergic diseases.

DRESS, una reacción alérgica no mediada por IgE / DRESS, a Non-IgE Mediated Allergic Reaction

Resumen El síndrome de reacción a medicamentos con eosinofilia y síntomas sistémicos (DRESS, por sus siglas en inglés) es una respuesta de hipersensibilidad multisistémica poco frecuente inducida por uno o varios medicamentos que puede inducir una reacción adversa cutánea grave, la cual es difícil de diagnosticar y pone en peligro la vida del paciente si no es identificada y no se recibe tratamiento. Frecuentemente, se manifiesta como una erupción cutánea amplia, linfadenopatía, signos de afectación de órganos viscerales y alteraciones hematológicas, como leucocitosis, eosinofilia y, en ocasiones, linfocitosis atípica que se presentan de 2 a 8 semanas posterior a la administración del fármaco responsable. Los medicamentos responsables con mayor número de reportes son la fenitoína, la carbamazepina, el alopurinol y el abacavir. Se han identificado algunos alelos específicos del antígeno leucocitario humano (HLA) que se asocian a la hipersensibilidad de estos fármacos. La fisiopatología del síndrome de DRESS aún no se conoce por completo, generalmente se trata de una respuesta de hipersensibilidad mediada por células T, al interactuar con el receptor del complejo principal de histocompatibilidad en individuos con factores de susceptibilidad genética, como ocurre en otros cuadros de reacciones graves secundarias a la ingesta de fármacos. Los criterios del European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) son los más utilizados para su diagnóstico. El síndrome de hipersensibilidad inducido por fármacos (DiHS), el síndrome de Stevens-Johnson (SSJ), la necrólisis epidérmica tóxica (NET), y la pustulosis exantemática generalizada aguda (PEGA) deben considerarse ante cualquier exantema que aparezca posterior a la administración de cualquier fármaco. La terapia incluye la eliminación del agente causal lo antes posible, así como los corticosteroides sistémicos, los cuales son los pilares del tratamiento.. Los agentes ahorradores de esteroides, como la ciclosporina, las inmunoglobulinas intravenosas (IVIGs) y otros agentes inmunosupresores, se han utilizado con éxito para contribuir al tratamiento.

Abstract DRESS (drug reaction syndrome with eosinophilia and systemic symptoms) is a rare drug-induced multisystemic hypersensitivity response that can induce a severe cutaneous adverse reaction that is difficult to diagnose and treat. It frequently manifests as an extensive skin rash, systemic symptoms, lymphadenopathy, visceral organ involvement, and hematological alterations, mainly leukocytosis, eosinophilia, and sometimes atypical lymphocytosis that manifest 2 to 8 weeks after continuous administration of the responsible drug. The most prevalent drugs related with this syndrome are phenytoin, carbamazepine, allopurinol, and abacavir. Some specific human leukocyte antigen (HLA) alleles have been identified that are associated with hypersensitivity to these drugs. The pathophysiology of DRESS syndrome is not yet fully understood; the main hypothesis is a T-cell mediated hypersensitivity response when interacting with the major histocompatibility complex receptor in individuals with genetic susceptibility factors. The criteria of the European Registry of Severe Cutaneous Adverse Reactions to Drugs (RegiSCAR) are the most commonly used for the diagnosis of DRESS syndrome. Drug-induced hypersensitivity syndrome (DiHS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) should be considered for any rash that appears following the administration of any drug. Therapy of DRESS includes the elimination of the causative agent as soon as possible, as well as systemic corticosteroids which are the cornerstones of treatment. Steroid-sparing agents such as cyclosporine, intravenous immunoglobulins (IVIGs), and other immunosuppressive agents have been used successfully to contribute to treatment.

Association of Allergic Sensitivity and Pollination in Allergic Respiratory Disease: The Role of Pollution.

Purpose: To evaluate the association between allergic sensitivity and pollen counts in patients with allergic respiratory disease (ARD) and its relationship with atmospheric pollutants. Methods: From 2012 to 2018, we evaluated the sensitivity by skin prick test in ARD patients. The pollen counts were analyzed according to international guidelines (2014-2018). The pollutant and meteorological data were obtained at the same time from AIRE-CDMX websites. We analyzed the association between allergic sensitivity and pollen counts using the χ2 test and stratified by disease allergic rhinitis (AR) and AR with asthma (ARwA), periods (before/after 2015), and pollination seasons (S1:2014-2015), (S2:2015-2016), (S3:2016-2017), (S4:2017-2018). Likewise, we correlated the pollen counts with the concentrations of pollutants using Pearson's correlation. For all analyses, we used SPSS v.21 software, and a p-value <0.05 was considered significant. Results: A total of 520 patients were enrolled, of whom 67.3% had ARwA and 33.7% had AR (p<0.05). The frequency of patients allergic to at least one pollen was higher compared with patients sensitive to indoor allergens (55.3% vs 44.6%, p<0.001). A total of 46.8% of the patients were only sensitive to trees in comparison to other outdoor allergens (p<0.001). The Fraxinus sp. and the Cupressaceae family allergens were approximately two times more frequent than the other tree allergens in both diseases (p<0.05). These pollens doubled their counts since 2015 (p<0.001), which was associated with increases in sensitivity for Fraxinus sp. and the Cupressaceae family compared to previous years (p<0.001). Regarding pollutants, the most significant correlations were with PM10, NO2, PMCO for Fraxinus sp. pollen concentrations in all seasons (p≤0.02). Conclusion: The high increases in pollen counts of the Fraxinus sp. and Cupressaceae family were associated with increases in the frequency of sensitization to these species, and this phenomenon correlated with increases in PM10, NO2, and PMCO.

IL10 rs1800872 Is Associated with Non-Steroidal Anti-Inflammatory Drugs Exacerbated Respiratory Disease in Mexican-Mestizo Patients.

Non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (N-ERD) is a disease integrated by asthma, nasal polyps, and hypersensitivity to non-steroidal anti-inflammatory drugs (NSAID). Genetic association studies have explored single nucleotide polymorphisms (SNPs) in genes involved in theoretical pathophysiological mechanisms, but most of these lack replication of findings in second populations. Our objective was to evaluate the association of SNPs in candidate genomic regions described in Asian and European subjects with N-ERD in Mexican-mestizo patients. We designed a replicative study in two stages. We included 381 SNPs selected by fine mapping of associated genes in a microarray, which were tested in three groups: N-ERD (N), asthma (A), and control group (CG); by means of GoldenGate array, positive results by genetic models were validated in the second stage in another population through qPCR with the same methodology. In the allelic model, we identified 11 SNPs in N vs. CG comparison, and five in N vs. A and A vs. CG, respectively. By genetics models, all SNPs in PPARG, rs13239058 in TBXAS1, and rs1554286 and rs1800872 in IL10 were associated in both models. In the second stage, only rs1800872CC showed an association in the dominant model comparing N vs. GC, p = 0.004, OR = 0.44. In conclusion, rs1800872 in IL10 was the only associated with N-ERD in Mexican-mestizo patients.

TNF promoter polymorphisms are associated with genetic susceptibility in COPD secondary to tobacco smoking and biomass burning.

Background: Smoking and smoke from biomass burning (BB) are the main environmental risk factors for COPD. Clinical differences have been described between COPD related to smoking and related to wood smoke, but no studies have shown genetic differences between patients exposed to these two risk factors. Methods: To investigate a possible association of tumor necrosis factor (TNF) promoter polymorphisms, we conducted a case-control study. A total of 1,322 subjects were included in four groups: patients with a diagnosis of COPD secondary to smoking (COPD-S, n=384), patients with COPD secondary to biomass burning (COPD-BB, n=168), smokers without COPD (SWOC, n=674), and biomass burning-exposed subjects (BBES n=96). Additionally, a group of 950 Mexican mestizos (MMs) was included as a population control. Three single nucleotide polymorphisms (SNPs) were selected in the TNF gene (rs1800629, rs361525, and rs1800750) and one SNP in the lymphotoxin alpha gene (rs909253). Results: Statistically significant differences were found with genotype GA of the rs1800629: COPD-S vs SWOC, (p<0.001, odds ratio [OR] =2.55, 95% CI=1.53-4.27); COPD-S vs COPD-BB (p,0.01). When performing the comparison of the less severe (G1: I + II) and the more severe (G2: III + IV) levels, differences were identified in G1 (p<0.05, OR=1.94, 95% CI=1.04-3.63) and G2 (p<0.001, OR=3.68, 95% CI=1.94-3.07) compared with SWOC. Regarding genotype GA of rs361525, it has been associated when comparing COPD-BB vs BBES (p=0.0079, OR=5.99, 95% CI=1.38-53.98). Conclusion: The heterozygous genotype GA of polymorphisms rs1800629 and rs361525 in the TNF promoter are associated with the risk of COPD.