[Frequency and clinical characterization of chronic urticaria in a tertiary care hospital]. / Frecuencia y caracterización clínica de la urticaria crónica en un hospital de tercer nivel.

OBJECTIVE: To estimate the frequency of chronic urticaria in patients who attended an allergy service in a tertiary care hospital; in addition, the main clinical characteristics are described. METHODS: In a period of 7 months, a total of 96 patients who were over 18 years of age were analyzed; they had been diagnosed with chronic spontaneous urticaria and chronic inducible urticaria. RESULTS: The frequency of chronic urticaria was of 1.31 % (n=98); 53 % were associated with some allergic pathology, and 54 % showed an alteration in the paraclinical tests. Chronic spontaneous urticaria was found in 80 % of the patients; and in 62 % of them, the urticaria was associated with angioedema. Chronic urticaria was controlled in 19 % of the studied population with the use of a single antihistamine. CONCLUSIONS: The frequency of chronic urticaria in our study was lower than the frequency reported nationwide.

Objetivo: Estimar la frecuencia de la urticaria crónica en pacientes que acudieron a un servicio de alergología en un hospital de tercer nivel; complementariamente, se hace una descripción de las principales características clínicas. Métodos: Se analizaron un total de 96 pacientes con UC espontánea y UC inducible, con edad > 18 años, en un lapso de 7 meses. Resultados: La frecuencia de UC fue de 1.31 % (n = 98); 53 % se asociaron con alguna enfermedad alérgica y 54 % mostró algún tipo de alteración en los estudios paraclínicos. En 80 % de los pacientes, la urticaria fue crónica espontánea y en 62 % se vio asociada con angioedema. El 19 % de los casos obtuvo control de la UC con el uso de un solo antihistamínico. Conclusiones: La frecuencia de UC en nuestro estudio fue inferior con respecto a la informada a nivel nacional.

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines.

BACKGROUND: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. METHODS: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. RESULTS: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. CONCLUSIONS: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.

Microbiota bacteriana intestinal en pacientes mexicanos con inmunodeficiencia común variable.

INTRODUCTION: Common variable immunodeficiency (CVID) is the main symptomatic primary immunodeficiency and is associated with complex immune disorders. Gut microbiota interacts closely with the immune system, and intestinal dysbiosis is related to multiple diseases. OBJECTIVE: To describe for the first time the composition of gut microbiota in Mexican patients with CVID. METHODS: Fecal samples from five patients with CVID were collected and massive sequencing of the V3-V4 region of 16S rRNA gene was carried out using illumina technology. RESULTS: Bacterial relative abundance was observed at all taxonomic levels. Firmicutes, Actinobacteria and Verrucomicrobia were the predominant phyla. The Clostridia class and the Clostridial order were the most common in their respective taxon; the Ruminococcaceae family predominated. A total of 166 genera were reported, with the most abundant being Faecalibacterium. Five species were identified, but only Bifidobacterium longum was present in all patients. CONCLUSIONS: Unlike healthy subjects' gut microbiota, where Firmicutes and Bacteroidetes predominate, the microbiota of the patients with CVID considered in this study was abundant in Firmicutes, Actinobacteria and Verrucomicrobia. The low presence of Bacteroidetes and high abundance of Firmicutes might indicate the existence of intestinal dysbiosis in these patients.

INTRODUCCIÓN: La inmunodeficiencia común variable (IDCV) es la principal inmunodeficiencia primaria sintomática y cursa con alteraciones inmunes complejas. La microbiota intestinal interactúa estrechamente con el sistema inmune y la disbiosis intestinal está relacionada con múltiples patologías. OBJETIVO: Describir por primera vez la composición de la microbiota intestinal en pacientes mexicanos con inmunodeficiencia común variable. MÉTODO: Se recolectaron muestras fecales de cinco pacientes con inmunodeficiencia común variable y se llevó a cabo secuenciación masiva de la región V3-V4 del gen 16S rRNA mediante tecnología Illumina. RESULTADOS: Se observó abundancia bacteriana relativa a todos los niveles taxonómicos. Firmicutes, Actinobacteria y Verrucomicrobia fueron los filos predominantes. La clase Clostridia y el orden Clostridiales fueron los principales en su respectivo taxón; predominó la familia Ruminococcaceae. Se reportaron 166 géneros, el más abundante fue Faecalibacterium. Se identificaron cinco especies, pero solo Bifidobacterium longum estuvo presente en todos los pacientes. CONCLUSIONES: A diferencia de la microbiota intestinal de sujetos sanos en quienes predominan Firmicutes y Bacteroidetes, en los pacientes con inmunodeficiencia común variable considerados en este estudio fueron abundantes Firmicutes, Actinobacterias y Verrucomicrobia. La baja abundancia de bacteroidetes y alta de firmicutes podrían significar disbiosis intestinal.

[GUIMIT 2019, Mexican Guideline on Immunotherapy. Guideline on the diagnosis of IgE-mediated allergic disease and immunotherapy following the ADAPTE approach]. / GUIMIT 2019, Guía Mexicana de Inmunoterapia. Guía de diagnóstico de alergia mediada por IgE e inmunoterapia aplicando el método ADAPTE.

BACKGROUND: In Mexico, allergen immunotherapy (AIT) and immunotherapy with hymenoptera venom (VIT) is traditionally practiced combining aspects of the European and American school. In addition, both types of extracts (European and American) are commercially available in Mexico. Moreover, for an adequate AIT/VIT a timely diagnosis is crucial. Therefore, there is a need for a widely accepted, up-to-date national immunotherapy guideline that covers diagnostic issues, indications, dosage, mechanisms, adverse effects and future expectations of AIT (GUIMIT 2019). METHOD: With nationwide groups of allergists participating, including delegates from postgraduate training-programs in Allergy/Immunology-forming, the guideline document was developed according to the ADAPTE methodology: the immunotherapy guidelines from European Academy of Allergy and Clinical Immunology, German Society for Allergology and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology and American College of Allergy, Asthma, and Immunology were selected as mother guidelines, as they received the highest AGREE-II score among international guidelines available; their evidence conforms the scientific basis for this document. RESULTS: GUIMIT emanates strong or weak (suggestions) recommendations about practical issues directly related to in vivo or in vitro diagnosis of IgE mediated allergic diseases and the preparation and application of AIT/VIT and its adverse effects. GUIMIT finishes with a perspective on AIT modalities for the future. All the statements were discussed and voted on until > 80 % consensus was reached. CONCLUSIONS: A wide and diverse group of AIT/VIT experts issued transculturized, evidence-based recommendations and reached consensus that might improve and standardize AIT practice in Mexico.

Antecedentes: En México, la inmunoterapia con alérgenos (ITA) y con veneno de himenópteros (VIT) se practica tradicionalmente combinando criterios de las escuelas europea y estadounidense; los dos tipos de extractos están comercialmente disponibles en México. Para una ITA adecuada es crucial un diagnóstico oportuno. Objetivo: Presentar GUIMIT 2019, Guía Mexicana de Inmunoterapia 2019, de base amplia, actualizada, que abarca temas de diagnóstico, indicaciones, dosificación, mecanismos, efectos adversos de la ITA y expectativas con esta modalidad de tratamiento. Método: Con la participación de múltiples grupos mexicanos de alergólogos, que incluían los centros formadores universitarios en alergia e inmunología, se desarrolló el documento de la guía según la metodología ADAPTE. Las guías de inmunoterapia de la European Academy of Allergy and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology, German Society for Allergology and Clinical Immunology y del American College of Allergy, Asthma, and Immunology se seleccionaron como guías fuente, ya que recibieron la puntuación AGREE-II más alta entre las guías internacionales disponibles; su evidencia conforma la base científica de GUIMIT 2019. Resultados: En GUIMIT 2019 se emiten recomendaciones fuertes o débiles (sugerencias) acerca de temas directamente relacionados con el diagnóstico in vivo o in vitro de las enfermedades alérgicas mediadas por IgE, la preparación y aplicación de ITA o VIT y sus efectos adversos; se incluye la revisión de las modalidades de ITA para el futuro. Todos los argumentos que se exponen fueron discutidos y votados con > 80 % de aprobación. Conclusión: Un grupo amplio y diverso de expertos en ITA y VIT emitió recomendaciones transculturizadas basadas en evidencia, que alcanzaron consenso; con ellas se pretende mejorar y homologar la práctica de la inmunoterapia en México.

Gut microbiota in Mexican patients with common variable immunodeficiency.

INTRODUCTION: Common variable immunodeficiency (CVID) is the main symptomatic primary immunodeficiency and is associated with complex immune disorders. Gut microbiota interacts closely with the immune system, and intestinal dysbiosis is related to multiple diseases. OBJECTIVE: To describe for the first time the composition of gut microbiota in Mexican patients with CVID. METHODS: Fecal samples from five patients with CVID were collected and massive sequencing of the V3-V4 region of 16S rRNA gene was carried out using illumina technology. RESULTS: Bacterial relative abundance was observed at all taxonomic levels. Firmicutes, Actinobacteria and Verrucomicrobia were the predominant phyla. The Clostridia class and the Clostridial order were the most common in their respective taxon; the Ruminococcaceae family predominated. A total of 166 genera were reported, with the most abundant being Faecalibacterium. Five species were identified, but only Bifidobacterium longum was present in all patients. CONCLUSIONS: Unlike healthy subjects' gut microbiota, where Firmicutes and Bacteroidetes predominate, the microbiota of the patients with CVID considered in this study was abundant in Firmicutes, Actinobacteria and Verrucomicrobia. The low presence of Bacteroidetes and high abundance of Firmicutes might indicate the existence of intestinal dysbiosis in these patients.

Recurrent Toxic Epidermal Necrolysis Syndrome: A Report of Two Cases.

An 81-year-old male and a 47-year-old female experienced recurrent severe bullous dermatosis secondary to an intake of drugs and alternative medicines indicated for arthralgias. The first patient had previously presented with Stevens-Johnson/toxic epidermal necrolysis (TEN) overlap syndrome in 2007 secondary to ingestion of trimethoprim/sulfamethoxazole indicated for a urinary tract infection; 6 years later, he presented with the same syndrome 2 days after ingestion of oral naproxen tablets 250 mg twice daily. The second patient had presented 5 years previously with TEN after receiving trimethoprim/sulfamethoxazole. In 2014, she presented with arthralgias and received a xenobiotic oral called 'miracle pills' (dosage is unknown); 3 weeks later, she again experienced TEN. Both patients were treated with intravenous immunoglobulin 400 mg/kg/day; duration of treatment was 5 days for the first patient and 3 days for the second. However, the male patient died from severe sepsis; the female patient experienced a favorable outcome. There are many risk factors for the development of cutaneous adverse drug reactions; a history of allergic reactions is one important risk factor, and both patients had it. This article reviews the scientific literature on this topic and analyzes the possible causes, including infectious processes, immunological defects, and immunogenetic factors.

BCG vaccination in patients with severe combined immunodeficiency: complications, risks, and vaccination policies.

BACKGROUND: Severe combined immunodeficiency (SCID) is a syndrome characterized by profound T-cell deficiency. BCG vaccine is contraindicated in patients with SCID. Because most countries encourage BCG vaccination at birth, a high percentage of patients with SCID are vaccinated before their immune defect is detected. OBJECTIVES: We sought to describe the complications and risks associated with BCG vaccination in patients with SCID. METHODS: An extensive standardized questionnaire evaluating complications, therapeutics, and outcomes regarding BCG vaccination in patients given a diagnosis of SCID was widely distributed. Summary statistics and association analysis was performed. RESULTS: Data on 349 BCG-vaccinated patients with SCID from 28 centers in 17 countries were analyzed. Fifty-one percent of the patients had BCG-associated complications, 34% disseminated and 17% localized (a 33,000- and 400-fold increase, respectively, over the general population). Patients receiving early vaccination (≤1 month) showed an increased prevalence of complications (P = .006) and death caused by BCG-associated complications (P < .0001). The odds of experiencing complications among patients with T-cell numbers of 250/µL or less at diagnosis was 2.1 times higher (95% CI, 1.4-3.4 times higher; P = .001) than among those with T-cell numbers of greater than 250/µL. BCG-associated complications were reported in 2 of 78 patients who received antimycobacterial therapy while asymptomatic, and no deaths caused by BCG-associated complications occurred in this group. In contrast, 46 BCG-associated deaths were reported among 160 patients treated with antimycobacterial therapy for a symptomatic BCG infection (P < .0001). CONCLUSIONS: BCG vaccine has a very high rate of complications in patients with SCID, which increase morbidity and mortality rates. Until safer and more efficient antituberculosis vaccines become available, delay in BCG vaccination should be considered to protect highly vulnerable populations from preventable complications.

Effect of D-limonene on immune response in BALB/c mice with lymphoma.

The monoterpene D-limonene and its metabolites have been shown to exert chemopreventive and chemotherapeutic activities against different tumors in animal models and clinical trials. However, it is unknown whether these compounds modulate the immune response in tumor-bearing mice. We evaluated the survival of lymphoma-bearing mice fed with a diet with D-limonene. To assess the cell immune response, we sensitized and challenged BALB/c mice with 2,4-dinitrofluorobenzene (DNFB) and evaluated the T-cell subpopulations by flow cytometry. We also examined phagocytosis, microbicidal activity and chemotactic function in peritoneal macrophages. In order to know the role of D-limonene and its metabolites, macrophage NO production and lymphocyte proliferation studies were performed in vitro with D-limonene, perillic acid and perillyl alcohol. The results showed that D-limonene increased the survival of lymphoma-bearing mice, delayed hypersensitivity reaction to DNFB, phagocytosis and microbicidal activity. In vitro studies indicate that D-limonene increased NO production in peritoneal macrophages obtained from tumor-bearing mice. Our data suggest that in addition to reported properties, D-limonene modulates the immune response with significant potential for clinical application.

Increased expression of p21(waf) cyclin-dependent kinase inhibitor in asthmatic bronchial epithelium.

Because the asthmatic bronchial epithelium is characterized by widespread damage, we postulated that this is associated with expression of cell cycle inhibitors that control proliferation. Using bronchial biopsies, the epithelium was the major site of expression of the cyclin-dependent kinase inhibitor, p21(waf). Immunostaining usually occurred in the cytoplasm of columnar cells; however, in severe asthma, nuclear staining was also evident in the proliferative, basal cell compartment. p21(waf) expression was significantly higher in asthmatic versus nonasthmatic epithelium and was unaffected by corticosteroid treatment; proliferating cell nuclear antigen was not significantly different in any group. p21(waf), but not p27(kip1), mRNA and protein were induced by treatment of bronchial epithelial cells in vitro with transforming growth factor (TGF)-beta or H2O2, but not by dexamethasone, which induced p57(kip2). TGF-beta and dexamethasone inhibited epidermal growth factor (EGF)-induced DNA synthesis, whereas low concentrations of H2O2 synergized with EGF; at higher doses, growth inhibition and induction of apoptosis occurred. TGF-beta caused p21(waf) to become nuclear, suggesting interaction with the replicative machinery; however, in oxidant-stressed cells, p21(waf) was predominantly cytoplasmic, where it has been linked to cell survival. We conclude that p21(waf) overexpression in asthma influences cell proliferation and survival. This may cause abnormal repair responses that contribute to airway inflammation and remodeling.

Pruebas in vitro e in vivo a ácaros / Test in vitro and in vivo to mites

Se estudiaron 40 niños con una o más enfermedades alérgicas perennes (asma bronquial, rinitis alérgica o dermatitis atópica) con el fin de determinar el valor en nuestro medio de las pruebas in vivo e in vitro más utilizadas para el diagnóstico de alergia, como la IgE total sérica, IgG alergenoespecífica (RAST) y pruebas cutáneas utilizando el método de punción en pacientes sensibles a D.pteronissinus, D. farinae o ambos. Todos los pacientes tuvieron pruebas cutáneas positivas. La IgE total sérica estuvo elevada en 95 porciento de los casos, con un pobre coeficiente de correlación (r) al comparar el grado de reacción cutánea y la concentración de IgE total sérica, no existiendo significancia estadística. Por otro lado, 95 porciento de los pacientes tuvieron RAST positivo con un coeficiente de correlación de 0.31 (p< 0.05). Se concluye que en nuestro país, la historia clínica y las pruebas cutáneas son suficientes en un porcentaje razonable para hacer el diagnóstico de alergia, en pacientes sensibles a ácaros de polvo casero.

Enterocolites necrosante neonatal: correlación clínico-patológica; experiencia de 6 años / Neonatal necrotizing enterocolitis: clinic-pathologic correlation; a 6 year's experience

Se hizo un estudio retrospectivo de 21 recién nacido que fallecieron con el diagnóstico de enterocolitis necrosante (ECN) durante el periodo de 1980 a 1985. La edad gestacional promedio fue de 33.9 semanas (variación de 29 a 42), con un peso medio de 1,789 (variación de 960 a 3600). Se documentaron antecedentes de riesgo en 86% de los pacientes. De estos, predominó la hipóxia perinatal, presentándose en 51% de los niños. El signo clínico inicial más común fue la distensión abdominal que se observó en todos los pacientes, seguido de sangre en las evacuaciones y letargia. El 76.1% de los recién nacido estuvieron en los estadios II y III de la clasificación de Bell. En todos los pacientes se encontraron cambios definitivos en el estudio de anatomía patológica, siendo el hallazgo más frecuente la presencia de quistessubmucosos llenos de gas, de las cuales 85% se localizaron en ileón y colon. Los hemocultivos y coprocultivos fueron positivos en el 36% de los casos con predominio e E. coli y Klebsiella. Finalmente, se presenta unn análisis de las hipótesis actuales sobre la fisiopatología y se hacen algunas recomendaciones para prevenir la enfermedad