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.

[MASK (Mobile Airways Sentinel Network), a mobile App with ARIA's comprehensive solution in Spanish-speaking countries]. / MASK (Mobile Airways Sentinel Network), una app móvil con la solución integral de ARIA en países de habla hispana.

Although there are high quality clinical guidelines about allergic rhinitis, many patients receive deficient treatment, partly due to the high level of self-medication. MASK (Mobile Airways Sentinel Network) is an integral part of a project against chronic diseases which it is focused on active and healthy aging and is supported by the European Union. It forms the third phase of ARIA (Allergic Rhinitis and its Impact on Asthma) in which, through a mobile app on a smart device, the purpose is to guide patients in the control of their multimorbidity, allergic rhinitis or conjunctivitis, or asthma. The "Allergy Diary" app by MACVIA-ARIA is free and it is available for Android and iOS; on it, patients indicate how unpleasant the symptoms are on a daily basis through five screens with an analogous visual scale; two more screens were recently added (sleep affectation). With the app, it is also possible to download the information of the "Allergy Diary" on the physician's computer through a QR code at the moment of the medical consultation. In this article, we review the first year of experience in Spain, Mexico and Argentina, where the Spanish version is used.

Aunque existen guías clínicas de alta calidad sobre rinitis alérgica, numerosos pacientes reciben tratamiento deficiente, en parte debido al alto grado de automedicación. MASK (Mobile Airways Sentinel Network) forma parte integral de un proyecto apoyado por la Unión Europea contra las enfermedades crónicas y enfocado al envejecimiento activo y saludable. Constituye la tercera fase de ARIA (Allergic Rhinitis and its Impact on Asthma), en la cual mediante una aplicación móvil en un dispositivo inteligente se intenta guiar al paciente en el control de su multimorbilidad, rinitis o conjuntivitis alérgicas o asma. La aplicación Diario de Alergia por MACVIA-ARIA es gratuita y está disponible para Android e iOS; en ella, los pacientes indican diariamente cuánto les molestan los síntomas a través de cinco pantallas con una escala visual análoga; recientemente se agregaron dos pantallas más (afectación del sueño). La aplicación también permite descargar los datos del "Diario de alergias" en la computadora del médico en el momento de la consulta a través de un código QR. En este artículo reseñamos el primer año de experiencia en España, México y Argentina, que utilizan la versión española.

[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.

[Executive Summary of ARIA 2019: Integrated care pathways for allergic rhinitis in Argentina, Spain and Mexico]. / Resumen ejecutivo de ARIA 2019: Vías integradas de atención para la rinitis alérgica en Argentina, España y México.

The health and economic impact of allergic diseases are increasing rapidly, and changes in management strategies are required. Its influence reduces the capacity of work and school performance by at least a third. The ICPs of the airways (integrated care pathways for respiratory diseases) are structured multidisciplinary healthcare plans, promoting the recommendations of the guidelines in local protocols and their application to clinical practice. This document presents an executive summary for Argentina, Mexico, and Spain. Next-generation ARIA guidelines are being developed for the pharmacological treatment of allergic rhinitis (AR), using the GRADE-based guidelines for AR, tested with real-life evidence provided by mobile technology with visual analogue scales. It is concluded that in the AR treatment, H1-antihistamines are less effective than intranasal corticosteroids (INCS), in severe AR the INCS represent the first line of treatment, and intranasal combination INCS + anti-H1 is more effective than monotherapy. However, according to the MASK real-life observational study, patients have poor adherence to treatment and often self-medicate, according to their needs.

El impacto sanitario y económico de las enfermedades alérgicas está aumentando rápidamente y se necesitan cambios en las estrategias para su manejo. Su influencia reduce al menos en un tercio la capacidad de desempeño laboral y escolar. Los ICP (Vías Integradas de Atención) de las enfermedades de las vías respiratorias son planes de atención estructurados y multidisciplinarios, que promueven las recomendaciones de las guías en protocolos locales y su aplicación a la práctica clínica. En este documento se presenta un resumen ejecutivo para Argentina, México y España. Se desarrollan las guías ARIA de próxima generación para el tratamiento farmacológico de la rinitis alérgica (RA) utilizando las pautas basadas en GRADE para RA, probadas con evidencia de la vida real proporcionada por tecnología móvil basada en escalas visuales analógicas. Se concluye que en el tratamiento de la RA, los antihistamínicos anti-H1 son menos efectivos que los corticoides intranasales (CINS), que en la rinitis gravelos CINS representan la primera línea de tratamiento, y que la combinación intranasal de CINS + anti-H1 es más eficaz que la monoterapia. Sin embargo, según el estudio MASK observacional en vida real, los pacientes tienen pobre adherencia al tratamiento y frecuentemente se automedican de acuerdo con sus necesidades.

[Mexican consensus on the diagnosis and treatment of atopic dermatitis in adolescents and adults]. / Consenso mexicano para el diagnóstico y tratamiento de la dermatitis atópica en adolescentes y adultos.

BACKGROUND: The diagnostic approaches and therapeutic strategies of atopic dermatitis (AD) are generally inconsistent among physicians and health institutions. OBJECTIVE: To develop a consensus statement among experts to reduce the variations in practice regarding the diagnosis and treatment of patients ≥ 12 years with AD to improve their care. METHODS: Systematic literature search in PubMed and GREAT. With methodological support and using the Delphi method, a formal consensus was developed among 16 experts in Dermatology and Allergology, based on the current evidence and its applicability in the Mexican context. Apart from intense electronic communication, several issues of disagreement were discussed in two face-to-face meetings. RESULTS: The clinical experts reached consensus on 46 statements related to the definition, classification, diagnostic strategies and treatment of AD. For the diagnosis we suggest the Williams criteria and for severity scoring the SCORAD (by the doctor) and POEM (by the patient). In addition to general care and treatment education (workshops), we suggest four steps for treatment, depending on severity: 1. Topical treatment with anti-inflammatory agents (and systemic: antihistamines/antileukotrienes -low level evidence-) 2. Phototherapy, 3. Cyclosporin A and 4. Dupilumab, with the possibility of managing this biological earlier on if a fast effect is needed. In extrinsic AD we suggest evaluating the addition of allergen immunotherapy or an elimination diet, if there is an IgE-mediated respiratory or food allergy, respectively. CONCLUSION: The panel of experts reached consensus on relevant aspects of AD with a focus on the transcultural adaptation of recent evidence.

Antecedentes: Los abordajes diagnósticos y las estrategias terapéuticas de la dermatitis atópica generalmente son inconsistentes entre los médicos y entre las instituciones de salud. Objetivo: Consensar las opiniones de expertos para reducir las variaciones en la práctica respecto al diagnóstico y tratamiento de pacientes ≥ 12 años con dermatitis atópica para mejorar su cuidado. Métodos: Búsqueda sistemática de la literatura en PubMed y GREAT. Con apoyo metodológico y utilizando el método Delphi se desarrolló un consenso formal entre 16 expertos en dermatología y alergología, basándose en la evidencia actual y su aplicabilidad en el contexto mexicano. A parte de una comunicación electrónica intensa, se discutieron los puntos en desacuerdo en dos reuniones presenciales. Resultados: Los expertos clínicos alcanzaron consenso en 46 declaraciones relacionadas con la definición, clasificación, estrategias de diagnóstico y tratamiento de la dermatitis atópica. Para el diagnóstico sugerimos se usan los criterios de Williams y el SCORAD (por parte del médico) y POEM (por parte del paciente) para definir la gravedad. Aunado a cuidados generales y educación terapéutica, sugerimos cuatro pasos para tratamiento, según gravedad: 1. Manejo tópico con antiinflamatorio (y sistémico: antihistamínico/antileucotrieno ­evidencia reducida­) 2. Fototerapia, 3. Ciclosporina A y 4. Dupilumab, con la posibilidad de manejarlo antes si se necesita efecto rápido. En la dermatitis atópica extrínseca sugerimos agregar inmunoterapia con alérgenos o una dieta de eliminación si existe una alergia IgE-mediada, inhalatoria o alimentaria, respectivamente. Conclusión: El panel de expertos realizó consenso en aspectos relevantes de la dermatitis atópica con enfoque en la adaptación transcultural de evidencia reciente.

Pediatric asthma treatment: What to do when international guideline recommendations do not agree.

BACKGROUND: There was a need for a solid asthma guideline in Mexico to update and unify asthma management. Because high-quality asthma guidelines exist worldwide, in which the latest evidence on asthma management is summarized, the ADAPTE approach allows for the development of a national asthma guideline based on evidence from already existing guidelines, adapted to national needs. OBJECTIVE: To fuse evidence from the best asthma guidelines and adapt it to local needs with the ADAPTE approach. METHODS: The Appraisal of Guidelines for Research and Evaluation (AGREE) II asthma guidelines were evaluated by a core group to select 3 primary guidelines. For each step of asthma management, clinical questions were formulated and replied according to (1) evidence in the primary guidelines, (2) safety, (3) Cost, and (4) patient preference. The Guidelines Development Group, composed of a broad range of experts from medical specialties, primary care physicians, and methodologists, adjusted the draft questions and replies in several rounds of a Delphi process and 3 face-to-face meetings, taking into account the reality of the situation in Mexico. We present the results of the pediatric asthma treatment part. RESULTS: Selected primary guidelines are from the British Thoracic Society and Scottish Intercollegiate Guidelines Network (BTS/SIGN), Global Initiative for Asthma (GINA), and Spanish Guidelines on the Management of Asthma (GEMA) 2015, with 2016 updates. Recommendations or suggestions were made for asthma treatment in Mexico. In this article, the detailed analysis of the evidence present in the BTS/SIGN, GINA, and GEMA sections on the (non) pharmacologic treatment of pediatric asthma, education, and devices are presented for 2 age groups: children 5 years or younger and children 6 to 11 years old with asthma. CONCLUSION: For the pediatric treatment and patient education sections, applying the AGREE II and Delphi methods is useful to develop a scientifically sustained document, adjusted to the Mexican situation, as is the Mexican Guideline on Asthma.

[Mexican Asthma Guidelines: GUIMA 2017]. / Guía Mexicana del Asma: GUIMA 2017.

BACKGROUND: The need for a national guideline, with a broad basis among specialists and primary care physicians was felt in Mexico, to try unifying asthma management. As several high-quality asthma guidelines exist worldwide, it was decided to select the best three for transculturation. METHODS: Following the internationally recommended methodology for guideline transculturation, ADAPTE, a literature search for asthma guidelines, published 1-1-2007 through 31-12-2015 was conducted. AGREE-II evaluations yielded 3/40 most suitable for transculturation. Their compound evidence was fused with local reality, patient preference, cost and safety considerations to draft the guideline document. Subsequently, this was adjusted by physicians from 12 national medical societies in several rounds of a Delphi process and 3 face-to-face meetings to reach the final version. RESULTS: Evidence was fused from British Thoracic Society Asthma Guideline 2014, Global Initiative on Asthma 2015, and Guía Española del Manejo del Asma 2015 (2016 updates included). After 3 Delphi-rounds we developed an evidence-based document taking into account patient characteristics, including age, treatment costs and safety and best locally available medication. CONCLUSIONS: In cooperation pulmonologists, allergists, ENT physicians, paediatricians and GPs were able to develop an evidence-based document for the prevention, diagnosis and treatment of asthma and its exacerbations in Mexico.

Antecedentes: Con el objetivo de unificar el manejo del asma en México se estructuró una guía clínica que conjunta el conocimiento de diversas especialidades y la atención en el primer nivel de contacto. Se seleccionaron 3 guías publicadas en el ámbito internacional para su transculturación. Métodos: Conforme a la metodología ADAPTE se usó AGREE II después de la búsqueda bibliográfica de guías sobre asma publicadas entre 2007 y 2015. Se fusionó la realidad local con la evidencia de 3/40 mejores guías. El documento inicial fue sometido a la revisión de representantes de 12 sociedades médicas en varias rondas Delphi hasta llegar a la versión final. Resultados: Las guías base fueron la British Thoracic Society Asthma Guideline 2014, la Global Initiative on Asthma 2015 y la Guía Española del Manejo del Asma 2015. Después de 3 rondas Delphi se desarrolló un documento en el que se consideraron las características de los pacientes según edad, costos de los tratamientos y perfiles de seguridad de los fármacos disponibles en México. Conclusión: Con la cooperación de neumólogos, alergólogos, otorrinolaringólogos, pediatras y médicos generales se llegó a un consenso basado en evidencia, en el que se incluyeron recomendaciones sobre prevención, diagnóstico y tratamiento del asma y sus crisis.

[Mexican guidelines on the diagnosis and treatment of urticaria]. / Guía Mexicana para el Diagnóstico y el Tratamiento de la Urticaria.

BACKGROUND: Urticaria is a disease that a fifth of the population shallsuffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups -both specialists and primary health care workers-, necessary in Mexico. MATERIAL AND METHOD: Internationally recognized tools for guidelinedevelopment were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline development) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development. RESULTS: By a formal process of discussion and voting during several working-sessions, experts and first level healthcare physicians determined the wording of the final guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as first line treatment is emphasized. CONCLUSION: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, first line health care physicians and specialists.

Antecedentes: la urticaria es una enfermedad que padece una quinta parte de la población en algún momento de su vida. Las guías internacionales recientes han propuesto unos cambios de fondo en su diagnóstico y tratamiento, por lo que había la necesidad de crear una guía nacional y multidisciplinaria, con base amplia en los gremios de especialistas y médicos de primer contacto en México. Material y método: un grupo interdisciplinario de expertos clínicos y algunos expertos en metodología determinó los objetivos y alcances de la Guía de Práctica Clínica Basada en Evidencia con el instrumento SCOPE. Se decidió llevar a cabo la adaptación y transculturización de guías internacionales para el diagnóstico y tratamiento de urticaria. Con el instrumento AGREE-II se seleccionaron las tres guías de alta calidad, como guías base (Zuberbier 2014, Sánchez-Borges 2012, Powell 2007) para formular y contestar la preguntas clínicas clave, en el contexto cultural y económico mexicano, según el método de desarrollo de recomendaciones GRADE. Resultados: mediante un proceso formal de discusión y votación durante varias juntas de expertos, se terminó la redacción de la forma final de la guía, con especial cuidado de lograr un ajuste a las realidades, valores y preferencias de los pacientes de México. Se hace hincapié en la administración de antihistamínicos vía oral de segunda generación, como tratamiento de primera elección. Conclusión: este documento es una Guía de Práctica Clínica Basada en Evidencia para el diagnóstico y tratamiento de urticaria aguda y crónica, basada en tres guías internacionales de alta calidad. Se desarrolló por un grupo multidisciplinario. Los cuadros y algoritmos hacen a la guía amigable para su uso por médicos de primer contacto y por especialistas.

[Risk factors associated with the development of atopic march. Case-control study]. / Factores de riesgo asociados al desarrollo de marcha atópica. Estudio de casos y controles.

BACKGROUND: The atopic march is characterized by the sequential presence of food allergy, atopic dermatitis, rhinitis and asthma. Risk factors for the progression of the allergic disease defined as atopic march have not been established. OBJECTIVE: To determine the associated factors with the development of atopic march in children between the ages of 2 and 12 years. METHODS: This case-control study included children between 2 and 12 years of age, 50 in the group of atopic march and 50 controls, characterized by an allergic disease. A questionnaire on atopic antecedents was given, skin tests with allergens were performed to the patients and their parents, and the level of serum IgE was measured. RESULTS: We found as associated risk factors for the development of atopic march, the following: male sex (OR= 3.62), positive skin tests in their parents (OR=2.66) and urinary tract and gynecologic infections during pregnancy (OR = 4.95). CONCLUSIONS: Male sex, sensitization to allergens in their parents and maternal infections during pregnancy are associated risk factors for the development of atopic march in children.

NFE2L2 gene variants and susceptibility to childhood-onset asthma.

INTRODUCTION: Environmental factors causing oxidative stress are known to be associated with asthma morbidity. The antioxidative gene NFE2L2 has been implicated in asthma development in mice models. In humans, the SNPs -617C/A and -653G/A, located at the promoter region of NFE2L2 gene, have been found associated with the susceptibility to develop diverse chronic-degenerative diseases. OBJECTIVE: To determine if there is association of the -617C/A and -653G/A NFE2L2 SNPs and childhood-onset asthma in a Mexican population. MATERIALS AND METHODS: In a case-control study 242 unrelated patients with diagnosis of asthma and 358 ethnically- and sex-matched healthy individuals were included. The -617C/A and -653G/A NFE2L2 genotyping was carried out using the TaqMan allelic discrimination assay. RESULTS: The risk allele of both polymorphisms showed a high frequency in our sample (-617A: 24% and -653A: 40%), similarly to those previously reported in Asiatic populations (-617A: 24-29% and -653A: 42-52%; p > 0.05). In contrast, the -617A allele frequency was higher than that reported in a European-African admixed population (10%, p < 0.001). The allelic and genotypic frequencies from both polymorphisms showed no significant differences among cases and controls in female and male samples. Likewise, haplotype analysis found no association between NFE2L2 gene variants and the disease. CONCLUSIONS: Despite the experimental evidence suggesting that NFE2L2 gene is involved in asthma pathogenesis, the -617C/A and -653G/A SNPs were not associated with childhood-onset asthma.

Transfer factor and allergy.

Although various mechanisms involving antibodies and various cell types participate, a Thl and Th2 cells imbalance seems to play a central role for allergy development. Other lymphocyte subpopulations, such as Th17, CD4 FOXP3, and Th9 positive regulatory T lymphocytes may also be involved in the allergic response. Regulatory processes are an appealing target for therapeutic approaches aiming to solve allergic reactions by restoring the delicate balance within the immune system. Transfer factor (TF) or dialyzable leukocyte extract is meant to transfer cell-mediated immunity from immune competent donors to unsensitized or deficient recipients. A PubMed search on the current knowledge on TF indicates that TF may restore the Th1/Th2 balance and improve immune regulatory mechanisms of patients receiving it. Our preliminary results demonstrate that TF induces mRNA expression of IFN-g, osteopontin, RANTES, and hBD-2 in human healthy subjects. TF has been used to treat a variety of immune dysfunction related-pathologies, such as allergy, autoimmunity, immunodeficiencies, infectious diseases and tumors. Patients receiving TF together with their conventional treatment often have better clinical evolution than without it, as we have witnessed, adding TF to the usual medical treatment of allergic diseases as an attempt to provide allergic patients with those regulatory elements that they apparently lack but require to achieve properly regulated immune responses and thus obtain a faster and better resolution of allergic reactions.

Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoid arthritis, and systemic lupus erythematosus in a Mexican pediatric population.

There is a great deal of evidence that points to the association of the tumor necrosis factor-alpha (TNF-alpha) gene as a common genetic factor in the pathogenesis of diseases that are caused by inflammatory and/or autoimmune etiologies. Two single nucleotide polymorphisms (SNPs) identified in the TNF-alpha promoter region have been associated with disease susceptibility and severity. We investigated whether -308G/A and -238G/A TNF-alpha polymorphisms were associated with asthma, systemic lupus erythematosus (SLE), and juvenile rheumatoid arthritis (JRA) in a pediatric Mexican population. In a case-control study of 725 patients (asthma: 226, JRA: 171, and SLE: 328) and 400 control subjects, the participants were analyzed using the allelic discrimination technique. The genotype distribution of both TNF-alpha polymorphisms was in Hardy-Weinberg equilibrium in each group. However, there were significant differences in the allele frequency of TNF-alpha-308A between the patients and the healthy controls. This allele was detected in 2.9% of the controls, 6.0% of asthmatic and JRA patients (p = 0.002 and p = 0.0086), and 6.7% of SLE patients (p = 0.00049); statistical significance was maintained after ancestry stratification (asthma: p = 0.0143, JRA: p = 0.0083, and SLE: p = 0.0026). Stratification by gender showed that the risk for the -308A allele in asthma and JRA was greater in females (OR = 4.16, p = 0.0008 and OR = 4.4, p = 0.0002, respectively). The TNF-alpha -238A allele showed an association only with JRA in males (OR = 2.89, p = 0.004). These results support the concept that the TNF-alpha gene is a genetic risk factor for asthma, SLE, and JRA in the pediatric Mexican population.

[IgE deficiency: a forgotten disease?]. / Deficiencia de IgE: un padecimiento olvidado?

BACKGROUND: Selective IgE deficiency is a profound deficiency (< 5 UI/mL) or absence of serum IgE levels without other immunologic abnormalities. It is usually asymptomatic, but may be associated with recurrent respiratory infections, chronic fatigue, and musculoskeletal complaints. OBJECTIVE: To describe the evolution and treatment in patients with selective IgE deficiency. PATIENTS AND METHOD: In selective IgE's deficiency patients identification note, atopy history, concurrent diseases, clinic of allergic diseases, Prick test and prior response to treatment were analyzed. RESULTS: Eleven patients were included, five women and six men within 16 months to 10 years old. The patients had serum IgE levels < 5 UI with other immunoglobulins and sub-classes in normal levels; except a patient with concomitant IgA and IgE deficiency. The treatment administered was since prophylactic antibiotic to intravenous gammaglobulin. DISCUSSION: We established the diagnosis of selective IgE deficiency in patient with serum IgE levels < 5 UI/mL associated with recurrent respiratory infections. CONCLUSIONS: We need more clinic studies to document with precision the selective IgE deficiency.

[Association between chronic urticaria and Helicobacter pylori]. / Asociación entre urticaria crónica y Helicobacter pylori.

BACKGROUND: Chronic urticaria is a multifactorial disease classified in three main groups: mechanical, autoimmune and idiopathic. So far we don't know the mechanisms that produces it, there are different theories and one of them is the presence of Helicobacter pylori. OBJECTIVE: To establish the relation between chronic urticaria and Helicobacter pylori trough endoscopic and histopatological studies. PATIENTS AND METHODS: Seventy-two patients older than 18 years old, 36 with chronic urticaria and 36 controls with the same sex and age. Complete clinical history, hematical biometry, cutaneous determination of IgE and tests was made to each one. High panendoscopy with gastric biopsy was asked to practice Warthin Starry method and determine Helicobacter pylori existence. The statistical analysis was made with SPSS program, version 11, to establish the bivariated correlation in search of variables dependency. RESULTS: In the group with chronic urticaria, there were 19 (52.8%) patients infected with Helicobacter pylori, and in the control group only 4 (11.1%). We found a chi2 with a value of 12.52 (p < 0.002). CONCLUSIONS: Association between chronic urticaria and Helicobacter Pylori is evident, so we propose a routinely scan for this microorganism in patients with the disease.

[Prevalence of chronic urticaria of autoimmune origin at the Regional Hospital Adolfo López Mateos]. / Prevalencia de urticaria crónica de origen autoinmunitario en el Hospital Regional Adolfo López Mateos.

BACKGROUND: Chronic urticaria is a common skin disorder characterized by recurrent, transitory, itchy wheals with individual lesions lasting less than 24 hours and affecting patients for six weeks or longer. In adults it has been shown that approximately 40% of the patients with chronic urticaria have autoimmune urticaria. OBJECTIVE: To determine the prevalence of autoimmune urticaria in adults with chronic urticaria. PATIENTS AND METHOD: We studied adult patients with chronic urticaria by means of autologous serum skin test (ASST), and by antinuclear and antithyroid (antityroglobulin, antiperoxidase) antibodies. We compared them with a group matched by sex and age. RESULTS: We included 68 patients: 34 cases (patients with chronic urticaria) and 34 controls (healthy individuals). In the cases we found high levels of TSH (p = 0.003) and positive autologous serum skin test (p = 0.04), while in the controls we observed a statistically significant difference of the levels of antithyroid antibodies (p = 0.002). The prevalence of autoantibodies (antithyroid or by autologous serum) was present in 55 and 44% of the patients with chronic urticaria. CONCLUSION: Autoimmunity is one of the most common causes of chronic urticaria; it may explain the pathogenesis in half of the studied cases.

[Pulse oxymetry in the diagnosis of asthma in children]. / Oximetría de pulso en el diagnóstico de asma en el niño.

BACKGROUND: Asthma is a chronic disease that requires an early diagnosis to avoid the phase of remodelation. OBJECTIVE: To evaluate transcutaneus tension of oxygen in challenge test with distilled water in pediatric patients with asthma. MATERIAL AND METHODS: Thirty patients of 1-5 years old were included: 15 with asthma and 15 control healthy subjects. Inclusion criteria were: clinical diagnosis of asthma (cough, respiratory difficulty and wheezes more than three times in the previous year), without using steroids four weeks before the study, or bronchodilators. Exclusion criteria were: respiratory infection and severe disease. A challenge test with cold distilled water was applied and O2 saturation and basal and 5, 10, 15, 20 and 30 minutes heart frequency were measured. RESULTS: O2 saturation statistically significant decreased from the basal to 5, 10, 15, 20 and 30 minutes; for cases: 96.4 and controls: 97.8, p = 0.00224. Heart frequency did not have a statistic change at basal, 5, 19, 15 and 20 minutes; but it had a statistically significant change at 30 minutes post-challenge (120.7 beats/min in cases vs 112.7 beats/min in controls, p = 0.0127). CONCLUSIONS: Pulse oxymetry has a significant value and is related to severity of illness.

[Airway hyperreactivity in patients with allergic and non-allergic rhinitis]. / Hiperrespuesta de las vías aéreas en los pacientes con rinitis alérgica y no alérgica.

BACKGROUND: Epidemiologically there is an association between allergic rhinitis and asthma due to a common inflammatory process. Asthma can affect 40% of the patients with rhinitis and 80% of asthmatics present rhinitis. The relationship between the two diseases is explained by the term of "a united airway". Some patients with allergic rhinitis have nonspecific bronchial hyper-responsiveness, specially during the exacerbation stage. These patients have a unique physiologic characteristic that differs from the asthmatic and healthy subjects developing bronchoconstriction not related to clinical bronchospasm, therefore, allergic rhinitis is considered a risk factor for the asthma development. OBJECTIVE: To determine if there is bronchial hyper-responsiveness in patients with allergic and not allergic rhinitis, by correlating with the eosinophilia in nasal mucosa. MATERIAL AND METHODS: We studied a total of 32 patients with an age range from 18 to 38 years, of both sexes (11 men and 17 women) of the Hospital Regional Lic. Adolfo Lopez Mateos, ISSSTE. They were submitted to clinical history, laboratory studies (blood count cell, serum IgE levels, eosinophils of nasal mucosa), roentgenograms (paranasal sinus and esophagus-gastroduodenal series) and allergy skin tests with 32 allergens. It was taken biopsy of nasal mucosa for the search of eosinophils and it was carried out bronchial challenge with distilled water. Twenty-eight patients concluded the study, they were divided in two groups: a group of 15 patients with diagnosis of allergic rhinitis and another group of 13 patients with diagnosis of non allergic rhinitis. RESULTS: Fifty-six spirometry studies were performed and only 4 patients (26.6%) with diagnosis of allergic rhinitis presented fall of the FEV1 in the bronchial challenge in comparison with the group of non allergic rhinitis in which there were no changes in the FEV1 later to the bronchial challenge. This difference was statistically significant (-4.3 and 0.15, respectively with a p < 0.0370, CI 95%). Moreover, only in the group of allergic rhinitis eosinophils were found in the biopsy of nasal mucosa (93.3%). CONCLUSIONS: Nonspecific bronchial hyper-responsiveness is present in patients with allergic rhinitis. The presence of nasal eosinophils is a persistent inflammation parameter suggesting the allergic origin in these patients.

[Psychological, immunological, and endocrinological implications of atopic dermatitis]. / Implicaciones psicológicas, inmunológicas y endocrinológicas en la dermatitis atópica.

BACKGROUND: The atopic dermatitis is a chronic disease with immunological alterations, neuro-immune-endocrine implications and repercussions in the psyche. OBJECTIVE: To determine the effectiveness of the use of psychological support in the treatment of atopic dermatitis. MATERIAL AND METHODS: This study included 20 patients (from 15 to 50 years old) with moderated and severe atopic dermatitis based on the Hanifin and Rafka modified criteria. They were classified in three groups of treatment: A) 10 patients with transfer factor and psychological support, B) 10 with transference factor without psychological support, C) 10 healthy individuals as a control group. At the beginning and ending of the analysis the degree of severity of the illness was determined using the SCORAD scale. RESULTS: There was a more statistically significant clinical improvement on group A than in group B, besides a decrease in anxiety and depression, at a laboratory level including hormonal behavior, without meaningful changes. CONCLUSIONS: It was demonstrated that the treatment with immune-modulator and psychological support on the moderated and severe atopic dermatitis improves the clinical and immunological evolution of this illness.

[Gastroesophageal reflux disease in pediatric patients with asthma]. / Enfermedad por reflujo gastroesofágico en pacientes pediátricos con asma.

BACKGROUND: Nowadays, the gastroesophageal reflux is a predisposing factor for the development of asthmatic attacks. OBJECTIVE: To determine the prevalence of gastroesophageal reflux in pediatric patients with asthma of the Service of Allergy and Immunology at the Hospital Regional Lic. Adolfo López Mateos. MATERIAL AND METHODS: It was made an observational study from July 2000 to July 2001. Gastroesophageal gammagraphic and endoscopy (with taking of esophageal biopsy) were carried out to each of the patients in order to find out if there was gastroesophageal reflux. RESULTS: 112 patients with moderate persistent asthma (54 women and 58 men) were included and divided in three different age groups (group I, from 1 to 5 years old; group II, from 6 to 10 and III, from 11 to 16 years old). The prevalence of gastroesophageal reflux was 138, 100 and 93, respectively, being specially high in males. Differences in the prevalence among different groups were statistically significant between group I and II (p < 0.001) and between I and III (p < 0.001). Significant changes were not observed between group II and III (p = NS). CONCLUSIONS: The prevalence of gastroesophageal reflux the structured was high, situation directly related with the diagnostic suspicion in our asthmatic population.