Coronavirus disease 2019, allergic diseases, and allergen immunotherapy: Possible favorable mechanisms of interaction.

Background: Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease. Objective: To review immune changes brought along by each of these entities and how they might interrelate. Methods: We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection. Results: We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation. Conclusion: As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

Cutaneous Manifestations Related to COVID-19 Immune Dysregulation in the Pediatric Age Group.

PURPOSE OF REVIEW: At the juncture of the COVID-19 pandemic, the world is currently in an early phase of collecting clinical data and reports of its skin manifestations, and its pathophysiology is still highly conjectural. We reviewed cutaneous manifestations associated with COVID-19 in the pediatric age group. RECENT FINDINGS: Children infected by SARS-CoV-2 usually develop milder respiratory symptoms, but cutaneous manifestations seem a little more prevalent than in adults. These skin features of infection by the coronavirus can be similar to those produced by other common viruses, but there are also reports of cases with more heterogeneous clinical pictures, which have made their classification difficult. To date, the more frequently reported skin variants featured in pediatric cases are purpuric (pseudo-chilblain, necrotic-acral ischemia, hemorrhagic macules, and/or cutaneous necrosis), morbilliform/maculopapular, erythema multiforme, urticarial, vesicular, Kawasaki-like, and miscellaneous (highly variable in both frequency and severity). Their pathophysiological mechanism is still elusive and is likely to be the result of the complex involvement of one or more mechanisms, like direct virus-induced skin damage, vasculitis-like reactions, and/or indirect injury as a consequence of a systemic inflammatory reaction. In this review, we presented and discussed clinical cases as examples of different cutaneous responses reported in some children with SARS-CoV-2 infection, differential diagnosis considerations, and a preliminary conceptual approach to some of their probable associated pathologic mechanisms.

Global Asthma Network Phase I study in Mexico: prevalence of asthma symptoms, risk factors and altitude associations-a cross-sectional study.

BACKGROUND: Global Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally. OBJECTIVE: To survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico. METHODS: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016-2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6-7-year-old primary school pupils (school children) and by 13-14-year-old adolescents. RESULTS: A total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres' sea level altitude higher than 1500 m above mean sea level (p<0.005). CONCLUSIONS: The most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.

Enhancing innate immunity against virus in times of COVID-19: Trying to untangle facts from fictions.

INTRODUCTION: In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. METHODS: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). RESULTS: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. CONCLUSION: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

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.

[The clinical practice of allergen immunotherapy in Mexico according to 277 allergists who were surveyed during a three-year AIT course]. / La práctica clínica de la inmunoterapia con alérgenos en México según 277 alergólogos encuestados durante un curso trianual.

BACKGROUND: There are different guidelines for the diagnosis of allergic diseases and the application of allergen immunotherapy (AIT). OBJECTIVE: To describe how Mexican allergists diagnose and treat respiratory and food allergies with AIT. METHODS: 227 allergists who attended an immunotherapy symposium were surveyed; the topics investigated were the daily practices in the diagnosis of respiratory and food allergies, as well as ways to apply AIT. RESULTS: The surveyed allergists use skin prick tests for the diagnosis of both respiratory and food allergies in 100 % and 87.7 % of their cases respectively; in vitro diagnosis through serum specific IgE in 55.5 % and 63 %, and molecular diagnostics in 14.1% and 13.2 %. For aeroallergens, 81 % prescribe subcutaneous AIT, 77.9 % use liquid sublingual AIT, and 1.8 % prefer SLIT in tablets; however, 45 % indicated that they would use tablets in the future. Regarding food allergens, most respondents did not prescribe AIT; however, 55% of them are interested in oral AIT and 59% of them are interested in sublingual AIT. CONCLUSIONS: Generally, the diagnosis and treatment of allergic diseases are carried out according to international guidelines; besides, the interviewed allergists expressed flexibility to adopt new schemes.

Antecedentes: Existen lineamientos para el diagnóstico de las enfermedades alérgicas y la aplicación de inmunoterapia con alérgenos (ITA). Objetivo: Describir cómo los alergólogos mexicanos diagnostican y tratan con ITA las alergias alimentaria y respiratoria. Métodos: Se encuestó a 227 alergólogos que acudieron a un simposio de inmunoterapia; se indagaron prácticas cotidianas en el diagnóstico de las alergias respiratoria y alimentaria, así como en la forma de aplicar la ITA. Resultados: Los alergólogos utilizan las pruebas cutáneas por punción para el diagnóstico de las alergias respiratorias y alimentarias en 100 y 87.7 % de los casos de una y otra; diagnóstico in vitro mediante determinación de IgE alérgeno-específica en 55.5 y 63 %; y diagnóstico molecular por componentes en 14.1 y 13.2 %. Para los aeroalérgenos, 81 % emplea ITA subcutánea; 77.9 %, ITA sublingual líquida; 1.8 %, ITA sublingual en tabletas; 45 % indicó que estaba dispuesto a emplear tabletas en el futuro. Para los alérgenos de alimentos, la mayoría no utilizaba ITA, aunque 55 % se interesa en la ITA oral y 59 %, en la ITA sublingual. Conclusiones: En términos generales, el diagnóstico y tratamiento de las enfermedades alérgicas se realizan conforme los lineamientos internacionales, además, los alergólogos encuestados mostraron flexibilidad para adoptar nuevos esquemas.

[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.

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.

Allergen sensitization linked to climate and age, not to intermittent-persistent rhinitis in a cross-sectional cohort study in the (sub)tropics.

BACKGROUND: Allergen exposure leads to allergen sensitization in susceptible individuals and this might influence allergic rhinitis (AR) phenotype expression. We investigated whether sensitization patterns vary in a country with subtropical and tropical regions and if sensitization patterns relate to AR phenotypes or age. METHODS: In a national, cross-sectional study AR patients (2-70 y) seen by allergists underwent blinded skin prick testing with a panel of 18 allergens and completed a validated questionnaire on AR phenotypes. RESULTS: 628 patients were recruited. The major sensitizing allergen was house dust mite (HDM) (56%), followed by Bermuda grass (26%), ash (24%), oak (23%) and mesquite (21%) pollen, cat (22%) and cockroach (21%). Patients living in the tropical region were almost exclusively sensitized to HDM (87%). In the central agricultural zones sensitization is primarily to grass and tree pollen. Nationwide, most study subjects had perennial (82.2%), intermittent (56.5%) and moderate-severe (84.7%) AR. Sensitization was not related to the intermittent-persistent AR classification or to AR severity; seasonal AR was associated with tree (p < 0.05) and grass pollen sensitization (p < 0.01). HDM sensitization was more frequent in children (0-11 y) and adolescents (12-17 y) (subtropical region: p < 0.0005; tropical region p < 0.05), but pollen sensitization becomes more important in the adult patients visiting allergists (Adults vs children + adolescents for tree pollen: p < 0.0001, weeds: p < 0.0005). CONCLUSIONS: In a country with (sub)tropical climate zones SPT sensitization patterns varied according to climatological zones; they were different from those found in Europe, HDM sensitization far outweighing pollen allergies and Bermuda grass and Ash pollen being the main grass and tree allergens, respectively. Pollen sensitization was related to SAR, but no relation between sensitization and intermittent-persistent AR or AR severity could be detected. Sensitization patterns vary with age (child HDM, adult pollen). Clinical implications of our findings are dual: only a few allergens -some region specific- cover the majority of sensitizations in (sub)tropical climate zones. This is of major importance for allergen manufacturers and immunotherapy planning. Secondly, patient selection in clinical trials should be based on the intermittent-persistent and severity classifications, rather than on the seasonal-perennial AR subtypes, especially when conducted in (sub)tropical countries.

In the (sub)tropics allergic rhinitis and its impact on asthma classification of allergic rhinitis is more useful than perennial-seasonal classification.

BACKGROUND: Two different allergic rhinitis (AR) symptom phenotype classifications exist. Treatment recommendations are based on intermittent-persistent (INT-PER) cataloging, but clinical trials still use the former seasonal AR-perennial AR (SAR-PAR) classification. This study was designed to describe how INT-PER, mild-moderate/severe and SAR-PAR of patients seen by allergists are distributed over the different climate zones in a (sub)tropical country and how these phenotypes relate to allergen sensitization patterns. METHODS: Six climate zones throughout Mexico were determined, based on National Geographic Institute (Instituto Nacional de Estadística y Geografía) data. Subsequent AR patients (2-68 years old) underwent a blinded, standardized skin-prick test and filled out a validated questionnaire phenotyping AR. RESULTS: Five hundred twenty-nine subjects participated in this study. In the tropical zone with 87% house-dust mite sensitization, INT (80.9%; p < 0.001) and PAR (91%; p = 0.04) were more frequent than in the subtropics. In the central high-pollen areas, there was less moderate/severe AR (65.5%; p < 0.005). Frequency of comorbid asthma showed a clear north-south gradient, from 25% in the dry north to 59% in the tropics (p < 0.005). No differences exist in AR cataloging among patients with different sensitization patterns, with two minor exceptions (more PER in tree sensitized and more PAR in mold positives; p < 0.05). CONCLUSION: In a (sub)tropical country the SAR-PAR classification seems of limited value and bears poor relation with the INT-PER classification. INT is more frequent in the tropical zone. Because PER has been shown to relate to AR severity, clinical trials should select patients based on INT-PER combined with the severity cataloging because these make for a better treatment guide than SAR-PAR.

[Mexican clinical practice guidelines of immunotherapy 2011]. / Guía Mexicana de Práctica Clínica de Inmunoterapia 2011.

BACKGROUND: Several international guidelines on immunotherapy exist, but they only apply partially in Mexico. The Mexican guideline of immunotherapy dates from 1998. OBJECTIVES: To establish clinical recommendations and suggestions for Allergy residents and specialists for skin testing and allergen immunotherapy based on evidence and Mexican expert opinion, according to the GRADE system. METHODS: The guidelines were developed following the methodology of a guideline for clinical practice starting with the formulation of clinical questions, in the context of Mexican environmental conditions and morbidity, with the participation of allergists from all regions of the country. External validation was obtained. Its development followed three steps: 1. formulation of 24 clinical questions. 2. Search for consensus on the answers among members of the Regional chapters of both Mexican Colleges of Allergists (CMICA and COMPEDIA) during regional meetings. 3. Literature search for articles related to the questions and grading of its quality according to GRADE. RESULTS: Based on the regional consensus, 116 articles and the safety, patient acceptance/ comfort and cost clinical recommendations and suggestions were developed on basic aspects of skin testing, subcutaneous and sublingual immunotherapy (patient preparation, vial preparation and application schedules) and the treatment of eventual adverse reactions. CONCLUSIONS: A clinical guideline was developed respecting particular methodology, validated by CMICA and COMPEDIA for its implementation among Mexican allergists. Several aspects deserve further study to improve scientific evidence. KEYWORDS: Allergen immunotherapy, subcutaneous immunotherapy, sublingual immunotherapy, skin testing, allergy diagnosis, rhinitis, asthma, atopic dermatitis, house dust mite, pollens, anaphylaxis, adrenaline, Mexico.

[Adverse reactions to skin tests and immunotherapy in the practice of Mexican allergologists]. / Reacciones adversas a pruebas cutáneas e inmunoterapia en la práctica de alergó1ogos mexicanos.

BACKGROUND: Immunotherapy is the only curative treatment recommended for allergic rhinoconjunctivitis and asthma, in which small amounts of allergen are administered sublingually or subcutaneously until the maximum tolerated dose has been reached. However, local or systemic adverse reactions (AR) -rarely even fatal- an occur. In Mexico there is no nationwide data on adverse reactions. OBJECTIVE: To document the frequency of adverse reactions secondary to skin tests (ST) or immunotherapy (IT) in the allergist's office in Mexico, paying special attention to fatal and near fatal allergic reactions. PARTICIPANTS AND METHODS: We mailed a survey to all members of the Mexican Colleges of Allergy (CMICA) and Pediatric Allergy (CoMPedIA). RESULTS: A response rate of 59 (16%) for the adverse reactions part of the questionnaire was obtained from the College members. We found a near fatal reaction rate of 0.005 cases per year per allergy practice for skin testing and the same number -0.005 cases- for immunotherapy. This can be extrapolated to a total of 1.5 cases per year in the whole country of Mexico. No fatalities were reported. CONCLUSIONS: In Mexico the frequency of severe or near fatal adverse reactions to immunotherapy or skin tests is low and no fatal case has been reported till today.

New types of immunotherapy in children.

Injection immunotherapy has been shown to be particularly beneficial in treating allergic rhinitis, mild to moderate asthma, and anaphylaxis caused by bee and wasp venom. It also produces a long-term, antigen-specific, protective immune effect and is the only treatment that offers the possibility of reducing the risk of asthma development in children with allergic rhinitis. Nonetheless, the potentially severe side effects associated with this form of immunotherapy limit its widespread use. Diverse preparations are being developed to increase its safety and improve its efficacy. These include alternative routes of administration, particularly the sublingual route; use of novel adjuvants, such as CpG oligonucleotides and mycobacterial vaccines; and other approaches, such as peptide immunotherapy, recombinant allergens, DNA vaccination, and combined therapy. Some of these immunotherapy forms have been evaluated in children.

Frequency of acute systemic reactions in patients with allergic rhinitis and asthma treated with sublingual immunotherapy.

BACKGROUND: Several studies have demonstrated the efficacy and safety of sublingual immunotherapy in the treatment of respiratory allergy. OBJECTIVE: To determine the frequency of systemic adverse reactions in patients treated with standardized extracts of sublingual immunotherapy. METHODS: Allergic patients with rhinitis with or without asthma and sensitized to at least 1 allergen were included. Increasing doses of standardized allergens were administered until reaching an average dose accumulated of 7,200 U after 26 weeks of treatment. Adverse events were graded according to the European Academy of Allergy and Clinical Immunology immunotherapy position paper. RESULTS: Forty-three patients with a median age of 11 years (interquartile range, 8-20 years) were included. All the patients had allergic rhinitis, and 63% had asthma; they were sensitized mostly to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Four patients (9%) presented with an immediate and 1 (2%) with a late systemic reaction. In total, 7 systemic reactions occurred in 23,154 doses, and all were associated with wheezing or worsening of nasal symptoms (grade 2); in addition, 1 patient had angioedema and urticaria (grade 3). CONCLUSIONS: In this group, systemic reaction frequency was 11.6%, and all were classified as grade 2 or 3. Further assessments in larger samples of patients are required in the context of randomized controlled trials.

[Safety of immunotherapy and skin tests with allergens in children younger than five years]. / Inocuidad de la inmunoterapia y pruebas cutáneas con alergenos en niños menores de cinco años de edad.

BACKGROUND: It has been demonstrated that specific immunotherapy, in addition to its preventive properties, is an effective and safe therapeutic resource for allergic asthma, allergic rhinitis and allergy to insect's venom; however, its use in patients younger than five years has been limited due to the risk of systemic reactions. OBJECTIVES: To know the frequency and severity of systemic reactions in children younger than five years and to know if a greater risk of systemic reactions in this group of age is real. PATIENTS AND METHODS: We included 239 patients from one to five years of age with diagnosis of allergic disease and verified its specific sensitivity with skin tests or RAST and were treated with specific immunotherapy. A detailed registry of the application of specific immunotherapy was kept from every patient, with special attention to any symptom present during the first 30 minutes post application of specific immunotherapy or skin test. RESULTS: From January 1996 to June 2005, 6,689 injections were applied to 239 patients. Only one patient of 36 months of age presented with a delayed systemic reactions characterized by generalized hives, itching, runny nose, water eyes, 90 minutes post injection. The patient was under treatment with Dermatophagoides farinae and pteronissinus (house dust mites) with a dose of 1AU for allergic rhinitis. The systemic reactions were treated easily and without complications with a single dose of intramuscular epinephrine (0.15cc, 1:1000) and oral antihistamine. CONCLUSION: Patients younger than five years are not in greater risk of systemic reactions from specific immunotherapy or skin tests than the older children or adults and the treatment of those systemic reactions does not imply greater difficulty. Because of its preventive properties, safety and effectiveness in lowering the severity of symptoms of allergic diseases, we concluded that specific immunotherapy should be considered at early age, prescribed and administered only by specialist in pediatric allergy and in optimal conditions of safety.

[Non-fatal systemic reactions caused by immunotherapy and skin tests]. / Reacciones sistémicas no fatales por inmunoterapia y pruebas cutáneas.

OBJECTIVE: The frequency and severity of systemic reaction (SR) from skin test (ST) and specific immunotherapy (SIT) in Mexico, have not been published before. In order to know that frequency and severity, a prospective study was performed in the Allergy Clinic at General Hospital of Matamoros from August, 1991 to July, 1996. SR from ST and SIT were monitored. Symptoms were recorded with respect to the time of onset, involvement of respiratory tract or skin and presence of hypotension. RESULTS: 65,397 injections were given to 1,149 patients; there were 25 SR in 20 patients (1:2,615 injections or 1:57 patients). Time of onset was between 10 and 30 minutes. SR were present more frequently during maintenance. There was a 3:1 rate in female patients and a predominance in the 15 to 24 age group. CONCLUSIONS: In Matamoros, Tamps., Mexico, frequency and severity of SR from ST and SIT is not different from published data. Small children are not in higher risk. Immunotherapy is a safe therapeutic procedure on expert hands.