[Guidelines on atopic dermatitis for Mexico (GUIDAMEX): using the ADAPTE methodology]. / Guía de dermatitis atópica para México (GUIDAMEX): lineamientos usando metodología ADAPTE.

With the advancement of knowledge in relation to the physiopathogenesis of atopic dermatitis (AD), several new therapeutic forms have been developed. There are also new guidelines for self-care. On the other hand, there is still an underdiagnosis of AD in Mexico. Thus, the need was seen to develop a national guide, with a broad base among the different medical groups that care for patients with AD. The Atopic Dermatitis Guidelines for Mexico (GUIDAMEX) was developed with the ADAPTE methodology, with the endorsement and participation of ten national medical societies, from physicians in Primary Healthcare to allergists and dermatologists. Throughout the manuscript, key clinical questions are answered that lead to recommendations and suggestions for the diagnosis of AD (including differential diagnosis with immunodeficiency syndromes), the recognition of comorbidities and complications, non-pharmacological treatment including therapeutic education, treatment of flares and maintenance therapy. The latter encompasses general measures to avoid triggering factors, first-line treatment focussed on repair of the skin barrier, second-line treatment (topical proactive therapy), and third-line phototherapy or systemic treatment, including dupilumab and JAK inhibitors.

Con el avance de los conocimientos en relación con la fisiopatogenia de la dermatitis atópica (DA) se han desarrollado varias formas terapéuticas nuevas. Asimismo, existen nuevos lineamientos para el autocuidado. Por otro lado, aún existe un subdiagnóstico de la DA en México. Así, se vio la necesidad de desarrollar una guía nacional, con base amplia entre las diferentes agrupaciones médicos que atienden pacientes con DA. Se desarrolló la Guía de DA para México (GUIDAMEX) con la metodología ADAPTE, con el aval y la participación de diez sociedades médicas nacionales, desde médicos del primer contacto hasta alergólogos y dermatólogos. A lo largo del escrito se contestan preguntas clínicas clave que llevan a recomendaciones y sugerencias para el diagnóstico de la DA (incluyendo diagnóstico diferencial con síndromes de inmunodeficiencia), el reconocer de las comorbilidades y complicaciones, las medidas generales (tratamiento no farmacológico) incluyendo la educación terapéutica, el tratamiento de los brotes y el tratamiento de mantenimiento. Este último abarca las medidas generales de evitar agravantes, el tratamiento de primera línea reparador de la barrera cutánea, de segunda línea (manejo proactivo tópico), hasta la fototerapia y el tratamiento sistémico de la tercera línea, incluyendo dupilumab y los inhibidores de la cinasa de Jano.

Global Variability in Administrative Approval Prescription Criteria for Biologic Therapy in Severe Asthma.

BACKGROUND: Regulatory bodies have approved five biologics for severe asthma. However, regional differences in accessibility may limit the global potential for personalized medicine. OBJECTIVE: To compare global differences in ease of access to biologics. METHODS: In April 2021, national prescription criteria for omalizumab, mepolizumab, reslizumab, benralizumab, and dupilumab were reviewed by severe asthma experts collaborating in the International Severe Asthma Registry. Outcomes (per country, per biologic) were (1) country-specific prescription criteria and (2) development of the Biologic Accessibility Score (BACS). The BACS composite score incorporates 10 prescription criteria, each with a maximum score of 10 points. Referenced to European Medicines Agency marketing authorization specifications, a higher score reflects easier access. RESULTS: Biologic prescription criteria differed substantially across 28 countries from five continents. Blood eosinophil count thresholds (usually ≥300 cells/µL) and exacerbations were key requirements for anti-IgE/anti-IL-5/5R prescriptions in around 80% of licensed countries. Most countries (40% for dupilumab to 54% for mepolizumab) require two or more moderate or severe exacerbations, whereas numbers ranged from none to four. Moreover, 0% (for reslizumab) to 21% (for omalizumab) of countries required long-term oral corticosteroid use. The BACS highlighted marked between-country differences in ease of access. For omalizumab, mepolizumab, benralizumab, and dupilumab, only two, one, four, and seven countries, respectively, scored equal or higher than the European Medicines Agency reference BACS. For reslizumab, all countries scored lower. CONCLUSIONS: Although some differences were expected in country-specific biologic prescription criteria and ease of access, the substantial differences found in the current study present a challenge to implementing precision medicine across the world.

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.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

[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.

Elevated oxytocin and noradrenaline indicate higher stress levels in allergic rhinitis patients: Implications for the skin prick diagnosis in a pilot study.

BACKGROUND & AIMS: The effects of acute stress on allergic symptoms are little understood. The intention of this clinical study was to study the effects of acute stress and related mediators in allergic rhinitis (AR), taking the wheal and flare reaction in skin prick testing (SPT) as a readout. METHODS: 19 healthy and 21 AR patients were first subjected to SPTs with grass pollen-, birch pollen- and house dust mite allergen extracts, histamine and negative control. Subsequently, participants were exposed to a standardized Trier Social Stress Test (TSST), followed by SPT on the contralateral forearm. Stress responders were identified based on the salivary cortisol levels and State-subscale of State-Trait-Anxiety Inventory (STAI-S). Blood samples were collected before and after TSST and adrenaline, noradrenaline, serotonin, oxytocin, platelet activating factor and prostaglandin D2 were analyzed by enzyme immunoassay (EIA). RESULTS: SPT results of 14/21 allergics and 11/19 healthy who responded with stress after TSST were evaluated. No significant differences regarding SPT to allergens or histamine before and after the stress test could be calculated at the group level. But, the wheal and flare sizes after TSST increased or decreased substantially in several individuals, and unmasked sensitization in one "healthy" person, which could not be correlated with any mediator tested. The most significant finding, however, was that, independent of TSST, the baseline levels of oxytocin and noradrenaline were significantly higher in allergics. CONCLUSION: High baseline levels of noradrenaline points toward higher stress levels in allergic patients, which might be counterregulated by elevated oxytocin. Moreover, our data indicate that acute stress may have a significant influence on SPT fidelity in susceptible individuals.

International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis.

BACKGROUND: Critical examination of the quality and validity of available allergic rhinitis (AR) literature is necessary to improve understanding and to appropriately translate this knowledge to clinical care of the AR patient. To evaluate the existing AR literature, international multidisciplinary experts with an interest in AR have produced the International Consensus statement on Allergy and Rhinology: Allergic Rhinitis (ICAR:AR). METHODS: Using previously described methodology, specific topics were developed relating to AR. Each topic was assigned a literature review, evidence-based review (EBR), or evidence-based review with recommendations (EBRR) format as dictated by available evidence and purpose within the ICAR:AR document. Following iterative reviews of each topic, the ICAR:AR document was synthesized and reviewed by all authors for consensus. RESULTS: The ICAR:AR document addresses over 100 individual topics related to AR, including diagnosis, pathophysiology, epidemiology, disease burden, risk factors for the development of AR, allergy testing modalities, treatment, and other conditions/comorbidities associated with AR. CONCLUSION: This critical review of the AR literature has identified several strengths; providers can be confident that treatment decisions are supported by rigorous studies. However, there are also substantial gaps in the AR literature. These knowledge gaps should be viewed as opportunities for improvement, as often the things that we teach and the medicine that we practice are not based on the best quality evidence. This document aims to highlight the strengths and weaknesses of the AR literature to identify areas for future AR research and improved understanding.

Dosing of European sublingual immunotherapy maintenance solutions relative to monthly recommended dosing of subcutaneous immunotherapy.

BACKGROUND: Recently, a series of assays has been conducted in which sublingual immunotherapy (SLIT) maintenance extracts of European manufacturers were compared with U.S. concentrated extracts by using U.S. Food and Drug Administration recommended in vitro testing. These test results have been published. We herein performed further data analysis to facilitate interpretation of SLIT dosing by U.S. physicians. OBJECTIVE: To express the allergen quantity of maintenance SLIT as recommended by European manufacturers relative to U.S. subcutaneous immunotherapy (SCIT) maintenance dosing. METHODS: We analyzed the maintenance SLIT solutions of Dermatophagoides pteronyssinus, timothy grass pollen, cat, and ragweed pollen from four European manufacturers and concentrated extracts from three U.S. manufacturers and from the U.S. Food and Drug Administration. Here, we expressed the potency of these European SLIT solutions in U.S. terms and from there calculated the monthly maintenance dose relative to the recommended monthly SCIT doses per allergen. RESULTS: Over the whole range of allergen extracts analyzed here, one of the manufacturers consistently dosed low ("EUR1," monthly SLIT dose 1-5 times the SCIT dose) and one of the manufacturers dosed high ("EUR4," monthly SLIT dose 16-237 times the SCIT dose). DISCUSSION: For more than half of the products, SLIT was not "high dose" as has originally been recommended. When reviewing the low- and high-dose products with respect to efficacy in clinical trials included in a meta-analysis on SLIT, some low-dose extracts showed efficacy. Thus, apart from the allergen dose, it might very well be possible that other factors also play an important role in determining clinical efficacy in SLIT.

Will sublingual immunotherapy offer benefit for asthma?

Evidence shows that sublingual immunotherapy (SLIT) is indicated in patients with allergic rhinitis (AR). In this article we discuss whether SLIT could offer benefit for children and adults with asthma.We reviewed individual trials on SLIT in asthmatic patients, but also asthma data reported in some SLIT trials conducted in AR patients. Findings were complemented with data from systematic reviews and metaanalysis on the subject since 2000 and some guidelines that mention immunotherapy for asthma treatment. In AR patients with concomitant persistent asthma, SLIT reduces medication needs while maintaining symptom control. This holds especially true for house dust mite SLIT. Data on pollen SLIT and lung symptom improvement with SLIT, however, are less convincing. Therefore, we suggest SLIT should be added as an optional add-on therapy for patients with asthma whenever a causative allergen has been demonstrated and AR is associated with asthma. For the future, SLIT should be studied in specifically designed asthma studies in allergic asthmatics without AR.

European and Mexican vs US diagnostic extracts of Bermuda grass and cat in skin testing.

BACKGROUND: Laboratory testing of various diagnostic extracts has shown lower potencies for several European and Mexican extracts relative to the US Food and Drug Administration (FDA) reference (10,000 BAU/mL). Quantitative skin prick testing (QSPT) with Dermatophagoides pteronyssinus extracts have previously shown a similar picture. OBJECTIVE: To compare European and Mexican Bermuda grass (BG) and cat diagnostic extracts against an FDA-validated extract using QSPT. METHODS: Six diagnostic BG and cat extracts (1 reference FDA extract, 3 European extracts, 1 imported nonstandardized extract from the United States, and 1 Mexican extract) were tested with quadruplicate QSPT, as a concentrate and as 2 serial 2-fold dilutions, in cat and BG allergic individuals. RESULTS: BG showed good dose response in wheal size for the concentrate (1:2-1:4 dilutions; steep part of the curve). Cat showed poorer dose response. The Wilcoxon test for linked random samples was used to investigate whether the distribution of the reference differed from each of the test extracts to a statistically significant degree (2-sided asymptotic significance, α = .05). All BG and 2 cat extracts were statistically less potent than the 10,000 BAU/mL US reference. European BG extracts were 7,700, 4,100, and 1,600 BAU/mL, and cat extracts were 12,500, 4,400, and 5,100 BAU/mL. CONCLUSIONS: The potency of some diagnostic extracts of BG and cat used in Europe, Mexico, and the United States differs, with the US extracts being generally more potent. On the basis of provocation tests, optimal diagnostic concentrations should be determined. Similar comparisons using other manufacturers and therapeutic extracts might be interesting.

Oralair Birch, a recombinant major birch pollen allergen tablet for sublingual immunotherapy of allergic rhinitis caused by birch pollen.

Oralair Birch is a dissolving tablet being developed for sublingual immunotherapy (SLIT) of allergic rhinitis caused by birch pollen allergy. Oralair Birch is being developed by Stallergenes SA and Canadian licensee Paladin Labs Inc. Oralair Birch is a recombinant protein that is synthesized from the DNA coding region of Bet v 1a, the major birch pollen allergen. During preclinical characterization, Oralair Birch had comparable structural and biological properties to the natural Bet v 1 allergen. However, Oralair Birch was more homologous than the natural Bet v 1 allergen, making a greater level of quality control possible. The administration of SLIT in tablet formulation provides a more uniform dose compared with liquid drops and better local application, which might enhance local uptake into dendritic cells of the sublingual submucosa and efficacy. Using skin prick testing, the performance of recombinant Bet v 1 was comparable to the natural Bet v 1 allergen. The results of a dose-finding phase IIb/III clinical trial of Oralair Birch were positive, with the primary endpoint met by all three tested doses. A confirmatory phase III trial was planned for 2011. Oralair Birch is a very promising treatment option for patients with birch pollen allergic rhinitis.

[Allergens used in skin tests in Mexico]. / AIérgenos usados en las pruebas cutáneas en México.

BACKGROUND: Immunotherapy is the only recognized causal treatment for allergies. It is prepared on an individual basis, based on the patient's clinical history and the result of the skin prick test (SPT). An adequate composition of the allergens with which to test the patient is crucial for an optimal diagnosis. OBJECTIVE: To know allergens used in tests in allergy practices in Mexico. MATERIALS AND METHOD: A national survey among all members of the Colegio Mexicano de Inmunología Clínica y Alergia (CMICA) and of the Colegio Mexicano de Pediatras Especialistas en Inmunología Clínica y Alergia (COMPEDIA) was carried out. In a second phase respondents were asked to send in the composition of a routine SPT in their clinic. The results are presented descriptively and the frequency is calculated by which certain allergen is tested in the interviewed practices. RESULTS: A survey response rate of 61 (17%) was obtained and 54% showed their SPT content. Weeds' representation in the SPT seems adequate; Atriplex is tested in all allergy practices. Some trees that show cross-reactivity might be eliminated from the SPT, but 20% doesn't test for Cynodon nor Holcus, and 25% doesn't for important allergens as cat, dog and cockroach. House dust and tobacco are still tested with certain frequency. CONCLUSIONS: The selection of which allergens to test in a SPT is based on multiple data, that change continuously with new investigations and discoveries. Our specialty is the most indicated--and obligated--to adjust constantly to these changes to have the best diagnostic tool to detect specific allergies.

European allergen extract units and potency: review of available information.

BACKGROUND: There is considerable variability in how allergen extract potency is measured and reported worldwide. In Europe, where many sublingual immunotherapy studies have been conducted, manufacturers report allergen extract potency as units based on an in-house reference, making it difficult to understand the exact doses used and to compare studies. OBJECTIVES: To describe the various methods of expressing extract potency that European allergen extract manufacturers use and to gather reports on the micrograms of major allergen of the in-house units of European allergen extract manufacturers. METHODS: Information was derived from 3 sources: data on extract potency in micrograms of major allergen in articles on sublingual immunotherapy found by PubMed (references through October 2005) and in reference articles, brochures on allergen extracts from the manufacturers, and information provided by structured questionnaires e-mailed to the manufacturers. RESULTS: All but 1 of the European allergen extract manufacturers use in-house reference standards that are based on titrated skin prick testing of allergic patients. Subsequently, in vitro tests compare the potency of commercial batches with the in-house reference and potency is assigned as arbitrary units. Most manufacturers measure major allergen content of their standardized products but do not release this information with the package insert. Diversity in major allergen content was found. CONCLUSIONS: Micrograms of major allergens given in articles on sublingual immunotherapy to express the dose administered cannot be used to translate the dose to US extracts. Extract potency can only be compared if uniform test methods and reference extracts are used.