Transcriptomics reveals a distinct metabolic profile in T cells from severe allergic asthmatic patients.

The reasons behind the onset and continuation of chronic inflammation in individuals with severe allergies are still not understood. Earlier findings indicated that there is a connection between severe allergic inflammation, systemic metabolic alterations and impairment of regulatory functions. Here, we aimed to identify transcriptomic alterations in T cells associated with the degree of severity in allergic asthmatic patients. T cells were isolated from severe (n = 7) and mild (n = 9) allergic asthmatic patients, and control (non-allergic, non-asthmatic healthy) subjects (n = 8) to perform RNA analysis by Affymetrix gene expression. Compromised biological pathways in the severe phenotype were identified using significant transcripts. T cells' transcriptome of severe allergic asthmatic patients was distinct from that of mild and control subjects. A higher count of differentially expressed genes (DEGs) was observed in the group of individuals with severe allergic asthma vs. control (4,924 genes) and vs. mild (4,232 genes) groups. Mild group also had 1,102 DEGs vs. controls. Pathway analysis revealed alterations in metabolism and immune response in the severe phenotype. Severe allergic asthmatic patients presented downregulation in genes related to oxidative phosphorylation, fatty acid oxidation and glycolysis together with increased expression of genes coding inflammatory cytokines (e.g. IL-19, IL-23A and IL-31). Moreover, the downregulation of genes involved in TGFß pathway together with a decreased tendency on the percentage of T regulatory cell (CD4 + CD25+), suggest a compromised regulatory function in severe allergic asthmatic patients. This study demonstrates a transcriptional downregulation of metabolic and cell signalling pathways in T cells of severe allergic asthmatic patients associated with diminished regulatory T cell function. These findings support a link between energy metabolism of T cells and allergic asthmatic inflammation.

Quality Standards for Allergen Immunotherapy Clinics in Spain: Consensus Document.

BACKGROUND AND OBJECTIVE: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. Objective: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology.

Quality standards for allergen immunotherapy clinics in Spain: consensus document

BACKGROUND: Allergen immunotherapy clinics (AITCs) in Spain differ widely in terms of structure, organization, resources, and portfolio of services. Therefore, it is essential to unify treatment criteria and define quality standards for the most complex AITCs. OBJECTIVE: To establish a series of recommendations that make it possible to guarantee quality and safety in the administration of immunotherapy and define quality standards for the most complex AITCs. METHODS: This project began with an online survey of 65 allergy departments/units throughout Spain in 2013. Next, a 2-phase consensus process was carried out. In the first phase, 10 experts defined and agreed on the standards using the RAND/UCLA Appropriateness method; in the second, the agreements were validated by means of a 2-round Delphi consultation with 84 experts. RESULTS: Consensus was reached on minimum safety and quality criteria in the administration of allergen immunotherapy, and 2 levels of highly complex AITCs were defined: accredited AITCs and accredited AITCs with excellence. Consensus was also reached on quality standards and accreditation criteria for both levels. CONCLUSIONS: This project is pioneering in terms of its purpose (the definition of quality standards for AITCs) and of the use of structured participation techniques (combination of the RAND/UCLA and Delphi methods). It enabled the design of minimum standards for quality and safety in administering AIT, as well as quality criteria for accreditation of AITCs supported by a broad panel of experts from the Spanish Society of Allergology and Clinical Immunology

ANTECEDENTES: Las unidades de inmunoterapia (UIT) en España son muy diferentes en cuanto a estructura, organización, recursos y cartera de servicios. Por ello, resulta esencial homogeneizar criterios de actuación y definir estándares de calidad para las UIT de mayor complejidad. OBJETIVO: Establecer recomendaciones que permitan garantizar la calidad y seguridad en la administración de la inmunoterapia y definir estándares de calidad para las UIT de mayor complejidad. MÉTODOS: Proyecto iniciado (año 2013) con una encuesta on-line a 65 servicios o unidades de alergología de toda España. Posteriormente, se desarrolló un proceso de consenso en dos fases. En la primera, diez expertos definieron y consensuaron los estándares mediante el método RAND/UCLA; en la segunda, los acuerdos se validaron mediante una consulta Delphi a dos rondas con 84 expertos. RESULTADOS: Se consensuaron criterios mínimos de seguridad y calidad en la administración de inmunoterapia con alérgenos (ITA) y se definieron dos niveles de UIT de mayor complejidad: las UIT acreditadas (UITA) y las UIT acreditadas con excelencia (UITAE), consensuándose también los estándares de calidad y criterios de acreditación para ambos niveles. CONCLUSIONES: Proyecto pionero en su objetivo - definición de estándares de calidad de UIT- y en el empleo de técnicas de participación estructuradas -combinación de los métodos RAND/UCLA y Delphi-. El resultado es la definición de unos mínimos de calidad y seguridad para administrar ITA, y un conjunto de criterios de calidad para la acreditación de las UIT que cuenta con el respaldo de un amplio panel de expertos de la SEAIC

New pets, new allergies

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Urticaria due to antihistamines.

H1-antihistamines are probably the most frequently used drugs in allergic diseases, with widely established efficacy, tolerance, and safety. We report a patient with urticaria due to ingestion of ebastine and fexofenadine. Skin prick tests, patch tests, and basophil activation tests with the implicated drugs and antihistamines from other families were negative. The oral challenges with the implicated antihistamines and other antihistamines tested were positive, but the patient tolerated an oral challenge with cetirizine. We present a patient with urticaria induced by different antihistamines in whom the diagnosis was established by oral challenge. The mechanism of sensitization remains unclear.

Systemic anaphylaxis caused by moxifloxacin

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Systemic dermatitis due to tetrazepam.

Cutaneous adverse reactions to benzodiazepines seem to be rare. We report a 61-year-old man with adverse reactions after ingestion of metamizole, diclofenac, and tetrazepam. Skin prick tests with metamizole, diclofenac, and tetrazepam were negative. Patch tests with metamizole, diclofenac, and tetrazepam (all at 5% in aqueous solution) were performed, and were positive for tetrazepam. Oral challenge was performed with metamizole, acetylsalicylic acid, diclofenac, and tetrazepam with a positive result for diclofenac and tetrazepam. The patient tolerated other benzodiazepines. We present a patient who can tolerate diazepam but who had a type IV hypersensitivity reaction to tetrazepam confirmed by patch testing and oral challenge. The patient also presented an immediate hypersensitivity reaction after taking diclofenac.

Pharmacological stimuli in asthma/urticaria.

BACKGROUND: The use of opioids as analgesics is becoming increasingly widespread, which may have repercussions in patients with urticaria or asthma, as these agents frequently cause adverse reactions. MATERIAL AND METHODS: We present three patients who developed allergic reactions after receiving codeine: two patients who developed acute urticaria, and a third asthmatic patient receiving specific immunotherapy who developed bronchospasm. Skin prick-testing (SPT) and intradermal reaction (IDR) tests with various opioids were performed, followed by controlled oral challenge. Prick tests and IDR were also carried out in 20 controls. RESULTS: Similar SPT and IDR results were recorded in the three patients and in the controls. In the case of controlled oral challenge with codeine, patient 1 suffered bronchospasm, while patient 2 developed generalized urticaria. The test was not performed in the third patient. All of the patients tolerated tramadol 50 mg without problems. We advised the use of tramadol as analgesic and fentanyl or remifentanil as anesthetics. DISCUSSION: In these types of manifestation, the pharmacological properties of the opioids used are highly important, particularly as regards their histamine-releasing potential. Codeine, morphine and pethidine present the greatest histamine-releasing capacity, while tramadol, fentanyl and remifentanil do not release histamine and their use is thus recommended in pulmonary disease requiring opioid administration. Cutaneous symptoms are more frequently caused by opioids than by respiratory symptoms, since these drugs act on the MTC mast cell population, which is more prevalent in the skin than in the lungs. Some of this action is inhibited by naloxone. CONCLUSIONS: In most patients, these reactions are not IgE-mediated. Consequently, SPT and IDR are of little diagnostic value, and controlled oral challenging with the suspect drug or with one of the non-histamine releasing agents should be used. The patch test is useful in occupational contact dermatitis.

Vasculitis during immunotherapy treatment in a patient with allergy to Cupressus arizonica.

UNLABELLED: Allergen immunotherapy dates back to 1911 and has been used successfully to treat large numbers of patients throughout the last century. CASE REPORT: a 66-year-old woman presented with symptoms of allergic rhinitis and asthma due to sensitization to Cupressus arizonica. Specific immunotherapy was prescribed as a continuous 2-year treatment with a depot preparation of standarized and characterized allergen extracts of Cupressus arizonica pollen. Forty-eight hours after one maintenance dose of 0.8 cc, the patient presented palpable violaceous purpuric lesions and pruritus on both legs. We performed skin prick and intradermal tests with Cupressus arizonica. Twenty-four hours later, the 1/1 dilution intradermal skin test was positive. Biopsy showed leukocytoclastic vasculitis. CONCLUSIONS: A middle-aged woman experienced cutaneous non-necrotizing vasculitis after 2 years of maintenance immunotherapy. The interval between injections and the first appearance of cutaneous lesions suggests a type III hypersensitivity immune reaction. Skin biopsy of the positive intradermal test also supports this hypothesis.

Vasculitis during immunotherapy treatment in a patient with allergy to Cupressus arizonica

Allergen immunotherapy dates back to 1911 and has been used successfully to treat large numbers of patients throughout the last century. Case report: a 66-year-old woman presented with symptoms of allergic rhinitis and asthma due to sensitization to Cupressus arizonica. Specific immunotherapy was prescribed as a continuous 2-year treatment with a depot preparation of standarized and characterized allergen extracts of Cupressus arizonica pollen. Forty-eight hours after one maintenance dose of 0.8 cc, the patient presented palpable violaceous purpuric lesions and pruritus on both legs. We performed skin prick and intradermal tests with Cupressus arizonica. Twenty-four hours later, the 1/1 dilution intradermal skin test was positive. Biopsy showed leukocytoclastic vasculitis. Conclusions: A middle-aged woman experienced cutaneous non-necrotizing vasculitis after 2 years of maintenance immunotherapy. The interval between injections and the first appearance of cutaneous lesions suggests a type III hypersensitivity immune reaction. Skin biopsy of the positive intradermal test also supports this hypothesis

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[Safety of rush immunotherapy with Hymenoptera venom]. / Seguridad de la inmunoterapia con una pauta rápida con veneno de himenópteros.

OBJECTIVES: To determine the incidence and nature of adverse events associated with the induction of rush Hymenoptera venom immunotherapy. MATERIAL AND METHODS: Between 1998 and 2003, we administered venom immunotherapy to 48 patients allergic to bee or wasp venom, by means of a rush immunotherapy protocol (3 days). RESULTS: We observed no severe adverse reactions in any patients. 12 patients developed only local reactions at the site of injections that did not required any pharmacological treatment. Two patients experienced mild systemic reactions consisting of diffuse urticaria on day 3. Both adverse reactions were treated with intravenous antihistamines. CONCLUSIONS: Our experience confirms that rapid venom immunotherapy is safe and should be considered in every case especially for patients during the stinging insect season when a rapid protection is required.

Seguridad de la inmunoterapia con una pauta rápida con veneno de himenópteros / Safety of rush immunotherapy with hymenoptera venom

Objetivos: El estudio pretende determinar la incidencia de reacciones adversas asociada a la administración de inmunoterapia con veneno de himenópteros mediante una pauta de iniciación rápida. Material y métodos: Entre 1998 y 2003 realizamos un estudio, consistente en administrar a 48 pacientes tratamiento hiposensibilizante con veneno de avispa o abeja utilizando un protocolo diseñado por nosotros con una pauta rápida (3 días). Resultados: No obtuvimos reacciones adversas graves en ninguno de los pacientes. Dos de los 48 pacientes presentaron reacciones sistémicas leves (urticaria) al tercer día del tratamiento. Ambos pacientes fueron tratados con antihistamínicos intravenosos. Doce de los pacientes presentaron reacciones locales en el lugar de la inyección. Conclusión: El estudio confirma que la pauta rápida empleada es segura y podría ser de elección en pacientes donde fuera necesario conseguir una protección rápida

Objetives: To determine the incidence and nature of adverse events associated with the induction of rush Hymenoptera venom immunotherapy. Material and methods: Between 1998 and 2003, we administered venom immunotherapy to 48 patients allergic to bee or wasp venom, by means of a rush immunotherapy protocol (3 days). Results: We observed no severe adverse reactions in any patients. 12 patients developed only local reactions at the site of injections that did not required any pharmacological treatment. Two patients experienced mild systemic reactions consisting of diffuse urticaria on day 3. Both adverse reactions were treated with intravenous antihistamines. Conclussions: Our experience confirms that rapid venom immunotherapy is safe and should be considered in every case especially for patients during the stinging insect season when a rapid protection is required

[Hereditary angioedema of delayed onset]. / Angioedema hereditario de comienzo tardío.

Hereditary angioedema is a disorder characterized by episodes of angioedema of the skin, respiratory and gastrointestinal tract resulting from a defect in the C1 esterase inhibitor. The disease is hereditary. Inheritance is autosomal dominant with incomplete penetration. We report a 56-year-old man with edema in different locations as forearm, testicles and palms. It started recently. The study showed low levels of C4, and C1 inhibitor. He was diagnosed of hereditary angioedema and it was necessary the family study.