IgE-Mediated Hypersensitivity to Lysine Clonixinate

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Olive, grass or both? Molecular diagnosis for the allergen immunotherapy selection in polysensitized pollinic patients.

BACKGROUND: Grass and olive are the most frequently pollens that induce seasonal allergic rhinitis in Spain. Cross-reactivity due to panallergens shared by them and overlapping pollination complicates the recognition of allergy-causing agents, making it difficult to identify the most appropriate allergen immunotherapy (AIT) to use. The aim of this study was to determine the sensitization pattern to major grass and olive pollen allergens using component-resolved diagnostics in patients with seasonal allergic rhinitis (SAR) and positive skin prick test to grass and olive pollens and evaluate how knowledge of the sensitization patterns might influence AIT prescription. METHODS: After informed written consent, a total of 1263 patients were recruited. A serum determination of specific IgE levels to Ole e 1 and Phl p 1 + 5 was performed to all patients. A comparison was made before and after obtaining the specific IgE results, and differences in diagnosis were stated. RESULTS: At the 0.35 kU/l cut-off point, 71.2% of patients were positive to Ole e 1 and Phl p 1 + 5, 14% were positive only to Phl p 1 + 5 and 12% were positive only to Ole e 1. Based on available clinical data and skin prick test results, 922 (73%) patients would have been indicated for a mixture of grass and olive pollens for AIT. In 56.8% of patients, there was non-coincidence in the composition of AIT that would be selected before and after investigators received the in vitro data. CONCLUSION: The diagnostic accuracy of the recombinant allergen-specific IgE test could help to improve the selection of specific-allergen immunotherapy in polysensitized patients.

New pets, new allergies

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Letter to the editor

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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.

Pharmacological stimuli in asthma/urticaria / Estimulos farmacológicos en el asma/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

Introducción: Como fármacos analgésicos, cada vez está más extendido el uso de opiáceos y éstos pueden tener repercusiones sobre pacientes con urticaria o asma. La mayoría de las veces la causa es un efecto secundario. Material y Métodos: Presentamos dos pacientes que han tenido una urticaria tras la toma de codeína y otra paciente asmática que está recibiendo inmunoterapia y tiene crisis de broncoespasmo tras la toma de éste fármaco. Se realizan prick-test e IDR con varios opiáceos, y tras esto se realiza exposición oral controlada. También se realizan pricks e IDR a 20 controles. Resultados: En los tres casos y en los controles se obtienen resultados similares de los pricks y de las IDR. En la exposición oral controlada con codeína, la paciente 1 sufre un broncoespasmo, la 2 una urticaria generalizada y la 3 no se realiza. Las tres toleran tramadol 50mg sin problemas. Se recomienda el uso de tramadol como analgésico y fentanilo o remifentanilo como anestésicos. Discusión: En este tipo de cuadros las propiedades farmacológicas de los opiáceos son muy importantes, puesto que van a venir marcados por la potencia de liberación de histamina. La codeína, la morfina y la petidina, son los mayores liberadores y por el contrario, el tramadol, el fentanilo y el remifentanilo no lo son y están recomendados en patología pulmonar que necesiten opiáceos. Los opiáceos suelen producir en mayor número de ocasiones cuadros cutáneos por que actúan sobre todo sobre los MTC que son más numerosos en la piel que en el pulmón. La Naloxona inhibe en parte ésta acción. Conclusiones: La mayoría de reacciones de este tipo no son IgE mediadas, por lo que los pricks e IDR no tienen ningún valor, y se debe de recurrir a la exposición controlada con el fármaco implicado o con uno de los no liberadores de histamina. Las pruebas del parche si que tienen utilidad en las dermatitis de contacto ocupacionales

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

A prospective safety study of allergen immunotherapy in daily clinical practice.

BACKGROUND: Despite its clinical effectiveness, allergen immunotherapy (AIT) remains controversial because serious systemic reactions can occur during its administration. Most of the studies on the safety of AIT are retrospective and use different methods, which frequently depart from daily clinical practice. OBJECTIVE: The aim of this study was to determine risk factors for adverse reactions, especially systemic adverse reactions, produced during routine AIT administration. METHODS: We registered 5,768 consecutive doses of standardized extracts administered to 273 patients in conventional schedules, following the recommendations on safety and data collection of the European Academy of Allergology and Clinical Immunology. Of the 273 patients, 236 were asthmatics, 28 had rhinitis and 9 received immunotherapy due to Hymenoptera anaphylaxis. RESULTS: We examined 143 local reactions (2.48 % of the doses) and 145 systemic reactions (78 immediate and 67 delayed). Risk factors for developing an immediate systemic reaction were asthma severity, sensitization to molds, the most concentrated vials and a fall in peak expiratory flow of more than 15 % or an immediate systemic reaction in the previous dose. Late systemic reactions were significantly more frequent with less concentrated vials and in patients with late local reactions in the previous dose. No serious reactions were registered. CONCLUSIONS: We believe that AIT is reliable when used with strict safety protocols and administered by specialized staff. Risk factors for adverse reactions to this type of treatment can be identified and reduced by systematic data collection.

A prospective safety study of allergen immunotherapy in daily clinical practice

Background: Despite its clinical effectiveness, allergen immunotherapy (AIT) remains controversial because serious systemic reactions can occur during its administration. Most of the studies on the safety of AIT are retrospective and use different methods, which frequently depart from daily clinical practice. Objective: The aim of this study was to determine risk factors for adverse reactions, especially systemic adverse reactions, produced during routine AIT administration. Methods: We registered 5,768 consecutive doses of standardized extracts administered to 273 patients in conventional schedules, following the recommendations on safety and data collection of the European Academy of Allergology and Clinical Immunology. Of the 273 patients, 236 were asthmatics, 28 had rhinitis and 9 received immunotherapy due to Hymenoptera anaphylaxis. Results: We examined 143 local reactions (2.48 % of the doses) and 145 systemic reactions (78 immediate and 67 delayed). Risk factors for developing an immediate systemic reaction were asthma severity, sensitization to molds, the most concentrated vials and a fall in peak expiratory flow of more than 15 % or an immediate systemic reaction in the previous dose. Late systemic reactions were significantly more frequent with less concentrated vials and in patients with late local reactions in the previous dose. No serious reactions were registered. Conclusions: We believe that AIT is reliable when used with strict safety protocols and administered by specialized staff. Risk factors for adverse reactions to this type of treatment can be identified and reduced by systematic data collection (AU)

Antecedentes: La inmunoterapia con alergenos es aún controvertida para algunos grupos, a pesar de su eficacia clínica, porque puede provocar reacciones sistémicas graves durante su administración. La mayoría de estudios sobre la seguridad de la inmunoterapia con alergenos son retrospectivos y emplean diferentes metodologías, muchas veces apartados de la realidad clínica diaria. Objetivos: El ánimo de este estudio fue conocer los factores de riesgo de las reacciones adversas, especialmente sistémicas, producidas durante la administración rutinaria de inmunoterapia. Métodos: Registramos 5.768 dosis consecutivas de extractos estandarizados administrados a 273 pa- cientes con pautas convencionales, siguiendo las recomendaciones de seguridad y recogida de datos de la EAACI (European Academy of Allergology and Clinical Immunology). De todos los pacientes 236 eran asmáticos, 28 riníticos y 9 recibieron inmunoterapia por anafilaxia por Himenópteros. Resultados: Registramos 143 reacciones locales (2,48 por ciento de las dosis), y 145 reacciones sistémicas (78 inmediatas y 67 tardías). Encontramos como factores de riesgo para el desarrollo de reacciones inmediatas sistémicas: la gravedad del asma, la sensibilización a hongos, los viales mas concentrados, la caída del PEF superior al 15 por ciento en la dosis previa y la presencia de otra reacción sistémica inmediata en la dosis anterior. Las reacciones sistémicas tardías fueron significativamente mas frecuentes con los viales menos concentrados y en los pacientes con reacciones locales tardías en la dosis previa. No se produjo ninguna reacción grave. Conclusiones: Creemos que la IT es segura cuando se emplean protocolos de seguridad estrictos y es administrada por personal especializado. La recogida sistemática de datos permite conocer y reducir los factores de riesgo relacionados con las reacciones adversas a este tipo de tratamiento (AU)

[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.

Angioedema hereditario de comienzo tardío / Hereditary angioedema of delayed onset

El angioedema hereditario es una patología caracterizada por episodios repetidos de edema que afecta a la piel y a mucosas de vías respiratorias superiores y del tubo digestivo, debido a un déficit o disfunción del inhibidor de la C1 esterasa. Tiene un carácter hereditario con una herencia autosómica dominante con penetración variable. Presentamos un paciente de 56 años con episodios leves de edema, de reciente comienzo, en diferentes localizaciones como antebrazos, testículos y palmas de manos. Tras el estudio se objetiva una disminución de los valores de C4, C1 inhibidor y C1 inhibidor funcional, diagnosticándole de angioedema hereditario, haciéndose obligatorio realizar un estudio familiar (AU)