Usefulness of omalizumab in rapid drug desensitization in patients with severe anaphylaxis induced by carboplatin: open questions

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Drug-induced enterocolitis syndrome due to amoxicillin-clavulanic acid with good tolerance to penicillin

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Specific allergen immunotherapy for the treatment of allergic asthma: a review of current evidence.

Asthma is frequently associated with atopy, characterized by the production of specific immunoglobulin E in response to environmental allergens. Currently, two types of allergen immunotherapy (AIT) are used in clinical practice: subcutaneous and sublingual immunotherapy, both accepted as key components of the therapeutic repertoire for allergic rhinitis and conjunctivitis. However, their role in asthma remains controversial. The present document is aimed at providing the clinicians with a review of the evidence on the use of AIT in asthma, focusing on the most relevant aspects of its mechanism of action, its efficacy, and existing data on safety, tolerability, and cost-effectivity, both in pediatric and adult populations. A systematic search of MEDLINE, Cochrane, and Clinical Trials databases from 2000 to April of 2016 was carried out by a panel of experts from the Spanish Allergy and Clinical Immunology Scientific Society. Relevant studies prior to the year 2000 included in ulterior systematic reviews were also considered. More than 4000 articles were identified during the search and 241 were selected to retrieve available evidence on AIT, which was graded according to the Oxford classification. All the group members reviewed the resulting text until the final version reached the consensual agreement. A summary of recommendations on the more relevant topics are proposed. The role of AIT as a valuable therapeutic strategy for prevention of exacerbation and progressive decline in lung function is highlighted. Future research should include specific tools for asthma evaluation when assessing AIT effectiveness in asthmatic patients.

Specific allergen immunotherapy for the treatment of allergic asthma: a review of current evidence

Asthma is frequently associated with atopy, characterized by the production of specific immunoglobulin E in response to environmental allergens. Currently, two types of allergen immunotherapy (AIT) are used in clinical practice: subcutaneous and sublingual immunotherapy, both accepted as key components of the therapeutic repertoire for allergic rhinitis and conjunctivitis. However, their role in asthma remains controversial. The present document is aimed at providing the clinicians with a review of the evidence on the use of AIT in asthma, focusing on the most relevant aspects of its mechanism of action, its efficacy, and existing data on safety, tolerability, and cost-effectivity, both in pediatric and adult populations. A systematic search of MEDLINE, Cochrane, and Clinical Trials databases from 2000 to April of 2016 was carried out by a panel of experts from the Spanish Allergy and Clinical Immunology Scientific Society. Relevant studies prior to the year 2000 included in ulterior systematic reviews were also considered. More than 4000 articles were identified during the search and 241 were selected to retrieve available evidence on AIT, which was graded according to the Oxford classification. All the group members reviewed the resulting text until the final version reached the consensual agreement. A summary of recommendations on the more relevant topics are proposed. The role of AIT as a valuable therapeutic strategy for prevention of exacerbation and progressive decline in lung function is highlighted. Future research should include specific tools for asthma evaluation when assessing AIT effectiveness in asthmatic patients (AU)

El asma se asocia frecuentemente con alergia, entendida ésta como la producción de IgE específica frente a alérgenos ambientales. Actualmente, existen dos tipos de inmunoterapia específica con alérgenos (ITE) para la práctica clínica habitual: subcutánea y sublingual, ambas indicadas en el tratamiento de la rinitis y la conjuntivitis alérgicas. Sin embargo, su papel en el asma resulta todavía controvertido. Este documento pretende ofrecer al clínico una revisión de la evidencia del uso de ITE en asma, centrándose en aspectos más relevantes como su mecanismo de acción, eficacia, seguridad, tolerabilidad y coste-eficacia, tanto en población adulta como pediátrica. Un panel de expertos de la Sociedad Española de Alergología e Inmunología Clínica, llevó a cabo una búsqueda sistemática en las bases de datos MEDLINE, Cochrane y Clinica Trials, desde 2000 a abril de 2016. También se revisaron algunos estudios anteriores al 2000, incluidos en revisiones sistemáticas posteriores. Se identificaron más de 4000 artículos en la búsqueda y se seleccionaron 241 para documentar la evidencia disponible y graduarla según la clasificación Oxford. Todos los miembros del panel revisaron el texto resultante hasta la versión final, alcanzando un acuerdo de consenso y se propusieron recomendaciones para los aspectos más relevantes. Se señala específicamente que la ITE resulta potencialmente valorable en la prevención de las exacerbaciones y el declive progresivo de la función pulmonar, aunque se necesitan nuevos estudios que incluyan variables específicas de evaluación de asma para verificar la eficacia de la ITE en esta patología (AU)

Immunotherapy with a Phleum pratense allergen extract induces an immune response to a grass-mix allergen extract.

BACKGROUND: Grass pollen allergy is one of the most common allergies worldwide, and patients often show sensitization to an array of phylogenetically related species. OBJECTIVE: To determine the effect of specific immunotherapy (SIT) with Phleum pratense extract on induction of the immune response to a mixture composed of 5 grass pollen extracts. METHODS: Forty-six adult patients suffering from rhinitis and sensitized to a mix of grass pollen allergen extracts were randomized 3:1 to receive a short course of SIT with P. pratense or to an open control group without SIT. At baseline and after 3-4 months, we evaluated levels of specific immunoglobulin (Ig) E and IgG4, as well as the immediate and delayed cutaneous responses to the grass mix and P. pratense. IgG4 to Lolium perenne was also determined. RESULTS: Levels of IgE and IgG4 to grass mix and P. pratense increased significantly during treatment (P<.001). However, this increase was only significantly higher in the SIT group than in the control group for IgG4 (P<.001). The levels of IgG4 to Phl p 5 and Lol p 5 were highly correlated (r=0.99, P<.001). The immediate and delayed cutaneous responses were significantly diminished to both extracts after SIT (P<.001). CONCLUSIONS: Patients with rhinoconjunctivitis diagnosed using skin prick testing with a grass mix allergen extract and treated with a short course of SIT based on a single species P. pratense allergen extract are able to develop an immune response that targets not only the immunizing species, but also the grass mix allergen extract.

In vivo and in vitro immunological changes induced by a short course of grass allergy immunotherapy tablets.

BACKGROUND: The fast-dissolving grass allergy immunotherapy tablet (grass AIT), Grazax, has proven effective in grass pollen-induced rhinoconjunctivitis. OBJECTIVE: To investigate the immunological and cutaneous changes induced after a short course with grass AIT. METHODS: We performed a randomized, double-blind placebo-controlled trial with 78 patients randomly assigned to receive either grass AIT or placebo in a 2:1 ratio. Treatment lasted at least 8 weeks before the grass pollen season (GPS), and continued until the season finished. Specific immunoglobulin (Ig) G4, IgE, and IgE-blocking factor to Phleum pratense were measured at the beginning of the trial and at different intervals during treatment. Immediate and delayed skin tests with P pratense were also performed. Safety endpoints were defined in terms of adverse events reported. RESULTS: A total of 75 patients completed the trial (50 active and 25 placebo). P pratense IgG4, IgE, and IgE-blocking factor in actively treated patients increased significantly from baseline to the start of the GPS compared to placebo (P > .001, P = .017, and P = .005, respectively). The immediate cutaneous response was reduced during therapy in actively treated subjects, whereas placebo-treated subjects showed a decrease only after the start of the GPS. The delayed response to the intradermal test in grass AIT-treated subjects diminished, although not in a significantly different way from the placebo-treated subjects. CONCLUSION: Treatment with grass AIT for grass pollen allergic rhinoconjunctivitis induces immunological changes after only 1 month of treatment.

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units.

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results.

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting β2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-γ], and tumor necrosis factor [TNF-α]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-γ, and TNF-α (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results (AU)

Se ha llevado a cabo un estudio prospectivo y multicéntrico con el objetivo de valorar la tolerancia y posible efecto a corto plazo de las vacunas alergénicas administradas bajo pauta cluster en los meses inmediatamente anteriores al inicio de la estación polínica. El estudio se realizó en 8 centros, incluyéndose un total de 191 pacientes (niños y adultos) con enfermedad alérgica respiratoria por sensibilización a polen de olivo y/o gramíneas. De ellos, 34 actuaron como controles y a los pacientes restantes se les administró inmunoterapia bajo una pauta cluster, en la fase de iniciación, de 8 dosis administradas en 4 visitas. Tras 3 meses de tratamiento, se registraron diferencias significativas entre ambos grupos en el consumo de medicación (antihistamínicos en colirio y orales -p = 0,045 y p = 0,001 respectivamente- y ß2 de corta duración -p = 0,004-) así como en síntomas pulmonares (sibilancias y tos -p = 0,035 y 0,014 respectivamente-). Por otro lado, se determinó el perfil de citocinas (IL-4, 5, 10 y 2, IFN-gamma y TNF-a) de forma previa al inicio del tratamiento y al finalizar el seguimiento (4-5 meses). Se observaron descensos en los niveles de IL-4, 5 y 10 (perfil TH2) y aumento en los valores de IL-2, IFN-gamma y TNF-a (perfil TH1), más marcados en el grupo activo que en el control, sin alcanzar significación estadística. No se registraron efectos adversos severos. Por tanto, podemos observar que la pauta ensayada mostró un adecuado perfil de tolerancia, y tras pocos meses de tratamiento se registraron cambios significativos en la puntuación de síntomas y medicación, siendo necesaria la realización de un estudio con un diseño doble ciego frente a placebo para confirmar los resultados obtenidos (AU)

Anisakis simplex: a cause of intestinal pseudo-obstruction.

OBJECTIVE: the ingestion of Anisakis simplex larvae may lead to the appearance of gastrointestinal symptoms. However, the number of reported cases of parasitization by Anisakis in Spain is lower than would be expected in a country with the second-highest fish consumption per inhabitant in the world, particularly since fish is often eaten raw or only slightly cooked. We suggest that the incidence of anisakiasis in Spain would be higher if complementary studies were used in all patients suspected of having anisakiasis. METHODS: we studied 6 patients with a diagnosis of intestinal obstruction who frequently ate fish. Skin prick tests with seafood, inhalant allergen and Anisakis extracts were done. Total and specific IgE against Anisakis larvae were tested with a CAP system radioimmunoassay and immunoblot assays. Oral challenge tests with frozen larvae were also used. RESULTS: a positive skin prick result and high levels of total and specific IgE were found in all patients. The results of immunoblot assays for IgE did not show a consistent pattern, but a group of several low (14-18 kDa) and intermediate molecular weight antigens (30-50 kDa) were found in all patients. All patients tolerated the oral challenge test well. CONCLUSIONS: in our patients with intestinal pseudo-obstruction and a history of frequent fish eating, the clinical and laboratory findings were suggestive of parasitization by Anisakis simplex larvae as the cause of the obstruction. Such complementary studies should be used whenever there is a suspicion of anisakiasis. The results of the oral provocation test show that the intake of dead larvae does not induce clinical parasitization.

Anisakis simplex: una causa de pseudobstrucción intestinal / Anisakis simplex: a cause of intestinal pseudo-obstruction

OBJETIVOS: la ingesta de la larva viva del parásito Anisakis simplex puede provocar la aparición de síntomas gastrointestinales. Siendo España el segundo país consumidor de pescado por habitante, es destacable el bajo número de casos de Anisakiasis gastrointestinal recogidos en la bibliografía, más aún cuando se consume frecuentemente crudo o poco cocinado, criterios que posibilitan dicha parasitación. Pretendemos demostrar que se observarían una mayor incidencia de casos si se realizasen técnicas complementarias cuando exista sospecha clínica. DISEÑO EXPERIMENTAL: se han estudiado seis pacientes diagnosticados de pseudobstrucción intestinal e ingesta de pescado previamente. Se realizaron pruebas cutáneas en prick con extractos de inhalantes, pescados y Anisakis simplex, determinación de IgE total, IgE específica frente a Anisakis mediante CAP radioinmunoensayo e inmunoblot y provocación oral controlada con larva de Anisakis previamente congelada. RESULTADOS: presentaron cifras elevadas de IgE total e IgE específica frente a Anísakís y Prick-test positivo con extracto del parásito. No se objetivó un patrón homogéneo en el inmunoblotting, pero todos reconocían antígenos de bajo peso molecular (14-18 Kd) y de mediano peso molecular (30-50). Los pacientes, sometidos a provocación, no refirieron sintomatología gastrointestinal o sistémica. CONCLUSIONES: presentamos seis pacientes en los que los hallazgos clínicos y de laboratorio orientan a considerar la parasitación por la larva de Anisakis simplex como factor etiológico del cuadro abdominal. Sería conveniente protocolizar el estudio complementario cuando exista sospecha clínica de anisakiasis. La ingesta de larva muerta no produce afectación clínica como así lo manifiesta la tolerancia al test de provocación (AU)

Desensitization to azathioprine.

Azathioprine is an immunosuppressant drug which is an analog to 6-mercaptopurine and has been used in the last 20 years to prevent organ transplant rejection. It has also been used in the treatment of some autoimmunological diseases. We present a case of a 24-year-old woman with systemic lupus erythematosus, suffering from nephritis, who developed angioedema after using azathioprine to control her illness. She had never reported similar episodes. The involvement of the drug was demonstrated by positive oral challenge test without changes in biochemical and complement blood determinations. She reached tolerance to the drug after a desensitization procedure (increasing 5 mg each day to reach 125 mg daily). We are not able to propose the involvement of an IgE-mediated mechanism, but rather a hypersensitive one with a non-dose-dependent effect. These desensitization procedures show great potential as therapeutic safeguards against harmful drugs in some patients. We have not found any other desensitization procedure for this drug.

Occupational asthma caused by champignon flies.

BACKGROUND: Occupational bronchial asthma in mushroom (champignon) workers is unusual, although reports on it appeared in 1938 and 1951; we have not found any others since those dates. Here we report the case of a 52-year-old man who works as a champignon cultivator. He suffered rhinoconjunctivitis and asthma attacks whenever he entered the champignon culture caves. We studied flies as a possible antigen source. We collected these insects from the growing sites in order to identify them, and then prepare an extract; the samples turned out to be of two families of insects of the order Diptera, 98% from the Phoridae family (Brachycera suborder) and 2% from the Sciaridae (Nematocera suborder). METHODS: Skin prick tests, conjunctival provocation tests, serum specific IgE, specific IgE-binding fractions in immunoblotting, and monitoring of PEFR (at work and off work) were performed. RESULTS: IgE-mediated hypersensitivity to these flies was demonstrated by skin prick test, conjunctival provocation test, serum specific IgE, and IgE-binding fractions in immunoblotting. Monitoring of PEFR both at work and off work showed a clear relationship between symptoms, or fall in PEFR, and the workplace. CONCLUSIONS: We report the case of a patient suffering from asthma and rhinoconjunctivitis caused by hypersensitivity to fly proteins.

A double-blind, placebo-controlled study of immunotherapy with grass-pollen extract Alutard SQ during a 3-year period with initial rush immunotherapy.

Thirty patients with asthma and/or monosensitized allergic rhinitis caused by grass pollen whose ages ranged from 15 to 35 years were selected. Two groups were established at random: an active group and a placebo group, and a double-blind study was done on treatment with immunotherapy for a period of 3 continuous years, with initiation doses administered according to the rush immunotherapy technique. Grass-pollen allergen extract Alutard SQ and histamine as a placebo were used. The objective parameters of efficacy evaluated were end-point cutaneous tests, conjunctival provocation, bronchial provocation, and symptom/medication scores, as well as specific immunoglobulin determinations. The statistical evaluation of the results was significant for the differences existing between the initial and final time of the active group, and there were significant differences between the two groups for all of the parameters considered. We found no relationship between clinical improvement and the range of specific immunoglobulin E values. Regarding the safety of the treatment, systemic adverse effects were manifested only in the initial phase (rush immunotherapy), and were easily controlled by treatment. We conclude that the efficacy and safety of immunotherapy with grass pollen make it possible to consider this treatment fundamental in these patients.