Key Issues in Hymenoptera Venom Allergy: An Update.

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis.

Key issues in hymenoptera venom allergy: an update

In this review, the Hymenoptera Allergy Committee of the SEAIC analyzes the most recent scientific literature addressing problems related to the diagnosis of hymenoptera allergy and to management of venom immunotherapy. Molecular diagnosis and molecular risk profiles are the key areas addressed. The appearance of new species of hymenoptera that are potentially allergenic in Spain and the associated diagnostic and therapeutic problems are also described. Finally, we analyze the issue of mast cell activation syndrome closely related to hymenoptera allergy, which has become a new diagnostic challenge for allergists given its high prevalence in patients with venom anaphylaxis (AU)

En esta revisión el Comité de Alergia a Himenópteros de la SEAIC ha analizado la literatura científica más reciente sobre los principales problemas diagnósticos de la alergia a himenópteros, así como sobre las dificultades que pueden surgir durante la inmunoterapia con venenos. Se revisan especialmente las novedades relacionadas con el diagnóstico molecular y los perfiles moleculares de riesgo. También se describe la alergia a himenópteros poco habituales y los problemas diagnósticos y terapéuticos que esta conlleva. Por último, se tratan los síndromes de activación mastocitaria clonal, íntimamente relacionados con la alergia a himenópteros, que se han convertido en un nuevo reto diagnóstico para el alergólogo (AU)

Insect Venom Immunotherapy: Analysis of the Safety and Tolerance of 3 Buildup Protocols Frequently Used in Spain.

INTRODUCTION: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. MATERIALS AND METHODS: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. RESULTS: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. CONCLUSIONS: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach.

Insect venom immunotherapy: analysis of the safety and tolerance of 3 buildup protocols frequently used in Spain

Introduction: Hymenoptera venom immunotherapy (VIT) is an effective treatment but not one devoid of risk, as both local and systemic adverse reactions may occur, especially in the initial phases. We compared the tolerance to 3 VIT buildup protocols and analyzed risk factors associated with adverse reactions during this phase. Materials and Methods: We enrolled 165 patients divided into 3 groups based on the buildup protocol used (3, 4, and 9 weeks). The severity of systemic reactions was evaluated according to the World Allergy Organization model. Results were analyzed using exploratory descriptive statistics, and variables were compared using analysis of variance. Results: Adverse reactions were recorded in 53 patients (32%) (43 local and 10 systemic). Local reactions were immediate in 27 patients (63%) and delayed in 16 (37%). The severity of the local reaction was slight/moderate in 15 patients and severe in 13. Systemic reactions were grade 1-2. No significant association was found between the treatment modality and the onset of local or systemic adverse reactions or the type of local reaction. We only found a statistically significant association between severity of the local reaction and female gender. As for the risk factors associated with systemic reactions during the buildup phase, we found no significant differences in values depending on the protocol used or the insect responsible. Conclusions: The buildup protocols compared proved to be safe and did not differ significantly from one another. In the population studied, patients undergoing the 9-week schedule presented no systemic reactions. Therefore, this protocol can be considered the safest approach (AU)

Introducción: La inmunoterapia con veneno de himenópteros (ITV) es un tratamiento eficaz, pero no está desprovisto de riesgo ya que pueden ocurrir reacciones adversas locales o sistémicas, especialmente en las etapas iniciales del tratamiento. Comparamos la tolerancia de tres protocolos de inicio de ITV y analizamos los factores de riesgo asociados con las reacciones adversas que se produjeron en esta fase. Métodos: Se incluyeron 165 pacientes divididos en tres grupos según el protocolo de iniciación utilizado (3, 4 o 9 semanas). Evaluamos la gravedad de las reacciones sistémicas de acuerdo con el modelo de la Organización Mundial de Alergia. Analizamos los resultados mediante estadística descriptiva exploratoria y comparamos variables mediante el análisis de la varianza. Resultados: Cincuenta y tres pacientes (32%) experimentaron algún tipo de reacción adversa; 43 eran locales y 10 sistémicas. Las reacciones locales fueron inmediatas en 27 pacientes (63%) y tardías en 16 (37%). La gravedad de la reacción local fue leve o moderada en 15 pacientes y grave en 13. Las reacciones sistémicas fueron de grado 1 o 2. No encontramos asociación significativa entre la modalidad de tratamiento y la aparición de reacciones adversas locales o sistémicas o el tipo de reacción local. Solo encontramos una asociación estadísticamente significativa de la gravedad de la reacción local con el sexo femenino. En cuanto a los factores de riesgo asociados con las reacciones sistémicas en la fase de inicio, no se encontraron diferencias significativas en estos valores en función del protocolo utilizado o el insecto responsable. Conclusiones: Los protocolos de inicio comparados demostraron ser seguros y no difirieron significativamente entre sí. En la población estudiada, el protocolo de 9-semanas no produjo reacciones sistémicas, por lo que se puede considerar el protocolo más seguro (AU)

Fungal allergens in a saxophonist who had never smoked with allergic bronchopulmonary aspergillosis previously diagnosed as COPD

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A protocol for induction of tolerance to apomorphine in patients with parkinson disease and hypersensitivity to apomorphine

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Monoclonal antibody desensitization in a patient with a generalized urticarial reaction following denosumab administration.

Denosumab is a human monoclonal antibody indicated for the treatment of osteoporosis in postmenopausal women with a high risk of fractures. To our knowledge, no cases of desensitization to this drug have been described in the literature. We report the first case of generalized urticarial reaction and facial angioedema after therapy with denosumab. A subcutaneous desensitization protocol was successfully completed in this patient. Rapid desensitization is a promising method for the delivery of denosumab after a hypersensitivity reaction, and should be considered in osteoporosis treatment when no acceptable therapeutic alternatives are available.

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.

Bleeding and Shock in a 44-Year-Old Woman With Systemic Mastocytosis

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Cefotaxim induced a near fatal anaphylactic shock in an infant

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Ibuprofen-induced aseptic meningoencephalitis confirmed by drug challenge.

Drug-induced aseptic meningitis (DIAM) is a diagnostic challenge. The major causative agents are nonsteroidal anti-inflammatory drugs (particularly ibuprofen), antibiotics, intravenous immunoglobulin, and OKT3 monoclonal antibodies. DIAM is more frequently observed in patients with autoimmune diseases. A 36-year-old woman was attended in our department 3 months after being diagnosed with aseptic meningoencephalitis. She had had 2 episodes in 9 months. Neurological symptoms were associated with ibuprofen. A challenge with acetylsalicylic acid was negative, whereas a drug challenge with ibuprofen was positive. Thirty minutes after ingesting 50 mg of ibuprofen, she experienced general malaise and progressively developed chills, fever (39.5 degrees C), headache, and nuchal rigidity. Lumbar puncture showed normal glucose and high protein levels. Neutrophilic pleocytosis was observed at the first admission; lymphocytosis was predominant in the second and third episodes. DIAM is a rare and severe hypersensitivity reaction. Drug challenge enabled us to make an accurate diagnosis.

Significance of infrequent and unspecific pathologies recorded in the Spanish Survey Alergológica-2005.

BACKGROUND: There are infrequent or unspecific diseases that occupy an important part of time in the job of the allergists. OBJECTIVE: We sought to evaluate the frequency and to determine the characteristics of uncommon or unspecific diseases seen by allergists in Spain, and to compare these data with findings obtained in a similar study undertaken in 1992. MATERIAL AND METHODS: An observational, prospective and cross-sectional study named "Alergológica 2005" was carried out in Spain. A part of this study analyzed the demographic, healthcare and clinical aspects of infrequent or unspecific diseases categorized as "Other allergic diseases" (OAD) or "Other non-allergic diseases" (ONAD). RESULTS: The survey comprised 4991 patients. In OAD, 45 patients were included. In ONAD, 290 patients were included. Significant diagnoses were gastroallergic anisakiasis (10 patients), idiopathic anaphylaxis (7 patients), and hypersensitivity pneumonitis (2 patients). In the ONAD group, non allergic respiratory diseases were the most frequent diagnosis. Mean time spent to reach a diagnosis was 14.2 days. However, the median of this time was only 1 day. Main diagnostic methods employed were a clinical history/physical examination in 86% of patients and skin tests in 73.7%. CONCLUSION: Several unspecific diseases affected more than 60% of patients in the two groups together. Findings show the current knowledge of allergic disorders due to Anisakis simplex. Diagnoses of hypersensitivity pneumonitis seem to be as frequent as previously published. Idiopathic anaphylaxis seems to be less frequent. The wide-range of times needed to reach a diagnosis was in agreement with the mixture of diseases included in both groups.

Epidemiologic observations on Hymenoptera allergy in Spain: the Alergológica-2005 study.

BACKGROUND: To date there has been an absence of nation-wide epidemiologic studies on insect allergy in Spain. OBJECTIVES: To measure the frequency and to determine the characteristics of Hymenoptera hypersensitivity in a Spanish population at a particular point in time and compare with the data obtained in a similar study carried out in 1992. MATERIAL AND METHODS: An observational, prospective and cross-sectional study (Alergológica-2005) was carried out all over Spain. RESULTS: The number of patients included in the study was 4991, of whom 77 (1.54%) were diagnosed with insect sting allergy. This represented an increase of 0.7% compared to Alergológica-1992. The honey bee was responsible for 45.5% of reactions, Vespula spp for 27.3% and Polistes spp for 23.4%. 64.9% of reactions were systemic. The group with Hymenoptera allergy had a predominance of males (69.1% vs. 42.7% in the general sample, P < .0001), older patients (median age 37,4 vs. 32,1, P < .013), and homes in rural zones (33% vs. 18.3%, P < .004). The median of days necessary to reach a diagnosis was lower (P < .0001). This population needed assistance in emergency units and hospitalisation more frequently. They had a low score on the mental component of the quality of life questionnaire. CONCLUSIONS: There was an increase in cases diagnosed with insect allergy with regard to Alergológica-1992. The typical patient profile is of a man, living in a small village, working outdoors with significant exposure to insect stings and in contact with farm animals, without atopic diseases. Bees and wasps are equally responsible of the stings. The need of emergency assistance in those patients is higher and the waiting time to be attended by an allergist is shorter.

Efficacy and quality of life with once-daily sublingual immunotherapy with grasses plus olive pollen extract without updosing.

OBJECTIVE: The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the clinical efficacy and tolerance of once-daily sublingual immunotherapy without updosing. Reduction in symptoms and medication use was the primary endpoint. METHODS: One hundred five patients with rhinitis and/or asthma due to grass and olive sensitization were randomized to be treated with placebo or active sublingual immunotherapy with the SLITone grass mix plus olive pollen extract for 6 months before the 2005 pollen season. Patients recorded symptoms and medication intake for 8 weeks during the pollen seasons in 2004 (n=37) and 2005 (n=85). RESULTS: Allergic symptoms were significantly decreased in the active immunotherapy group (P = .004) but not in the placebo group. There were no differences in scores between groups during the 2005 pollen season. Subjective assessments on a visual analog scale and a quality-of-life questionnaire indicated an improvement in actively treated patients with significant differences in both symptoms and medication use (P = .006). The rate of systemic adverse reactions was comparable in the 2 groups. No anaphylactic or severe adverse reactions were reported. Local adverse reactions, which were more common in the active immunotherapy group, were mostly immediate, were limited to the lips and mouth, and did not require treatment. CONCLUSION: Once-daily sublingual immunotherapy without updosing was well tolerated. The actively treated patients showed a significant reduction in symptom and medication scores and an improvement in their quality of life although there were no significant differences between the groups probably due to the low allergen season in which the study was evaluated.

Occupational asthma due to carrot in a cook.

BACKGROUND: Few previous reports of carrot-induced asthma have been confirmed by objective tests. Hypersensitivity to carrot is frequently associated with allergy to Apiaceae spices and sensitization to birch and mugwort pollens. CLINICAL CASE: A 40-year-old cook woman was seen with sneezing, rhinorrhea, contact urticaria and wheezing within few minutes of handling or cutting raw carrots. She needed to leave out of the kitchen while the other cooks cut raw carrots. METHODS AND RESULTS: Skin tests were positive to carrot, celery, aniseed and fennel. Rubbing test with fresh carrot was positive. Specific IgE to carrot was 4.44 kU/L. Determinations of specific IgE to mugwort, grass and birch pollens were negative. Inhalative provocation test, performed as a handling test, was positive. The IgE-immunoblotting showed two bands in carrot extract: a band with apparent molecular weight of 30 kd and other band of 18 kd. This band of 18 kd was Dau c 1. The band of 30 kd could correspond a phenylcoumaran benzylic ether reductase. Dau c 1 did not appear to be the unique allergen in this case. Additional allergens may induce the sensitization. Primary sensitization due to airborne allergens of foods and the lack of pollen allergy in this patient are notorious events.

Occupational asthma due to carrot in a cook

Background: Few previous reports of carrot-induced asthma have been confirmed by objective tests. Hypersensitivity to carrot is frequently associated with allergy to Apiaceae spices and sensitization to birch and mugwort pollens. Clinical case: A 40-year-old cook woman was seen with sneezing, rhinorrhea, contact urticaria and wheezing within few minutes of handling or cutting raw carrots. She needed to leave out of the kitchen while the other cooks cut raw carrots. Methods and results: Skin tests were positive to carrot, celery, aniseed and fennel. Rubbing test with fresh carrot was positive. Specific IgE to carrot was 4.44 kU/L. Determinations of specific IgE to mugwort, grass and birch pollens were negative. Inhalative provocation test, performed as a handling test, was positive. The IgE-immunoblotting showed two bands in carrot extract: a band with apparent molecular weight of 30 kd and other band of 18 kd. This band of 18 kd was Dau c 1. The band of 30 kd could correspond a phenylcoumaran benzylic ether reductase. Dau c 1 did not appear to be the unique allergen in this case. Additional allergens may induce the sensitization. Primary sensitization due to airborne allergens of foods and the lack of pollen allergy in this patient are notorious events

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