The diamine oxidase gene is associated with hypersensitivity response to non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in hypersensitivity drug reactions. Histamine is released in the allergic response to NSAIDs and is responsible for some of the clinical symptoms. The aim of this study is to analyze clinical association of functional polymorphisms in the genes coding for enzymes involved in histamine homeostasis with hypersensitivity response to NSAIDs. We studied a cohort of 442 unrelated Caucasian patients with hypersensitivity to NSAIDs. Patients who experienced three or more episodes with two or more different NSAIDs were included. If this requirement was not met diagnosis was established by challenge. A total of 414 healthy unrelated controls ethnically matched with patients and from the same geographic area were recruited. Analyses of the SNPs rs17740607, rs2073440, rs1801105, rs2052129, rs10156191, rs1049742 and rs1049793 in the HDC, HNMT and DAO genes were carried out by means of TaqMan assays. The detrimental DAO 16 Met allele (rs10156191), which causes decreased metabolic capacity, is overrepresented among patients with crossed-hypersensitivity to NSAIDs with an OR  = 1.7 (95% CI  = 1.3-2.1; Pc  = 0.0003) with a gene-dose effect (P = 0.0001). The association was replicated in two populations from different geographic areas (Pc  = 0.008 and Pc  = 0.004, respectively). CONCLUSIONS AND IMPLICATIONS: The DAO polymorphism rs10156191 which causes impaired metabolism of circulating histamine is associated with the clinical response in crossed-hypersensitivity to NSAIDs and could be used as a biomarker of response.

Erythema Nodosum as Azathioprine Hypersensitivity Reaction in a Patient with Bullous Pemphigoid.

A 65-year-old woman with bullous pemphigoid presented with fever and several red-purple nodular subcutaneous lesions on both lower legs 1 week after starting treatment with azathioprine (AZA). Biopsy of a skin nodule was compatible with erythema nodosum (EN) and hypersensitivity reaction to AZA was suspected. AZA was subsequently discontinued, observing complete remission of fever and EN within 2 weeks. This case highlights the importance of recognizing EN as a possible manifestation of hypersensitivity reaction to AZA.

In vitro methods for diagnosing nonimmediate hypersensitivity reactions to drugs.

Nonimmediate drug hypersensitivity reactions (DHRs) are difficult to manage in daily clinical practice, mainly owing to their heterogeneous clinical manifestations and the lack of selective biological markers. In vitro methods are necessaryto establish a diagnosis, especially given the low sensitivity of skin tests and the inherent risks of drug provocation testing. In vitro evaluation of nonimmediate DHRs must include approaches that can be applied during the different phases of the reaction. During the acute phase, monitoring markers in both skin and peripheral blood helps to discriminate between immediate and nonimmediate DHRs with cutaneous responses and to distinguish between reactions that, although they present similar clinical symptoms, are produced by different immunological mechanisms and therefore have a different treatment and prognosis. During the resolution phase, in vitro testing is used to detect the response of T cells to drug stimulation; however, this approach has certain limitations, such as the lack of validated studies assessing sensitivity. Moreover, in vitro tests indicate an immune response that is not always related to a DHR. In this review, members of the Immunology and Drug Allergy Committee of the Spanish Society of Allergy and Clinical Immunology (SEAIC) provide an overview of the most widely used in vitro tests for evaluating nonimmediate DHRs.

Asma en la edad pediátrica : proceso asistencial integrado

Este documento (2003), junto con el de Asma en la edad adulta (2004), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma del adulto : proceso asistencial integrado

Este documento (2004), junto con el de Asma en la edad pediátrica (2003), han sido unificados en un único Proceso Asistencial Integrado: Asma (2012)[http://hdl.handle.net/10668/674]. Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social/ Profesionales / Nuestro Compromiso por la Calidad / Proceso Asistencial Integrado Asma / Histórico de documentos del PAI Asma)

Asma : proceso asistencial integrado

Este Proceso (2012) integra los dos publicados anteriormente de Asma en la edad pediátrica (2003) y Asma en la edad adulta (2004). Fichero en formato pdf, publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

The involvement of thaumatin-like proteins in plant food cross-reactivity: a multicenter study using a specific protein microarray

Cross-reactivity of plant foods is an important phenomenon in allergy, with geographical variations with respect to the number and prevalence of the allergens involved in this process, whose complexity requires detailed studies. We have addressed the role of thaumatin-like proteins (TLPs) in cross-reactivity between fruit and pollen allergies. A representative panel of 16 purified TLPs was printed onto an allergen microarray. The proteins selected belonged to the sources most frequently associated with peach allergy in representative regions of Spain. Sera from two groups of well characterized patients, one with allergy to Rosaceae fruit (FAG) and another against pollens but tolerant to food-plant allergens (PAG), were obtained from seven geographical areas with different environmental pollen profiles. Cross-reactivity between members of this family was demonstrated by inhibition assays. Only 6 out of 16 purified TLPs showed noticeable allergenic activity in the studied populations. Pru p 2.0201, the peach TLP (41%), chestnut TLP (24%) and plane pollen TLP (22%) proved to be allergens of probable relevance to fruit allergy, being mainly associated with pollen sensitization, and strongly linked to specific geographical areas such as Barcelona, Bilbao, the Canary Islands and Madrid. The patients exhibited >50% positive response to Pru p 2.0201 and to chestnut TLP in these specific areas. Therefore, their recognition patterns were associated with the geographical area, suggesting a role for pollen in the sensitization of these allergens. Finally, the co-sensitizations of patients considering pairs of TLP allergens were analyzed by using the co-sensitization graph associated with an allergen microarray immunoassay. Our data indicate that TLPs are significant allergens in plant food allergy and should be considered when diagnosing and treating pollen-food allergy.

Graph based study of allergen cross-reactivity of plant lipid transfer proteins (LTPs) using microarray in a multicenter study.

The study of cross-reactivity in allergy is key to both understanding. the allergic response of many patients and providing them with a rational treatment In the present study, protein microarrays and a co-sensitization graph approach were used in conjunction with an allergen microarray immunoassay. This enabled us to include a wide number of proteins and a large number of patients, and to study sensitization profiles among members of the LTP family. Fourteen LTPs from the most frequent plant food-induced allergies in the geographical area studied were printed into a microarray specifically designed for this research. 212 patients with fruit allergy and 117 food-tolerant pollen allergic subjects were recruited from seven regions of Spain with different pollen profiles, and their sera were tested with allergen microarray. This approach has proven itself to be a good tool to study cross-reactivity between members of LTP family, and could become a useful strategy to analyze other families of allergens.

Asma en Adulto Joven: Proceso de Enfermería

Asthma is a chronic disease and as such, is inexorably tied to periods of exacerbations in which quality of life is affected. This represent not only a threat to physical integrity of the sick person but also an increase in both workloads and expenses supported by health services. The key point of this case is that if we make our patients to get a major implication in their own disease control, we are going to reduce umber and severity of episodes, to optimize resources and the most important to improve the quality of life of our patients

A three-year aeropalynological study in Estepona (southern Spain).

An aeropalynological study was carried out in the atmosphere of Estepona, a very popular tourist resort situated in the "Costa del Sol", (southern Spain) based on the data obtained during a three year air-monitoring programme (March 1995 to March 1998) using a volumetric pollen trap. The 34 taxa that reached a 10-day mean air pollen concentration equal to or greater than 1 grain of pollen/m(3) of air are reflected in the calendar. The first 10 taxa, in order of abundance, were: Cupressaceae, Olea europaea, Quercus, Poaceae, Urticaceae, Plantago, Pinus, Chenopodiaceae-Amaranthaceae, Ericaceae and Castanea, the first 3 of which accounted for approximately 56 % of the annual total pollen count. The greatest diversity of pollen type occurred during spring, while the highest pollen concentrations were reached from February-June, when approximately more than 80 % of the annual total pollen was registered. The lowest concentrations were obtaining during January, August and September. The annual quantity of pollen collected, the intensity and the dates on which the maximum peaks were recorded differed for the 3 years studied, which can be explained by reference to various meteorological parameters, especially rainfall and temperature. The pollen calendar spectrum is typically Mediterranean and similar to those of nearby localities, in which many pollen types are represented and the long tails indicating long flowering periods.

Anaphylaxis caused by imported red fire ant stings in Málaga, Spain.

A 27-year-old woman suffered from anaphylaxis after being stung by Solenopsis invicta ants while she was handling wood from South America. The patient reported no previous adverse reactions to stings by other hymenopteran species. Intradermal skin tests with hymenoptera venom (Vespula vulgaris, Polistes species, Apis melifera) were negative. Serum specific immunoglobulin (Ig) E yielded positive results for S invicta (5.28 kU/L) and negative results for A melifera, Ves v 5 and Pol a 5. Immunodetection assays showed the presence of serum IgE against the Sol i 2 allergen. The patient had probably been stung previously although inadvertently by red fire ants while she handled infested wood from South America, and precautionary measures are thus advisable when this material is to be handled. To our knowledge this is the first case of anaphylaxis from red fire ant stings reported in Europe.

Antigenic proteins involved in occupational rhinitis and asthma caused by obeche wood (Triplochiton scleroxylon).

BACKGROUND Obeche wood dust is a known cause of occupational asthma where an IgE-mediated mechanism has been demonstrated. OBJECTIVE To characterize the allergenic profile of obeche wood dust and evaluate the reactivity of the proteins by in vitro, ex vivo and in vivo assays in carpenters with confirmed rhinitis and/or asthma MATERIALS AND METHODS An in-house obeche extract was obtained, and two IgE binding bands were purified (24 and 12 kDa) and sequenced by N-terminal identity. Specific IgE and IgG, basophil activation tests and skin prick tests (SPTs) were performed with whole extract and purified proteins. CCD binding was analyzed by ELISA inhibition studies. RESULTS Sixty-two subjects participated: 12 with confirmed occupational asthma/rhinitis (ORA+), 40 asymptomatic exposed (ORA-), and 10 controls. Of the confirmed subjects, 83% had a positive SPT to obeche. There was a 100% recognition by ELISA in symptomatic subjects vs. 30% and 10% in asymptomatic exposed subjects and controls respectively (p<0.05). Two new proteins were purified, a 24 kDa protein identified as a putative thaumatin-like protein and a 12 kDa gamma-expansin. Both showed allergenic activity in vitro, with the putative thaumatin being the most active, with 92% recognition by ELISA and 100% by basophil activation test in ORA+ subjects. Cross-reactivity due to CCD was ruled out in 82% of cases. CONCLUSIONS Two proteins of obeche wood were identified and were recognized by a high percentage of symptomatic subjects and by a small proportion of asymptomatic exposed subjects. Further studies are required to evaluate cross reactivity with other plant allergens.

Synergistic Effect between Amoxicillin and TLR Ligands on Dendritic Cells from Amoxicillin-Delayed Allergic Patients.

Amoxicillin, a low-molecular-weight compound, is able to interact with dendritic cells inducing semi-maturation in vitro. Specific antigens and TLR ligands can synergistically interact with dendritic cells (DC), leading to complete maturation and more efficient T-cell stimulation. The aim of the study was to evaluate the synergistic effect of amoxicillin and the TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively) in TLR expression, DC maturation and specific T-cell response in patients with delayed-type hypersensitivity (DTH) reactions to amoxicillin. Monocyte-derived DC from 15 patients with DTH to amoxicillin and 15 controls were cultured with amoxicillin in the presence or absence of TLR2, 4 and 7/8 agonists (PAM, LPS and R848, respectively). We studied TLR1-9 gene expression by RT-qPCR, and DC maturation, lymphocyte proliferation and cytokine production by flow cytometry. DC from both patients and controls expressed all TLRs except TLR9. The amoxicillin plus TLR2/4 or TLR7/8 ligands showed significant differences, mainly in patients: AX+PAM+LPS induced a decrease in TLR2 and AX+R848 in TLR2, 4, 7 and 8 mRNA levels. AX+PAM+LPS significantly increased the percentage of maturation in patients (75%) vs. controls (40%) (p=0.036) and T-cell proliferation (80.7% vs. 27.3% of cases; p=0.001). Moreover, the combinations AX+PAM+LPS and AX+R848 produced a significant increase in IL-12p70 during both DC maturation and T-cell proliferation. These results indicate that in amoxicillin-induced maculopapular exanthema, the presence of different TLR agonists could be critical for the induction of the innate and adaptive immune responses and this should be taken into account when evaluating allergic reactions to these drugs.

Enhanced diagnosis of pollen allergy using specific immunoglobulin E determination to detect major allergens and panallergens.

BACKGROUND Pollen is one of the main causes of allergic sensitization. It is not easy to make an etiological diagnosis of pollen-allergic patients because of the wide variety of sensitizing pollens, association with food allergy, and increasing incidence of polysensitization, which may result from the presence of allergens that are common to different species, as is the case of panallergens. OBJECTIVE To compare the results of skin prick tests (SPT) using whole pollen extract with specific immunoglobulin (Ig) E determination for several allergens (purified panallergens included) in the diagnosis of polysensitized pollen-allergic patients. METHODS The study sample comprised 179 pollen-sensitized patients who underwent SPT with pollen extract and allergen-specific IgE determination against different allergens. RESULTS The level of concordance between the traditional diagnostic test (SPT) and IgE determination was low, especially in patients sensitized to the panallergens profilin and polcalcin. In the case of SPT, the results demonstrated that patients who are sensitized to either of these panallergens present a significantly higher number of positive results than patients who are not. However, IgE determination revealed that while patients sensitized to polcalcins are sensitized to allergens from a higher number of pollens than the rest of the sample, this is not the case in patients sensitized to profilins. On the other hand, sensitization to profilin or lipid transfer proteins was clearly associated with food allergy. CONCLUSIONS Sensitization to panallergens could be a confounding factor in the diagnosis of polysensitized pollen-allergic patients as well as a marker for food allergy. However, more studies are required to further investigate the role of these molecules.

Sensitization to Anisakis simplex species in the population of northern Morocco.

OBJECTIVE To investigate sensitization to third-stage Anisakis simplex larvae in a randomly selected population in northern Morocco. METHODS We studied sera obtained from clinical analysis laboratories in Tangier and Tetuouan and from fishermen at Tangier port. The age of the study population ranged from 6 to 83 years. ImmunoCAP and immunoblotting techniques were used to determine total and specific immunoglobulin (Ig) E values and the chi2 and Fisher exact tests were applied to analyze relationships between study variables. RESULTS A seroprevalence of 5.1% was found, with a higher percentage of positive sera in the 31-to-43-year age group. Sensitization was not significantly associated with the origin, sex, occupation, or age of the individuals studied. In sera positive by InmunoCAP, immunoblotting studies detected numerous bands of between 7 kDa and >209 kDa, with a predominance of bands in the approximately 20-kDa to 24-kDa range. CONCLUSIONS Although no cases of human anisakiasis have been reported in Morocco to date, part of a randomly selected population in Northern Morocco shows sensitization to A simplex proteins.