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Tetrazepam is a benzodiazepine that is widely used in Spain as a muscle relaxant, with occasional cutaneous side effects. We report a patient who developed a generalized pruriginous cutaneous reaction compatible with acute generalized exanthematous pustulosis (AGEP) due to tetrazepam. Patch tests with bromazepam, diazepam, and tetrazepam were negative at 48 and 72 hours; however, the tetrazepam patch showed a positive reaction at 10 days. Immunohistochemical studies revealed a mononuclear infiltrate composed of CD4+ and CD8+ T lymphocytes. Analysis of interleukin (IL) 8 expression by quantitative polymerase chain reaction revealed increased IL-8 mRNA levels in patch test-positive skin. Lymphoblast transformation test (LTT) was positive with tetrazepam but not with diazepam. Positive patch test and LTT suggested that tetrazepam-specific lymphocytes might be responsible for a T cell-mediated reaction. These results support previous data suggesting an important role for IL-8 and drug-specific T cells in the pathogenesis ofAGEP and imply that the reaction was specific to tetrazepam with no cross-reactivity to other benzodiazepines.

Cold urticaria can be associated with blood and thyroid disorders, drugs, or infections. Celiac disease is an autoimmune enteropathy caused by permanent gluten intolerance. It is often associated with other autoimmune diseases, such as chronic idiopathic urticaria. Nevertheless, association with cold urticaria has not yet been described. A boy aged 3 years 8 months presented local urticaria-angioedema when exposed to cold temperatures. An ice cube test was positive and iron deficiency anemia was demonstrated. He later developed legume intolerance, rhinoconjunctivitis related to pollen sensitization, and asthma. Due to persistence of cold urticaria symptoms and refractory anemia, a test for immunoglobulin A autoantibodies to tissue transglutaminase and an intestinal biopsy were performed. Results of both tests were compatible with celiac disease.A study of human leukocyte antigen indicated a high risk phenotype (HLA, DR6/DR7; DQA 0501, 0201; DQB 0301, 0201). After 7 months of a gluten-free diet, the boy's anemia resolved and he is free of symptoms when exposed to cold. This is a first description of the possibility of an association between celiac disease and cold urticaria. A poor course of cold urticaria in the absence of evidence of another underlying condition should lead to suspicion of celiac disease.

Background: Allergic reactions to food can be produced by contaminants that induce sensitization. Among these, Anisakis simplex can cause seafood infestation, and allergic symptoms (urticaria-angioedema, anaphylaxis, and asthma) can follow the eating or handling of affected fish. Although seafood is the principal source of human infections by this parasite, we have found allergic symptoms in 8 patients previously diagnosed as having A simplex sensitization after they ate chicken meat. Chicken feed usually has a high proportion of fishmeal, which might possibly be contaminated by this nematode., Objective: The aim of our study was to determine whether parasite proteins present in chicken meat could be responsible for the symptoms reported by these subjects., Methods: We carried out in vivo tests (prick, bronchial challenge, and double-blind placebo-controlled challenge with meat chicken) in these 8 patients. We performed immunoblotting using the sera from the 8 patients and controls in order to detect A simplex sensitization. We also investigated the presence of A simplex proteins in sera from chickens fed with fishmeal and in other sera from chickens fed only with cereals. We excluded sensitization to other chicken nematodes by serologic methods., Results: All 8 patients presented positive prick and challenges to A simplex. When we used serum from chickens fed with fishmeal as the antigen in blotting, patients 3, 4, 5, 6, 7, and 8 recognized a band of 16 kd, also obtained when using pools of fish-shellfish and A simplex larva. No detection was observed with sera from chickens fed with only cereals., Conclusion: We provide evidence, based on in vivo and in vitro tests, that subjects highly sensitized to A simplex can detect the presence of Anisakis species allergens in chicken meat.

Background: Lentils are among the main plant foods causing allergic reactions in pediatric patients in the Mediterranean area and in many Asian communities. However, very few reports have been devoted to identifying lentil allergens. Seed storage proteins of the vicilin family have been characterized as major allergens in several seed legumes and tree nuts., Objective: We sought to evaluate the role of lentil vicilins as food allergens., Methods: A serum pool and individual sera from 22 patients with lentil allergy were used in different IgE-binding assays. Mature lentil vicilin was isolated by means of cation-exchange chromatography, followed by reverse-phase HPLC, and characterized by means of N-terminal amino acid sequencing, matrix-assisted laser desorption/ionization mass spectrometry (MALDI) analysis, complex asparagine-linked glycan detection, specific IgE immunodetection with individual sera, and ELISA inhibition assays. Complete cDNAs encoding lentil vicilin variants were isolated by means of PCR with primers based on the amino acid sequence of the allergen., Results: A major IgE-binding component of approximately 50 kd was detected in lentil extracts. This component was isolated and characterized, showing a single N-terminal amino acid sequence homologous to those of legume vicilins and a broad peak (maximum at 48613 d) in MALDI analysis. The purified allergen was recognized by 77% (17/22) of the individual sera from patients with lentil allergy and reached up to 65% inhibition of the IgE binding to the crude lentil extract. The allergen showed 3 isoforms varying in their degree of N-glycosylation. Two cDNA clones encoding different allergen variants were isolated. The amino acid sequences deduced from both clones (415 and 418 residues; 47.4 and 47.8 kd) showed greater than 50% identity with major peanut (Ara h 1) and soybean (conglutinin subunits) allergens belonging to the vicilin family. Furthermore, these sequences included those of the previously characterized lentil allergen Len c 1.02 (108 amino acid residues of the C-terminal domain) and those of a novel lentil IgE-binding protein of 26 kd., Conclusion: The mature 48-kd lentil vicilin, designated Len c 1.01, is a major allergen. Two of its processing fragments, corresponding to subunits of 12 to 16 kd (previously named Len c 1) and 26 kd, are also relevant lentil IgE-binding proteins. The sequence homology of Len c 1.01 to those of major allergens from peanut, soybean, walnut, and cashew can help to investigate potential cross-reactions among these plant foods.

Background: It is thought that the natural evolution of food allergy has a good tolerance prognosis. However, there are few follow-up studies that determine the exact probability of tolerance to a given food or that analyze prognostic factors that can help us to understand the evolution of a child who begins life with a food allergy., Objective: We sought to determine the likelihood that children younger than 2 years of age with allergy to egg would eventually have tolerance to it and to analyze several prognostic predictors using egg white-specific IgE level as the main variable., Methods: We performed a prospective study of 58 children younger than 2 years of age with egg allergy, who were studied periodically until tolerance developed or until the end of the study. During the follow-up period, open challenge tests were carried out according to previously established criteria to verify tolerance to egg. Factors such as egg white-specific IgE level, serum total IgE level, symptoms after egg ingestion, size of skin prick test reactions to egg white, atopic dermatitis, and sex were analyzed as prognostic markers. Kaplan-Meier survival curves were used to calculate cumulative tolerance probability. Predictor influence and relative prognostic importance were estimated with the Cox proportional regression model., Results: The median time from the appearance of the first symptoms to tolerance was 35 months. Cumulative tolerance probability was 16% at 12 months of follow-up, 28% at 24 months, 52% at 36 months, 57% at 48 months, and 66% at 60 months. The relative weight of prognostic factors, expressed as the hazard ratio, was 50.95 for symptoms and 3.74 for the size of skin prick test reactions, with both being independent effects. The hazard ratio was 1.173 for every 0.1-unit decrease in the concentration log (decimal logarithm) of specific IgE level, with this effect being associated with tolerance only in children with cutaneous symptoms., Conclusions: Half of the children younger than 2 years of age with egg allergy will tolerate the food at 35 months of follow-up, and the proportion could be 66% after 5 years. At that age, the main predictors were the symptoms experienced after egg ingestion, followed by the size of skin prick test reactions. In addition, the specific IgE antibody level is an important prognostic marker in children who only had cutaneous symptoms.

Gastro-allergic anisakiasis has been reported as an entity in which an acute parasitism by Anisakis simplex is accompanied by an immunoglobulin (Ig)E-mediated systemic allergic reaction. Serum samples were obtained from 24 patients within 24 h after the onset of symptoms (day 0) and after 1 month (day 30) and in 13 patients after 6 months. Total IgE was assessed by the Imx method. Specific IgE was assessed by CAP-FEIA. Specific IgM, IgG, IgG4 and IgA antibodies were assessed by enzyme-linked immunosorbent assay against crude extract (CE) and excretory-secretory products (ESP). IgE immunoblotting (IB) was directed against CE or ESP (day 0 and day 30). We found a rise of total IgE, specific IgE, number of bands in IgE-IB, IgG and IgG4 between day 0 and day 30 with a fall to near basal levels after 6 months. IgM levels were highest at day 0, falling over the next 6 months and IgA levels remained almost unchanged. Correlation studies revealed a parallel stimulation of nearly all Ig isotypes, except IgM anti-ESP, whose antibody levels correlated negatively with specific IgG levels. We found an extension of the IgE antibody repertoire in IB. We conclude that the allergic IgE-mediated reaction in the course of gastro-allergic anisakiasis involves a parallel secondary Th2 type memory response and a primary immunologic stimulation of both Th2 and Th1 lymphocyte subsets against previously unrecognized antigens.

Background: A milk-free diet with substitute formula should be established when immediate symptomatic hypersensitivity to cows' milk protein (CMP) is diagnosed, and therefore an accurate diagnosis is very important., Objective: This study aims to find the optimal cutoff values for specific IgE antibody levels that discriminate between allergic and tolerant infants by using cows' milk and its principal proteins as allergens., Methods: A prospective study was carried out on 170 patients under 1 year old (mean, 4.8 months). These patients were seen consecutively over a 4-year period in our outpatient clinic and for the first time because of a reaction suggesting immediate hypersensitivity after ingestion of cows' milk formula. A clinical history, prick test with cows' milk and its proteins (alpha-lact-albumin, beta-lactoglobulin, and casein), determination of specific IgE antibodies with the CAP system FEIA for the same allergens as for the prick test, and a challenge test according to the diagnostic protocol were performed in all of the children. A study of validity of the prick test (cutoff point, 3 mm) and CAP system by using different cutoff points in the specific IgE values for cows' milk and its proteins were also analyzed., Results: Prevalence of immediate symptomatic hypersensitivity to CMP in this study was 44%. When both the whole milk and its principal milk proteins were used in the prick test, the negative predictive value was very high, and a negative value excluded allergy in 97% of the patients. When the different cutoff points of the specific IgE for milk were analyzed, 2.5 KU(A)/L had a positive predictive value of 90% and 5 KU(A)/L had a positive predictive value of 95%., Conclusions: When diagnosing immediate hypersensitivity to CMP in infants, negative skin test responses exclude allergy in most of the patients. If the prick test response is positive, specific IgE levels for cows' milk may be helpful. If these values are 2.5 KU(A)/L or greater, the challenge test should not be performed because of its high positive predictive value (90%).

Background: Lentils seem to be the most common legume implicated in pediatric allergic patients in the Mediterranean area. However, no lentil allergen has been isolated and characterized., Objective: We sought to purify and characterize relevant IgE-binding proteins from boiled lentil extracts., Methods: IgE-binding proteins from crude and boiled lentil extracts were detected with a pool of sera from patients with lentil allergy. Allergens were isolated by gel-filtration chromatography followed by cation- and anion-exchange chromatography or by reverse-phase HPLC. Their characterization included N-terminal amino acid sequencing, complex asparagine-linked glycan detection, specific IgE immunodetection with 22 individual sera from allergic patients, and immunoblot and CAP inhibition assays., Results: Heat treatment of lentils produced substantial changes in the SDS-PAGE patterns of whole extracts, mainly a strong increase of 12- to 16-kd bands and a decrease of 25- to 45-kd components. Major IgE-binding proteins from the boiled lentil extract were located in the 12- to 16-kd and 45- to 70-kd ranges. Two allergens of 16 kd, proteins L1 and L2, and another one of 12 kd, protein L3, were purified. N-terminal sequencing indicated that all 3 were related and allowed their identification as gamma-vicilin subunits. Protein L1 was recognized by 68% of the individual sera tested and inhibited 64% of the IgE binding by commercial lentil CAPs. A second type of allergen of 66 kd, named protein H, was also isolated and identified as a seed-specific biotinylated protein. Protein H reacted with 41% of the individual sera and produced 45% inhibition in CAP inhibition assays., Conclusions: Two different types of allergens have been identified in boiled lentils. Those of 12 to 16 kd, called Len c 1, correspond to gamma-vicilin subunits, and those of 66 kd, designated Len c 2, correspond to seed-specific biotinylated protein. Homology with proteins from other legume species can explain potential cross-reactions among these foods.

Background: Pollen from olive trees (Olea europaea ) is a cause of pollinosis and an aggravating of asthma in Mediterranean regions. Recently, Ole e 1, the major allergen from olive tree pollen, has been isolated and its amino acid sequence has been elucidated. It is a glycoprotein whose carbohydrate moiety is involved in an IgE-binding epitope responsible for cross-reactivity among plant glycoproteins. However, the allergenicity of the free carbohydrate side chains remains to be clarified., Objective: The purpose of this study was to isolate the main carbohydrate component of Ole e 1 allergen and analyze its IgE-binding and histamine-release capabilities., Methods: Deglycosylation treatment of Ole e 1 with PNGase F and gel exclusion chromatography were used to isolate the main sugar component of the allergen. Sera of patients who are allergic to olive pollen and sera sensitive to Ole e 1 have been used in dot blotting assays of IgE binding to the isolated carbohydrate. Heparinized whole blood obtained from patients sensitive to Ole e 1 were stimulated by the free carbohydrate; the resulting histamine release was measured., Results: The main sugar component of Ole e 1 has been isolated. Free carbohydrate was able to bind IgE from sera of patients allergic to olive pollen; the sera of 65% of these patients contained anticarbohydrate reacting IgE, and 100% of those patients were sensitive to Ole e 1. The free carbohydrate promoted in vitro histamine release from basophils of sensitized patients., Conclusion: The carbohydrate moieties of allergenic glycoproteins can constitute significant determinants on the binding to IgE of the sera from patients who are hypersensitive and can be responsible for inducing histamine release from blood cells.

The occurrence of allergic diseases depends on genetic and environmental factors. Genetic factors determine individual risk and these persons should undergo early detection. However, the methods currently available (mainly clinical history and IgE in umbilical cord blood) have poor predictive value so their use in the general population is not practical. In contrast, the feeding habits of newborns and infants can influence the development of food allergies in children at risk. Therefore, several modes of action have been proposed, based mainly on prolonging breast-feeding (with the mother avoiding allergenic foods) and delaying the introduction of complementary foods considered to be a risk. Use of cow milk protein hydrolysates may have a preventive effect similar to that of breast-feeding, but their administration is not problem-free. The preventive effect of partial hydrolysates or soybean formulas is even more questionable.

Over the last three decades several authors have described the existence of an association between sensitivity to different pollens and sensitivity to diverse edible vegetables. An association between ragweed pollinosis and hypersensitivity to Cucurbitaceae vegetables (e.g., watermelon, melon, cucumber) and banana has been reported. Other authors have found a relationship between birch pollinosis and sensitization to hazelnut, apple, carrot, potato, kiwi and other vegetables. Additionally, several papers have shown the association between mugwort pollinosis and sensitization to celery, carrot, spices, nuts, mustard and Leguminoseae vegetables. Later, some studies showed association between grass pollinosis and sensitization to tomato, potato, green- pea, peanut, watermelon, melon, apple, orange and kiwi. Finally, an association between sensitization to plantain pollen and melon hypersensitivity was also described. The association between pollinosis and edible vegetable sensitization has been explained by the combination of different hypotheses, such as the following: 1) presence of lectins in edible vegetables; 2) existence of IgE to carbohydrates of the glycoproteins (cross-reactive carbohydrate determinants); and, 3) existence of common allergens between pollens and edible vegetables. Up to now three allergens have been identified as responsible for cross-reactivity in these associations: profilin, a 14 kd protein that regulates actin; Bet v 1, the 18 kd birch pollen allergen; and a 60-69 kd allergen. It is important to study in depth these associated sensitizations and the common allergens responsible for them in order to improve diagnostic methods and treatment of these syndromes.