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Introduction and Objectives: Allergy to galactose-α-1,3-galactose (alpha-gal) is a peculiar form of food allergy generally manifesting as an anaphylactic reaction hours after mammalian meat consumption, due to the presence of specific IgE against this oligosaccharide. In addition, immediate anaphylaxis may develop after exposure to other sources of alpha-gal, such as monoclonal antibody cetuximab, vaccines, plasma expanders or anti-snake venoms. Sensitization to alpha-gal has also been implicated in the rapid degeneration of biological valve implants, and recognized as a cause of occupational disease in cattle raisers. The implication of tick bites in this type of sensitization has been accepted by all the research groups dedicated to this disease., Patients and Method: The present study describes the clinical and sensitization characteristics of 39 patients diagnosed with alpha-gal allergy in the hospitals of our province (Lugo, Monforte de Lemos and Burela, Spain)., Results: Most patients were middle-age males. Of note, is the fact that the series includes the first pediatric patient reported in Spain to date. The predominant clinical manifestations were urticaria or delayed anaphylaxis after consumption of mammalian meat. Seventy-four percent of the patients reported having suffered a previous tick bite, and the clinical presentation of anaphylaxis was significantly more prevalent in those with a persistent local reaction following the bite than in those with no such reaction (p = 0.032)., Conclusions: A review is also made of the disorder which, due to its variable clinical expression, is referred to as alpha-gal syndrome. The study concludes that a diagnosis of alpha-gal allergy should be considered in patients with urticaria-anaphylaxis of uncertain origin or manifesting after the administration of vaccines or products of bovine/porcine origin., (Copyright © 2019 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Acquired cold urticaria (ACU) is characterized by the development of itchy wheals after cold exposure. Generalized urticarial skin rashes triggered by cold exposure characterize certain monogenic autoinflammatory diseases (AIDs). The objective of this study is to investigate the presence of variants in genes causing AIDs that present with cold-induced urticarial skin rashes in patients clinically diagnosed with ACU, in order to look for susceptibility factors for the disease. Fifty patients with primary ACU were studied. Germline and post-zygotic variants on the NLRP3, NLRP12, NLRC4 and PLCG2 genes were investigated using next-generation sequencing technology. Seven patients (14%) carried 8 heterozygous germline variants in the following genes: NLRP3 (n = 1), NLRP12 (n = 3), NLRC4 (n = 1), PLCG2 (n = 3). No pathogenic or likely pathogenic variants were detected, and deep analyses of the sequences obtained did not identify any post-zygotic variant. In conclusion, ACU is not related to post-zygotic or germline pathogenic variants in the NLRP3, NLRP12, NLRC4 and PLCG2 genes.

Background: The objectives of this study were to investigate the prevalence of sIgE to galactose-α-1,3-galactose (α-gal) in individuals with acute urticaria or anaphylaxis from different geographical areas of Spain and to evaluate the relevance of demographics and lifestyle as risk factors for this immune response., Methods: Participants were recruited from allergy departments at 14 Spanish hospitals. Patients aged 18 years or older presenting with urticaria or anaphylaxis were enrolled into one of 2 arms: cases and controls. An interviewer-administered questionnaire collecting demographic data, lifestyle habits, and the presence of cofactors was obtained from each participant. sIgE to α-gal and total IgE were determined using ImmunoCAP. sIgE levels ≥0.35 kU/L were considered a positive result., Results: The study population comprised 160 cases and 126 controls. The median age was 44 years. The overall prevalence of a positive result of sIgE to α-gal was 15.7%; this was higher in cases (26.3%) than in controls (2.4%). The sIgE anti-α-gal positivity rate ranged from 37.68% (rural) to 15.38% (semiurban), and 7.85% (urban). The rates of positivity were 46.32%, (Northern), 0.72% (Center), and 0% (Mediterranean). A positive result for sIgE to α-gal was associated with a history of tick bites, participation in outdoor activities, pet ownership, and ingestion of mammalian meats or innards before the onset of symptoms. Only alcohol consumption could be implicated as a cofactor., Conclusion: Sensitization to α-gal in patients with urticaria or anaphylaxis differs considerably between the 3 geographical areas studied and is related to tick bites.

Background: Peanut allergens are common triggers of food allergy. Analyses of sensitization patterns, relationships with other allergens, clinical symptoms, and variation with age are needed. We studied sensitization to Ara h 2, Ara h 9, and Pru p 3 in a peanut allergic children/adolescents and the relationship with peach and pollen., Methods: Peanut allergic patients aged between 1 and 20 years old were classified into two groups: A) allergic to peanut only and B) allergic to peach and peanut. The IgE response was measured to Ara h 2, Ara h 9, and Pru p 3., Results: Of 964 subjects evaluated, 28% were allergic to peanut. From this group, 68% were also sensitized to pollen. Urticaria was the most frequent entity followed by anaphylaxis and OAS. Fifty-eight percent had Ara h 2- and/or Ara h 9-specific IgE. More than half reported symptoms with peanut alone (Group A) and 35% to peanut and peach (Group B). We observed significant differences in sex, age, onset of symptoms, and sensitization to Artemisia between groups. IgE response to Ara h 2 was more frequent in Group A, and Ara h 9 and Pru p 3 in Group B. We observed a decrease in sensitization to Ara h 2 and an increase to Ara h 9 and Pru p 3 with increasing age., Conclusion: Peanut allergy is frequent in subjects with allergy to plant foods, with Ara h 2 and Ara h 9 being two important allergens. In younger patients, Ara h 2 predominates over Ara h 9. The reverse was observed in older patients., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The ubiquitous fish-nematode Anisakis simplex produces acute urticaria or angioedema in the course of gastro-allergic anisakiasis. We studied the relationship between this nematode and chronic urticaria (CU), as well as the clinical usefulness of measuring specific IgG4 in A. simplex-sensitized patients with CU., Methods: First, the prevalence of sensitization to A. simplex was estimated in 135 consecutive CU patients and the result was compared with known data about sensitization in a healthy population. Then, clinical response to a 2-month diet without fish was analyzed in 76 CU patients. The improvement rate in patients with and without sensitization to A. simplex was compared. Finally, the improvement rate, other clinical data and specific immunoglobulins in sensitized patients with and without detectable specific IgG4 were compared., Results: a) The A. simplex sensitization rate in CU patients was 52.6 % compared with a known prevalence of between 16 and 20 % in our region. b) Of 65 sensitized patients, 52 experienced clinical improvement after the diet compared with only three of 11 patients without sensitization to A. simplex (p = 0.001). c) Of 43 patients with detectable specific IgG4, 38 showed clinical improvement compared with only 14 of 22 patients without detectable IgG4 (p = 0.02). Eight of nine patients with previous fish-associated cutaneous symptoms had detectable specific IgG4 compared with 15 of 32 patients who reported no previous fish-associated symptoms or acute urticaria (p = 0.03)., Conclusions: Our results indicate that A. simplex is a possibly widespread etiologic agent able to induce CU. This parasite model constitutes the first report that associates an infectious agent with CU on a large scale. The detection of IgG4 antibodies reflects a previous acute parasitic infection and a temporary diet without fish improves symptoms in most patients with detectable specific IgG4.

Background: In spite of the frequency of chronic urticaria there are very few epidemiological studies of its prevalence and distribution., Objective: We wanted to approach the real prevalence of chronic urticaria in a population-based study and to depict demographic distribution and personal perception of the disease. We also wanted to describe the frequency of acute urticaria episodes in the population studied., Methods: We conducted a population-based study among adults in Spain. We questioned 5003 individuals after calculating a sample size for a maximum variability (conservative approach p=q=0.5)., Results: We found a 0.6% (95% CI: 0.4-0.8) prevalence of chronic urticaria. The prevalence is significantly higher in women than in men with a OR=3.82 (95%CI 1.56-9.37). Chronic urticaria is a self-limited disease, yet in 8.7% of cases chronic urticaria lasts from one to 5 years and in 11.3%, for more than 5 years. The average age of onset is 40 years., Conclusions: We offer large epidemiology study data on the prevalence of chronic urticaria. The prevalence of chronic urticaria has not yet been defined in an adult population-based study. With this work we offer such data to describe the prevalence and features of this disease.

Background: There are no studies assesing whether patients with idiopathic anaphylaxis are a heterogenous population, Objective: A study has been carried out to assess whether clinical and functional differences (mast cell releasability) exist between two sub-types of Idiopathic Anaphylaxis (Generalized Idiopathic Anaphylaxis -IA-G- and Idiopathic Anaphylaxis with Angioedema -IA-A-)., Methods: Patients were selected from the Idiopathic Anaphylaxis (IA) patient population of Hospital General de Albacete (Albacete, Spain) and this data were collected between 1990 and 1995. This series is composed of 81 patients. In the interest of seeing whether an IA classification is warranted between IA-G and IA-A, a logistic regression model was constructed in order to know if differences exist between IA-G and IA-A. To evaluate mast cell releaseability in different groups (IA-G, IA-A, atopic patients, urticaria and healthy subjects) we analysed the log 10 wheal area produced by four consecutive concentrations of codeine (from 90 to 3,3 mg/ ml). In those patients with IA-G, the variable urticaria was controlled, but not in those with IA-A. A parallel line assay was used to study the differences arising among all groups. When the conditions of parallelism and linearity were not fulfilled, a Hotelling's T2 test was performed., Results: In the logistic regression equation total IgE, with an O.R. of 1.006 (95% C.I. 1.001-1.01) favoured the presence of IA-G; whereas the presence of urticaria did not favour the presence of IA-G, with an O.R. of 0.159 (95% C.I. 0.04-0.507). IA-G and IA-A patients showed a higher cutaneous reaction to codeine than atopic patients (p=0.005 and p=0.001 respectively). However, IA-G patients had a lower reaction to codeine than those patients with urticaria (p=0.048). No differences were observed among patients with IA-A and patients with urticaria, as was the case between IA-A and IA-G patients with respect to cutaneous response to codeine., Conclusion: Apparently, IA-G patients appear to be closely related to the presence of atopy, while IA-A patients are closely related to the presence of urticaria. Along with other unknown factors, an enhanced mast cell releaseability may explain these episodes of Idiopathic Anaphylaxis among atopic patients.

Background: Peach is among the main foods causing allergic reactions in the Mediterranean adult population. Only a single peach allergen, named Pru p 3, has been characterized. However, a potential role of profilin has also been suggested in grass pollen-associated allergy to peach., Methods: Complementary DNA clones for two different peach profilin isoforms were obtained by reverse transcriptase polymerase chain reaction using non-degenerated primers. Expression of recombinant peach profilin was performed in Escherichia coli, and confirmed using rabbit polyclonal antibodies to sunflower pollen profilin. Twenty-nine individual sera from patients with peach allergy proved by double-blind, placebo-controlled food challenges (DBPCFC), either with (n = 15) or without (n = 14) specific IgE to Bet v 2, were used in immunodetection assays to test recombinant peach profilin reactivity., Results: Each peach profilin cDNA included an open reading frame coding for a 131 amino acid protein. The peach profilin isoforms, designated Pru p 4.01 and Pru p 4.02, showed 80% of amino acid sequence identity, and were very similar (>70% identity) to allergenic profilins from plant foods and pollens. Recombinant Pru p 4.01 was expressed in E. coli as a nonfusion protein, displaying the expected molecular size and reacting with anti-profilin antibodies. rPru p 4.01 was recognized by all sera (15 of 15) with specific IgE to Bet v 2, whereas no sera (zero of 14) without IgE to this birch allergen reacted with rPru p 4.01., Conclusions: Peach profilin Pru p 4 is very closed to other allergenic profilins from plant foods and pollens. A complete correlation between reactivity to rPru p 4 and rBet v 2 has been found in sera from peach allergic patients.

Nowadays, caterpillars are included among the agents that elicit contact urticaria by a non-immunologic mechanism. Our objective was to find the rôle that an IgE-mediated mechanism could have among patients with suspected contact urticaria from pine processionary caterpillars. 16 patients with suspected contact urticaria from this caterpillar were studied by prick testing and specific IgE detection by immunoblotting. 87% of the patients had a positive prick test and immunoblotting for caterpillar extract. In these allergic patients, the symptoms associated with urticaria were: angioedema (79%), conjunctivitis (36%) and severe anaphylaxis (14%). The most frequent localizations of the wheals were the neck (100%) and forearms (93%). Angioedema was more frequent on the eyelids (79%). The IgE-immunoblot detected in the caterpillar extract several reactive bands, with apparent MWs from to 45 to 4kDa. A total of 5 major allergens were identified, but a band around 14kDa proved to be the dominant allergen. Sensitization to Thaumetopoea pityocampa was found to be the most important mechanism of airborne contact urticaria from this caterpillar. Low-MW proteins are the main IgE binding components of crude caterpillar extract.

Objectives: 1) To study the clinical and analytic features of infectious disease associated to urticaria in children. 2) To look into the probable etiology of the infectious disease. 3) To determine atopic predisposition and previous urticarial episodes and to rule out the involvement of antibiotics., Design: Transversal and observational study., Setting: Pediatric Allergy Outpatient Clinic of a tertiary Hospital., Patients: Forty-four children, aged 1 to 12 years with acute urticaria associated to clinically infectious or febrile illness attending an Emergency Pediatric Department., Intervention: Symptoms evaluation and physical examination in the seventh first days and follow over 3-6 weeks by the same physician., Measurements: Clinical features of urticaria (duration, angioedema associated); Clinic diagnosis of illness infectious (acute respiratory infection, gastroenteritis, febrile syndrome); white blood cells count, C-reactive protein, aminotransferases (AST, ALT), L-Y-glutamyl transferase; viral culture and antigen detection: enterovirus (EV), adenovirus, respiratory syncytial virus (RSV), parainfluenza 1, 2 and 3, influenza A y B and cytomegalovirus (CMV); serological assay: CMV, enterovirus, mycoplasma pneumoniae, Epstein-Barr, parvovirus B19., Result: 22 children (50%) are between 1-2 years old. 40 patients (90,9%) had symptoms of respiratory tract infection and only four patients had a pneumonia. The other 4 children had a gastroenteritis. The analytic was suggestive of viral infection in 35 (79.5%) and unknown on seven patients. In 20 children (45.4%) was identified a probable infection. The viral detection was positive in 3 patients: CMV, herpes simplex 1 and influenza A. Twenty microbiological findings for seventeen patients was found by serological criterion of probable infection: enterovirus (10); parvovirus B19 (4); Epstein-Barr (3) y mycoplasma (3). Evidence of a double serologic infection was found in three patients. In comparison with a serological control group encountered that acute urticaria during a infectious disease is significantly associated (p = 0.0054) to high titer to enterovirus by complement-fixation. The urticaria was associated with angioedema in 38.6% and 9 children (20.4%) related an previous similar episode. Twenty-one (47.7%) had been treated with antibiotics before development the urticaria. All patients was given the suspected antibiotic and no patient developed any adverse reaction., Conclusions: The clinically infectious associated to urticarial rash in children, usually is a viral respiratory infections. Is more frequent at infant. In spite of antibiotic therapy is often related to development the urticaria, the subsequent challenge with the same antibiotic is good tolerated.

Urticaria is characterized by the appearance of hives and pruritus. Those hives are formed by oedema and vasodilatation and they disappear when they are pressed on. The acute presentation is extremely common and affects between 10 and 20% of the population at a determined moment. In its simplest form, urticaria is envisioned to represent the same sort of wheal-and-flare reaction observed when histamine is injected into the skin. It produces erythema because of capillary vasodilatation, oedema because of increased permeability in capillary and pruritus secondary at local specific receptors stimulation. Angioedema is caused by the same pathologic alterations that occur in the deep dermis and subcutaneous tissue. Thus, an area involved with angioedema has swelling as the prominent manifestation and appearance of the skin itself may be normal. Due to reduced nerve supply in dermis, angioedema is associated with oppression and not pruritus. Immunoallergological study of urticaria and/or angioedema was requested in 133 cases from 648 from the first patient's visits to the surgery. It supposes a 20.52%. The family suspicion of etiology was food in 62 cases, chemical products in 39 cases, other factors (physical, stings, balloons and other manufactured products.) in 7 cases and 25 cases without a direct relation. Out of 100 children diagnosed of allergic urticaria-angioedema 67 was by food; the foods implicated in frequency order were: eggs and nuts, fruit, milk, vegetables, fish and shellfish. In second place, chemical products were responsible of urticaria in 12 children; five of them were positive in diagnosed proof (prick, oral challenge) for penicillin and amoxicillin, both from beta-lactamic group; two of them had and adverse reaction to anesthetic agents; other two cases were after administration of vaccination and due to tetanus toxin; and three cases were due to aspirin, confirmed by oral provocation test. In 10 children the etiological agent was latex. Other etiologies were: three cutaneous reactions after stings (two by wasps and one by mosquito) three reactions due to spices (paprika, cumin, anise, mustard) and two reactions caused by manufactures products containing additives as yellow-orange.