BACKGROUND: Cholinergic urticaria (UCOL) is a highly disabling inducible urticaria triggered by an increase in core body temperature. OBJECTIVE: To explore the safety and efficacy of omalizumab in controlling UCOL. METHODS: We conducted a multicenter randomized mixed double-blind and open-label (first 4 months blinded followed by 8 months open-label) placebo-controlled clinical trial in 22 patients suffering from UCOL who were unresponsive to a double dose of antihistamines. We performed an exercise challenge test during each visit as our main outcome variable. RESULTS: The overall rate of exercise challenge test negative at week 48 was 31.3%, with an average increase in exercise challenge test negative rate of 2.9% points (95% CI, 1.5-4.2) per visit. Statistically significant differences in the negative exercise challenge test rate between the placebo and active intervention groups were not observed during the blinded period (first 4 months of the study). However, from the fourth dose, a progressive improvement was observed. When comparing before and after treatment, statistically significant improvements in all secondary outcome measures were noted after 4 doses (UCOL score: P = .0015; visual analog scale score: P = .0108; days with symptoms: P [.0125) and after 8 doses (UCOL score: P = .0005; chronic urticaria quality of life questionnaire: P = .0105; visual analog scale score: P = .0008; and days with symptoms: P = .0144). In the followup visit after the cessation ...

BACKGROUND: Suspicion of allergic drug reaction can cause important disturbances in the patient's life. OBJECTIVE: We evaluated in a prospective multicenter study the quality of life of patients who suffered a possible allergic drug reaction, and analyzed the effect of a drug allergy evaluation. METHODS: Patients (>18 years old) answered the specific questionnaire twice: before the drug allergy evaluation, and 1 month after it was completed. Statistics were performed using STATA. RESULTS: A total of 360 patients (240, 66.6% female; mean age, 45.4 years; standard deviation [SD], 15.6 years) completed the first questionnaire. After the evaluation, 150 of 346 patients (43.4%) were diagnosed as allergic to the drug (115 of 150 immediate; 35 of 150 delayed) and 196 of 346 patients (56.6%) as nonallergic. The mean value of the first questionnaire was 32.14 (SD, 11.84); patients with anaphylaxis, nonanaphylactic immediate reaction, with more than 1 drug reaction, or a chronic osteoarticular disease, had a statistically significant higher score in Q0 (worse quality of life). After the allergy study, the mean of the second questionnaire was 27.27 (SD, 9.96), showing a global improvement (P < .001). No statistically significant difference was found between drug allergic and non-drug allergic patients (P = .340); however, being >40 years old (P = .030), having a chronic osteoarticular disease (P = .003) and having more than 1 reaction to drugs (P < .001) were associated with a statistically significant worse quality of life after the evaluation. CONCLUSIONS: Having suffered anaphylaxis, more than 1 reported drug allergy or presenting a musculoskeletal disease are factors that worsen the quality of life. Quality of life improved significantly after completing a drug allergy evaluation. (C) 2019 American Academy of Allergy, Asthma & Immunology

BACKGROUND: Differentiating between immunoglobulin E (IgE)-dependent and IgE-independent hypersensitivity reactions may improve the etiologic orientation and clinical management of patients with allergic reactions in the anesthesia setting. Serum tryptase levels may be useful to discriminate the immune mechanism of allergic reactions, but the diagnostic accuracy and optimal cutpoint remain unclear. We aimed to compare the diagnostic accuracy of tryptase during reaction (TDR) alone and the TDR/basal tryptase (TDR/BT) ratio for discriminating IgE- from non-IgE-mediated allergic reactions, and to estimate the best cut point for these indicators. METHODS: We included 111 patients (45% men; aged 3-99 years) who had experienced an allergic reaction, even though the allergic reaction could be nonanaphylactic. Allergy tests were performed to classify the reaction as an IgE- or non-IgE-mediated one. The area under the curve (AUC) of the receiver operating characteristic analysis was performed to estimate the discriminative ability of TDR and TDR/BT ratio. RESULTS: An IgE-mediated reaction was diagnosed in 49.5% of patients, of whom 56% met anaphylaxis criteria. The median (quartiles) TDR for the IgE-mediated reactions was 8.0 (4.9-19.6) and 5.1 (3.5-8.1) for the non-IgE-mediated (P = .022). The median (quartiles) TDR/BT ratio was 2.7 (1.7-4.5) in IgE-mediated and 1.1 (1.0-1.6) in non-IgE-mediated reactions (P < .001). The TDR/BT ratio showed the greatest ability to discriminate IgE- from non-IgE-mediated reactions compared to TDR (AUC TDR/BT = 0.79 [95% confidence interval (CI), 1.1-2.2] and AUC TDR = 0.66 [95% CI, 1.1-2.2]; P = .003). The optimal cut point for TDR/BT (maximization of the sum of the sensitivity and specificity) was 1.66 (95% CI, 1.1-2.2). CONCLUSIONS: The TDR/BT ratio showed a significantly better discriminative ability than TDR to discriminate IgE- from non-IgE-mediated allergic reactions. An optimal TDR/BT ratio threshold of approximately 1.66 may be useful in clinical practice to classify allergic reactions as IgE- or non-IgE-mediated.

The study of anaphylactoid reactions during perioperative procedures and anaesthesia represents a diagnostic challenge for allergists, as many drugs are administered simultaneously, and approximately half of them trigger allergic reactions without a verifiable IgE-mediated mechanism. Recently, mast cell receptor MRGPRX2 has been identified as a cause of pseudo-allergic drug reactions. In this study, we analyse the ability of certain drugs used during perioperative procedures and anaesthesia to induce MRGPRX2-dependent degranulation in human mast cells and sera from patients who experienced an anaphylactoid reaction during the perioperative procedure. Using a ß-hexosaminidase release assay, several drugs were seen to cause mast cell degranulation in vitro in comparison with unstimulated cells, but only morphine, vancomycin and cisatracurium specifically triggered this receptor, as assessed by the release of ß-hexosaminidase in the control versus the MRGPRX2-silenced cells. The same outcome was seen when measuring degranulation based on the percentage of CD63 expression at identical doses. Unlike that of the healthy controls, the sera of patients who had experienced an anaphylactoid reaction induced mast-cell degranulation. The degranulation ability of these sera decreased when MRGPRX2 was silenced. In conclusion, MRGPRX2 is a candidate for consideration in non-IgE-mediated allergic reactions to some perioperative drugs, reinforcing its role in mast cell responses and their pathophysiology.

Allergy tests are routinely performed in most hospitals everyday. However, measuring the outcomes of these tests is still a very laborious manual task. Current methods and systems lack of precision and repeatability. This paper presents a novel mechatronic system that is able to scan a patient's entire arm and provide allergists with precise measures of wheals for diagnosis. The device is based on 3-D laser technology and specific algorithms have been developed to process the information gathered. This system aims to automate the reading of skin prick tests and make gains in speed, accuracy, and reliability. Several experiments have been performed to evaluate the performance of the system.

Background: Allergy to mollusks has been the focus of fewer studies than allergy to crustaceans. Furthermore, allergy to mollusks is less well characterized. Objectives: To describe the clinical characteristics of mollusk-allergic patients, to identify the responsible allergens, and to assess cross reactivity. Methods: We performed a prospective multicenter study including 45 patients with mollusk allergy, which was diagnosed based on a suggestive clinical history and a positive skin test result with the agent involved. Fractions were identified using SDS-PAGE and immunoblotting. The proteins responsible were subsequently identified using mass spectrometry. ELISA inhibition studies were performed with mollusks, dust mites, and crustaceans. Results: We found that 25 patients (55%) were allergic to cephalopods, 14 (31%) to bivalves, and 11 (24%) to gastropods. Limpet was the third most frequent cause of allergy (15% of cases). In 31 patients (69%), the manifestation was systemic; 10 (22%) exhibited oral allergy syndrome, and 7 (15%) experienced contact urticaria. Most major allergens were found between 27 kDa and 47 kDa. ELISA inhibition assays revealed a high degree of inhibition of cephalopods and bivalves from all the groups of mollusks, mites, and crustaceans. Mass spectrometry identified tropomyosin, actin, and myosin as the major allergens. Conclusions: Cephalopods, especially squid, are the mollusks that most frequently trigger allergic symptoms. The very frequent occurr

Omalizumab (OmAb) is a humanized anti-IgE antibody approved for the treatment of chronic spontaneous urticaria (CSU). OmAb's mechanism of action is known to include actions on free IgE and on pre-bound IgE. However, OmAb is equally and rapidly effective against autoimmune and non-autoimmune urticaria where IgE involvement is not clear, suggesting the involvement of additional mechanisms of action. In this study, we sought to investigate the ability of OmAb to inhibit mast cell and basophil degranulation induced by sera from CSU patients. For this purpose, we performed a comparison between the in vitro incubation of sera from CSU patients treated with OmAb and the in vivo administration of OmAb in a clinical trial. We found that OmAb added in vitro to sera from CSU patients did not modify the ability of the sera to induce cell degranulation. Similarly, the sera from patients treated with OmAb in the context of the clinical trial who had a good clinical outcome maintained the capacity to activate mast cells and basophils. Thus, we conclude that the beneficial activity of OmAb does not correlate with the ability of patient sera to induce cell degranulation

Background: Peanut allergy is the most common cause of anaphylaxis and food-related death. However, there is currently no approved immunotherapy treatment. Hence, this warrants the need for relevant and convenient animal models to test for adequate immunotherapies. Materials & methods: In this study, we compared three mouse strains: CD1, BALB/c and C57, to select a model of peanut allergy. After that, we conducted then a therapeutic study using an immunogenic peanut extract encapsulated in nanoparticles made with polymer Gantrez((R)) following the solvent displacement method. Results & conclusion: After implementing a dosing schedule with oral commercial peanut butter, the antibody responses, cytokine profiles and, above all, the anaphylaxis induced after a challenge with peanut proteins, showed that the outbred CD1 strain was the most susceptible to peanut sensitization. CD1 sensitized mice were orally immunized with three doses of the nanoparticle formulation capable of protecting them against the severe anaphylactic symptoms induced by the peanut challenge.

LTP syndrome occurs in a non-Mediterranean area and is related to multiple sensitizations to foods and pollens such as plane tree and mugwort. In these pollen sensitizations, Pru p 3 seems to be the primary sensitizer.

The prick test is one of the most common medical methods for diagnosing allergies, and it has been carried out in a similar and laborious manner over many decades. In an attempt to standardize the reading of the test, many researchers have tried to automate the process of measuring the allergic reactions found by developing systems and algorithms based on multiple technologies. This work reviews the techniques for automatic wheal measurement with the aim of pointing out their advantages and disadvantages and the progress in the field. Furthermore, it provides a classification scheme for the different technologies applied. The works discussed herein provide evidence that significant challenges still exist for the development of an automatic wheal measurement system that not only helps allergists in their medical practice but also allows for the standardization of the reading and data exchange. As such, the aim of the work was to serve as guideline for the development of a proper and feasible system.

Our data prove the existence of common mechanisms of action of OmAb in mast cells and basophils that would explain its effectiveness and rapid effect in chronic urticaria and provide a basis for its use in other diseases mediated by these cells.

Fifteen of 201 patients with negative results for LTP in the SPT were sensitized to this allergen in the in vitro tests, and 18 of 41 patients with positive results for LTP in the SPT were not sensitized according to the in vitro tests. Seventeen of 186 patients with negative results for profilin in the SPT were sensitized to Phl p 12 by serum sIgE, and 30 out of 56 patients with positive results for profilin in SPT were not sensitized to Phl p 12 according to the other tests. Moderate agreement was observed between the 3 techniques studied. CONCLUSIONS: SPT is a sensitive technique for detecting sensitization to LTP and profilin. Its results are similar to those of in vitro techniques, especially in patients with negative SPT results for peach LTP and palm tree profilin.

Perioperative reactions are more common than previously reported. Mild hypersensitivity perioperative reactions-involving only skin-should be considered in evaluating patients because a substantial number of these reactions are IgE mediated.

In the last decade, peanut allergy has increased substantially. Significant differences in the prevalence among different countries are attributed to the type of thermal processing. In spite of the high prevalence and the severe reaction induced by peanuts, there is no immunotherapy available. The aim of this work was to evaluate the potential application of poly(anhydride) nanoparticles (NPs) as immunoadjuvants for peanut oral immunotherapy. NPs loaded with raw or roasted peanut proteins were prepared by a solvent displacement method and dried by either lyophilization or spray-drying. After physicochemical characterization, their adjuvant capacity was evaluated after oral immunization of C57BL/6 mice. All nanoparticle formulations induced a balanced T(H)1 and T(H)2 antibody response, accompanied by low specific IgE induction. In addition, oral immunization with spray-dried NPs loaded with peanut proteins was associated with a significant decrease in splenic T(H)2 cytokines (interleukin 4 [IL-4], IL-5, and IL-6) and enhancement of both T(H)1 (gamma interferon [IFN-¿]) and regulatory (IL-10) cytokines. In conclusion, oral immunization with poly(anhydride) NPs, particularly spray-dried formulations, led to a pro-T(H)1 immune response.

Allergic skin tests have to be performed 4-6 weeks after an allergic anesthetic reaction. Patients with allergic reactions during anesthesia were prospectively included (n = 44). Skin tests were performed in two stages: (i) Stage 1 (S1), 0-4 days after the reaction; and (ii) Stage 2 (S2), 4-8 weeks after. Five (11.5%) surgical procedures were suspended due to the reaction. Positive skin tests were obtained in 25/44 patients (57%). Allergic diagnosis was carried out at S1 in 15/25 (60%) and at S2 in 10/25 (40%). Three patients resulted positive only in S1. Overall agreement among S1 and S2 skin tests was 70.45%. The kappa statistic was 0.41 (P-value = 0.002). Odds ratio of obtaining a false negative in S1 (compared with S2) was 3.33. Early allergological study is useful, could minimize false negatives, but should be considered as a complement to late skin tests.

The purpose of this investigation was to compare the genotypic profiles of Staphylococcus aureus isolated from atopic dermatitis (AD) patients and from control subjects, and to study the relationship between clinical severity, immune response, and genomic pattern of S. aureus isolated from AD patients. We selected 32 patients with AD and S. aureus skin colonization and 31 atopic controls with no history of AD who where asymptomatic carriers of S. aureus. Microarray-based genotyping was performed on S. aureus isolates. In AD patients, clinical severity was assessed using the Scoring Atopic Dermatitis index and total IgE levels and staphylococcal superantigen-specific IgE levels (SEA, SEB, SEC, TSST1) were determined. The genes lukE, lukD, splA, splB, ssl8, and sasG were more frequent in isolates from AD patients. CC30 was more common in isolates from atopic controls than in AD patients. There was a correlation between total IgE and clinical severity, but an association between clinical severity, immune response, and the presence of S. aureus superantigen genes, including enterotoxin genes, could not be demonstrated. Finally, a correlation was found between AD severity and other S. aureus genes, such as sasG and scn. S. aureus factors besides superantigens could be related to the worsening and onset of AD.

Anaesthetic hypersensitivity reactions can be IgE- or not IgE-mediated and are a challenge to find the causal agent. Histamine and tryptase determination are classically considered useful in the diagnosis of these reactions. The aim of our study was to assess the diagnostic usefulness of plasma histamine and different cut-off points of serum tryptase. MethodsPatients suffering a reaction suggestive of hypersensitivity during general anaesthesia in Clinica Universidad de Navarra (2008-2012) were included. Serum tryptase and plasma histamine were measured at the time of the reaction and 2h later. Baseline tryptase was also determined. Four to eight weeks after the reaction an allergological study was performed to all the drugs or products involved in the reaction. ResultsSixty-five patients suffered an immediate hypersensitivity reaction during the period of the study. Thirty-seven patients (20 male) with median age 48years (12-79) were included because they completed allergological study, and histamine and tryptase were correctly obtained. Elevated plasma histamine was observed in 34 cases (92%). Tryptase exceeded twice the basal values in 10 patients (31%). Using different cut-off points of tryptase, the number of patients with elevated tryptase would be 15 patients (41%) for a cut-off point of 5g/L; 12 patients (32%) for a cut-off point of 8.23g/L; nine patients (24%) for 10.5g/L; and eight patients (22%) for 11.4g/L. The median tryptase level for the IgE-mediated reactions was 9.0g/L (2-70g/L) and 4.0g/L (3-13g/L) in non-IgE-mediated reactions (P<0.01). Median tryptase levels were higher in more severe reactions (grade 2 or 3) in comparison with grade 1. The best ratio for serum-tryptase-during-reaction/basal-serum-tryptase to discriminate between IgE and non-IgE reactions was 2.0. ConclusionThe best criterion for discriminating IgE- and non IgE-mediated hypersensitivity reactions in anaesthesia was a tryptase value exceeding twice the basal one.

La inmunoterapia para el tratamiento de enfermedades alérgicas implica ciertas desventajas, que pueden ser reducidas si se emplean adyuvantes adecuados, que sean capaces de amplificar la respuesta inmune con un efecto alergénico mínimo. En ese contexto, las formas farmacéuticas más prometedoras para aumentar la eficacia y seguridad de la inmunoterapia, parecen ser las micro y nanopartículas, de polímeros biodegradables y liposomas. En esta revisión describimos estudios previos de nuestro grupo en los que empleamos como adyuvante nanopartículas Gantrez® AN y demostramos su capacidad de estimular el sistema inmune. Empleamos dos tipos de nanopartículas, con y sin lipopolisacárido de Brucella ovis como inmunomodulador en un modelo de ratón alérgico a L. perenne. Encontramos que los ratones sensiblizados a Phleum cuando recibían inmunoterapia con nanopartículas Lolium-Gantrez® estaban protegidos de la anafilaxia inducida por el alérgeno tanto en las tasas de mortalidad como en los niveles de MCP-1. Probamos asimismo estas formulaciones por vía oral en un modelo animal sensibilizado a ovoalbúmina y comprobamos que les protegía también del shock anafiláctico.

Desensitization is a useful procedure in patients who are allergic to their chemotherapy agents..

The precipitin technique has been used in insulin resistance and immunity studies since the 1940s [7]. In the case described, the technique proved, once again, to be a valid method for choosing the most appropriate insulin. However, whether or not an immunological mechanism was involved in the lipoatrophic process remains uncertain, and further studies with adequate immunological assessment are necessary.

Component-based microarray ISAC CRD103 and whole-allergen CAP showed high Se and Sp diagnosing equally grass and cypress pollen allergy. The cut-off point for each allergen should be properly applied for both techniques.

Further studies are needed to evaluate latex-sublingual immunotherapy, since efficacy could not be demonstrated in adult patients with avoidance of the allergen.

La clase de los insectos es muy amplia y se divide en diferentes órdenes, según diferentes características como: la presencia o no de alas en el adulto, tipo de metamorfosis, aparato bucal, etc. En un primer término se dividen en los insectos alados (Pterigotas) y los no alados (Apterigotas). Dentro de cada una de estas divisiones hay numerosas subdivisiones.