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Background: Patients with mastocytosis (MC) have an increased risk of severe anaphylaxis. They report hypersensitivity reactions to drugs and food, but causality often remains questionable. Most allergy centers avoid oral challenge tests (OCT) in MC patients., Objective: To determine the safety of food and drug OCT in patients with MC., Methods: To evaluate the safety and outcome of challenges to drugs and food including food additives retrospectively, of 126 adult MC inpatients, 83 were suspected to have food or drug hypersensitivity and 445 OCTs were performed. History, clinical data, and allergy test results highlighting OCTs were analyzed., Results: Only 10 of 445 OCTs (2.2%) in nine patients resulted in anaphylaxis. Drugs elicited reactions in four of 170 patients (2.4%): two to acetylsalicylic acid (two in 39 patients tested; 5.1%), one to tramadol (one in 12; 8.3%), and one to flurbiprofen (100%). Anaphylaxis to food was recorded in six of 275 OCTs (2.2%); two of 48 (4.1%) to galactose-α-1,3-galactose, two to other foods, and two to sulfites. Flushing or diarrhea occurred owing to histamine in five of 48 patients (10.4%), but also in five of 50 placebo challenges (10.0%), strongly questioning its relevance. Patients with proven anaphylaxis had more bone marrow MC and higher basal serum tryptase (71.3 vs 44.3 μg/L; P < .05)., Conclusions: Challenge-confirmed food and drug anaphylaxis was rare in MC patients. Results have to be interpreted cautiously because placebo reactions occurred. Severe anaphylaxis was infrequent but may occur and should be met by emergency preparedness., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Wheat allergy dependent on augmentation factors (WALDA) is the most common gluten allergy in adults. IgE-mediated sensitizations are directed towards ω5-gliadin but also to other wheat allergens. The value of the different in vitro cellular tests, namely the basophil activation test (BAT) and the active (aBHRA) and passive basophil histamine-release assays (pBHRA), in the detection of sensitization profiles beyond ω5-gliadin has not been compared. Therefore, 13 patients with challenge-confirmed, ω5-gliadin-positive WALDA and 11 healthy controls were enrolled. Specific IgE (sIgE), skin prick tests, BATs, aBHRA, and pBHRA were performed with allergen test solutions derived from wheat and other cereals, and results were analyzed and compared. This study reveals a distinct and highly individual reactivity of ω5-gliadin-positive WALDA patients to a range of wheat allergens beyond ω5-gliadin in cellular in vitro tests and SPT. In the BAT, for all tested allergens (gluten, high-molecular-weight glutenin subunits, α-amylase/trypsin inhibitors (ATIs), alcohol-free wheat beer, hydrolyzed wheat proteins (HWPs), rye gluten and secalins), basophil activation in patients was significantly higher than in controls ( p = 0.004- p < 0.001). Similarly, significant histamine release was detected in the aBHRA for all test substances, exceeding the cut-off of 10 ng/mL in all tested allergens in 50% of patients. The dependency of tests on sIgE levels against ω5-gliadin differed; in the pBHRA, histamine release to any test substances could only be detected in patients with sIgE against ω5-gliadin ≥ 7.7 kU/L, whereas aBHRA also showed high reactivity in less sensitized patients. In most patients, reactivity to HWPs, ATIs, and rye allergens was observed. Additionally, alcohol-free wheat beer was first described as a promising test substance in ω5-gliadin-positive WALDA. Thus, BAT and aBHRA are valuable tools for the identification of sensitization profiles in WALDA.

Background: Mastocytosis is characterized by an accumulation of clonal mast cells (MCs) in tissues such as the skin. Skin lesions in mastocytosis may be clinically subtle or heterogeneous, and giving the correct diagnosis can be difficult., Methods: This study compiles personal experiences together with relevant literature, discussing possible obstacles encountered in diagnosing skin involvement in mastocytosis and cutaneous mastocytosis (CM)., Results: The nomenclature of the term "CM" is ambiguous. The WHO classification defines CM as mastocytosis solely present in the skin. However, the term is also used as a morphological description, e.g., in maculopapular cutaneous mastocytosis (MPCM). This is often seen in systemic, as well as cutaneous, mastocytosis. Typical CM manifestations (MPCM), including mastocytoma or diffuse cutaneous mastocytosis (DCM), all share a positive Darier's sign, and can thus be clinically recognized. Nevertheless, distinguishing monomorphic versus polymorphic MPCM may be challenging, even for experienced dermatologists. Less typical clinical presentations, such as MPCM with telangiectatic erythemas (formerly called telangiectasia macularis eruptiva perstans), confluent, nodular or xanthelasmoid variants may require a skin biopsy for histopathological confirmation. Because MC numbers in CM have a large overlap to those in healthy and inflamed skin, detailed histopathological criteria to diagnose mastocytosis in MPCM are needed and have been proposed. D816V KIT mutational analysis in tissue is helpful for confirming the diagnosis. Biomarkers allow the prediction of the course of CM into regression or evolution of the disease. Further diagnostic measures should screen for concomitant diseases, such as malignant melanoma, and for systemic involvement., Conclusions: Whereas in typical cases the diagnosis of CM may be uncomplicated, less typical manifestations may require specific investigations for making the diagnosis and predicting its course.

Background: Histamine intolerance (HIT) is frequently diagnosed in patients with polysymptomatic otherwise unexplained symptoms., Objectives: To exclude HIT by a single-blind placebo-controlled histamine challenge (SBPCHC), to study clinical features of patients with positive challenge, and to examine the predictability of HIT by biomarkers., Methods: SBPCHC was performed in 59 patients with suspected HIT. History and clinical data, including serum diamine oxidase (DAO) and histamine skin test wheal size of patients with positive versus negative SBPCHC, were compared., Results: Patients were predominantly middle-aged women (84.7%). Three-quarters reported improvement but never resolution of symptoms during a histamine-low diet. Histamine provocation was safe; only 1 patient was treated with antihistamines. Thirty-seven patients (62.7%) displayed symptoms to placebo. HIT was excluded in 50 patients (84.7%). Objective symptoms occurred in 4 of 59 cases (6.8%) after histamine but not after placebo challenge. These were diagnosed with "plausible HIT" because reactions occurring by chance could not be excluded. Another 5 patients (8.5%) were diagnosed with "possible HIT" after case-dependent detailed analysis. Patients with plausible/possible HIT had reported more gastrointestinal symptoms (P = .01), but comparable diet response and equal histamine skin prick test wheal sizes to those without HIT. Serum DAO activity tended to be lower in patients with HIT (P = .08), but was highly variable in those without, limiting its value as a biomarker., Conclusions: SBPCHC disproves HIT in the majority of patients. Placebo-controlled challenges are needed as placebo reactions were frequent. Gastrointestinal symptoms after food intake and reduced DAO levels are markers for HIT; however, specificity is not sufficient enough for making the diagnosis., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Food allergies including cofactor-dependent allergies such as cofactor-dependent wheat allergy (CDWA) decrease the quality of life (QOL) of patients., Objective: To define the health-related QOL and fears in patients with CDWA and to evaluate the impact of diagnosis confirmation by oral challenge test (OCT)., Methods: Patients with CDWA diagnosed by clinical history, sensitization, and OCT were invited to participate. Clinical characteristics, patients' fears, self-perceived overall QOL, the Food Allergy Quality of Life Questionnaire-Adult Form score, and the risks and benefits of OCT were evaluated after the final diagnosis., Results: A total of 22 adults with CDWA (13 male, 9 female; mean age 53.5 years; median 5 years until diagnosis) were included. Specific immunoglobulin E (IgE) levels for gluten proteins were inversely correlated with the reaction threshold (P < .05). Higher reaction severity in the patients' histories correlated with increased basal serum tryptase levels (P = .003) and gluten and gliadin specific IgE (P < .05), but not to QOL. After the first allergic reaction, patients reported a drop in QOL (P < .001). Challenge-confirmed diagnosis and medical consultation could restore the patients' QOL (P < .05) and reduce their fear of further reactions (P < .01). No severe reactions occurred during OCT, which was rated as not stressful and highly beneficial. Compared with patients with CDWA diagnosed without OCT in the literature, health-related QOL was less impaired (mean Food Allergy Quality of Life Questionnaire-Adult Form score 3.8), especially regarding the emotional impact (P < .001 vs existing literature)., Conclusion: Until final diagnosis, patients with CDWA have a severe physical and psychological burden. OCT is a safe method to confirm the diagnosis, restore the patients' severely affected QOL, and reduce their fear of further reactions., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Vaccination of the population is required to combat the COVID-19 pandemic. Allergy testing could reduce anxiety towards COVID-19 vaccination and thereby may increase vaccination rate, however, its effectiveness remains unclear., Methods: One hundred and thirty prospective real-life patients in need of but not daring to get vaccinated asked for allergy workup for COVID-19 vaccine hypersensitivity in 2021/2022. Characterization of patients, identification of anxieties, decrease of patient's anxiety levels, overall vaccination rate and adverse reactions after vaccination were assessed., Results: Tested patients were characterized by being female (91.5%) and having a high rate of previous allergies (e.g. to food 55.4%, drugs 54.6%, or previous vaccinations 50%) and dermatological disease (29.2%) but not always had medical contraindications for COVID-19 vaccination. Sixty one patients (49.6%) were highly concerned (4-6, Likert scale 0-6) about vaccination and 47 (37.6%) expressed resolving thoughts about vaccinaion anaphylaxis (3-6, Likert scale 0-6). However only 35 patients (28.5%) were scared of getting COVID-19 within 2 months (4-6, Likert scale 0-6) and only 11 (9%) patients had high expectations of getting COVID-19 (4-6, Likert scale 0-6). Allergy testing significantly (p < 0.01 to p < 0.05 respectively) reduced the median anxiety of allergic symptoms following vaccination: dyspnoea (4.2-3.1), to faint (3.7-2.7), long-term consequences (3.6-2.2), pruritus (3.4-2.6), skin rash (3.3-2.6) and death (3.2-2.6). After allergy testing, most patients (108/122, 88.5%) let themselves be vaccinated within 60 days. Revaccinated patients with previous symptoms experienced a reduction of symptoms (p < 0.05) upon revaccination., Conclusions: Patients not daring to get vaccinated have more anxiety towards vaccination than to acquire COVID-19. For those, allergy testing excludes vaccine allergy, and is a tool to increase vaccination willingness and thereby helps to combat vaccination hesitancy., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Polyethylene glycol (PEG) has been used for decades, but only caused allergic reactions exceptionally. Introduction of PEG-containing COVID-19 vaccines might have fostered public interest beyond medical reasoning., Objectives: To investigate the impact of the SARS-CoV-2 pandemic on the public interest in PEG allergy in Germany and the published PEG allergy cases worldwide., Methods: A retrospective longitudinal study was conducted to measure public interest in PEG allergy analyzing Google search volume in Germany from February 2018 to January 2022. Medically confirmed "PEG allergy" cases were analyzed by looking at the numbers of PubMed case reports and case series from 1977 until January 2022., Results: Web results in Germany before COVID-19 show search volumes related to "PEG allergy/testing" was negligible, with 10 search queries per month. The pandemic led to a >200-fold increase from 250 queries 2 years before to 55 720 queries 2 years thereafter, reflecting tremendous public interest. Additionally, the maximum monthly search volume from before to during the pandemic increased immensely for "vaccination" (57-fold), "vaccination and adverse effects" (85-fold), "vaccination and allergy" (71-fold). In contrast, the increase of publication numbers for the search term "PEG allergy" was small from 2019 to 2021 (2.5-fold). Only a very low number of 211 cases with "PEG allergy" worldwide since 1977 could be identified., Conclusion: PEG allergy became a topic of major public interest because of COVID-19 vaccination. Scientific publications have increased to a lesser extent, probably promoted by public awareness. Conversely, the overall number of cases published with PEG allergy remain very low. The current high demand for COVID-19 vaccination allergy testing is triggered by public interest instead of medical reasoning., (© 2022 The Author(s).)