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Background: In 2002-2005, we conducted a phase I/II clinical trial where a new allergy immunotherapy (AIT) route was introduced: intralymphatic immunotherapy (ILIT). Ultrasound guidance allowed injection of allergen directly into inguinal lymph nodes. Grass pollen-allergic patients received 3 injections with 1-month intervals. The short ILIT was more patient-friendly, required lower dosing, and was comparable with SCIT regarding short-term efficacy, which was used as a reference., Objective: Nineteen years after ILIT, the same patients were followed up to assess the long-term effect on quality of life and efficacy of the treatment., Methods: Patients who received ILIT and SCIT in 2002-2005 and an additional group of patients, who completed SCIT in 2015-2018, were recruited. All participants received a trial-specific in-house questionnaire and a standardized Rhinoconjunctivitis Quality of Life Questionnaire. Data were recorded off- (February 2021) and on- (May-June 2021) season. Descriptive statistics were applied., Results: Of 58 and 54 patients who originally received ILIT or SCIT, 25 (43%) and 29 (54%) patients, respectively, returned the questionnaires for analysis. Four (16%) and 3 (11%) of the ILIT and SCIT patients, respectively, developed complete protection against grass pollen-mediated rhinitis, whereas another 15 (60%) and 20 (69%) expressed satisfaction with the received AIT. In both groups, any persistent symptoms were reported as mild. Medication usage in the ILIT and SCIT groups was comparable. Nineteen (76%) and 23 (79%) patients, respectively, expressed satisfaction with their AIT., Conclusions: Grass pollen ILIT leads to long-term significant improvement in rhinitis-associated quality of life 19 years after treatment, and the ILIT quality-of-life effect was not inferior to that of SCIT., (© 2022 The Author(s).)

Background: Subcutaneous venom immunotherapy (VIT) represents an effective treatment against bee venom allergy. However, it involves long treatment times, high costs, and the risk of adverse events (AEs). Shorter, safer, and cheaper treatment options are therefore pursued., Objective: To determine the safety, immunogenicity, and efficacy of bee venom intralymphatic immunotherapy (ILIT)., Methods: In an open pilot study, 12 patients received bee venom ILIT in three sessions with 14-day intervals: 0.1-5 μg/dose. Ultrasound imaging was applied to guide an injection and to document the lymph node structure. In a second study, 67 patients from 15 centers in Europe and Australia were randomized to receive four doses of either 10- or 20-μg bee venom ILIT with 28-day intervals. Clinical endpoints included specific IgE and IgG and protection after a bee sting challenge. These studies were performed in the years 2000-2003., Results: In a proof-of-concept study, no serious AEs were observed. An increase in allergen-specific IgG1 but no IgG4 and IgE was observed. ILIT induced the protection against a bee sting challenge in 7 out of 8 challenged patients. In a multicenter study, an increase in allergen-specific IgG and IgE was observed, with the highest increase in patients receiving a higher ILIT dose. The study was terminated due to several serious AEs upon the sting challenge provocation after the completion of treatment. However, out of 45 patients challenged, 15 (65%) and 18 (82%) patients in the 10- and 20-μg group, respectively, showed an improvement of two grades or more. No correlation was observed between antibody levels and sting protection., Conclusions: While a pilot study suggested the safety and efficacy of bee venom ILIT, a high number of AEs seen after the sting challenge following a randomized study indicate that the immunology protection offered by bee venom ILIT is insufficient. Of note, the bee venom allergen extract used in the two studies were from the two different providers. While the first study used a formulation approved for use in subcutaneous VIT, the second study used a nonapproved formulation never tested in humans. Further studies on approved formulations should be performed to generate conclusive results regarding the safety and efficacy of bee venom ILIT., Competing Interests: At the time of the study, TK was scientific advisor to MannKind Corp (Valencia, CA) and received financial support for the conduction of the described trials. TK and PJ have received research funding and travel grants from Allergy Therapeutics (Worthing, UK), which however has no involvement related to the current report. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chabot, Senti, Erdmann, Prinz, Wüthrich, Šošić, Kündig and Johansen.)

Hypersensitivity reactions to alcoholic beverages (particularly red wine) are relatively frequent, affecting 10% of the general population. Hypersensitivity reactions due to alcoholic drinks, mainly in the form of airway reactions (rhinitis and asthma), occur significantly more frequently in persons with pre-existing rhinitis and asthma. In terms of pathogenesis, it has to be differentiated between immunologic, mainly IgE-mediated, hypersensitivity reactions (wine allergies), and intolerance reactions in which no causative allergen-specific immune mechanisms can be detected. Allergens responsible for wine allergy could be: grape ( Vitis vinifera ) proteins (particularly the major allergen lipid transfer protein Vit v1), proteins and ingredients used for the fining of wines such as fish gelatin or isinglass (swim bladder of the fish huso, family of sturgeons), ovalbumin, dairy (casein) products, gum arabic, enzymes (lysozyme, pectinase, glucanase, cellulase, glucosidase, urease, aromatic enzymes), molds (particularly Botrytis cinerea ) responsible for the noble rot in wines, yeasts and proteins from insects that contaminated the mash. Type 1 allergic reactions (positive prick tests) have been described for inorganic components like ethanol, acetaldehyde, acetic acid and sulfites, but no specific IgE could be detected in the serum. Ethanol, acetaldehyde and acetic acid, flavonoids (anthocyanins and chatechines), sulfites, histamine and other biogenic amines are the main causative agents of intolerance reactions (pseudoallergic reactions) to wine. After a short historic review of viticulture and the importance of wine in classical antiquity, we go into the chemical processes of alcoholic fermentation and the genetically inherited "flush syndrome" caused by an acetaldehyde dehydrogenase 2 polymorphism, subsequently we focus on the different etiologic factors of allergies and intolerance reactions to wine. The most frequent intolerance reactions to sulfites occur particularly after the ingestion of white wine and in asthma patients. Intolerance reactions to histamine and other biogenic amines occur mainly after ingestion of red wine and in persons with diamine oxidase (DAO) deficiency., (© Dustri-Verlag Dr. K. Feistle.)

Atopic dermatitis (AD) patients mount IgE antibody responses to a variety of environmental allergens and also to autoantigens. We analyzed serum samples from four AD patients who had received oral cyclosporine A (CyA) treatment for up to 17 months regarding IgE autoreactivity to nitrocellulose-blotted human epithelial cell extracts and IgE levels to environmental allergens by quantitative ImmunoCap measurements. Skin inflammation was assessed by SCORAD. During full-dose treatment, a strong reduction in T-cell-mediated skin symptoms was observed which reappeared when CyA treatment was reduced or stopped. The intensity of IgE autoreactivity seemed to follow skin inflammation as it was reduced during full-dose treatment and increased upon inflammation. Interestingly, IgE levels to exogenous allergens were boosted by allergen exposure, declined thereafter, and seemed to be unaffected by CyA. Our data thus indicate that allergen-specific IgE production is boosted by allergen contact and cannot be reduced by CyA-mediated T-cell suppression., (© 2015 The Authors. Allergy Published by John Wiley & Sons Ltd.)