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Introduction Onion (Allium cepa) handling can induce contact dermatitis, rhinoconjunctivitis and asthma. However, only sporadic reports exist on allergic reactions to onion consumption. Aim We describe herein a case of a 35-year-old man who had an episode of anaphylaxis following cooked onion ingestion. We evaluated onion-specific IgE, the possible cross-reactivity between onion and peach and lymphocyte proliferation in response to onion. Material and methods Specific IgE was evaluated using two techniques: skin test and ImmunoCAP technology. Cross-reactivity between onion and peach was evaluated by IgE-ELISA inhibition test. As for lymphocyte proliferation, blood mononuclear cells were stained with CFSE dye and cultured with an in-house onion extract. Proliferation and phenotype was assessed by flow-cytometry. Results The skin test and ImmunoCAP confirmed the IgE-dependent response towards onion. The incubation of the patient serum with increasing concentrations of the peach extract reduced only scarcely (~30%) onion-specific IgE. Interestingly, B cells but not T cells showed proliferation in response to onion extract. Conclusions In conclusion, our report shows that cooked onion can induce severe allergic reactions, suggesting the presence of thermostable components. Moreover, we applied for the first time a B-cell-based approach to the diagnosis of food allergy. This latter approach might also be applied to other allergic conditions.

Background: Subcutaneous immunotherapy (SCIT) is an effective treatment of respiratory allergies including house dust mite (HDM) and Hymenoptera venom allergy. During the build-up phase, the allergen is administered weekly at increasing doses, while during the maintenance phase, it is administered at a fixed high dose every 4 weeks. Upon SCIT injection, the allergen is driven to the draining lymph nodes where it most likely induces an immune response. Immunologic changes are thus supposedly induced at each injection. Objectives: It is now established that SCIT induces tolerance in the long term, but the precise underlying immunologic mechanisms remain unclear. Therefore, we wanted to analyze the immunologic changes induced in both innate and adaptive immune cells at each individual SCIT administration during the maintenance phase in HDM-allergic patients. More specifically, we wondered whether the changes in regulatory T cell (Treg) and IgE+ B cell percentages, which are observed at the end of a 3-year course of SCIT, already occurred during the maintenance phase and whether these possible changes were sustained. Methods: We enrolled 6 patients suffering from HDM allergic rhinitis and undergoing maintenance HDM SCIT for 18–24 months. The same SCIT extract was used for all patients. We collected blood samples at 5 time points: T1 (immediately before a given SCIT injection), T2 (9 days after T1), T3 (29 days after T1 and right before the successive administration), T4 (39 days after T1), and T5 (61 days after T1 and just before the next injection). Six non-allergic age-matched healthy individuals were used as controls. Using flow cytometry, we assessed the following cell subsets in peripheral blood mononuclear cells: CD4 and CD8 T cells, Tregs, B cells, IgE+ B cells, NK and NKT cells, and total and activated basophils. Results: HDM-allergic patients displayed increased percentages of CD4 and CD8 T cells and NK cells compared to healthy controls. In contrast, NKT cells, total B cells, and basophils were diminished. These differences were maintained throughout the time course and seemed to be independent of the periodical SCIT injections. On the contrary, Treg percentages were significantly reduced in all HDM-allergic patients at T1. However, they increased at T2 and T4 (9 days after each SCIT injection) but decreased again at T3 and T5, just before the next one, resulting in cyclic changes. IgE+ B cells were significantly increased at T1, even more increased after each administration (T2, T4), and went back to their initial levels at T3 and T5, also resulting in a cyclic pattern. Conclusions: Our data suggest that during the SCIT maintenance phase, cycles of expansion/contraction of Tregs and IgE+ B cells occur at each SCIT injection. Therefore, the sustained induction of immune tolerance by SCIT, through the increase of Tregs, seems to depend on the periodical exposure to the allergen, at least during the early steady state.

Background. Low molecular weight heparins (LMWHs) are administered routinely to COVID-19 patients. Systemic reactions to LMWHs (both IgE-mediated and non IgE-mediated) are considered rare. Particularly, a single case of drug-related reaction with eosinophilia and systemic symptoms (DRESS) due to enoxaparin has been described in the literature. Here, we report on the first case of DRESS related to administration of fondaparinux.Case presentation. An elderly woman was diagnosed with COVID-19, during the “first wave” of the pandemics in Italy, and treated with enoxaparin (for anti-coagulation). A DRESS syndrome developed after two weeks (RegiSCAR score = 7). Enoxaparin was considered the culprit drug and replaced with the fully synthetic LMWH fondaparinux. At the same time, high-dosage prednisone was added to the therapy. The DRESS slowly subsided and the patient survived. Upon recovery and corticosteroid washout, a lymphocyte proliferation test for both LMWHs was performed, yielding a positive response not only for enoxaparin but also for fondaparinux. Conclusions. By lymphocyte proliferation test we demonstrated that both enoxaparin and fondaparinux were implicated in this case of DRESS, occurring in an elderly COVID-19 patient. In retrospect, the choice of using a sustained high-dose corticosteroid treatment while maintaining anti-coagulation by fondaparinux proved to be right. Ultimately, the patient recovered from both DRESS and COVID-19.

Background Hymenoptera venom immunotherapy (VIT) is a clinically effective treatment. However, little is known about its long-term clinical efficacy and biological effects. Several mechanisms have been proposed to account for VIT efficacy, including reduction of specific IgE and induction of allergen-specific IgG4, but the overall picture remains elusive. We investigated Vespula VIT clinical efficacy up to 8 years after discontinuation and the kinetics of Vespula-specific IgE and IgG4. Out of 686 consecutive patients we retrospectively selected and analysed a series of 23 patients with Vespula allergy that underwent a 5-year IT course, followed by a prolonged follow-up. Methods Clinical efficacy of VIT was assessed as number and severity of reactions to Vespula re-stinging events. The presence of Vespula-specific IgE and IgG4 was also monitored over time. Results During the VIT treatment, patients were protected, reporting no reactions or mild reactions in occasion of re-stinging events. This protection was entirely maintained during the follow-up, up to 8 years. Skin reactivity (reflecting mast cell-bound Vespula-specific IgE) and circulating Vespula-specific IgE levels declined substantially during VIT. Notably, this reduction was maintained over time during the follow-up. Moreover, all the patients were analysed for IgG4. A robust induction of Vespula-specific IgG4 was observed during the VIT course, with a substantial decline during the follow-up. Conclusions We conclude that Vespula VIT is a clinically effective treatment, which induces long-term protection after discontinuation. The reduction of specific IgE, assessed by skin tests and RAST, closely matches the VIT- induced protection, while the IgG4 induction seems not to be associated with VIT clinical efficacy in the long term.

Background Randomized Controlled Trials showed that omalizumab exhibited a good safety and tolerability profile in patients with moderate-to-severe asthma. However, safety data of long-term treatment with omalizumab are scarce. Our aim was to assess the safety of omalizumab in patients under long-term treatment in a real-life setting. Methods Difficult-to-control asthmatic patients treated with omalizumab up to 9 years were retrospectively evaluated. Mild to severe adverse events any and reasons for discontinuation were recorded. Results Ninety-one patients (26.4% males, mean age 49.9 ± 14.9 years) were included: mean treatment length, 3.8 ± 2.6 years; mean individual monthly dose, 514.5 ± 345.7 mg (range, 150–1200 mg). A total of 10,472 single injections were given cumulatively to the 91 patients (115 single injections per patients, on average, over a treatment period up to 9 years). Fifty-nine patients (64.8%) were treated for a period of time from 3 to 9 years, 14 of whom from 6 to 9 years. A high proportion of patients who discontinued treatment dropped out within the first year (18, 39.1%), mainly for reasons unrelated to treatment. Six patients (6.6%) discontinued omalizumab for treatment-related adverse events: arthralgia/myalgia (3 patients); urticaria, angioedema (1 patients); metrorrhagia (1 patient); relapsing herpes labialis (1 patient). Four other patients complained of mild adverse events (rhinitis/conjunctivitis, injection site reaction, fatigue, thrombosis) but continued the treatment. Anaphylaxis was not reported. Conclusions Long-term treatment with omalizumab appears remarkably safe and well tolerated in real-life setting. Prolonged omalizumab treatment for many consecutive years did not increase the risk of side effects, particularly anaphylaxis.

Background Epidemiology of food allergy is currently the focus of considerable research interest. Particularly important appears the recognition of novel food allergens and the characterization of specific food allergy patterns, relevant to homogeneous geographic areas with distinct alimentary habits, such as the Mediterranean area. Here we report on recent findings on allergy to Mediterranean fruits and vegetables.