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Introduction: The co-presence of bronchiectasis (BE) in severe eosinophilic asthma (SEA) is common. Data about the effectiveness of benralizumab in patients with SEA and BE (SEA + BE) are lacking. Aim: The aim of this study was to evaluate the effectiveness of benralizumab and remission rates in patients with SEA compared to SEA + BE, also according to BE severity. Methods: We conducted a multicentre observational study, including patients with SEA who underwent chest high-resolution computed tomography at baseline. The Bronchiectasis Severity Index (BSI) was used to assess BE severity. Clinical and functional characteristics were collected at baseline and after 6 and 12 months of treatment. Results: We included 74 patients with SEA treated with benralizumab, of which 35 (47.2%) showed the co-presence of bronchiectasis (SEA + BE) with a median BSI of 9 (7–11). Overall, benralizumab significantly improved the annual exacerbation rate (p < 0.0001), oral corticosteroids (OCS) consumption (p < 0.0001) and lung function (p < 0.01). After 12 months, significant differences were found between SEA and SEA + BE cohorts in the number of exacerbation-free patients [64.1% vs. 20%, OR 0.14 (95% CI 0.05–0.40), p < 0.0001], the proportion of OCS withdrawal [−92.6% vs. −48.6, p = 0.0003], and the daily dose of OCS [−5 mg (0 to −12.5) vs. −12.5 mg (−7.5 to −20), p = 0.0112]. Remission (zero exacerbations + zero OCS) was achieved more frequently in the SEA cohort [66.7% vs. 14.3%, OR 0.08 (95% CI 0.03–0.27), p < 0.0001]. Changes in FEV1% and FEF25–75% were inversely correlated with BSI (r = −0.36, p = 0.0448 and r = −0.41, p = 0.0191, respectively). Conclusions: These data suggest that benralizumab exerts beneficial effects in SEA with or without BE, although the former achieved less OCS sparing and fewer respiratory-function improvements.

Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aims to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on disposable immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy.

Background: Eosinophils have a double-edged role in the human body, being essential in important physiologic functions but whose presence is conspicuous in a variety of diseases characterized by a T2 inflammation phenotype. Eosinophils are exquisitely sensitive to corticosteroids, and the latter have, until recently, represented the cornerstone of treatment of eosinophilic diseases. However, most patients remain dependent on oral corticosteroids, with a notable adverse effect burden and experience a chronic relapsing disease that leads to high morbidity and mortality. Treatment prospects have changed with the advent of biologic drugs that target the eosinotropic cytokine interleukin (IL) 5 or its receptor. The success of the latter drugs in severe eosinophilic asthma has paved the way for their use in other, rarer, eosinophilic lung diseases. Recently, mepolizumab, a humanized monoclonal antibody that works against IL-5, was approved for the add-on treatment of relapsing-remitting or refractory eosinophilic granulomatosis with polyangiitis (EGPA) in patients ages ≥ 6 years. Benralizumab, a humanized antibody that binds to the α portion of the IL-5 receptor, is also being tested for its efficacy in EGPA in two clinical trials, after a growing number of case reports and case series supported its use as a steroid-sparing agent in the treatment of EGPA. Methods: In this review, we summarized the scientific literature evaluating the efficacy of benralizumab treatment in patients afflicted with rare primary eosinophilic lung diseases. Results: The literature we found, largely case reports, reported that the use of benralizumab in EGPA, chronic eosinophilic pneumonia (CEP) and allergic bronchopulmonary aspergillosis (ABPA) often led to a depletion of eosinophils, less exacerbations and a decreased systemic corticosteroid burden. No adverse effects were reported. Conclusion: Benralizumab has a prospective role in the treatment of rare eosinophilic lung diseases, which needs to be further elucidated in randomized controlled trials.

Key words: university autonomy, higher education, Kazakhstan, Italy, TRUNAK, Erasmus plus.

INTRODUCTION Asthma symptoms can be relieved through a maintenance treatment combining long-acting β2-agonist and inhaled corticosteroids (LABA/ICS). However, for patients with inadequately controlled asthma, the LABA/ICS combination might not be sufficient. Under these conditions, clinical guidelines recommend the administration of inhaled long-acting muscarinic antagonists (LAMA) as an add-on therapy to LABA/ICS to better control asthma and improve lung function. For nearly two decades, the only LAMA to be approved on the market has been tiotropium. AREAS COVERED We reviewed recent clinical studies evaluating the safety and efficacy of LABA/LAMA/ICS fixed dose combinations by searching PubMed database. Molecular mechanisms and clinical data support the use of a once-daily, single-inhaler fixed dose combination of the LABA/LAMA/ICS indacaterol/glycopyrronium/mometasone (IND/GLY/MF), the first therapy combining three agents in a fixed dose approved in Europe for the treatment of uncontrolled asthma. EXPERT OPINION IND/GLY/MF was superior to both IND/MF and salmeterol/fluticasone (SAL/FLU), a well-established LABA/ICS combination improving lung function in uncontrolled asthma. Moreover, IND/GLY/MF, delivered through the Breezhaler inhaler in a single inhalation, is the first inhaled therapy prescribed alongside a digital companion, a sensor and the Propeller app, allowing for improved treatment adherence, reduced rescue inhaler usage and hospitalizations, increased patient satisfaction and asthma control.

BACKGROUND Alexithymia is among psychological factors reported to interfere with asthma management. Severe allergic asthma (SAA) is characterized by uncontrolled asthma despite maximal standard pharmacological treatment which can benefit from an add-on treatment with Omalizumab, an anti-IgE monoclonal antibody. OBJECTIVE To evaluate if alexithymia influences the efficacy of omalizumab in SAA. METHODS The total alexithymia score 20 (TAS 20) questionnaire allowed to detect alexithymia. SAA was monitored recording number of exacerbations, asthma control test (ACT) and asthma quality of life questionnaire (AQLQ) scores, as well as forced expiratory volumes in 1 second % (FEV1%) levels before starting omalizumab, 1 and 2 years after. RESULTS The study was conducted on 18 patients; Group 1, TAS 20 ≥ 61, was of 2 males and 4 females with SAA and alexithymia, while Group 2 , TAS 20 ≤ 51, was of 8 males and 4 females, without alexithymia. Group 1 had a statistically significant decrease in asthma exacerbations "p = 0.004", while ACT "p = 0.008" and AQLQ scores statistically increased. FEV1 values increased but not statistically significantly. Group 2 had a highly statistically significant decrease in the number of exacerbations and a highly statistically significant increase of ACT "p < 0.0001", FEV1 "p = 0.008" and AQLQ scores. CONCLUSIONS Regardless the presence or not of alexithymia, all patients with SAA obtained a marked improvement after starting treatment with omalizumab. Therefore alexithymia does not seem to influence the treatment outcome of omalizumab.

The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences.This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844).Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease.MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Background Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

Hymenoptera venom allergy is an epidemiologically underestimated condition and a major cause of morbidity worldwide. Preventing future allergic reactions in patients who experience a systemic reaction is based on the correct management of the emergency followed by an accurate diagnosis, prescription of adrenaline autoinjectors, and, where indicated, specific venom immunotherapy. Some epidemiological studies highlight our poor knowledge of this disease and the frequent inadequacy of its management. Moreover, they emphasize the importance of such a life-saving treatment as specific immunotherapy. The availability of high-quality hymenoptera venom extracts for diagnostic and therapeutic use has dramatically improved the prognosis and quality of life of allergic patients. Subcutaneous venom immunotherapy is currently the most effective form of allergen-based immunotherapy, with a carry-over effect lasting up to several years after its interruption. This report on the management of hymenoptera venom-allergic children and adults was prepared by a panel of Italian experts. The main objective of this consensus document is to review the scientific evidence related to diagnosis, therapy, and management of patients allergic to hymenoptera venom. Thus, we can improve our knowledge of the disease and promote good clinical practices. The present document provides practical suggestions for correct diagnosis, prescription of emergency therapy and immunotherapy, and strategies for patient care.

Background: Cross-reactivity between pollens and plant food has been widely described. Pollen extract subcutaneous immunotherapy in patients with pollens and plant food allergy has been shown to improve tolerance not only to inhalant allergens but also to reduce symptoms in patients with various food allergies. Methods: We retrospectively report our experience with 15 female patients with a positive history for moderate, persistent allergic rhinitis due to grass pollen and oropharyngeal symptoms after ingestion of different plant food. These patients followed a five-grass pollen sublingual tablet immunotherapy for three years in a discontinuous pre-co-seasonal scheme. Results: All 15 patients treated with the 5-grass pollen sublingual tablet immunotherapy, taken once daily for 3 years on a 7-month course, showed improved ocular/nasal symptoms, with a reduction in the use of symptomatic drugs (e.g., nasal corticosteroids and H1 antihistamines). After the first seven-month course of immunotherapy, all patients declared a good tolerance to the intake of fruits and vegetables, and in particular, good tolerance to the offending foods. Conclusions: In conclusion, we have observed improvement of both respiratory and plant food allergies after sublingual immunotherapy (SLIT) with a five-grass pollen tablet.

Introduction There is, so far, no universal definition of severe asthma. This definition usually relies on: number of exacerbations, inhaled therapy, need for oral corticosteroids, and respiratory function. The use of such parameters varies in the different definitions used. Thus, according to the parameters chosen, each patient may result in having severe asthma or not. The aim of this study was to evaluate how the choice of a specific definition of severe asthma can change the allocation of patients. Methods Data collected from the Severe Asthma Network Italy (SANI) registry were analyzed. All the patients included were then reclassified according to the definitions of U-BIOPRED, NICE, WHO, ATS/ERS, GINA, ENFUMOSA, and TENOR. Results 540 patients, were extracted from the SANI database. We observed that 462 (86%) met the ATS/ERS criteria as well as the GINA criteria, 259 (48%) the U-Biopred, 222 (41%) the NICE, 125 (23%) the WHO, 313 (58%) the Enfumosa, and 251 (46%) the TENOR criteria. The mean eosinophil value were similar in the ATS/ERS, U-Biopred, and Enfumosa (528, 532 and 516 cells/mcl), higher in WHO and Tenor (567 and 570 cells/mcl) and much higher in the NICE classification (624 cells/mcl). Lung function tests resulted similarly in all groups, with WHO (67%) and ATS/ERS-GINA (73%), respectively, showing the lower and upper mean FEV1 values. Conclusions The present observations clearly evidence the heterogeneity in the distribution of patients when different definitions of severe asthma are used. However, the recent definition of severe asthma, provided by the GINA document, is similar to that indicated in 2014 by ATS/ERS, allowing mirror reclassification of the patients examined. This lack of homogeneity could complicate the access to biological therapies. The definition provided by the GINA document, which reflects what suggested by ATS/ERS, could partially overcome the problem.

Biological therapies used for severe asthma may be useful even for middle-aged or older patients who have a history of severe allergic asthma with a chronic obstructive pulmonary disease (COPD) overlap phenotype.To show omalizumab efficacy in severe allergic asthma-COPD overlap disease.Material and methods: We report our data of a retrospective study on 11 patients (mean age: 67.18 years) with a positive history of severe allergic asthma treated with omalizumab. They all presented limited reversibility of airway obstruction and signs of chronic bronchitis at radiological examinations, as in asthma-COPD overlap. Omalizumab improved conditions in terms of reduced exacerbations as well as asthma control test (ACT) and Asthma Quality of Life Questionnaire (AQLQ) scores.Clinical improvement was seen already in the first year with significantly increased ACT scores (Omalizumab may be relevant as a therapeutic option even in middle-aged and older patients with severe asthma.

Background: Adherence to medications is crucial in patients with severe asthma in light of the negative clinical impact and costs of non-adherence. Adherence to omalizumab has not been well studied in real-world settings. The aim of this study was to assess adherence to omalizumab and evaluate treatment effectiveness in relation to adherence. Methods: This was a retrospective, observational, and multicenter real-world study. Omalizumab dose, timing of administration, and duration of treatment ( 4 years) were analyzed. Adherence was evaluated by examining rates of expected and missing doses. Good adherence (10% doses missed) were determined. For effectiveness in relation to adherence of omalizumab we considered asthma exacerbations, hospitalizations, asthma control test (ACT), and Forced Expiratory Volume in 1 s (FEV1). Results: A total of 196 patients were evaluated, and 161 were suitable for data analyses. Good adherence was shown in 90.7% of patients and poor adherence in 9.3%. Considering adherence in relation to treatment duration: 4 years, 100% were adherent (expected doses, 6120; missed doses, none). Indices of efficacy between pre- and post-treatment showed significant improvement (p

Common variable immunodeficiency (CVID) is a primary immunodeficiency due to a disorder of the adaptive immune system which causes hypogammaglobulinemia and therefore an increased susceptibility to infection; noninfectious, inflammatory conditions including systemic autoimmunity and lymphoproliferative complications are also commonly associated with CVID. Castleman disease (CD) is a systemic disease clinically characterized by diffuse lymphadenopathy, splenomegaly, anemia, and systemic inflammatory symptoms. This makes CD a great mimicker of more common benign and malignant masses in the neck, chest, abdomen, and pelvis. A novel case of primary immunodeficiency (CVID) in a middle-aged woman, who developed multicentric CD (MDC) with splenomegaly, is described. The authors suggest that the onset of MCD and of the correlated splenomegaly was due to incorrect management of the hypogammaglobulinemia as immunoglobulin G (IgG) levels were not kept within normal ranges. Correct management of the hypogammaglobulinemia allowed splenectomy to be performed without any infectious surgical complications. MCD is reported for the first time in association with an adult case of CVID. The above reported case highlights the need for a timely correct diagnosis and treatment of CVID to avoid complications, which could cause recourse to splenectomy, such as in our case or development of malignancies.

Background Kounis syndrome (KS) has been described as the coincidental occurrence of acute coronary syndromes during an allergic reaction with cardiac anaphylaxis. It is caused by inflammatory mediators released after exposure to drugs, food, environmental and other triggers. Oxidative stress occurring in various inflammatory disorders causes molecular damage with the production of advanced oxidation products (AOPPs) and advanced glycation end products (AGEs). Case presentation Markers of oxidative stress were evaluated in a patient who had experienced KS after antibiotic administration in order to investigate the possible role of these molecules in KS. No data, up to now, are available on biomarkers of oxidative stress in patients with drug-induced KS. Conclusions AOPPs, but not AGEs, were significantly increased in the KS affected patient compared to controls as already reported in mastocytosis affected patients.

Background Hymenoptera sting reactions are among life-threatening causes of allergy. Several epidemiology studies have assessed the risk of these kind of reactions, among the general population, around 3% of adults. This incidence increases among highly at risk populations such as outdoor workers. Hymenoptera stings among forestry workers (FW) are occupational triggers but it has not yet been well defined which is the real incidence of anaphylaxis in these workers, not even in Italy. Two Italian studies reported on the risk of hymenoptera stings (HS) in northern Italy (NI) and central Italy (CI) FW while no data is available on the prevalence in southern Italy (SI) ones. Methods A population of 341 SI FW (301 males and 40 females, mean age 51 years, range 43–63 years), who worked in Sicily, was investigated submitting a standardized questionnaire dealing with reactions to Hymenoptera stings, such as large local reactions (LLR) and systemic reactions (SR). Results HS occurred in 203 FW (59%) and caused reactions in 77 (22%); LLR occurred in 46 (13%) and SR in 31 (9%); SR were life threatening in 9/341 (3%) FW and were treated with epinephrine at the emergency unit as workers did not carry an epinephrine auto-injector. A SR at a subsequent HS followed a LLR in 21/46 FW (46%). Conclusions FW in SI have a generic risk of HS anaphylaxis as in the general population but a higher risk of SR and LLR respect to forestry populations from different Italian geographical areas.SR among SI FW occurred in 9% of them, while published data report the incidence of SR around 2 and 4%, respectively, in the Centre and North Italy FW. The incidence of LLR in SI FW was also higher (13%) than in CI (2%) and NI (10%) ones. Previous LLR in our SI population represented a high risk factor for developing a SR and therefore a red flag for future anaphylaxis and prescription of an epinephrine auto-injector.

In the last decade, the ingestion of gluten, a heterogeneous complex of proteins present in wheat, rice, barley and probably in oats, has been associated with clinical disorders, such as celiac disease, wheat allergy and recently to non-celiac gluten sensitivity or wheat intolerance syndrome. Gluten-related disorders, which are becoming epidemiologically relevant with an estimated global prevalence of about 5%, require the exclusion of gluten from the diet. For the past 5 years, an important shift in the availability of gluten-free products, together with increased consumption in the general population, has been recorded and is estimated to be about 12-25%. Many people follow a self-prescribed gluten-free diet, despite the fact that the majority have not first been previously excluded, or confirmed, as having gluten disorders. They rely on claims that a gluten-free diet improves general health. In this review, we provide an overview of the clinical disorders related to gluten or wheat ingestion, pointing out the current certainties, open questions, possible answers and several doubts in the management of these conditions. KEY MESSAGE Incidence of gluten-related disorders is increased in the last decade and self-diagnosis is frequent with inappropriate starting of a gluten-free diet. Gluten and wheat are considered as the most important triggers to coeliac disease, wheat allergy and non-celiac gluten sensitivity. Pediatricians, allergologist and gastroenterologist are involved in the management of these conditions and appropriate diagnostic protocols are required.

Introduction: Sublingual immunotherapy (SLIT) was introduced as a safer option to subcutaneous immunotherapy (SCIT) which was associated with the possible occurrence of systemic reactions including anaphylaxis and, though very rarely, fatalities. Some anaphylactic reactions to SLIT are reported, mainly in adults but also in children. It is therefore important to investigate the risk factors related to such reactions.Areas covered: Data from the literature on the safety of SLIT in children were reviewed. The data reviewed concerned the application of this treatment to patients with respiratory allergy and also possible new indications such as food allergy, atopic dermatitis and latex allergy. Reports of anaphylactic reactions were analyzed to identify the potential risk factors.Expert opinion: SLIT is a well tolerated treatment, the common side effect being local reactions in the mouth. Systemic reactions, concerning the skin and the airway, are rare and anaphylactic reactions are extremely rare.

Background: This is the first randomized, double-blind, placebo-controlled trial (EUDRACT No. 2009-013923-43) evaluating nickel oral hyposensitizing treatment (NiOHT) in patients with “systemic nickel allergy syndrome” (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food. Methods: Adults with positive Ni-patch test, who reported symptoms suggesting SNAS, which improved after Ni-poor diet, and were positive to Ni-oral challenge were eligible. Patients were randomly assigned to three treatments (1.5 μg, 0.3 μg, or 30 ng Ni/week) or placebo for a year, with progressive reintroduction of Ni-rich foods form the 5th month. Out of 141 patients randomized, 113 completed the trial. Endpoints were efficacy and tolerability of treatment. Results: During Ni-rich food re-introduction, the 1.5 μg Ni/week group had a mean VAS score significantly higher than placebo (p = 0.044), with significant improvement of gastrointestinal symptoms (p = 0.016;) and significantly fewer rescue medications. Cutaneous manifestations also improved but without reaching statistical significance. After the treatment, oral challenge with higher Ni doses than at baseline were needed to cause symptoms to flare-up in significantly more patients given 1.5 μg Ni/week than placebo (p = 0.05). Patients reported no side-effects. Conclusions: NiOHT is effective in SNAS, in particular on gastrointestinal manifestations, with trend toward improvement of cutaneous symptoms.

Chronic heart failure (CHF) is a complex and heterogeneous clinical syndrome and because of its rising incidence and prevalence, it can be considered a global epidemic. Interleukin (IL)-22 is a pro-inflammatory cytokine, belonging to the IL-10 family. Forty-seven consecutive older patients, hospitalized with an admitting diagnosis of CHF at the Geriatric Medicine Unit (University of Messina, Italy), from 01/01/06 to 30/06/06, were enrolled in the study. Serum concentrations of IL-22 were measured by a quantitative enzyme immunoassay technique. IL-22 levels in all CHF patients were significantly higher than those in controls, in particular, only the II and III NYHA class had IL-22 values significantly higher than the controls, whereas there was no difference between the IL-22 levels of NYHA class IV and the controls. The reason may be the declining immune function in CHF older patients, in fact we can hypothesize that the fall in IL-22 levels, with the progression of NYHA class, is due to the reduced ability in CHF patients to respond to infections, as IL-22 has anti-microbial properties. We detected different outcomes correlated to different IL-22 levels, and the Kaplan-Meier curves suggest a trend.

Venom immunotherapy is an effective method for the treatment of Hymenoptera venom allergy. Different extracts and treatment schedules are available.To compare the safety and efficacy of immunotherapy in 3 cohorts of patients sensitized to Vespula species.In this open study, 43 patients were treated with a subcutaneous aqueous extract for induction and maintenance (AA), 34 with a subcutaneous depot extract for induction and maintenance (DD), and 29 with subcutaneous aqueous and subcutaneous depot extracts for induction and maintenance, respectively (AD). Cluster schedules were followed to reach maintenance, and adverse effects during treatment and after naturally occurring stings were recorded.Depot immunotherapy was better tolerated mainly owing to the lower frequency of local adverse effects in the induction phase (5.9% vs 42.5% and 1.3% vs 5.1% on a per patient and per dose basis, respectively; P.001 for both) and for effects occurring within 60 minutes after vaccination (2.9% vs 19.2% and 0.2% vs 2.8% on a per patient and per dose basis; P = .03 and P.001, respectively). Furthermore, 19 of 20 AA, 9 of 9 AD, and 10 of 10 DD patients who were restung experienced only minor local effects.Venom immunotherapy is efficacious. Although there was no decrease in systemic reactions, depot immunotherapy to Vespula venom induced fewer early local adverse effects. Patients undergoing an induction phase with an aqueous extract can benefit from switching to a depot extract during maintenance. Increasing the flexibility of the immunization schedules may improve compliance with this potentially lifesaving treatment.

Aims The study aimed to evaluate the effects of probiotic Lactobacillus reuteri DSM 17938 strain supplementation in patients suffering from systemic nickel allergy syndrome, in terms of modulation of faecal LAB population linked to a reduction of GI and cutaneous symptoms and to an increase of patient's quality of life. Methods and Results A preliminary double-blind randomized placebo-controlled study was planned and a culture-independent method based on denaturing gradient gel electrophoresis (DGGE) analysis coupled to the 16S rRNA gene sequencing was applied to investigate on the dynamics of faecal LAB communities before and during a low-Ni diet, supplemented with the probiotic strain. Moreover, the severity and the frequency of GI and cutaneous reactions as well as patient's clinical condition perception (VAS scores) were estimated by statistical analysis. PCR-DGGE fingerprinting obtained using LAB-specific primers revealed significant shift in faecal community with an increase in biodiversity in patients supplemented with probiotic Lact. reuteri strain. In addition, GI reactions such as symptoms related to meals and type of stools significantly improved only in patients treated with Lact. reuteri, while severity and frequency of cutaneous symptoms (urticaria, itch and eczema) and recurrent abdominal pain (RAP) as well as VAS scores statistically decreased in both groups. Conclusions Our preliminary findings suggest that probiotic Lact. reuteri could be a useful supplementation during a low-Ni diet of patients with SNAS, to increase LAB population diversity, which could contribute to restore the intestinal homoeostasis conditions. Significance and Impact of the Study To date, no information is available on probiotics application and on their effects, in terms of intestinal microbiota modulation, on patients suffering from SNAS. Therefore, the identification of dominant LAB community and the study of its shift during the probiotic supplementation could enhance the knowledge of the SNAS syndrome.

The prevalence of nickel hyper-sensitivity varies widely in different countries, nevertheless it is the leading cause of contact dermatitis. The presence of nickel in the diet (mainly plant foods) in some nickel-sensitive subjects can provoke/aggravate eczema and systemic contact dermatitis as well as cause extra-cutaneous symptoms (respiratory, gastrointestinal, neurological). These symptoms, correlated to the ingestion of nickel-containing foods and beverages, in nickel patch test positive individuals, defines the so called Systemic Nickel Allergy Syndrome (SNAS), a condition successfully treated by oral desensitization. Although numerous studies have investigated the prevalence of contact nickel allergy or addressed the relationship between nickel intake and onset of systemic symptoms, to our knowledge no epidemiological studies have attempted to estimate the prevalence of SNAS. Therefore, we decided to evaluate consecutive patients (1,696), afferent to four allergy units in Sicily, a region of southern Italy, from October 2010 to March 2011. SNAS was confirmed in 98 patients (5.78 percent) of the 1,696 studied, suggesting that this clinical entity may be an emergent allergological condition rather than an occasional finding. The most common symptoms complained of in our population were cutaneous (51 patients), gastrointestinal (87 patients) and other systemic clinical manifestations (37 patients). Furthermore, 16 out of the 98 SNAS patients (16.3 percent) presented IgE-mediated food allergy with a statistically significant association (X2=16.950; P