Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment.

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 aimed 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 available 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.

Food immunotherapy practice: Nation differences across Europe, the FIND project.

BACKGROUND: Food allergen immunotherapy (FA-AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA-AIT. METHODS: An EAACI task force conducted an online survey to gather relevant information regarding FA-AIT practice and setting-specific resources after reviewing the published literature and congress abstracts throughout Europe. RESULTS: We identified 102 FA-AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital-based (77.5%), publicly funded (80.4%) and delivered FA-AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA-AIT for a median of 9 years [1-24] to a median of 105 [5-2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4-6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%-63%), eosinophilic esophagitis (56%-48%) and age below 5 years (47%-41%). CONCLUSIONS: In Europe, FA-AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization.

Quality of life in patients with allergic and immunologic skin diseases: in the eye of the beholder.

Allergic and immunologic skin diseases negatively impact the quality of life (QoL) of affected patients with detrimental consequences. Nonetheless, in everyday clinical practice the evaluation of QoL is often overlooked. Considering the increasing prevalence of atopic dermatitis, allergic contact dermatitis, hereditary angioedema, cutaneous mastocytosis, and urticaria, it is essential to determine the effects of allergic and immunologic skin diseases on QoL. A joint meeting (GET TOGETHER 2021) of the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) aimed to summarize the features of the main QoL tools used in these diseases and to describe the extent of QoL impairment as well as the impact of treatments on QoL, particularly biologic therapies. The assessment of QoL in patients with allergic and immunologic skin diseases relies on generic, organ-specific and disease-specific questionnaires. While generic and organ-specific questionnaires allow comparison between different diseases, disease-specific questionnaires are designed and validated for specific cohorts: the QoL Index for Atopic Dermatitis (QoLIAD) and the Childhood Atopic Dermatitis Impact Scale (CADIS) in atopic dermatitis, the ACD-11 in allergic contact dermatitis, the Angioedema QoL Questionnaire (AE-QoL) and the Hereditary Angioedema QoL questionnaire (HAE-QoL) in hereditary angioedema, the Mastocytosis QoL Questionnaires (MCQoL e MQLQ) in cutaneous mastocytosis, and the Chronic Urticaria QoL questionnaire (CU-Q2oL) in urticaria. Among the many factors that variably contribute to QoL impairment, pruritus can represent the leading cause of patient discomfort. Biologic therapies significantly ameliorate QoL in atopic dermatitis, hereditary angioedema, mastocytosis and chronic urticaria. In general, adequate management strategies are essential for improving QoL in patients with allergic and immunologic skin diseases.

Omalizumab for prevention of anaphylactic episodes in a patient with severe mosquito allergy.

Anaphylaxis after mosquito bite is rare, but life threatening. No approved preventive therapy is available to date, but omalizumab could be a promising therapeutic option for reducing risk and improving quality of life in these patients.

A meta-analysis on allergen-specific immunotherapy using MCT® (MicroCrystalline Tyrosine)-adsorbed allergoids in pollen allergic patients suffering from allergic rhinoconjunctivitis.

BACKGROUND: The World Allergy Organization and the European Academy of Allergy and Clinical Immunology recommend to perform product-specific meta-analyses for allergen-specific immunotherapies because of the high degree of heterogeneity between individual products. This meta-analysis evaluates the efficacy and safety of Glutaraldehyde-modified and MCT® (MicroCrystalline Tyrosine)-adsorbed allergoids (MATA). METHODS: The databases MEDLINE, LILACS, embase, LIVIVO, Web of Science and Google (Scholar) were searched for publications on MATA up to June 2019. Primary endpoint was the combined symptom and medication score (CSMS). Secondary endpoints were single scores, immunogenicity and improvement of allergic condition. Secondary safety endpoints were the occurrence of side effects. A random effects model was applied with (standardized) mean differences ([S]MDs) including confidence intervals (CI). Heterogeneity was analyzed using the I2 index and publication bias using Egger's test and Funnel plots. Subgroups were analyzed regarding age and asthma status. RESULTS: Eight randomized double-blind placebo-controlled trials were selected for efficacy and 43 publications for safety analysis. In total, 4531 patients were included in this analysis including eight studies containing data on children and adolescents. AIT with MATA significantly reduced allergic symptoms and medication use with a SMD for CSMS of -0.8 (CI: -1.24, -0.36) in comparison to placebo. Heterogeneity was moderate between the studies. The total symptom score (-1.2 [CI: -2.11, -0.29]) and the total medication score (-2.2 [CI: -3.65, -0.74]) were also significantly reduced after MATA treatment. Patient's condition improved significantly after treatment with MATA, with an odds ratio of 3.05 (CI: 1.90, 4.90) when compared to placebo. The proportion of patients, who developed side effects was 38% (CI: 19%, 57%). No serious side effects occurred. Safety in the subgroups of asthmatic patients, children and adolescents did not differ from the overall patient population. CONCLUSIONS: This meta-analysis reveals a large body of evidence from publications investigating MATA. MATA significantly improved allergic symptoms and reduced the use of anti-allergic medication in comparison to placebo, with an excellent safety profile. Especially for children and asthmatic patients, the use of MATAs can be considered as safe, because the safety profiles in these groups did not differ from the total patient population.

Urticaria: recommendations from the Italian Society of Allergology, Asthma and Clinical Immunology and the Italian Society of Allergological, Occupational and Environmental Dermatology.

BACKGROUND: Urticaria is a disorder affecting skin and mucosal tissues characterized by the occurrence of wheals, angioedema or both, the latter defining the urticaria-angioedema syndrome. It is estimated that 12-22% of the general population has suffered at least one subtype of urticaria during life, but only a small percentage (estimated at 7.6-16%) has acute urticaria, because it is usually self-limited and resolves spontaneously without requiring medical attention. This makes likely that its incidence is underestimated. The epidemiological data currently available on chronic urticaria in many cases are deeply discordant and not univocal, but a recent Italian study, based on the consultation of a national registry, reports a prevalence of chronic spontaneous urticaria of 0.02% to 0.4% and an incidence of 0.1-1.5 cases/1000 inhabitants/year. METHODS: We reviewed the recent international guidelines about urticaria and we described a methodologic approach based on classification, pathophysiology, impact on quality of life, diagnosis and prognosis, differential diagnosis and management of all the types of urticaria. CONCLUSIONS: The aim of the present document from the Italian Society of Allergology, Asthma and Clinical Immunology (SIAAIC) and the Italian Society of Allergological, Occupational and Environmental Dermatology (SIDAPA) is to provide updated information to all physicians involved in diagnosis and management of urticaria and angioedema.

Effects of a Synbiotic Formula on Functional Bowel Disorders and Gut Microbiota Profile during Long-Term Home Enteral Nutrition (LTHEN): A Pilot Study.

Long-term enteral nutrition (LTEN) can induce gut microbiota (GM) dysbiosis and gastrointestinal related symptoms, such as constipation or diarrhoea. To date, the treatment of constipation is based on the use of laxatives and prebiotics. Only recently have probiotics and synbiotics been considered, the latter modulating the GM and regulating intestinal functions. This randomized open-label intervention study evaluated the effects of synbiotic treatment on the GM profile, its functional activity and on intestinal functions in long-term home EN (LTHEN) patients. Twenty LTHEN patients were recruited to take enteral formula plus one sachet/day of synbiotic (intervention group, IG) or enteral formula (control group, CG) for four months and evaluated for constipation, stool consistency, and GM and metabolite profiles. In IG patients, statistically significant reduction of constipation and increase of stool consistency were observed after four months (T1), compared to CG subjects. GM ecology analyses revealed a decrease in the microbial diversity of both IC and CG groups. Biodiversity increased at T1 for 5/11 IG patients and Methanobrevibacter was identified as the biomarker correlated to the richness increase. Moreover, the increase of short chain fatty acids and the reduction of harmful molecules have been correlated to synbiotic administration. Synbiotics improve constipation symptoms and influences Methanobrevibacter growth in LTHEN patients.

The EAACI-AAAAI-WAO Junior Members' joint survey: A worldwide snapshot of Allergy and Clinical Immunology specialty.

BACKGROUND: Education and training in Allergy and Clinical Immunology (A/I) are characterized by a great variability worldwide. However, objective and worldwide data regarding this topic are lacking. METHODS: To investigate personal information, education, and involvement in scientific societies of juniors engaged in A/I field, a questionnaire was developed by representatives from the JMs' boards of the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the World Allergy Organization (WAO). RESULTS: A total of 543 questionnaires were collected from 76 regions of all continents. The geographic distribution of responders was as follows: Africa-Middle East 3.0%, Asia-Pacific 21.4%, Europe 48.2%, Latin America 12.1%, and North America 15.3%. 59.0% of responders declared that A/I is recognized as a separate specialty in their country, Europe mostly accounting for that proportion. Primary interest in the field represents the main motivation for choosing A/I specialty. Concerning involvement in scientific societies, 41.1% of responders ever attended an EAACI Congress, 20.6% an AAAAI Congress, and 20.4% a WAO Congress. According to 40.3% of responders, scientific societies do not provide enough opportunities for young members, and 96.4% believes in a more intensive cooperation between the A/I Societies. CONCLUSIONS: The survey provides the first worldwide perspective about A/I specialty. It represents the first ever example of a structured collaboration between the junior members (JMs) of the three main A/I Societies. The findings suggest the need for harmonization, at least in terms of training and formation in the field of A/I worldwide.

Safety of uSCIT-MPL-4: prevalence and risk factors of systemic reactions in real life.

Aim: We assessed the safety of allergoid adjuvanted by monophosphoryl lipid A (uSCIT-MPL-4) in a real-life setting. Materials & methods: Patients treated with uSCIT-MPL-4 were followed-up for 1 year. Systemic reactions (SRs) were registered and the association with potential risk factors was evaluated. Results: 2929 patients were included. Grade 0, 1, 2, 3 and 4 SR reactions were observed respectively in 3.3, 1.5, 0.31, 0.07 and 0.07% of patients. A significant association was detected between Grade ≥1 SRs and: female gender, number of administrations, previous local reactions. Conclusion: uSCIT-MPL-4 is safe. Local reactions should be accurately assessed as they may represent a risk factor for Grade ≥1 SRs, together with gender and number of doses/year.

Lactose Maldigestion, Malabsorption, and Intolerance: A Comprehensive Review with a Focus on Current Management and Future Perspectives.

Milk is a fundamental component of the diet of every mammal; nevertheless, not every individual can tolerate this kind of food, especially in adulthood. However, lactose intolerance has only been recognized in the last 50 years, and currently, lactose intolerance is defined as a clinical syndrome characterized by pain, abdominal distention, flatulence, and diarrhoea that occur after lactose consumption. Lactose is currently a common disaccharide in human nutrition, both in breastfed infants and in adults, but its digestion requires a specialized enzyme called lactase. The genetically programmed reduction in lactase activity during adulthood affects most of the world's adult population and can cause troublesome digestive symptoms, which may also vary depending on the amount of residual lactase activity; the small bowel transit time; and, especially, the amount of ingested lactose. Several diagnostic tests are currently available for lactose intolerance, but the diagnosis remains challenging. The treatment for lactose intolerance mainly consists of reducing or eliminating the dietetic amount of lactose until the symptoms disappear, but this is hard to achieve, as lactose is present in dairy products and is even commonly used as a food additive. In addition to dietetic restriction of lactose-containing foods, lactase can be administered as an enzymatic food supplement, but its efficacy is still controversial. Recently, probiotics have been proposed for the management of lactose intolerance; certain probiotic strains have shown specific ß-galactosidase activity, thus aiding in the digestion of lactose. The aim of this paper was to review the current knowledge about lactose intolerance and to discuss the potential for the use of specific probiotic strains such as dietary supplements in lactose-intolerant patients.

House dust mite-related respiratory allergies and probiotics: a narrative review.

The socio-economic burden of allergic respiratory conditions on continental Europe is even higher than that of mainstream diseases, such as diabetes and cardiovascular disease, as allergic rhinitis alone accounts for billions of Euros in healthcare expenses across Europe. House dust mites (HDM) are one of the most common triggers behind allergic rhinitis and asthma. The role of probiotics in the treatment and prevention of some allergic conditions, such as atopic dermatitis, is already well recognized, whereas evidence about their efficacy in patients with respiratory allergies-while increasing-is still limited. Here the current evidence for the use of probiotics in patients with allergic rhinitis and/or asthma is discussed.

Therapeutic Efficacy of Autologous Non-Mobilized Enriched Circulating Endothelial Progenitors in Patients With Critical Limb Ischemia　- The SCELTA Trial.

BACKGROUND: The therapeutic efficacy of bone marrow mononuclear cells (BM-MNC) autotransplantation in critical limb ischemia (CLI) has been reported. Variable proportions of circulating monocytes express low levels of CD34 (CD14+CD34lowcells) and behave in vitro as endothelial progenitor cells (EPCs). The aim of the present randomized clinical trial was to compare the safety and therapeutic effects of enriched circulating EPCs (ECEPCs) with BM-MNC administration.Methods and Results:ECEPCs (obtained from non-mobilized peripheral blood by immunomagnetic selection of CD14+and CD34+cells) or BM-MNC were injected into the gastrocnemius of the affected limb in 23 and 17 patients, respectively. After a mean of 25.2±18.6-month follow-up, both groups showed significant and progressive improvement in muscle perfusion (primary endpoint), rest pain, consumption of analgesics, pain-free walking distance, wound healing, quality of life, ankle-brachial index, toe-brachial index, and transcutaneous PO2. In ECEPC-treated patients, there was a positive correlation between injected CD14+CD34lowcell counts and the increase in muscle perfusion. The safety profile was comparable between the ECEPC and BM-MNC treatment arms. In both groups, the number of deaths and major amputations was lower compared with eligible untreated patients and historical reference patients. CONCLUSIONS: This study supports previous trials showing the efficacy of BM-MNC autotransplantation in CLI patients and demonstrates comparable therapeutic efficacy between BM-MNC and EPEPCs.

Kounis syndrome: A concise review with focus on management.

Kounis syndrome is defined as the co-incidental occurrence of an acute coronary syndrome with hypersensitivity reactions following an allergenic event and was first described by Kounis and Zavras in 1991 as an allergic angina syndrome. Multiple causes have been described and most of the data in the literature are derived from the description of clinical cases - mostly in adult patients - and the pathophysiology remains only partly explained. Three different variants of Kounis syndrome have been defined: type I (without coronary disease) is defined as chest pain during an acute allergic reaction in patients without risk factors or coronary lesions in which the allergic event induces coronary spasm that electrocardiographic changes secondary to ischemia; type II (with coronary disease) includes patients with pre-existing atheromatous disease, either previously quiescent or symptomatic, in whom acute hypersensitive reactions cause plaque erosion or rupture, culminating in acute myocardial infarction; more recently a type-III variant of Kounis syndrome has been defined in patients with preexisting coronary disease and drug eluting coronary stent thrombosis. The pathogenesis of the syndrome is discussed, and a therapeutic algorithm is proposed.

Escaping the trap of allergic rhinitis.

Rhinitis is often the first symptom of allergy but is frequently ignored and classified as a nuisance condition. Ironically it has the greatest socioeconomic burden worldwide caused by its impact on work and on daily life. However, patients appear reticent to seek professional advice, visiting their doctor only when symptoms become 'intolerable' and often when their usual therapy proves ineffective. Clearly, it's time for new and more effective allergic rhinitis treatments. MP29-02 (Dymista®; Meda, Solna, Sweden) is a new class of medication for moderate to severe seasonal and perennial allergic rhinitis if monotherapy with either intranasal antihistamine or intranasal corticosteroids is not considered sufficient. MP29-02 is a novel formulation of azelastine hydrochloride (AZE) and fluticasone propionate (FP). It benefits not only from the incorporation of two active agents, but also from a novel formulation; its lower viscosity, smaller droplet size, larger volume (137 µl) and wider spray angle ensure optimal coverage of, and retention on the nasal mucosa and contribute to its clinical efficacy. In clinical trials, patients treated with MP29-02 experienced twice the symptom relief as those treated with FP and AZE, who in turn exhibited significantly greater symptom relief than placebo-patients. Indeed, the advantage of MP29-02 over FP was approximately the same as that shown for FP over placebo. The advantage of MP29-02 was particularly evident in those patients for whom nasal congestion is predominant, with MP29-02 providing three times the nasal congestion relief of FP (p = 0.0018) and five times the relief of AZE (p = 0.0001). Moreover, patients treated with MP29-02 achieved each and every response up to a week faster than those treated with FP or AZE alone and in real life 1 in 2 patients reported the perception of well-controlled disease after only 3 days. MP29-02's superiority over FP was also apparent long-term in patients with perennial allergic rhinitis or non-allergic rhinitis, with statistical significance noted from the first day of treatment, with treatment difference maintained for a full year. Taken together, these data suggest that MP29-02 may improve the lives of many of our patients, enabling them to finally escape the allergic rhinitis trap.

Kounis syndrome (allergic acute coronary syndrome): different views in allergologic and cardiologic literature.

The clinical picture of myocardial ischemia accompanying allergic reactions is defined in the cardiologic literature as Kounis syndrome (KS) or allergic angina/myocardial infarction. In PubMed, a search for "Kounis syndrome", "allergic angina" or "allergic myocardial infarction" retrieves more than 100 results (among case reports, case series and reviews), most of which are published in cardiology/internal medicine/emergency medicine journals. In allergologic literature, heart involvement during anaphylactic reactions is well documented, but Kounis syndrome is hardly mentioned. Single case reports and small case series of angina triggered by allergic reactions have been reported for many years, and involvement of histamine and others mast cell mediators in the pathogenesis of coronary spasm has long been hypothesized, but the existence of an allergic acute coronary syndrome (ACS) is still questioned in the allergologic scientific community. Putative mechanisms of an allergic acute coronary syndrome include coronary spasm or heart tissue-resident mast cell activation (precipitating coronary spasm or inducing plaque rupture and coronary or stent thrombosis) due to systemic increase of allergic mediators, or heart tissue-resident mast cell activation by local stimuli. Indeed, the pathogenic mechanism of an ACS after an allergic insult might be related to direct effects of mast cell mediators on the myocardium and the atherosclerotic plaque, or to exacerbation of preexisting disease by the hemodynamic stress of the acute allergic/anaphylactic reaction. Which of these mechanisms is most important is still unclear, and this review outlines current views in the cardiologic and allergologic literature.

The 10th anniversary of the Junior Members and Affiliates of the European Academy of Allergy and Clinical Immunology.

This year is the 10th anniversary of the European Academy of Allergy and Clinical Immunology (EAACI) Junior Members and Affiliates (JMAs). The aim of this review is to highlight the work and activities of EAACI JMAs. To this end, we have summarized all the initiatives taken by JMAs during the last 10 yr. EAACI JMAs are currently a group of over 2380 clinicians and scientists under the age of 35 yr, who support the continuous education of the Academy's younger members. For the past decade, JMAs enjoy a steadily increasing number of benefits such as free online access to the Academy's journals, the possibility to apply for Fellowships and the Mentorship Program, travel grants to attend scientific meetings, and many more. In addition, JMAs have been involved in task forces, cooperation schemes with other scientific bodies, organization of JMA focused sessions during EAACI meetings, and participation in the activities of EAACI communication platforms. EAACI JMA activities represent an ideal example of recruiting, training, and educating young scientists in order for them to thrive as future experts in their field. This model may serve as a prototype for other scientific communities, several of which have already adapted similar policies.