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BackgroundAtopic dermatitis (AD) is a chronic relapsing inflammatory skin disease in which patients are sensitized towards a plethora of allergens. The hosts fungal microbiota, the mycobiota, that is believed to be altered in patients suffering from AD acts as such an allergen. The correlation context of specific sensitization, changes in mycobiota and its impact on disease severity however remains poorly understood.ObjectivesWe aim to enhance the understanding of the specific sensitization towards the mycobiota in AD patients in relation to their fungal skin colonization.MethodsSensitization pattern towards the Malassezia spp. and Candida albicans of 16 AD patients and 14 healthy controls (HC) were analyzed with the newly developed multiplex-assay ALEX2® and the established singleplex-assay ImmunoCAP®. We compared these findings with the fungal skin colonization analyzed by DNA sequencing of the internal transcribed spacer region 1 (ITS1).ResultsSensitization in general and towards Malassezia spp. and C. albicans is increased in AD patients compared to HC with a quantitative difference in severe AD when compared to mild to moderate AD. Further we saw an association between sensitization towards and skin colonization with Candida spp. yet a negative correlation between sensitization towards and skin colonization with Malassezia spp.ConclusionWe conclude that AD in general and severe AD in particular is associated with increased sensitization towards the hosts own mycobiota. There is positive correlation in Candida spp. skin colonization and negative in Malassezia spp. skin colonization when compared to AD, AD severity as well as to specific sensitization patterns.

Background: The level of environmental exposure throughout life may contribute to the prevalence of allergic sensitization and allergic disease. The alpine climate has been considered a healthy climate with little allergen exposure and pollution. We conducted a cross-sectional study to investigate local environmental exposure and concomitant prevalence of allergic sensitization among local school children born and raised in an alpine environment. Methods: Clinical and demographic data were collected with a questionnaire. Allergen content was assessed in residential settled dust samples, lifetime exposure to pollen and air pollution was calculated using data from national pollen and air pollution monitoring stations, and the allergic sensitization profile was determined with component resolved diagnostics (ISAC®). Univariate and multivariate regression models were used to estimate the relation between exposure and sensitization. Results: In a cohort of children born and raised in an alpine environment, sensitization to aeroallergens is quite common (38%), especially to grass (33%) and cat (16%). House dust mite allergen was detected in up to 38% of residential dust samples, but sensitization to HDM was low (2.5%). Pollutant levels were low, but an increasing trend was observed in the amount of ozone and PM10. Living close to a busy road was associated with increased odds OR (95% CI) for being sensitized to any allergen 2.7 (1.0–7.2), to outdoor allergens 2.8 (1.1–7.1) and being sensitized plus reporting symptoms of rhinoconjunctivitis 4.4 (1.3–14.8) and asthma 5.5 (1.4–21). Indoor living conditions, including the presence of visible mold, increased the odds of being sensitized to indoor allergens (1.9 (1.1–3.2) and being sensitized plus reporting symptoms of rhinoconjunctivitis 1.9 (1.0–3.6) and asthma 2.1 (1.0–4.1). Conclusion: In a healthy alpine environment, pollution might still be an important factor contributing to allergic sensitization.

Urticaria, independent of or associated with allergies, is commonly seen in horses and often shows a high reoccurrence rate. Managing these horses is discouraging, and efficient treatment options are lacking. Due to an incidental finding in a study on horses affected by insect bite hypersensitivity using the eosinophil-targeting eIL-5-CuMV-TT vaccine, we observed the prevention of reoccurring seasonal urticaria in four subsequent years with re-vaccination. In an exploratory case series of horses affected with non-seasonal urticaria, we aimed to investigate the role of eosinophils in urticaria. Skin punch biopsies for histology and qPCR of eosinophil associated genes were performed. Further, two severe, non-seasonal, recurrent urticaria-affected horses were vaccinated using eIL-5-CuMV-TT, and urticaria flare-up was followed up with re-vaccination for several years. Eotaxin-2, eotaxin-3, IL-5, CCR5, and CXCL10 showed high sensitivity and specificity for urticarial lesions, while eosinophils were present in 50% of histological tissue sections. The eIL-5-CuMV-TT vaccine reduced eosinophil counts in blood, cleared clinical signs of urticaria, and even prevented new episodes of urticaria in horses with non-seasonal recurrent urticaria. This indicates that eosinophils play a leading role in urticaria in horses, and targeting eosinophils offers an attractive new treatment option, replacing the use of corticosteroids.

Abstract Introduction The integrated care pathways for atopic dermatitis (AD‐ICPs) aim to bridge the gap between existing AD treatment evidence‐based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co‐ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD‐ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results The AD‐ICPs outline the diagnostic procedures, possible co‐morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion The AD‐ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Abstract Background Specific immunotherapy for patients with honey bee hypersensitivity is commonly applied. Re-challenge with venom is performed to prove protection in individual cases. Case presenation We report a case of near fatal anaphylaxis with asystole for 24 min in a 35-years-old patient with mastocytosis after honey bee sting challenge, despite 5-years of specific immunotherapy. Successful cardio-pulmonary resuscitation was applied for 32 min. Conclusion This intervention demonstrates, that in anaphylaxis with cardio-vascular arrest, prolonged cardio-pulmonary resuscitation for up to 40 min may be appropriate to overcome the half-life of massively released histamine. Failure of specific immunotherapy was possibly due to sensitization to the allergen Api m10, potentially underrepresented in commercial honey bee venom extracts. Molecular analyses may provide additional clues to the potentially unsuccessful outcome of venom specific immunotherapy, especially in high-risk patients such as mastocytosis.

Introduction: Patients with atopic dermatitis (AD) have several potential stressors including the symptoms of the disease itself, the stigmatization due to their appearance, and emotional and psychological strain. Psychological factors and stress can trigger and exacerbate the symptoms of skin diseases and there is evidence that stress has a relevant clinical effect on the function of skin cells in vivo. Our objective was to evaluate in a pilot study the feasibility, acceptance, and effectiveness of a Mindfulness-Based Stress Reduction (MBSR) programme in AD patients in a clinical setting. Methods: 10 patients took part in an 8-week MBSR programme, which included, e.g., mindful and conscious awareness of the body and bodywork, and seated meditation. We assessed sociodemographics and disease related variables with standardized measures at predefined time points including Score of Atopic Dermatitis, Patient Oriented Eczema Measure, Dermatology Life Quality Index, Perceived Stress Questionnaire, Freiburg Mindfulness Inventory (FMI), and others. Participants also gave qualitative feedback regarding the effects of the intervention. Results: The mean age was 53.10 years (SD = 15.04), seven patients were female, and disease duration was 36.6 years (SD = 25.5). Calculating pre-post effect sizes (Cohen’s d), the FMI indicated significant improvement in the “presence” and “acceptance” subscales. There was also tendency for less stress. This was confirmed by the qualitative statements of the participants. Conclusions: The MBSR programme is feasible and acceptable for AD patients. Considering the long disease history and the severity of disease burden, the effects of this intervention seem promising as an adjunct to conventional treatments for patients with AD.

BackgroundType 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases.AimsTo improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future.MethodologyThis qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach.ResultsEighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients.ConclusionPatients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care.

Here, the authors characterize immunological and microbiome alterations in a cohort of obese asthmatics, finding that disease severity negatively correlates with fecal abundance of Akkermansia muciniphila, and show in a mouse model that administration of A. muciniphila reduces airway hyper-reactivity and airway inflammation.

Background: The diagnostic approach for beta-lactam (BL) drug hypersensitivity reactions (DHR) is based on the history, clinical signs, skin tests (ST), in vitro tests, and drug provocation tests (DPT). The aim of this study was to assess the performance of an allergy workup with ST in a real-world use. Methods: In this cross-sectional study the rate of positive ST in subjects with suspected DHR to penicillins and cephalosporins was investigated. Of special interest were correlations of ST positivity: 1) to the time intervals between index reaction and the allergic work-up, 2) time interval from drug exposure to the onset of signs, 3) pattern of manifestation in delayed DHR and involvement of test area in the index reaction, and 4) potential advantage of patch testing in delayed DHR. Results: 175 patients were included between January 2018 and April 2019 (63.4% female), 45 (25.7%) with immediate DHR manifestation and 130 with delayed DHR manifestation (74.3%). A total of 44 patients (25.1%) had a positive ST (immediate DHR 37.8% versus 20.0% in delayed DHR). ST positivity decreased in both groups after 3 years from 47.8% [95%CI 29.2–67] to 23.5% [95%CI 9.6–47.3] in immediate DHR and 23.0% [95%CI 15-4-32.9] to 12.9% [95%CI 5.1–28.9] in delayed DHR. The proportion of positive ST was higher in patients with more severe forms of delayed DHR, and in subjects with a shorter latency period of onset of symptoms after drug exposure: 0-3d: 29.5% [95%CI 19.6–41.9] vs. >3d: 11.6% [95%CI 6.0–21.2]). No sensitization was shown in delayed urticaria or angioedema. ST done outside the skin area involved during the index reaction were negative in all cases (0/38 vs. 26/84 in cases with involved area). The combination of patch test and intradermal test (IDT) revealed an additional positive result in 2/77 cases. Additional in vitro testing reduced the proportion of negative test results to 72%. Conclusion: In most patients with negative test results, we could not clarify the cause of the BL-associated adverse events even with further investigations (including DPT). How to prevent new drug-induced adverse events in such patients has hardly been investigated yet. Corresponding cohort studies could improve the data situation.

Atopic dermatitis is a chronic inflammatory skin disease characterised by eczematous skin lesions and intense pruritus. It is often associated with other atopic diseases such as allergic rhinitis and conjunctivitis, bronchial asthma and eosinophilic oesophagitis. Dupilumab is the first biologic approved for the treatment of moderate-to-severe atopic dermatitis in Switzerland. Dupilumab targets the interleukin (IL)-4/IL-13 receptor and thus inhibits the signalling of IL-4 and IL-13, two key mediators of type 2 inflammation, resulting in an improvement of clinical signs and symptoms of atopic dermatitis. Patients with atopic dermatitis present more often with ocular surface diseases (OSDs), such as allergic conjunctivitis, blepharitis and keratitis as well as infectious conjunctivitis and keratoconus compared with the general population. Upon dupilumab therapy, increased rates of ocular surface diseases have been reported in clinical trials. Interestingly, dupilumab-associated (da) OSD is restricted to atopic dermatitis patients and has not been observed in asthma and chronic rhinosinusitis trials. Fortunately, most cases of dupilumab-associated OSD are mild-to-moderate and transient. Thus, ocular surface disease presents a particular adverse event of treatment with dupilumab in dermatology. This article aims at providing a practical guide for physicians, with a special focus on dermatologists, allergists and ophthalmologists in Switzerland, to the diagnosis and management of dupilumab-associated OSD in atopic dermatitis patients. For this purpose, an expert group of dermatologists and ophthalmologists from university and cantonal hospitals in Switzerland reviewed data on ocular surface diseases published in clinical trial and real-life reports of dupilumab therapy, published case reports and case series on the management of dupilumab-associated OSD, as well as recent recommendations provided by experts of national and international boards. Based on the observations of dupilumab-associated OSD and practical experiences in identifying and treating OSD, an algorithm has been developed that is specific to the needs in Switzerland. Considering concomitant ocular diseases and differential diagnoses, the clinical presentation of dupilumab-associated OSD and its response to therapeutic measures, a stepwise approach is recommended. Mild dupilumab-associated OSD can be managed by dermatologists and allergists, whereas patients with moderate-to-severe OSD requiring corticosteroid or calcineurin inhibitor therapy should necessarily be referred to an ophthalmologist. The effects of preventive measures, such as artificial tears, are uncertain. The recommendations provided here should guarantee a prompt and effective treatment of OSD for patients under dupilumab therapy in order to prevent that an otherwise potent therapy has to be ceased because of ocular adverse events.

Background: Few studies have explored the association between obstructive sleep apnea (OSA) and chronic urticaria (CU). Our study aims to fill this gap by determining the frequency of the risk categories for OSA and how they might correlate with the specific CU patient reported outcome measures urticaria activity score (UAS7), urticaria control test (UCT) and CU quality of life questionnaire (CU-Q2oL). Methods: We conducted a cross-sectional study involving a cohort of 171 Latin American CU patients. Descriptive statistics were used to determine frequency and proportions for demographic and clinical variables, while a chi-squared test for association between STOP-Bang OSA questionnaire categories and both UAS7 and UCT categories was performed to analyze how such variables interact. To further assess the strength of the correlation a Cramer's V coefficient was reported. Finally, a Kendall-Tau b correlation coefficient was performed to measure the correlation between the STOP-Bang score and other independent continuous variables. Results: The average STOP-Bang score was 2.5, with 24% and 21% of patients falling into the intermediate and high-risk category for moderate-to-severe OSA, respectively. There was a strong statistically significant association (Cramer's V = 0.263; p = .000) between UAS-7 categories and STOP-Bang risk categories. A similar pattern of strong significant association (Cramer's V = .269; p = .002) was observed between UCT categories and STOP-Bang risk categories. A weak positive correlation between the STOP-Bang score and the CU-Q2oL average score (τb = 0.188, p = .001) was identified. Overall, 72.5% patients reported limitations with respect to sleep in a varied degree according to the CU-Q2oL. Conclusions: Our results suggest that a considerable proportion of patients with CU are at intermediate to high risk for OSA. Higher disease activity, poor CU control, and worse quality of life were all found to be associated with an increased risk. Additional studies are needed to determine the exact link between these conditions, and to determine whether screening and treatment for OSA might benefit patients with CU.

Allergic rhinitis in childhood has been often missed, mistreated and misunderstood. It has significant comorbidities, adverse effects upon quality of life and educational performance and can progress to asthma or worsen control of existing asthma. Accurate diagnosis and effective treatment are important. The new EUFOREA algorithm provides a succinct but wide- ranging guide to management at all levels, based on previous guidelines with updated evidence and has been adjusted and approved by experts worldwide.

Abstract Background Hymenoptera stings are a major cause of anaphylaxis. Various risk factors are discussed in literature. This study aims to investigate potential risk factors for severe sting reactions in wasp (Vespula spp.) and honeybee (Apis mellifera) venom allergic patients and analyses the correlation between diagnostic test results and the severity of the allergic reaction. Methods 480 patients suffering from wasp or honeybee venom allergy were included in this retrospective case series. Only individuals allergic to Vespula spp. but not to other vespids such as Polistes were considered. The severity of their systemic field sting reaction was analysed with regard to the amount of specific IgE antibodies to whole venom extracts and to major allergens of honeybee and/or wasp venom. Furthermore, the following potential risk factors for severe sting reactions were examined: age, sex, latency time, skin symptoms, baseline serum tryptase levels and the concentration of venom inducing a positive intracutaneous test. Results The two following indicators for severe systemic sting reactions in honeybee and wasp venom allergic patients have been identified: a short latency time and the absence of skin symptoms. The patient’s age and baseline serum tryptase levels have been found to positively correlate with the grade of the sting reaction only in individuals allergic to wasp venom. No correlation could be found between the degree of sensitisation and the severity of the allergic reaction. Neither the amount of specific IgE antibodies to whole venom extracts nor to major allergens were significantly associated with the severity of the sting reaction. Conclusion The clinical history is essential for the allergological workup and therapeutic decision on Hymenoptera venom allergies. A short latency time and the absence of skin symptoms are indicators for severe systemic sting reactions, followed by the patient’s age and baseline serum tryptase levels.

Precision allergy molecular diagnostic applications (PAMD@) is increasingly entering routine care. Currently, more than 130 allergenic molecules from more than 50 allergy sources are commercially available for in vitro specific immunoglobulin E (sIgE) testing. Since the last publication of this consensus document, a great deal of new information has become available regarding this topic, with over 100 publications in the last year alone. It thus seems quite reasonable to publish an update. It is imperative that clinicians and immunologists specifically trained in allergology keep abreast of the new and rapidly evolving evidence available for PAMD@.PAMD@ may initially appear complex to interpret; however, with increasing experience, the information gained provides relevant information for the allergist. This is especially true for food allergy, Hymenoptera allergy, and for the selection of allergen immunotherapy. Nevertheless, all sIgE tests, including PAMD@, should be evaluated within the framework of a patient's clinical history, because allergen sensitization does not necessarily imply clinical relevant allergies. Keywords: Diagnosis, Molecular allergy, Cross reactivity, Panallergen, Specific IgE, PAMD@

Abstract Background Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is a rare inherited disease. In most HAE-affected subjects, defined trigger factors precede angioedema attacks. Mechanisms of how trigger factors stimulate the contact activation pathway with bradykinin generation are not well elucidated. In recent studies, hypersensitivity reactions and food were stated as relevant triggers. We investigated HAE affected people for possible hypersensitivity reactions or intolerances and their relation in triggering angioedema attacks. Methods A questionnaire was filled in, recording date of birth, gender, and self-reported angioedema attacks associated with the ingestion of foodstuffs, administration of drugs, hymenoptera stings and hypersensitivity reactions against inhalation allergens. All participants performed a skin prick test against inhalation allergens and food. In patients who stated an association of possible hypersensitivity with angioedema, a serological ImmunoCAP test was also performed. Results From the 27 women and 15 men analyzed, 79% stated trigger factors. From those food was mentioned in 36%. The suspected food included tomato, green salad, fish, citrus fruits, apple, onion, garlic, cheese, chili, kiwi, milk, tree nuts, strawberry, pineapple, shrimps, bread, banana, leek, chicken and alcohol, and were associated with abdominal angioedema. Neither the skin prick test nor the ImmunoCAP-test turned out positive for the tested food allergens. Conclusion Food seems to be a relevant trigger factor, causing angioedema in HAE affected patients. The reason, however, is not IgE-mediated hypersensitivity, but most probably an intolerance reaction to food products.

In this review, we outline and reflect on the important differences between allergen-specific immunotherapy for inhalant allergies (i.e., aeroallergens) and venom-specific immunotherapy (VIT), with a special focus on Venomil® Bee and Wasp. Venomil® is provided as a freeze-dried extract and a diluent to prepare a solution for injection for the treatment of patients with IgE-mediated allergies to bee and/or wasp venom and for evaluating the degree of sensitivity in a skin test. While the materials that make up the product have not changed, the suppliers of raw materials have changed over the years. Here, we consolidate relevant historical safety and efficacy studies that used products from shared manufacture supply profiles, i.e., products from Bayer or Hollister–Stier. We also consider the characterization and standardization of venom marker allergens, providing insights into manufacturing controls that have produced stable and consistent quality profiles over many years. Quality differences between products and their impacts on treatment outcomes have been a current topic of discussion and further research. Finally, we review the considerations surrounding the choice of depot adjuvant most suitable to augmenting VIT.

Background: Existing clinical guidelines do not offer an efficient alternative for the collection of data on relevant clinical traits during history and physical of the patient with chronic urticaria. Objective: Our aim was to provide a clinical data checklist together with its guide to allow for thorough information to be obtained and for a physical exam that identifies the main features and triggering factors of the disease to be carried out. Methods: A search was conducted for relevant literature on chronic urticaria in Medline, the Cochrane library and PubMed. Results: We developed an easy-to-use clinical data checklist with its corresponding clinical guide, comprised by 42 items based on two components: essential clues for history taking and chronic urticaria diagnosis (typical symptoms according to subgroups, etiology and laboratory results). Some components are the time of disease onset, wheals’ duration, shape, size, color and distribution, associated angioedema, atopy, triggering factors and others. Conclusions: The clinical data checklist and its guide constitute a tool to focus, guide and save time in medical consultation, with the main purpose to aid physicians in providing better diagnosis and management of the disease.

Abstract Background Existing guidelines do not offer a quick, efficient alternative to the patient’s recollection of relevant clinical features during anamnesis and physical examination for chronic urticaria (CU). This study aimed to identify specific items reflecting the main characteristics of CU that should be included in a comprehensive medical history for patients with CU. We also aimed to clarify possible eliciting factors for CU to support accurate diagnosis of the disease. Methods A panel of postgraduate dermatologists conducted a literature search for relevant studies on CU using Medline, the Cochrane database, and PubMed. Results We identified82 articles from which we drew a collection of items to inform development of an easy-to-use checklist and collection of items that should be included in a correct medical history. The final version of the checklist included42 items across two areas: essential clues for anamnesis and diagnosis of CU; and typical symptoms/parameters or characteristics according to subtype, etiology, and laboratory findings. Items included time of disease onset; duration, shape, size, color, and distribution of wheals; associated angioedema; atopy; and triggering factors. Conclusions Our guide provides an easy-to-use tool to support clinicians to focus, orient themselves, and save time in medical consultations for CU, allowing better diagnosis and management of this disease.

Background: Second hand tobacco smoke (SHS) and overweight/obesity are risk factors for asthma and lower airway respiratory symptoms. We investigated whether SHS or overweight/obesity were also associated with allergic or non-allergic rhinitis. Methods: Cross-sectional data were obtained during the second SAPALDIA Study. Interviewer administered questionnaires were completed by 8047 participants from 8 communities in Switzerland. Blood was collected from 5841 participants and tested for allergen specific IgE. Allergic rhinitis was defined as nasal symptoms with detectable IgE. Data were analysed by multinomial logistic regression with four outcome categories defined according to the presence or absence of rhinitis and/or atopy. Results: The prevalence of allergic rhinitis was 885 (15.2%) and non-allergic rhinitis 323 (5.5%). The risk of allergic rhinitis was increased in subjects with physician diagnosed asthma (Relative Risk Ratio 6.81; 95%CI 5.39, 8.6), maternal atopy (1.56; 1.27, 1.92) and paternal atopy (1.41; 1.11, 1.79). Older subjects were at lower risk (0.96; 0.95,0.97 per year), as were those raised on a farm (0.64; 0.49,0.84), with older siblings (0.92; 0.86,0.97 per sib) or from rural areas. The risk of non-allergic rhinitis was also increased in subjects with physician diagnosed asthma (4.02; 2.86, 5.67), reduced in males (0.59; 0.46, 0.77), but not associated with upbringing on a farm or older siblings. There were no significant associations of SHS or overweight/obesity with either form of rhinitis. Conclusions: Allergic and non-allergic rhinitis have different risk factors apart from asthma. There are significant regional variations within Switzerland, which are not explained by the factors examined.

Food intolerances are estimated to affect up to 20% of the population but complete understanding of diagnosis and management is complicated, given presentation and non-immunological mechanisms associated vary greatly. This review aims to provide a scientific update on common food intolerances resulting in gastrointestinal and/or extra-intestinal symptoms. FODMAP sensitivity has strong evidence supporting its mechanisms of increased osmotic activity and fermentation with the resulting distention leading to symptoms in those with visceral hypersensitivity. For many of the other food intolerances reviewed including non-coeliac gluten/wheat sensitivity, food additives and bioactive food chemicals, the findings show that there is a shortage of reproducible well-designed double-blind, placebo-controlled studies, making understanding of the mechanisms, diagnosis and management difficult. Enzyme deficiencies have been proposed to result in other food sensitivities including low amine oxidase activity resulting in histamine intolerance and sucrase-isomaltase deficiency resulting in reduced tolerance to sugars and starch. Lack of reliable diagnostic biomarkers for all food intolerances result in an inability to target specific foods in the individual. As such, a trial-and-error approach is used, whereby suspected food constituents are reduced for a short-period and then re-challenged to assess response. Future studies should aim to identify biomarkers to predict response to dietary therapies.

Toxic epidermal necrolysis (TEN) is a rare, life-threatening drug-induced skin disease with a mortality rate of approximately 30%. The clinical hallmark of TEN is a marked skin detachment caused by extensive keratinocyte cell death associated with mucosal involvement. The exact pathogenic mechanism of TEN is still uncertain. Recent advances in this field have led to the identification of several factors that might contribute to the induction of excessive apoptosis of keratinocytes. In addition, specific human leukocyte antigen types seem to be associated with certain drugs and the development of TEN. As well-controlled studies are lacking, patients are treated with various immunomodulators (e.g. intravenous immunoglobulin) in addition to the best supportive care.

We report 2 patients with cold urticaria with different response to treatment with omalizumab (Xolair®). Cold contact urticaria (CCU) is a common subtype of physical urticaria. It is characterized by the development of wheal and/or angioedema within minutes after cold contact. Clinical manifestation of CCU can range from mild, localized whealing to life-threatening anaphylactic shock reactions. Omalizumab has been described to be useful in cases of chronic urticaria and may be an interesting option for treatment of CCU. We describe one patient with significant and long-lasting improvement of symptoms and one without any improvement after anti-immunoglobulin E therapy. In our case reports, we want to highlight that there is still a small group of patients without benefit from omalizumab treatment. It is necessary to identify this minor subgroup of patients where omalizumab does not represent an effective treatment possibility.