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Background: Mastocytosis comprises a heterogeneous group of disorders characterized by an accumulation of mast cells in 1 or more organs. Symptoms range from mild complaints to severe and life-threatening events. Impact on quality of life seems to vary widely, but influencing factors are poorly understood so far., Objective: To examine impairments, psychological burden, health-related quality of life (HRQOL), and possible influencing factors in patients with mastocytosis., Methods: In semistructured telephone interviews, patients provided information on impairments in everyday life and psychological burden caused by mastocytosis. HRQOL was measured using the Mastocytosis Quality of Life (MC-QoL) questionnaire. Clinical data were collected from patient files., Results: A total of 101 adult patients with mastocytosis (74.3% women; mean age, 47.7 ± 13.5 years) were included. Half of the interviewed patients (50.6%) reported disease-related impairments in everyday life, and 42.4% stated a psychological burden. MC-QoL questionnaire scores showed a broad distribution, with a mean total score at a "mild" impairment level (mean total score, 34.7 ± 22.5). One-third of patients felt moderately (22.8%) or severely (13.9%) impaired, whereas one-third reported no impairment at all (30.7%). Symptoms of mast cell activation and perceived food intolerance had the highest impact on HRQOL. Higher age, higher body mass index, higher tryptase level, and longer duration of symptoms, as well as current drug therapy and pathological bone density, were each associated with reduced HRQOL., Conclusions: A high level of suffering and strong associations between impairments and symptom-related factors indicate the importance of addressing patients' concerns and adequate symptom management in mastocytosis., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Not available., (© Dustri-Verlag Dr. K. Feistle.)

Mastocytosis is a rare neoplasm characterized by the expansion and accumulation of mast cells in various organ systems. Systemic mastocytosis (SM) may or may not present with cutaneous lesions. To examine the frequency and clinical impact of cutaneous involvement, data on 1,510 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis were analyzed. Cutaneous involvement was found in 1,195 of 1,510 patients (79.1%). Of these, 286 had cutaneous mastocytosis, and 721 had SM with skin involvement. Adult patients with skin involvement who did not have a bone marrow examination (n = 188) were defined as having mastocytosis in the skin. In 315 patients, SM without skin involvement was found. The percentage of cases with cutaneous involvement was higher in indolent SM (100%) and smoldering SM (87.9%) compared to aggressive SM (46.8%) or mast cell leukemia (38.5%). After a median follow-up of 5.6 years, no patient with cutaneous mastocytosis had died, but 2.6% of the patients with mastocytosis in the skin, 5.7% of the patients with SM with skin involvement, and 28.95% of the patients with SM without skin involvement had died. Overall survival was longer in patients with skin involvement (cutaneous mastocytosis and/or mastocytosis in the skin and/or SM with skin involvement) than in patients with SM without skin involvement (P < 0.0001). These data argue for a thorough examination of both the skin and bone marrow in adult patients with mastocytosis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Mastocytosis is a neoplasm characterized by an accumulation of mast cells in various organs and increased risk for severe anaphylaxis in patients with concomitant allergies. Coronavirus disease 2019 (COVID-19) is a pandemic that is associated with a relatively high rate of severe lung disease and mortality. The mortality is particularly high in those with certain comorbidities and increases with age. Recently, several companies have developed an effective vaccination against COVID-19. Although the reported frequency of severe side effects is low, there is an emerging discussion about the safety of COVID-19 vaccination in patients with severe allergies and mastocytosis. However, even in these patients, severe adverse reactions are rare. We therefore recommend the broad use of COVID-19 vaccination in patients with mastocytosis on a global basis. The only well-established exception is a known or suspected allergy against a constituent of the vaccine. Safety measures, including premedication and postvaccination observation, should be considered in all patients with mastocytosis, depending on the individual personal risk and overall situation in each case. The current article provides a summary of published data, observations, and expert opinion that form the basis of these recommendations., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline., Methods: We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis., Results: It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar., Conclusions: Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Allergic diseases of the (upper and lower) airways, the skin and the gastrointestinal tract, are on the rise, resulting in impaired quality of life, decreased productivity, and increased healthcare costs. As allergic diseases are mostly tissue-specific, local sampling methods for respective biomarkers offer the potential for increased sensitivity and specificity. Additionally, local sampling using noninvasive or minimally invasive methods can be cost-effective and well tolerated, which may even be suitable for primary or home care sampling. Non- or minimally invasive local sampling and diagnostics may enable a more thorough endotyping, may help to avoid under- or overdiagnosis, and may provide the possibility to approach precision prevention, due to early diagnosis of these local diseases even before they get systemically manifested and detectable. At the same time, dried blood samples may help to facilitate minimal-invasive primary or home care sampling for classical systemic diagnostic approaches. This EAACI position paper contains a thorough review of the various technologies in allergy diagnosis available on the market, which analytes or biomarkers are employed, and which samples or matrices can be used. Based on this assessment, EAACI position is to drive these developments to efficiently identify allergy and possibly later also viral epidemics and take advantage of comprehensive knowledge to initiate preventions and treatments., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)," we critically appraised evidence on systemic treatments for moderate-to-severe AD., Methods: We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate., Results: 50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon-gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta-analyses were indicated for the efficacy of baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (ie 16-week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short-term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI., Conclusion: The most robust, replicated high-quality trial evidence is present for the efficacy and safety of dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies., (© 2020 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Mastocytosis in adults often presents with skin lesions. A bone marrow biopsy is necessary to confirm or exclude the presence of systemic mastocytosis (SM) in these cases. When a bone marrow biopsy is not performed, the provisional diagnosis is mastocytosis in the skin (MIS). No generally accepted scoring system has been established to estimate the risk of SM in these patients., Objective: To develop a risk score to predict SM in adults with MIS., Methods: We examined 1145 patients with MIS from the European Competence Network on Mastocytosis Registry who underwent a bone marrow biopsy. A total of 944 patients had SM and 201 patients had cutaneous mastocytosis; 63.7% were female, and 36.3% were male. Median age was 44 ± 13.3 years. The median serum tryptase level amounted to 29.3 ± 81.9 ng/mL. We established a multivariate regression model using the whole population of patients as a training and validation set (bootstrapping). A risk score was developed and validated with receiver-operating curves., Results: In the multivariate model, the tryptase level (P < .001), constitutional/cardiovascular symptoms (P = .014), and bone symptoms/osteoporosis (P < .001) were independent predictors of SM (P < .001; sensitivity, 90.7%; specificity, 69.1%). A 6-point risk score was established (risk, 10.7%-98.0%) and validated., Conclusions: Using a large data set of the European Competence Network on Mastocytosis Registry, we created a risk score to predict the presence of SM in patients with MIS. Although the score will need further validation in independent cohorts, our score seems to discriminate safely between patients with SM and with pure cutaneous mastocytosis., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The prevalence of all cutaneous manifestations directly associated with COVID-19 infection is unknown, but the number of reports is rapidly increasing and provisional knowledge is rapidly evolving. Skin manifestations reported can be classified into (1) manifestations unspecifically indicating possible infectious diseases, i.e. maculopapular exanthem, urticaria and erythema multiforme, and (2) manifestations more specifically indicating COVID-19 infection, i.e. varicella-like, livedo reticularis or chilblain-like eruptions. The latter appear to be associated with thrombovascular events and vascular pathologies., (© 2021 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Mastocytosis is characterized by the pathological accumulation of mast cells (MC) in various organs. In these patients, MC may degranulate and thereby contribute to clinical symptoms, especially when a concomitant allergy is present. However, MC activation can not only be induced by high-affinity receptors for IgE, but also by anaphylatoxins, neuropeptides, IgG immune complexes, complement-components, drugs, products of bacteria or parasites, as well as physical factors such as heat, cold, vibration, stress, sun, or physical effort. Symptoms due to mediators released by activated MC may develop in adults suffering from systemic mastocytosis, but also evolve in children who usually have cutaneous mastocytosis (CM). Clinically, CM is otherwise characterized by typical brown, maculopapular skin lesions or mastocytoma associated with a positive Darier's sign. Pruritus and flushing are common and blistering may also be recorded, especially in diffuse CM (DCM). Pediatric patients with mastocytosis may also have gastrointestinal, respiratory, and neurologic complaints. Although anaphylaxis is not a typical finding, pediatric patients with massive skin involvement and high tryptase levels have a relatively high risk to develop anaphylaxis. This paper reviews MC mediator-related symptoms and anaphylaxis in children with mastocytosis, with special emphasis on risk factors, triggers, and management.

Pediatric mastocytosis is a heterogeneous disease characterized by accumulation of mast cells in the skin and less frequently in other organs. Somatic or germline mutations in the KIT proto-oncogene are detected in most patients. Cutaneous mastocytosis is the most common form of the disease in children. In the majority of cases, skin lesions regress spontaneously around puberty. However, in few patients, mastocytosis is not a self-limiting disease, but persists into adulthood and can show signs of systemic involvement, especially when skin lesions are small-sized and monomorphic. Children with mastocytosis often suffer from mast cell mediator-related symptoms. Severe hypersensitivity reactions can also occur, mostly in patients with extensive skin lesions and blistering. In a substantial number of these cases, the triggering factor of anaphylaxis remains unidentified. Management of pediatric mastocytosis is mainly based on strict avoidance of triggers, treatment with H1 and H2 histamine receptor blockers, and equipment of patients and their families with epinephrine auto-injectors for use in severe anaphylactic reactions. Advanced systemic mastocytosis occurs occasionally. All children with mastocytosis require follow-up examinations. A bone marrow investigation is performed when advanced systemic mastocytosis is suspected and has an impact on therapy or when cutaneous disease persists into adulthood.

Primary and secondary mast cell activation syndromes (MCAS) can occur in patients with mastocytosis. During the past few years our knowledge about the pathogenesis and disease-triggering mechanisms in MCAS and mastocytosis have increased substantially. Whereas mastocytosis is characterized by an accumulation of neoplastic (clonal) mast cells (MC) in various organ systems, MCAS is defined by a massive and systemic activation of these cells. Mast cells are crucial effector cells in allergic diseases, thus their elevated number and activation can cause severe anaphylactic reactions and MCAS in patients with mastocytosis. However, these cells may also degranulate spontaneously or degranulate in response to non-allergic triggers leading to clinical symptoms. In mastocytosis patients, such symptoms may lead to the diagnosis of a primary MCAS. The diagnosis of a concomitant allergy in mastocytosis patients is challenging. In these patients, a mixed form (primary and secondary) of MCAS may be diagnosed. These patients may also suffer from life-threatening anaphylactic reactions when exposed to allergens. In these cases, the possibility of severe side effects of in vivo provocations can sometimes also limit diagnostic evaluations. In the current article, we discuss the diagnosis and management of patients suffering from mastocytosis and concomitant MCAS, with special emphasis on novel diagnostic tests and management, including allergen microarrays, recombinant allergen analysis, basophil activation tests, optimal prophylaxis, and specific therapies., Competing Interests: The authors declare no conflict of interest.

Not available., (© Dustri-Verlag Dr. K. Feistle.)

Severe allergic reactions to vaccines are very rare. Single severe reactions have occurred worldwide after vaccination with the new mRNA-based COVID-19 vaccines. PEG2000 is discussed as a possible trigger. We provide guidance on risk assessment regarding COVID-19 vaccination in patients with allergic diseases and suggest a standardized, resource-oriented diagnostic and therapeutic procedure. Reports of severe allergic reactions in the context of COVID-19 vaccination can be made via www.anaphylaxie.net using an online questionnaire., (© Dustri-Verlag Dr. K. Feistle.)

Background: For the preventive treatment of the 2019 coronavirus disease (COVID-19) an unprecedented global research effort studied the safety and efficacy of new vaccine platforms that have not been previously used in humans. Less than one year after the discovery of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral sequence, these vaccines were approved for use in the European Union (EU) as well as in numerous other countries and mass vaccination efforts began. The so far in the EU approved mRNA vaccines BNT162b2 and mRNA-1273 are based on similar lipid-based nanoparticle carrier technologies; however, the lipid components differ. Severe allergic reactions and anaphylaxis after COVID-19 vaccination are very rare adverse events but have drawn attention due to potentially lethal outcomes and have triggered a high degree of uncertainty., Methods: Current knowledge on anaphylactic reactions to vaccines and specifically the new mRNA COVID-19 vaccines was compiled using a literature search in Medline, PubMed, as well as the national and international study and guideline registries, the Cochrane Library, and the Internet, with special reference to official websites of the World Health Organization (WHO), US Centers for Disease Control and Prevention (CDC), Robert Koch Institute (RKI), and Paul Ehrlich Institute (PEI)., Results: Based on the international literature and previous experience, recommendations for prophylaxis, diagnosis and therapy of these allergic reactions are given by a panel of experts., Conclusion: Allergy testing is not necessary for the vast majority of allergic patients prior to COVID-19 vaccination with currently licensed vaccines. In case of allergic/anaphylactic reactions after vaccination, allergy workup is recommended, as it is for a small potential risk population prior to the first vaccination. Evaluation and approval of diagnostic tests should be done for this purpose., Competing Interests: Conflict of interestL. Klimek reports grants and/or personal fees from Allergopharma, MEDA/Mylan, HAL Allergie, ALK Abelló, LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT Biotech, Lofarma, Allergy Therapeutics, AstraZeneca, GSK, Inmunotek, Cassella med and Novartis, outside of the submitted work; and memberships in the following organizations: AeDA, DGHNO, German Academy for Allergology and Clinical Immunology, ENT-BV, GPA, EAACI. L. Klimek is editor in chief of Allergo Journal International. R. Brehler reports fees and/or research support from ALK, Allergopharma, Bencard, HAL, Leti, Stallergenes, Astra Zeneca, GSK, MedUpdate, Novartis, BiotechTools, Genentech and Circassia, outside of the submitted work. W. Pfützner reports grants and/or personal fees and/or non-financial support from ALK-Abello, Biomay, Cilag-Janssen, Lilly, Novartis and Thermo Fisher outside of the submitted work. T. Zuberbier reports grants and/or personal fees from AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES, HAL, Leti, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Stallergenes, Takeda, Teva, UCB, Henkel, Kryolan and L’Oréal outside of the submitted work; and the following organizational affiliations: Member of the committee: WHO initiative “Allergic Rhinitis and its Effects on Asthma” (ARIA), Board member: German Society for Allergy and Clinical Immunology (DGAKI), Chairman of the Board: Foundation of the European Center for Allergy Research (ECARF), President: Global European Network on Allergy and Asthma (GA2LEN), Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). K. Hartmann has received research grants outside of the present work from Euroimmun and Thermofisher as well as consulting or lecture fees from Allergopharma, ALK-Abelló, Blueprint, Deciphera, Menarini, Novartis and Takeda. T. Jakob reports grants and/or personal fees and/or non-financial support from Novartis, ALK-Abello, Allergy Therapeutics/Bencard, Allergopharma, and Thermo Fisher outside of the submitted work. T. Jakob is editor in chief of Allergo Journal International. N. Novak reports grants and/or personal fees from Alk Abelló, HAL Allergy, Stallergenes Geer, Leti Pharma, Novartis, Leo Pharma, Abbvie, Sanofi Genzmye, Lofarma and Bencard Allergy Therapeutics, outside of the submitted work. J. Ring reports fees from Mylan and Allergika outside of the submitted work. T. Ankermann received fees outside the submitted work from the following companies and organizations: Abbvie, Allergopharma, Chiesi, Infectopharm, Novartis, UKSH Akademie, RG, Springer Verlag, Wissenschaftliche Verlagsgesellschaft, GPP eV, GPA eV, nappa eV and ÖGKJ eV and is an advisory agent active for Boehringer Ingelheim, Aimmune and Allergopharma. S. Schmidt reports grants and/or personal fees and/or non-financial support from Allergopharma, ALK, Bencard, Gilead, Mundipharma, Novartis, Vertex, HAL, Sanofi, Olympus, Infectopharm, Pari and Pfizer outside of the submitted work. V. Mahler The positions stated in this work represent the personal views of the author as an expert in the field of allergology and must not be understood or cited as the view of the Federal Institute for Vaccines and Biomedical Medicines, the European Medicines Agency or one of its Committees or working groups. There are no conflicts of interest. M. Worm reports fees for consulting and lecture activities from Regeneron Pharmaceuticals, DBV Technologies SA, Stallergenes GmbH, HAL Allergie GmbH, Bencard Allergie GmbH, Allergopharma GmbH & Co. KG, ALK-Abelló Arzneimittel GmbH, Mylan Germany GmbH, Leo Pharma GmbH, Sanofi-Aventis Deutschland GmbH, Aimmune Therapeutics UK Limited, Actelion Pharmaceuticals Deutschland GmbH, Novartis AG, Biotest AG, AbbVie Deutschland GmbH & Co. KG and Lilly Deutschland GmbH, outside of the submitted work. K.-C. Bergmann, H. Merk, E. Hamelmann, E. Untersmayr, W. Hötzenecker, E. Jensen-Jarolim and K. Brockow declare that they have no competing interests., (© The Author(s) 2021.)

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate-to-severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD -30,72; 95% CI -34,65% to -26,79%) and EASI-75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD -7.29; 95% CI -8.23 to -6.35) and anxiety/depression (MD -3.08; 95% CI -4.41 to -1.75) and improves quality of life (MD -4.80; 95% CI -5.55 to -4.06). The efficacy for adolescents is similar. Dupilumab-related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab-related serious AE is uncertain. The incremental cost-effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645)., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Competing Interests: Conflict of interestConflict-of-interest declarations are tabulated—in addition to the guideline report—on the corresponding AWMF website for the S2 guideline on “Acute Therapy and Management of Anaphylaxis—Update 2020” and can be accessed there (www.awmf.org/leitlinien/detail/ll/061-025.html).

Background: The alpha-gal syndrome (AGS) describes a new type I allergy entity to the carbohydrate epitope galactose-α-1,3-galactose (alpha-gal), which is mainly found in mammalian food products (e.g., beef, pork, and venison). Apart from meat products, alpha-gal can also be found in products containing gelatin of bovine or porcine origin. Recent case reports pointed to severe anaphylaxis in patients suffering from AGS after vaccination with vaccines containing hydrolyzed gelatin. It was the objective of this study to evaluate if basophil activation tests (BATs) performed with such vaccines were positive in patients with AGS., Methods: BAT was performed with different dilutions of a gelatin-containing measles, mumps, and rubella (MMR) live vaccine; an attenuated varicella (V) vaccine; an attenuated V-zoster (VZ) vaccine; a MMR live vaccine not containing gelatin (non-gelatin MMR vaccine) in 2 patients with confirmed AGS, 2 patients highly suspicious for AGS, and 2 healthy individuals without any previous medical history for allergies., Results: All patients showed strongly positive results for all gelatin-containing vaccines (MMR vaccine, V vaccine, and VZ vaccine). Non-gelatin MMR vaccine was negative. The 2 healthy controls did not show any basophil activation., Conclusions: Gelatin-containing vaccines should be administered with caution or avoided in patients with AGS because of their high potential to activate basophils indicating a risk for anaphylaxis. Also, BAT is a useful additional tool when it comes to screening for potentially high-risk alpha-gal-containing drugs., (© 2021 S. Karger AG, Basel.)

This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) -5; 95%CI -7.75 to -2.25), and the itch severity score (ISS)7 (MD -2.15; 95% CI -3.2 to -1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD -2.01; 95%CI -3.22 to -0.81) and decreases (moderate certainty) rescue medication use (MD -1.68; 95%CI -2.95 to -0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD -11.05; 95%CI -12.87 to -9.24), the ISS7 (MD -4.45; 95%CI -5.39 to -3.51), and QoL (high certainty) (DLQI; MD -4.03; 95% CI -5.56 to -2.5) and decreases (moderate certainty) rescue medication use (MD -2.04; 95%CI -3.19 to -0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91)., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Competing Interests: Conflict of interestConflict of interest statements—in addition to the guideline report—can be found in tabular form and accessed on the AWMF website for the S2k guideline on “acute therapy and management of anaphylaxis: 2020 update” (www.awmf.org/leitlinien/detail/ll/061-025.html).

In systemic mastocytosis (SM), the clinical features and survival vary greatly. Patient-related factors determining the outcome in SM are largely unknown. Methods: We examined the impact of sex on the clinical features, progression-free survival (PFS), and overall survival (OS) in 3403 patients with mastocytosis collected in the registry of the European Competence Network on Mastocytosis (ECNM). The impact of cytogenetic and molecular genetic aberrations on sex differences was analyzed in a subset of patients. Results: Of all patients enrolled, 55.3% were females. However, a male predominance was found in a subset of advanced SM (AdvSM) patients, namely SM with an associated hematologic neoplasm (SM-AHN, 70%; p < 0.001). Correspondingly, organomegaly (male: 23% vs. female: 13%, p = 0.007) was more, whereas skin involvement (male: 71% vs. female: 86%, p = 0.001) was less frequent in males. In all patients together, OS ( p < 0.0001) was significantly inferior in males, and also within the WHO sub-categories indolent SM, aggressive SM (ASM) and SM-AHN. PFS was significantly ( p = 0.0002) worse in males when all patients were grouped together; due to low numbers of events, this significance persisted only in the subcategory smoldering SM. Finally, prognostically relevant cytogenetic abnormalities (10% vs. 5%, p = 0.006) or molecular aberrations ( SRSF2 / ASXL1 / RUNX1 profile; 63% vs. 40%, p = 0.003) were more frequently present in males. Conclusions: Male sex has a major impact on clinical features, disease progression, and survival in mastocytosis. Male patients have an inferior survival, which seems related to the fact that they more frequently develop a multi-mutated AdvSM associated with a high-risk molecular background., Competing Interests: Competing Interests: Hanneke C. Kluin-Nelemans: institutional financial support from Novartis; honoraria from Novartis for participating in e-learning program. Andreas Reiter: Novartis Pharma - research support, advisory board, honoraria, travel reimbursement, Blueprint Medicines - advisory board, honoraria, travel reimbursement, Deciphera - advisory board, travel reimbursement. Bjorn van Anrooij: financial support from Novartis for research and advisory boards. Jason Gotlib: Funding to support conduct of clinical trial: Blueprint Medicines, Deciphera; advisory board/honoraria: Blueprint Medicines, Deciphera, Allakos. Karin Hartmann: advisory board/honoraria: Allergopharma, ALK-Abelló, Blueprint, Deciphera, Menarini, Novartis and Takeda; research grant: Euroimmun. Hanneke Oude Elberink: honoraria from ALK-Abelló, Chiesi, MEDA Pharma, Novartis, and Blueprint. Magdalena Lange: honoraria from Novartis for lectures. Chiara Elena: advisory board Novartis, Pfizer. David Fuchs, Julien Rossignol: advisory board Novartis. Khalid Shoumariyeh: travel support from Abbvie and consultancy fees from Novartis. Nikolas von Bubnoff: institutional financial support from Novartis. Massimo Triggiani: advisory board BluePrint Medicines, Deciphera, Novartis. Akif SelimYavuz: honoraria from Novartis. Jens Panse: funding to support conduct of clinical trial: Blueprint Medicines, Deciphera; advisory board/honoraria: Blueprint Medicines, Novartis. Vito Sabato: advisory board/honoraria: Blueprint Medicines, Novartis. Madlen Jentzsch: honoraria from Novartis. Olivier Hermine: Research funding support from AB science and Novartis. Advisory board of AB science. Wolfgang R. Sperr: honoraria from Novartis, Pfizer, AbbVie, Daiichi Sankyo, Amgen, Thermo Fisher, Deciphera, Incyte, Celgene and Jazz. Michel Arock: advisory board/honoraria Blueprint Medicines, Deciphera. All other authors: none., (© The author(s).)

Mast cell activation (MCA) is seen in a variety of clinical contexts and pathologies, including IgE-dependent allergic inflammation, other immunologic and inflammatory reactions, primary mast cell (MC) disorders, and hereditary alpha tryptasemia (HAT). MCA-related symptoms range from mild to severe to life-threatening. The severity of MCA-related symptoms depends on a number of factors, including genetic predisposition, the number and releasability of MCs, organs affected, and the type and consequences of comorbid conditions. In severe systemic reactions, MCA is demonstrable by a substantial increase of basal serum tryptase levels above the individual's baseline. When, in addition, the symptoms are recurrent, involve more than one organ system, and are responsive to therapy with MC-stabilizing or mediator-targeting drugs, the consensus criteria for the diagnosis of MCA syndrome (MCAS) are met. Based on the etiology of MCA, patients can further be classified as having i) primary MCAS where KIT -mutated, clonal, MCs are detected; ii) secondary MCAS where an underlying IgE-dependent allergy or other reactive MCA-triggering pathology is found; or iii) idiopathic MCAS, where neither a triggering reactive state nor KIT -mutated MCs are identified. Most severe MCA events occur in combined forms of MCAS, where KIT -mutated MCs, IgE-dependent allergies and sometimes HAT are detected. These patients may suffer from life-threatening anaphylaxis and are candidates for combined treatment with various types of drugs, including IgE-blocking antibodies, anti-mediator-type drugs and MC-targeting therapy. In conclusion, detailed knowledge about the etiology, underlying pathologies and co-morbidities is important to establish the diagnosis and develop an optimal management plan for MCAS, following the principles of personalized medicine.

Background: Penicillins and other β-lactam antibiotics are the most common elicitors of allergic drug reaction. However, data on the pattern of clinical reaction types elicited by specific β-lactams are scarce and inconsistent. We aimed to determine patterns of β-latam allergy, i.e. the association of a clinical reaction type with a specific β-lactam antibiotic., Methods: We retrospectively evaluated data from 800 consecutive patients with suspected β-lactam hypersensitivity over a period of 11 years in a single German Allergy Center., Results: β-lactam hypersensitivity was definitely excluded in 595 patients, immediate-type (presumably IgE-mediated) hypersensitivity was diagnosed in 70 and delayed-type hypersensitivity in 135 cases. Most (59 out of 70, 84.3%) immediate-type anaphylactic reactions were induced by a limited number of cephalosporins. Delayed reactions were regularly caused by an aminopenicillin (127 out of 135, 94.1%) and usually manifested as a measles-like exanthem (117 out of 135, 86.7%). Intradermal testing proved to be the most useful method for diagnosing β-lactam allergy, but prick testing was already positive in 24 out of 70 patients with immediate-type hypersensitivity (34.3%). Patch testing in addition to intradermal testing did not provide additional information for the diagnosis of delayed-type hypersensitivity. Almost all β-lactam allergic patients tolerated at least one, usually several alternative substances out of the β-lactam group., Conclusions: We identified two patterns of β-lactam hypersensitivity: aminopenicillin-induced exanthem and anaphylaxis triggered by certain cephalosporins. Intradermal skin testing was the most useful method to detect both IgE-mediated and delayed-type β-lactam hypersensitivity.

Women's work has traditionally been considered less hazardous to health in comparison with men's work. The increased women's participation in the workforce has led to an increased attention to women's working conditions. Women and men are unequally represented in individual professions or sectors (horizontal segregation), with women also under-represented in leadership positions (vertical segregation). The selection of specific occupations can result in differences between types and levels of occupational exposures among women and men and can affect prevalence of occupational allergy. Gender distribution of work-related asthma appears to vary across countries without clear global difference. Occupational rhinitis tends to be higher in women, although is not clear if this is related to a sex/gender effect or to differences in work exposure. Women are more likely to have occupational contact dermatitis, mainly due to wet work. No clear effects of gender on rates of hypersensitivity pneumonitis have been shown. Besides variation in exposures, physical and physiological characteristics, different behaviours and health consciousness have an impact on the occupational health hazards of women and men. Occupational allergy health promotion strategies need to consider approaches for women and men adjusted by gender, and legislative actions similarly could be implemented in a more gender-sensitive way., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Coronavirus disease 2019 (COVID-19), a respiratory tract infection caused by a novel human coronavirus, the severe acute respiratory syndrome coronavirus 2, leads to a wide spectrum of clinical manifestations ranging from asymptomatic cases to patients with mild and severe symptoms, with or without pneumonia. Given the huge influence caused by the overwhelming COVID-19 pandemic affecting over three million people worldwide, a wide spectrum of drugs is considered for the treatment in the concept of repurposing and off-label use. There is no knowledge about the diagnosis and clinical management of the drug hypersensitivity reactions that can potentially occur during the disease. This review brings together all the published information about the diagnosis and management of drug hypersensitivity reactions due to current and candidate off-label drugs and highlights relevant recommendations. Furthermore, it gathers all the dermatologic manifestations reported during the disease for guiding the clinicians to establish a better differential diagnosis of drug hypersensitivity reactions in the course of the disease., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Background: Patients with mastocytosis have an increased risk for severe anaphylaxis, particularly to Hymenoptera venoms. These patients may also develop more often systemic hypersensitivity reactions to certain foods. However, this issue has not been systematically investigated., Objective: To determine prevalence and severity of food hypersensitivity (FH) reactions among patients with clonal mast cell disorders (CMDs)., Methods: A retrospective study was conducted among 204 (age ≥18 years) consecutive patients who presented with confirmed CMD (170 with mastocytosis and 34 with monoclonal mast cell activation syndrome). All patients underwent thorough allergy workup where self-reported FH reactions were evaluated., Results: The prevalence of self-reported FH was 20.6%. The frequency of immunologically mediated reactions was uncommon, because only 3.4% were confirmed by relevant history and IgE sensitization. Among patients with FH, 5 had severe anaphylaxis corresponding to an overall prevalence of 2.5%. Most symptoms were restricted to skin (86%), followed by gastrointestinal tract symptoms (45%)-similar to symptoms that occur in patients with mastocytosis also without food intake. Nuts, spicy foods, seafood, and alcohol were the most common incriminated elicitors. There was no significant difference between the groups regarding age, sex, atopic status, or IgE levels., Conclusions: Anaphylaxis from foods in mastocytosis does exist and is severe, although foods are less frequent elicitors than insect venoms. Furthermore, the frequency of overall FH reactions is comparable with that in the general population and most reactions are mild, nonallergic, and unconfirmed. Consequently, our results do not support the elimination of any diet in patients with CMD without a history of FH., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years. MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs. In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings. The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells. The clinical consequences of the expansion and/or activation of MCs are best established in mastocytosis and in allergic inflammation. However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes. In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease. We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The pandemic outbreak of coronavirus disease 2019 (COVID-19) affects health care systems globally and leads to other challenges besides infection and its direct medical consequences. The aim of this study was to investigate the impact of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic on the university dermatology outpatient clinic (UDOC) of the Technical University of Munich, Germany. We analyzed datasets from 2015 until 2020 extracted from the hospital information system database and our documented outpatient files regarding patient numbers, gender, age, and diagnoses. In 2020, case numbers of outpatient care declined significantly ( p = 0.021) compared to previous years and was related to the timing of political announcements answering SARS-CoV-2 pandemic. Additionally, during calendar week 10 to 15-the peak time of the spread of COVID-19 in Germany-the proportion of patients missing their consultation was significantly higher in 2020 than in 2019 (22.4% vs. 12.4%; p < 0.001). Gender-associated differences regarding absences were not detected, but patients aged 85 years or older were significantly more likely to miss their consultation compared to all other age groups ( p = 0.002). Regarding different disease clusters, patients with chronic inflammatory skin diseases and infectious and malignant diseases were more likely to miss their consultation ( p = 0.006). Noticeably, less patients with malignant diseases, and particularly malignant melanoma, were registered during this pandemic. Our data support the hypothesis that medically constructive prioritization might not be implemented properly by patients themselves. Identifying missed patients and catching up on their medical care apart from COVID-19 will pose an enormous challenge for health care systems globally.

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM., Methods: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM., Results: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly., Conclusion: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Snake antivenom is the only specific treatment for snakebite envenoming, but life-threatening anaphylaxis is a severe side effect and drawback for the use of these typically mammalian serum products. The present study investigates the hypotheses whether serum IgE antibodies against the epitope galactose-alpha-1,3-galactose (α-gal) located on the heavy chain of non-primate mammalian antibodies are a possible cause for hypersensitivity reactions to snake antivenom. Serum samples from 55 patients with snakebite envenoming were obtained before administration of snake antivenom and tested for serum IgE (sIgE) against α-gal and total IgE. Early anaphylactic reactions (EARs) during the first 3 h after antivenom administration were classified into mild, moderate or severe and correlated with the presence of sIgE against α-gal. Fifteen (27%) out of 55 patients (37 male, 18 female, median 34 years, range 9-90 years) developed EARs after antivenom administration. Eleven, three and one patients had mild, moderate and severe EARs, respectively. Serum IgE against α-gal was detected in 17 patients (31%); in five (33%) out of 15 patients with EARs and in 12 (30%) out of 40 patients without EAR (Odds Ratio = 1.2; 95%-confidence interval: 0.3-4.2) with no correlation to severity. Although the prevalence of serum IgE against α-gal was high in the study population, very high levels of total IgE in the majority of patients question their clinical relevance and rather indicate unspecific sIgE binding instead of allergy. Lack of correlation between α-gal sIgE and EARs together with significantly increased total IgE levels suggest that sIgE against α-gal is not the major trigger for hypersensitivity reactions against snake antivenom., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Authors.)

A recent survey of the European Academy of Allergy and Clinical Immunology (EAACI) Drug Allergy Interest Group (DAIG) on how European allergy specialists deal with beta-lactam (BL) hypersensitivity demonstrated a significant heterogeneity in current practice, suggesting the need to review and update existing EAACI guidelines in order to make the diagnostic procedures as safe and accurate, but also as cost-effective, as possible. For this purpose, a bibliographic search on large studies regarding BL hypersensitivity diagnosis was performed by an EAACI task force, which reviewed and evaluated the literature data using the GRADE system for quality of evidence and strength of recommendation. The updated guidelines provide a risk stratification in BL hypersensitivity according to index reaction(s), as well as an algorithmic approach, based on cross-reactivity studies, in patients with a suspicion of BL hypersensitivity and an immediate need for antibiotic therapy, when referral to an allergist is not feasible. Furthermore, the update addresses availability and concentrations of skin test (ST) reagents, ST and drug provocation test (DPT) protocols, and diagnostic algorithms and administration of alternative BL in allergic subjects. Specifically, distinct diagnostic algorithms are suggested depending on risk stratification of the patient into high and low risk based on the morphology and chronology of the reaction, immediate (ie, occurring within 1-6 hours after the last administered dose) or nonimmediate (ie, occurring more than 1 hour after the initial drug administration), and the reaction severity. Regarding the allergy workup, the main novelty of this document is the fact that in some low-risk nonimmediate reactions ST are not mandatory, especially in children. For DPT, further studies are necessary to provide data supporting the standardization of protocols, especially of those regarding nonimmediate reactions, for which there is currently no consensus., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

This guideline on diagnostic procedures for suspected beta-lactam antibiotic (BLA) hypersensitivity was written by the German and Austrian professional associations for allergology, and the Paul-Ehrlich Society for Chemotherapy in a consensus procedure according to the criteria of the German Association of Scientific Medical Societies. BLA such as penicillins and cephalosporins represent the drug group that most frequently triggers drug allergies. However, the frequency of reports of suspected allergy in patient histories clearly exceeds the number of confirmed cases. The large number of suspected BLA allergies has a significant impact on, e.g., the quality of treatment received by the individual patient and the costs to society as a whole. Allergies to BLA are based on different immunological mechanisms and often manifest as maculopapular exanthema, as well as anaphylaxis; and there are also a number of less frequent special clinical manifestations of drug allergic reactions. All BLA have a beta-lactam ring. BLA are categorized into different classes: penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors with different chemical structures. Knowledge of possible cross-reactivity is of considerable clinical significance. Whereas allergy to the common beta-lactam ring occurs in only a small percentage of all BLA allergic patients, cross-reactivity due to side chain similarities, such as aminopenicillins and aminocephalosporins, and even methoxyimino cephalosporins, are more common. However, the overall picture is complex and its elucidation may require further research. Diagnostic procedures used in BLA allergy are usually made up of four components: patient history, laboratory diagnostics, skin testing (which is particularly important), and drug provocation testing. The diagnostic approach - even in cases where the need to administer a BLA is acute - is guided by patient history and risk - benefit ratio in the individual case. Here again, further studies are required to extend the present state of knowledge. Performing allergy testing for suspected BLA hypersensitivity is urgently recommended not only in the interests of providing the patient with good medical care, but also due to the immense impact of putative BLA allergies on society as a whole., (© Dustri-Verlag Dr. K. Feistle.)

Background: Intradermal tests (IDTs) are performed and interpreted differently in drug allergy centers making valid comparison of results difficult. Objective: To reduce method-related and intercenter variability of IDTs by the introduction of a standardized method. Materials and methods: In 11 centers of the European Network for Drug Allergy, IDTs were prospectively performed with saline and with amoxicillin (20 mg/ml) using (1) the local method and (2) the standardized European Network in Drug Allergy (ENDA) method (0.02 ml). The diameters of the initial injection wheal (Wi) for the different volumes and sites injected obtained from each center were analyzed. Results: The most reproducible method was to fill a syringe with test solution, then expel the excess fluid to obtain exactly 0.02 ml. The median Wi diameter with 0.02 ml injection using the standardized method was 5 mm [range 2-10 mm; interquartile range (IQR) 5-5 mm; n = 1,096] for saline and 5 mm (range 2-9 mm; IQR = 4.5-5 mm; n = 240) for amoxicillin. IDT injection sites did not affect the Wi diameter. Training improved precision and reduced the variability of Wi diameters. Conclusion: Using the standardized IDT method described in this multicenter study helped to reduce variability, enabling more reliable comparison of results between individuals and centers., (Copyright © 2020 Barbaud, Weinborn, Garvey, Testi, Kvedariene, Bavbek, Mosbech, Gomes, Aberer, Elberink, Torres, Ponvert, Ayav, Gooi and Brockow.)

Drug hypersensitivity reactions (DHRs) are associated with high global morbidity and mortality. Cutaneous T cell-mediated reactions classically occur more than 6 hours after drug administration and include life-threatening conditions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, and hypersensitivity syndrome. Over the last 20 years, significant advances have been made in our understanding of the pathogenesis of DHRs with the identification of human leukocyte antigens as predisposing factors. This has led to the development of pharmacogenetic screening tests, such as HLA-B*57:01 in abacavir therapy, which has successfully reduced the incidence of abacavir hypersensitivity reactions. We have completed a PRISMA-compliant systematic review to identify genetic associations that have been reported in DHRs. In total, 105 studies (5554 cases and 123 548 controls) have been included in the review reporting genetic associations with carbamazepine (n = 31), other aromatic antiepileptic drugs (n = 24), abacavir (n = 11), nevirapine (n = 14), trimethoprim-sulfamethoxazole (n = 11), dapsone (n = 4), allopurinol (n = 10), and other drugs (n = 5). The most commonly reported genetic variants associated with DHRs are located in human leukocyte antigen genes and genes involved in drug metabolism pathways. Increasing our understanding of genetic variants that contribute to DHRs will allow us to improve diagnosis, develop new treatments, and predict and prevent DHRs in the future., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Systemic mastocytosis (SM) is frequently associated with eosinophilia. To examine its prevalence and clinical impact in all WHO classification-based subcategories, we analyzed eosinophil counts in 2350 mastocytosis patients using the dataset of the European Competence Network on Mastocytosis. Ninety percent of patients had normal eosinophil counts, 6.8% mild eosinophilia (0.5-1.5 × 10 9 /l), and 3.1% hypereosinophilia (HE; >1.5 × 10 9 /l). Eosinophilia/HE were mainly present in patients with advanced SM (17%/19%), and only rarely recorded in patients with indolent and smoldering SM (5%/1%), and some patients with cutaneous mastocytosis. The eosinophil count correlated with organomegaly, dysmyelopoiesis, and the WHO classification, but not with mediator-related symptoms or allergy. Eosinophilia at diagnosis had a strong prognostic impact (p < 0.0001) on overall survival (OS) and progression-free survival (PFS), with a 10-year OS of 19% for patients with HE, 70% for those with mild eosinophilia, and 88% for patients with normal eosinophil counts. In 89% of patients with follow-up data (n = 1430, censored at start of cytoreductive therapy), eosinophils remained stable. In those with changing eosinophil counts (increase/decrease or mixed pattern), OS and PFS were inferior compared with patients with stable eosinophil counts. In conclusion, eosinophilia and HE are more prevalent in advanced SM and are predictors of a worse outcome.

Mobile health (mHealth) uses mobile communication devices such as smartphones and tablet computers to support and improve health-related services, data and information flow, patient self-management, surveillance, and disease management from the moment of first diagnosis to an optimized treatment. The European Academy of Allergy and Clinical Immunology created a task force to assess the state of the art and future potential of mHealth in allergology. The task force endorsed the "Be He@lthy, Be Mobile" WHO initiative and debated the quality, usability, efficiency, advantages, limitations, and risks of mobile solutions for allergic diseases. The results are summarized in this position paper, analyzing also the regulatory background with regard to the "General Data Protection Regulation" and Medical Directives of the European Community. The task force assessed the design, user engagement, content, potential of inducing behavioral change, credibility/accountability, and privacy policies of mHealth products. The perspectives of healthcare professionals and allergic patients are discussed, underlining the need of thorough investigation for an effective design of mHealth technologies as auxiliary tools to improve quality of care. Within the context of precision medicine, these could facilitate the change in perspective from clinician- to patient-centered care. The current and future potential of mHealth is then examined for specific areas of allergology, including allergic rhinitis, aerobiology, allergen immunotherapy, asthma, dermatological diseases, food allergies, anaphylaxis, insect venom, and drug allergy. The impact of mobile technologies and associated big data sets are outlined. Facts and recommendations for future mHealth initiatives within EAACI are listed., (© 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Objective: This review provides an overview of the literature on hypersensitivity reactions during procedures to commonly used contrast agents and dyes. A synthesis of current knowledge on clinical symptoms, epidemiology and risk factors, pathomechanism, and management of hypersensitivity reactions to these substances is presented., Data Sources: A literature search was conducted through Medline. Included were peer-reviewed articles written in English between 2000 and 2019., Study Selections: Relevant clinical studies, experimental studies, and review articles have been selected. Additionally, case reports have been included if they carried significant information about rare clinical forms of hypersensitivity reactions, disease mechanisms, or therapy., Results: An allergological workup is only indicated for patients with a history of immediate (IHR) and nonimmediate hypersensitivity reactions (NIHR) but not for toxic or unrelated adverse events. Skin tests with or without experimental cellular laboratory tests in patients with previous reactions can provide evidence for an allergic mechanism. Positive skin tests indicating allergy are more common in severe reactions. If the adverse event was allergic, skin testing of alternatives is helpful for the selection of other contrast agents for future procedures. Premedication alone may be insufficient in these cases, and breakthrough reactions occur. For nonallergic reactions, change of contrast agent and premedication is often but not always sufficient to suppress reactions., Conclusion: Patients with previous NIHR or IHR, especially moderate and severe IHR, needing potential re-administration of contrast agents should be skin tested to identify an allergic mechanism as well as alternative agents to be used for future procedures., (Copyright © 2019 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Biologics are an innovative class of drugs that can selectively influence immunological responses at a cellular level. Although their use is usually restricted to some specific diseases, such as autoimmune pathologies and tumors, their "off-label" administration has increased widely in the last years. Drug treatment may induce hypersensitivity reactions which currently lack any gold standard therapy but maybe a future field of application for biologics. Agents like anti-IgE (Omalizumab) and Tumor Necrosis Factor-α inhibitors might be used in immediate-type and cell-mediated hypersensitivity caused by medications, respectively, and the first trials in that direction are being reported in the literature. In fact, the refined immunological mechanisms involved in the pathogenesis of drug hypersensitivity might respond successfully to this new class of drugs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: For eosinophilic esophagitis (EoE) recently an association with immunoglobulin (Ig)G4 rather than IgE has been reported. Gastroesophageal reflux disease (GERD) is the most important differential diagnosis of EoE. We compared esophageal IgG4 plasma cell infiltration and serum IgG4 levels of EoE patients (before and after budesonide therapy) with GERD patients., Methods: Prospectively collected serum samples of 17 EoE patients before and after 8 weeks of therapy with budesonide (1 mg BID) were analyzed for total and antigen-specific IgG4 and IgE levels. Also, immunohistochemical analysis of total and IgG4-positive plasma cells was performed on esophageal biopsies of these patients. In total, 14 GERD patients without histologic proof of eosinophilic infiltration were taken as a control group., Results: Total IgG4 serum levels in EoE patients were significantly higher than in GERD patients (121.0 vs. 71.2 mg/dL; P=0.038) and decreased under budesonide therapy (121.0 vs. 104.2 mg/dL; P=0.019). IgE levels did not differ significantly between all groups. In EoE patients also a high number of esophageal IgG4-positive plasma cells was detected and significantly reduced under therapy (29.1 vs. 0.1 IgG4-positive cells; P<0.001). In GERD patients no relevant esophageal plasma cell infiltration could be seen., Conclusions: In EoE patients elevated systemic IgG4 serum levels compared with GERD patients can be seen and decrease under topical steroid therapy. Also, local IgG4 plasma cells expression is high in EoE, but not in GERD patients and normalize under therapy. These findings are further proof for a possible association of EoE with IgG4.