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Background: Identification of biomarkers is required for a systems medicine approach and personalized treatment in atopic dermatitis (AD). These biomarkers may not only aid in diagnosing but also might be suitable to predict the effectiveness of targeted treatment. Objective: We aimed to identify proteomic, microbial and miRNA biomarkers in AD patients and investigated their course in relation to the clinical response upon anti‐IL‐4Rα therapy. Methods: Proteomic and miRNA screening was performed in AD patients in comparison to healthy controls. Differentially regulated serum proteins, miRNA and selected skin microbiota were measured consecutively in 50 AD patients before and upon systemic dupilumab treatment. A random forest classifier was used to predict the outcome of dupilumab therapy based on the initial biomarker patterns. Results: We identified 27 proteomic candidates, miRNA and three microbial strains to be dysregulated in AD. CCL17, CCL13, CCL22, E‐selectin and BDNF were differently regulated and significantly associated with treatment response. In contrast, neither the microbial composition nor the miRNA pattern was associated with treatment response upon dupilumab treatment. Conclusion: AD patients display defined dysregulations regarding their systemic proteomic serum profile, miRNA patterns and their skin microbiome. The proteomic profile and selected skin bacteria changed profoundly upon anti‐IL‐4Rα therapy which was associated with an overall clinical response. This was not seen in miRNA‐related biomarkers. Our findings support the hypothesis that biomarker profiles reflect treatment responses and may in the future be used to develop a personalized medicine approach for the treatment of AD patients. [ABSTRACT FROM AUTHOR]

This document is a response to concerns raised by Cheng et al. regarding a previous paper on the short-term efficacy of pre-seasonal subcutaneous administration of PQ Grass for grass allergy. The authors acknowledge the importance of long-term efficacy and safety and state that separate Phase III studies will address these aspects. They also address concerns about adverse events (AEs) by highlighting the extensive safety monitoring procedures implemented during the study. Additionally, the authors mention that underlying immunological mechanisms were evaluated through biomarker analysis, with findings indicating immune tolerance induction by PQ Grass AIT. The document concludes by acknowledging the contributions of individuals involved in editing and publishing the manuscript and disclosing conflicts of interest. [Extracted from the article]

This Anaphylaxis Manifesto calls on communities to prioritise 10 practical actions to improve the lives of people at risk of serious allergic reactions. The Global Allergy and Asthma European Network and the European Federation of Allergy and Airways Diseases Patients' Associations (EFA) compiled patient-centric priorities. We used qualitative consensus methods, research evidence and feedback from over 200 patient groups, stakeholder organisations and healthcare professionals. We encourage healthcare, education and food organisations to collaborate with people at risk of serious allergic reactions to tackle safety, anxiety and financial burdens for individuals and societies. Key priorities for prevention include awareness-raising campaigns for the public and professionals, school and workplace initiatives and mandatory precautionary allergen labels on food. Priorities for improving immediate and long-term management include educating healthcare professionals, patients and schools about when and how to use adrenaline, funding two approved adrenaline devices for everyone at risk, and facilitating access to allergy specialists. Integrated care pathways should include clinical and non-clinical management options such as individualised risk assessment and quality of life assessment, self-management plans, dietetic and psychosocial support and peer support. Organisations around the world are committing to work together towards these priorities., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

The development of targeted therapies for atopic diseases, urticaria, and angioedema with biologics is progressing rapidly: New "targets" of clinical-therapeutic relevance have been identified, the corresponding targeted antibodies developed, tested in clinical trials, and approved for therapy. These include the anti-IgE antibody omalizumab (also effective and approved for the treatment of urticaria), the anti-IL-4/13 receptor-specific antibody dupilumab, the two anti-IL-13 antibodies lebrikizumab and tralokinumab, the anti-TSLP antibody tezepelumab, the two anti-IL-5 antibodies mepolizumab and reslizumab, and the anti-IL5 receptor-specific antibody benralizumab for the treatment of atopic diseases. For the treatment of hereditary angioedema, C1 inhibitor and the antibody lanadelumab (directed against kallikrein) have also long been approved as biologics in addition to low-molecular substances. Other therapeutic antibodies are in various stages of development. Furthermore, the range of indications for some very effective biologics has been successfully expanded to include additional diseases. In this context, the first results on biologic therapy of food allergy and eosinophilic esophagitis are interesting. Biologics that address different target structures are also increasingly being administered in combination, either simultaneously or sequentially, in order to achieve optimal efficacy. A developing area is the use of biologics in children and the observation of immunological and non-immunological side effects. In some cases, new unexpected side effects and hypersensitivity reactions have emerged, which in turn raise pathomechanistic questions, such as conjunctivitis with dupilumab therapy, which only appears to occur in the treatment of atopic dermatitis but not in the treatment of other atopic diseases. In dermatology, paradoxical reactions have been described under therapy with some biologics. And immune reactions of type alpha to epsilon to biologics (hypersensitivity reactions) continue to be a clinically relevant problem, whereby the selection of an alternative therapeutic agent is a challenge and the diagnostics that support this have not yet been sufficiently incorporated into routine work., Competing Interests: CT, AG, VF, KCB, and FB have no conflict of interest. UJ received hotel accommodation and meals for a lecture and for leading a workshop organized by ALK Abello. The fee went to her organization, the RCB. In addition, another hotel night and dinner were recently provided by ALK Abello. Her research on molecular allergology is funded by the Federal Ministry of Education and Science, the Federal Ministry of Food and Agriculture (BMEL), the German Research Foundation and the Kanert Foundation: all outside the topic of this article. The Federal Ministry of Technology, Economics and Technology has funded their research on assays for the detection of anti-drug antibodies via the AiF-ZIM program. ST reports support for consultancy, lectures, and other scientific activities from AbbVie, Janssen/ JNJ, Leo Pharma, Lilly, Novartis, and Regeneron/Sanofi outside the submitted work, memberships: DGAKI, DDG, EAACI. RT received research support from Sanofi-Genzyme and the Hautnetz Leipzig/Westsachsen e.V. as well as fees for lectures and consultations from ALK-Abello, Takeda, Novartis, Sanofi-Genzyme, Abbvie, and support for congress visits from Takeda. LK reports grants and/or personal fees from Allergopharma, MEDA / Mylan, HAL Allergie, ALK Abelló, LETI Pharma, Stallergenes, Quintiles, Sanofi, ASIT Biotech, Lofarma, Allergy Therapeut., AstraZeneca, GSK, Inmunotk and Cassela med outside the submitted work; and memberships: AeDA, DGHNO, German Academy of Allergology and Clinical Immunology, HNO-BV, GPA, EAACI. MWo reports support for consultancies, lectures and other scientific activities from ALK-Abelló Arzneimittel GmbH, Abbvie, Eli Lilly, Mylan Germany GmbH, Bencard Allergie GmbH, Novartis AG, Biotest AG, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Regeneron Pharmaceuticals, Inc, Stallergenes GmbH. S. Seurig reports support for consultations, lectures, and other scientific activities by Allergopharma, ALK-Abelló Arzneimittel GmbH, AstraZeneca, Takeda outside the submitted work, memberships: DGAKI, DGP, EAACI TZ reports support for consultations, lectures and other scientific activities by AstraZeneca, AbbVie, ALK, Almirall, Astellas, Bayer Health Care, Bencard, Berlin Chemie, FAES, HAL, Henkel, Kryolan, Leti, Lofarma, L’Oreal, Meda, Menarini, Merck, MSD, Novartis, Pfizer, Sanofi, Sanoflore, Stallergenes, Takeda, Teva, UCB as well as responsible participation in the following organizations: Committee member, WHO initiative “Allergic Rhinitis and its Impact on Asthma” (ARIA), Member of the Board, German Society for Allergy and Clinical Immunology (DGAKI), Head, European Centre for Allergy Research Foundation (ECARF), Secretary General, Global Allergy and Asthma European Network (GA2LEN), Member, Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). TW reports support for consultancy, lectures, and other scientific activities from AbbVie, ALK Abello, Almirall, Astellas, Bencard, Galderma, Janssen/JNJ, Leo Pharma, Leti, Lilly, Novartis, Pfizer, Regeneron/Sanofi, Stallergen. MWa has received fees for consulting, lectures or research support from the following companies in the past 3 years: Allergopharma, ALK-Abelló, AstraZeneca, CSL Behring, Genzyme, GSK, HAL Allergie, Infectopharm, LETI Pharma, Novartis, Regeneron, Sanofi, Stallergenes, Takeda. HR: Co-Founder STERNA Biologicals and SECARNA Pharmaceuticals. Table 1.Frequency of hypersensitivity reaction to biologics. BiologicTargetAuthorYearHSR %IR %ISR %Urticaria %Anaphylaxis %AdalimumabTNF-αPuxeddu et al. [243]20123.5–1.51.50Tarkiainen et al. [244]201518.117.0––EMA [245]20231.0 – 10.012.91.0 – 10.00.01 – 0.1FDA [246]20236.05.0 – 20.06.0–BenralizumabIL-5RCastro et al. [247]2014–16.0––Park et al. [248]2019–00 – 2.0–Liu et al. [249]2019–2.6–17.5––FDA [250]20193.02.23.03.0Bourdin et al. [251]20190 – 3.23.2 – 6.5––EMA [252]2023up to 10.02.2up to 10.0–Yamaguchi et al. [253]20240.3––0.3BrodalumabIL-17RAFDA [254]2017–1.51.0–Iznardo et al. [255]2020< 1.01.8––Kim et al. [256]2023–1.3––EMA [257]2023–1.0 – 10.0–0.01 – 0.1CertolizumabTNFαFDA [258]2022–1.7 – 3.2––EMA [259]2023–1.0 – 10.0–0.01 – 0.1Kim et al. [256]2023–3.9––DupilumabIL-4RαOu et al. [260]2018–13.2––Halling et al [261]2021–5.3––EMA [262]2023–1.0 – 10.0–0.01 – 0.1Kim et al. [256]2023–11.3––FDA [263]2024< 1.06.0 – 38.0< 1.0< 1.0Simpson et al. [264]2024–3.0––Yew et al. [265]2024–2.05.9–EtanerceptTNF-α-RIIPuxeddu et. al. [243]20125.3–1.62.00.8Tarkiainen et al. [244]201511.37.5––Girolomoni et al. [266]2018–10 – 49.0––Codreanu et al. [267]2019–0.8–0.8FDA [268]2023< 1.015 – 43.0< 2.0< 2.0EMA [269]2024–13.6 – 36.00.1 – 1.00.01 – 0.1EtokimabIL-33Chen et al. [270]2019––25.016.7–Chinthrajah et al. [271]2019––26.76.70NCT03614923 - Eclipse [272]2022––2.8 – 5.7––FezakinumabIL-22–––––––GaradacimabFXIIaCraigh et al. [273]20230–5.0–0GuselkumabIL-23Langley et al. [274]201801.10FDA [275]2020–4.5< 1.0–European Comission [276]20200.1 – 1.01.0 – 10.00.1 – 1.00.1 – 1.0Coates et al. [277]2021–1.80.40McInnes et al. [278]2022–2.5 – 2.7-0Danese et al. [279]202404.0-0InfliximabTNF-αMaggi et al. [280]2011–1.0 – 27.0–––Puxeddu et al. [243]201213.8–04.49.3Tarkiainen et al. [244]201534.1–1.9–1.9Lichtenstein et al. [281]2015–5.0 – 23.0–4.0–Panés et al. [282]2019–13.0–––FDA [283]2023–< 20.0–< 1.0< 1.0EMA [284]2024–> 10.01.0 – 10.01.0 – 10.00.1 – 1.0IxekizumabIL-17AFDA [285]2022≤ 0.117.0≤ 0.1≤ 0.1EMA [286]2023–> 10.00.1 – 1.00.01 – 0.1Kim et al. [256]2023–11.2––Mastorino et al. [287]2023–3.1––Ying et al. [288]20230.33.0 – 9.73.3–LanadelumabPlasma kallikreinFDA [289]20181.045.0 – 57.0––Craig et al. [290]2021–5.1 – 62.5––Hide et al. [291]2023–50.0––EMA [292]20241.252.4––LebrikizumabIL-13Hanania et al. [293]20150 – 0.911.1 – 20.5–0 – 0.9Hanania et al. [294]2016–6.0 – 10.0–< 1.0Simpson et al. [295]2018–1.3–0Korenblat et al. [296]2018–2.9–1.0Austin [297]202007.0–0EMA [289]2023–2.6––Paller et al. [299]2023–2.42.90Stein Gold et al. [300]202302.6–0LigelizumabCε3 domain of IgEGauvreau et al. [301]2016–12.5 – 25.000Maurer et al. [302]2019–4.0 – 7.0–0Wood et al. [239]2022––17.00.4Maurer et al. [303]20246.0 – 11.04.0 – 11.0–< 1.0MepolizumabIL-5Pavord et al. [304]2012≤ 1.05.0–12.0––0Lugogo et al. [305]2016< 1.0<1.03.0–0Leung et al. [306]20170 – 1.05.0 – 12.03.0 – 9.04.0 – 16.00.002Khatri et al. [307]20192.0–12.0–0Chapman et al. [308]2019< 1.0–3.0< 1.00EMA [309]20221.9 – 3.0–6.0 – 7.0–0FDA [310]20231.0 – 4.02.0 – 15.0––Ishii et al. [311]2023< 1.0––< 1.0NemolizumabIL-31RαNemoto et al. [312]2016–––0Kabashima et al. [313]2018–2.02.0 – 6.0–Silverberg et al. [314]2020–1.8 – 3.5––Ständer et al. [315]2020–3.0––Kabashima et al. [185]2022–< 1.0––Igarashi et al. [316]2023–2.2––OmalizumabIgECox et al. [317]2007< 0.2––0.09Di Bona et al. [318]2017–3.41.00FDA [319]a2023–12.0 – 45.00.20.1FDA [319]b2023–0.6 – 2.7––EMA [320]2023–2.70.1–1.00.2Kim et al. [256]2023–4.5––ReslizumabIL-5Castro et al. [321]2015––1.0 – 2.0–< 1.0Murphy et al. [322]2017< 1.0< 1.0< 1.0< 1.00FDA [323]2019––––0.3Virschow et al. [324]2020––––< 1.0Bernstein et al. [325]20200–6.0 – 11.0––EMA [326]20230.190.19––0.19RituximabCD20Terrier et al. [327]2010–9.0––1.4Maggi et al. [280]2011–10 – 77.0–––FDA (s.c.) [328]2021––13–26.0––FDA (i.v.) [329]2021–≥ 25.0–2.0 – 8.0< 2.0BCCA [330]20241.0 – 10.014 – 77.020.07.0–EMA [331]20241.0 – 10.0> 10.0< 20.01.0 – 10.00.01 – 0.1Riveiro-Barciela et al. [332]2024–9.0––2.8SecukinumabIL-17ABlauvelt [333]2016–0.7––Deodhar et al. [334]20192.40.8–1.3––Grace et al. [335]2020–25.0––Asawanonda et al. [336]2022–0.6––Li et al. [337]2022–2.3––FDA [338]20230.01 – 0.1–0.6 – 1.2–EMA [339]2023––0.1 – 1.00.01 – 0.1Kim et al. [256]2023–1.9––TezepelumabAnti-TSLPMenzies-Gow et al. [340]2021–3.6–0Corren et al. [341]2023–4.0–0EMA [342]2024–3.8––TralokinumabIL-13Wollenberg et al. [343]2019–5.2––Panettieri et al. [344]2018–4.0–5.4–0Busse et al. [345]2019–15.7–0Carlsson et al. [346]201913.2 – 25.9–< 1.00Silverberg et al. [347]20216.7FDA [348]2023–7.4 – 11.1––EMA [349]2023–7.2––Paller et al. [40]2023–2.1 – 9.2–0UpadacitinibJAK inhibitorFDA [350]20232.0 – 3.0–2.0 – 3.02.0 – 3.0EMA [351]20230.1 – 1.01.0 – 10.00.1 – 1.0UstekinumabIL-12 / IL-23Ghosh et al. [352]2019<1.00.1–< 1.00FDA [353]20230.08–1.0 – 5.0–0.1EMA [354]20230.1 – 1.01.90.1 – 10.00.080.01 – 0.1Kim et al. [256]2023––2.80.1 – 1.0– aResults of clinical studies with asthma in FDA 2023 label. bResults of pooled chronic idiopathic urticaria trials in FDA 2023 label. JAK = Janus kinase; TSLP = thymic stromal lymphopoietin; HSR = hypersensitivity reaction; IR = infusion reaction, substance-specific; ISR = injection-site reaction. Figure 1The incidence of anaphylaxis (%).Figure 2The incidence of hypersensitivity reactions (%).Figure 3The incidence of injection-site reactions (%). Figure 4The incidence of urticaria (%). Table 2.Laboratory tests before administration of immunosuppressive or immunomodulating drugs [1]. Infectious agentsTestHepatitis B virus– anti-HBS quantified – HBs Antigen, anti-HBs and – anti-HBc Hepatitis C virus(anti-Hepatitis C)Hepatitis A virus(anti-HAV IgG)Epstein-Barr virusanti-EBVCytomegalovirusanti-CMV IgG and IgMHerpes virusanti-HSV q and 2: IgG and IgMVaricella zoster virusAnti-VZ IgGSyphilis VDRL or TPPA Table 4.Biologics investigated in ongoing studies for the indication of eosinophilic esophagitis. NameTargetPhaseBarzolvolimabKIT-TKIPhase II [228]EtrasimodSphingosine 1P-R modulatorPhase II [229]CendakimabIL-13 inhibitorPhase III [230]TezepelumabAnti-TSLP antibodyPhase III [231] Table 3.Biologics investigated in ongoing studies for the indication of chronic spontaneous urticaria.NameTargetPhaseUB-221IgER antagonistsPhase II [221]LirentelimabSiglec-8 agonistPhase II [222]BarzolvolimabKIT-TKIPhase II [223]RilzabrutinibBruton-TKIPhase II [224]TAS-5315Bruton-TKIPhase II [225], (© Dustri-Verlag Dr. K. Feistle.)

Background: Amlitelimab, a fully human nondepleting monoclonal antibody targeting OX40 ligand on antigen-presenting cells, could prevent T-cell-driven inflammation seen in atopic dermatitis (AD)., Objective: This trial evaluated the efficacy and safety of amlitelimab in adults with AD., Methods: In this 2-part, phase 2b, randomized, double-blinded placebo-controlled trial (NCT05131477), patients received subcutaneous amlitelimab every 4 weeks at doses of 250 mg with 500-mg loading dose, 250 mg, 125 mg, or 62.5 mg, or placebo for 24 weeks in Part 1 (1:1:1:1:1 randomization). In Part 2, clinical responders were reallocated 3:1 to withdraw amlitelimab or continue the previous dose regimen for 28 weeks. The primary end point was percent change in Eczema Area and Severity Index (EASI) from baseline to Week 16., Results: 390 and 190 patients enrolled in Part 1 and Part 2, respectively. Significant percent change decreases in EASI were observed with amlitelimab vs. placebo (P<.001). Clinical responses at Week 24 (Investigator Global Assessment 0/1 and/or EASI-75) were maintained at Week 52 in patients continuing or withdrawn from amlitelimab. In patients maintaining clinical response at Week 52 while off-treatment, >80% had serum amlitelimab concentrations below a 4-μg/mL threshold for several weeks prior to Week 52. Reductions in AD-related biomarkers during Part 1 were maintained through Part 2. Amlitelimab was well tolerated over 52 weeks., Conclusions: Amlitelimab treatment significantly reduced clinical and biomarker responses, and was well tolerated in adults with AD through Week 52. Sustained responses were observed in the majority of patients after amlitelimab withdrawal for 28 weeks., (Copyright © 2024. Published by Elsevier Inc.)

Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA 2 LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: The prevalence of allergies to beta-lactam antibiotics is significantly overestimated based on anamnestic data - with significant medical and economic consequences. The aim of the study was to determine the frequency of immediate and delayed type reactions to beta-lactam antibiotics in order to optimize diagnostics and therapy. One focus was on the time interval between reaction and testing., Patients and Methodology: Anamnestic and diagnostic data of patients with suspected allergy to beta-lactam antibiotics who were examined in our department between 2020 and 2022 were analyzed., Results: 27/116 (23%) patients reacted in the skin tests. Type I sensitizations were detected in 4/35 patients (11%), type IV sensitizations in 23/83 (28%). In the case of negative in vitro diagnostics and skin testing, inpatient provocation tests were performed in 41/89 (46%). Type I allergies were confirmed in two of the 13 provoked patients (15%) with immediate type reactions, type IV allergies in three of 29 (10%) with delayed type reactions. The results were clearly related to the time interval after reaction. At less than one year, 19% (22/116) reacted, whereas only 4% (5/116) reacted at more than one year (for type I reaction 9% vs. 3%; for type IV reaction 23% vs. 5%).  CONCLUSIONS: The importance of the time interval between clinical event and allergological testing supports the guideline recommendation for skin testing within one year. Guideline recommendations on the diagnostic procedure for unclear reactions that occurred in the more distant past are desirable in order to rule out allergies to beta-lactam antibiotics., (© 2024 The Author(s). Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Permanent tattooing is the invasive introduction of tattoo ink (pigments) into the dermis. The ink and aftercare cosmetics applied on pre-damaged skin may contain skin sensitisers., Objectives: To identify patient characteristics and the pattern of sensitisation in tattooed patients patch tested within the Information Network of Departments of Dermatology (IVDK)., Patients and Methods: Comparative analysis of patient characteristics and reaction frequencies to baseline series allergens in 1648 consecutive patients with and 8045 consecutive patients without permanent tattoos. Non-overlapping 95%-confidence intervals were considered as significant., Results: Having permanent tattoos was related with female sex, age <40 years, tobacco smoking, atopic dermatitis, (occupational) hand dermatitis and being employed in particular occupational groups (e.g., healthcare workers, mechanics, hairdressers). Sensitisation to nickel was increased in tattooed patients and associated with female sex (OR 4.23 [95%-CI, 3.48-5.18]), age ≥40 years (OR 1.26 [95%-CI, 1.08-1.49]), tobacco smoking (OR 1.19 [95%-CI, 1.01-1.40]) and having permanent tattoos (OR 1.27 [95%-CI, 1.05-1.53])., Conclusions: The association between nickel sensitisation and permanent tattoos is probably confounded by past reactions to pierced costume jewellery. Socio-economic factors most probably contribute to the connection between tattoos, tobacco smoking, occupational or hand dermatitis, and being employed in particular occupational groups., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care. 1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Background: The basophil activation test (BAT) is a functional whole blood-based ex vivo assay to quantify basophil activation after allergen exposure by flow cytometry. One of the most important prerequisites for the use of the BAT in the routine clinical diagnosis of allergies is a reliable, standardized and reproducible data analysis workflow. (2) Methods: We re-analyzed a public mass cytometry dataset from peanut (PN) allergic patients ( n = 6) and healthy controls ( n = 3) with our binning approach " p attern r ecognition of i mmune cells" (PRI). Our approach enabled a comprehensive analysis of the dataset, evaluating 30 markers to achieve optimal basophil identification and activation through multi-parametric analysis and visualization. (3) Results: We found FcεRIα/CD32 (FcγRII) as a new marker couple to identify basophils and kept CD63 as an activation marker to establish a modified BAT in combination with our PRI analysis approach. Based on this, we developed an algorithm for automated raw data processing, which enables direct data analysis and the intuitive visualization of the test results including controls and allergen stimulations. Furthermore, we discovered that the expression pattern of CD32 correlated with FcεRIα, anticorrelated with CD63 and was detectable in both the re-analyzed public dataset and our own flow cytometric results. (4) Conclusions: Our improved BAT, combined with our PRI procedure (bin-BAT), provides a reliable test with a fully reproducible analysis. The advanced bin-BAT enabled the development of an automated workflow with an intuitive visualization to discriminate allergic patients from non-allergic individuals.

Background: Hymenoptera venom is one of the most frequent causes of anaphylaxis. Studies from adults indicate the clinical profiles and risk factors of Hymenoptera venom-induced anaphylaxis (VIA). Much less is known about pediatric VIA., Objective: To understand elicitor- and age-related factors determining pediatric VIA by analyzing data from the anaphylaxis registry., Methods: We selected pediatric VIA, pediatric food-induced anaphylaxis (FIA), and adult VIA cohorts from the anaphylaxis registry and performed a comparative data analysis regarding elicitors, symptoms, and management., Results: We identified 725 pediatric patients with VIA, 3,149 with pediatric FIA, and 5,534 with adult VIA. In pediatric VIA, boys were more frequently affected, atopy was not increased, and the onset of the reaction after exposure was fast (≤30 min; 91%) compared with pediatric FIA. Symptoms in pediatric VIA were age dependent, and although respiratory symptoms occurred most frequently besides skin symptoms in both pediatric patients with VIA and FIA, cardiovascular symptoms were more frequently reported in pediatric patients with VIA than pediatric patients with FIA. The analysis of pediatric versus adult VIA revealed clear differences in the frequency of involved organ systems (skin: 93% vs 78%; respiratory: 77% vs 64%; and cardiovascular: 61% vs 85%). For both pediatric and adult VIA, the rates of adrenaline application by a professional were low (29% vs 31%) but hospitalization rates were higher in children than in adults (61% vs 42%). Venom immunotherapy was frequently initiated regardless of age (78% each)., Conclusions: Pediatric VIA is more frequent in boys, symptoms are age dependent, and hospitalization is often required. Adrenaline should be applied according to current guidelines. Venom immunotherapy is an important treatment option in pediatric VIA and should be considered in severely affected children., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study investigates the care provision and the role of infectious disease (ID) specialists during the coronavirus disease-2019 (COVID-19) pandemic., Methods: A survey was conducted at German study sites participating in the Lean European Open Survey on SARS-CoV-2 infected patients (LEOSS). Hospitals certified by the German Society of Infectious diseases (DGI) were identified as ID centers. We compared care provision and the involvement of ID specialists between ID and non-ID hospitals. Then we applied a multivariable regression model to analyse how clinical ID care influenced the mortality of COVID-19 patients in the LEOSS cohort., Results: Of the 40 participating hospitals in the study, 35% (14/40) were identified as ID centers. Among those, clinical ID care structures were more commonly established, and ID specialists were always involved in pandemic management and the care of COVID-19 patients. Overall, 68% (27/40) of the hospitals involved ID specialists in the crisis management team, 78% (31/40) in normal inpatient care, and 80% (28/35) in intensive care. Multivariable analysis revealed that COVID-19 patients in ID centers had a lower mortality risk compared to those in non-ID centers (odds ratio: 0.61 (95% CI 0.40-0.93), p = 0.021)., Conclusion: ID specialists played a crucial role in pandemic management and inpatient care., (© 2024. The Author(s).)

Interleukin-33 (IL-33) is a proinflammatory alarmin cytokine released by damaged epithelial tissue cells that initiates and amplifies both type 1 and type 2 inflammatory cascades. A role for IL-33 in atopic dermatitis (AD; a chronic, relapsing type 2 inflammatory disease of the skin) has been proposed. Itepekimab is a novel human IgG4P monoclonal antibody against IL-33, currently in clinical development for chronic obstructive pulmonary disease (COPD). Two global phase II studies-a dose-ranging itepekimab monotherapy study (NCT03738423) and a proof-of-concept study of itepekimab alone and in combination with dupilumab (NCT03736967)-were conducted in patients with moderate-to-severe AD to assess safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy; both studies were terminated following an interim analysis of the proof-of-concept study, which failed to demonstrate the efficacy of itepekimab. In these two studies, itepekimab exhibited linear and dose-proportional pharmacokinetics. Pharmacodynamics of total IL-33 indicated that itepekimab saturated binding to the target in serum at 300 mg q2w and q4w doses, and decreased blood eosinophil counts. Concentration-time profiles of itepekimab and total IL-33 were similar for itepekimab with or without dupilumab, and between East Asian and non-East Asian subgroups. Itepekimab was generally well tolerated, both alone and in combination with dupilumab. The lack of clinical efficacy for itepekimab observed in these studies suggests that IL-33 may not be a key pathogenic driver in moderate-to-severe AD., (© 2024 Regeneron Pharmaceuticals Inc and The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: Interdisciplinary medical treatment is required to care for patients with complex autoimmune diseases. Although there are an increasing number of interdisciplinary centers for autoimmune diseases in Germany, they are not yet available throughout the country and the focuses and interdisciplinary structures are not organized according to a generally agreed standard. Furthermore, they are not regularly reflected in the general care structure., The Aim of the Work: To analyze the care structure using as an example an established center and a clinical case to demonstrate the usefulness of in-house standardized procedures., Material and Methods: In order to determine the status quo regarding interdisciplinary centers for autoimmune diseases in Germany, a university hospital is exemplarily presented for a structural analysis and a case presentation from another center to demonstrate the importance of an interdisciplinary patient care., Results: At the selected center for autoimmune diseases of the university hospital, patients with autoimmune diseases receive interdisciplinary care from experts from various disciplines. The structures are anchored in an organizational chart. The case report demonstrates a standardized diagnostic and therapeutic pathway (standardized operating procedures, SOP) in a patient with systemic sclerosis and lung involvement., Discussion: The article discusses which measures are necessary across disciplines for comprehensive diagnostics and treatment of certain autoimmune diseases, which challenges arise during implementation and which advantages can arise compared to guidelines because, among other things, they can be immediately adapted. The establishment of a national consensus for the structure, necessary settings and implementation into patient care within an interdisciplinary center for autoimmune diseases is desirable., (© 2024. The Author(s).)

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this consensus provides clinicians with an overview of the diagnosis and treatment of scleromyxoedema and scleroedema (of Buschke)., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Bullous pemphigoid (BP) is a rare, autoimmune, blistering skin disease associated with high disease burden, profoundly decreased quality of life and increased morbidity. Emerging evidence supports an important role for type 2 inflammation in disease pathogenesis. Current management relies on topical and/or systemic corticosteroids, non-selective immunosuppressants and antibiotics with anti-inflammatory properties, which are all limited by side effects and toxicities. Therefore, targeted, efficacious and safe therapies are needed. Dupilumab blocks the shared receptor component for interleukin (IL)-4 and IL-13, key and central drivers of type 2 inflammation. Several reports of patients successfully treated with dupilumab have been published; however, dupilumab has not been formally assessed in a double-blind, placebo-controlled trial., Objectives: We report the design of LIBERTY-BP ADEPT, a multicenter, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of dupilumab in adults with BP., Methods: LIBERTY-BP ADEPT comprises a 35-day screening, 52-week treatment and 12-week follow-up period. Approximately 98 adults aged 18-90 years with moderate-to-severe BP are being enrolled at 51 sites on 4 continents and randomized 1:1 to subcutaneous dupilumab or placebo every 2 weeks. All participants will receive concomitant oral corticosteroids (OCS)., Planned Outcomes: The primary endpoint is the proportion of patients achieving complete remission off steroid therapy at week 36. Key secondary endpoints include total cumulative OCS dose to week 36, percent change and proportion of patients with ≥ 4-point reduction in the weekly average of daily Peak Pruritus Numerical Rating Scale from baseline to week 36 and percent change in Bullous Pemphigoid Area Index score from baseline to week 36., Conclusion: The trial results will provide evidence on whether the efficacy and safety of dupilumab support its use as a potential novel treatment approach for BP and will provide new insights into the role of type 2 inflammation in BP pathogenesis., Clinical Trial Registration: ClinicalTrials.gov identifier NCT04206553., (© 2024. Crown.)

In this review, we compare different refractory anaphylaxis (RA) management guidelines focusing on cardiovascular involvement and best practice recommendations, discuss postulated pathogenic mechanisms underlining RA and highlight knowledge gaps and research priorities. There is a paucity of data supporting existing management guidelines. Therapeutic recommendations include the need for the timely administration of appropriate doses of aggressive fluid resuscitation and intravenous (IV) adrenaline in RA. The preferred second-line vasopressor (noradrenaline, vasopressin, metaraminol and dopamine) is unknown. Most guidelines recommend IV glucagon for patients on beta-blockers, despite a lack of evidence. The use of methylene blue or extracorporeal life support (ECLS) is also suggested as rescue therapy. Despite recent advances in understanding the pathogenesis of anaphylaxis, the factors that lead to a lack of response to the initial adrenaline and thus RA are unclear. Genetic factors, such as deficiency in platelet activating factor-acetyl hydrolase or hereditary alpha-tryptasaemia, mastocytosis may modulate reaction severity or response to treatment. Further research into the underlying pathophysiology of RA may help define potential new therapeutic approaches and reduce the morbidity and mortality of anaphylaxis., (© 2024 The Author(s). Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes., (© 2024 European Academy of Dermatology and Venereology.)

Background: The 300IR house dust mite (HDM) sublingual immunotherapy (SLIT) tablet is approved for treatment of HDM-induced allergic rhinitis (AR). To provide a comprehensive review of the 300IR HDM-SLIT tablet safety profile based on randomized controlled trial (RCT) pooled data and post-marketing (PM) pharmacovigilance data., Methods: Subjects (5-65 years) with confirmed HDM-AR with or without controlled asthma were treated with 300IR or placebo in 8 RCTs. Reported treatment-emergent adverse events (TEAEs) were pooled and analyzed descriptively in subsets of adults/adolescents and children. Adverse reactions (ADRs) collected from spontaneous reporting and PM studies through a pharmacovigilance system since the first marketing authorization were also analyzed., Results: Across RCTs, 1853 subjects were treated with the 300IR HDM-SLIT tablet and 1846 with placebo. In both subsets of adults/adolescents and children whichever their asthma status, treatment-related TEAEs of higher incidence in active groups vs placebo were mostly consistent with mild or moderate local application-site reactions. They were mainly reported on the first days of treatment and decreased over time. 4 severe laryngopharyngeal reactions (2 requiring adrenaline/epinephrine) and 1 moderate eczema considered serious rapidly resolved with medications; no anaphylaxis was reported. In PM settings, ADRs reported in more than 235,000 patients were in line with RCT findings. Severe systemic reactions occurred rarely; 12 anaphylactic reactions resolved safely (5 with adrenaline). No new safety signal was raised., Conclusion: Safety data from RCTs and more than 7 years of real-life experience confirmed the favorable safety profile of 300IR HDM-SLIT tablet in patients across different regions, regardless of age and asthma status., Clinical Trial Registrations: NCT00674700; Retrospectively registered 06 May 2008.NCT01199133; Retrospectively registered 09 September 2010.NCT01527188; Retrospectively registered 01 February 2012.NCT02443805; Registered 29 April 2015/EudraCT 2014-004223-46; Registered 16 September 2015.jRCT2080221872/JapicCTI-121917; Registered 01 August 2012.jRCT2080222929/JapicCTI-15298; Registered 04 August 2015., Competing Interests: M. Worm reports consulting fees and payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Novartis Pharma GmbH, Sanofi-Aventis Deutschland GmbH, DBV Technologies S.A, Aimmune Therapeutics UK Limited, Leo Pharma GmbH, AstraZeneca GmbH, ALK-Abelló Arzneimittel GmbH, Lilly Deutschland GmbH, Kymab Limited, Amgen GmbH, Abbvie Deutschland GmbH & Co. KG, Pfizer Pharma GmbH, Mylan Germany GmbH (a Viatris Company), Boehringer Ingelheim Pharma GmbH & Co. KG, GlaxoSmithKline GmbH & Co. KG, Almirall S. A., Pfizer Deutschland GmbH, Bristol-Myers Squibb GmbH & Co. KGaA and FomF GmbH, outside the submitted work. P. Demoly reports grants paid to his institutions from ALK-Abelló, AstraZeneca, GlaxoSmithKline, Menarini, Puressentiel, Stallergenes Greer, ThermoFisher Scientific, Viatris, and support for attending meetings and/or travel from Stallergenes Greer outside the submitted work. Y. Okamoto reports consulting fees and/or payment or honoraria for lecture, presentations, speakers bureaus, manuscript writing or educational events from Torii Co., Ltd., Kirin Holding Co., Ltd., Stallergenes Greer, ALK-Abelló, Shionogi Co., Ltd., Yansen Co., Ltd., Tanabe-Mitsubishi Co., Ltd., Meiji Pharma, Novartis Co., Ltd.; support for attending meetings and/or travel from Torii Co., Ltd., Stallergenes Greer; participation on Data Safety Monitoring Board or Advisory Board from Stallergenes Greer, Kirin Holding Co., Ltd., Greer outside the submitted work. C. Vidal reports consulting fees paid to her institution from Stallergenes Greer, ALK- Abelló; honoraria from Stallergenes Greer; participation on Data Safety Monitoring Board or Advisory Board from Stallergenes Greer, Leti, ALK- Abelló, outside the submitted work. K. Daghildjian is an employee of Stallergenes Greer. K. Yan declares he has no conflicts of interests regarding the submitted work. T.B. Casale reports grants paid to his institution for conduct of original study from Stallergenes Greer. K.C. Bergmann reports payment for expert testimony, support for attending meetings and/or travel and participation on Data Safety Monitoring Board or Advisory Board from Bencard, Leti, Sanofi, GlaxoSmithKline, AstraZeneca, Novartis, Stallergenes Greer, HAL, outside the submitted work., (© 2024 The Authors.)

Anaphylaxis is an acute, potentially fatal, systemic hypersensitivity reaction that warrants prompt diagnosis and management. It continues to be challenging to anticipate who may be at risk of a severe, life-threatening allergic reaction. Anaphylaxis can be caused by a range of allergens, such as certain foods, medications, latex, insect stings, etc. Cofactors that augment the severity of clinical symptoms and increase the risk of poor outcomes include exercise, stress, infectious diseases, underlying mast cell disease, active allergic disease such as asthma, advanced age, intake of certain medications, history of previous anaphylaxis, and delayed or missed administration of adrenaline. According to the European Anaphylaxis Registry, food is the major elicitor of anaphylaxis, especially eggs, cow milk, and nuts, in children and adolescents. Reaction to insect venom has also been noted in young adulthood. Early recognition of signs and symptoms and prompt treatment are crucial in anaphylaxis management to avoid serious and even fatal outcomes. It is crucial for both individuals and clinicians to identify the cause of anaphylaxis. Biomarkers of anaphylaxis, such as histamine, tryptase, platelet activation factor (PAF), chymase, carboxypeptidase A3, dipeptidyl peptidase I (DPPI), basogranulin, CCL-2, hsa-miR-451a, may be useful in diagnosis and management. The purpose of this review article is to present a comprehensive overview of current evidence and expert opinions regarding the risk factors that predispose individuals to anaphylaxis. Additionally, it provides insights into potential biomarkers and genetic markers for accurate diagnosis and management. This review underscores the significance of expert guidance in enhancing patient outcomes and enabling self-management of anaphylactic episodes., Competing Interests: George DuToit has received financial funding and honorarium from Aimmune and DBV. He has received speaker fees from BSAG, ALK-Abello, and DBV. Peter Smith received research grant from Mylan (now Viatris), GSK and Sanofi. He has also received honoria for participating in AZ and Viatris Advisory Boards. Antonella Muraro serves as a consultant for Novartis, Viatris, DVB Technology, and Aimmune Therapeutics Ireland. She has received speaker fees from Novartis, Viatris, DVB Technology, Nestle Health Sciences and Aimmune Ireland. Adam T Fox serves as a member of consultant for Independent Drug Monitoring Committee for ALK-Abello sublingual immunotherapy trials and has received consultancy fees from GS1 and LG. Graham Roberts has received consultant fees from ALK-Abello, Viatris, DBV, and Astra Zeneca. Johannes Ring serves as a consultant for Viatris. He has received speaker fees from Galderma, Viatris, Bencard, Sanofi and AbbVie. Margitta Worm has received speaker fees from ALK-Abelló Arzneimittel GmbH, Mice Service GmbH, Bencard Allergie GmbH Novartis AG, Biotest AG, Actelion Pharmaceuticals Deutschland GmbH, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, Aimmune Therapeutics UK Ltd., Lilly Deutschland GmbH, med update GmbH, streamedup! GmbH, DERFO mbH, Meinhardt Congress GmbH, Phadia GmbH, Agentur Herzberg, ECM GmbH, Amgen GmbH, FomF GmbH. She also received honoria from Bencard Allergie GmbH, Novartis Pharma GmbH, Biotest AG, Sanofi-Aventis Deutschland GmbH, HAL Allergie GmbH, DBV Technologies S.A., Aimmune Therapeutics UK Ltd., Regeneron Pharmaceuticals, Inc, Mice Service GmbH, Leo Pharma GmbH, Boehringer Ingelheim Pharma GmbH & Co.KG, Stallergenes GmbH, Swixx Biopharma, RTI Health Solutions, Pharm Research Associates (UK) Ltd, AstraZeneca GmbH, Worg Pharmaceutics (Hangzhou) Co. Ltd. for participating as an advisory board member., (© 2024 Published by Elsevier Inc. on behalf of World Allergy Organization.)

Background: Despite high disease burden, systemic treatment options for patients with atopic hand and/or foot dermatitis (H/F AD) are limited., Objectives: To evaluate efficacy and safety of dupilumab in H/F AD using specific instruments for assessing disease severity on hands and feet., Methods: In this multicenter phase 3 trial, adults and adolescents with moderate-to-severe H/F AD were randomized to dupilumab monotherapy (regimen approved for generalized AD), or matched placebo. The primary endpoint was proportion of patients achieving Hand and Foot Investigator's Global Assessment score 0 or 1 at week 16. Secondary prespecified endpoints assessed the severity and extent of signs, symptom intensity (itch, pain), quality of life, and sleep., Results: A total of 133 patients (adults = 106, adolescents = 27) were randomized to dupilumab (n = 67) or placebo (n = 66). At week 16, significantly more patients receiving dupilumab (n = 27) than placebo (n = 11) achieved Hand and Foot Investigator's Global Assessment score 0 or 1 (40.3% vs 16.7%; P = .003). All other prespecified endpoints were met. Safety was consistent with the known AD dupilumab profile., Limitations: Short-term, 16-week treatment period., Conclusion: Dupilumab monotherapy resulted in significant improvements across different domains of H/F AD with acceptable safety, supporting dupilumab as a systemic treatment approach for this often difficult to treat condition., Competing Interests: Conflicts of interest Dr Simpson has received personal fees from AbbVie, Advances in Cosmetic and Medical Dermatology Hawaii, Amgen, AOBiome, Arcutis Biotherapeutics, Arena Pharmaceuticals, Aslan Pharmaceuticals, BenevolentAI Bio Limited, BiomX Ltd., Bluefin Biomedicine, Boehringer Ingelheim, Boston Consulting Group, BMS, Castle Biosciences, Collective Acumen, CorEvitas, Coronado Biosciences, Dermira, Eli Lilly and Company, Evelo Biosciences, Evidera, Excerpta Medica B.V., FIDE, Forté Biosciences, Fraunhofer, Gesselschaft Z, Gilead Sciences., Galderma, GSK, Incyte, Innovaderm Research Inc., Janssen, Johnson & Johnson, Kyowa Kirin, LEO Pharma, Medscape, Merck, Maui Derm, Med Learning Group, Medscape, Merck, MJH Life Sciences, MLG Operating, Ortho Dermatologics, Pfizer, Physicians World, Pierre Fabre, PRImE, Recludix Pharm, Regeneron Pharmaceuticals Inc., Revolutionizing Atopic Dermatitis, Roivant Sciences, Sanofi, Trevi Therapeutics, Valeant, Vindico Medical Education, and WebMD; he has received grants from and/or is Principal Investigator for AbbVie, Amgen, Acrotech Biopharma Inc., Arcutis Biotherapeutics, Aslan Pharmaceuticals, Castle Creek Biosciences, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte, Kymab, Kyowa Kirin, Merck, LEO Pharma, National Jewish Health, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., Sanofi, and Target RWE. Dr Silverberg is a consultant and/or has received grants/honoraria from AbbVie, Aldena Therapeutics, Amgen, AOBiome, Arcutis, Arena Pharmaceuticals, AnaptysBio, Asana BioSciences, ASLAN Pharmaceuticals, Attovia Therapeutics, BiomX, Biosion, Bodewell, Boehringer Ingelheim, Cara Therapeutics, Castle Biosciences, Celgene, Connect Biopharma, Corrona, Dermavant Sciences, Eli Lilly, Galderma, Glenmark, GSK, Incyte, Kiniksa Pharmaceuticals, LEO Pharma, Maui Derm, MedImmune, Menlo Therapeutics, Novartis, Optum, Pfizer, PuriCore, RAPT Therapeutics, Regeneron Pharmaceuticals Inc., Sanofi, Shaperon, Target Pharma, and Union Therapeutics. Dr Worm is an advisory board member and/or has received consulting fees from AbbVie, Aimmune Therapeutics UK, Amgen, ALK-Abelló Arzneimittel, AstraZeneca, Boehringer Ingelheim, DBV Technologies S.A., Eli Lilly, GSK, Kymab, LEO Pharma, Mylan Germany, Novartis, Pfizer, Regeneron Pharmaceuticals Inc., and Sanofi. Dr Honari has received research funding from Nipera, Regeneron Pharmaceuticals Inc., and is a consultant for Biolinq, and Myesontooth. Dr Masuda is a speaker for Eli Lilly Japan K.K., Maruho Co., Ltd, Mitsubishi Tanabi Pharma Corporantion and Sanofi, and an investigator for Eli Lilly Japan K.K. Dr Syguła has no conflict of interest to disclose. Dr Schuttelaar is an advisor, consultant, speaker and/or investigator for AbbVie, Pfizer, LEO Pharma, Regeneron, Sanofi Genzyme, Eli Lilly, Galderma, and Amgen; she has received grants from Regeneron, Sanofi Genzyme, Novartis and Pfizer. Drs Mortensen, Akinlade, Maloney, Paleczny, Delevry, Xiao and Bansal are employees and shareholders of Regeneron Pharmaceuticals Inc. Drs Laws, Patel and Dubost-Brama are employees of Sanofi, and may hold stock and/or stock options in the company., (Copyright © 2024 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Concerns regarding contact allergies and intolerance reactions to dental materials are widespread among patients. Development of novel dental materials and less frequent amalgam use may alter sensitization profiles in patients with possible contact allergy., Objectives: To analyse current sensitization patterns to dental materials in patients with suspected contact allergy., Methods: This retrospective, multicentre analysis from the Information Network of Departments of Dermatology (IVDK) selected participants from 169 834 people tested in 2005-2019 and registered with (i) an affected area of 'mouth' (and 'lips'/'perioral'), (ii) with the dental material in question belonging to one of three groups (dental filling materials, oral implants or dentures or equivalents) and (iii) with patch-testing done in parallel with the German baseline series, (dental) metal series and dental technician series., Results: A total of 2730 of 169 834 tested patients met the inclusion criteria. The patients were predominantly women (81.2%) aged ≥ 40 years (92.8%). The sensitization rates with confirmed allergic contact stomatitis in women (n = 444) were highest for metals (nickel 28.6%, palladium 21.4%, amalgam 10.9%), (meth)acrylates [2-hydroxyethyl methacrylate (HEMA) 4.8%] and the substances propolis (6.8%) and 'balsam of Peru' (11.4%). The most relevant acrylates were HEMA, 2-hydroxypropyl methacrylate, methyl methacrylate, ethylene glycol dimethacrylate and pentaerythritol triacrylate. Few men were diagnosed with allergic contact stomatitis (n = 68); sensitization rates in men were highest for propolis (14.9%) and amalgam (13.6%)., Conclusions: Allergic contact stomatitis to dental materials is rare. Patch testing should not only focus on metals such as nickel, palladium, amalgam and gold, but also (meth)acrylates and the natural substances propolis and 'balsam of Peru'., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Due to their dual sensory impairment, people with congenital deafblindness (CDB) are rarely naturally involved in other people's conversations. Their communication partners find it challenging to include them in group conversations. However, overhearing others communicate is important for developing social and communication skills. Hence, we developed an intervention program to guide communication partners in offering multiparty communication to people with CDB. This article describes how the program was developed through an intervention mapping approach., Method: Intervention mapping is a six-step process: logic model, model of change, program design, program production, program implementation plan, and evaluation plan. These six steps were applied to systematically develop a program to foster multiparty communication in people with CDB. Representatives of the involved groups participated in the project group and the working group to ensure feasibility and acceptability., Results: Following the intervention mapping steps resulted in creation of a program for communication partners that consists of an education session, practicals, and four video-feedback sessions. Information sessions for practitioners and managers were also developed. The program was implemented incrementally with program implementers in each organization. A subjective evaluation and an impact evaluation were done after each implementation phase., Discussion: Intervention mapping was used to develop a program that connects theory to practice. The program appeared to meet the communication partners' needs and be feasible in terms of time investment. This article offers suggestions for broadening the scope of the program to other settings and for further investigating the effects of the program on the social and communication skills of people with CDB., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Worm et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance., Methods: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period., Discussion: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children., Trial Registration: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023., (© 2024. The Author(s).)

The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects., (© 2024 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by Wiley‐VCH GmbH on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Epidemiologic data on occupational anaphylaxis is scarce, and there is a need of more knowledge about work-related anaphylactic episodes., Methods: Based on the data of the Anaphylaxis Registry, we identified cases related to occupational exposure and analyzed the elicitors, demographics, severity of clinical reaction and management., Results: Since 2017, 5851 cases with an information about the occupational relation of the anaphylactic episode were registered whereby 225 (3.8%) were assigned to be caused by an occupational allergen. The vast majority of these occupational anaphylaxis cases were caused by insects (n = 186, 82.7%) followed by food (n = 27, 12.0%) and drugs (n = 8, 3.6%). Latex elicited occupational anaphylaxis in only two cases. Beekeepers, gardeners, farmers, and individuals working in professions associated with food handling, for example, employees in restaurants, bakery, pastry, and cooks were most frequently affected. The comparison of the occupational insect venom-induced anaphylaxis to a group of non-occupational insect anaphylaxis in adults (n = 1842) revealed a significant younger age in occupational anaphylaxis (46 vs. 53 years), a predominance of bee-induced cases (38% vs. 17%), and a higher rate of venom immunotherapy in a primary care setting (3.3% vs. 1.3%, p = .044). In the occupational- versus non-occupational adults with food-induced anaphylaxis atopic dermatitis as concomitant atopic disease was observed more frequently (n = 486; 20% vs. 10%), although this was not significant., Conclusion: Our data demonstrate the impact of venom allergy in work-related anaphylaxis. Foods and drugs are less frequently elicitors, and latex-induced occupational anaphylaxis was rare. More data are needed to determine risk factors associated with occupational anaphylaxis., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

There is a lack of consensus over the description and severity assignment of allergic adverse reactions to immunotherapy, although there seems to be a consensus at least in terms of using the World Allergy Organization (WAO) grading systems to describe local adverse events for Sublingual Immunotherapy (SLIT) and Systemic Allergic Reactions (SARs) to Subcutaneous Immunotherapy (SCIT) amongst the major national/regional allergy societies. In this manuscript, we propose a modification of the previous WAO Grading system for SARs, which aligns with the newly-proposed Consortium for Food Allergy Research (CoFAR) Grading Scale for Systemic Allergic Reactions in Food Allergy (version 3.0). We hope this can facilitate a unified grading system appropriate to SARs due to allergen immunotherapy, independent of allergen and route of administration, and across clinical and research practice., (© 2024 The Authors.)

The present S3 guideline was created based on the European English-language S3 guideline, with special consideration given to the medical conditions in the German-speaking region, and with additions from the previous German-language version, in accordance with the criteria of the AWMF. This second part of the guideline addresses the systemic therapy of atopic dermatitis (AD). It covers topics such as the indication for systemic therapy in children, adolescents, and adult patients with AD. Furthermore, it addresses all medications approved for AD, such as the biologics dupilumab and tralokinumab, the Janus kinase inhibitors abrocitinib, baricitinib, and upadacitinib, as well as conventional immunosuppressive therapies with systemic glucocorticosteroids and ciclosporin. Additionally, it discusses systemic off-label therapies. The first part of the guideline, published separately, includes the definition and diagnostic aspects of AD, describes topical therapy, non-drug therapy approaches, and addresses aspects related to special patient groups., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published the first systematic review that summarized the prevalence of food allergy (FA) and food sensitization in Europe for studies published 2000-2012. However, only summary estimates for tree nut allergy (TNA) were feasible in that work. In the current update of that systematic review, we summarized the prevalence of tree nut allergy/sensitization to individual tree nuts. Six databases were searched for relevant papers published 2012-2021 and 17 eligible studies were added to the 15 studies already identified between 2000 and 2012, giving a total of 32 studies. Of the investigated tree nuts, meta-analysis was possible for hazelnut, walnut, almond, and in few cases, for cashew, and Brazil nut. The lifetime self-reported prevalence was 0.8% (95% CI 0.5-1.1) for hazelnut and 0.4% (0.2-0.9) for walnut. The point self-reported prevalence was 4.0% (2.9-5.2) for hazelnut, 3.4% (2.0-4.9) for Brazil nut, 2.0% (1.1-2.9) for almond, and 1.8% (1.1-2.5) for walnut. Point prevalence of food challenge-confirmed TNA was 0.04% (0.0-0.1) for hazelnut and 0.02% (0.01-0.1) for walnut. Due to paucity of data, we could not identify any meaningful and consistent differences across age groups and European regions., (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: Pulmonary involvement is the leading cause of death in systemic sclerosis (SSc) and may manifest as interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), or in combination of both (ILD with pulmonary hypertension [ILD-PH]). The aim of this analysis was to determine prevalence, clinical characteristics, and survival of these different forms within the registry of the German Network for Systemic Sclerosis., Research Question: Does SSc-associated ILD-PH or ILD without PH affect survival differently, and are there any risk factors that have an additional impact?, Study Design and Methods: Clinical data of 5,831 patients with SSc were collected in the German Network for Systemic Sclerosis registry. Kaplan-Meier estimates were used to compare overall survival in patients with SSc-associated ILD-PH and ILD without PH with patients without pulmonary involvement and those with PAH. The Cox proportional hazard model was used to analyze the influence of pulmonary involvement and other potential predictors on patient survival., Results: Clinical data of 3,257 patients with a mean follow-up time of 3.45 ± 1.63 years have been included in our analysis. At baseline, ILD was present in 34.5%, whereas PH without ILD had a lower prevalence with 4.5%. At the end of follow-up, 47.6% of patients with SSc had ILD, 15.2% had ILD-PH, and 6.5% had PAH. ILD was more frequent in the diffuse cutaneous form (57.3%), whereas PAH did not differ significantly between SSc subtypes. Significant differences in baseline characteristics between PAH vs ILD-PH vs ILD without PH were found for age at diagnosis, sex, SSc subsets, antibody status, FVC, diffusing capacity of the lung for carbon monoxide, and therapy. Overall survival at 5 years was 96.4% for patients without pulmonary involvement and differed significantly between patients with ILD without PH, PAH, and being worst in patients with ILD-PH. Female sex (hazard ratio [HR], 0.3), higher BMI (HR, 0.9), and higher diffusing capacity of the lung for carbon monoxide values (HR, 0.98) were associated with a lower mortality risk., Interpretation: ILD is the most prevalent pulmonary involvement in SSc, whereas the combination of ILD and PH is associated with the most detrimental survival., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: M. K. reports grants and personal fees from Boehringer Ingelheim and Roche, and personal fees from Galapagos. P. M. reports lecture fees from Boehringer Ingelheim. F. B. reports grants and personal fees from Boehringer Ingelheim, Roche, Galapagos, and Savara Pharma. N. B. reports personal fees from Actelion, Boehringer Ingelheim, Roche, Pfizer, MSD, and AbbVie; and grants and personal fees from Novartis and SOBI. C. P. reports personal fees from Boehringer Ingelheim, Pfizer, and Takeda; grants and personal fees from Actelion and Novartis; and grants from Corbus and Amgen. M. S. reports grants and personal fees from Roche/Chugai, Hexal/Sandoz, Janssen, and BMS; and personal fees from AbbVie, Novartis, UCB, Boehringer Ingelheim, and Gilead. P. K. reports personal fees and nonfinancial support from AbbVie, Chugai, Novartis, and Pfizer, unrelated to the present manuscript; and personal fees from Bristol-Myers Squibb, Gilead, and GlaxoSmithKline, unrelated to the present manuscript. N. H. reports lecture fees from Boehringer Ingelheim and Janssen. Nothing declared (M. O., J. W., G. R., U. M.-L., J. H., E. S., C. G., I. K., G. Z., L. S., A. J., M. W., I. J., J. E., C. S., G. K., A. R., T. S., A. K., H. M.-L.)., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

This S3 guideline was created based on the European S3 guideline, with special consideration of the medical conditions in the German-speaking region and incorporating additions from the previous German-language version. The interdisciplinary guideline commission consisted of representatives from the German Dermatological Society, the Professional Association of German Dermatologists, the Austrian Society of Dermatology and Venereology, the Swiss Society of Dermatology and Venereology, the German Society for Allergology and Clinical Immunology, the German Society for Pediatric and Adolescent Medicine, the Professional Association of Pediatricians and Adolescent Medicine, the Society for Pediatric Allergology and Environmental Medicine, the German Society for Pediatric Rehabilitation and Prevention, the German Society for Psychosomatic Medicine and Medical Psychotherapy, the German Network for Health Services Research, the German Eczema Association and the German Allergy and Asthma Association. This first part of the guideline focuses on the definition and diagnostic aspects of atopic dermatitis (AD), addressing topical therapy as well as non-pharmacological treatment approaches such as UV therapy, psychoeducational therapy, dietary interventions for AD, allergen immunotherapy for AD, and complementary medicine. This part of the guideline also covers specific aspects of AD in children and adolescents, during pregnancy and lactation, and in the context of family planning. Additionally, it addresses occupational aspects of AD and highlights the perspective of the patients. The second part of the guideline, published separately, addresses the systemic therapy of AD., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Background: Anaphylaxis is a serious systemic reaction-data on fatal and near-fatal reactions are limited., Objective: To better understand clinical patterns and risks factors of severe anaphylaxis by a deep analysis of data from fatal and near-fatal anaphylaxis., Methods: Data from the European Anaphylaxis Registry on fatal/near-fatal anaphylactic reactions and national data on anaphylaxis fatalities were investigated., Results: A total of 305 fatal/near-fatal reactions among children and adults including 35 fatalities from the European Anaphylaxis Registry were identified. The most frequent elicitors were drugs, insects, and food. Male patients (66%/60%) were more frequently affected. Male sex, higher age, concomitant mastocytosis, and cardiovascular disease were associated with a more severe outcome. With increasing reaction severity, skin symptoms were less frequently observed (45% of fatal reactions). In parallel, anaphylaxis mortality rates were studied. The data show that anaphylaxis mortality rates increased in Germany from 0.48 (2009) to 0.59 per 1,000,000 population per year (2020). This increase was apparent only in the female population. In this data set, drugs were the most frequent elicitor of anaphylaxis fatalities, and the rate for this increased over time., Conclusions: We identified not only elicitors but also individual factors to be associated with an increased risk of fatal anaphylaxis. Such patients should be recognized and managed with great caution. The increase in drug-induced fatalities points to the need for a better allergological care of patients suffering from drug hypersensitivity., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)