Epithelial-immune cell interactions in allergic diseases.

Epithelial/immune interactions are characterized by the different properties of the various epithelial tissues, the mediators involved, and the varying immune cells that initiate, sustain, or abrogate allergic diseases on the surface. The intestinal mucosa, respiratory mucosa, and regular skin feature structural differences according to their primary function and surroundings. In the context of these specialized functions, the active role of the epithelium in shaping immune responses is increasingly recognizable. Crosstalk between epithelial and immune cells plays an important role in maintaining homeostatic conditions. While cells of the myeloid cell lineage, mainly macrophages, are the dominating immune cell population in the skin and the respiratory tract, lymphocytes comprise most intraepithelial immune cells in the intestine under healthy conditions. Common to all surface epithelia is the fact that innate immune cells represent the first line of immunosurveillance that either directly defeats invading pathogens or initiates and coordinates more effective successive immune responses involving adaptive immune cells and effector cells. Pharmacological approaches for the treatment of allergic and chronic inflammatory diseases involving epithelial barriers target immunological mediators downstream of the epithelium (such as IL-4, IL-5, IL-13, and IgE). The next generation of therapeutics involves upstream events of the inflammatory cascade, such as epithelial-derived alarmins and related mediators.

Skin microdialysis detects distinct immunologic patterns in chronic inflammatory skin diseases.

BACKGROUND: Insight into the pathophysiology of inflammatory skin diseases, especially at the proteomic level, is severely hampered by the lack of adequate in situ data. OBJECTIVE: We characterized lesional and nonlesional skin of inflammatory skin diseases using skin microdialysis. METHODS: Skin microdialysis samples from patients with atopic dermatitis (AD, n = 6), psoriasis vulgaris (PSO, n = 7), or prurigo nodularis (PN, n = 6), as well as healthy controls (n = 7), were subjected to proteomic and multiplex cytokine analysis. Single-cell RNA sequencing of skin biopsy specimens was used to identify the cellular origin of cytokines. RESULTS: Among the top 20 enriched Gene Ontology (GO; geneontology.org) annotations, nicotinamide adenine dinucleotide metabolic process, regulation of secretion by cell, and pyruvate metabolic process were elevated in microdialysates from lesional AD skin compared with both nonlesional skin and controls. The top 20 enriched Kyoto Encyclopedia of Genes and Genomes (KEGG; genome.jp/kegg) pathways in these 3 groups overlapped almost completely. In contrast, nonlesional skin from patients with PSO or PN and control skin showed no overlap with lesional skin in this KEGG pathway analysis. Lesional skin from patients with PSO, but not AD or PN, showed significantly elevated protein levels of MCP-1 compared with nonlesional skin. IL-8 was elevated in lesional versus nonlesional AD and PSO skin, whereas IL-12p40 and IL-22 were higher only in lesional PSO skin. Integrated single-cell RNA sequencing data revealed identical cellular sources of these cytokines in AD, PSO, and PN. CONCLUSION: On the basis of microdialysates, the proteomic data of lesional PSO and PN skin, but not lesional AD skin, differed significantly from those of nonlesional skin. IL-8, IL-22, MCP-1, and IL-12p40 might be suitable markers for minimally invasive molecular profiling.

Meta-analysis of ACE inhibitor-induced angioedema identifies novel risk locus.

BACKGROUND: Angioedema is a rare but potentially life-threatening adverse drug reaction in patients receiving angiotensin-converting enzyme inhibitors (ACEis). Research suggests that susceptibility to ACEi-induced angioedema (ACEi-AE) involves both genetic and nongenetic risk factors. Genome- and exome-wide studies of ACEi-AE have identified the first genetic risk loci. However, understanding of the underlying pathophysiology remains limited. OBJECTIVE: We sought to identify further genetic factors of ACEi-AE to eventually gain a deeper understanding of its pathophysiology. METHODS: By combining data from 8 cohorts, a genome-wide association study meta-analysis was performed in more than 1000 European patients with ACEi-AE. Secondary bioinformatic analyses were conducted to fine-map associated loci, identify relevant genes and pathways, and assess the genetic overlap between ACEi-AE and other traits. Finally, an exploratory cross-ancestry analysis was performed to assess shared genetic factors in European and African-American patients with ACEi-AE. RESULTS: Three genome-wide significant risk loci were identified. One of these, located on chromosome 20q11.22, has not been implicated previously in ACEi-AE. Integrative secondary analyses highlighted previously reported genes (BDKRB2 [bradykinin receptor B2] and F5 [coagulation factor 5]) as well as biologically plausible novel candidate genes (PROCR [protein C receptor] and EDEM2 [endoplasmic reticulum degradation enhancing alpha-mannosidase like protein 2]). Lead variants at the risk loci were found with similar effect sizes and directions in an African-American cohort. CONCLUSIONS: The present results contributed to a deeper understanding of the pathophysiology of ACEi-AE by (1) providing further evidence for the involvement of bradykinin signaling and coagulation pathways and (2) suggesting, for the first time, the involvement of the fibrinolysis pathway in this adverse drug reaction. An exploratory cross-ancestry comparison implicated the relevance of the associated risk loci across diverse ancestries.

Contact allergies to dental materials in patients.

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'.

Symptom severity reflected by NYHA grade is independently associated with pruritus in chronic heart failure patients.

BACKGROUND: Pruritus is a symptom profoundly impairing patients' quality of life (QoL). It is a common symptom in chronic heart failure (CHF) patients of yet unknown nature. The aim of this study was to evaluate the risk factors of pruritus in CHF patients. METHODS: For this monocentric, prospective cohort study, CHF patients were recruited and CHF symptoms, comorbidities and drug intake were assessed using a structured report. Additionally, a questionnaire evaluated pruritus symptoms. Detailed medical histories including laboratory test results were retrieved from patient files for all participants. RESULTS: We evaluated data from 550 CHF patients. Of those, 25.3% reported pruritus to occur frequently (3-5 times per week), often (1-2 times per week) or daily. Patients of higher NYHA classes (NYHA III + IV) experienced significantly more pruritus (31.2%) than lower NYHA classes (NYHA I + II) (21.1%, p = 0.024). Patients with pruritus reported disproportionately often concomitant stasis dermatitis (p = 0.026) and chronic lung disease (p = 0.014). Other parameters reflecting cardiac, liver, kidney and thyroid function, as well as medical therapies showed no significant differences between patients with and without pruritus. In the multivariate logistic regression analysis, only NYHA class (p = 0.016, OR 1.55, 95% confidence interval (CI): [1.09; 2.20]) and elevated leukocyte count (p = 0.007, OR 1.11, CI [1.03; 1.21]) remained significantly associated with pruritus in CHF patients. CONCLUSIONS: NYHA class is an independent predictor for pruritus in CHF patients. Besides NYHA class, leukocyte count was also associated with increased pruritus. Pruritus may impair QoL in CHF patients and should thus be included in the assessment of those patients. We suggest that providing best care for CHF patients can be achieved through an interdisciplinary approach of cardiologists and dermatologists and should include a pruritus assessment.

Inconsistent Skin Prick Tests for Allergy to Birch Homologous Trees May Result from Cross-Reacting Allergens or Technical Errors.

INTRODUCTION: Skin prick tests (SPTs) are the gold standard for diagnosis of allergic rhinitis (AR). A decrease in the number of allergens included in standard SPT panels has recently been debated - particularly regarding the cross-reacting homologous pollen from birch, alder, and hazel trees - but has not yet been implemented in clinical guidelines. METHODS: A subgroup of patients with AR (n = 69) who showed inconsistent SPT results among birch, alder, and hazel was investigated in detail. Beyond SPT, patient workup included assessment of clinical relevance and various serological parameters (total IgE, and specific IgE to birch, alder, and hazel and to Bet v 1, Bet v 2, and Bet v 4). RESULTS: More than half the study group had negative SPT results for birch but positive results for alder and/or hazel, and 87% of the study group was polysensitized, showing at least one more positive SPT result for other plants. Whereas 30.4% of patients showed serological sensitization to birch pollen extract, only 18.8% displayed positive specific IgE to Bet v 1. Clinical assessment revealed that most patients with AR were polysensitized and had perennial symptoms or symptoms also occurring during times other than tree flowering times. If the SPT panel is limited to testing birch only, 52.2% of patients in this subgroup would have been overlooked. CONCLUSION: Inconsistent SPT results in the birch homologous group may result from cross-reacting allergens or technical errors. If patients report convincing clinical symptoms despite negative results from a reduced SPT panel or inconsistent results for homologous allergens, SPT should be repeated, and molecular markers should be added to achieve a correct diagnosis.

Skin Tests versus Serology: Specific IgE May Suffice for Diagnosis of Vespid Venom Allergy and Follow-Up of Allergen Immunotherapy.

INTRODUCTION: In adults, allergic reactions to insect stings are among the most frequent causes of anaphylaxis, a potentially life-threatening condition. Recurrent anaphylaxis following vespid stings may be prevented by allergen immunotherapy (AIT). The aim of this study was to evaluate the benefit of measuring venom-induced wheal area in intracutaneous skin tests (ICT), in comparison to various serological and clinical parameters, for the diagnosis of severe vespid venom allergy and during follow-up of AIT. METHODS: We conducted a monocentric, retrospective evaluation of 170 patients undergoing AIT against vespid venoms. We scanned ICT wheals at baseline and at three time points after AIT initiation and measured wheal area using objective data analysis software. RESULTS: We found that ICT histamine-induced and venom-induced wheal areas did not correlate. In addition, the venom-induced wheal area was independent from the minimal venom concentration required to elicit a wheal in an ICT and all other parameters. No correlation was found between wheal area and the severity of anaphylaxis. Wheal area standardized to the application of 0.1 µg/mL venom inversely correlated with anaphylaxis severity and positively correlated with venom-specific IgE levels. During AIT, mean areas of venom-induced wheals did not change. In contrast, venom-specific IgG and IgG4 levels, and the minimal venom concentration required to induce a positive ICT result increased, while the venom wheal area standardized to 0.1 µg/mL venom application and specific IgE levels decreased over time. CONCLUSION: Wheal area evaluation did not provide additional information over specific IgE analysis. We therefore recommend that ICTs are used only as a secondary measure for confirming serological test results.

Limited Reimbursement and Underuse of Digital Healthcare Concepts Are Major Barriers to Clinical Allergological Care in Germany.

INTRODUCTION: Allergic diseases represent a broad spectrum of high-prevalence, chronic conditions that remain underdiagnosed and undertreated. The aims of this interdisciplinary, questionnaire-based, non-interventional study were to identify and analyze potential barriers to clinical allergological care in Germany. METHODS: All hospitals listed in the German hospital register involved in the treatment of allergological patients (n = 899) were invited to participate. The study yielded a response rate of 52.1% (n = 468). RESULTS: Overall, 88.5% of clinics agreed that allergological care in Germany needs improvement, especially in terms of reimbursement for diagnostics and therapy. More than 80% of participating clinics reported that the decreased availability of test substances and the time-intensity of allergological testing represent relevant barriers. For dermatology and pulmonology, the former is the strongest barrier, while for pediatric and ENT clinics, time-intensity is regarded as the strongest barrier. The availability of good therapy and appropriate guidelines present no barriers to allergological care. Regarding the use of digital healthcare concepts, a very large majority of clinics (n = 352; 91.4%) do not offer video consultations or the use of health applications in patient care. CONCLUSION: In conclusion, we have identified several structural barriers to allergological care in Germany. Reimbursement and the use of digital healthcare concepts in German clinics providing allergological care need improvement. Based on the results of this study, there is an urgent need for researchers and policymakers to further investigate and support allergology departments in their clinical work and in their implementation of digital healthcare concepts.

The PLAUR signaling promotes chronic pruritus.

Chronic itch is a complex sensation of the skin frequently associated with skin diseases, such as atopic dermatitis (AD) and psoriasis. Although Serpin E1 is implicated in chronic itch, its receptor and signaling pathways involved in itch are not known. In this study, the clinical relevance of a putative Serpin E1 receptor PLAUR to chronic itch, and the neuro-cutaneous Serpin E1-PLAUR signaling are explored. We found that PLAUR is overexpressed in skin specimens of human lesional AD and lesional psoriasis, and sensory neurons innervating MC903-induced AD-like murine skin. Murine PLAUR+ sensory neurons responded to Serpin E1, resulting in enrichment of numerous itch- and inflammation-related genes and their protein release. PLAUR resides in TLR2+ neurons and Serpin E1 stimulus led to transcriptional upregulation of TLR2 and its co-signaling proteins. Agonists of TLR2 propagated itch-related gene transcription including BNP, OSM, and PAR2. OSM induced acute itch in mice and promoted G-CSF and IL-8 release from human keratinocytes. Serpin E1 inhibitor reduced MC903-induced itch, epidermal hyperplasia, immunocyte infiltration, and resulted in lower transcription/expression levels of Serpin E1 and OSM. Taken together, the PLAUR-TLR2-OSM signaling promotes skin-nerve communication, cutaneous inflammation, and itch, all feeding into an aggravation of AD and exaggerated itch circuits.

Treatment with delgocitinib cream improves itch, pain and other signs and symptoms of chronic hand eczema: Results from the Hand Eczema Symptom Diary in a phase IIb randomized clinical trial.

BACKGROUND: Measuring patient-reported outcomes is crucial to fully capture the burden of chronic hand eczema (CHE). OBJECTIVES: To assess the effect of delgocitinib cream on itch, pain and nine additional key signs and symptoms reported by patients with CHE using the Hand Eczema Symptom Diary (HESD). METHODS: In a double-blind, phase IIb dose-ranging trial (NCT03683719), 258 adults with mild to severe CHE were randomized to delgocitinib cream 1, 3, 8 or 20 mg/g or cream vehicle twice daily for 16 weeks. Patients assessed 11 signs and symptoms of CHE daily through the HESD using an 11-point numeric rating scale; this was an exploratory endpoint. RESULTS: Delgocitinib cream 20 mg/g was associated with an early and sustained reduction in itch and pain, along with clinically relevant reductions of ≥4 points from baseline to Week 16 in 48.4% and 63.6% of patients, respectively (17.9% and 5.9% with cream vehicle). There were improvements versus cream vehicle in all assessed CHE signs and symptoms (20 mg/g, p < 0.05). CONCLUSIONS: Delgocitinib cream reduced itch, pain and other signs and symptoms in patients with CHE. This data correlated with clinician-reported outcomes, indicating that the HESD may be a useful assessment tool for CHE management.

Patch testing hydroperoxides of limonene and linalool in consecutive patients-Results of the IVDK 2018-2020.

BACKGROUND: Hydroperoxides of limonene (Lim-OOHs) and linalool (Lin-OOHs) are potent contact sensitizers. OBJECTIVES: To investigate the prevalence of positive patch test (PT) reactions to Lim-OOHs and Lin-OOHs in consecutive patients, their demographic factors and concomitant reactions. METHODS: Between 7/2018 and 12/2020, Lim-OOHs 0.3% pet. and Lin-OOHs 1% pet. were patch tested in 5511 consecutive patients. We assessed PT reactivity and analysed data from patients with either positive or negative PTs to Lim-OOHs and Lin-OOHs. RESULTS: Positive PT results to Lim-OOHs (n = 170, 3.1%) and Lin-OOHs (n = 483, 8.8%) were frequent. Most of the positive reactions were weak (LimOOHs n = 134/LinOOHs n = 429), and even more frequently, doubtful (n = 252/n = 578) or irritant reactions (n = 81/n = 178) were documented. PT reactivity to Lim-OOHs and Lin-OOHs was increased in patients with irritant reactions to sodium lauryl sulphate (SLS). The proportion of leg dermatitis and concomitant positive reactions to fragrances and essential oils was increased in patients with reactivity to these hydroperoxides. CONCLUSION: The observed reaction pattern suggests that both test preparations display an irritant potential with an increased risk of false positive reactions. Preparations should be chemically monitored in order to reduce irritancy. Mindful interpretation of PT results and aimed patch testing of lower concentrations is recommended.

Atopic dermatitis - Perspectives and unmet medical needs.

Atopic dermatitis (AD) is a chronic inflammatory skin disease for which many new insights have been gained in recent years through a better understanding of pathophysiology, concomitant diseases and therapeutics in particular. In this review, new and practice-relevant results from current research are presented. Many studies have been performed on the diagnosis of AD and on different subtypes, yet no diagnostic biomarker or clinical predictor of treatment response has been established. For topical treatment, some agents such as Janus kinase (JAK) inhibitors are in advanced stages of clinical trials or already approved in some countries, which will be available in Europe for the treatment of certain eczema subtypes in the foreseeable future. Current systemic therapies in Europe include two antibodies for inhibition of the interleukin (IL)-4/13 signaling cascades and three oral JAK inhibitors with somewhat different efficacy and safety profiles. Among the antibody therapies for AD already advanced in development, promising new targets include blockade of IL-31, of neurokinin-1 receptor on sensory neurons, and inhibition of the OX40/OX40L axis for cutaneous dendritic cell and T lymphocyte interaction. Primary prevention and modulation of sequential disease progression as well as effects on concomitant diseases by early therapeutic intervention will be important questions in future research on AD.

Current situation of allergological health care at German hospitals.

BACKGROUND: Allergic medical care in Germany is organized on an interdisciplinary basis. An overview of the current care situation is necessary to manage and improve interdisciplinary cooperation. METHODS: Between January and February 2022, questionnaires were sent online and by mail to chief physicians of inpatient clinical departments to which most allergological diseases are assigned (dermatology, otorhinolaryngology [ENT], pulmonology, pediatrics, environmental/occupational medicine, gastroenterology; n = 899). RESULTS: The response rate was 52.1%. Allergology departments of dermatology, ENT and pulmonology were predominantly located in metropolitan areas (> 100,000 inhabitants), whereas responses of pediatric departments were mostly from smaller towns. 76.8% of the respondents reported existing interdisciplinary treatment plans with other specialties. Pediatric and pulmonology clinics stated disproportionately few interdisciplinary treatment concepts with dermatology and ENT clinics, especially in smaller cities with < 100,000 inhabitants. Diagnosis and therapy of allergic rhinitis were performed in particular by the departments of ENT, asthma mainly by the pulmonology departments. Care of other allergological diseases was most frequently reported by chief physicians of dermatology and pediatrics. CONCLUSIONS: In metropolitan areas, participating departments provide allergology care in a cooperative manner. A large spectrum of care is covered in cooperation with dermatological clinics. In more rural areas, cooperation is rarer; here, mainly pediatric departments provide allergological care, which may explain the more limited range of services compared to metropolitan areas.

Full-body blue light irradiation as treatment for atopic dermatitis: a randomized sham-controlled clinical trial (AD-Blue).

BACKGROUND: Visible blue light (wavelength 400-495 nm) is a promising new treatment option for both psoriasis and atopic dermatitis (AD). Whilst previous clinical trials featured various devices and blue light at a variety of wavelengths, none of these interventions were challenged in objective clinical criteria. PATIENTS AND METHODS: Eighty-seven patients diagnosed with AD were enrolled in AD-Blue, an international, prospective, double-blinded, three-armed (415 nm vs. 450 nm vs. sham control), randomized trial designed to investigate the safety and efficacy of prototype full-body blue light devices. RESULTS: Full-body irradiation with 450 nm blue light but not 415 nm had a significant impact on itch (Itch-VAS, -1.6 ± 2.3; p  =  0.023 vs. sham irradiation). PO-SCORAD values also decreased significantly in response to irradiation at 415 nm (-11.5 ± 18.4; p = 0.028 vs. sham irradiation). None of the other outcome measures (EASI, SCORAD, IGA, DLQI) changed significantly. No safety signals were observed. Evaluation of skin transcriptomes, cytokine levels in serum, and ELISpots from peripheral blood mononuclear cells isolated from a subset of patients revealed moderate decreases in IL-31 in response to irradiation with blue light. CONCLUSIONS: Despite its favorable safety profile and moderate reductions in itch and IL-31 levels, full-body blue light irradiation did not lead to an amelioration of any of the objective measures of AD.

Identification of novel biomarkers to distinguish bradykinin-mediated angioedema from mast cell-/histamine-mediated angioedema.

BACKGROUND: The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood. METHODS: To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE-inhibitor induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous urticaria (CSU-AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin-lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme-linked immunosorbent assay. RESULTS: New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast cell-/histamine-mediated CSU-AE. However, FAP-α and tPA were significantly increased in all AE compared to controls. In HAE, FAP- α, tPA, uPAR, pentraxin-3, Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and VE-Cadherin were significantly increased, whereas for Ang-2 the difference was significant compared to CSU-AE only. Tie-2 correlated strongly negatively with C4, C1-INH activity, and C1-INH function. CONCLUSIONS: This study is the first to compare HAE, ACE-AE, and CSU-AE. Although significance is limited by small sample size, Tie-2 was identified as a new promising biomarker candidate for HAE. FAP- α and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 were increased in BK-AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.

The benefit of late readings in patch testing depends both on allergen and patient characteristics.

BACKGROUND: Patch test (PT) readings are recommended after 48 h and 72 h (D3). An additional day 7 (D7) reading has been suggested by some, although data on efficient patient selection are scarce. We investigated positive D7 reactions regarding (i) allergens in the baseline series and additional PT series of the German Contact Dermatitis Research Group (DKG) and (ii) characteristics of the patients tested. METHODS: Retrospective, multicentre analysis of 190 allergens derived from 17 DKG test series in 4687 patients with an additional D7 reading. Patients were patch tested with the baseline series and additional series, if required. Occurrence of novel D7 reactions as well as increasing skin reactions from D3 to D7 was analysed separately. RESULTS: Depending on the allergen tested, waiving D7 readings would have missed 4.4-26.8% of positive PT results. Patch test series with the highest number of novel D7 reactions were baseline series, metal series, and leather/shoe series. New positive reactions on D7 were associated with age over 50 years and with a negative irritant control containing sodium lauryl sulphate. Of note, application of the PT allergens for 48 h instead of 24 h was positively associated with late PT reactions. CONCLUSION: Within the most frequently tested allergens, without late readings, on average 11.7% of sensitizations would have been missed. Novel late reacting allergens were identified. This study comprehensively dissects patient-, allergen- and test-dependent parameters in support for D7 readings. We propose to always consider late readings individually based on effort-benefit considerations.

Management of suspected and confirmed COVID-19 (SARS-CoV-2) vaccine hypersensitivity.

BACKGROUND: Systemic allergic reactions to vaccines are very rare. In this study we assessed the management and outcome of suspected SARS-CoV-2 vaccine hypersensitivity. METHODS: Totally, 334 individuals underwent an allergy work up regarding SARS-CoV-2 vaccination (group A: 115 individuals suspected to be at increased risk for vaccine-related reactions before vaccination and group B: 219 patients with reactions after COVID vaccination). The large majority of the SPT/IDT with the vaccines were negative; however, we identified in 14.1% (n = 47) a possible sensitization to the SARS-CoV-2 vaccine and/or its ingredients defined as one positive skin test. Of the 219 individuals (group B) who experienced symptoms suspicious for a hypersensitivity reaction after vaccination, 214 were reported after the first vaccination with a mRNA vaccine (157 mRNA (Comirnaty®, 38 Spikevax®) and 18 with a vector vaccine (Vaxzevria®), 5 cases were after the second vaccination. RESULTS: The symptom profile in group B was as follows: skin symptoms occurred in 115 cases (n = 59 angioedema, n = 50 generalized urticaria and n = 23 erythema/flush. Seventy individuals had cardiovascular, 53 respiratory and 17 gastrointestinal symptoms. Of the overall 334 individuals, 78 patients tolerated (re)-vaccination (out of skin test positive/negative 7/19 from group A and 17/35 from group B). CONCLUSION: Proven IgE-mediated hypersensitivity to SARS-CoV-2 vaccines is extremely rare and not increased in comparison with reported hypersensitivity to other vaccines. The value of skin tests is unclear and nonspecific reactions, in particular when intradermal testing is applied, should be considered.

European patch test results with audit allergens as candidates for inclusion in the European Baseline Series, 2019/20: Joint results of the ESSCAA and the EBSB working groups of the ESCD, and the GEIDACC.

BACKGROUND: In 2019, a number of allergens (haptens), henceforth, "the audit allergens," were considered as potential additions to the European Baseline Series (EBS), namely, sodium metabisulfite, 2-bromo-2-nitropropane-1,3-diol, diazolidinyl urea, imidazolidinyl urea, Compositae mix II (2.5% or 5% pet), linalool hydroperoxides (lin-OOH), limonene hydroperoxides (lim-OOH), benzisothiazolinone (BIT), octylisothiazolinone (OIT), decyl glucoside, and lauryl glucoside; Evernia furfuracea (tree moss), was additionally tested by some departments as well. OBJECTIVES: To collect further data on patch test reactivity and clinical relevance of the audit allergens in consecutive patients across Europe. METHODS: Patch test data covering the audit allergens in 2019 and 2020 were collected by those departments of the European Surveillance System on Contact Allergies testing these, as well as further collaborators from the EBS working group of the European Society of Contact Dermatitis (ESCD), and the Spanish Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea. As patch test outcome, reactions between day (D) 3 and D5 were considered. RESULTS: Altogether n = 12 403 patients were tested with any of the audit allergen. Positive reactions were most common to lin-OOH 1% pet. (8.74% [95%CI: 8.14-9.37%]), followed by lin-OOH 0.5% pet., and lim-OOH 0.3% pet (5.41% [95% CI: 4.95-5.89%]). Beyond these terpene hydroperoxides, BIT 0.1% pet. was the second most common allergen with 4.72% (95% CI: 4.2-5.28%), followed by sodium metabisulfite 1% pet. (3.75% [95%CI: 3.32-4.23%]) and Compositae mix 5% pet. (2.31% [95% CI: 1.84-2.87%]). For some allergens, clinical relevance was frequently difficult to ascertain. CONCLUSIONS: Despite many positive patch test reactions, it remains controversial whether lin- and lim-OOH should be tested routinely, while at least the two preservatives BIT and sodium metabisulfite appear suitable. The present results are a basis for further discussion and ultimately decision on their implementation into routine testing among the ESCD members.

Patch test results with the European baseline series, 2019/20-Joint European results of the ESSCA and the EBS working groups of the ESCD, and the GEIDAC.

BACKGROUND: Continual analyses of patch test results with the European baseline series (EBS) serve both contact allergy surveillance and auditing the value of included allergens. OBJECTIVES: To present results of current EBS patch testing, obtained in 53 departments in 13 European countries during 2019 and 2020. METHODS: Anonymised or pseudonymised individual data and partly aggregated data on demographic/clinical characteristics and patch test rest results with the EBS were prospectively collected and centrally pooled and analysed. RESULTS: In 2019 and 2020, 22 581 patients were patch tested with the EBS. Sensitization to nickel remained most common (19.8 [19.2-20.4]% positivity [95% confidence interval]). Fragrance mix I and Myroxylon pereirae yielded very similar results with 6.80 (6.43-7.19)% and 6.62 (6.25-7.00)% positivity, respectively. Formaldehyde at 2% aq. yielded almost one percentage point more positive reactions than 1% concentration (2.49 [2.16-2.85]% vs. 1.59 [1.33-1.88]); methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) and MI alone up to around 5% positives. Among the new additions, propolis was most commonly positive (3.48 [3.16-3.82]%), followed by 2-hydroxyethyl methacrylate (2.32 [2.0-2.68]%). CONCLUSION: Ongoing surveillance on the prevalence of contact sensitization contributes to an up-to-date baseline series containing the most frequent and/or relevant contact sensitizers for routine patch testing in Europe.

[New interdisciplinary teaching concept for the cross-sectional subject of allergology in human medicine studies]. / Interdisziplinäre Neukonzeption der Lehre im Querschnittsfach "Allergologie" im Studiengang Humanmedizin.

BACKGROUND: Although allergic diseases are among the most important health disorders, allergology is not anchored as an independent subject in the clinical part of medical studies in Germany. OBJECTIVE: As all universities and institutes face the same challenge, the aim of our project was to establish exemplary coordination and networking of education in allergology at one location in agreement with all involved departments and institutes. Particularly, Comprehensive Allergy Centers (CAC) offer an established infrastructure via which the revised allergology education program can be transferred to other universities. MATERIALS AND METHODS: After an extensive inventory of the current allergological curriculum at the University Medical Center Göttingen, a new teaching concept was developed in interdisciplinary consensus, supplemented by first-time provision of additional digital contents ("blended learning"), and finally evaluated. RESULTS: Initially, we observed a high level of fragmentation in the teaching of allergology in the clinical study sections of human medicine, with no coordination between the 12 clinical departments/institutes involved and no coherent framework for the specific learning content. Within the established structure of the interdisciplinary CAC, we revised, coordinated, and defined key areas for improved student education in clinical allergology. The allocation of new interactive learning elements as well as supplementary materials for self-studies was welcomed by the students and positively evaluated. A survey among students after completing the former vs. current curricula showed significant improvements in achieving the desired educational objectives.