De novo transcriptome assembly of the oak processionary moth Thaumetopoea processionea.

OBJECTIVES: The oak processionary moth (OPM) (Thaumetopoea processionea) is a species of moth (order: Lepidoptera) native to parts of central Europe. However, in recent years, it has become an invasive species in various countries, particularly in the United Kingdom and the Netherlands. The larvae of the OPM are covered with urticating barbed hairs (setae) causing irritating and allergic reactions at the three last larval stages (L3-L5). The aim of our study was to generate a de novo transcriptomic assembly for OPM larvae by including one non-allergenic stage (L2) and two allergenic stages (L4 and L5). A transcriptomic assembly will help identify potential allergenic peptides produced by OPM larvae, providing valuable information for developing novel therapeutic strategies and allergic immunodiagnostic assays. DATA: Transcriptomes of three larval stages of the OPM were de novo assembled and annotated using Trinity and Trinotate, respectively. A total of 145,251 transcripts from 99,868 genes were identified. Bench-marking universal single-copy orthologues analysis indicated high completeness of the assembly. About 19,600 genes are differentially expressed between the non-allergenic and allergenic larval stages. The data provided here contribute to the characterization of OPM, which is both an invasive species and a health hazard.

"Delabeling" by direct provocation testing in children and adolescents with a suspected history of a delayed reaction to ß-lactam antibiotics: Consensus paper of Gesellschaft für pädiatrische Allergologie und Umweltmedizin (GPAU), Deutsche Gesellschaft für Allergologie und klinische Immunologie (DGAKI), and Ärzteverband deutscher Allergologen (ÄDA).

BACKGROUND: Approximately 10% of European children are classified as allergic to drugs. In the majority of these children, no allergy to ß-lactam antibiotics (BLA) can be found. In most cases, the exanthema is caused by the infection. MATERIALS AND METHODS: The objective of this paper is to describe the causes and consequences of a misdiagnosis of drug allergy. We propose a method for establishing a correct diagnosis in the case of a history of a delayed reaction during treatment with a BLA. For this purpose, a proposal was discussed via e-mail communication, and consensus was reached among the members of the drug allergy working groups of the participating medical societies. RESULTS: The suspicion of a BLA allergy based on the medical history alone can have a negative impact on future antibiotic treatment. Exanthema associated with febrile infections not related to drug administration is a frequent finding in children. This makes it all the more important to be able to recommend a standardized procedure for clarification in children and adolescents with suspected hypersensitivity reactions. The medical history should be the basis on which to diagnose either a drug allergy or another possible differential diagnosis. A mild maculopapular exanthema (MPE) can be an expression of a drug allergy or a nonspecific viral exanthema. Uncomplicated MPE is not associated with significant systemic involvement, and there is no involvement of the mucous membranes or cutaneous blistering. Only a small number of children with uncomplicated MPE show positive skin tests and only ~ 7 - 16% of suspected BLA diagnoses can be confirmed by provocation tests. Thus, in children with uncomplicated MPE, drug provocation can be performed in an outpatient setting even without prior skin testing. This paper presents a 3-day outpatient direct provocation scheme for BLA delabeling in children with uncomplicated MPE. CONCLUSION: Many children and adolescents are unnecessarily denied treatment with BLA after an uncomplicated MPE while being treated with a BLA.

Hand eczema symptoms, exposures and skin care in orthodontics : A national, cross-sectional questionnaire-based survey.

OBJECTIVES: Occupational hand eczema is a common inflammatory skin condition among healthcare professionals. Orthodontists are frequently exposed to a variety of irritating and allergenic substances, and therefore they belong to a predisposed group to develop hand eczema. However, current data on the prevalence and predisposing factors among orthodontists to provide adequate prophylaxis are lacking. METHODS: An anonymous online survey was conducted in Germany between January and February 2023 and distributed to 2402 orthodontists. The questionnaire addressed general information on current skin status, as well as occupational skin exposure and skin care. RESULTS: A total of 209 orthodontists responded to the survey. Seventy-four percent reported experiencing hand eczema-specific symptoms within the last 12 months, with 24% describing moderate and 10% describing severe symptoms. The average daily glove wearing time was stated to be 6 ± 2 h. The most frequently reported triggers at work were frequent hand washing (62.7%) and hand disinfection (59.1%). Among all the respondents, 22.6% stated not using either barrier cream or moisturizer. CONCLUSIONS: This study showed a high prevalence of hand eczema symptoms among orthodontists, which is probably due to frequent disinfection, hand washing, and contact with allergens such as acrylates. In this professional group especially, against a background of future increasing acrylate and epoxy resin exposures due to in-office three-dimensional printing processes, timely education and skin protection could decisively counteract the pathogenesis of hand eczema.

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.

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.

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.

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'.

A human 3D immune competent full-thickness skin model mimicking dermal dendritic cell activation.

We have integrated dermal dendritic cell surrogates originally generated from the cell line THP-1 as central mediators of the immune reaction in a human full-thickness skin model. Accordingly, sensitizer treatment of THP-1-derived CD14-, CD11c+ immature dendritic cells (iDCs) resulted in the phosphorylation of p38 MAPK in the presence of 1-chloro-2,4-dinitrobenzene (DNCB) (2.6-fold) as well as in degradation of the inhibitor protein kappa B alpha (IκBα) upon incubation with NiSO4 (1.6-fold). Furthermore, NiSO4 led to an increase in mRNA levels of IL-6 (2.4-fold), TNF-α (2-fold) and of IL-8 (15-fold). These results were confirmed on the protein level, with even stronger effects on cytokine release in the presence of NiSO4: Cytokine secretion was significantly increased for IL-8 (147-fold), IL-6 (11.8-fold) and IL-1ß (28.8-fold). Notably, DNCB treatment revealed an increase for IL-8 (28.6-fold) and IL-1ß (5.6-fold). Importantly, NiSO4 treatment of isolated iDCs as well as of iDCs integrated as dermal dendritic cell surrogates into our full-thickness skin model (SM) induced the upregulation of the adhesion molecule clusters of differentiation (CD)54 (iDCs: 1.2-fold; SM: 1.3-fold) and the co-stimulatory molecule and DC maturation marker CD86 (iDCs ~1.4-fold; SM:~1.5-fold) surface marker expression. Noteworthy, the expression of CD54 and CD86 could be suppressed by dexamethasone treatment on isolated iDCs (CD54: 1.3-fold; CD86: 2.1-fold) as well as on the tissue-integrated iDCs (CD54: 1.4-fold; CD86: 1.6-fold). In conclusion, we were able to integrate THP-1-derived iDCs as functional dermal dendritic cell surrogates allowing the qualitative identification of potential sensitizers on the one hand, and drug candidates that potentially suppress sensitization on the other hand in a 3D human skin model corresponding to the 3R principles ("replace", "reduce" and "refine").

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.

Guideline for allergological diagnosis of drug hypersensitivity reactions: S2k Guideline of the German Society for Allergology and Clinical Immunology (DGAKI) in cooperation with the German Dermatological Society (DDG), the Association of German Allergologists (ÄDA), the German Society for Pediatric Allergology (GPA), the German Contact Dermatitis Research Group (DKG), the German Society for Pneumology (DGP), the German Society of Otorhinolaryngology, Head and Neck Surgery, the Austrian Society of Allergology and Immunology (ÖGAI), the Austrian Society of Dermatology and Venereology (ÖGDV), the German Academy of Allergology and Environmental Medicine (DAAU), and the German Documentation Center for Severe Skin Reactions (dZh).

Not available.

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.

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.

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.

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.

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.