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Multiple environmental exposures may derange the regulatory and repair mechanisms of the skin and lead to dermatological disease.Provide an overview of non-allergic skin diseases associated with environmental factors.Review of current scientific evidence for associations of non-allergic skin diseases with environmental exposures: irritation, chemicals, infection, UV-radiation, temperature.Predisposition (constitution e. g. for atopic dermatitis, psoriasis and filaggrin gene mutations) and exposure (environment) are crucial for disease development or maintenance of health in an individual. Specific chemical and contagious agents lead to characteristic skin diseases (e. g. halogen acne) which under certain conditions may be recognized as occupational disease. The most frequent cause for irritant contact dermatitis is water (wet work). Natural optical radiation of different wavelength may cause light-induced inflammatory skin diseases. Phototoxic reactions due to psoralens, furocoumarins and drugs are frequent. The polymorphous light eruption is not an exogenous delayed type allergy, but seems to be a reaction against a UV-induced neoantigen of the skin. UVB exhibits direct mutagenic effects on DNA. Sun exposure and defective DNA-repair mechanisms are risk factors for skin tumors. Heat/cold exposure under specific conditions also triggers skin diseases (primary: congelations, frostbite, heat burn, scalding, chronic-inducible urticaria; secondary: deterioration of preexisting inflammatory diseases (e. g. systemic sclerosis)).To keep the skin healthy, an early identification and elimination of harmful environmental factors and treatment of early disease stages is necessary. This requires strategies of environmental prevention and behavioral prevention, as well as global action (e. g. with regard to increasing incidence of skin cancer).

Background Omalizumab, a recombinant anti-IgE antibody, effectively treats chronic spontaneous urticaria. Evidence is lacking in patients with chronic inducible urticarias (CIndUs), which are frequently H 1 -antihistamine resistant. Objective From the current published literature, we aimed to determine the strength of evidence for omalizumab efficacy and safety in the treatment of CIndUs. Methods We performed a PubMed search to identify evidence on omalizumab use in the following 9 CIndU subtypes: symptomatic dermographism, cold urticaria, delayed-pressure urticaria, solar urticaria, heat urticaria, vibratory angioedema, cholinergic urticaria, contact urticaria, and aquagenic urticaria. Results Forty-three trials, case studies, case reports, and analyses were identified. Our review indicates that omalizumab has substantial benefits in patients with various CIndUs. The evidence is strongest for symptomatic dermographism, cold urticaria, and solar urticaria. Little/no evidence was available on vibratory angioedema and aquagenic and contact urticaria. Our review supports rapid onset of action demonstrated through early symptom control in most cases, sometimes within 24 hours. Many patients gained complete/partial symptom relief and substantially improved quality of life. Adverse events were generally low, with omalizumab being well tolerated by most patients, including children. Conclusions A strong body of evidence supports the use of omalizumab in the treatment of patients with therapy-refractory CIndU. More data from randomized controlled studies are warranted.

Because of their ubiquitous distribution and high level of cross-reactivity, profilins and polcalcins are classified as panallergens. To date, 43 profilin and 15 polcalcin allergens have been identified. Panallergens frequently cause a pattern of multiple sensitizations in skin prick tests. Moreover, IgE specific for a number of biologically unrelated allergen sources exist. These sensitizations and cross-reactivities are usually irrelevant and, only sporadically, do panallergens represent clinically relevant major allergens. On rare occasions, severe allergic reactions to food have been observed among profilin-allergic patients. Pronounced sensitization to polcalcins may possibly be linked to an elevated risk of asthma. Moreover, panallergens affect the analytical specificity of pollen and food allergen extracts in skin prick tests and in IgE-based diagnosis. Thus, sensitization toward panallergens resembles an important indication to complement allergy diagnosis with source-related, species-specific marker major allergens. These marker allergens contribute significantly to the analytical specificity necessary for identifying the disease-eliciting allergen sources for allergen-specific immunotherapy.

The most common food allergies in adults are to plant foods (nuts, legumes, fruits, and vegetables) and a few animal products (milk, eggs, crustacean shellfish, and fish muscle). Eliminating relevant allergens (specific proteins) in specific plants represents a new approach to allergen avoidance for the prevention of sensitization and elicitation of food allergies. A variety of methods have been used to date with varying success in proof-of-concept investigations to develop hypoallergenic foods. This chapter provides an overview of the current status of hypoallergenic foods produced in model allergenic plants (rice, soy, apple, tomato, carrot, peanut). Perspectives and challenges are discussed. However, marketing of hypoallergenic foods produced from genetically modified crops is currently not feasible as these varieties would have to be accurately differentiated from unmodified, fully allergenic varieties.

BackgroundAllergic contact dermatitis caused by biocides is common and causes significant patient morbidity. ObjectiveTo describe the current frequency and pattern of patch test reactivity to biocide allergens included in the baseline series of most European countries. MethodsData collected by the European Surveillance System on Contact Allergies (ESSCA) network between 2009 and 2012 from 12 European countries were analysed. ResultsMethylisothiazolinone 0.2% aq. produced the highest prevalence of sensitization during the study period, with an overall prevalence of 4.5%. The mixture methylchloroisothiazolinone /methylisothiazolinone tested at 0.02% aq. followed closely, with 4.1% of positive reactions. Other preservatives with lower rates of sensitization, but still over 1%, include methyldibromo glutaronitrile (MDBGN) 0.5% pet. and iodopropynyl butylcarbamate (IPBC) 0.2% pet. Formaldehyde releasers and parabens yielded less than 1% positive reactions during the study period. Some regional differences in the prevalence of contact allergy to biocides among European countries were observed. ConclusionsContact allergy to biocides is common throughout Europe, and regional differences could be explained by differences in exposure or characteristics of the population tested. Timely regulatory action for isothiazolinones is required. Although MDBGN is banned from cosmetics products since 2005, sensitization prevalence has not appeared to plateau. IPBC is an emerging allergen with an increasing prevalence over the last few years, and its inclusion in the European baseline series may be appropriate.

Background Skin diseases constitute up to 40% of all notified occupational diseases in most European countries, predominantly comprising contact dermatitis, contact urticaria, and skin cancer. While insufficient prevention of work-related skin diseases (WRSD) is a top-priority problem in Europe, common standards for prevention of these conditions are lacking. Objective To develop common European standards on prevention and management of WRSD and occupational skin diseases (OSD). Method Consensus amongst experts within occupational dermatology was achieved with regard to the definition of minimum evidence-based standards on prevention and management of WRSD/OSD. Results By definition, WRSDs/OSDs are (partially or fully) caused by occupational exposure. The definition of OSD sensu stricto additionally includes diverging national legal requirements, with an impact on registration, prevention, management, and compensation. With the implementation of the classification of WRSD/OSD in the International Classification of Diseases (ICD) 11th Revision in future, a valid surveillance and comparability across countries will be possible. Currently, WRDS and OSD are still under-reported. Depending on legislation and regulations, huge differences exist in notification procedures in Europe, although notification is crucial to prevent chronic and relapsing disease. Facilities for early diagnosis, essential for individual patient management, should be based on existing guidelines and include a multidisciplinary approach. Patch testing is essential if contact dermatitis persists or relapses. Workplace exposure assessment of WRSD/OSD requires full labelling of product ingredients on material safety data sheets helping to identify allergens, irritants and skin carcinogens. Comparable standards in primary, secondary and tertiary prevention must be established in Europe to reduce the burden of WRSD/OSD in Europe. Conclusion The adoption of common European standards on prevention of WRSD/OSD will contribute to reduce the incidence of OSD and their socio-economic burden.

BACKGROUND: Contact allergy is a common condition and can severely interfere with daily life or professional activities. Due to changes in exposures, a consequence of introduction of new substances, new products or formulations, and regulatory intervention, the spectrum of contact sensitisation changes. OBJECTIVE: To evaluate the current spectrum of contact allergy to allergens present in the European baseline series (EBS) across Europe. METHODS: Retrospective analysis of data collected by the European Surveillance System on Contact Allergies (ESSCA, www.essca-dc.org) in consecutively patch tested patients, 2013/14, in 46 departments in 12 European countries. RESULTS: Altogether, 31689 patients were included in the analysis. Compared to a similar analysis in 2004, the prevalence of contact allergy to methylisothiazolinone went up to around 20% in several departments. In comparison, contact allergy to the metals nickel, cobalt and chromium remained largely stable, at 18.1, 5.9 and 3.2%, respectively, similar to mostly unchanged prevalences with fragrance mix I, II and Myroxylon pereirae (Balsam of Peru) at 7.3, 3.8 and 5.3%, respectively. In the subgroup of departments diagnosing (mainly) patients with occupational contact dermatitis, the prevalence of work-related contact allergies such as to epoxy resin or rubber additives was increased, compared to general dermatology departments. CONCLUSION: Continuous surveillance of contact allergy based on network data offers the identification of time trends or persisting problems, and thus enables focussing in-depth research (subgroup analyses, exposure analysis) on areas where it is needed. This article is protected by copyright. All rights reserved.

Background Fluorescence-labeled MHC class II/peptide tetramer complexes are considered as optimal tools to characterize allergen-specific CD4(+) T cells, but this technique is restricted to frequently expressed HLA class II molecules and knowledge of immunodominant epitopes. In contrast, allergen-stimulated proliferation assessed by CFSE dilution is less sophisticated and widely applicable. The major mugwort allergen, Art v 1, contains only one single, immunodominant, HLA-DR1-restricted epitope (Art v 125-36 ). Thus, essentially all Art v 1-reactive cells should be identified by a HLA-DRB1*01:01/Art v 119-36 tetramer. Methods We compared specificity and sensitivity of tetramer(+) and allergen-induced proliferating (CFSE(lo) ) CD4(+) T cells by flow cytometry. Results The frequency of tetramer(+) CD4(+) T cells determined ex vivo in PBMC of mugwort-allergic individuals ranged from 0 to 0.029%. After 2-3 weeks of in vitro expansion, sufficient tetramer(+) T cells for phenotyping were detected in 83% of Art v 125-36 -reactive T-cell lines (TCL) from mugwort-allergic individuals, but not in TCL from healthy individuals. The tetramers defined bona fide Th2 cells. Notably, Art v 125-36 -reactive TCL depleted of tetramer(+) T cells still reacted to the peptide, and only 44% of Art v 125-36 -specific T-cell clones were detected by the tetramer. CFSE(lo) CD4(+) T cells contained only 0.3-10.7% of tetramer(+) T cells and very low proportions of Th2 cells. Conclusion Allergen-specific T cells can be identified by HLA class II tetramers with high specificity, but unexpected low sensitivity. In contrast, allergen-stimulated CFSE(lo) CD4(+) T cells contain extremely high fractions of bystander cells. Therefore, for T-cell monitoring, either method should be interpreted with caution.

Summary Background The Occupational Contact Dermatitis Disease Severity Index (ODDI) was designed in Australia to measure severity and functional disability in patients with occupational contact dermatitis (OCD) of the hands. The ODDI was translated into the German language with a linguistic validation process. The psychometric properties of the German version of the ODDI are still unclear. Objectives To report the linguistic validation procedure and to perform a psychometric validation by investigating the validity and reliability of the German ODDI version in a sample of patients with OCD. Methods Data were drawn from the baseline assessment (T0) and first follow-up (T1) of the German chronic hand eczema (CHE) registry (CARPE). Spearman correlations of the ODDI with reference measures were computed to assess validity. Cronbach's alpha was calculated as a measure of internal consistency, and the intraclass correlation coefficient (ICC) was calculated to assess retest reliability. The smallest real difference (SRD) and minimal clinically important difference (MCID) were calculated to assess sensitivity to change. Physician Global Assessment (PGA) was used as an anchor for the MCID. Results Four hundred and twenty-two patients (54.5% female, mean age 45.1 years) were included for analysis. Cronbach's alpha was found to be 0.73. The ICC was 0.79. Correlations between the ODDI total and the Dermatology Life Quality Index (rho = 0.36), and between PGA (rho = 0.48) and patient-assessed disease severity (rho = 0.40), were of moderate strength. The MCID (1.29) was found to be smaller than the SRD (1.87). Conclusions The German ODDI version is reliable and valid for the measurement of functional impairment and disease severity in patients suffering from OCD.

Zusammenfassung Hintergrund Anlagebedingte Erkrankungen stellen bei der berufsdermatologischen Begutachtung eine besondere Herausforderung dar. Es muss dabei exakt differenziert werden, ob die berufliche Tatigkeit in einem ursachlichen Zusammenhang steht oder ob der Spontanverlauf der Erkrankung im Vordergrund steht. In einer kurzlich erschienen S1-Leitlinie wurden Begutachtungsempfehlungen zur Beurteilung von Psoriasis im Erwerbsleben konsentiert, die in der vorliegenden Arbeit an Gutachtenfallen aus der klinischen Praxis verdeutlicht werden. Patienten und Methodik 129 Begutachtungsfalle der Hautklinik Universitatsklinikum Erlangen und Falle aus der deutschen Rechtsprechung (recherchiert in etablierten juristischen Datenbanken) wurden bezuglich Psoriasisfallen und Anwendbarkeit der o. g. Begutachtungsempfehlungen untersucht. Ergebnisse Die o. g. Begutachtungsempfehlungen wurden in den sechs Gutachtenfallen der Klinik mit Psoriasis (3,6 %) eingesetzt. Die darauf basierenden gutachterlichen Beurteilungen wurden gemas Bescheiden der zustandigen Berufsgenossenschaft uneingeschrankt anerkannt. Die Recherche nach Urteilen zu berufsbedingter Psoriasis in der deutschen Rechtsprechung erbrachte insgesamt vier Urteile, wobei in einem Fall die Psoriasis als Berufserkrankung nach BK 5101 anerkannt wurde. Schlussfolgerungen Die Psoriasis der Hande stellt im Vergleich zum Handekzem eine seltenere Erkrankung dar. Nach der deutschen Rechtsordnung ist, wie in der vorliegenden Fallserie dargestellt, die Anerkennung einer anlagebedingten Erkrankung als Berufserkrankung nach BK 5101 moglich, wenn ein Berufsbezug hinreichend wahrscheinlich gemacht werden kann und die anderen Voraussetzungen der Berufskrankheitenverordnung erfullt sind.

Summary Background Constitutional diseases represent a challenge in the expert assessment of occupational diseases. It is necessary to distinguish professional causes from the spontaneous course of the disease. Recently, a guideline for the assessment of work-related psoriasis has been consented in Germany. We present a case series in which it was applied. Patients and Methods 129 expert assessments from the Department of dermatology University hospital Erlangen and court cases in established juridical databases were researched for cases with psoriasis and the applicability of the guideline. Results The guideline was applicable in the n = 6 (3.6 %) identified medical expert opinions. They were fully recognized by the workers compensation boards. The search for law sentences on work-related psoriasis in German court cases yielded a total of four sentences, in one of which the psoriasis was recognized as an occupational disease (BK 5101). Conclusions In comparison with hand eczema psoriasis of the hands is rare. As has been demonstrated in our case series psoriasis as a constitutional disease may be recognized as an occupational disease (BK 5101) according to the legal system in Germany, if the influence of occupational exposure can be made sufficiently probable and other legal conditions of an occupational disease are met.

Zusammenfassung Hintergrund und Ziele Die Bedeutung einzelner Kontaktallergene ist einem bestandigen Wandel unterworfen, der wesentlich durch veranderte Expositionen aufgrund von Verbrauchervorlieben und der Gesetzesvorgaben beeinflusst wird. Ziele der Arbeit sind, Trends aus dem Epikutantest-Kollektiv der DKG- und IVDK-Kliniken darzustellen, die zur aktuellen Anderung (gultig ab 1.1.2014) der DKG-Standardreihe gefuhrt haben und die aktuell geltenden gesetzlichen Rahmenbedingungen darzulegen, die Einfluss auf diese Trends und die Durchfuhrung der Epikutantestung zur Aufklarung von Kontaktallergien haben. Patienten und Methodik Das Epikutantestkollektiv aus 56 DKG-/IVDK-Kliniken der Jahre 2010 (n = 13 117), 2011 (n = 13 320), 2012 (n = 12 529) wurde bezuglich der Sensibilisierungshaufigkeiten (Hitliste) auf Kontaktallergene und Lokalisationen allergischer Kontaktekzeme ausgewertet. Ergebnisse Mit uber 15 % Sensibilisierungshaufigkeit stellt Nickel noch immer das am haufigsten erkannte Kontaktallergen dar. Eine Zunahme der Sensibilisierungshaufigkeit auf Duftstoff-Mix I auf 9,1 % und auf das Konservierungsmittelgemisch aus Chlormethylisothiazolinon/Methylisothiazolinon (MCI/MI) auf 4,5 %, sowie auf Methylisothiazolinon (MI) alleine auf 6,8 % ist zu verzeichnen. Ein Abwartstrend zeigt sich fur Kaliumdichromat von uber 6 % (2007) auf 3 % (2012) und fur Bufexamac (derzeit bei 0,6 %). Die Hintergrunde, gesetzliche Rahmenbedingungen und resultierende Aktualisierung der DKG-Standardreihe werden dargestellt. Schlussfolgerungen Die aufgezeigten Trends demonstrieren die Bedeutung der klinischen Epidemiologie und „Wachterfunktion“ von DKG und IVDK im Hinblick auf offentliche Gesundheitsfursorge und die Pravention von Kontaktallergien.

Summary Background and objectives The relevance of contact allergens is subject to constant change due to changing exposures according to consumers’ preferences and legal requirements. The objective of this paper is to present trends in contact sensitization from the DKG and IVDK patch test clinics, which have led to changes in the DKG standard series (as of 1.1.2014), as well as the current legal framework which has influenced these trends and the way patch testing is performed. Patients and methods The patients from 56 DKG and IVDK patch test clinics from 2010 (n = 13,117), 2011 (n = 13,320) and 2012 (n = 12,529) were analyzed with regard to frequencies of sensitization (hit list) to contact allergens as well as the location of allergic contact dermatitis. Results With a sensitization rate of 15 % nickel is still the most frequently recognized contact allergen. An increase can be observed for fragrance mix I (9.1 %), the preservative composition of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) (4.5 %) and methylisothiazolinone (MI) alone (6.8 %). A decline is present for potassium dichromate from above 6 % (2007) to 3 % (2012) and for bufexamac (currently at 0.6 %). Backgrounds, legal requirements and resulting changes to the DKG standard series are illustrated. Conclusions The indicated trends demonstrate the relevance of clinical epidemiology and the “sentinel function” of DKG and IVDK with regard to public health and prevention of contact allergies.

ZusammenfassungHintergrund Die Psoriasis ist eine anlagebedingte Erkrankung. Krankheitsschube konnen durch exogene mechanische oder irritative Reize ausgelost werden. Bei der berufsdermatologischen Behandlung/Begutachtung muss differenziert werden, ob die berufliche Tatigkeit mit der Erkrankung in ursachlichem Zusammenhang steht oder ob der Spontanverlauf der Psoriasis im Vordergrund steht. Ziel der vorliegenden Arbeit ist, die sozialrechtlich bedingten Grundlagen fur eine einheitliche Beurteilung darzustellen. Patienten und Methodik Unter Kenntnis der bestehenden Begutachtungsempfehlungen und Rechtsprechung wurden Empfehlungen zur Begutachtung von Patienten mit Psoriasis und arbeitsbedingten Einflussen in einer Arbeitsgruppe der Arbeitsgemeinschaft fur Berufs- und Umweltdermatologie (ABD) und der Deutschen Kontaktallergie-Gruppe (DKG) in der Deutschen Dermatologischen Gesellschaft (DDG) entwickelt. Ergebnisse Voraussetzung fur eine Berufskrankheit ist, dass zwischen versicherter Tatigkeit und Hautkrankheit ein ursachlicher Zusammenhang (im Sinne der Entstehung oder der Verschlimmerung) besteht. Dies ist der Fall, wenn die berufliche Tatigkeit die alleinige oder eine rechtlich wesentlich mitwirkende Bedingung fur die Erkrankung darstellt. Ein rechtlich wesentlicher Ursachenzusammenhang ist zu verneinen, wenn fur die Auslosung der Krankheitserscheinungen gewohnliche Belastungen des taglichen Lebens ausreichen (Gelegenheitsursache). 1995–2010 wurden 130 Psoriasisfalle von den Unfallversicherungstragern als berufsbedingt anerkannt. Schlussfolgerungen Bei der berufsdermatologischen Begutachtung von Psoriasiserkrankungen handelt es sich um eine Einzelfallbeurteilung durch den Gutachter. Im vorliegenden Positionspapier werden Empfehlungen zur einheitlichen Beurteilungsgrund­lage im Hinblick auf Diagnosesicherung, Beurteilung arbeitsbedingter Verursachung/Verschlimmerung der Psoriasis, MdE-Schatzung und rehabilitative Leistungen vorgestellt.

Summary Background Psoriasis is an immune-mediated disease with a genetic background. Local psoriatic changes can be triggered by exogenous mechanical or irritant factors. Causative occupational factors have to be distinguished from the spontaneous course of psoriasis in occupational medical evaluations. The objective of this work is to demonstrate the medico-legal grounds for a homogenous assessment. Patients and methods The presented recommendations were developed in a working group for Occupational and Environmental Dermatology (ABD) and the German contact dermatitis group (DKG) of the German Dermatologic Society (DDG) based on the German medico-legal framework. Results Causality between the insured activity and the appearance of psoriasis is a prerequisite for the recognition of the occupational nature of the disease. This is the case if the occupational activity is the exclusive or a legally essential contributing factor either for first manifestation or aggravation of the disease. A connection must be denied if everyday events are sufficient to trigger the psoriasis. From 1995 to 2010, 130 cases of psoriasis have been recognized as occupationally related by the German statutory accident insurance. Conclusions The appraisal of psoriatic disease in the occupational medical evaluation is subject to the case assessment of the expert witness. In this position paper we present recommendations for a homologous basis for diagnosis, causality assessment, estimation of reduction in earning capacity and rehabilitation of occupational psoriasis.

Scope The aim was to investigate the potential contribution of a major birch pollen Bet v 1-homologous allergen to birch pollen-associated tomato fruit allergy. Methods and results Two isoforms of a Bet v 1-homologous protein (designated Sola l 4) from tomato fruit were identified by cDNA-cloning and produced as recombinant proteins. Allergen-specific IgE levels to tomato, birch pollen, Bet v 1, and Sola l 4 were determined in birch pollen allergic patients with allergy or tolerance to tomato. Sola l 4 was recognized in 76% of birch/tomato allergic patients, while tomato- and Bet v 1-specific IgE was detectable in 64% and 81% of sera. Almost all patients sensitized to Bet v 1 reacted with Sola l 4. Both Sola l 4 isoforms displayed allergenic potency and IgE-cross-reactivity with Bet v 1 as investigated by competitive ELISA and in vitro mediator release assay. Nevertheless, the reactivity pattern of patients' sera was diverse. Conclusion Sola l 4, a novel pathogenesis related-10 protein, qualifies as major allergen in tomato fruits. Data suggest Sola l 4 as class II allergen. IgE-testing using Sola l 4 showed low clinical specificity, but high sensitivity in tomato allergic patients and will further improve component-resolved allergy diagnosis.

Periodontitis and psoriasis are suggested to be co-occurring, chronic inflammatory conditions with overlapping characteristics. However, respective evidence is rare and data on risk factors of periodontitis in psoriasis patients are minimal. The aim of this study was to expand the evidence of psoriasis-associated periodontitis and establish a potential risk profile for periodontitis. In total, data from 209 exacerbated psoriasis patients were retrospectively analyzed on recordings of periodontitis and compared with those of 91 patients with chronic spontaneous urticaria (CSU). Analysis showed a significantly increased prevalence of periodontitis in psoriasis compared to CSU patients with an odds ratio of 3.76 (95% CI = 1.60-10.27, p = 0.001). Within the psoriatic subtypes, the presence of the inverse type (affecting intertriginous body areas) was strongly linked to periodontitis with an odds ratio of 5.11 (95% CI = 1.36-20.38, p = 0.006). These results are enlarging the evidence for psoriasis-associated periodontitis and identify a link between the inverse type of psoriasis and periodontitis.

Ziele: Mastzellen (MZ) und Nerven spielen eine wichtige Rolle bei allergischer Rhinitis (AR), doch über ihre Interaktion untereinander im Rahmen der AR ist wenig bekannt. Das Ziel dieser Studie war die Untersuchung der Interaktion zwischen MZ und Nerven in der menschlichen Nasenschleimhaut bei AR. Methoden: Die Assoziation zwischen MZ und Nerven, die Expression von Neuropeptid-Rezeptoren (Neurokinin-1-Rezeptor (NK1R), Neurokinin-2-Rezeptor (NK2R), Calcitonin Gene-Related Peptide Receptor (CGRPR) und MrgX2) auf MZ und die Expression von Protease-aktiviertem Rezeptor 2 (PAR2) und Tyrosinkinase-Rezeptor A (TrkA) auf Nervenfasern in der menschlichen Nasenschleimhaut wurden mit Immunfluoreszenz und Echtzeit-PCR untersucht. Ergebnisse: Zwischen MZ und Nerven wurde eine signifikant erhöhte Assoziation festgestellt, obwohl die Anzahl der MZ und Nervenfasern bei AR unverändert war. Tryptase-Chymase exprimierende MZ (MZTC) waren häufig mit Nervenfasern assoziiert, und diese Kontakte lagen bei AR in signifikant erhöhtem Maße vor. Die Neuropeptid Rezeptoren NK1R, NK2R und CGRPR wurden erstmals in hohem Maße auf MZ lokalisiert nachgewiesen. Die Anzahl der NK1R- und NK2R-, nicht aber CGRPR-exprimierenden MZ war bei AR signifikant erhöht. Interessanterweise exprimierten vor allem MZTC diese Neuropeptid-Rezeptoren. Der neu entdeckte Tachykinin-Rrezeptor MrgX2 wurde nicht von den nasalen MZ, aber von Drüsenzellen und bei AR in erhöhtem Maße exprimiert. Darüber hinaus wurde festgestellt, dass tachykinerge Nervenfasern PAR2 oder TrkA als Rezeptoren für MZ exprimieren. Schlussfolgerungen: Diese Studie belegt erstmals eine verstärkte MZ-Nerven-Assoziation und Neuropeptid-Rezeptor-Expression auf MZ bei AR sowie Nervenfasern mit Rezeptoren für MZ. Diese Ergebnisse deuten darauf hin, dass das Targeting oder die Kontrolle der sensorischen Nervenfunktion der Atemwege als Modulator der MZ allergische Atemwegsentzündungen wie die AR verhindern könnte.

Hintergrund Die Implantatallergiedatenlage ist luckenhaft. Deshalb verglichen wir Allergieanamnese, Epikutantest (ECT) und Lymphozytentransformationstest (LTT) einer Patientenserie der Munchner Implantatallergiesprechstunde mit beschwerdefreien Endoprothesentragern.

Patients with lower leg dermatitis, chronic venous insufficiency or chronic leg ulcers have a high prevalence of contact sensitization.To identify the current spectrum of contact allergens in these patients.Data of the Information Network of Departments of Dermatology on 5264 patients with the above diagnoses from the years 2003 to 2014 (study group) were compared with data on 4881 corresponding patients from 1994 to 2003 (historical control group) and with a current control group without these diagnoses (n = 55 510).Allergic contact dermatitis was diagnosed less frequently in the study group than in the historical control group (25.9% versus 16.9%; p 0.001), and contact sensitization to most allergens had declined. The allergen spectrum, however, was largely unchanged. Important allergens are Myroxylon pereirae (balsam of Peru) (14.8% positive reactions), fragrance mix I (11.4%), lanolin alcohol (7.8%), colophonium (6.6%), neomycin sulfate (5.0%), cetearyl alcohol (4.4%), oil of turpentine (3.1%), and paraben mix (2.6%). Patch testing with additional series showed sensitization to Amerchol L-101 (9.7%), tert-butyl hydroquinone (8.7%), framycetin sulfate (5.0%), and gentamicin sulfate (3.1%).Topical preparations for treating the above-mentioned conditions should not contain fragrances, Myroxylon pereirae, and colophonium. The special allergen spectrum has to be considered in patch testing.

Rubber additives constitute an important group of contact allergens, particularly in certain occupations.To collect information regarding the current practice of using a 'rubber series' in Europe, and discuss this against the background of evidence concerning the prevalence of allergy in order to derive a recommendation for a 'European rubber series'.The following were performed: (i) a survey targeting all members of the COST action 'StanDerm' consortium, (ii) analysis of rubber contact allergy data in the database of the European Surveillance System on Contact Allergies, and (iii) a literature review.Information from 13 countries was available, from one or several departments of dermatology, and occasionally occupational health. Apart from some substances tested only in single departments, a broad overlap regarding important allergens was evident, but considerable variation existed between departments.An up-to-date 'European rubber series' is recommended, with the exclusion of substances only of historical concern. A 'supplementary rubber series' containing allergens of less proven importance, requiring further analysis, is recommended for departments specializing in occupational contact allergy. These should be continually updated as new evidence emerges.

Introduction House dust mite (HDM) allergens are major causes for the development of allergic diseases. A disease modifying effect and clinical benefit of allergen immunotherapy (AIT) has been demonstrated in a number of clinical trials. Clinical trials, however, are carried out in selected populations under specific conditions based on inclusion and exclusion criteria and may not represent the entire patient population from medical practice. Objective of this study conducted in patients with HDM allergy was to systematically collect information about the benefit of AIT under clinical routine conditions. Methods In this prospective, multi‐center non‐interventional study, 220 patients (117 adults, 103 children) with HDM allergy receiving subcutaneous AIT with Depigoid® were monitored for 2 years. Organ‐specific key symptoms, health‐related quality of life (QoL), and the use of concomitant anti‐allergic medication were assessed at baseline and after 12 and 24 months. Effectiveness and tolerability of the AIT was assessed by physicians and patients. Occurrence of adverse events (AEs) was continuously monitored. Results Two hundred and nineteen patients (116 adults, 103 children) were evaluated. A major improvement of the total symptom‐score was observed after 24 (12) months in 76% (72%) and 80% (79%) of adults and children, respectively, accompanied by a reduction in concomitant anti‐allergic medication and a pronounced improvement in QoL. The effectiveness and tolerability of the AIT was estimated as very good/good by 80–90% of physicians and patients. AEs were observed in 4/117 adults (3.4%) and in 7/103 children (6.8%). Serious AEs were reported in three adults and one child: A grade‐II anaphylactic reaction (one adult) controlled by oral antihistamines (no hospitalization) classified as “definitely,” three others as not (2) or possibly (1) drug‐related. Conclusions The data collected from 220 patients confirm the efficacy, tolerability/safety, and acceptance of AIT with Depigoid® in adults and children with HDM allergy under routine clinical conditions.

BACKGROUND Contact allergy to rubber additives is common, particularly in patients with occupational dermatitis. OBJECTIVES To descriptively analyse and compare patch test reactions in patients patch tested both with the baseline series and with an additional 'rubber series' as used in the department. METHODS Patch test data from those members of the European Surveillance System on Contact Allergies (ESSCA) network (www.essca-dc.org) who also contributed data on rubber series patch test results were retrospectively analysed. RESULTS Among 29 522 patients patch tested, 2870 were eligible, that is, patch tested both with the baseline series and with a special rubber series. Of these, 8.8% had positive reaction(s) to one of the baseline screening rubber allergens (as compared with 4.2% in all patients), most often to carba mix, 12.3% had positive reaction(s) to allergens from an additional rubber series, and 6.4% had positive reaction(s) to both. CONCLUSIONS Additional testing with a dedicated rubber series, containing break-down single ingredients of mixes from the baseline series and additional rubber allergens, is warranted in patients with suspected contact allergy to rubber, to avoid false-negative results.

Background Most data on chronic spontaneous urticaria (CSU) originate from highly selected patient populations treated at specialized centres. Little is known about CSU patient characteristics and the burden of CSU in routine clinical practice. AWARE (A World-wide Antihistamine-Refractory chronic urticaria patient Evaluation) is an ongoing global study designed to assess chronic urticaria in the real-life setting. Objective To describe the baseline characteristics of the first 1539 German AWARE patients with H1-antihistamine-refractory CSU. Methods This prospective non-interventional study included patients (18-75 years) with a diagnosis of H1-antihistamine-refractory CSU for > 2 months. Baseline demographic and disease characteristics, comorbidities, and pharmacological treatments were recorded. Quality of life (QoL) was assessed using the dermatology life quality index (DLQI), chronic urticaria QoL questionnaire (CU-Q(2)oL), and angioedema QoL questionnaire (AE-QoL, in cases of angioedema). Previous healthcare resource utilization and sick leave data were collected retrospectively. Results Between March and December 2014, 1539 patients were assessed in 256 sites across Germany. The percentage of females, mean age, and mean body mass index were 70%, 46.3 years, and 27 kg/m(2), respectively. The mean urticaria control test score was 7.9, one in two patients had angioedema, and the most frequent comorbidities were chronic inducible urticaria (CIndU;24%), allergic rhinitis (18.2%), hypertension (18.1%), asthma (12%), and depression (9.5%). Overall, 57.6% of patients were receiving at least one pharmacological treatment including second-generation H1-antihistamines (46.3%), first-generation H1-antihistamines (9.1%), and corticosteroids (15.8%). The mean DLQI, total CU-Q(2)oL, and total AE-QoL scores were 8.3, 36.2, and 46.8, respectively. CSU patients reported frequent use of healthcare resources, including emergency services (29.7%), general practitioners (71.9%), and additional allergists or dermatologists (50.7%). Conclusions and Clinical Relevance This study reveals that German H1-antihistamine-refractory CSU patients have high rates of uncontrolled disease, angioedema, and comorbid CIndU, are undertreated, have impaired QoL, and rely heavily on healthcare resources.

Background Chronic spontaneous urticaria (CSU), a mast cell-driven condition, is debilitating, common, and hard to treat. Miltefosine, a lipid raft modulator, can inhibit mast cell responses in vivo. Objective To study the safety and efficacy of systemic miltefosine treatment in CSU patients resistant to standarddosed antihistamines. Methods In this investigator-initiated multicentre, randomized, double-blind, placebo-controlled study, CSU patients were treated for 4 weeks with daily doses of up to 150-mg miltefosine (n = 47) or placebo (n = 26). Disease activity was assessed using the urticaria activity score. Safety and tolerability of miltefosine were also assessed. Results After 4 weeks of treatment, Urticaria Activity Score (UAS7) levels were substantially more reduced in miltefosine-treated patients ()6.3 vs. )3.5 in placebo-treated patients; P = 0.05). Also, the number of weals, but not the intensity of pruritus, was significantly reduced in miltefosine-treated patients vs. placebo-treated patients (P = 0.02). In general, adverse events were frequent in both groups (miltefosine: 88%, placebo: 65% of patients) but mostly mild to moderate in severity. We did not observe any serious adverse events. Conclusions The results of this study indicate that miltefosine is an effective and safe treatment option for CSU

Background. Allergic contact dermatitis caused by rubber gloves is not infrequent, and has almost exclusively been attributed to contact sensitization to accelerators. Thiurams have been the most frequent allergens, followed by dithiocarbamates. Objectives. To describe the current allergen pattern in patients with occupational allergic contact dermatitis caused by rubber gloves. Methods. This study was a retrospective analysis of data from the Information Network of Departments of Dermatology (IVDK), 2002–2010. Results. Of 93 615 patients patch tested in the IVDK, 3448 both suffered from occupational dermatitis and were tested because of suspected glove allergy. Among these, healthcare workers were the largest group (n = 1058). Of all occupational dermatitis patients, 13% were sensitized to thiurams, 3.5% to dithiocarbamates, 3% to mercaptobenzothiazole and/or its derivatives, and 0.4% to thioureas. Positive test reactions to 1,3-diphenylguanidine were seen in 3.0%. Reaction frequencies varied with the years, but showed no uniform time trend. Conclusions. As compared with a former IVDK data analysis (1995–2001), there was no change in sensitization pattern and no decline in sensitization frequencies. This is in line with data from the literature. Particularly in healthcare, there is a need for (i) allergen declaration on the glove package, and (ii) gloves with reduced accelerator content.

Plant profilins are important panallergens, contributing to numerous food and pollen allergies. They fulfil essential functions in all eukaryotic cells, including yeast and mammals, making breeding of profilin-deficient crop plants an impossible task. To obtain hypoallergenic profilin-variants, a novel yeast based screening system to select for fully active but hypoallergenic profilins was developed. Despite similar biological functions, plant profilins share only limited amino acid sequence identity to nonplant profilins. Thus, it should be possible to select for hypoallergenic profilin variants that have kept their biological function. These variants were subsequently tested for IgE-binding and their 3D folding was analyzed. As prerequisites, we developed a conditional profilin-deficient yeast mutant strain and made use of a newly-discovered profilin variant from tomato that enabled pre-selection for efficient mutagenesis. After random mutagenesis and transformation of tomato profilin (Lyc e 1) into the designed yeast strain, we were able to screen for functional tomato profilin variants. Testing these variants for IgE binding revealed that two variants showed a strong reduction in IgE binding of four Lyc e 1 sensitized patients and one birch pollen allergic patient. This result, for the first time, provides strong evidence that selection of hypoallergenic Lyc e 1 variants is possible. Furthermore, this knowledge provides the basis for the molecular breeding of hypoallergenic profilin alleles in tomato.

Background Anaphylaxis is the most severe manifestation of an IgE-dependent allergy. Standardized acquired clinical data from large cohorts of well-defined cases are not available. The aim of this study was to analyse the symptom profile and risk factors of anaphylaxis in a large Central European cohort. Methods We acquired data from patients in Germany, Austria and Switzerland who experienced a severe allergic reaction defined by the onset of severe pulmonary and/or severe cardiovascular symptoms. The data were gained via an online questionnaire from 83 medical centres specialized in allergy. Data were collected from 2006 to 2010 and analysed by using a multinomial regression model. Results A total of 2012 paediatric and adult patients were included into the present analysis. The skin (84%) was the most frequently affected organ followed by the cardiovascular (72%) and the respiratory (68%) system. The regression model analysing the onset of cardiovascular versus respiratory symptoms revealed a strong impact of age (adjusted OR = 6.08; 95% CI, 3.35–11.01; P

BACKGROUND Up to 25% of food allergic subjects in central Europe suffer from carrot allergy. Until now, two isoforms of the major carrot (Daucus carota) allergen Dau c 1 have been described: Dau c 1.01, comprising five variants (Dau c 1.0101-Dau c 1.0105) and Dau c 1.02. OBJECTIVE To investigate potential allergenic properties of a Dau c PRPlike protein, a novel isoform of the PR-10 protein family in carrot. METHODS Dau c PRPlike cDNA from carrot roots (cv Rodelika) was cloned after RT-PCR and 5'RACE. Dau c PRPlike protein was expressed in E. coli, purified under native conditions by Ni-NTA chromatography and analysed by CD spectroscopy. Immuno-reactivity of the rDau c PRPlike protein was compared with rDau c 1.0104 and rDau c 1.0201 in terms of IgE binding (immunoblotting, ImmunoCAP), IgE cross-reactivity (ELISA inhibition) and in vitro mediator release with sera from carrot allergic patients. mRNA expression of Dau c PRPlike protein in wild-type and transgenic carrot roots was analysed by qRT-PCR. RESULTS The Dau c PRPlike protein was identified as a new allergenic isoform, Dau c 1.03, in carrot roots. 68% of carrot allergic patients were sensitized to rDau c 1.03. The IgE-reactivity of rDau c 1.03 strongly correlated with reactivity to rDau c 1.0104, but not to rDau c 1.0201. The extent of IgE cross-reactivity and allergenic potency of Dau c 1 isoforms varied between the individual sera tested. Dau c 1.03 mRNA transcripts were up-regulated in Dau c 1.01 and Dau c 1.02 gene-silenced carrot roots. CONCLUSION AND CLINICAL RELEVANCE Dau c 1 isoforms display distinct IgE epitope heterogeneity. Dau c 1.03 appears to contribute to the allergenicity of carrots and the manifestation of carrot allergy. The epitope diversity of different Dau c 1 isoforms should be considered for component-resolved diagnosis and gene silencing of carrot allergens.

Summary Background: The aim of the CARPE (German acronym: Chronisches Handekzem-Register zum Patienten-Langzeitmanagement; meaning: chronic hand eczema registry on long-term patient management) registry is to investigate characteristics and treatment modalities in patients affected by chronic hand eczema in Germany. Methods: The registry was built up under the auspices of the German Dermatological Society (Deutsche Dermatologische Gesellschaft, DDG). Patients with chronic hand eczema are prospectively assessed by dermatolog-ical examination and patient questionnaire. Socio-economic data and data on diagnostics, skin status, severity and treatment of chronic hand eczema and atopy criteria are repeatedly assessed. Here, we present baseline characteristics of the first 515 patients. Results: 53.8 % of the patients were female, mean age was 47.3 years. The average duration of CHE was 7.7 years. 30.4 % had already received inpatient care, 31.2 % had been on sick leave in the past 12 months. 94.5 % had received topical corticosteroids prior to inclusion in the registry, 31.9 % topical calcineurin inhibitors, 38.3 % UV therapy, 28.6 % systemic antihistamines, 36.5 % systemic treatments, 14.9 % systemic corticosteroids, 25.8 % systemic retinoids. Conclusions: The CARPE project demonstrates the high medical burden and therapeutic challenge of chronic hand eczema and presents first data for health care research. Furthermore, the designed follow-up study will present important data about the natural history and prognosis of this chronic skin disease.

Gene silencing of Lyc e 1 leads to reduced allergenicity of tomato fruits but impaired growth of transgenic tomato plants. The aim of the study was to restore growth of Lyc e 1-deficient tomato plants while retaining reduced allergenicity by simultaneous complementation of profilin deficiency by expression of nonallergenic yeast profilin. Transgenic plants were generated and tested by RT-PCR and immunoblotting; allergenicity of yeast profilin and transgenic fruits was investigated by IgE binding, basophil activation, and skin-prick tests. Lyc e 1 content of transgenic tomato fruits was