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Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with a multifactorial genesis including genetic predispositions and environmental risk and trigger factors. One of the latter possibly is smoking, indicated by an increased prevalence of AD in adults and children that are actively or passively exposed to cigarette smoke. Objectives In this study AD characteristics and its atopic comorbidities are compared in smoking and nonsmoking AD patients. Methods TREATgermany is a non-interventional clinical registry which includes patients with moderate to severe AD in Germany. Baseline data of patients included into TREATgermany from inception in June 2016 to April 2020 in 39 sites across Germany was analyzed comparing AD disease characteristics and comorbidities in smokers versus non-smokers. Results Of 921 patients, 908 (male: 58.7%) with a mean age of 41.9 ± 14.4 reported their smoking status. The objective Scoring of Atopic Dermatitis (oSCORAD) did not differ between smokers (n=352; 38.8%) and nonsmokers, however lesions' intensity of oozing/crusts and excoriations as well as patient global assessment scores (PGA) of AD severity were higher in smoking as opposed to nonsmoking patients. Smokers reported a lower number of weeks with well-controlled AD and more severe pruritus than nonsmokers. Total IgE levels were more elevated in smokers and they displayed a younger age at initial diagnosis of bronchial asthma. After adjustment for potential confounders, the increased intensity of oozing/crusts, the reduced number of weeks with well-controlled AD and the greater pruritus remained different in smokers compared to nonsmokers. In addition, smoking patients with adult-onset AD showed a 2.5 times higher chance of involvement of the feet. Conclusions German registry data indicate that AD patients who smoke have a higher disease burden with a different distribution pattern of lesions in adult-onset AD.

Background Atopic dermatitis (AD) is one of the most common inflammatory skin diseases worldwide and Staphylococcus aureus colonization and secondary infections occur in the majority of AD patients. Allergic sensitizations against microbial antigens have been discussed as possible trigger factors of AD. Recently, we reported IgE sensitization against fibronectin-binding protein 1 (FBP1), an essential virulence component in S. aureus, in a subgroup of patients suffering from AD. To expand these findings by investigating delayed-type immune reactions, the objective of this study was to detect and phenotypically characterize FBP1-specific T cells as possible trigger factors in AD. Methods Immunodominant T-cell epitopes were mapped by proliferation testing of patient-derived FBP1-specific T-cell lines after stimulation with single 15mer peptides, which were derived from different functional domains of the FBP1 sequence. Major histocompatibility complex class II tetramers carrying immunodominant epitopes successfully stained T helper cells in 8 out of 8 HLA-matched, IgE-sensitized AD patients. Results Cytokine profiling of multimer-sorted cells revealed that predominantly the type 2 cytokines IL-13 and IL-4 were secreted by these cells. In contrast, IL-17, the marker cytokine for response to extracellular pathogens, was scarcely detectable. Conclusions We demonstrate that FBP1 contains immunodominant peptides that induce a specific pro-inflammatory T helper cell response with increased Th2 levels that can drive an allergic inflammation in sensitized AD patients.

The coronavirus disease 2019 (COVID-19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi-organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression1 .

The increased permeability of the skin barrier towards environmental factors such as allergens is considered a key factor in the pathogenesis of atopic dermatitis (AD). Strengthening the skin barrier through basic skin therapy represents the basis of any therapy for AD. It is well known that genetic factors as well as the skin inflammation itself contribute to the weakening of the barrier; here, recent studies have led to a deeper understanding of the complex structures of the epidermis. The possibility of counteracting the disease preventively by the use of basic skin therapy from birth on has been studied intensively in recent years. This article summarizes recent findings on the effects of basic skin therapy as a primary and secondary preventive measure.

In chronic skin diseases such as atopic dermatitis (AD), therapeutic failure due to poor patient adherence to treatment is commonly reported. Therapeutic patient education (TPE) is an approach to improve self-management and adherence. Several studies demonstrated that TPE programmes have positive effects on disease management resulting in decreased disease severity and improved quality of life in AD patients. Various healthcare professionals (dermatologists, nurses, psychologists, dieticians) have been involved. TPE performed by trained dermatology nurses are highly efficient and improve various health-related outcomes. The aim of this position paper is to analyse the aims, modalities and efficacy of TPE in AD, to identify specific roles of dermatology nurses, to assess qualification requirements, and to propose practical recommendations. Potential activities of nurses in ongoing and future TPE programmes for AD patients will be discussed.

atopic dermatitis (AD) patients are commonly sensitized to house dust mite (HDM). The current consensus-based European guideline underlines the impact of allergens inducing AD flares and the importance of allergen reduction in AD patients1,2 . With regard to preventive measures in patients with AD, the use of mattress encasings aiming to reduce skin contacts to mite allergens in bed may be considered in HDM-sensitized patients.

Since the introduction of active vaccination against SARS-CoV-2 infection, there has been a debate about the risk of developing severe allergic or anaphylactic reactions among individuals with a history of allergy. Indeed, rare cases of severe allergic reactions have been reported in the United Kingdom and North America. By february 2021 a rate of 4,5 severe allergic reactions occurred among 1 million patients vaccinated with the mRNA-based COVID-19 vaccines, which is higher than the generally expected rate of severe allergic reactions to vaccinations of around 1 in 1 million.

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

This guideline is an update from August 2020 the S2k-guideline "Atopic dermatitis" published in 2015. The reason for updating this chapter of the guideline were the current developments in the field of systemic therapy of atopic dermatitis. The agreed recommendations for systemic treatment in atopic dermatitis of the present guideline are based on current scientific data. Due to the approval of dupilumab for the treatment of moderate to severe atopic dermatitis, which cannot be treated sufficiently with topical drugs alone, this part of the guideline has now been adapted and newly consented. The indication for systemic therapy and the therapeutic response to topical and systemic treatment should be recorded and documented in a suitable form in clinic and practice. A standardized documentation of the indication for system therapy in atopic dermatitis can be recommended and is also part of the updated chapter of this guideline.

Allergic diseases are characterized by a complex complex chronic pathophysiology. Therapeutic patient education (TPE) programs are an important part of health care for allergic patients. These programs aim to increase the patient's adherence to evidence-based treatment and improve their ability to cope with the disease. TPE led by a multiprofessional team covers the complex pathogenesis of the disease, trigger factors, nursing and dietary issues, and the broad variety of treatment options available including psychological and behavioral aspects.Regarding atopic dermatitis (AD), randomized, controlled studies have demonstrated the beneficial effects of delivering structured group training to children, their caregivers, and adult patients with AD. Such intervention achieved substantial improvements in quality of life and objective clinical disease parameters. Besides AD, training programs have also been developed and evaluated for patients with anaphylaxis and asthma. This article provides an overview of the multitude of TPE concepts and their impact on subjective and objective outcomes. It focuses on AD but also sheds light on other allergic diseases such as anaphylaxis and asthma.

Clinical practice guidelines are systematically developed decision aids for specific medical conditions. In Germany, national dermatology guidelines are developed chiefly under the aegis of the German Dermatological Society in collaboration with the Professional Association of German Dermatologists. European and international dermatological guidelines also exist and are developed by a range of organisations, such as the European Centre for Guidelines Development, which was founded by the European Dermatology Forum in 2018. In the years 2019 and 2020, new or updated German national guidelines were published on topics such as pathological scars (hypertrophic scars and keloids), cutaneous lupus erythematosus, pyoderma grangrenosum, anal pruritus, anal eczema, anal canal and anal rim carcinomas, as well as the prevention of HPV-associated neoplasms through vaccination, syphilis and the systemic treatment of neurodermitis. A new European guideline on lichen planus closes a gap in the spectrum of guidelines available in Germany. Key recommendations and relevant changes in the guidelines are presented in this article., Medizinische Leitlinien sind systematisch entwickelte Entscheidungshilfen für die angemessene Vorgehensweise bei speziellen gesundheitlichen Problemen. Dermatologische Leitlinien in Deutschland werden führend von der Deutschen Dermatologischen Gesellschaft in Kooperation mit dem Berufsverband Deutscher Dermatologen herausgegeben. Darüber hinaus werden auch europäische und internationale dermatologische Leitlinien erstellt, u. a. durch das im Jahr 2018 vom European Dermatology Forum gegründete European Centre for Guidelines Development. In den Jahren 2019 und 2020 wurden unter anderem deutsche Leitlinien zu den Themen pathologische Narben (hypertrophe Narben und Keloide), kutaner Lupus erythematodes, Pyoderma gangraenosum, analer Pruritus, Analekzem, Analkanal- und Analrandkarzinome, Impfprävention HPV(humane Papillomviren)-assoziierter Neoplasien sowie Syphilis und Systemtherapie bei Neurodermitis überarbeitet oder neu erstellt. Auf der europäischen Ebene schließt die Leitlinie zum Lichen planus eine in Deutschland noch bestehende Lücke der vorhandenen Leitlinien. Schlüsselempfehlungen und wesentliche Neuerungen in den Leitlinien werden hier vorgestellt.

Die vorliegende Leitlinie ist eine Aktualisierung vom August 2020 zu Systemtherapeutika der 2015 publizierten AWMF-S2k-Leitlinie Neurodermitis. Anlass fur die Aktualisierung dieses Kapitels der Leitlinie waren die aktuellen Entwicklungen zur Systemtherapie der Neurodermitis. In der vorliegenden Leitlinie sind die wissenschaftliche Datenlage und die konsentierten Empfehlungen zur Systemtherapie bei Neurodermitis aufgefuhrt. Aufgrund der Neuzulassung von Dupilumab fur die Behandlung mittelschwer bis schwer ausgepragter Neurodermitis, die mit topischen Medikamenten alleine nicht ausreichend behandelbar ist, wurde dieser Teil der Leitlinie jetzt angepasst und neu konsentiert. Die Indikation zur Systemtherapie und das therapeutische Ansprechen auf die topische und systemische Behandlung sollen in Klinik und Praxis in geeigneter Form erfasst und dokumentiert werden. Eine standardisierte Dokumentation der Indikation zur Systemtherapie bei Neurodermitis kann empfohlen werden und ist ebenfalls Bestandteil des hier vorliegenden aktualisierten Kapitels der Leitlinie.

International audience; Background: Surgery is a radical treatment for hidradenitis suppurativa (HS) and may be considered as the only one potentially curative. Objectives: To characterize HS recurrence in patients after surgery and assess the risk factors of recurrence. Methods: We conducted a monocentric retrospective cohort study. All consecutive patients who had surgery (January 1, 2012 to March 31, 2017) were included. We estimated the rate of recurrence of HS lesions after surgery (

International audience; Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilu-mab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

Background The Atopic Dermatitis (AD) TREATgermany registry was initiated by the German Society for Dermatology (DDG) in 2011 to evaluate the ‘real‐life’ situation of health care for patients with AD. Objectives Interim data analysis on baseline characteristics as well as current and prescribed systemic treatments of the TREATgermany registry patients. Methods Patients (≥18 years) with moderate‐to‐severe AD [objective (o)SCORAD > 20], or with current or previous anti‐inflammatory systemic treatment for AD within 24 months, were included and are followed up over at least 24 months. To assess clinical signs, the eczema area severity index (EASI, 0–72), the oSCORAD (0–83) and the Investigator Global Assessment (IGA; 6‐point scale) were used. The disease severity was globally scored by the patients [Patient Global Assessment (PGA); six‐step Likert scale]. Disease symptoms were assessed by the patient‐oriented eczema measure (POEM, 0–28) and numeric rating scales (NRS, 0–10). Health‐related quality of life was measured using the dermatological life quality index (DLQI, 0–30). Results A total of 612 patients were recruited across 32 sites between 06/2016 and 01/2019 (mean age: 42.6 ± 14.2 years; mean oSCORAD: 40.8 ± 16.3). The mean POEM score was 16.3 ± 7.5. Pruritus was rated highest among subjective symptoms (NRS: 5.4 ± 2.7). The mean DLQI value was 11.3 ± 7.5. The frequency of arterial hypertension was lower (20.8%) compared with the general population, whilst this was higher for depression (10%). More than 60% of the patients had received systemic glucocorticosteroids, and 36.8% had received cyclosporine A prior to inclusion. Dupilumab was the leading substance documented as either ‘current’ (12.1%) or ‘prescribed’ (31.4%) at baseline. Conclusions These ‘real‐life’ data clearly demonstrate the substantial disease burden. Most of TREATgermany patients were already treated with or prescribed dupilumab at baseline. Moreover, current findings indicate the urgent need for further alternative agents in order to achieve a perceptible improvement of quality of life of patients with moderate‐to‐severe AD.

Atopic dermatitis (AD) is a complex disease with elevated risk of respiratory comorbidities.1,2 Severely affected patients are often treated with immune-modulating systemic drugs.3,4 On March 11th 2020, the World Health Organization declared the 2019 novel coronavirus severe acute respiratory syndrome (SARS-Cov-2) epidemic to be a pandemic. The number of cases worldwide is increasing exponentially and poses a major health threat, especially for those who are elderly, immuno-compromised, or have comorbidities. This also applies to AD patients on systemic immune-modulating treatment. In these days of uncertainty, reallocation of medical resources, curfew, hoarding, and shutdown of normal social life, patients, caregivers and doctors ask questions regarding the continuation of systemic immune-modulating treatment of AD patients. The ETFAD decided to address some of these questions here.

Atopic dermatitis (AD) is a disease that can have a high impact on quality of life, especially due to itch and skin pain. This paper utilizes expertise from members of the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force to review the epidemiology, pathophysiology and exacerbating factors of itch and pain in atopic dermatitis. General principles of treatment are provided, as well as a more detailed evaluation of topical and systemic therapies. Educational and psychological approaches to itch and pain in atopic dermatitis are proposed, along with expert recommendations for the management of itch and pain in atopic dermatitis.

Summary Background Parents of school-age children with food allergies and potential anaphylactic reactions want their children to have an unburdened and risk-free everyday school life. Thus, particularly in the case of peanut allergy, demands for peanut-free schools are put forward. Results and discussion The position paper of the food allergy working group of the German Society for Allergology and Clinical Immunology (Deutsche Gesellschaft für Allergologie und klinische Immunologie) highlights why the concept of peanut-free schools does not protect peanut allergic children, but rather bears potential disadvantages and risks for all those involved. The focus on peanut as a potential trigger of anaphylactic reactions ignores other relevant triggers. Conclusion In order to address the fears and concerns of patients, parents, and school staff, it is mandatory to develop various coping strategies. These should enable and ensure the safety and participation of food-allergic pupils in classes and other school activities. Therefore, it is important to implement adequate measures for allergen avoidance and emergency treatment for students with confirmed food allergies.

Background: Clinical registries may provide high-quality evidence on the use and effectiveness of therapeutic interventions under real-life conditions. Adults with moderate-to-severe atopic eczema (atopic dermatitis [AD]) are enrolled into TREATgermany and prospectively followed over at least 2years. This paper analyses the association between dermatological quality of life and work limitations.Materials and Methods: Treatment modalities and abroad set of physician- and patient-reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI [Eczema Area and Severity Index], objective SCORAD [objective-SCORing Atopic Dermatitis]), quality of life (DLQI [Dermatology Life Quality Index]), symptoms (POEM [Patient-oriented Eczema Measure]), global disease severity, as well as patient satisfaction and work limitations including presenteeism (WLQ [Work Limitation Questionnaire]). From 06/2016 until 12/2017, 241 individuals (mean age 43 +/- 15years, 38.6% female) were enrolled at 19recruitment centers;69% of the patients were employed.Results: Employed persons had DLQI and WLQ scores of 10.6 +/- 6.9points and 17.7 +/- 18.1%, respectively. Mean presenteeism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presenteeism scores significantly correlate with DLQI (p

Atopic eczema is a chronic recurrent inflammatory skin disease characterized by intensive pruritus and a high burden of disease. Based on a genetically determined skin barrier dysfunction, xerosis cutis and a tendency towards microbial skin infections are the leading clinical features. Mild and moderate disease manifestations are common, and usually treated with topical agents only. Treatment concepts are usually based on a combination of (i) topical basic therapy consisting of skin cleansing and barrier stabilizing emollients and (ii) topical anti-inflammatory therapy of visible skin lesions with topical corticosteroids and topical calcineurin inhibitors. Proactive therapy of the commonly affected and usually relapsing areas of skin is an important therapeutic option for long-term maintenance treatment of moderate to severe disease. Patients should be actively involved in planning of treatment, which should be adapted to individual patient factors such as age, involved body areas, type of skin lesions, as well as seasonal and climatic factors. New promising treatment options including topical phosphodiesterase inhibitors and topical Janus kinase inhibitors are currently being evaluated in clinical trials and may become a future treatment option for atopic eczema. This review article summarizes the current topical treatment options and new perspectives in the topical therapy of atopic eczema.

In schweren Fallen einer atopischen Dermatitis (AD) ist eine Systemtherapie indiziert. Bislang waren fur diese Indikation lediglich Ciclosporin und systemische Glukokortikosteroide zugelassen. Daneben liegen mittlerweile positive Erfahrungen aus der Praxis zum (Off‑label‑)Einsatz von weiteren Wirkstoffen, wie Mycophenolsaure, Methotrexat, Alitretinoin, Azathioprin und Ustekinumab, vor. Intensive Forschungsbemuhungen zielen auf ein besseres Verstandnis im Hinblick auf genetische und immunologische Faktoren dieser chronisch-entzundlichen Hauterkrankung ab. Dabei wurden kurzlich fur eine Behandlung mit Mycophenolsaure relevante Genpolymorphismen bei Patienten mit AD identifiziert, die ein Therapieansprechen auf diesen Wirkstoff vorhersagen konnten. Derzeit befindet sich eine Vielzahl vollig neuer Wirksubstanzen in der klinischen Erprobung, die spezifisch in das Entzundungsgeschehen bei AD eingreifen und fur die erste vielversprechende Behandlungseffekte auf den Hautzustand bzw. die Juckreizsymptomatik bei AD beobachtet werden konnten. Als ein herausragendes Ergebnis dieser Entwicklungen wurde im September dieses Jahres in Europa und damit auch in Deutschland erstmals ein Biologikum als „First-line“-Therapie fur die Indikation einer mittelschweren bis schweren AD im Erwachsenenalter zugelassen: Dupilumab ist ein humaner monoklonaler Immunglobulin(Ig)G4-Antikorper und blockiert eine Untereinheit sowohl des Interleukin(IL)-4- als auch des IL-13-Rezeptors, sodass die Wirkung dieser beiden fur die akute Krankheitsphase bei AD entscheidenden Zytokine gehemmt wird. Aber auch das IL-13 selbst, der fur den Juckreiz bei AD relevante IL-31-Rezeptor, der Histamin-4-Rezeptor und Januskinasen stellen neue therapeutische Zielstrukturen klinischer Studien zur Behandlung der AD dar.

Die atopische Dermatitis (AD) ist eine chronisch entzundliche Hauterkrankung mit einer 1‑Jahres-Pravalenz im Erwachsenenalter von 2–3 %. Zur Verbesserung der ambulanten Versorgungssituation dieser Patienten wurde durch die Arbeitsgemeinschaft Neurodermitisschulung im Erwachsenenalter (ARNE) im Rahmen einer nationalen randomisierten, kontrollierten Multicenterstudie mit Wartekontrollgruppendesign ein Programm zur strukturierten Schulung im ambulanten Setting entwickelt und evaluiert. Die Teilnahme an dieser 12-stundigen, interdisziplinar geleiteten Kleingruppenschulung fuhrte bei den Patienten (n = 168) im Vergleich zur Wartekontrollgruppe (n = 147) 1 Jahr nach Teilnahme an der Schulung zu einer signifikant starkeren Verbesserung sowohl der Coping-Strategien im Hinblick auf Juckreiz (erfasst anhand des Juckreiz-Kognitions-Fragebogens, p

Background Dental technicians (DTs) are at increased risk for allergic contact sensitization. Objectives To assess the current spectrum of occupational sensitization in DTs with occupational contact dermatitis (OCD). Methods A retrospective analysis of Information Network of Departments of Dermatology patch test data from the years 2001-2015 concerning DTs with OCD was performed. Results Patients of the study group (226 DTs with OCD) were significantly more often diagnosed with allergic contact dermatitis (37.6% versus 18.5%; p = 0.0002) than patients of the control group (124 DTs without OCD). In the study group, positive reactions were most frequently observed to methacrylates and/or acrylates (n = 67). Of these, 61 patients showed positive reactions to at least one of the five most frequent allergens in this group, namely 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, methyl methacrylate, ethyl methacrylate, and/or ethylene glycol dimethacrylate. In contrast, no positive reactions to diurethane dimethacrylate (DUDMA) occurred. Among allergens of the German Contact Dermatitis Research Group series 'dental metals', positive reactions were less frequent and were mainly to palladium chloride (n = 6). Conclusions The present data analysis showed that the sensitization spectrum and spectrum of cross-reactivity are largely unchanged as compared with the 1990s. It can be concluded that test recommendations are still valid and useful, except for the methacrylate DUDMA, which could be omitted.

Atopic dermatitis is a chronic inflammatory skin disease with a complex pathogenesis and different exogenous and endogenous trigger factors. One important factor is the sensitization to inhalant and/or food allergens. The detection of total IgE and specific IgE antibodies to inhalant and/or food allergens is one central aspect in diagnosing atopic dermatitis, especially if skin prick tests are not feasible. Many patients are polysensitized, but not all sensitizations are of clinical relevance. The challenge is to identify the sensitizations with clinical relevance and to initiate suitable therapeutic options. In this article we go into detail for the allergens house dust mite, pollen, food, and Malassezia sympodialis. Furthermore, the authors comment on the impact of the detection of specific IgG/IgG4 antibodies in the diagnosis of food allergy in atopic dermatitis. Moreover, new options in the in-vitro diagnostic will be explained briefly and their actual diagnostic significance in patients with atopic dermatitis will be highlighted. These options are the detection of specific IgE antibodies to recombinant allergens and the allergen chip.

SummaryBackground Textile dyes, rubber, elements or textile resins carry the risk of inducing allergic contact sensitization. Objectives To assess clinical data and patch test results for dermatitis patients with suspected textile allergy. Methods A retrospective analysis of Information Network of Departments of Dermatology data of the years 2007–2014 of patients patch tested because of suspected textile allergy was performed. Results Patients of the study group (n = 3207) suffered more frequently from leg, trunk and generalized dermatitis than patients of the control group (n = 95210). Among the allergens of the textile dye series, the highest frequency of positive reactions was observed for p-aminoazobenzene (5.1%) and p-phenylenediamine (PPD) (4.5%), followed by Disperse Orange 3 (3.1%), Disperse Blue 124 (2.3%), Disperse Blue 106 (2.0%), Disperse Red 17 (1.1%), and Disperse Yellow 3 (1.1%), partly with concomitant reactions. Patch testing with the patients' own textiles was performed in 315 patients, with positive reactions in 18 patients. These were mostly elicited by blue or black textiles with tight skin contact. Only 2 of these patients also reacted to textile dyes from the German Contact Dermatitis Research Group series. Conclusions For the comprehensive diagnosis of contact sensitization in patients with suspected textile dermatitis, combined patch testing is indicated, with (i) PPD and a textile dye series and (ii) patients' own clothing.

Purpose of review This review summarizes the mode of action of IL-4 and IL-13 in skin allergy, upcoming therapeutics and depicts key outcomes of the latest clinical trials. Recent findings Atopic dermatitis is considered to be one of the most common inflammatory skin disease in industrialized countries. Accompanied by strong pruritus, atopic dermatitis has a significant impact on quality of life in severely affected individuals. Aside from unspecific immunosuppressant medications, therapeutics targeting the key cytokines IL-4 and IL-13 and their downstream mediators are under development or have been approved just recently with outstanding potential. Summary The recent development of several biologics and small compounds has the potential to revolutionize the treatment of atopic dermatitis, and applying this set of state-of-the-art drugs will provide a unique chance to gain insights into this skin disorder, patient subgroups, and key inflammatory mediators.

Dermatoscopes are routinely used in skin cancer screening but are rarely employed for the diagnosis of other skin conditions. Broader application is promising from a diagnostic point of view as biopsies for differential diagnosis may be avoided but it requires non-contact devices allowing a comparably large field of view that are not commercially available today. Autofocus and color reproducibility are specific challenges for the development of dermatoscopy for application beyond cancer screening. We present a prototype for such a system including solutions for autofocus and color reproducibility independent of ambient lighting. System performance includes sufficiently high feature resolution of up to 30 &micro, m and feature size scaling fulfilling the requirements to apply the device in regular skin cancer screening.

Background: Altered quantities, activity, and composition of natural killer (NK) cells in blood as well as expression changes of genes involved in NK-cell function in skin lesions of patients with atopic dermatitis (AD) were recently reported. Objectives: We sought to comprehensively analyze cutaneous NK-cell transcriptomic signatures in AD, and to examine changes under treatment. Methods: We analyzed NK-cell signatures in skin transcriptome data from 57 patients with moderate to severe AD and 31 healthy controls. In addition, changes after 12 weeks of systemic treatment (dupilumab n = 21, cyclosporine n = 8) were analyzed. Deconvolution of leucocyte fractions was conducted. Immunofluorescence staining of NK cells was performed on paraffin-embedded skin sections. Results: Immunofluorescence staining revealed a relatively high abundance of both NK cells and CD3+ CD56+ cells in lesional as compared with nonlesional and healthy skin. Lesional and to a lesser extent nonlesional skin showed a strong upregulation of NK-cell markers together with a dysbalanced expression of inhibitory and activating receptors, which was not reverted under treatment. Digital cytometry showed a decrease in activated and an increase in resting NK cells in both lesional and nonlesional skin, which was reverted by both treatment with dupilumab and cyclosporine. The NK-cell transcriptomic signature remained upregulated after treatment, but there was a shift on the qualitative level, indicating a compositional change in NK-cell subsets toward CD56bright NK cells. Conclusions: Lesional AD skin shows a NK-cell dysregulation, which despite clinical improvement under systemic therapy was only partially reverted, and which may represent a yet underappreciated disease mechanism

Bei dem Krankheitsbild der Neurodermitis handelt es sich um eine chronische oder chronisch-rezidivierende nicht kontagiose, entzundliche Hauterkrankung mit in der Regel starkem Juckreiz. Daruber hinaus besteht ein Risiko fur komplizierte Verlaufe mit bakteriellen oder viralen Superinfektionen. Sowohl die genetische Pradisposition als auch zahlreiche Auslosefaktoren spielen fur die Erst manifestation und das Auftreten der Erkrankungsschube eine wichtige Rolle, sodass auch das Therapiekonzept vielfaltig ist. Bei zahlreichen fur die Neurodermitis zur Verfugung stehenden Behandlungsoptionen gilt es, in Abstimmung mit den Patienten beziehungsweise Eltern erkrankter Kinder fallorientiert einen optimalen Behandlungsplan aufzustellen, der im Verlauf gegebenenfalls erneut angepasst werden muss. Die vorliegende Kurzfassung der S2k-Leitlinie gibt einen Uberblick uber alle bisher zur Verfugung stehenden, evidenzbasierten Diagnoseverfahren und Therapiemoglichkeiten sowie uber die entsprechenden Empfehlungen, die durch die an dieser Leitlinie beteiligten Fachgesellschaften und Verbande ausgesprochen werden. Diese Empfehlungen wurden auf der Grundlage der bislang zu dem jeweiligen Verfahren vorliegenden klinisch-wissenschaftlichen Datenlage, die in der ausfuhrlichen Fassung dieser Leitlinie (unter www.awmf.org und jddg.org) beschrieben ist, konsentiert.

Autoreactivity may play a critical role in the chronification of atopic dermatitis (AD). Several studies showed that AD patients produce IgE Abs specific for autoantigens, and we described Th as well as CD8+ T cells specific for the autoallergen Hom s 2, the α-chain of the nascent polypeptide-associated complex (α-NAC). This study aimed to investigate the frequency and inflammatory phenotype of autoallergen-specific CD8+ T cells. CD8+ T cell immunodominant epitopes of α-NAC were mapped by applying prediction softwares, and binding affinity was confirmed by stabilization of empty MHC complexes. MHC class I tetramers were assembled and binding cells were analyzed directly ex vivo by flow cytometry and in terms of single-cell assessment by ChipCytometry. We report significantly elevated numbers of α-NAC–specific peripheral T cells in sensitized patients compared with nonatopic controls. These cells secrete IL-4 and IFN-γ, and surface markers revealed significantly elevated frequencies of circulating terminally differentiated α-NAC–specific CD8+ T cells in patients with AD compared with nonatopic donors. The observed phenotype of α-NAC–specific CD8+ T cells indicates a role in the pathogenesis of AD.

BACKGROUND Previous studies have indicated that in patients with atopic dermatitis (AD) and birch pollen allergy pollen-related foods are able to cause late eczematous response. However, the relevance of AD worsening by ingestion of birch pollen-related foods is still a matter of debate. OBJECTIVE The purpose of this retrospective study was to determine how frequently birch pollen-related foods induce a deterioration of eczema. Additionally, the diagnostic value of specific IgE (sIgE) determination was evaluated. METHODS A total of 182 children and adults with AD and suspected birch pollen-related food allergy underwent 261 double-blind placebo-controlled food challenges (DBPCFC). Total and sIgE levels were determined prior to DBPCFC. RESULTS Sixty-five patients developed allergic reactions (responders) upon DBPCFC with birch pollen-related foods (n = 103 DBPCFC). Of these, 32 patients exhibited significant deterioration of AD defined as a median increase of 15.4 severity scoring of atopic dermatitis index points (95% CI 12.4-16.3) from baseline making up 37% of all positive reactions. Responders showed significantly higher sIgE levels to birch pollen and apple as well as a higher prevalence of allergic rhinoconjunctivitis compared to nonresponders (P

Patient education in atopic dermatitis (AD) represents an essential therapeutic tool, which should be offered in addition to routine care, since previous studies have revealed that AD outpatients are often insufficiently treated and show severe limitations of quality of life. Considering the multifactorial pathogenesis of this chronic skin disease, the success of therapeutic patient education seems to depend on the involvement of a multidisciplinary team of professionals. The training program should include aspects on dermatology and allergy, but also on diet and nursing, as well as on disease-specific psychological issues. Synergistic beneficial effects upon interaction between affected patients or parents should be considered by performing the training in small groups. The overall aim of therapeutic patient education in AD should be an improvement of self-management strategies to finally achieve a decrease in disease severity and an increase in quality of life. For children (and their parents) and adolescents with AD, successful programs have already been developed. However, in many countries, there is still a need for official recommendations in order to regulate reimbursement for the costs of such programs. Since the preliminary results from pilot studies in adults have been promising, further large controlled trials on patient education in this age group are needed to finally improve outpatient care also in adulthood AD.

Resistance to bacterial skin infections, for example with Staphylococcus aureus (S. aureus), is based on the function of intact innate immune mechanisms. Toll-like receptor (TLR)-2 recognizes components of S. aureus and is known to be expressed on monocytes. Staphylococcal exotoxins such as staphylococcal enterotoxin B (SEB) or α-toxin are produced by many S. aureus strains. To investigate TLR-2 regulation and function on human monocytes upon stimulation with staphylococcal exotoxins to elucidate a putative feedback loop between different staphylococcal components. Monocytes were stimulated with α-toxin or SEB, respectively. TLR-2 expression and regulation as well as functional effects of TLR-2 stimulation with Pam3Cys (TLR-2/TLR-1), lipoteichoic acid (LTA) (TLR-2/TLR-6) and peptidoglycan (PGN) (TLR-2 and Nod) were then investigated both at the mRNA and protein level and compared to monocytes from patients with psoriasis. α-toxin significantly upregulated TLR-2 expression. TLR-2 mediated IL-1β, IL-6 and IL-8 secretion was significantly augmented after upregulation with staphylococcal exotoxins. CD36 expression was significantly more downregulated after TLR-2 upregulation with SEB and consecutive LTA stimulation and TLR-2 upregulation with α-toxin following LTA and PGN stimulation, respectively. PGN enhanced CD54 expression after upregulation of the receptor with α-toxin. Expression of HLA-DR was unaffected. However, no differences were observed in monocytes from psoriasis patients compared to healthy controls. Together, our findings provide a new link between staphylococcal α-toxin and TLR-2 signalling in monocytes which may have implications for skin diseases where skin colonization with S. aureus and dysregulation of TLR-2 have been described.

The pathogenesis of atopic dermatitis (AD) is multifactorial and complex. Consequently, clinical signs and symptoms vary strongly depending on individually relevant trigger factors and the stage of the disease. So far, treatment of AD was commonly limited to topical treatment or, in more severe cases, to systemic drugs mostly approved for other indications than AD. However, emerging data on new anti-inflammatory agents have been published in the recent years. As these new substances specifically focus on immune responses in AD, these are partially considered as possible 'breakthrough' in the treatment of AD. Therapeutic strategies of the future appear to be 'customized' for inflammation in AD as they target pro-inflammatory, highly relevant cytokines and cytokine receptors, such as IL-4Rα, IL-13, IL-31, and IL-17. Further innovative therapeutic approaches aim to block the function of relevant molecules such as thymic stromal lymphopoietin, chemoattractant-receptor homologous molecule expressed on Th2 lymphocytes (CRTh2), and phosphodiesterase (PDE)-4 inhibitors. Recently, anti-inflammatory effects in AD by antagonizing the histamine (H)-4 receptor have also been detected. Finally, specific immunotherapy is under further investigation as treatment option for AD patients with clinically relevant sensitization.

Purpose of review Atopic dermatitis is a chronic relapsing inflammatory skin disease. In the presence of a complex genetic background, there is increasing evidence for the role of specific allergenic trigger factors in perpetuating skin inflammation in sensitized atopic dermatitis patients. In this review, clinical and in-vitro data so far published on allergen-induced adaptive immune responses in atopic dermatitis are summarized. Recent findings Emerging new data have been published particularly on adaptive immune responses to inhalant allergens in atopic dermatitis. In a randomized controlled study, the induction of a flare-up by grass pollen exposure in sensitized atopic dermatitis patients could be demonstrated for the first time. T cells directed to the two major allergens of house dust mite have been characterized to display a Th2, and moreover, a Th17 and Th2/Th17 phenotype in sensitized atopic dermatitis patients. With regard to microbial antigens, T cell-mediated immune responses directed to proteins of the species themselves can be observed - as has been published for Staphylococcus aureus and Malassezia spp. Beyond this, specific T-cell activation to cross-reacting human proteins might further trigger the disease in distinct patients. The role of 'autoallergic' phenomena in atopic dermatitis, because of human antigens without known cross-reactivity to environmental allergens, is currently under investigation as well. Summary Recent findings on immunological and clinical characteristics of adaptive immune responses to allergens in atopic dermatitis, but also on the identification of new, potentially relevant allergen sources might contribute to the development of effective treatment strategies 'customized' for allergic inflammation in atopic dermatitis in future.

In atopic dermatitis (AD), the skin inflammation is believed to occur due to a misdirected immune reaction against harmless antigens on the one hand, and to a disturbed skin barrier on the other. In recent years, vast efforts have been made to investigate the relevance and details of the immune response to allergens. Clinically, it was demonstrated for the first time that aeroallergen exposure leads to worsening of AD symptoms. An overexpression of Th2 cytokines has been observed in acute and subacute lesions of AD. The clinical impact of the key Th2 cytokines IL-4 and IL-13 on atopic dermatitis has recently been shown in clinical studies with dupilumab, a monoclonal antibody which blocks the IL-4/IL-13 receptor. In vitro data indicate, however, that the T cell response is not solely Th2-polarized but may lead to heterogeneous cytokine production involving IFN-γ and IL-17 in an allergen-dependent manner. Classical thymus-derived Foxp3 T cells have interestingly been detected in elevated numbers in the circulation of AD patients. Therapeutic approaches with allergen specific immunotherapy aim to induce regulatory T cells of the Tr1 type. The strikingly altered microbiome of AD skin with diminished diversity of bacteria on lesional skin but increases of S. aureus colonization and the sensitization against microbial allergens and homologue self-proteins deserve special attention. For the treatment of itch symptoms, which still represent a challenge in daily practice, promising data have been published on the relevance of the H(histamine)4-receptor and on mediators such as IL-31, TSLP.

Von Nahrungsmittelallergien sind deutlich mehr Kinder als erwachsene Patienten mit atopischer Dermatitis (AD) betroffen. Sensibilisierungen in fruhester Kindheit sind signifikant haufiger mit einer AD assoziiert. Drei verschiedene klinische Reaktionsmuster sind bei Patienten mit AD zu unterscheiden: i. eine Soforttypreaktion, ii. eine isolierte Spattypreaktion, iii. kombinierte Reaktionen (i + ii). Wahrend Kinder allergische Reaktionen v. a. gegen Grundnahrungsmittel sowie Erdnuss oder Baumnusse aufweisen, scheinen bei erwachsenen Patienten aus Mittel- und Nordeuropa die birkenpollenassoziierten Nahrungsmittel eine grosere Rolle zu spielen. Defekte der Hautbarrierefunktion scheinen die Entwicklung einer Sensibilisierung gegenuber Allergenen nach vorausgegangenem epikutanem Kontakt zu erleichtern. Zur klinischen Relevanz von Defekten der Darmbarriere ebenso zu genetischen Charakteristika, die mit einem erhohten Risiko der Entstehung einer Nahrungsmittelallergie assoziiert sind, sind weitere Untersuchungen erforderlich. Etliche Studien legen den Schwerpunkt auf hinlangliche Praventionsstrategien, wie z. B. aktuell Stillen oder Ernahrung mit hydrolysierter Milchersatznahrung in den ersten 4 Lebensmonaten.

The complement system has emerged as a bridge between innate and adaptive immune responses. An involvement of C3aR has been described during skin inflammation. The aim of the study was to investigate the role of C3a in a mouse model of allergic skin inflammation, such as allergic contact dermatitis (ACD) which is a clinical manifestation of contact sensitivity (CS). The sensitization phase was studied using the local lymph node test: Mice were sensitized on three consecutive days by application of non-irritant concentrations of toluene-2,4-diisocyanate (TDI; 0.5%) onto the ear skin. On day 5, auricular draining lymph nodes were obtained. The elicitation phase was investigated by sensitization with TDI on the depilated and tape-stripped abdominal skin and challenge with TDI on the ear skin and measuring of ear swelling in vivo and cytokine secretion in activated splenocytes in vitro respectively. Complement 3a receptor deficient (C3aRKO) mice showed increased cytokine responses (interleukin[IL]-5, IL-6, IL-17, granulocyte macrophage-colony stimulating factor [GM-CSF]) in the sensitization phase of ACD to TDI. However, no differences in CS responses to TDI were observed in C3aR KO mice compared with WT controls in the elicitation phase of ACD as assessed by measuring of ear swelling in vivo and cytokines in skin and in activated splenocytes in vitro, namely IL-1α, IL-2, IL-4, IL-5, IL-6, IL-10, IL-17, interferon-γ (IFN-γ), GM-CSF and tumor necrosis factor (TNF)-α. These findings provide a new insight into the participation of C3a in the sensitization phase of CS immune responses.

Grosere retrospektive Studien zeigen, dass epikutane Sensibilisierungen bei atopischen und nichtatopischen Patienten ahnlich haufig vorkommen. Auch bei Kindern und Jugendlichen scheint die Wahrscheinlichkeit fur eine epikutane Sensibilisierung unabhangig von der Diagnose einer atopischen Dermatitis (AD) zu sein. Hingegen sind Patienten mit einer AD nach einer neueren Untersuchung in der Gruppe der polysensibilisierten Patienten uberreprasentiert. Als mogliche Risikofaktoren fur eine epikutane Sensibilisierung bei AD wurden das Vorliegen IgE-vermittelter Sensibilisierungen und die Krankheitsdauer bzw. ein fruher Krankheitsbeginn bei AD identifiziert. Ferner fordert eine gestorte Hautbarriere bei AD die Penetration von Kontaktallergenen und Irritanzien in die Epidermis und stellt einen wichtigen Kofaktor fur die Sensibilisierung dar. Es konnte eine Assoziation zwischen dem Vorliegen von Mutationen im Filaggrin-Gen bei AD und einer klinisch relevanten Sensibilisierung gegenuber Nickel, nicht jedoch gegenuber anderen Kontaktallergenen nachgewiesen werden. Weitere prospektive Studien an grosen Patientenkohorten sind notwendig, um den Zusammenhang zwischen gestorter Hautbarriere bei AD und dem Risiko der Entstehung einer Kontaktallergie naher zu untersuchen.

In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus (S. aureus). Resistance to bacterial skin infections, e.g. S. aureus, is based on the function of intact innate immune mechanisms in the epidermis, mainly provided by keratinocytes. Toll-like receptor (TLR)-2 recognizes components of S. aureus and is known to be expressed on keratinocytes. The aim of this study was to investigate intrinsic TLR-2 expression and cytokine secretion upon TLR-2 stimulation with peptidoglycan (PGN), lipoteichoic acid (LTA) and N-palmitoyl-S-[2,3-bis(palmitoyl)-(2RS)-propyl]-(R)cysteinyl-alanyl-glycine (Pam3Cys) in keratinocytes from patients with AD compared to healthy controls. Human primary keratinocytes (HPKs) were cultivated from hair follicles of patients with AD and non-atopic healthy controls and stimulated with Pam3Cys, LTA and PGN. TLR-2, TLR-1 and TLR-6 expression were investigated at the mRNA level. IL-6, IL-8, chemokine C-C motif ligand (CCL)-20 and MMP-9 production were studied at the protein level. TLR-2, TLR-1 and TLR-6 were expressed on both HPKs from patients with AD as well as healthy controls without significant differences between these groups. HPKs from patients with AD had an intrinsically reduced capacity to produce IL-6, IL-8, CCL-20 and MMP-9 and responded less to TLR-2 stimulation compared to HPKs from healthy controls. Our findings show evidence for intrinsic alterations in HPKs from patients with AD compared to healthy controls and diminished responses upon TLR-2 stimulation that might contribute to the enhanced susceptibility to skin infections with S. aureus.

Summary Background A subgroup of patients with atopic dermatitis (AD) produces IgE autoantibodies to human proteins which may be present in inflamed skin and perpetuate cutaneous inflammation. Objectives In order to investigate mechanisms of ‘autoallergy’ for AD we studied T-cell responses to the autoallergen Hom s 2, the human transcriptional coactivator α-nascent polypeptide-associated complex (α-NAC). Methods Specific proliferation of blood lymphocytes from 30 patients and 12 healthy control individuals was investigated by flow cytometry. The proliferation of skin- and blood-derived T cells was assessed in limiting-dilution assays. T-cell clones (TCC) were generated from peripheral blood and from biopsies of lesional skin of patients with AD and the phenotype and cytokine patterns were determined. Results α-NAC-specific T-cell responses were detected in patients and control individuals. α-NAC induced a significantly higher proliferation of CCR4+ (compared with CCR4−) and CLA+ (compared with CLA−) T cells from the circulation. Limiting-dilution assays revealed a high proliferation of blood and skin-infiltrating lymphocytes in the presence of α-NAC compared with control cultures. α-NAC-specific TCC generated from lesional skin of AD predominantly produced interferon-γ and some TCC also produced interleukin-17. The cytokine pattern of α-NAC TCC may contribute to keratinocyte apoptosis and eczema formation in AD. Conclusions α-NAC-specific TCC can be generated from blood and lesional skin of patients with AD. These TCC produce not only Th2 but also Th1 cytokines which may explain the Th1 phenotype of inflammation in AD.

Background: Patients with atopic dermatitis (AD) are frequently colonized with α-toxin-producing Staphylococcus aureus which is in turn positively correlated with the severity of eczema. Methods: In this study we addressed T cell proliferation and T cell as well as monocyte cytokine secretion upon α-toxin stimulation in peripheral blood mononuclear cells (PBMCs) from AD patients compared to healthy controls. Results: We found that α-toxin stimulation of PBMCs markedly enhanced T cell proliferation both in patients with AD and healthy controls and was significantly increased in AD patients compared to healthy controls. PBMCs of AD patients secreted significantly more IL-31 compared to those of healthy controls upon α-toxin and SEB stimulation. Moreover, α-toxin stimulation yielded an increase in T cell (IL-2, IL-9, IL-10 and IFN-γ) as well as monocyte (IL-1β and TNF-α) cytokine secretion. Conclusion: Our results could partly explain how skin colonization and infection with S. aureus can contribute to chronic skin inflammation and pruritus in AD.