Search

Background: Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation. Methods: By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnr −/− ) mouse model lacking both genes including the intergenomic sequence. Results: Neonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnr −/− mice displayed a markedly reduced granular layer and a condensed cornified layer. Functionally, FlgHrnr −/− mice showed permeability abnormalities and metabolic aberrations regarding the production of natural moisturizing factors (NMFs) in the stratum corneum. Surprisingly, although the immune system revealed no aberrations under steady-state conditions, FlgHrnr −/− mice are predisposed to mount an allergic contact dermatitis, especially at hapten threshold levels eliciting allergic reactions. Conclusions: Together, our FlgHrnr −/− mouse model nicely reflects the epicutaneous sensitization susceptibilities and inflammatory reactions to environmental insults in humans with impaired skin barrier functions.

Background Studies on patch testing with workplace materials and evaluation of current occupational relevance of positive patch test reactions are scarce in patients with occupational dermatitis (OD). Objectives To identify frequent sensitizations with occupational relevance and to determine the value of patch testing with workplace materials in OD patients. Patients and methods Results and clinical data of 654 patients with suspected OD patch tested between 2013 and 2017 were analysed. Results Occupational allergic contact dermatitis was diagnosed in 113 (17.3%) patients. Mechanics had the widest range of occupational sensitizations. Sensitization to epoxy resin was rated occupationally relevant in almost all handicraft trades. Among positive patch test reactions to workplace products, those to water-based metal working fluids and leave-on cosmetic products were most frequent. Despite frequent testing, protective gloves only rarely elicited positive reactions. Preservatives and rubber compounds were most frequently identified as currently occupationally relevant. Conclusions Rubber allergy is occupationally relevant especially in healthcare workers and cleaners. Generally, preservatives including formaldehyde releasers are important allergens in OD patients. Leave-on cosmetic products must not be forgotten as allergen sources. Patch testing both workplace materials and standardized test preparations has a complementary value and is beneficial for the diagnostic work-up of OD patients.

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.

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

Background Metalworkers occupationally exposed to metals, tools, metalworking fluids (MWFs), technical oils, gloves, skin care products etc. frequently suffer from occupational dermatitis (OD). Objectives To investigate occupational exposure and to identify relevant occupational sensitizers in metalworkers with OD, and to evaluate suitability of current German patch test recommendations for this occupational group. Patients and methods As part of the OCCUDERM project, occupational exposure of 230 metalworkers with suspected OD patch tested in the departments of dermatology in Gottingen and Osnabruck (both Lower Saxony, Germany) in 2012-2017 was recorded by questionnaire. These data, as well as results, of patch testing with standardized allergens and with workplace material were analysed. Results Metalworking fluids and skin care products were the most important exposures. Among MWF allergens, most frequently sensitizations to formaldehyde and formaldehyde releasers, colophony/abietic acid and monoethanolamine were observed. Sensitization to methylisothiazolinone (MI) was frequent, probably as part of the general European epidemic of contact allergy to MI in leave-on cosmetics. Sensitization to glove ingredients only played a minor role. Conclusions The known occupational allergen spectrum could largely be confirmed. In order not to miss relevant sensitizations, patch testing with material from the patients' workplaces in parallel to baseline and MWF series is recommended. Sensitizations diagnosed could not always be linked to particular occupational exposures.

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 AD are enrolled into TREATgermany and prospectively followed over at least 2 years. The paper analyses the association between dermatological quality of life and work limitations. Materials and methods: Treatment modalities and a broad set of physician and patient reported outcome measures are documented using validated instruments to assess clinical disease severity (EASI, objective SCORAD), quality of life (DLQI), symptoms (POEM), global disease severity, as well as patient satisfaction and work limitations including presentism (WLQ). From 06/2016 until 12/2017. 241 individuals (mean age 43 +/- 15 years. 38.6% female) were enrolled at 19 recruitment centers. 69% of them were currently employed. Results: Employed persons had DLQI and WLQ scores of 10.4 +/- 6.9 points and 17.7 +/- 18.1%, respectively. Mean presentism was substantial accounting for 9.2%. With coefficients of 0.39 and 0.33 WLQ and presentism scores significantly correlate with DLQI (p < 0.000). Bootstrapped regression models showed that the limitations in coping with work requirements increase by 1.7% as DLQI increases by one point. Lower quality of life due to AD is most strongly associated with limitations in the area of physical and performance requirements in general. Presentism decreases by 0.5% as DLQI increases by one point. Conclusion: Moderate-to-severe AD has substantial adverse economic impact with mean productivity loss of patients of almost 10%. Future analyses from TREATgermany will address the impact of innovative treatment modalities on quality of life and work productivity of patients with moderate-to-severe AD., Hintergrund: Klinische Register tra- gen zur Evidenzbasierung der Gesund- heitsversorgung und zur Umsetzung von Forschungsergebnissen in die Praxis bei. TREATgermany schließt Erwachsene mit moderater bis schwerer Neurodermitis (AD) mit prospektiver Beobachtung über min- destens 2 Jahre ein. Der Beitrag zeigt ers- te Ergebnisse zum Zusammenhang von krankheitsbezogener Lebensqualität und Leistungseinschränkungen im Beruf. Ma- terial und Methoden: Dokumentiert werden objektive und subjektive Outcomes mit vali- dierten Messinstrumenten: klinischer Schwe- regrad (EASI, oSCORAD), Lebensqualität (DLQI), Symptome (POEM), globaler Schweregrad (IGA/PGA), Patientenzufrie- denheit und berufsbezogene Leistungsein- schränkungen (WLQ) inkl. Präsentismus (Produktivitätsverlust bei der Arbeit) so- wie der Therapieverlauf. 06/2016 – 12/2017 wurden 241 Patienten (Alter 43 ± 15 Jahre; 38,6% Frauen) in deutschlandweit 19 Zent- ren eingeschlossen, 69% waren berufstätig. Ergebnisse: Erwerbstätige hatten DLQI- und WLQ-Mittelwerte von 10,4 ± 6,9 Punkten bzw. 17,7 ± 18,1%. Der mittlere Präsentis- mus betrug 9,2%. Mit r = 0,39 und 0,33 kor- relierten die WLQ- und Präsentismus-Scores signifikant mit dem DLQI (p < 0,001). Eine geringere Lebensqualität war am stärks- ten mit körperlichen und allgemeinen Leis- tungseinschränkungen im Beruf assoziiert. Regressionsmodelle zeigten einen Zuwachs von Limitationen bei der Bewältigung von Arbeitsanforderungen um 1,7% und des Prä- sentismus um 0,5% mit der Zunahme des DLQI um einen Punkt. Diskussion: eine mo- derate bis schwere AD hat negative wirt- schaftliche Auswirkungen mit einem mittle- ren Produktivitätsverlust der Patienten von fast 10%. Weitere Analysen sollten den Ein- fluss innovativer Behandlungsmethoden auf Lebensqualität und Arbeitsproduktivität in den Fokus rücken.

Filaggrin (Flg) and hornerin (Hrnr) share similar structural and functional features. Both proteins have been implicated as essential proteins for skin barrier maintenance. Loss-of-function mutations of these genes constitute a risk factor for atopic dermatitis and eczema-related asthma. Furthermore, both FLG and HRNR protein levels are downregulated in patients with atopic dermatitis. Thus, mice deficient for Flg and Hrnr provide a novel model to study skin barrier impairment and the susceptibility for cutaneous inflammation.By using appropriate targeting vectors and breeding strategies, we established a homozygous FlgHrnr double-deficient (FlgHrnrNeonates appeared normal, but developed a transient scaly phenotype with overall flaky appearance, but no overt skin phenotype in adulthood, thereby reflecting a subclinical barrier defect seen in humans. Structurally, FlgHrnrTogether, our FlgHrnr

Das atopische Ekzem des Kindesalters ist mit einer stadiengerechten topischen Therapie in der Mehrheit der Falle gut behandelbar. Herausforderungen stellen die schweren Verlaufsformen mit rezidivierenden Superinfektionen, das Management assoziierter Nahrungsmittelallergien sowie die psychosozialen Aspekte einer chronischen Erkrankung im Familienkontext dar. In dieser Altersgruppe liegt ein besonderer Fokus auf der Pravention – primar und im Hinblick auf die Entwicklung weiterer Erkrankungen des atopischen Formenkreises. In einigen dieser Bereiche haben sich in den letzten Jahren neue Aspekte ergeben, die das praktische Management des atopischen Ekzems im Kindesalter verandert haben oder in Zukunft verandern konnten.

Zusammenfassung Die uberwiegende Zahl der malignen Melanome („schwarzer Hautkrebs”) treten an der sichtbaren Haut auf. Werden sie rechtzeitig erkannt, ist die Behandlung nach Exzision mit Sicherheitsabstand abgeschlossen. Dagegen haben Patienten mit metastasiertem Melanom trotz neuer Therapien weiterhin eine sehr schlechte Prognose. Daher hat die Fruherkennung beim malignen Melanom einen sehr hohen Stellenwert. Der „weise Hautkrebs” ist aufgrund des geringen Metastasierungsrisikos prognostisch deutlich gunstiger, jedoch konnen auch hier durch fruhzeitige Behandlung eingreifende Therapien vermieden werden. Der Artikel gibt praktische Hinweise, auf welche Hautveranderungen Therapeuten bei ihren Patienten achten sollten.

Bacterial infections of the skin are often seen by dermatologists. The majority of infections are caused by the gram-positive bacteria Staphylococcus aureus and Streptococcus pyogenes. These induce blistering/erosive (impetigo, ecthymata) and abceeding (folliculitis) infections of the skin, respectively. Owing to their differences in virulence factors and host immunity, these strains can lead to varying presentations and courses of the infections. This review focuses on impetigo, folliculitis, perianal streptococcal dermatitis, and ecthymata.

Background B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization. Methods B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days. Results Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation. Conclusions Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.

Patients with atopic dermatitis (AD) tend to have greatly elevated levels of serum immunoglobulin E (IgE). However, the role of IgE in the pathogenesis of AD is debated. This investigator-initiated open-label pilot study evaluates an anti-IgE-treatment approach by combining extracorporeal immunoadsorption and anti-IgE antibody omalizumab in 10 patients with severe, therapy-refractory AD. IgE levels decreased after immunoadsorption and decreased continuously in all patients during anti-IgE therapy. The reverse trend was observed during 6 months follow-up without treatment. In parallel with these observations, an improvement in AD was observed during the treatment period, with aggravation during follow-up. Further research is needed, based on the principle of reducing IgE levels in order to improve clinical symptoms, using a combination anti-IgE treatment approach, adjusted according to IgE levels.