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Impfungen gehoren zu den erfolgreichsten vorbeugenden Masnahmen der Medizin. Da sie bei gesunden Menschen appliziert werden, sind regulatorische Hurden besonders hoch, und es mussen vor jeder Zulassung Daten aus klinischen kontrollierten Studien und im weiteren Verlauf aus Registermeldungen evaluiert werden. Die Wahrscheinlichkeit und Bedeutsamkeit von Impfreaktionen mussen gegen mogliche Schaden durch die Wildinfektion, aber auch den induzierten Infektionsschutz abgewogen werden. Unvertraglichkeiten von Impfungen werden haufiger vermutet, als tatsachlich bewiesen und sind insgesamt selten. Dazu gehoren auch Hautveranderungen, die spezifischen Erkrankungen wie der Psoriasis, Neurodermitis oder dem Lichen ruber zugeordnet werden konnen oder unspezifische Reaktionen darstellen. Neben einer Provokation oder Exazerbation dieser Erkrankungen sind auch verschiedene Intoleranzreaktionen moglich, die klassisch-allergologisch oder anaphylaktoid sein konnen. Gerade Menschen mit chronischen Hauterkrankungen, insbesondere auch unter einer immunsuppressiven oder -modulatorischen Therapie, sollten alle empfohlenen Standardimpfungen dem Lebensalter entsprechend erhalten haben. Impfungen sollten nicht bei akuten Hauterscheinungen durchgefuhrt werden. Eine Begleitmedikation, insbesondere wenn diese immunsuppressiv oder immunmodulatorisch ist, muss in die Entscheidung zur Impfung und Festlegung deren Zeitpunkts einbezogen werden. Wahrend Totimpfungen auch unter immunsuppressiver Therapie moglich sind, dies aber zu einer verminderten Impfantwort und damit vermindertem Infektschutz fuhren kann, sind Lebendimpfstoffe eher kontraindiziert.

Background: Bullous pemphigoid (BP), the by far most frequent autoimmune blistering skin disease (AIBD), is immunopathologically characterized by autoantibodies against the two hemidesmosomal proteins BP180 (collagen type XVII) and BP230 (BPAG1 or dystonin). Several comorbidities and potentially disease-inducing medication have been described in BP, yet a systematic analysis of these clinically relevant findings and autoantibody reactivities has not been performed. Objective: To determine associations of autoantibody reactivities with comorbidities and concomitant medication. Methods: In this prospective multicenter study, 499 patients diagnosed with BP in 16 European referral centers were included. The relation between anti-BP180 NC16A and anti-BP230 IgG ELISA values at the time of diagnosis as well as comorbidities and concomitant medication collected by a standardized form were analysed. Results: An association between higher serum anti-BP180 reactivity and neuropsychiatric but not atopic and metabolic disorders was observed as well as with the use of insulin or antipsychotics but not with dipeptidyl peptidase-4 (DPP4) inhibitors, inhibitors of platelet aggregation and L-thyroxine. The use of DPP4 inhibitors was associated with less anti-BP180 and anti-BP230 reactivity compared with BP patients without these drugs. This finding was even more pronounced when compared with diabetic BP patients without DPP4 inhibitors. Associations between anti-BP180 and anti-BP230 reactivities were also found in patients using insulin and antipsychotics, respectively, compared with patients without this medication, but not for the use of inhibitors of platelet aggregation, and L-thyroxine. Conclusion: Taken together, these data imply a relation between autoantibody reactivities at the time of diagnosis and both neuropsychiatric comorbidities as well as distinct concomitant medication suggesting a link between the pathological immune mechanisms and clinical conditions that precede the clinically overt AIBD.

PERSIST was a prospective, non-interventional, long-term, German multicentre study of patients with moderate-to-severe psoriasis receiving guselkumab, an approved monoclonal antibody that binds to the p19 subunit of interleukin (IL)-23, in a real-world setting.Evaluation of the efficacy and safety of guselkumab, and its effect on health-related quality of life (HRQoL), in patients with moderate-to-severe psoriasis who have received 52 weeks of treatment.Patients (≥18 years old) were prescribed guselkumab as per routine clinical practice. End points assessed include Psoriasis Area and Severity Index (PASI), Physician's Global Assessment (PGA), target Nail Psoriasis Severity Index (NAPSI), and the Dermatology Life Quality Index (DLQI).Overall, 303 patients were enrolled and treated with guselkumab. Mean disease duration was 21.0 years, and 77.2% and 51.2% of patients had received ≥1 prior conventional systemic or ≥1 prior biologic therapy, respectively. Mean PASI score decreased from 16.4 at baseline to 3.0 by Week (W) 28, and further decreased to 2.4 by W52, while the proportion of patients achieving an absolute PASI score of ≤1 increased from 1.3% at baseline, to 50.8% at W28 and to 58.4% by W52. PASI90 and PASI100 responses also showed marked improvements between W28 and W52, regardless of biologic treatment history. Clearance of psoriatic skin was observed in difficult-to-treat areas, with the percentage of patients achieving a PGA score ≤1 increasing between W28 and W52. Guselkumab improved HRQoL; mean DLQI score decreased from 13.7 at baseline to 2.8 by W28, and further decreased to 2.4 by W52. At W52, 64.6% of patients achieved a DLQI score ≤1. The cumulative probability of drug survival was 92.4% at W52.Guselkumab is efficacious and well tolerated regardless of previous biologic therapies, comorbidities or psoriasis manifestation in difficult-to-treat areas. No new safety signals were observed.

Vaccinations are among the most successful prophylactic measures in medicine. As they are applied to healthy subjects, regulatory steps before licensing of any vaccination are strictly based on clinically controlled studies as well as on registry data in the further course. The probability and relevance of adverse reactions to vaccinations have to be weighed against any harm through the respective natural infection as well as the vaccination-induced protection against infections. Intolerance reactions to vaccinations are far more suspected than proven and altogether rare. Among these, specific dermatoses like psoriasis, atopic dermatitis and lichen planus are found as well as allergic reactions and a number of more nonspecific skin symptoms. Apart from provocation or exacerbation of an underlying dermatological disease, various intolerance reactions may be encountered which are classically allergologic or anaphylactoid. People with chronic dermatoses, especially those on immunosuppressive and immunomodulatory therapy, should have all recommended standard vaccinations. Vaccinations should not be administered during acute skin manifestations and relevant comedication-especially if immunomodulatory or immunosuppressive-has be taken into account in the decision to vaccinate and to define the time point of any vaccination. Inactivated vaccines may be administered even during ongoing immunosuppressive therapy, but may result in decreased immunological reactions and protection to infection. Live vaccines should be avoided.Impfungen gehören zu den erfolgreichsten vorbeugenden Maßnahmen der Medizin. Da sie bei gesunden Menschen appliziert werden, sind regulatorische Hürden besonders hoch, und es müssen vor jeder Zulassung Daten aus klinischen kontrollierten Studien und im weiteren Verlauf aus Registermeldungen evaluiert werden. Die Wahrscheinlichkeit und Bedeutsamkeit von Impfreaktionen müssen gegen mögliche Schäden durch die Wildinfektion, aber auch den induzierten Infektionsschutz abgewogen werden. Unverträglichkeiten von Impfungen werden häufiger vermutet, als tatsächlich bewiesen und sind insgesamt selten. Dazu gehören auch Hautveränderungen, die spezifischen Erkrankungen wie der Psoriasis, Neurodermitis oder dem Lichen ruber zugeordnet werden können oder unspezifische Reaktionen darstellen. Neben einer Provokation oder Exazerbation dieser Erkrankungen sind auch verschiedene Intoleranzreaktionen möglich, die klassisch-allergologisch oder anaphylaktoid sein können. Gerade Menschen mit chronischen Hauterkrankungen, insbesondere auch unter einer immunsuppressiven oder -modulatorischen Therapie, sollten alle empfohlenen Standardimpfungen dem Lebensalter entsprechend erhalten haben. Impfungen sollten nicht bei akuten Hauterscheinungen durchgeführt werden. Eine Begleitmedikation, insbesondere wenn diese immunsuppressiv oder immunmodulatorisch ist, muss in die Entscheidung zur Impfung und Festlegung deren Zeitpunkts einbezogen werden. Während Totimpfungen auch unter immunsuppressiver Therapie möglich sind, dies aber zu einer verminderten Impfantwort und damit vermindertem Infektschutz führen kann, sind Lebendimpfstoffe eher kontraindiziert.

BackgroundThe first vaccine against SARS-CoV-2 was approved in December 2020. Immunogenicity of SARS-CoV2 vaccines in patients with immune-mediated inflammatory disease (IMID) have so far been evaluated in the 2-6 weeks following complete vaccination and risk groups for poor early vaccine response have been identified leading to specific vaccination recommendations. However, data on the long-term course and persistence of vaccine response in IMID patients, as well as the outcomes of the specific recommendations are lacking.ObjectivesTo evaluate the long-term course of humoral response to SARS-CoV-2 vaccination in a large prospective cohort of IMID patients and non-IMID controls with a follow-up duration of up-to to 10 months after the first vaccine dose.MethodsWe have initiated a prospective dynamic cohort of IMID patients and healthy controls in February 2020 to monitor immune response to SARS-CoV-2 and respiratory infections including COVID-19 (1). Participants who contributed data starting from the 4 weeks before their first vaccination onwards were included in this analysis. Antibodies against SARS-CoV-2 spike protein were quantified with an ELISA from Euroimmun (Lübeck, Germany) with an optical density cutoff of 0.8. We fitted linear mixed-effect models for log-transformed antibody levels using time splines with adjustment for age and sex. Marginal mean antibody levels with 95% confidence intervals (CI) were estimated at selected time points for IMID patients and controls with double vaccination. We descriptively analyzed the observed antibody levels over time in cohort participants receiving two vaccinations vs. three vaccinations.ResultsAmong 5076 cohort participants, 3147 IMID patients and healthy controls (mean (SD) age 49 (16)) provided 4756 samples for this analysis between December 2020 and 2021, with a median (IQR) 28 (14-31) weeks of follow-up after the first vaccination (Table 1). 2965 (94%) participants had received at least 2 and 223 (7%) participants had received three vaccine doses by the date of their latest sampling. In IMID patients, age and sex-adjusted estimated marginal mean antibody levels waned after week 16 and were substantially reduced at all time points compared to the controls, finally dropping to the borderline range (1.01, 95%CI 0.86 to 1.19) at week 40 (Figure 1A, Table 1). A third dose was given to 128 (7%) of IMID patients with a poor response to 2 vaccine doses after a median 20 weeks of the second dose (IQR 10 to 26 weeks). After the third dose, antibody levels in IMID patients were comparable to those of healthy controls at 40 weeks who had three vaccine doses. These were also higher than that of IMID patients and controls who did not receive a third dose (Figure 1B).Table 1.Participant characteristics and antibody levelsHealthy controlsIMID N11991948 Age, mean (SD)40.8 (13.5)54.3 (14.8) Follow-up, weeks, median (IQR)31.1 (23.8-36.6)19.6 (12.3-26.6) Follow-up range, weeks,1.6-46.11.7-46.3Sex, n(%) Female554 (46.2)1136 (58.3)Vaccine intervals, ´median (IQR) 1st to 2nd dose4.6 (3.0-6.0)6.0 (5.0-6.1) 2nd to 3rd dose29.6 (26.9-36.4)19.9 (10.0-26.1)Diagnosis, n (%) Spondyloarthritis-713 (36.6) Rheumatoid arthritis-489 (25.1) Autoimmune disease, systemic+-420 (21.5) Inflammatory bowel disease-219 (11.2) Psoriasis-107 (5.5)Mean* antibody levels after 1st dose Week-84.16 (3.89 to 4.45)2.97 (2.83 to 3.12) Week-168.39 (7.81 to 9.02)5.04 (4.81 to 5.28) Week-325.02 (4.73 to 5.33)2.52 (2.32 to 2.74) Week-402.14 (1.95 to 2.35)1.01 (0.86 to 1.19)+ Systemic lupus, systemic sclerosis, Sjögren’s syndrome, vasculitis* Estimated marginal means adjusted for age and sex.Figure 1.ConclusionHumoral response to vaccination against SARS-CoV-2 was weaker in IMID patients compared to controls at all time points after the first vaccine dose and practically disappeared after 1 year. IMID patients can still achieve a good antibody response with a third dose even after a weak response with two doses.References[1]Simon D et al Nat Commun 2020Disclosure of InterestsNone declared

BackgroundMonitoring disease activity in patients with inflammatory arthritis is essential for effective treatment. While the health assessment questionnaire (HAQ) is commonly used to assess physical function, additional functional tests, such as isometric grip strength and the Moberg Pick-Up-Test (MPUT), provide objective measures for hand function and allow assessing hand function across different diseases (1). It remains unclear to date, if measured hand function is already reflected by the HAQ, as the most widely used patient reported outcome measure of physical function in arthritis.ObjectivesTo estimate the proportion of hand function and grip strength variability explained by HAQ, patient-reported hand function, and between-person variation in patients with inflammatory arthritis and non-arthritic controls.MethodsPatients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), psoriasis without PsA (PsO) and healthy controls (HC) were investigated. Subject characteristics (age, sex, disease) and HAQ were recorded. Hand function was assessed by vigorimetric grip strength, MPUT, and a patient-reported tool (Michigan Hand Questionnaire, MHQ). Mixed pure-random-effect linear regression models were used to estimate the proportion of variance in measured hand function or grip strength explained by subject characteristics (age, hand dominance, sex, reported hand function, disease group).Results299 subjects were tested, 101 with RA (Age: 59.1±13.3 years, BMI: 27.2±5 kg/m2, HAQ-DI score: 0.9±06), 92 with PsA (Age: 58.8±11.6 years, BMI: 29±6.1kg/m2, HAQ-DI score: 0.6±0.7) and 106 non-arthritic controls (51 with Pso (Age: 47.3±14.1 years, BMI: 29.8±7.3 kg/m2, HAQ-DI score: 0.4±06) and 55 HC (Age: 54.6±16.5 years, BMI: 25.2±3.3 kg/m2, HAQ-DI score: 0.1±0.2). Overall variation of MPUT is mostly accounted for by between-person variation (43.1%), followed by HAQ (20.3%) and MHQ (20.2%) (Figure 1A). Overall variation in grip strength is mostly accounted for by sex (59.8%), between-person variation (21.1%) and HAQ (11.3%) (Figure 1B). Overall variation in MHQ is mostly accounted for by HAQ (59.2%) and residual variation (28.3%). Study group specific result are summarized in Table 1.Table 1.Variance proportions for each of the four study groups.Variance proportions (%)Hand function (MPUT)Grip strengthGroupControlPsAPsORAControlPsAPsORAMHQ3.439.00.00.00.02.10.00.0ID34.836.251.652.816.112.921.327.9Age0.013.80.00.78.48.40.00.0HAQ35.810.834.316.43.83.110.312.0Dominant hand0.60.20.00.03.50.61.30.2Sex12.10.00.04.364.268.963.755.0Residual13.30.014.125.83.94.03.45.0ConclusionWhile the variance variation in grip strength is mainly explained by sex and between-person variation for all subject groups, the proportions of explained variance for measured hand function is not similar between diseases. In all groups > 50% of the variation in measured hand function remains unexplained by the variables used. Especially in arthritis patients, HAQ explained less than 25% of the variance in measured hand function. Grip-strength can be considered a poor surrogate for hand function in this context due to its large gender dependence. The explainability of MHQ variation largely by HAQ indicates that it has limited potential to provide further information beyond overall functional impairment. In contrast, the large between-person variation in MPUT likely indicates unexplored movement patterns of hand motion that may be further dissected using sensor-based analyses (2) and can help identify movement components a potential for an in-depth assessment of subtle hand-function alterations in inflammatory arthritis.References[1]Liphardt AM et al. ACR Open Rheumatol 2020, 2, 734-740. 2. Phutane U et al. Sensors (Basel) 2021, 21.AcknowledgementsThis study was supported by the German Research Council (SFB 1483 – Project-ID 442419336, INST 90 / 985-1 FUGG, FOR2438/2886; SFB1181), the German Ministry of Science and Education (project MASCARA), the European Union (H2020 GA 810316 - 4D-Nanoscope European Research Council Synergy Project) and Novartis Germany GmbH.Disclosure of InterestsNone declared

BackgroundSpreading of inflammation from skin to joint is a key question behind the pathogenesis of psoriatic arthritis (PsA). Psoriasis (PsO), being one of the most prevalent skin diseases, usually anticipates joint manifestations, suggesting spreading of skin to joint disease, which happens in about 30% of the patients with psoriasis.1 To date, it is still obscure why the inflammatory process in some patients with PsO remains restrained to the skin, whereas in other patients it extents to tendons and joints.ObjectivesUsing a pre-clinical model of PsA, we aimed to unveil the skin-joint axis, i.e. the spreading of psoriatic inflammation from the skin to the joints.MethodsKAEDE transgenic mice expressing a photo-convertible fluorescent reporter were used to assess cell trafficking from inflamed skin to other organs in the mouse model of IL-23 overexpression (IL-23OE) induced PsA. Psoriatic skin lesions were irradiated with UV light to trigger the photoswitch from KAEDEGREEN to KAEDERED. Migration to different organs was determined by flow cytometry. Imaging flow cytometry was used to characterize the type of cells migrating from the skin to the joints. Migrating cells were further characterized by single-cell RNA-sequencing (scRNAseq) and functional analyses.ResultsMRI imaging and histological evaluation of IL-23OE mice revealed skin inflammation preceding joint inflammation in both wild-type and KAEDE-transgenic mice. Specific leukocyte migration from the skin to the joints started shortly after the onset of skin inflammation and before onset of inflammation within the joints of KAEDE transgenic mice. No migration was observed in healthy control animals. Other organs such as spleen or lymph nodes showed no model-dependent migration. Imaging flow cytometry revealed that the cells migrating to the joints were predominantly CD45+ CD11b+ cells. ScRNAseq analysis of sorted KAEDERED cells from inflamed joints confirmed that approximately 80% of the migrating cells were macrophages. Differential gene expression and pathway analysis revealed an imbalance between pro- and anti-inflammatory macrophages in the joints of experimental psoriatic arthritis.ConclusionWe describe IL-23-mediated migration of skin-derived macrophages from the skin to the joints during the onset of experimental psoriatic arthritis. This process may explain the spreading from psoriatic skin to joint disease as these cells foster the development by local cytokine production once arrived in the joints.References[1]Veale, D.J. & Fearon, U. The pathogenesis of psoriatic arthritis. Lancet391, 2273-2284 (2018).Disclosure of InterestsNone declared.

BackgroundWhile MRI evaluation of joints has been primarily used to quantify inflammation at a cross-sectional and longitudinal level, less is known about the potential of MRI in distinguishing different patterns of inflammation in the various forms of arthritis.ObjectivesTo evaluate (i) whether deep learning using neural networks can be trained to distinguish between seropositive rheumatoid arthritis (RA+), seronegative RA (RA-), and psoriatic arthritis (PsA) based on structural inflammatory patterns on hand magnetic resonance imaging and (ii) to assess if psoriasis patients with subclinical inflammation fit into such patterns.MethodsResNet 3D [1] neural networks were trained to distinguish (i) RA+ vs. PsA, (ii) RA- vs. PsA and (iii) RA+ vs. RA- with respect to hand MRI data. Diagnosis of patients was determined using the following guidelines: ACR/EULAR 2010 [2] for RA and CASPAR [3] for PsA. Results from T1 coronal, T2 coronal, T1 coronal and axial fat suppressed contrast-enhanced (CE) and T2 fat suppressed axial sequences were used. The performance of such trained networks was analyzed by the area-under-the-receiver-operating-characteristic curve (AUROC) with and without imputation of demographic and clinical parameters (Figure 1A). Additionally, the trained networks were applied to psoriasis patients without clinical signs of PsA.Figure 1.(A) Neural network combining MR sequences with optional additional clinical data. The prediction for a single case is formed by averaging the prediction of all sequences and the clinical data. (B) Plot of the AUROC for increasing percentages (0.6 – 60%) of training data for the differentiation between RA+ and PsA by the neural network. The light blue area around the dark blue mean indicates the uncertainty measured using a 5-fold cross-validation.ResultsMRI scans from 649 patients (135 RA-, 190 RA+, 177 PsA, 147 psoriasis) were included (Table 1). The AUROC for differentiation between disease entities was 75% (SD 3%) for RA+ vs. PsA, 74% (SD 8%) for RA- vs. PsA, and 67% (6%) for RA+ vs. RA-. All MRI sequences were relevant for classification, however, when deleting CE sequences, the loss of performance was only marginal. The addition of patient-specific data to the networks did not provide significant improvements. Increasing amounts of training data demonstrated improved performance of the networks (Figure 1B). Psoriasis patients were mostly assigned to PsA by the neural networks, suggesting that PsA-like MRI pattern may be present early in the course of psoriatic disease.Table 1.Overview of demographic and clinical information.RA+RA-PsAPsoriasisTotal Number (N)649Number (N)190135177147Age (years), mean±SD56.9±12.660.5±10.356.3±12.049.6±13.8Sex (female/male)126/6493/4292/8571/76BMI (kg/m2), mean±SD26.6±10.527.6 ±9.329.1±11.326.7±6.9Disease duration (years), mean±SD2.6±4.91.3±2.30.8±2.34.2±5.1DAS28, mean±SD3.3±1.33.4±1.23.2±1.3-CRP (mg/L), mean±SD0.9±2.50.7±1.20.5±0.80.5±1.3HAQ, mean±SD0.8±0.60.9±0.80.6±0.60.3±0.4MedicationbDMARD88.46%83.87%81.32%35.01%csDMARD89.52%88.89%80.54%12.28%ConclusionDeep learning can be successfully applied to differentiate MRI inflammatory patterns related to RA+, RA-, and PsA. Early changes in psoriasis patients can be recognized by neural networks and are characterized by a pattern that allowed the networks to classify them as PsA.References[1]Kensho Hara, Hirokatsu Kataoka, and Yutaka Satoh 2018. Can Spatiotemporal 3D CNNs Retrace the History of 2D CNNs and ImageNet? In Proceedings of the IEEE Conference on Computer Vision and Pattern Recognition (CVPR) (pp. 6546–6555).[2]Aletaha D, Neogi T et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010 Sep;62(9):2569-81.[3]Helliwell PS, Taylor WJ. Classification and diagnostic criteria for psoriatic arthritis. Annals of the Rheumatic Diseases 2005;64:ii3-ii8.AcknowledgementsThe study was supported by the Deutsche Forschungsgemeinschaft (DFG-FOR2886 PANDORA and the CRC1181 Checkpoints for Resolution of Inflammation). Additional funding was received by the Bundesministerium für Bildung und Forschung (BMBF; project MASCARA), the ERC Synergy grant 4D Nanoscope, the IMI funded projects HIPPOCRATES and RTCure, the Emerging Fields Initiative MIRACLE of the Friedrich-Alexander-Universität Erlangen-Nürnberg and the Else Kröner-Memorial Scholarship (DS, no. 2019_EKMS.27). Furthermore, infrastructural and hardware support was provided by the d.hip Digital Health Innovation Platform.Disclosure of InterestsNone declared

BackgroundMicroRNAs (miRNAs) are small non-coding RNAs that control gene expression. Specific miRNA signatures have been identified in numerous diseases and may serve as potential biomarkers or new drug targets. Whether certain miRNA signatures are associated with psoriatic joint disease is currently unknown.ObjectivesTo search for circulating miRNA signatures in psoriasis patients with subclinical joint disease and in patients with psoriatic arthritis (PsA).MethodsAnalyses of serum miRNA were done in three groups: (1) PsA patients fulfilling CASPAR criteria (PsA), (2) healthy controls without past or present signs of musculoskeletal disease (HC) and (3) psoriasis patients with musculoskeletal pain but no signs of clinical PsA (PsO). PsO and PsA patients received a hand MRI, which was scored according to PsAMRIS method. miRNA analysis of serum samples was performed stepwise using RT-qPCR (TAmiRNA Vienna). In the discovery phase 192 miRNA assays were analyzed in 48 samples (N=16 each group). In the validation phase 17 miRNAs (Table 1) were selected and analyzed in 94 samples (N=35 PsA, N=24 PsO, N=35 HC) based on results of discovery phase and previous reports in literature. Results presented as mean±SD/median (IQR), p-values are adjusted for multiple testing.Table 1.miRNAsPsA vs HCPsO vs HCPsA vs PsODiscovery PhaseValidation PhaseDiscovery PhaseValidation PhaseDiscovery PhaseValidation Phasep-adj.p-adj.p-adj.p-adj.p-adj.p-adj.miR-93-5p0.00010.0080.0050.0390.947miR-29b-3p0.00010.0040.00020.1910.522miR-19b-3p0.0070.7080.00020.0200.1380.147miR-320d0.0010.6190.1350.9410.247miR-144-5p0.0030.0060.00010.1690.3500.444miR-188-5p0.0140.9900.9750.6470.0530.839let-7b-5p0.0250.00030.8890.0260.00030.472miR-92a-3p0.0430.0010.0050.7730.0005miR-324-3p0.1381.0000.2570.3920.8140.518miR-126-3p0.0140.1690.0130.5980.9220.654miR-223-3p0.1690.8720.6170.7460.5191.000miR-130a-3p0.0390.0350.5560.0090.0060.724miR-140-3p0.3500.0530.0020.0060.1180.683miR-155-5p0.1590.9950.1690.5490.9220.604miR-21-5p0.2970.9900.0030.1160.080.014miR-146a-5p0.7060.0040.8360.0380.9050.941miR-122-5p0.9600.7340.6950.7990.9050.444Results51 PsA patients (age: 51.3±11.4 years; 56.9% females), 40 PsO patients (51.4±11.0; 37.5%) and 50 HC (51.0±10.5; 52.9%) were assessed. Duration of psoriasis was 12(25) years in PsA and 15(22.8) years in PsO. Duration of joint disease in PsA was 1.0(4.8) year. 51% of PsA and 5% of PsO patients were on biological disease modifying drugs (bDMARDs), 49% vs. 10% on conventional DMARDs. The most frequent findings in the MRI were erosions (PsA 59.6%; PsO 40%) and synovitis (PsA 48.9%; PsO 42.5%). PsA patients had higher number of tenosynovitis compared to PsO (p=0.04). In discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared to HC, with an overlap of 33 miRNAs changed in PsA and PsO (pConclusionPsA and PsO patients show miRNA signatures different from HC. Top candidate miRNAs differentially regulated in PsA and PsO have been previously reported in alteration of bone metabolism and osteoarthritis indicating the intimate association of psoriatic inflammation with bone and cartilage changes.References[1]Faustini F et al. Ann Rheum Dis 2016 Dec;75(12):2068-2074[2]Hackl, M et al. Molecular and Cellular Endocrinology Elsevier Ireland Ltd 432, pp 83–95[3]Feichtinger X et al. Sci Rep 2018 Mar 20;8(1):4867Disclosure of InterestsNone declared

Der behaarte Kopf kann durch vielfaltige Erkrankungen in ebenso vielfaltiger Weise betroffen werden. Neben Rotung und Schuppung findet sich haufig qualender Juckreiz, der zu massiven Beeintrachtigungen der Patienten fuhrt. Die Kopfpsoriasis und das seborrhoische Kopfekzem gehoren zu den haufigsten Erkrankungen, die im klassischen Fall einfach zu unterscheiden sind, aber auch Uberschneidungen und klinische Ahnlichkeiten zeigen konnen. Die scharf begrenzten, die Stirn-Haar-Grenze uberschreitenden erythematosquamosen Plaques der Psoriasis stehen eher unscharf begrenzten, dusterroten Erythemen mit einer gelblich-fettigen Schuppung des seborrhoischen Ekzems gegenuber. Bei Letzterem findet sich haufig eine diffuse Alopezie, wahrend Haarausfall bei der Psoriasis eher selten ist, aber auch als unerwunschte Wirkung verschiedener Therapeutika auftreten kann. Die Behandlung richtet sich nach Akuitat und Ausdehnung der Erkrankung wie auch Einschrankung der Betroffenen. Sie ist zunachst topisch unter Einsatz von Kortikosteroiden, bei der Psoriasis auch von Vitamin-D-Derivaten, beim seborrhoischen Ekzem von topischen Antimykotika. In schweren Fallen unter Beteiligung des ubrigen Integuments bedarf insbesondere die Psoriasis einer systemischen Therapie mit den klassischen Wirkstoffen Methotrexat, Fumaraten oder Ciclosporin bis zu den Biologika, die Tumornekrosefaktor-α, Interleukin-12/23 oder Interleukin-17 hemmen. Eine Systemtherapie des seborrhoischen Ekzems ist nur selten notig und kann mit Kortikosteroiden, Antimykotika oder Vitamin-A-Derivaten erfolgen. Wichtig ist eine intensive Beratung der Patienten uber die Notwendigkeit einer konsequenten und lang wahrenden Anwendung der Therapeutika sowie zur Anwendung von hautschonenden Pflegeprodukten und Masnahmen.

The specific dermatoses of pregnancy represent a heterogeneous group of inflammatory skin diseases related to pregnancy and/or the postpartum period. A clinically relevant classification has been well established over the past 10 years and includes pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. The hallmark of all four entities is severe pruritus that is accompanied by characteristic skin changes. While some of these dermatoses are distressing only to the mother because of pruritus, others may be associated with significant fetal risks. Early diagnosis and prompt treatment are therefore essential. In this review, we discuss in detail pemphigoid gestationis, polymorphic and atopic eruptions of pregnancy whereas intrahepatic cholestasis of pregnancy is discussed in a separate article (Kremer A, Stander S, DOI 10.1007/s00105-016-3923-y ). Furthermore, we present a helpful algorithm for diagnosis and management of pruritus in pregnancy.

Background Hypertension (HTN) is one of the most common cardiovascular risk factors in patients with atrial fibrillation (AF). As a potential risk factor for cerebral white matter lesions (WML), HTN might explain the increased risk of cognitive dysfunction in AF patients. Methods In a multicenter cohort study of patients with documented AF in Switzerland, systolic and diastolic blood pressure (SBP, DBP) was measured up to three times in a supine position and the mean was calculated. HTN was defined as controlled, when SBP was Results Overall, 1738 patients were enrolled in this cross-sectional analysis (mean age 73 years, 73% males). Mean BP was 135/79 mmHg, 69% had a history of HTN. Any WMLs were found in 99% of the patients and 54% had at least moderate WMLs. The prevalence of Fazekas ≥2 was 47%, 50% and 61% among AF patients with SBP Association between blood pressure and white matter lesions Blood pressure Fazekas ≥2 OR (95% CI) Volume WML β-coefficient (95% CI) Conclusion Moderate or severe cerebral WMLs are highly prevalent in AF patients and strongly associated with SBP. Our data suggests that optimal treatment of HTN might play an essential role in preventing WMLs. Acknowledgement/Funding Swiss National Science Foundation

ZusammenfassungDer Begriff Sklerodermie beschreibt eher ein dermatologisches Symptom als eine eigenständige Erkrankung. Insbesondere ist eine systemische Sklerodermie als Multiorganerkrankung mit einer schlechten Prognose von der zirkumskripten oder lokalisierten Sklerodermie abzugrenzen, die je nach Lokalisation und Subtyp erhebliche funktionelle und ästhetische Einschränkungen hervorrufen kann, quoad vitam aber eine gute Prognose hat. Die Ätiopathogenese ist bis heute im Detail unklar, neben dem Bindegewebe sind auch das Gefäß- und Immunsystem beteiligt. Klinisch lassen sich der Plaque-Typ als klassische Morphea mit einzelnen oder disseminierten bzw. generalisierten Herden bis zur pansklerotischen Form, eine profunde Morphea und die Atrophodermia Pasini Pierini von linearen Formen an Gesicht und Extremitäten unterscheiden, von denen die beiden letzten Formen in der Kindheit am häufigsten sind. Die Therapie ist abhängig von der Lokalisation, Verteilung und Progress der Erkrankung und umfasst bei milderen aktiven Formen den topischen Einsatz von Kortikosteroiden, Vitamin-D-Derivaten und Calcineurininhibitoren, für schwere Formen systemische Kortikosteroide und Methotrexat, alternativ andere immunsuppressiv und immunmodulierend wirkende Substanzen. Wichtig ist die weitere klinische Kontrolle der Patienten auf Rezidive und Progress der Erkrankung.

The scalp may be affected by various diseases with equally varying manifestations. Erythema and scaling is often accompanied by agonizing itch. Scalp psoriasis and seborrheic eczema represent the most frequent diseases, which can be differentiated into classical cases; however, overlap and similarities are seen. Sharply demarcated erythematosquamous plaques across the natural hairline in psoriasis are opposed to blurred dark-red erythema and yellowish, greasy scales in seborrheic eczema. Whereas with the latter diffuse alopecia may frequently be found, hair loss is rarely seen in psoriasis and may also be related to therapeutic agents. Treatment is based on acuity as well as extent of disease and individual life quality aspects of the patients. It is mainly based on topical corticosteroids, combined with vitamin D derivatives in psoriasis and antimycotic agents in seborrheic eczema. In severe cases and widespread psoriatic disease, systemic treatment may be necessary, including the classic agents methotrexate, fumarates and ciclosporin as well as biologicals. Systemic treatment of seborrheic eczema is rarely necessary and resides on corticosteroids, antimycotic agents and vitamin A derivatives. In addition, intensive counseling of patients on the necessity of consequent and long-term treatment as well as use of mild skin care products is mandatory.

Hautmanifestationen finden sich beim Lupus erythematodes (LE) haufig und in vielfaltiger Weise. Es lassen sich unspezifische und spezifische Symptome unterscheiden, wobei Letztere dem akut kutanen LE, dem subakut kutanen LE, dem chronisch kutanen und dem intermittierenden LE zuzuordnen sind und in unterschiedlichem Zusammenhang zu einem systemischen LE stehen. Anamnestische und klinische Untersuchungen, klinisch-chemische, immunserologische sowie je nach verdachtigtem Organbefall apparative Untersuchungen belegen die Krankheitsaktivitat und bestimmen Zeitpunkt und Ausmas einer Therapie. Neben Einstellen von Zigarettenrauchen und Alkoholgenuss sowie konsequentem UV-Schutz ist dabei eine topische Therapie mit Glukokortikosteroiden, ggf. Calcineurininhibitoren bei umschriebenen Formen moglich. Vielfach wird jedoch eine systemische Therapie, allen voran mit Antimalariamitteln als Basistherapie erforderlich sein. Verschiedene Immunsuppressiva sind je nach Krankheitsaktivitat, ggf. in Kombination mit systemischen Kortikosteroiden Alternativen. Wichtig ist eine fruhzeitige und effektive Therapie, um eine irreversible Vernarbung der Haut oder eine innere Organschadigung zu vermeiden.

Die Psoriasis ist mit einer kumulativen Haufigkeit von 1,76% bis zum 18. Lebensjahr auch in diesem Lebensabschnitt haufig. Als Auslosefaktoren sind bei Kindern v. a. Infekte, mechanische und Stressfaktoren bedeutsam. Neben den klassischen Pradilektionsstellen zeigt sich bei Kindern besonders eine Beteiligung des Windelbereiches, der Kopfhaut und des Gesichtes. Als spezifische klinische Manifestation des Kindesalters ist die Psoriasis guttata in der Folge von Streptokokkeninfekten zu sehen. Die Psoriasisarthritis, die innerhalb der Gruppe der juvenilen idiopathischen Arthritis erfasst wird, tritt im Kindesalter typischerweise vor oder zeitgleich mit der Hautpsoriasis auf. Samtliche empfohlenen Impfungen konnen bei Kindern mit Psoriasis, idealerweise allerdings im erscheinungsfreien Stadium, durchgefuhrt werden. Schwerpunkt der dermatologischen Therapie ist die topische Anwendung von Cignolin, Glukokortikoiden, alternativ topischen Calcineurininhibitoren neben einer konsequenten und individuell angepassten Hautpflege. Bei schweren Fallen, die auf eine topische Therapie nicht ausreichend ansprechen, ist auch eine Systemtherapie mit den klassischen Therapeutika Methotrexat, Ciclosporin, Retinoiden und ggf. Fumarsaureestern zu bedenken, die jedoch im Off-label-Einsatz erfolgen. Einzig zugelassen zur Therapie der Psoriasis ab dem 8. Lebensjahr ist Etanercept bei Versagen einer konventionellen Systemtherapie. Reha-Masnahmen im Hochgebirgs- oder Seeklima sind zur Stabilisierung des Krankheitsbildes und Forderung eines adaquaten Umganges mit der Erkrankung sinnvoll.

Die Haut ist das extrovertierteste Organ des Menschen und kann isoliert oder im Rahmen von Systemerkrankungen betroffen und dann ein Spiegel dieser Erkrankungen sein. Darmerkrankungen konnen sich aufgrund von resorptiven Mangelerscheinungen an der Haut mit Juckreiz und Schuppung oder mit charakteristischen Erkrankungen wie der Pellagra oder Acrodermatitis enteropathica ausern. Als eigenstandige Hauterkrankung zeigt die Dermatitis herpetiformis Duhring immunologische Ahnlichkeiten mit der Zoliakie, wie beispielsweise einen Nachweis von Anti-Transglutaminase-Antikorpern, gleichzeitig jedoch charakteristische Besonderheiten. Chronisch-entzundliche Darmerkrankungen konnen mit Erythema nodosum oder Pyoderma gangraenosum assoziiert sein, die als dermatologische Entitaten hinweisend, aber nicht beweisend sind. Entzundliche Veranderungen der Mundhohle sowie der Perianalregion sind haufig eher unspezifisch, konnen jedoch mit aphthosen Veranderungen und Fisteln sowie vegetierenden Stomatitiden pathognomonisch fur Darmerkrankungen sein. Neben diesen mehr oder weniger typischen Hautveranderungen sind eine Reihe von Hauterkrankungen als mit Darmerkrankungen assoziiert beschrieben worden. Meist ist jedoch der pathogenetische Zusammenhang nicht geklart. Haufig ist eine Therapie der Hautveranderungen nur erfolgreich, wenn die zugrunde liegende Darmerkrankung mit- oder gezielt therapiert wird.

ZusammenfassungDas atopische Ekzem ist eine häufig bei Kindern vorkommende, oftmals chronisch-rezidivierend verlaufende, teilweise stark juckende Hauterkrankung, die im Arbeitsalltag eines Facharztes für Kinder- und Jugendmedizin oder eines Dermatologen eine wichtige Rolle spielt. Bis heute ist die Ätiopathogenese nicht vollständig geklärt. Im akuten Schub stehen eine Vielzahl von topischen und systemischen immunsuppressiven oder immunmodulatorischen Substanzen zur Verfügung, die eine kontinuierlich durchzuführende regelmäßige Hautpflege ergänzen. Des Weiteren gilt es, mögliche Triggerfaktoren zu erkennen und zu meiden.

Chronisch entzundliche Dermatosen wahrend der Schwangerschaft konnen unterschiedliche Verlaufe bei Mutter und Kind zeigen. Aufgrund der typischerweise TH2-dominierten Immunreaktionen verschlechtern sich haufig atopische Ekzeme oder ein Lupus erythematodes, wahrend sich eine Psoriasis vulgaris verbessern kann. Die Impetigo herpetiformis als schwangerschaftsassoziierte Sonderform der Psoriasis verlauft hingegen haufig schwer. Beim Lupus erythematodes und anderen Autoantikorper-getriggerten Dermatosen wie dem Pemphigus vulgaris findet sich im Gegensatz zur linearen IgA-Dermatose ein erhohtes Risiko fur das Kind aufgrund der diaplazentaren Ubertragung von Autoantikorpern, sodass eine Plazentainsuffizienz mit Wachstumsverzogerung und Fruhgeburt sowie spezifische Hautveranderungen oder Systemmanifestationen beim Kind auftreten konnen. Eine schwere Pityriasis rosea fuhrt bis zur 20. Schwangerschaftswoche zu einer erhohten Rate an Aborten und Fruhgeburten. Die fruhzeitige Diagnose und individuell angepasste Therapie von Hauterkrankungen sind damit sowohl fur die Schwangere als auch ihr Kind bedeutsam.

ZusammenfassungEs existiert eine Vielzahl von Dermatosen, die im Rahmen einer Adipositas entweder direkt oder indirekt assoziiert auftreten können. Eine begleitende Fettstoffwechselstörung kann zu Xanthomen oder Xanthelasmen führen, eine begleitende Hyperinsulinämie und Diabetes mellitus zu einer Acanthosis nigricans oder Hyperandrogenismus mit Virilisierung. Indirekt assoziierte Folgen der Adipositas an der Haut sind u. a. eine Candidose, Keratosis pilaris, Follikulitiden oder plantare Hyperkeratosen. Wichtig ist in jedem Fall der kausale Therapieversuch durch Gewichtsreduktion sowie gegebenenfalls eine zusätzliche spezifische Therapie der Dermatose. Manche der Hautveränderungen sind nicht nur kosmetischer Natur, sondern können auch auf ein erhöhtes kardiovaskuläres Risiko mit erhöhter Mortalität hindeuten, wie etwa Xanthome oder eine Psoriasis vulgaris.

ZusammenfassungDie Psoriasis ist eine der häufigsten chronisch entzündlichen Erkrankungen des Menschen. Sie ist mit einer Reihe anderer Erkrankungen assoziiert, die den Verlauf wie die Therapie maßgeblich beeinflussen. Die verschiedenen Manifestationsformen des metabolischen Syndroms treten bei Patienten mit Psoriasis statistisch signifikant häufiger auf als in der Normalbevölkerung und führen zu einer erhöhten kardiovaskulären Mortalität. Diese ist mit der entzündlichen Aktivität in der Haut wie der systemischen Inflammation korreliert. Insbesondere die Adipositas scheint über die endokrinologische und immunologische Aktivität des intraabdominellen Fettes in das entzündliche Geschehen der Erkrankung direkt mit einbezogen. Daher ist die Psoriasis als eine Systemerkrankung zu werten. Insbesondere Hochrisiko-Patienten, zu denen solche mit einer begleitenden Adipositas vorrangig zu rechnen sind, bedürfen daher einer frühzeitigen und effizienten Therapie ihrer Schuppenflechte und einer engen klinischen Kontrolle.

ZusammenfassungExanthematische Hautausschläge stellen im Neugeborenenalter ein häufiges Symptom dar. Üblicherweise handelt es sich um harmlose Krankheitsbilder mit transientem Verlauf. Dennoch ist der Wunsch besorgter Eltern nach einer Beurteilung durch den Pädiater oder Dermatologen in der Praxis ein wiederholtes Anliegen und stellt den behandelnden Arzt mitunter vor eine differenzialdiagnostische Herausforderung. Die Effloreszenzen sind häufig monomorph, umfassen jedoch eine große Bandbreite möglicher Ausprägungen mit Vesikeln, Pusteln oder eher makulösem Bild. Für den erfahrenen Kliniker ist das klinische Bild oft bereits diagnostisch zielführend. Ergänzend können die Anamnese, die körperliche Untersuchung und einfache mikroskopische Untersuchungen von Haut- oder Pustelabstrichen rasch die Differenzialdiagnosen eingrenzen. Das Erkennen schwerwiegender, teils lebensbedrohlicher Krankheitsbilder durch eine gezielte Untersuchung des klinischen Befundes unter Berücksichtigung der Anamnese kann für den therapeutischen Erfolg von größter Bedeutung sein und erleichtert die gezielte Einleitung weiterer diagnostischer Maßnahmen.

Many skin diseases may affect the oral and genital mucous membranes but involvement is generally uncommon. Mucous membranes are most often affected by lichen planus and less frequently by psoriasis or lupus erythematosus. Macroscopic changes may vary from increased vulnerability, erythema and erosions to leukoplakia. Subjective symptoms of burning sensations or localized pain must be distinguished from underlying psychiatric disorders. Furthermore, neoplasia may complicate chronic lichen planus. Therefore, depending on the location and extent of mucous membrane symptoms, both local and systemic therapy may be necessary. Short- and long-term dermatologic care are required.

ZusammenfassungDie Psoriasis ist eine der häufigsten chronisch-entzündlichen Erkrankungen des Menschen. 30 % aller Psoriasisfälle manifestieren sich bereits vor dem 20. Lebensjahr. Virale und bakterielle, allen voran Streptokokkeninfekte scheinen bei Kindern und Jugendlichen eine größere Rolle zu spielen wie auch eine Manifestation im Gesicht und Inguinalbereich sowie am Kopf häufiger als bei Erwachsenen ist. Angesichts des Nebenwirkungsspektrums, der fehlenden Zulassung der meisten Therapeutika sowie fehlender klinischer Studien zu deren Anwendung im Kindesalter müssen sowohl die lokale als auch systemische Therapie kritisch eingesetzt werden. Topische Glukokortikosteroide und Dithranol sind VitaminD-Derivaten zu bevorzugen. Auch eine Therapie mit ultraviolettem Licht ist angesichts der chronischen Lichtschädigung und Induktion von Hauttumoren sehr kritisch zu sehen. Nur bei Versagen der topischen Therapie und schwerem, rezidivfreudigem Krankheitsbild ist eine systemische Therapie indiziert. Zu Methotrexat besteht in der Kinderrheumatologie die größte Erfahrung, gefolgt von Ciclosporin. Orale Retinoide sind angesichts ihres Nebenwirkungsspektrums problematisch. Insgesamt muss die Therapie der kindlichen Psoriasis kritisch und in enger Rücksprache mit den Eltern erfolgen, andererseits aber sind die sozialen und emotionalen Folgen der Erkrankung für das Kind mit einzubeziehen.

Background: Drug-eluting stents become increasingly popular for the treatment of coronary artery disease. Consequently, side effects including hypersensitivity reactions have to be anticipated. Case Report: Here we report on a patient with an anaphylactic reaction 2 weeks after implantation of a polymer-based paclitaxel-eluting stent (Taxus™, Boston Scientific). The patient presented with disseminated wheals, pruritus, bronchial asthma and acute synovitis. The reaction was successfully treated with initial intravenous injection followed by oral antihistamine treatment for 1 month until all stent-bound paclitaxel was assumed to be eluted. Thereafter no further anaphylactic reaction occurred. Conclusion: This sequence of events points towards a causal relation of the stent implantation and hypersensitivity reaction with a central role of paclitaxel. The increasing use of this type of stent should therefore be carefully monitored for such adverse reactions.

We present a patient with prolonged and therapeutically resistant pemphigus foliaceus despite appropriate immunosuppressive treatment. As a severe and life-threatening complication, the patient acquired a herpes simplex superinfection with bilateral keratitis herpetica as well as bacteriemia following streptococcus pyogenes superinfection. After disease control, extensive thrombosis and pulmonary embolism occurred which may be partially caused by the prednisolone therapy. This case demonstrates the high risk potential of patients with pemphigus foliaceus.

In Deutschland ist von etwa 1,2–1,6 Mio. an Psorasis Erkrankten auszugehen. Etwa 1/3 der Erkrankungen manifestieren sich vor dem 20. Lebensjahr. Als eine klassische Komplikation der Psoriasis wird eine so genannte Psoriasisarthritis (PsA) beschrieben, die nach neuesten Erkenntnissen bis zu 20% aller Psoriatiker betrifft. Die PsA tritt ebenfalls im Kindesalter auf und wird unter dem Begriff der juvenilen idiopathischen Arthritis (JIA) subsumiert.

Adalimumab ist der erste vollstandig humane monoklonale Antikorper gegen TNF α und zur Behandlung der aktiven Rheumatoidarthritis, der ankylosierenden Spondylitis und der Psoriasisarthritis zugelassen. Die Wirksamkeit ist sowohl fur die Hautlasionen als auch die Gelenkbeteiligung durch kontrollierte GCP-basierte Studien belegt. Die Dosierung fur die Psoriasisarthritis betragt 40 mg subkutan alle 14 Tage; eine Kombination mit Methotrexat ist moglich. Alle topischen Antipsoriatika konnen gemeinsam mit Adalimumab eingesetzt werden. Vor Behandlungsbeginn sind bestehende Infektionen und septische Krankheitsbilder auszuschliesen. Der Wirkeintritt zeigt sich bereits nach wenigen Tagen in einer Verbesserung der Gelenkbeschwerden. Unerwunschte Wirkungen von Adalimumab sind dokumentiert, auch eine Verminderung der Infektresistenz ist moglich. Eine benutzerfreundliche Fertigspritze bzw. PEN ermoglicht eine Applikation durch den Patienten selbst. Adalimumab ist angezeigt bei erwachsenen Patienten mit Psoriasisarthritis, die nur unzureichend auf krankheitsmodifizierende Basistherapeutika angesprochen haben. Mit Adalimumab steht perspektivisch ein weiteres Biologic auch fur die Behandlung der Psoriasis zur Verfugung. Da bei Unwirksamkeit die TNF-α-Antagonisten untereinander austauschbar sind, erweitert sich das therapeutische Spektrum.

Large data bases and the projects arising from them have led to a much improved understanding of systemic sclerosis over the last decade. Serology has developed further so that more autoantibodies are available for routine testing. Capillary microscopy has become standard and relevant progress has also been made in therapy. Many diagnostic terms found in medical documentation do not adequately reflect this progress. The nomenclature is inconsistent and, therefore, confusing. The international classification of diseases (ICD) nomenclature is, from our point of view, also in need of improvement. This article aims to reestablish a common German language standard for systemic sclerosis, which reflects current knowledge and is suitable for implementation in the clinical routine.

Cold urticaria is a disease which after contact to cold objects, fluids and air can lead to wheals in lighter and shock reactions in more severe cases. Diagnostically, many different clinical and serological tests have been reported to secure the diagnosis and possible causes. Therapeutical approaches include antihistamines and cold tolerance induction baths amongst other options. The main objectives of the present study were to evaluate a wide range of diagnostic data, to compare different treatment measures and to follow-up clinical symptoms and therapeutic success within a large group of patients. 82 patients, 46 with an isolated cold urticaria and 36 with other additional factors of wheal formation were examined and followed-up 1 - 20 years later by questionnaire. With a median age of onset at 20 years, the disease duration was 1 year in spontaneously healed and 15 years in still affected patients. The mean border temperature below which wheals developed was 22 °C before and 17 °C after therapy. No statistically relevant abnormalities were discovered in serological and hematological examinations. Isolated infectious hearths were rarely found, particularly in consiliary ear-nose-throat examinations. Whereas 52% of patients treated with cetirizine (12 out of 23 patients) reported a significant improvement of their symptoms, no patient who had undergone a therapy with cold water baths continued this for longer than 1 year due to limited effects and gross inconvenience. This study underlines the clinical dilemma of cold urticaria that, despite a defined physical provocation factor, the etiopathogenic as well as therapeutic knowledge are still limited until today. Furthermore, the results of these examinations of diverse parameters in a large and well-characterized patient group show that elaborate diagnostic testing makes sense only if individually fitted and after thorough history taking. Intensive and long-term care of these patients is mandatory.

A 63-year-old woman presented simultaneously with two rare forms of bullous pemphigoid. Initially she had a dyshidrotic palmoplantar eczema. Repeated epicutaneous patch tests ruled out a type IV allergic reaction to common allergens. Six months later the patient developed disseminated pruritic nodules. After 4.5 years she then demonstrated scattered bullae within erythematous plaques indicative of bullous pemphigoid. A skin biopsy showed linear IgG and IgM as well as C3 deposits at the dermo-epidermal junction and circulating autoantibodies against the basement membrane could be found in serum. Accordingly, the diagnosis of bullous pemphigoid was made. In retrospect, the vesicular palmoplantar eczema and pruritic nodules could be interpreted in this case as early manifestations of bullous pemphigoid. We recommend that in patients with persistent pruritic skin lesions, which are resistant to standard therapy, bullous pemphigoid should be excluded by adequate immunological examinations.

X-rays, gamma-radiation, UV and visible light are part of the electromagnetic radiation but in ascending energy dosage. UV light is a well known trigger factor e. g. for lupus erythematosus. In contrast x-rays and γ-radiation have only rarely been described or studied as provocating specific dermatoses. A patient with long-standing SCLE and metastasizing lung cancer is reported with atypical skin lesions at the area of cranial radiotherapy that may be interpreted in different ways. One possible explanation in our case might be exacerbation of SCLE because of the Koebner phenomenon induced by electromagnetic radiation apart from ultraviolet light.

Vascular dysregulation is centrally involved in the pathogenesis of diverse rheumatological diseases. The resulting pulmonary arterial hypertension as well as Raynaud's phenomenon may be accompanied by distinct tissue fibrosis. The pleiotropic cytokine endothelin may represent a link between these vascular and fibrotic processes, which are most evidently seen in systemic sclerosis. Among three closely related isoforms, endothelin-1 (ET-1) is the most common in humans, and is often referred to as ET in the literature. ET-1 is involved in physiological processes of vascular tone and mitogenesis, whereas under pathological conditions fibrosis, vascular hypertension and inflammation are induced. Its expression is dependent on tissue and cell type as well as on the underlying disease entity and its stage. Elevated plasma and tissue levels have been demonstrated in idiopathic pulmonary hypertension, systemic sclerosis as well as in other connective tissue diseases and correlate to haemodynamic parameters and disease outcome. The biological effects are mediated by two membrane receptors (ET-1-receptor A and B) belonging to the G-protein-coupled serpentine family. Both receptors are differentially expressed by different cell types as well as in different diseases entities. Antagonizing these receptors therapeutically has already been successful. However, the differential action of ET is counterbalanced by other mediators, prominently nitric oxide. Consequently, the suspected direct relation of vascular and fibrotic processes through ET still needs to be further evaluated.

Skin manifestations are frequently observed in lupus erythematosus (LE) and are manifold. Nonspecific and specific symptoms can be differentiated with the latter belonging to the dermatologically well-characterized clinical entities of acute cutaneous, subacute cutaneous, chronic cutaneous as well as intermittent cutaneous LE. These forms are differentially related to systemic LE. Patient history and clinical examinations, laboratory and immunoserological findings as well as organ imaging results determine the time point as well as the intensity of therapy. Apart from cessation of smoking and alcohol consumption as well as stringent UV protection, topical therapy with corticosteroids or calcineurin inhibitors may suffice with limited forms of the disease. In many cases, however, systemic treatment with antimalarial drugs as a basic treatment is mandatory. Several immunosuppressive agents can alternatively be used in conjunction with systemic corticosteroids. Early and effective therapy is important to prevent irreversible scarring of the skin and to avoid internal organ damage.

Eosinophil (Eo) granule proteins and, rarely, intact Eos represent a characteristic histopathologic feature of the dermal part of affected tissue in atopic dermatitis and some allergic reactions. Dermal fibroblasts are a rich source of cytokines and inflammatory mediators; therefore, we have investigated whether these cells release Eo chemoattractants when stimulated with different stimuli. Eo-chemotactic activity was detected after stimulation of cells with TNF-alpha and IL-1, but not when phorbol ester, PHA, or medium alone was used. Biochemical characterization of Eo-chemotactic activity in supernatants of NF-alpha-stimulated cells revealed both heparin-binding and nonbinding activity. HPLC purification with subsequent N-terminal sequencing and mass spectrometric analysis showed that the heparin-binding Eo-chemotactic peak corresponded to the chemokine [Tyr-RANTES]66 that also contained [Ser-RANTES]68 as contaminant, whereas the nonheparin-binding activity was identified as granulocyte-macrophage CSF (GM-CSF) by the use of neutralizing Abs. [Tyr-RANTES]66 was found to show identical behavior in the chemotaxis assay system with respect to potency and efficacy as natural [Ser-RANTES]68. These findings support the hypothesis that dermal fibroblasts can play an important role in the recruitment of Eo by release of the chemokine RANTES together with GM-CSF.

Juvenile psoriasis shows a cumulative incidence of 1.76% until the 18th year of life and thus is important for both pediatricians and dermatologists. In contrast to psoriasis in adults, the main trigger factors are infections, mechanical trauma and stress factors and to a much lesser extent medical and recreational drugs. Apart from the classical predilection sites, the diaper area, scalp and face are mainly involved. Guttate psoriasis following streptococcal infections is a specific clinical manifestation in childhood and adolescence. Psoriasis arthritis of childhood falls into the group of juvenile idiopathic arthritis and typically presents before or simultaneously with skin symptoms. All recommended childhood vaccinations should be administered, ideally when the disease is under remission. Therapy relies heavily on topical agents like dithranol, corticosteroids, and alternatively topical calcineurin inhibitors in addition to individually adapted skin moisturizing measures. In severe cases which do not adequately respond to topical therapy, systemic treatment with classical immunomodulatory agents like methotrexate, cyclosporin, retinoids and fumarates may be initiated but all usage is off-label. The only agent licensed for the treatment of psoriasis in patients above the age of 8 years is etanercept if classical treatment has failed. Rehabilitative measures in mountain and seaside areas are reasonable for maintaining improvement and helping patient learn to deal with disease.

Normal melanocytes require a number of exogenous growth factors in contrast to most metastatic malignant melanomas. This investigation demonstrates that endogenously produced human IL-8 can act as an important growth factor for human melanoma cells. In the present study, six out of eight human melanoma cell lines tested secrete IL-8 protein into the culture supernatant. In two of these IL-8-secreting melanoma cell lines, SK-MEL 13 and SK-MEL 23, we have determined the IL-8 requirement for their proliferative capacity. These melanoma cell lines produced significant amounts of bioactive IL-8 as measured by the ELISA technique. Secretion of human IL-8 was inducible by IL-1 and by PMA. Human IL-8-specific mRNA was already detected in unstimulated melanoma cells. In addition, human IL-8-R mRNA could be detected for the first time in human melanoma cells. Exposure of the two melanoma cell lines in vitro to antisense oligonucleotides targeted against two different sites of human IL-8 mRNA-inhibited cell proliferation, colony formation in soft agar, and secretion of IL-8 protein into culture supernatant in a dose dependent fashion. Effects were reversible either by removal of the oligomers or by addition of exogenous IL-8 protein. In contrast, exposure to IL-8 sense probes or oligonucleotides in sense or antisense orientation specific for IL-7, TGF-alpha, TGF-beta, and MGSA had no such effect. A monospecific immune serum and two IL-8-specific mAb were also capable of inhibiting melanoma cell proliferation in the same manner. These results provide strong evidence for an autocrine IL-8 synthesis and for an IL-8-dependent proliferation in a subgroup of human melanomas. Furthermore, they suggest that IL-8 may play a role not only in immunomodulation but also in melanoma progression and metastatic spread.

Polymorphonuclear neutrophils (PMN) are known to participate in the development of tissue injury during myocardial infarction due to both free oxygen radicals release, as well as to their involvement in the “no-reflow” phenomenon. We have previously shown that pheripheral blood plasma (obtained from patients with acute myocardial infarction) has chemotactic activity for PMN and is able to induce PMN adherence as well as superoxide anion production. To investigate whether interleukin-8 (IL-8/NAP-1), a potent chemotactic factor for PMN, is involved in plasma-mediated PMN stimulation, we measured plasma levels of IL-8 in five patients with transmural myocardial infarction with highly sensitive enzyme-linked immunosorbent assay (ELISA) using specific antibodies. Blood samples were taken immediately after patients' admission, within 15 and 30 min of treatment with intravenous nitrates, as well as after 1, 2, 3, and 7 days. All samples expressed IL-8 activity within the detection limit (0.4 ng/ml) as observed at the basal state. Thus, IL-8 may not be considered as responsible for the chemotactic activity in peripheral blood in patients with myocardial infarction.

Chronic inflammatory dermatoses during pregnancy can take varying courses in mother and child. The dominant Th2-response characteristic for pregnancy may explain why atopic eczema or lupus erythematosus may deteriorate while psoriasis vulgaris may improve. In contrast, impetigo herpetiformis frequently shows a severe course. Lupus erythematosus and other autoantibody-triggered dermatoses like pemphigus vulgaris pose an increased risk for the child because of placental transfer of autoantibodies with specific skin changes or systemic manifestations of the disease as well as placental insufficiency, growth retardation and premature birth. Such risks are not associated with linear IgA dermatosis. A severe pityriasis rosea during the first 20 weeks of pregnancy may lead to an increased risk of abortion or premature delivery. Early diagnosis and individually adjusted therapy of skin diseases is mandatory to avoid any risk for mother or child.