Laccase-Treated Polystyrene Surfaces with Caffeic Acid, Dopamine, and L-3,4-Dihydroxyphenylalanine Substrates Facilitate the Proliferation of Melanocytes and Embryonal Carcinoma Cells NTERA-2.

This study presents the effects of treating polystyrene (PS) cell culture plastic with oxidoreductase enzyme laccase and the catechol substrates caffeic acid (CA), L-DOPA, and dopamine on the culturing of normal human epidermal melanocytes (NHEMs) and human embryonal carcinoma cells (NTERA-2). The laccase-substrate treatment improved PS hydrophilicity and roughness, increasing NHEM and NTERA-2 adherence, proliferation, and NHEM melanogenesis to a level comparable with conventional plasma treatment. Cell adherence dynamics and proliferation were evaluated. The NHEM endpoint function was quantified by measuring melanin content. PS surfaces treated with laccase and its substrates demonstrated the forming of polymer-like structures. The surface texture roughness gradient and the peak curvature were higher on PS treated with a combination of laccase and substrates than laccase alone. The number of adherent NHEM and NTERA-2 was significantly higher than on the untreated surface. The proliferation of NHEM and NTERA-2 correspondingly increased on treated surfaces. NHEM melanin content was enhanced 6-10-fold on treated surfaces. In summary, laccase- and laccase-substrate-modified PS possess improved PS surface chemistry/hydrophilicity and altered roughness compared to untreated and plasma-treated surfaces, facilitating cellular adherence, subsequent proliferation, and exertion of the melanotic phenotype. The presented technology is easy to apply and creates a promising custom-made, substrate-based, cell-type-specific platform for both 2D and 3D cell culture.

Developments and perspectives in allergology.

Allergology is a key part of dermatological care. This paper reviews current pathophysiological, diagnostic and therapeutic developments in immediate-type allergies. Type-2 inflammation is involved in several allergological diseases such as allergic rhinitis and asthma. Allergen immunotherapy as an important therapeutic procedure is regulated in Germany by an official legal directive (Therapieallergene-Verordnung). Therapeutically, several biologics are already available that target interleukin (IL)-4, -5, -13, -33, or TSLP (thymic stromal lymphopoietin). Collateral efficacy may result in simultaneous treatment of allergological comorbidities. In mast cell mediated diseases (urticaria, anaphylaxis), there is increasing understanding of mast cell activation pathways. Several mast cell receptors such as MRGPRX2 (mas-related G protein coupled receptor X2) and Siglec-8 (sialinic acid binding Ig like lectin-8) as well as intracellular signaling pathways have recently been identified. Clinical trials are underway with drugs acting on mast cell receptors and intracellular signaling, i.e., Bruton's tyrosine kinase inhibitors. Further perspectives on biomarkers, novel therapeutics and unmet needs for future research activities are presented.

Food allergy - New risks through vegan diet? Overview of new allergen sources and current data on the potential risk of anaphylaxis.

A vegan diet is increasingly en vogue, i.e., a diet based on plants, in which animal products are completely avoided, often for health and environmental reasons. The menu is supplemented with pulses (e.g., soy, lentils, peas), nuts (e.g., cashew, macadamia, almond, pecan, para, walnut) and seeds (e.g., chia, flaxseed) or pseudo-grains (quinoa, buckwheat). Indeed, the product range is expanding to include vegan foods such as milk alternatives (e.g., oat, almond, soy drinks) and cheese or meat substitutes (e.g., soy-based). Food allergies are also on the rise, with an increasing prevalence worldwide. It is worthy of note that the main allergens of anaphylactic reactions to food in adults are predominantly of plant origin, mainly pulses and nuts - the very foods that form the main source of protein in the vegan diet. In this context, allergies to storage proteins (e.g., Gly m 5 and Gly m 6 from soya beans) can lead to severe anaphylactic reactions, while highly processed substitute products containing plant protein isolates (e.g., pea flour) in concentrated form continue to be of particular concern and may therefore be allergologically problematic. In this article, we aim to provide an overview of allergens and emerging allergen sources in vegan foods and highlight the anaphylaxis risk of the vegan diet.

Atypical fibroxanthoma and pleomorphic dermal sarcoma - gene expression analysis compared with undifferentiated cutaneous squamous cell carcinoma.

BACKGROUND: The histogenetic origin of atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) has not been definitively elucidated. In addition to a fibroblastic origin, a keratinocytic differentiation is discussed due to strong clinical, histomorphological and molecular genetic similarities with undifferentiated cutaneous squamous cell carcinoma (cSCC). PATIENTS AND METHODS: 56 cases (36 AFXs, 8 PDSs, 12 undifferentiated cSCCs) were evaluated for their clinical, histomorphological, and immunohistochemical characteristics. RNA transcriptome analysis was performed on 18 cases (6 AFXs/PDSs, 6 undifferentiated cSCCs, 6 differentiated cSCCs). RESULTS: Clinically, the strong similarities in age, gender and tumor location were confirmed. Without further immunohistochemical staining, histomorphological differentiation between AFX/PDS and undifferentiated cSCC is often impossible. Principal component analysis of the RNA transcriptome analysis showed that AFX/PDS and differentiated cSCC each formed their own cluster, while the undifferentiated cSCCs fall in between these two groups, but without forming a cluster of their own. When examining differentially expressed genes (DEGs), the heat maps showed that there were cases within the undifferentiated cSCC that were more likely to be AFX/PDS than differentiated cSCC based on their expression profile. CONCLUSIONS: The results provide evidence of molecular similarities between AFX/PDS and undifferentiated cSCC and suggest a common histogenetic origin.

Depression, Anxiety, and Suicidal Ideation in Patients with Atopic Eczema in a Prospective Study in Leipzig, Germany.

BACKGROUND: Atopic eczema (AE) is known to be associated with depression and anxiety. We aimed at investigating the occurrence of selected psychological comorbidities in patients with AE under treatment in our university dermatological department. METHODS: Monocentric prospective examination of adult AE patients using PO-SCORAD (Patient-Oriented Severity Scoring of AD), EASI (Eczema Area and Severity Index), POEM (Patient-Oriented Eczema Measure), DLQI (Dermatologic Life Quality Index), LSNS-6 (Lubben Social Network Scale 6), CES-D (Center for Epidemiologic Studies Depression Scale), HADS-D and -A (Hospital Anxiety and Depression Scale), and GAD-7 (Generalized Anxiety Disorder Scale-7) was carried out. We looked for correlations between AE severity and psychosocial comorbidities. Data were compared with age- and sex-matched controls from nonatopic subjects. STATISTICS: Mann-Whitney U test and Spearman's rank correlation were used. RESULTS: Eighty-four patients (44 women, median age 35.0 years, range: 19.4-92.8 years) were included. PO-SCORAD was 40.4 [23.4-55.4] (median [interquartile range]), EASI 9.3 [3.4-18.9], POEM 16 [8-24], and DLQI 10 [4-18]. Compared with 161 from the healthy LIFE-Adult cohort controls, our patients with AE had significantly higher scores for HADS, GAD-7, and CES-D (p < 0.001, respectively), but there was no increase in the LSNS score (18 vs. 19; p = 0.067). Within the group of AE patients, there was a significant correlation of the subjective skin severity and the depression and anxiety values: POEM significantly correlated with GAD-7, CES-D, and HADS-A and -D (p < 0.001). PO-SCORAD significantly correlated with GAD-7 and CES-D (p < 0.05). EASI correlated neither with HADS-A or -D nor with CES-D. Patients with suicidal thoughts, plans, or attempts in the last 12 months had significantly more severe AE than those without (POEM 25 [15.3-26] vs. 15 [7-23]; p = 0.013, and PO-SCORAD 51.6 [40.2-63] vs. 20.5 [20.7-52]; p = 0.014). CONCLUSION: Patients with AE being currently under treatment in our department had significantly increased scores indicating depression and anxiety. Suicidal tendency was increased in patients with severe AE. KEY MESSAGE: AE patients may develop depression, anxiety, and suicidal ideation. Patient-oriented scores may help identifying high-risk patients.

Update on Type-1 Allergy Diagnostics.

Diagnostics in type-1 allergy rely on medical history and clinical examination. Extent and severity of signs and symptoms can be documented by standardized scores and questionnaires. Both skin prick test and intradermal test are useful for search of immunoglobulin E-mediated sensitizations but the availability of commercially available diagnostic extracts has been markedly reduced during the last years. Investigation of total and of specific serum IgE is the most important in vitro diagnostic analyte in type-1 allergy. Identification of the individual molecules to which patients are sensitized, known as molecular or component-resolved diagnostics (CRD), has recently markedly improved management of type-1 allergy to pollen, food and hymenoptera venoms. Main features of CRD are increased analytic sensitivity, detection of cross-reactivity and determination of individual sensitization profiles which allow for risk assessment and facilitate decisions for or against allergen immunotherapy. Basophil activation test as well as determination of selected biomarkers (e.g. tryptase) may also be helpful in some cases. If any allergy test is positive, one will have to distinguish reactions, which are clinically relevant, from those, which are not. In vivo provocation tests (e.g. nasal provocation, oral drug or food challenge) may help to clarify the relevance of a sensitization.

Covering of large scalp defects prior to postoperative irradiation.

BACKGROUND AND OBJECTIVE: After R0 resection of extensive cutaneous squamous cell carcinoma of the scalp with indication for postoperative radiotherapy, closure techniques should be chosen that allow rapid initiation of radiotherapy. The aim of this retrospective analysis is to evaluate defect coverage by transverse transposition flap and split skin grafting of the donor site in such a scenario with regard to oncologic safety (recurrence rate) and permanence of wound closure. PATIENTS AND METHODS: Eleven patients were identified who had histologic cutaneous squamous cell carcinoma treated by microscopically controlled excision and defect coverage using a transverse transposition flap and split skin grafting of the donor site and who received postoperative radiotherapy. Patients were evaluated for recurrence, wound healing disorders and side effects of radiotherapy. RESULTS: The mean age was 81 years. Follow-up time averaged 1.4 years after the last radiotherapy session. Wound healing disorders of the transposition flap or graft necrosis were not detected. All therapy-associated side effects had resolved at follow-up. Local recurrence or metastasis did not occur. CONCLUSIONS: Combined transverse transposition flap plasty with split-skin grafting of the donor site is a safe treatment concept with few side effects for large scalp defects with exposed calvaria requiring postoperative radiotherapy.

Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Nivolumab and ipilimumab, alone or in combination, are widely used immunotherapeutic treatment options for patients with advanced-ie, unresectable or metastatic-melanoma. This criterion, however, excludes patients with stage IV melanoma with no evidence of disease. We therefore aimed to evaluate the safety and efficacy of adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus a placebo in this patient population. METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 trial in 20 German academic medical centres. Eligible patients were aged 18-80 years with stage IV melanoma with no evidence of disease after surgery or radiotherapy. Key exclusion criteria included uveal or mucosal melanoma, previous therapy with checkpoint inhibitors, and any previous immunosuppressive therapy within the 30 days before study drug administration. Eligible patients were randomly assigned (1:1:1), using a central, interactive, online system, to the nivolumab plus ipilimumab group (1 mg/kg of intravenous nivolumab every 3 weeks plus 3 mg/kg of intravenous ipilimumab every 3 weeks for four doses, followed by 3 mg/kg of nivolumab every 2 weeks), nivolumab monotherapy group (3 mg/kg of intravenous nivolumab every 2 weeks plus ipilimumab-matching placebo during weeks 1-12), or double-matching placebo group. The primary endpoint was the recurrence-free survival in the intention-to-treat population. The results presented in this report reflect the prespecified interim analysis of recurrence-free survival after 90 events had been reported. This study is registered with ClinicalTrials.gov, NCT02523313, and is ongoing. FINDINGS: Between Sept 2, 2015, and Nov 20, 2018, 167 patients were randomly assigned to receive nivolumab plus ipilimumab (n=56), nivolumab (n=59), or placebo (n=52). As of July 2, 2019, at a median follow-up of 28·4 months (IQR 17·7-36·8), median recurrence-free survival was not reached in the nivolumab plus ipilimumab group, whereas median recurrence-free survival was 12·4 months (95% CI 5·3-33·3) in the nivolumab group and 6·4 months (3·3-9·6) in the placebo group. The hazard ratio for recurrence for the nivolumab plus ipilimumab group versus placebo group was 0·23 (97·5% CI 0·12-0·45; p<0·0001), and for the nivolumab group versus placebo group was 0·56 (0·33-0·94; p=0·011). In the nivolumab plus ipilimumab group, recurrence-free survival at 1 year was 75% (95% CI 61·0-84·9) and at 2 years was 70% (55·1-81·0); in the nivolumab group, 1-year recurrence-free survival was 52% (38·1-63·9) and at 2 years was 42% (28·6-54·5); and in the placebo group, this rate was 32% (19·8-45·3) at 1 year and 14% (5·9-25·7) at 2 years. Treatment-related grade 3-4 adverse events were reported in 71% (95% CI 57-82) of patients in the nivolumab plus ipilimumab group and in 27% (16-40) of those in the nivolumab group. Treatment-related adverse events of any grade led to treatment discontinuation in 34 (62%) of 55 patients in the nivolumab plus ipilimumab group and seven (13%) of 56 in the nivolumab group. Three deaths from adverse events were reported but were considered unrelated to the study treatment. INTERPRETATION: Adjuvant therapy with nivolumab alone or in combination with ipilimumab increased recurrence-free survival significantly compared with placebo in patients with stage IV melanoma with no evidence of disease. The rates of grade 3-4 treatment-related adverse events in both active treatment groups were higher than the rates reported in previous pivotal trials done in advanced melanoma with measurable disease. FUNDING: Bristol-Myers Squibb.

Reduced lipolysis in lipoma phenocopies lipid accumulation in obesity.

BACKGROUND: Elucidation of lipid metabolism and accumulation mechanisms is of paramount importance to understanding obesity and unveiling therapeutic targets. In vitro cell models have been extensively used for these purposes, yet, they do not entirely reflect the in vivo setup. Conventional lipomas, characterized by the presence of mature adipocytes and increased adipogenesis, could overcome the drawbacks of cell cultures. Also, they have the unique advantage of easily accessible matched controls in the form of subcutaneous adipose tissue (SAT) from the same individual. We aimed to determine whether lipomas are a good model to understand lipid accumulation. METHODS: We histologically compared lipomas and control SAT, followed by assessment of the lipidome using high-resolution 1H NMR spectroscopy and ESI-IT mass spectrometry. RNA-sequencing was used to obtain the transcriptome of lipomas and the matched SAT. RESULTS: We found a significant increase of small-size (maximal axis < 70 µm) and very big (maximal axis > 150 µm) adipocytes within lipomas. This suggests both enhanced adipocyte proliferation and increased lipid accumulation. We further show that there is no significant change in the lipid composition compared to matched SAT. To better delineate the pathophysiology of lipid accumulation, we considered two groups with different genetic backgrounds: (1) lipomas with HMGA2 fusions and (2) without gene fusions. To reduce the search space for genes that are relevant for lipid pathophysiology, we focused on the overlapping differentially expressed (DE) genes between the two groups. Gene Ontology analysis revealed that DE genes are enriched in pathways related to lipid accumulation. CONCLUSIONS: We show that the common shared lipid accumulation mechanism in lipoma is a reduction in lipolysis, with most gene dysregulations leading to a reduced cAMP in the adipocyte. Superficial lipomas could thus be used as a model for lipid accumulation through altered lipolysis as found in obese patients.

Prophylactic Treatment in Hereditary Angioedema Is Associated with Reduced Anxiety in Patients in Leipzig, Germany.

BACKGROUND: Hereditary angioedema (HAE) is associated with relevant disease-related burden. We aimed at investigating prevalence of depression and anxiety in patients with HAE in Leipzig, Germany. METHODS: Questionnaire-based evaluation of medical history, Angioedema Control Test (AECT), Angioedema Quality of Life Questionnaire (AE-QoL), Generalized Anxiety Disorder Scale-7 (GAD-7), and Hospital Anxiety and Depression Scale (HADS). RESULTS: Thirty-seven patients with HAE were included (31 females, mean age 49.6 ± 17.5 years). A mean diagnostic delay between first symptoms and correct diagnosis of 14.2 ± 14.5 years was detected. Patients aged <50 years (n = 18) had been diagnosed significantly earlier with HAE than older patients (p = <0.001). In 6 patients (16.2%), unnecessary medical interventions were performed and 14 patients (43.8%) reported at least 1 HAE-related death of a family member. Psychological stress was the most common triggering factor (96.2%). HADS scores revealed depression in 5/37 patients (13.5%) and anxiety in 16/37 (43.2%), GAD-7 score indicated anxiety in 9/36 (25%) participants. Patients receiving long-term prophylactic treatment (n = 17, 45.9%) showed significantly better disease control (AECT; p = <0.001) and quality of life (AE-QoL; p = <0.001) compared to those with on-demand treatment only. Patients with long-term prophylactic treatment showed significantly lower scores for anxiety and depression at GAD-7 (p = 0.011) and HADS (anxiety: p = 0.021; depression: p = 0.008). In 5 patients, treatment regime was changed as AECT score indicated insufficient disease control. Subsequently, we measured significant improvement of quality of life (AE-QoL, p = 0.04) and disease control (AECT; p = 0.032). CONCLUSION: Anxiety was a frequent burden in our study group and showed a significant association with low disease control. Our data indicate that prophylactic HAE treatment can improve psychosocial burden of HAE.

Distinct Immune Signatures Indicative of Treatment Response and Immune-Related Adverse Events in Melanoma Patients under Immune Checkpoint Inhibitor Therapy.

To identify potential early biomarkers of treatment response and immune-related adverse events (irAE), a pilot immune monitoring study was performed in stage IV melanoma patients by flow cytometric analysis of peripheral blood mononuclear cells (PBMC). Overall, 17 patients were treated with either nivolumab or pembrolizumab alone, or with a combination of nivolumab and ipilimumab every three weeks. Of 15 patients for which complete response assessment was available, treatment responders (n = 10) as compared to non-responders (n = 5) were characterized by enhanced PD-1 expression on CD8+ T cells immediately before treatment (median ± median absolute deviation/MAD 26.7 ± 10.4% vs. 17.2 ± 5.3%). Responders showed a higher T cell responsiveness after T cell receptor ex vivo stimulation as determined by measurement of programmed cell death 1 (PD-1) expression on CD3+ T cells before the second cycle of treatment. The percentage of CD8+ effector memory (CD8+CD45RA-CD45RO+CCR7-) T cells was higher in responders compared to non-responders before and immediately after the first cycle of treatment (median ± MAD 39.2 ± 7.3% vs. 30.5 ± 4.1% and 37.7 ± 4.6 vs. 24.0 ± 6.4). Immune-related adverse events (irAE) were accompanied by a higher percentage of activated CD4+ (CD4+CD38+HLADR+) T cells before the second treatment cycle (median ± MAD 14.9 ± 3.9% vs. 5.3 ± 0.4%). In summary, PBMC immune monitoring of immune-checkpoint inhibition (ICI) treatment in melanoma appears to be a promising approach to identify early markers of treatment response and irAEs.

Osteogenic Potential of Mesenchymal Stem Cells from Adipose Tissue, Bone Marrow and Hair Follicle Outer Root Sheath in a 3D Crosslinked Gelatin-Based Hydrogel.

Bone transplantation is regarded as the preferred therapy to treat a variety of bone defects. Autologous bone tissue is often lacking at the source, and the mesenchymal stem cells (MSCs) responsible for bone repair mechanisms are extracted by invasive procedures. This study explores the potential of autologous mesenchymal stem cells derived from the hair follicle outer root sheath (MSCORS). We demonstrated that MSCORS have a remarkable capacity to differentiate in vitro towards the osteogenic lineage. Indeed, when combined with a novel gelatin-based hydrogel called Osteogel, they provided additional osteoinductive cues in vitro that may pave the way for future application in bone regeneration. MSCORS were also compared to MSCs from adipose tissue (ADMSC) and bone marrow (BMMSC) in a 3D Osteogel model. We analyzed gel plasticity, cell phenotype, cell viability, and differentiation capacity towards the osteogenic lineage by measuring alkaline phosphatase (ALP) activity, calcium deposition, and specific gene expression. The novel injectable hydrogel filled an irregularly shaped lesion in a porcine wound model displaying high plasticity. MSCORS in Osteogel showed a higher osteo-commitment in terms of calcium deposition and expression dynamics of OCN, BMP2, and PPARG when compared to ADMSC and BMMSC, whilst displaying comparable cell viability and ALP activity. In conclusion, autologous MSCORS combined with our novel gelatin-based hydrogel displayed a high capacity for differentiation towards the osteogenic lineage and are acquired by non-invasive procedures, therefore qualifying as a suitable and expandable novel approach in the field of bone regeneration therapy.

[What is the role of allergen immunotherapy in IgE-mediated food allergy?] / Welche Rolle spielt die Allergenimmuntherapie bei Immunglobulin-E-vermittelter Nahrungsmittelallergie?

In food allergy, allergen avoidance and emergency treatment are still therapeutic hallmarks but, recently, allergen immunotherapy (AIT), with different application routes, has gained more attention. In primary food allergy, oral immunotherapy has been frequently used in clinical trials. This year, an oral immunotherapy preparation for treatment of peanut allergy was licensed in Europe. In secondary food allergy, sublingual and subcutaneous extracts have been used in clinical trials, mostly with cross-reactive pollen allergens. As there is no AIT preparation licensed for this indication, therapy should only be started when there also is a need for treating associated respiratory symptoms.

[Treatment of psoriasis with secukinumab : Practical guidance]. / Behandlung der Psoriasis mit Secukinumab : Praxisrelevante Hinweise.

BACKGROUND: Moderate to severe plaque psoriasis can be treated effectively with immunomodulating biologicals such as the interleukin-17A inhibitor secukinumab. In practice, however, questions often arise as to how to proceed in special situations, such as infections, comorbidity, pregnancy, or surgery. OBJECTIVES: To address frequent questions about the treatment of plaque psoriasis with secukinumab in a consensus document of German psoriasis experts that supplements current guidelines. METHODS: In a virtual expert meeting in May 2020, practical aspects of the treatment of psoriasis were discussed based on the experience of the participants and on current literature. The results of this discussion were summarized in the present consensus document. RESULTS: This article provides practical guidance on case history, documentation of previous therapies, severity of psoriasis, and comorbidities before starting therapy with secukinumab. For patients treated with secukinumab, the course of action in case of vaccinations, chronic or acute infections, surgical interventions, special manifestations of psoriasis, and comorbidities including history of cancer and autoimmune disorders is discussed. Questions regarding family planning and health policy regulations are also addressed. DISCUSSION: The recommendations for the treatment of psoriasis with secukinumab summarized in this consensus document may contribute to achieve optimal therapy for patients and to improve their quality of life.

Lupus erythematosus: correlation of clinical and histological findings and proposal for a modified disease classification.

BACKGROUND: Classification of lupus erythematosus (LE) is conflicting as it is carried out from different starting points. Whereas dermatological classifications categorize LE morphologically based on specific cutaneous lesions, rheumatologic classifications are based on symptomatic aspects. Indeed, LE is a systemic autoimmune disease with variable acuity and organ involvement. All cutaneous disease patterns may occur in both limited-cutaneous and systemic LE. PATIENTS AND METHODS: 76 LE-patients with complete clinical data, clinical photographs and biopsy of cutaneous manifestations as well as paraclinical findings were retrospectively analyzed. Based on a published two-dimensional classification system that considers disease-specific skin manifestations and final disease diagnosis separately, patients' diagnoses were revised and compared with those in medical records. In addition, the extent to which patients could be clustered by diagnosis based on their LE-specific skin manifestations, corresponding histopathological changes, and paraclinical data was investigated. RESULTS: After re-evaluation, the proportion of patients with limited-cutaneous LE decreased from 82% previously to 24%. More than two-thirds of patients indeed showed intermediate or systemic LE. Disease-specific skin manifestations, histologic characteristics and paraclinical data did not cluster with final diagnoses. CONCLUSIONS: First, the work underlines the systemic character of the disease. Second, a two-dimensional approach can help overcome classification difficulties in LE, as skin-morphologic and symptomatic aspects can be considered separately.

Inpatient care for skin diseases in Germany: multi-source analysis on the current and future health care needs.

BACKGROUND: In Germany, skin diseases are mainly treated in the 115 dermatological hospitals. METHODS: Health care and health economic analysis of dermatological inpatient care and prediction of future care needs based on primary and secondary data. RESULTS: Outpatient and inpatient care for dermatologic treatment indications is predominantly provided by dermatology specialists. Inpatient treatment was provided for 833,491 cases in 2018, corresponding to 4.21 % of all inpatient cases (19,808,687). Most common treatment cases were: epithelial skin cancer (total 87,386, of which dermatology clinics 52,608), followed by melanoma (23,917/17,774), psoriasis (19,291/13,352), erysipelas (73,337/11,260), other dermatitis (12,671/10,842), atopic dermatitis (AD) (11,421/9,734), and herpes zoster (26,249/9,652). With an average length of stay of 5.69 days, dermatology hospitals were in the bottom third. The proportion of inpatient indications cared for in dermatology hospitals was highest for prurigo (95.2 %), pemphigus (94.9 %), parapsoriasis (94.6 %), pemphigoid (90.3 %), eczema other than AD (85.6 %), and AD (85.2 %). While the total number of inpatient treatment cases in Germany has increased by an average of 17.5 % between 2000 and 2018, this is the case for 26.6 % of skin diseases and over 150 % for individual ones. The projection of current to future inpatient care suggests a continued high demand for inpatient care by dermatology hospitals. CONCLUSION: Inpatient dermatological care will continue to be an indispensable component of qualified, socially necessary care in Germany.

[Drug-induced interstitial lung disease (DILD) during treatment with ustekinumab]. / Medikamentös induzierte interstitielle Lungenerkrankung (DILD) unter Ustekinumab.

We report on a patient with severe psoriasis vulgaris who developed drug-induced interstitial lung disease (DILD) during treatment with ustekinumab. The diagnosis was based on coincidence with start of therapy, high-resolution computer tomography of the thorax and bronchoalveolar lavage. After discontinuation of the treatment with ustekinumab the clinical symptoms and the chest scan results improved. This case highlights a possible adverse event of ustekinumab.

[Complex treatment of pyoderma gangrenosum after minor trauma and primary surgical intervention with suspected necrotizing fasciitis]. / Komplexe Therapie des Pyoderma gangraenosum nach Bagatelltrauma und primär chirurgischer Intervention bei Verdacht auf nekrotisierende Fasziitis.

This article presents the case of a rapidly progressing pyoderma gangrenosum (PG) following a minor trauma and surgical intervention. A 46-year-old patient was admitted to hospital after a minor trauma of the right lower leg with a suspected diagnosis of erysipelas bullosum. A magnetic resonance imaging (MRI) scan showed the suspicion of necrotizing fasciitis (NF) with indications for immediate incision and fascia resection. According to the results of the histopathological analysis and microbiological assessment without signs for a bacterial infection, high-dose steroid treatment and immunosuppressive treatment with cyclosporin A were initiated under the assumption of PG. Additionally, the patient was treated with hyperbaric oxygenation (HBO). The 2­year follow-up showed a gradual restitution of the soft tissues.

Atopic dermatitis and psychosocial comorbidities.

Atopic dermatitis (AD) is a chronic inflammatory disease that may be associated with a number of comorbidities including psychosocial disorders, which are the primary focus of this article. The data presented is based on a literature search in PubMed and subsequent screening of relevant review articles and guidelines. There is a greater prevalence of depression, anxiety, sleep disorders and suicidal ideation among individuals with AD. The disease negatively impacts patients' quality of life. Children with AD have been shown to more commonly exhibit signs of attention-deficit/hyperactivity disorder. Only little data exists on the association of AD with schizophrenia, eating disorders or obsessive-compulsive disorder. There is a great need for research in the field of AD-related comorbidities, especially with respect to the question as to whether and how novel treatment options may potentially affect these comorbidities.

[Possible effect of interleukin-17 blockade in pemphigus foliaceus and neutrophilic diseases]. / Mögliche Wirkung einer Interleukin-17-Blockade beim Pemphigus foliaceus und neutrophilen Erkrankungen.

The role of interleukin-17 (IL-17) in pemphigoid diseases is not fully understood. Both pemphigus vulgaris (PV) as well as pemphigus foliaceus (PF) show intralesional IL-17 positive cells. A patient with initially assumed coexisting PF and psoriasis pustulosa (PP) was treated with the anti-IL-17 antibody secukinumab. The clinical skin picture markedly improved and the level of anti-desmoglein-1 antibodies clearly decreased; however, with the prolongation of injection intervals of secukinumab, autoantibody levels started to rise again. A dose-dependent effect of secukinumab on autoantibody production in PF is suspected. Retrospectively, a neutrophilic PF can be discussed in the present case, where almost complete healing was achieved under IL-17 blockade treatment.