Secukinumab in adult patients with lichen planus: efficacy and safety results from the randomized placebo-controlled proof-of-concept PRELUDE study.

BACKGROUND: Patients with lichen planus (LP) refractory to available therapies often experience a high disease burden, representing a population with a clear unmet need for new treatments. OBJECTIVES: To evaluate the efficacy and safety of secukinumab 300 mg over 32 weeks in adult patients with biopsy-proven cutaneous LP (CLP), mucosal LP (MLP) or lichen planopilaris (LPP) that is inadequately controlled by topical corticosteroids. METHODS: PRELUDE was a randomized double-blind placebo-controlled phase II proof-of-concept study that enrolled patients with CLP, MLP or LPP. Eligible patients were randomized to either secukinumab 300 mg every 4 weeks for 32 weeks (SECQ4W) or placebo for 16 weeks followed by secukinumab 300 mg every 2 weeks (SECQ2W) for 16 weeks. The primary endpoint was achievement of the newly designed Investigator's Global Assessment (IGA) score ≤ 2 at week 16. RESULTS: Overall, 111 patients were randomized (n = 37 each) to CLP, MLP and LPP cohorts. As the proof-of-concept criteria were not met for any of the three cohorts, the primary objective was not met. A numerically higher proportion of patients achieved IGA ≤ 2 response at week 16 with SECQ4W vs. placebo in the MLP {37.5% [95% credibility interval (Crl) 20.3-57.2] vs. 23.1% (95% Crl 6.5-49.2)} and LPP cohorts [37.5% (95% Crl 20.2-57.3) vs. 30.8% (95% Crl 10.8-57.6)]. In the LPP cohort, a sustained response for IGA ≤ 2 from week 16 to week 32 was achieved with SECQ4W (week 16, 37.5%; week 32, 45.8%), and a substantial improvement was observed in IGA ≤ 2 response in patients from this cohort who switched from placebo (week 16, 30.8%) to SECQ2W after week 16 (week 32, 63.6%). The safety profile was consistent with the known profile of secukinumab and showed no new or unexpected signals. CONCLUSIONS: PRELUDE is the first randomized controlled basket trial evaluating interleukin (IL)-17A inhibition with secukinumab across three subtypes of LP. Secukinumab was well tolerated and safe, showing different response rates across the three subtypes, with numerical IGA improvements in MLP and LPP, and no response in CLP. The study raises the question of a differential role of IL-17A across LP subtypes. The novel IGA score showed significant correlation with both patient- and physician-reported outcome measurements.

Lichen planus (LP) is a skin disease that causes itchy, reddish-purple bumps on the skin. LP can affect different parts of the body, including the skin, mouth, genitals and nails. People with LP often experience intense itch, pain and discomfort, which can affect their daily lives. Secukinumab is a drug specifically designed to target and block a protein called 'interleukin-17A', which is found in high amounts in the lesions of LP. We carried out a clinical study to look at the effect of secukinumab separately in three different types of LP: cutaneous LP (CLP), mucosal LP (MLP) and lichen planopilaris (LPP). The study was conducted in the USA, France and Germany. A total of 111 adults who had not responded to topical treatment (treatment applied directly on the skin) took part in the study. Patients were divided into two groups. In one group, patients were treated with secukinumab 300 mg every 4 weeks for 16 weeks and continued with the treatment for another 16 weeks. In the other group, patients received placebo for 16 weeks and then received secukinumab 300 mg every 2 weeks for the next 16 weeks. All the patients were followed up for 8 weeks after stopping treatment. We measured whether secukinumab could reduce symptoms associated with LP using both doctor- and patient-assessed severity and quality-of-life measures. We also measured the side-effects related to the drug. We found that secukinumab was safe for people with LP, but it did not substantially reduce symptoms in people with CLP and only showed a tendency for improvement in people with MLP and LPP.

Efficacy and safety of adjuvant immunoadsorption in pemphigus vulgaris and pemphigus foliaceus (IA-Pem Study): a multicentre randomized controlled trial.

BACKGROUND: Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are potentially life-threatening autoimmune blistering diseases. Treatment is based on long-term immunosuppression with high doses of glucocorticosteroids in combination with potentially corticosteroid-sparing agents and/or rituximab. Immunoadsorption (IA) has emerged as a fast-acting adjuvant treatment option. OBJECTIVES: To assess the clinical efficacy of IA in addition to best medical treatment (BMT). METHODS: We conducted a multicentre (26 centres from Germany and Austria) randomized controlled trial in 72 patients with newly diagnosed, relapsed or chronic active PV or PF (34 female patients and 38 male patients, aged 42-72 years) comparing BMT (prednisolone 1.0 mg kg-1 per day plus azathioprine or mycophenolate) with adjuvant IA (BMT + IA). Central 1 : 1 randomization was done at the coordinating centre for clinical trials (KKS Marburg). The primary endpoint was analysed using Kaplan-Meier and Cox regression methods. RESULTS: The study was ended prematurely owing to safety concerns after random allocation of 72 patients to BMT + IA (n = 34) or BMT (n = 38). The primary endpoint, time to complete remission on therapy, was not significantly different for the two groups [hazard ratio (HR) 1.35, 95% confidence interval (CI) 0.68-2.69; P = 0.39]. The cumulative dose of prednisolone was significantly lower in the BMT + IA group compared with BMT alone (difference -1214, 95% CI -2225 to -70; P = 0.03). In a post hoc analysis, patients with more extensive PV/PF showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group (HR 1.87, P = 0.17 in patients with baseline Pemphigus Disease Area Index ≥ 15). While more adverse events were observed in patients in the BMT group (29 vs. 25), severe adverse events were more frequent in patients in the BMT + IA group (17 events in 10 patients vs. 11 events in 8 patients). CONCLUSIONS: In this study, adjuvant IA did not demonstrate a shorter time to clinical remission, but a corticosteroid-sparing effect was observed. In patients with extensive PV/PF, post hoc analysis suggests that adjuvant IA may lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Pemphigus vulgaris and pemphigus foliaceus are potentially life-threatening autoantibody-driven blistering diseases, which present with erosions or blisters on skin and/or mucous membranes. Treatment is based on long-term immunosuppressive agents. Immunoadsorption (IA) is a procedure that removes autoantibodies from the blood and has emerged as a fast-acting treatment option for pemphigus.We conducted a trial comparing best medical treatment (BMT) (prednisolone 1.0 mg kg per day plus azathioprine or mycophenolate) with best medical treatment plus IA (BMT + IA). A total of 26 centres from Germany and Austria recruited 72 patients with active pemphigus (34 women and 38 men, aged 42­72 years) who were randomly allocated in a ratio of 1 : 1 to the treatment groups.Following inclusion of 72 patients in the BMT + IA (n = 34) or BMT (n = 38) groups, the study ended prematurely owing to safety concerns. The main outcome, time to complete remission (relief of all symptoms) while still receiving therapy, was not significantly different for the two groups. In contrast, the cumulative dose of prednisolone was significantly lower in the BMT + IA compared with BMT alone. In an additional analysis, patients with more extensive pemphigus showed a tendency towards a shorter time to remission in the BMT + IA group compared with the BMT group. While more adverse events were observed in the BMT group (29 vs. 25), severe adverse events were more frequent in the BMT + IA group (17 vs. 11). In this study, IA did not show a shorter time to clinical remission, but a prednisolone-sparing effect was observed. In patients with extensive pemphigus, adjuvant IA may possibly lead to earlier remission, but potential adverse events must be carefully weighed against the expected benefits.

Catalytic antibodies in arrhythmogenic cardiomyopathy patients cleave desmoglein 2 and N-cadherin and impair cardiomyocyte cohesion.

AIMS: Arrhythmogenic cardiomyopathy (AC) is a severe heart disease predisposing to ventricular arrhythmias and sudden cardiac death caused by mutations affecting intercalated disc (ICD) proteins and aggravated by physical exercise. Recently, autoantibodies targeting ICD proteins, including the desmosomal cadherin desmoglein 2 (DSG2), were reported in AC patients and were considered relevant for disease development and progression, particularly in patients without underlying pathogenic mutations. However, it is unclear at present whether these autoantibodies are pathogenic and by which mechanisms show specificity for DSG2 and thus can be used as a diagnostic tool. METHODS AND RESULTS: IgG fractions were purified from 15 AC patients and 4 healthy controls. Immunostainings dissociation assays, atomic force microscopy (AFM), Western blot analysis and Triton X-100 assays were performed utilizing human heart left ventricle tissue, HL-1 cells and murine cardiac slices. Immunostainings revealed that autoantibodies against ICD proteins are prevalent in AC and most autoantibody fractions have catalytic properties and cleave the ICD adhesion molecules DSG2 and N-cadherin, thereby reducing cadherin interactions as revealed by AFM. Furthermore, most of the AC-IgG fractions causing loss of cardiomyocyte cohesion activated p38MAPK, which is known to contribute to a loss of desmosomal adhesion in different cell types, including cardiomyocytes. In addition, p38MAPK inhibition rescued the loss of cardiomyocyte cohesion induced by AC-IgGs. CONCLUSION: Our study demonstrates that catalytic autoantibodies play a pathogenic role by cleaving ICD cadherins and thereby reducing cardiomyocyte cohesion by a mechanism involving p38MAPK activation. Finally, we conclude that DSG2 cleavage by autoantibodies could be used as a diagnostic tool for AC.

Palliative care in dermatooncology - Current practice in German dermatooncological centers and specialist offices.

BACKGROUND: Dermato-oncology patients are often treated in certified skin cancer centers or dermato-oncological specialist offices. Especially in higher tumor stages, patients develop symptoms, either disease-related or due to therapy-related side effects, requiring treatment. Despite a markedly improved prognosis since the introduction of targeted therapies and immunotherapies, advance care planning is required in progressive disease. It is unclear how palliative care of skin cancer patients is currently organized in dermato-oncology. PATIENTS AND METHODS: In a nationwide survey, all certified skin cancer centers and dermato-oncological specialist offices in Germany were contacted and asked to participate in this anonymized survey. RESULTS: Overall, 45 responses (42%) were received. The majority (98%) of the respondents screen the patients on a regular basis for distressing symptoms, and all centers are connected to palliative medical care providers. Only 5% of the medical staff members have the additional qualification "palliative medicine". In 68% of the participating institutions, the opportunity for care planning is offered to patients. For 89%, palliative care is relevant for everyday work, and 82% desire more research opportunities on this topic. CONCLUSIONS: This survey has shown that palliative care plays a major role in dermato-oncological work. Given that only a small proportion of the staff have received specialized training in palliative care, however, an increase of this proportion would be desirable for comprehensive care.

Pathogenic relevance of antibodies against desmoglein 3 in patients with oral lichen planus.

BACKGROUND AND OBJECTIVES: Oral lichen planus (OLP) is a T cell driven disorder that significantly impairs patients' quality of life. Previous reports suggest that both cellular and humoral activities against desmoglein (dsg) 1 and 3 may be involved in OLP pathogenesis. Here, we aim to analyze the frequency of occurrence and pathological significance of anti-dsg antibodies in a large cohort of OLP patients. MATERIALS AND METHODS: OLP patients were screened for anti-dsg antibodies by enzyme-linked immunosorbent assay in three tertiary referral centers. OLP sera with anti-dsg antibodies were further analyzed by Western blot and dispase-based keratinocyte dissociation assay (DDA) to identify the targeted dsg ectodomains and to assess their pathogenicity. RESULTS: Of 151-screened individuals with OLP, only four patients (2.6%) with erosive OLP showed serum IgG against dsg1/3. Western blot analysis with recombinant dsg3 ectodomains revealed preferential recognition of the extracellular domain 5. By DDA with spontaneously immortalized human keratinocytes, none of the sera from these four patients induced acantholysis. CONCLUSIONS: Activation of humoral immunity occurs prevalently in patients with erosive OLP, probably due to epitope spreading. OLP serum antibodies are unable to induce loss of intercellular adhesion in vitro, strongly suggesting that they are not disease causing but rather an epiphenomenon.

Autoimmune skin disorders and SARS-CoV-2 vaccination - a meta-analysis.

BACKGROUND AND OBJECTIVES: The coronavirus SARS-CoV-2, which is the cause of COVID-19 disease in infected patients, has led to an ongoing worldwide pandemic. Although SARS-CoV-2 vaccination had a dramatic positive effect on the course of COVID-19, there has been increasing evidence of adverse effects after SARS-CoV-2 vaccination. This meta-analysis highlights the association between SARS-CoV-2 vaccination and de novo induction or aggravation of inflammatory and autoimmune skin diseases. MATERIAL AND METHODS: A systematic meta-analysis of the literature on new onset or worsening of inflammatory and autoimmune diseases after SARS-CoV-2 vaccination was performed according to the PRISMA guidelines. The search strategy included following terms: "COVID-19/SARS-CoV-2 vaccine bullous pemphigoid/pemphigus vulgaris/systemic lupus erythematosus/dermatomyositis/lichen planus/leukocytoclastic vasculitis." Moreover, we describe representative cases from our dermatology department. RESULTS: The database-search in MEDLINE identified 31 publications on bullous pemphigoid, 24 on pemphigus vulgaris, 65 on systemic lupus erythematosus, nine on dermatomyositis, 30 on lichen planus, and 37 on leukocytoclastic vasculitis until June 30th, 2022. Severity and response to treatment varied among the described cases. CONCLUSIONS: Our meta-analysis highlights a link between SARS-CoV-2 vaccination and new onset or worsening of inflammatory and autoimmune skin diseases. Moreover, the extent of disease exacerbation has been exemplified by cases from our dermatological department.

Immunophenotyping in pemphigus reveals a TH17/TFH17 cell-dominated immune response promoting desmoglein1/3-specific autoantibody production.

BACKGROUND: TH2 cells were thought to be a pivotal factor for initiation of the autoimmune blistering disease pemphigus. However, the role of other T-cell subsets in pemphigus pathogenesis remained unclear. OBJECTIVE: We aimed to characterize the exact phenotype of T cells responsible for the development of pemphigus. METHODS: Whole transcriptome shotgun sequencing was performed to determine differential gene expression in pemphigus lesions and skin of healthy individuals. The cutaneous cytokine signature was further evaluated by real-time quantitative PCR. In peripheral blood, the distribution of TH cell and folliclular helper (TFH) cell subsets was analyzed by flow cytometry. Finally, the capacity of TH and TFH cell subsets to induce desmoglein (Dsg)-specific autoantibodies by memory B cells was evaluated in coculture experiments. RESULTS: Transcriptome analysis of skin samples identified an IL-17A-dominated immune signature in patients with pemphigus, and Kyoto Encyclopedia of Genes and Genomes pathway analysis confirmed the dominance of the IL-17A signaling pathway. Increased expression of IL17A and associated cytokines was also detected by real-time quantitative PCR comparing lesional with perilesional or healthy skin. Interestingly, utilization of flow cytometry showed that patients with active pemphigus had elevated levels of circulating IL-17+, TH17, TFH17, and TFH17.1 cells. Notably, levels of TH17 and TFH17 cells correlated with levels of Dsg-specific CD19+CD27+ memory B cells, and patients with acute pemphigus showed higher levels of Dsg3-autoreactive TFH17 cells. Coculture experiments revealed TFH17 cells as primarily responsible for inducing Dsg-specific autoantibody production by B cells. CONCLUSION: Our findings show that TFH17 cells are critically involved in the pathogenesis of pemphigus and offer novel targets for therapeutic intervention.

Disease progression and response to therapy in pemphigus based on a registry.

BACKGROUND AND OBJECTIVES: Pemphigus diseases are potentially life-threatening and rare autoimmune bullous disorders characterized by blisters and erosions of the skin and mucous membranes. These disorders can be largely divided into two major subtypes: pemphigus vulgaris (PV) and pemphigus foliaceus (PF). The objective of this study was to evaluate the autoantibody profile and response to therapy of PV and PF patients by analyzing the clinicopathological data from a registry for bullous autoimmune dermatoses. PATIENTS AND METHODS: In a retrospective study, data from 69 patients with PV and PF were included in the analysis. The Autoimmune Bullous Skin Intensity Score (ABSIS) was used to assess the clinical course, remissions, relapses and severity of the disease at first manifestation and throughout the observation period. ELISA was performed to assess levels of anti-desmoglein (Dsg)-1 and anti-Dsg3 IgG serum autoantibodies. RESULTS: The mean remission time in PV and PF patients was 63 weeks. PV patients with mucosal involvement showed a more favorable healing process. In PV patients with a moderate/high anti-Dsg1 IgG serum level at baseline, anti-Dsg3 IgG levels decreased during the observation period. CONCLUSIONS: Our study provides additional insights into the clinical course of patients with PV and PF, revealing that a mucosal phenotype is associated with a higher tendency towards remission.

Register-Studie zu Krankheitsentwicklung und Therapieansprechen bei Pemphigus.

HINTERGRUND UND ZIELE: Pemphigus gehört zu den seltenen, aber potentiell lebensbedrohlichen Autoimmunerkrankungen. Typisch sind Blasen und Erosionen der Haut und der Schleimhäute. Grundsätzlich unterscheiden wir zwei Subtypen: Pemphigus vulgaris (PV) und Pemphigus foliaceus (PF). In dieser Studie wurden die klinisch-pathologischen Daten aus einem Register für bullöse Autoimmundermatosen analysiert mit dem Ziel, das Autoantikörperprofil und das Therapieansprechen bei Patienten mit PV und PF genauer zu charakterisieren. PATIENTEN UND METHODEN: In einer retrospektiven Studie wurden die Daten von 69 Patienten mit PV und PF analysiert. Zur Beurteilung des klinischen Verlaufs, der Remissionen und Rezidive sowie des Schweregrads der Krankheit bei Erstmanifestation und während des gesamten Beobachtungszeitraums diente der ABSIS (Autoimmune Bullous Skin Intensity Score) (ABSIS). Mittels ELISA wurden die Spiegel von Anti-Desmoglein (Dsg)-1- und Anti-Dsg- IgG-Autoantikörpern im Serum bestimmt. ERGEBNISSE: Die mittlere Remissionszeit bei Patienten mit PV und PF betrug 63 Wochen. PV-Patienten mit Schleimhautbeteiligung zeigten eine schnellere Heilung. Bei PV-Patienten mit moderat oder stark erhöhten Anti-Dsg1-IgG-Autoantikörpern im Serum zu Beginn erfolgte im Lauf des Beobachtungszeitraums ein Absinken der Anti-Dsg3-IgG-Spiegel. SCHLUSSFOLGERUNGEN: Unsere Studie liefert neue Erkenntnisse zum Krankheitsverlauf bei Patienten mit PV und PF und offenbart, dass ein Phänotyp mit Schleimhautbeteiligung eine stärkere Neigung zur Remission aufweist.

Lichen planus in Germany - epidemiology, treatment, and comorbidity. A retrospective claims data analysis.

BACKGROUND AND OBJECTIVES: Lichen planus (LP) is a chronic inflammatory skin disease and is a major burden for affected patients. However, data on this condition are scarce. This study aims to expand the knowledge on the epidemiology and treatment patterns of LP using German health claims data. PATIENTS AND METHODS: This retrospective observational study was based on the InGef research database. Prevalent and incident LP patients were identified in the years 2015 and 2018. Descriptive statistics were calculated for demographic characteristics, treatment patterns, and comorbidity. RESULTS: The prevalence of LP was 95.9 and the incidence was 20.1 per 100,000 individuals in 2018, corresponding to 79,605 prevalent LP cases in Germany. The first LP diagnosis was generally documented by a dermatologist or a primary care physician. Three-quarters of the incident and half of the prevalent patients received topical therapy, mostly without further systemic therapy. Comorbidity in LP patients was consistent with previously known associations. CONCLUSIONS: Available treatment options remain limited, underscoring the unmet need for safe and efficacious systemic treatment modalities. Lichen planus is frequently accompanied by clinically relevant systemic comorbidity. Taken together, these observations may improve our understanding of the burden of this disease and increase diagnostic awareness among clinicians.

Lichen planus in Deutschland - Epidemiologie, Behandlung und Komorbidität. Eine retrospektive Krankenkassendatenanalyse.

HINTERGRUND UND ZIELE: Lichen planus (LP) ist eine chronisch entzündliche Hauterkrankung, die eine große Belastung für die betroffenen Patienten darstellt. Es liegen jedoch nur wenige Daten zu dieser Erkrankung vor. Ziel dieser Studie ist es, das Wissen über die Epidemiologie und die Behandlungsmuster des LP anhand von Abrechnungsdaten deutscher Krankenkassen zu erweitern. PATIENTEN UND METHODEN: Diese retrospektive Beobachtungsstudie nutzte die InGef-Forschungsdatenbank. Es wurden prävalente und inzidente LP-Patienten aus den Jahren 2015 und 2018 identifiziert. Für demografische Charakteristika, Behandlungsmuster und Komorbidität wurden deskriptive Statistiken berechnet. ERGEBNISSE: Die Prävalenz des LP lag bei 95,9 und die Inzidenz bei 20,1 pro 100 000 Personen im Jahr 2018, was 79 605 prävalenten LP-Fällen in Deutschland entspricht. Die erste LP-Diagnose wurde in der Regel von einem Dermatologen oder Hausarzt gestellt. Drei Viertel der inzidenten und die Hälfte der prävalenten Patienten erhielten eine topische Therapie, meist ohne zusätzliche systemische Therapie. Die Komorbidität des LP stand im Einklang mit bereits bekannten Assoziationen. SCHLUSSFOLGERUNGEN: Die verfügbaren Therapieoptionen sind nach wie vor begrenzt, was den ungedeckten Bedarf an sicheren und wirksamen systemischen Behandlungsmodalitäten unterstreicht. Der LP ist häufig mit klinisch relevanter systemischer Komorbidität verbunden. Zusammengenommen könnten diese Beobachtungen zu einem verbesserten Verständnis der Krankheitslast führen und das diagnostische Bewusstsein für diese Erkrankung unter Klinikern schärfen.

Status quo and perspectives of dermatology hospitals in Germany: spectra of health care and staff situation.

BACKGROUND: Inpatient care in Germany has been subject to change since the introduction of the DRG-based payment system. There have been no publications on important differentiating factors such as the spectrum of care and the staffing situation in dermatology. METHODS: Health care analysis of 115 dermatology hospitals in October 2019 using a structured survey questionnaire. RESULTS: On average, the spectrum of care included 31.0 % general dermatology, 33.6 % surgical dermatology, 15.6 % oncology, and 10.1 % allergology. The clinics had an average of 14 full-time positions and 3 part-time positions (university clinics: 23/5, non-university clinics: 9/2). The mean nationwide proportion of women in the physician teams showed the following distribution: postgraduate physicians 73.3 %, senior physicians 53.0 %, directors 20.0 %. The applicant situation of senior physicians and specialists was assessed as predominantly poor, that of residents as predominantly good. Worse applicant situations were present in non-university hospitals and in rural areas. The satisfaction of the medical directors with the current conditions of inpatient care showed a variable assessment independent of university hospital and non-university hospital status. However, the threat to inpatient care was predominantly assessed as low (71.6 %). CONCLUSIONS: The overall situation of inpatient dermatological care can be classified as predominantly good. In addition, the majority of dermatology clinics provide a wide range of care with regard to the variety of indications. The general conditions, which in some cases are rated as inadequate, require further measures.

Structures and performance characteristics of dermatology hospitals in Germany. Current status and long-term development.

BACKGROUND: The objective of the study was to characterize the performance of German dermatology hospitals. METHODS: A structured survey questionnaire was sent out to all dermatology hospitals in October 2019 as part of a cross-sectional analysis based on health care research. RESULTS: Of the 115 hospitals, 95 (82.6 %) responded, including 34 (35.8 %) university hospitals (UC) and 61 (64.2 %) non-university hospitals (NUC), of which 78 % were urban (43 % UC, 57 % NUC) and 22 % rural (10 % UC, 90 % NUC). The dermatology departments comprised an average of 45 inpatient and 11 day-care beds (UC: 52/13, NUC: 40/9). An average of 2,302 inpatients were cared for in 2018 (UC: 2,874, NUC: 1,983), and the case mix index was 0.76 (UC: 0.74, NUC: 0.77, overall range: 0.40-0.96). Mean length of stay was 5.5 days for UC, relevantly lower than 2013 (5.9 days) and 2011 (7.1 days) data, and also significantly lower for NUC at 5.9 (2018) versus 5.1 days (2013). CONCLUSIONS: German dermatology hospitals continue to have a high volume of inpatient care, with a comparison of the last six years again showing a compression with shorter length of stay and higher occupancy density. Dermatological hospitals represent an essential pillar of dermatological care.

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.

Diagnosis and management of pemphigus: Recommendations of an international panel of experts.

BACKGROUND: Several European countries recently developed international diagnostic and management guidelines for pemphigus, which have been instrumental in the standardization of pemphigus management. OBJECTIVE: We now present results from a subsequent Delphi consensus to broaden the generalizability of the recommendations. METHODS: A preliminary survey, based on the European Dermatology Forum and the European Academy of Dermatology and Venereology guidelines, was sent to a panel of international experts to determine the level of consensus. The results were discussed at the International Bullous Diseases Consensus Group in March 2016 during the annual American Academy of Dermatology conference. Following the meeting, a second survey was sent to more experts to achieve greater international consensus. RESULTS: The 39 experts participated in the first round of the Delphi survey, and 54 experts from 21 countries completed the second round. The number of statements in the survey was reduced from 175 topics in Delphi I to 24 topics in Delphi II on the basis of Delphi results and meeting discussion. LIMITATIONS: Each recommendation represents the majority opinion and therefore may not reflect all possible treatment options available. CONCLUSIONS: We present here the recommendations resulting from this Delphi process. This international consensus includes intravenous CD20 inhibitors as a first-line therapy option for moderate-to-severe pemphigus.

Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis.

Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.

[European Guidelines (S1) on the use of high-dose intravenous immunoglobulin in dermatology]. / Europäische Leitlinien (S1) für die Verwendung von hoch dosierten intravenösen Immunglobulinen in der Dermatologie.

BACKGROUND AND OBJECTIVES: Treatment of severe dermatological autoimmune diseases and toxic epidermal necrolysis (TEN) with high-dose intravenous immunoglobulin (IVIg) is a well-established procedure in dermatology. As treatment with IVIg is usually considered for rare clinical entities or severe cases, the use of immunoglobulin is not generally based on data from randomized controlled trials usually required for evidence-based medicine. Since the indications for the use of IVIg are rare, it is unlikely that such studies will be available in the foreseeable future. Because first-line use is limited by the high costs of IVIg, the first clinical guidelines on the use of IVIg in dermatological conditions were established in 2008 and renewed in 2011. METHODS: The European guidelines presented here were prepared by a panel of experts nominated by the European Dermatology Forum (EDF) and European Academy of Dermatology and Venereology (EADV). The guidelines were developed to update the indications for treatment currently considered effective and to summarize the evidence for the use of IVIg in dermatological autoimmune diseases and TEN. RESULTS AND CONCLUSION: The current guidelines represent consensual expert opinions and definitions on the use of IVIg reflecting current published evidence and are intended to serve as a decision-making tool for the use of IVIg in dermatological diseases.

COVID-19 and implications for dermatological and allergological diseases.

COVID-19, caused by the coronavirus SARS-CoV-2, has become pandemic. A further level of complexity opens up as soon as we look at diseases whose pathogenesis and therapy involve different immunological signaling pathways, which are potentially affected by COVID-19. Medical treatments must often be reassessed and questioned in connection with this infection. This article summarizes the current knowledge of COVID-19 in the light of major dermatological and allergological diseases. It identifies medical areas lacking sufficient data and draws conclusions for the management of our patients during the pandemic. We focus on common chronic inflammatory skin diseases with complex immunological pathogenesis: psoriasis, eczema including atopic dermatitis, type I allergies, autoimmune blistering and inflammatory connective tissue diseases, vasculitis, and skin cancers. Since several other inflammatory skin diseases display related or comparable immunological reactions, clustering of the various inflammatory dermatoses into different disease patterns may help with therapeutic decisions. Thus, following these patterns of skin inflammation, our review may supply treatment recommendations and thoughtful considerations for disease management even beyond the most frequent diseases discussed here.