A narrative review of fixed combination calcipotriol/betamethasone aerosol foam (Enstilar®) in the management of psoriasis with scalp involvement.

The scalp is the most common site affected in patients with psoriasis with up to 80% of these patients having some degree of scalp involvement. In this narrative review, we evaluate available data on the use of an innovative aerosol foam formulation of calcipotriol plus betamethasone dipropionate (Cal/BD) to treat patients with psoriasis and scalp involvement. The full PubMed database was searched using the terms "calcipotriol", "betamethasone dipropionate" and "aerosol foam", and all articles relating to "psoriasis with scalp involvement" were retrieved and used in the preparation of this review. The evidence supporting the clinical effectiveness, tolerability and impact on health outcomes of Cal/BD aerosol foam in patients with scalp psoriasis was obtained from a phase II clinical trial and real-world evidence data from a non-interventional study as well as from two case series. The findings from these studies show that Cal/BD aerosol foam is rapidly effective, improves skin condition, alleviates symptoms such as itch, and has a positive impact on patient quality of life. These attributes address several unmet needs for patients with psoriasis with scalp involvement and have the potential to improve individual adherence to treatment.

[Recommendations for individual comorbidity risk assessment in adult patients with psoriasis]. / Handlungsempfehlungen zur individuellen Risikoermittlung von Komorbidität bei erwachsenen Patienten mit Psoriasis.

It has long been known that chronic inflammatory systemic diseases, such as psoriasis, pose a high risk of developing comorbidities. In everyday clinical practice, it is therefore of particular importance to identify patients who have an individually increased risk profile. In patients with psoriasis, the comorbidity patterns "metabolic syndrome", "cardiovascular comorbidity" and "mental illness" were identified as particularly relevant in epidemiological studies depending on the duration and severity of the disease. In the everyday care of patients with psoriasis in dermatological practice, the use of an interdisciplinary checklist for risk analysis and the initiation of professional follow-up care has proven valuable. On the basis of an existing checklist, the contents were critically evaluated by an interdisciplinary group of experts and a guideline-oriented update was prepared. In the opinion of the authors, the new analysis sheet represents a practicable, factually focused and updated tool for comorbidity risk assessment in patients with moderate and severe psoriasis.

Bimekizumab efficacy and safety in patients with moderate-to-severe plaque psoriasis who switched from adalimumab, ustekinumab or secukinumab: results from phase III/IIIb trials.

BACKGROUND: Discontinuation of biologics is common among patients with psoriasis due to treatment failure or adverse events. To achieve improvements in disease management, patients and clinicians may choose to switch biologics. OBJECTIVES: To evaluate the efficacy and safety of switching to bimekizumab from adalimumab, ustekinumab and secukinumab. METHODS: Data are reported for up to 80 weeks after patients switched to bimekizumab from adalimumab at week 24 in BE SURE, ustekinumab at week 52 in BE VIVID [upon entry into the BE BRIGHT open-label extension (OLE)] and secukinumab at week 48 in BE RADIANT (upon entry into the BE RADIANT OLE). Efficacy outcomes are reported by number of weeks after switching to bimekizumab and were split based on whether patients had achieved a ≥ 90% improvement from baseline in Psoriasis Area and Severity Index (PASI 90) at the time of switch. Treatment-emergent adverse events (TEAEs) are reported using exposure-adjusted incidence rates (EAIRs) per 100 patient-years. Trial registration: BE SURE (NCT03412747), BE VIVID (NCT03370133), BE BRIGHT (NCT03598790), BE RADIANT (NCT03536884). RESULTS: Rapid and durable improvements in clinical responses and benefits in health-related quality of life were observed among PASI 90 nonresponders who switched to bimekizumab. Most PASI 90 nonresponders achieved PASI 90 4 weeks after switching to bimekizumab from adalimumab (67%), ustekinumab (79%) and secukinumab (53%). After 48 weeks of bimekizumab, 91%, 90% and 79% of PASI 90 nonresponders had achieved PASI 90 after switching from adalimumab, ustekinumab or secukinumab, respectively. Durable improvements were also observed for PASI 100, Investigator's Global Assessment score 0/1, body surface area affected by psoriasis ≤ 1%, absolute PASI ≤ 2, and Dermatology Life Quality Index 0/1. Among PASI 90 responders, existing treatment responses were maintained or improved after switching to bimekizumab. The majority of TEAEs were mild or moderate. EAIRs were generally similar between active-comparator treatment periods and after switching to bimekizumab. EAIRs typically decreased with a longer duration of bimekizumab exposure. CONCLUSIONS: High proportions of patients who did not adequately respond to adalimumab, ustekinumab or secukinumab achieved high levels of skin clearance after switching to bimekizumab. Bimekizumab was well tolerated and there were no new safety findings.

Documentation of psoriasis in routine care - expert consensus on a German data set.

BACKGROUND AND OBJECTIVES: Documenting patient data in psoriasis clinical practice can improve care, but standardized and transparent documentation is rare. The current project aimed to develop a data set for the documentation of psoriasis in daily practice. MATERIAL AND METHODS: In four online Delphi rounds and one in-person meeting, 27 psoriasis experts allocated variables to a standard, an optimal and an optional data set. Most of the questions were standardized. Open questions were included to allow for the provision of reasons and to enlarge the data sets. Furthermore, in the in-person meeting we considered a) patients' attitudes and b) dermatologists' information on the current usage and acceptability in Germany. RESULTS: The consensus approach resulted in a data set with 69 variables. The standard data set includes 20, the optimal data set 31 and the optional data set 18 variables. In summary, the data set can mainly be grouped into master data, general status and medical history data, medical history of psoriasis, status of psoriasis, diagnostics and comorbidity, therapies and patient-reported outcomes. CONCLUSIONS: The consensus recommendation of a standard, an optimal and an optional data set for routine care of psoriasis intends to be a decision-making aid and an orientation for both daily practice and further development of documentation systems.

[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.

Immunomodulatory aged neutrophils are augmented in blood and skin of psoriasis patients.

BACKGROUND: Neutrophil accumulation in the skin is a hallmark of psoriasis. Novel insights on neutrophil phenotypic and functional heterogeneity raise the question to what extent these cells contribute to the sustained inflammatory skin reaction. OBJECTIVE: We sought to examine the phenotype and functional properties of neutrophils in blood and skin of patients with psoriasis, and the effect of TNF-α and p40(IL-12/IL-23) antibody therapy on circulating neutrophils. METHODS: Thirty-two patients with psoriasis were enrolled in an observational study performed in 2 university hospitals. We evaluated neutrophil phenotype and function using in vitro (co)culture stimulation assays, flow cytometry, multiplex immunohistochemistry, and multispectral imaging of patient-derived blood and skin samples. RESULTS: Cluster of differentiation (CD)10pos and CD10neg neutrophils were increased in peripheral blood of patients with psoriasis. In CD10neg neutrophils, different maturation stages were observed, including a subset resembling aged neutrophils that was 3 times more abundant than in healthy individuals. These aged neutrophils displayed suboptimal canonical neutrophil functions and induced IL-17 and IFN-γ production by T cells in vitro, mediated by neutrophil extracellular trap formation. Also, mature and aged neutrophils were present in psoriatic skin and were found in the vicinity of T cells. Upon antibody therapy, numbers of these cells in circulation decreased. CONCLUSIONS: Patients with psoriasis reveal a unique neutrophil profile in circulation, and 2 distinct neutrophil subsets are present in psoriatic skin. Targeted biological treatment may aid in the containment of sustained neutrophil-mediated inflammation.

Psychological burden of psoriatic patients in a German university hospital dermatology department.

Psoriasis has a strong impact on patients' lives and is closely linked to psychiatric disorders such as depression, anxiety and substance-related disorders, especially dependence on alcohol and nicotine. The aim of our study was to systematically assess the psychiatric comorbidity and possible associations between psychological factors, disease severity and dermatology-related quality of life in psoriatic patients from a high-need university hospital dermatology department. Consecutive psoriatic patients (new and permanent patients) at the Department of Dermatology, University Hospital Essen, Germany, were asked to fill out a paper-based questionnaire. In the first part of the questionnaire, baseline demographics, pre-existing mental disorders and data on substance abuse were collected. In the second part of the questionnaire, mental and physical health was explored using different validated self-rating tests. The current Psoriasis Area and Severity Index (PASI) was documented by a dermatologist. Patients with signs of mental disorders were offered an appointment with a board-certified psychiatrist. Between August 2016 and February 2019, 228 consecutive psoriatic patients (138 men [60.5%], 90 women [39.5%]; mean age, 48.3 years [standard deviation, 13.6; range, 18-80]) participated in the study. Approximately 50% of the patients had evidence of suffering from mental health problems, mostly depression and anxiety, as well as alcohol dependence. Patients with a PASI of 3 or more showed a statistically significant reduced Dermatology Life Quality Index (DLQI) and a significantly impaired psychological as well as physical quality of life. DLQI correlated with all psychological test results. The data indicate a significant psychological burden in a tertiary psoriatic population. Our findings underscore the importance of screening psoriatic patients for psychiatric disorders, with a focus on depression, anxiety as well as alcohol and nicotine dependence, in a multidimensional approach involving psychiatrists and psychologists.

Psychosocial burden and body mass index are associated with dermatology-related quality of life in psoriasis patients.

BACKGROUND: Scientific evidence indicates that inflammatory processes may be involved in the progression of both psoriasis and depression via elevated peripheral proinflammatory cytokines. OBJECTIVES: The aim of our study was to assess the association among psychological burden, depressive symptoms and proinflammatory mediators in psoriasis patients. MATERIALS AND METHODS: Forty psoriasis patients were recruited from the Department of Dermatology, University Hospital Essen. In addition to the Psoriasis Area and Severity Index (PASI), mental and physical health were explored using different questionnaires. Furthermore, proinflammatory cytokines were analysed. RESULTS: Patients in the high PASI group showed reduced Dermatology Life Quality Index (DLQI), higher body mass index (BMI), elevated CRP levels as well as impaired physical aspects of quality of life. Regression analyses revealed that somatic and anxiety symptoms accounted for more than 32% of the variance in DLQI, independent of PASI and cytokine levels. CONCLUSION: The data indicate somatic and anxiety symptoms, as well as BMI, to be closely linked to dermatology-related quality of life.

Absolute and relative psoriasis area and severity index (PASI) treatment goals and their association with health-related quality of life.

Background: Relative Psoriasis Area and Severity Index (PASI) improvement, also called 'PASI response', is recommended in major guidelines for assessment of treatment response in psoriasis patients. However, under certain circumstances it has some limitations, e.g. when baseline values are missing or during long-term treatment. Improvement of health-related quality of life (HrQoL) can be measured by the Dermatology Life Quality Index (DLQI).Objective: To evaluate the association of HrQoL and relative and absolute PASI outcomes during therapy.Material and methods: Data of plaque psoriasis patients of two clinical trials (CLEAR and SCULPTURE) were pooled. The rates of patients achieving DLQI 0/1 at week 16 were compared for different categories of absolute PASI and PASI response values. The correlation of DLQI and absolute or relative PASI goals was assessed over 52 weeks.Results: One thousand and fifty-four patients with available assessments of PASI and DLQI were included. 76% of the patients with an absolute PASI ≤ 2 (N = 548) and patients with a 90% improvement in PASI (N = 559) achieved DLQI 0/1 at week 16. Achievement of DLQI 0/1 was equally reflected by absolute PASI and PASI response.Conclusion: Absolute PASI appeared to be a feasible alternative to PASI response for determining treatment success, reflecting HrQoL improvements in an equal manner.

Diagnosis and treatment of xerosis cutis - a position paper.

BACKGROUND AND RATIONALE: Xerosis cutis (also referred to as xeroderma, dry skin, asteatosis) affects more than 10 million individuals in Germany. It is among the most common dermatological diagnoses and a cardinal symptom of many dermatological, internal and neurological diseases. Even though it has been established that basic skin care plays a significant role in the management of patients with xerosis cutis, there are as yet no evidence-based algorithms for diagnosis and treatment. OBJECTIVE: The present position paper provides physicians across all specialties with a practical, symptom-based approach to the prevention, diagnosis and treatment of xerosis cutis. METHODS: Within a structured decision-making process, a panel of experienced dermatologists first defined questions relevant to everyday clinical practice, which were then addressed by a systematic review of the literature. Based on the evidence available as well as expert consensus, diagnostic and treatment algorithms were subsequently developed and agreed upon. RESULTS: Xerosis cutis is generally diagnosed on clinical grounds. Possible trigger factors must be avoided, and comorbidities should be adequately and specifically treated. Suitable skin care products should be chosen with a view to improving skin hydration and restoring its barrier function. They should therefore contain both rehydrating and lipid-replenishing components. The "drier" the skin appears, the greater the lipid content should be (preferably using water-in-oil formulations). The choice of ingredients is based on a patient's individual symptoms, such as scaling (e.g., urea), fissures/rhagades (e.g., urea or dexpanthenol), erythema (e.g., licochalcone A) and pruritus (e.g., polidocanol). Other factors to be considered include the site affected and patient age. Ingredients or rather combinations thereof for which there is good clinical evidence should be preferentially used. The best evidence by far is available for urea, whose efficacy in the treatment of xerosis is further enhanced by combining it with other natural moisturizing components and ceramides. The "xerosimeter" is a tool developed in an effort to facilitate patient management and for training purposes. It not only includes practical tools for diagnosis and follow-up but also a classification of ingredients and a structured treatment algorithm. CONCLUSION: The structured symptom- and evidence-based approach proposed herein contains a road map for diagnosis and treatment of xerosis cutis. It aims to raise awareness in terms of prevention and early treatment of this condition and may thus improve quality of life and prevent potential sequelae.

Dermatological complications of therapy with biologics in inflammatory autoimmune diseases.

BACKGROUND AND OBJECTIVE: Cutaneous adverse events (CAEs) occur in up to 10 % of patients with immune-mediated inflammatory disease (IMID) treated with antitumor necrosis factor (TNF)α agents. The aim of this clinical study was to track and observe the course of CAEs in all biologic therapies. PATIENTS AND METHODS: The population for this study consisted of patients with CAEs under biologic therapy who were examined by experienced board-certified dermatologists in the outpatient department of the University Hospital Essen, Department of Dermatology. RESULTS: Altogether 39 patients with a total of 45 CAEs were included in this study. In 60 % of the cases a form of paradoxical psoriasis was diagnosed. Two thirds (66.6 %) of the patients with CAEs were diagnosed with an underlying inflammatory bowel disease (IBD). TNFα antagonists were the triggering agents in about 95 % of the cases. Changes in biological therapy were required in nearly half of the cases (46.2 %). Almost 90 % of the patients had either a complete (42.1 %) or a partial response (47 %). CONCLUSIONS: Management of CEAs under biological therapy can be challenging in clinical practice. Case discussions between gastroenterologists, rheumatologists and dermatologists should be undertaken to best manage patients with CAEs and avoid unnecessary changes of therapy.

[Gastrointestinal side effects of apremilast : Characterization and management]. / Gastrointestinale Beschwerden unter Apremilast : Charakterisierung und Management.

Apremilast is an oral inhibitor of phosphodiesterase-4 (PDE4) that is licensed for the second-line treatment of psoriasis and psoriatic arthritis. Data from several phase III clinical trials and real-world studies showed a good benefit-risk profile, with diarrhea and nausea as the most common adverse events. Diarrhea and nausea most frequently occurred during the first month of treatment. In most cases, they were mild or moderate in severity and tended to resolve over time with continued dosing and without intervention. In this review we summarize available data on gastrointestinal side effects of apremilast in patients with psoriasis and psoriasis arthritis and provide practical strategies for managing these symptoms.

Increased dermal expression of chromatin-associated protein HMGB1 and concomitant T-cell expression of the DNA RAGE in patients with psoriasis vulgaris.

PURPOSE: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease of the skin, with both vascular and metabolic effects. Aggravating factors have been identified that initiate and maintain inflammation, including expression of Th1-, Th17-, and Th22-cell derived cytokines. Recently, we showed that the evolutionarily ancient and highly conserved damage-associated molecular pattern molecule "high mobility group box 1 (HMGB1)" is significantly increased in the serum of PV patients with disease progression and is decreased under standard therapies. MATERIALS AND METHODS: To better understand the role of HMGB1 in the pathogenesis of PV, we recruited 22 untreated psoriatic patients with either mild or severe disease, defined by the Psoriasis Area Severity Index. We assessed HMGB1 and receptor for advanced glycation end products (RAGE) expression in the skin by immunohistochemistry and analyzed the immune-phenotype of Treg and Th17 cells by flow cytometry. RESULTS: We found increased staining for HMGB1 in the dermis of psoriatic plaques in comparison to uninvolved skin of patients with PV. In addition, the major histocompatibility complex class III-encoded DNA and HMGB1 RAGE, induced by HMGB1, were highly expressed on psoriatic CD8+ T cells and CD4+ Treg. High expression of HMGB1 in the lesional skin was associated with even higher expression of its receptor, RAGE, on the cell surface of keratino-cytes in patients with severe PV. CONCLUSION: The presence of HMGB1 and RAGE signaling may impact orchestration of chronic inflammation in PV which might have implications for Treg and Th17 cells.

Mucosal melanoma of the cranio-facial region: Surgical challenges and therapeutic options.

OBJECTIVE: Although current therapeutic options for cutaneous melanoma (CM) are constantly improving survival, mucosal melanoma (MM) remains a rare tumor disease with a poor clinical outcome. While radical surgery is the gold standard, clear margin resections in the head and neck area are particularly critical due to high density of vulnerable structures. Adjuvant therapeutic options increases local control and data on the effect of systemic agents is sparse. The aim of this study was to elucidate surgical challenges in the craniofacial area and to evaluate the effect of local and systemic therapy in Head and Neck Mucosal Melanoma (HNMM). METHODS: In total, 21 patients with nasal mucosal malignant melanoma were included in this study over the course of 20 years in two German tertiary referral centers. Patient characteristics and conducted therapy as well as clinical outcomes were analyzed retrospectively. RESULTS: By performing survival analysis for multimodal therapies, we observed a superiority effect of interferon therapy compared to surgery with radiation and surgery alone in the first therapeutic approach. However, patients treated with surgery alone in a recurrent setting showed the best outcome. CONCLUSION: Both, Interferon and radiation as adjuvant therapies, demonstrated survival benefits in initial treatment compared to surgery alone. Analysis after recurrence, however, revealed salvage surgery as a reliable and powerful tool to prolong post-recurrence survival without exposing palliative patients to the risk of severe adverse events from systemic therapies.

Impact of Secukinumab on Endothelial Dysfunction and Other Cardiovascular Disease Parameters in Psoriasis Patients over 52 Weeks.

Psoriasis increases the risk of cardiovascular (CV) disease. Secukinumab, a fully human monoclonal antibody against IL-17A, shows significant efficacy in psoriasis, but effects on CV markers are unknown. CARIMA (Evaluation of Cardiovascular Risk Markers in Psoriasis Patients Treated with Secukinumab) was a 52-week, randomized, double-blind, placebo-controlled, exploratory trial in patients with moderate to severe plaque psoriasis without clinical CV disease. Patients were randomly assigned to receive 300 mg or 150 mg secukinumab until week 52 or to receive placebo until week 12 and then 300 mg or 150 mg secukinumab until week 52. The primary outcome was endothelial function measured by flow-mediated dilation (FMD). Baseline FMD was significantly lower in psoriasis patients than healthy volunteers (4.4 ± 3.9% vs. 6.1 ± 3.3%, P = 0.01). At week 12, baseline-adjusted mean FMD was numerically higher in patients receiving secukinumab versus those receiving placebo, but this difference (300-mg group, +1.2%; 150-mg group, +0.76%; P = 0.223 and P = 0.403 by analysis of covariance) did not reach significance. At week 52, FMD increased across groups. FMD was significantly higher than baseline in patients receiving the label dose of 300 mg secukinumab for 52 weeks (+2.1%, 95% confidence interval = 0.8-3.3; P = 0.0022). Other relevant CV markers were unchanged. CARIMA indicates that secukinumab might have a beneficial effect on CV risk by improving the endothelial function of patients with plaque psoriasis.

Positionspapier: Diagnostik und Therapie der Xerosis cutis.

HINTERGRUND UND RATIONALE: Die Xerosis cutis (Synonym: Xerodermie, trockene Haut, hydrolipidarme Haut) ist mit > 10 Millionen Betroffenen nicht nur eine der häufigsten dermatologischen Diagnosen in Deutschland, sondern auch Leitsymptom vieler dermatologischer, internistischer und neurologischer Erkrankungen. Trotz der medizinischen Relevanz der topischen Basistherapie für die Xerosis cutis gibt es in Deutschland für ihr Management bisher keinen wissenschaftlich belegten Diagnostik- und Therapiealgorithmus. ZIEL: Dieses Positionspapier vermittelt Ärzten fachübergreifend einen an individuellen Symptomen orientierten, praxisnahen Leitfaden für die Prävention, Diagnostik und Therapie der Xerosis cutis. METHODIK: Im Rahmen eines strukturierten Entscheidungsprozesses wurden von erfahrenen dermatologischen Experten zunächst praxisrelevante Fragestellungen definiert und systematisch aufgearbeitet. Auf der Basis von Evidenz und Expertenkonsens wurden daraus diagnostische und therapeutische Algorithmen mit Empfehlungen für die Praxis entwickelt und konsentiert. ERGEBNIS: Die Xerosis cutis kann grundsätzlich klinisch diagnostiziert werden. Auslöser und/oder Grunderkrankungen müssen abgeklärt und vermieden bzw. spezifisch behandelt werden. Bei der Wahl der geeigneten Basistherapie ist es wichtig, dass nicht nur die Hauthydratation verbessert, sondern auch die Barrierefunktion der Haut wiederhergestellt wird. Sie sollte daher aus einer Kombination von rückfeuchtenden und rückfettenden Inhaltsstoffen bestehen. Je trockener die Haut, desto lipidhaltiger sollte die Hautpflege sein (bevorzugt Wasser-in-Öl-Formulierungen). Die individuelle Auswahl der Inhaltsstoffe orientiert sich nach kausaler Prüfung an den Symptomen Schuppung (v.a. Urea), Fissuren/Rhagaden (v.a. Urea oder Dexpanthenol), Rötung (v.a. Licochalcone A) und Pruritus (v.a. Polidocanol), sowie an der Lokalisation und dem Alter der Patienten. Inhaltsstoffe bzw. Inhaltsstoffkombinationen mit guter Studienevidenz sind zu bevorzugen. Die mit Abstand beste Evidenz bei der Xerosis cutis weist Urea auf, dessen Wirksamkeit in Kombination mit anderen natürlichen Feuchthalte-Komponenten und Ceramiden noch gesteigert werden kann. Zur Arbeitserleichterung am Patienten und zum besseren Erlernen wurde das Xerosimeter entwickelt, das die praktische Umsetzung der Diagnostik und Verlaufskontrolle, eine Klassifikation der Inhaltsstoffe und einen strukturierten Therapiealgorithmus enthält. SCHLUSSFOLGERUNG: Das hier vorgeschlagene strukturierte symptom- und evidenzorientierte Vorgehen mit Diagnostik- und Behandlungspfad soll für die Prävention und frühzeitige Behandlung der Xerosis cutis sensibilisieren. Damit können die Lebensqualität verbessert und Folgeerkrankungen verhindert werden.