A Comparative Analysis of the Predictors, Extent and Impacts of Self-stigma in Patients with Psoriasis and Atopic Dermatitis.

The impact of dermatological diseases goes beyond symptoms and often includes psychosocial burden. Self-stigmatization plays a key role in this relationship and was compared in patients with psoriasis and atopic dermatitis to evaluate the validity of cross-disease stigmatization models. In total, 101 patients per indication were included in this cross-sectional study. Besides sociodemographic and clinical data, patient-reported outcome measures relating to self-stigmatization, depression, anxiety, and quality of life were compared across groups. Sociodemographic and clinical factors were tested for their moderating effects between self-stigmatization and quality of life. Group mean comparisons yielded no significant differences in self-stigmatization between patient groups. In both diseases, self-stigmatization significantly predicted depression and anxiety symptoms as well as quality of life. Current symptoms, not having close social relationships, and lower age predicted self-stigma in patients with psoriasis, whereas the involvement of sensitive body areas, the sum of previous treatments, and female sex were predictors in patients with atopic dermatitis. In both groups, symptoms had significantly moderating effects. The results underline the relevance of self-stigmatization in patients with chronic skin diseases. Awareness should be raised, screening implemented, and psychosocial support offered early on. Assessments, conceptual models of self-stigma, and interventions are probably applicable for both diseases.

Real-world effectiveness and safety of tildrakizumab in long-term treatment of plaque psoriasis: Results from the non-interventional, prospective, multicentre study TILOT.

BACKGROUND: Plaque psoriasis is a chronic inflammatory disorder affecting the skin and impacting quality of life. Tildrakizumab (TIL) is an IL-23 inhibitor licensed for moderate-to-severe plaque psoriasis. Regulatory approval of medicinal products is based on safety and efficacy data from randomized controlled trials (RCTs) which impose stringent selection criteria. Long-term non-interventional studies (NIS) are needed to establish effectiveness and safety in daily practice bridging the gap between RCTs and the real-world setting. OBJECTIVES: This analysis of the NIS TILOT seeks to evaluate effectiveness and safety of TIL in patients with moderate-to-severe plaque psoriasis in a real-world setting. Secondary objectives include the assessment of the Dermatology Life Quality Index (DLQI), treatment satisfaction and course of scalp and nail disease using Physician Global Assessment (PGA). METHODS: Interim analysis at 52 weeks (W) of the ongoing non-interventional, prospective, long-term multicentre study TILOT. RESULTS: The effectiveness analysis included 412 patients. The mean [standard deviation, SD] Psoriasis Area and Severity Index (PASI) score was 16.0 [9.1] at baseline improving by 82.4% (95% confidence interval [CI], 78.9-86.0) to 2.1 [2.9] at W52. The proportion of patients achieving PASI scores of <3 and <5 increased over time peaking at 74.6% (95% CI, 69.3-79.4) and 88.4% (95% CI, 84.3-91.8) at W52. Scalp-PGA and nail-PGA improved by 79.8% (95% CI, 75.6-84.0) and 72.7% (95% CI, 63.9-81.6), respectively. DLQI of 0/1 was achieved by 48.2% (95% CI, 42.3-54.2). Nine out of 10 physicians and patients expressed a high level of treatment satisfaction. No new safety signals were observed. CONCLUSIONS: This prospective cohort study demonstrates a high degree of effectiveness and a reassuring safety profile of TIL in a real-world setting over 52 weeks. Patients with scalp and nail involvement or pruritus showed marked improvements.

Comparison of different skin care regimens in patients with moderate to severe atopic dermatitis receiving systemic treatment: A randomized controlled trial.

BACKGROUND: Moderate to severe AD can be successfully managed by systemic treatments. Current guidelines also recommend emollients or emollients 'plus' and eudermic cleansers for all AD patients to improve the skin barrier and provide anti-irritant and anti-pruritic effects. OBJECTIVES: To investigate the efficacy of skin care (in addition to systemic treatment) with an Emollient 'plus' balm designed to improve the skin barrier and skin microbiome plus a corresponding syndet compared to usual commercial emollients and cleansers. METHODS: In a randomized controlled multicenter study, patients with moderate to severe AD (Severity scoring of atopic dermatitis [SCORAD] score ≥ 40) receiving systemic treatment (cyclosporin A, dupilumab or a Janus kinase inhibitor) were randomized 1:1 to apply twice daily for 10 weeks Emollient 'plus' after pre-cleaning with the syndet (Emollient 'plus' group) or to continue with their usual emollient and cleanser (Control group). Assessments included SCORAD, pruritus on a Visual Analog Scale, Dermatology quality of life questionnaire (DLQI), efficacy and tolerance questionnaires. RESULTS: Included were 57 patients with mean age of 38 years (range 19-70 years). The mean amount of emollient used after 10 weeks was 447.3 g (range 29-1099 g) and 613.2 g (range 97-2565 g) for the Emollient 'plus' versus the Control, respectively (p = 0.0277). After 10 weeks, subjects in the Emollient 'plus' had a significantly greater reduction in current pruritus (p = 0.0277) and a greater reduction in some DLQI items compared to the Control group. CONCLUSIONS: In patients with moderate to severe AD receiving systemic treatment, the Emollient 'plus' regimen significantly improved pruritus and quality of life items compared to the control, while using 23% less product over a 10-week period. These results stress the importance of daily use of emollients, especially emollients 'plus' to improve signs, symptoms and quality of life in patients with AD.

How important is subjective well-being for patients? A qualitative interview study of people with psoriasis.

PURPOSE: This qualitative study aimed to investigate the importance of subjective well-being (SWB) as an outcome of psoriasis treatment from patient's perspective. We focused on the affective component of SWB as assessed with the Daily Experience Sampling Questionnaire (DESQ), a validated daily diary. METHODS: Semi-structured qualitative telephone interviews were conducted with in-patients of a dermatological rehabilitation clinic, after participants had completed the DESQ for up to seven days to get familiar with the concept of SWB. Patients were asked to reflect on the importance of SWB as treatment goal and on its relative importance as compared with other treatment outcomes. We also addressed whether SWB could be an indirect measure of benefit in that it reflects other important outcomes. Transcripts were analyzed using content analysis. RESULTS: Eleven patients participated (24-63 years, mean 53 years, 8 male, 3 female). Participants uniformly confirmed that changes in SWB reflected treatment benefit. All but one considered SWB to be a central aspect of treatment benefit-either as the most important treatment goal or as an indirect benefit indicator. In particular, participants described positive associations of SWB with other outcomes, such as symptoms. They reported that both the disease and the medical treatment had an impact on their SWB, which was reflected in the DESQ. CONCLUSION: Our findings suggest that SWB is a relevant indicator of treatment benefit for patients with psoriasis. Therefore, SWB measures, such as the DESQ, could be used to operationalize patient-relevant benefit of psoriasis treatment, complementing outcome measures currently used.

Introduction of a Specific Dermatological Rehabilitation Programme for Patients with Chronic Pruritus: A Pilot Study.

Chronic pruritus is a common symptom, associated with several severe medical conditions, great psychological burden, and reduced quality of life. It also poses socio-economic challenges concerning patients' work loss and healthcare costs. In Germany, medical rehabilitation programmes represent an integral part of the medical care of patients with chronic inflammatory skin diseases. However, such programmes play only a rudimentary role in the treatment of other dermatological diseases, such as dermatological oncology, genetic skin diseases, and chronic pruritus. Therefore, a specific antipruritic dermatological rehabilitation programme was developed in cooperation between the Department of Dermatology of the Medical Rehabilitation Center Bad Bentheim and the Center for Chronic Pruritus of the University Hospital of Muenster, Germany. This prospective study compared short-term patient-reported outcomes (n = 121) at the beginning and end of the rehabilitation programme. The majority of subjects had chronic pruritus on primary diseased, inflamed skin. Significant improvements in pruritus intensity (p ≤ 0.001), quality of life (p ≤ 0.001), anxiety symptoms (p ≤ 0.001) and depression (p ≤ 0.001), as well as an overall patient-relevant benefit (Patient Benefit Index 2.6 ± 1.06) and treatment-related patients' satisfaction, were shown. This suggests that implementation of this standardized rehabilitation programme for treatment of patients with chronic pruritus was successful.

[Erythrodermic psoriasis after COVID-19]. / Erythroderme Psoriasis nach COVID-19-Erkrankung.

We present a clinical case of a patient with acutely exacerbated erythrodermic psoriasis vulgaris after symptomatic infection with SARS-CoV­2 (severe acute respiratory syndrome coronavirus 2). Various factors are already known that can lead to an exacerbation of psoriasis, such as drugs or infections with, for example, streptococcus. An association between psoriasis and an infection with SARS-CoV­2 has been described so far in individual case reports, in which, however, drug treatment with for example hydroxychloroquine, a known trigger of psoriasis, often took place. Later cases of exacerbation of psoriasis, partly as pustular psoriasis have been published also without drug induction. However we present for the first time a case of erythrodermic psoriasis triggered by COVID-19 (coronavirus disease 2019) without an obvious drug trigger.

[Influence of an adjuvant treatment with an emollient containing 10 % urea, ceramides, glycerin und glyceryl glucoside in patients with psoriasis vulgaris]. / Einfluss einer adjuvanten Basistherapie mit 10 % Urea, Ceramiden, Glycerin und Glyceryl Glucoside bei Patienten mit Psoriasis vulgaris.

BACKGROUND: Guidelines generally recommend an adjuvant treatment with emollients for patients suffering from psoriasis. However evidence for this purpose is limited. PATIENTS AND METHODS: We performed a prospective observational study with an emollient containing 10% urea, ceramides, glycerin and glyceryl glucoside in patients suffering from mild to moderate psoriasis. The patients had to be stable for at least 12 weeks on prior antipsoriatic therapy including topical therapy, systemic treatment or phototherapy which was continued during the trial. RESULTS: A 4-week daily application of the emollient resulted in significant improvement regarding quality of life (measured by DLQI, Dermatology Life Quality Index) and clinical outcome (measured by local PASI, Psoriasis Area and Severity Index) among the treated patients. CONCLUSION: The trial results show that a daily adjuvant treatment with emollients can support a basic antipsoriatic therapy both in aspects of clinical efficacy and quality of life in mild to moderate patients suffering from psoriasis.

Content and value of rehabilitation in dermatology.

The therapy of chronic skin diseases is challenging for both the dermatologist and the patient. Current standards of therapy and individual circumstances of the patient have to be considered. Furthermore, chronic skin diseases are often associated with comorbidities that require treatment adapted to the individual. Therefore, optimal education of the patient and a holistic concept of therapy are needed, in many cases in collaboration with various medical disciplines. In this case, rehabilitation provides an opportunity to address important aspects such as comorbidities, psychosocial burden and limitations at work, in addition to treating the underlying disease. This article describes the differences between acute and rehabilitation health care in dermatology, and illustrates the importance of rehabilitation in dermatology, based on examples of chronic inflammatory skin diseases, chronic pruritus and dermato-oncological diseases.

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.

Efficacy and safety of the histamine H4 receptor antagonist ZPL-3893787 in patients with atopic dermatitis.

BACKGROUND: H4 receptor antagonists are potential novel treatments for inflammatory skin diseases, including atopic dermatitis (AD). OBJECTIVE: We sought to study the efficacy and safety of ZPL-3893787 (a selective H4 receptor antagonist) in patients with moderate-to-severe AD. METHODS: A randomized, double-blind, placebo-controlled, parallel-group study was conducted to evaluate ZPL-3893787 (30 mg) once-daily oral therapy in adults with moderate-to-severe AD. Patients were randomized (2:1) to ZPL-3893787 (n = 65) or placebo (n = 33) for 8 weeks. Patients had a history of AD for more than 12 months, Eczema Area and Severity Index (EASI) scores of 12 or greater and 48 or less, Investigator's Global Assessment (IGA) scores of 3 or greater, pruritus scores of 5 or greater (0- to 10-point scale), and AD on 10% or greater of body surface area. Efficacy parameters included EASI, IGA, SCORAD, and pruritus assessment. RESULTS: Treatment with oral ZPL-3893787 showed a 50% reduction in EASI score compared with 27% for placebo. The placebo-adjusted reduction in EASI score at week 8 was 5.1 (1-sided P = .01). Clear or almost-clear IGA scores were 18.5% with ZPL-3893787 versus 9.1% with placebo. SCORAD scores exhibited 41% reduction with ZPL-3893787 versus 26% with placebo (placebo-adjusted reduction of 10.0, P = .004). There was a 3-point reduction (scale, 1-10) in pruritus with ZPL-3893787, but there was a similar reduction with placebo, resulting in a nonsignificant difference (P = .249). Patient-reported pruritus subscores obtained from SCORAD were reduced with ZPL-3893787 compared with placebo at week 8 (nonsignificant). ZPL-3893787 was well tolerated. CONCLUSION: For the first time, these results showed that ZPL-3893787 improved inflammatory skin lesions in patients with AD, confirming H4 receptor antagonism as a novel therapeutic option.

[Dermatological rehabilitation : Program content, opportunities and application submission]. / Rehabilitation in der Dermatologie : Inhalte, Chancen und der Weg dorthin.

Among dermatologists, the opportunities regarding medical dermatological rehabilitation for cutaneous chronic inflammatory and dermato-oncological diseases are not fully exhausted. However, rehabilitation offers the chance to approach important aspects such as comorbidities, psychosocial burden and limitations at work in addition to treating the underlying disease itself. Furthermore, rehabilitation has the potential to relieve the dermatologist from healthcare responsibilities and to achieve treatment and healthcare targets much faster. The patients themselves are the ones who profit from a holistic dermatological and social medical regimen. In the following article the reader learns about the details of a specific dermatological rehabilitation program, how to successfully apply for it and which wording is essential.

Exploratory Study of Intracutaneous Histamine Stimulation in Patient Populations with Chronic Pruritus.

Chronic pruritus can be a diagnostic sign of an underlying disease. In the intracutaneous histamine test, histamine (one of the best-known inducers of pruritus) may cause different reaction patterns depending on the underlying disease. The aim of this study was to determine if an intracutaneous injection of histamine can differentiate between the causes of chronic pruritus and thus be used as a diagnostic test in chronic pruritus of unknown aetiology. A total of 140 subjects with chronic pruritus with various dermatological, systemic or neurological diseases were included. The intracutaneous histamine test was performed once on each subject. Erythema, wheal and pruritus intensity were measured and analysed. Significantly greater wheal size was observed in patients with systemic or multifactorial causes. In general, there was a significant correlation between age and wheal size. Also, noticeable differences were found between males and females regarding pruritus and wheal size. In summary, the exact type of chronic pruritus could not be clearly determined based on the results of the intracutaneous histamine test. However, the results provide valuable insights into specific reaction patterns to experimental histamine-induced itch, e.g. sex-specific differences in the neurophysiology of pruritus, which should be considered in future studies.

Aprepitant in Anti-histamine-refractory Chronic Nodular Prurigo: A Multicentre, Randomized, Double-blind, Placebo-controlled, Cross-over, Phase-II trial (APREPRU).

The aim of this multicentre, randomized, double-blind, placebo-controlled, cross-over, phase-II study was to determine the antipruritic effect of aprepitant vs. placebo in 58 patients with anti-histamine-refractory chronic pruritus in chronic nodular prurigo. Patients were randomized to receive either first oral aprepitant 80 mg/day or placebo for 4 weeks. Following a 2-week wash-out phase, the patients were crossed-over to receive the other treatment for 4 weeks. Primary efficacy criterion was the intra-individual difference between mean itch intensity (visual analogue scale) at baseline compared with the end of treatment period. Prurigo lesions, pruritus course, quality of life, patient benefits, and safety were secondary parameters. No significant differences were found between aprepitant treatment and placebo for any of the parameters investigated. Under the experimental conditions of the study, aprepitant, 80 mg daily for 4 weeks, did not have an antipruritic effect in patients with chronic prurigo. (DRKS00005594; EudraCT Number: 2013-001601-85).

Mogamulizumab versus vorinostat in previously treated cutaneous T-cell lymphoma (MAVORIC): an international, open-label, randomised, controlled phase 3 trial.

BACKGROUND: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. METHODS: In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB-II vs III-IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. FINDINGS: Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7-10·3] in the mogamulizumab group vs 3·1 months [2·9-4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41-0·69; stratified log-rank p<0·0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. INTERPRETATION: Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. FUNDING: Kyowa Kirin.

Chronic Prurigo of Nodular Type: A Review.

Prurigo nodularis (PN) is a subtype of chronic prurigo presenting single to multiple symmetrically distributed, hyperkeratotic and intensively itching papules and nodules. PN evolves along with chronic pruritus in the context of diverse dermatological, systemic, neurological or psychiatric conditions. Permanent scratching is possibly a major trigger of PN, although its exact pathophysiology remains unclear. Current state-of-the-art therapy for PN consists of topical steroids, capsaicin, calcineurin inhibitors, ultraviolet (UV) therapy, systemic administration of gabapentinoids, µ-opioid receptor antagonists, antidepressants or immunosuppressants. Novel treatment concepts, such as inhibitors of neurokinin-1, opioid and interleukin-31 receptors, have been developed and are currently being clinically tested.

Efficacy and safety of canakinumab in Schnitzler syndrome: A multicenter randomized placebo-controlled study.

BACKGROUND: Schnitzler syndrome is an adult-onset autoinflammatory disease characterized by urticarial exanthema and monoclonal gammopathy accompanied by systemic symptoms such as fever, bone, and muscle pain. Up to now, approved treatment options are not available. OBJECTIVE: We assessed effects of the anti-IL-1ß mAb canakinumab on the clinical signs and symptoms of Schnitzler syndrome. METHODS: In this phase II, randomized placebo-controlled multicenter study, 20 patients with active disease enrolled in 4 German study centers. Patients were randomly assigned to receive single subcutaneous canakinumab 150 mg or placebo injections for 7 days, followed by a 16-week open-label phase with canakinumab injections on confirmed relapse of symptoms. The primary end point was the proportion of patients with complete clinical response evaluated by physician global assessment at day 7. Key secondary end points included changes in patient-reported disease activity (Schnitzler activity score), inflammation markers (C-reactive protein and serum amyloid A), and quality-of-life assessments (Dermatology Life Quality Index and 36-item short form health survey). RESULTS: The proportion of patients with complete clinical response at day 7 was significantly higher (P = .001) in the canakinumab-treated group (n = 5 of 7) than in the placebo group (n = 0 of 13). Levels of inflammation markers C-reactive protein and serum amyloid A and quality-of-life scores were significantly reduced in canakinumab-treated but not in placebo-treated individuals. Positive effects continued up to 16 weeks. Adverse events were manageable and included respiratory tract infections, gastrointestinal symptoms, and hypertension. CONCLUSIONS: In this first placebo-controlled study, canakinumab was effective in patients with Schnitzler syndrome, and thus canakinumab may be further evaluated as a therapeutic option for this rare disease.