Consensus statement on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: Localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present consensus provides an update to the 2017 European Dermatology Forum Guidelines, focusing on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, updated strategies for the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this consensus provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes.

Disparate effects of adalimumab and fumaric acid esters on cardiovascular risk factors in psoriasis patients: results from a prospective, randomized, observer-blinded head-to-head trial.

BACKGROUND: The effect of adalimumab and fumaric acid esters (FAE) on the cardiovascular risk associated with psoriasis has only been investigated scarcely in randomized controlled studies. OBJECTIVE: The aim of this prospective, randomized controlled head-to-head trial was to compare the influence of adalimumab and FAE on cardiovascular disease markers in psoriasis patients. METHODS: Sixty-five patients with moderate to severe plaque psoriasis were randomly assigned to adalimumab or FAE treatment for 6 months. Cardiovascular haemodynamic parameters [flow-mediated dilation (FMD), nitro-glycerine mediated dilation (NMD) and carotid intima-media thickness (CIMT), blood pressure] were assessed at baseline (v0) and after 6 months (v6). Cutaneous disease severity, inflammatory and lipid cardiovascular risk markers were analysed at baseline(v0), after 3 (v3) and 6 months (v6). RESULTS: After 6 months of treatment FMD in the adalimumab group increased significantly [v0 5.9% (6.4% SD), v6 8.0% (4.8% SD), P = 0.048) but not in the FAE group. (v0 7.0% (4.1% SD), v6 8.4% (6.1% SD), P = 0.753]. This was paralleled by a significant decrease of high sensitive C-reactive protein (hsCRP) in the adalimumab group in comparison to the FAE group (v0: 0.39 mg/dL (0.38 SD), v6: 0.39 mg/dL (0.48 SD), P = 0.043). No significant changes were observed in any other haemodynamic parameters. FAE, however, additionally decreased total cholesterol (P = 0.046) and apolipoprotein B (P = 0.041) levels compared to adalimumab. Mean Psoriasis Area and Severity Index (psoriasis area severity score) reduction was greater but not significant (P = 0.116) under adalimumab treatment compared to FAE treatment [-71.1% (29.9 SD) vs. -54.6% (45.7%)]. CONCLUSION: In our study, both treatments were documented to exert effects on the cardiovascular system. While adalimumab showed anti-inflammatory effects and improved FMD, FAE interacted favourably with the cholesterol metabolism.

Biologic drug survival rates in the era of anti-interleukin-17 antibodies: a time-period-adjusted registry analysis.

BACKGROUND: Drug survival rates reflect efficacy and safety and may be influenced by the availability of alternative treatment options. Little is known about time-dependent drug survival in psoriasis and the effect of increasing numbers of biologic treatment options. OBJECTIVES: To determine whether drug survival is influenced by the availability of treatment options and by factors such as gender, psoriatic arthritis or previous biologic treatment. METHODS: This observational, retrospective, multicentre cohort study analysed data from patients registered in the Austrian Psoriasis Registry (PsoRA) who were treated with biologics between 1 January 2015 and 30 November 2019. RESULTS: A total of 1572 patients who received 1848 treatment cycles were included in this analysis. The highest long-term Psoriasis Area and Severity Index improvement was observed after treatment with ixekizumab, followed by ustekinumab and secukinumab, adalimumab and etanercept. Overall, ustekinumab surpassed all other biologics in drug survival up to 48 months. However, when adjusted for biologic naïvety, its superiority vanished and drug survival rates were similar for ixekizumab (91·6%), secukinumab (90·2%) and ustekinumab (92·8%), all of them superior to adalimumab (76·5%) and etanercept (71·9%) at 12 months and beyond. Besides biologic non-naïvety (2·10, P < 0·001), the introduction of a new drug such as secukinumab or ixekizumab (relative hazard ratio 1·6, P = 0·001) and female gender (1·50, P = 0·019) increased the risk of treatment discontinuation overall, whereas psoriatic arthritis did not (1·12, P = 0·21). CONCLUSIONS: The time-dependent availability of drugs should be considered when analysing and comparing drug survival. Previous biologic exposure significantly influences drug survival. Women are more likely to stop treatment.

5-Aminolevulinic acid patch (Alacare) photodynamic therapy for actinic cheilitis: data from a prospective 12-month follow-up study on 21 patients.

BACKGROUND: Actinic cheilitis (AC) is a variant of actinic keratosis (AK) affecting the lips and caused by chronic ultraviolet exposure. OBJECTIVE: Alacare is a self-adhesive, skin-coloured 5-aminolaevulinic acid patch that has been developed for use in photodynamic therapy (PDT) of mild-to-moderate AK. Based on promising preliminary results in the treatment of AC with Alacare patch PDT, we decided to extend our previous investigation to gain more data on the efficacy, tolerability, safety and cosmetic outcome of Alacare patch PDT for AC. METHODS: Twenty-one patients with a clinical diagnosis of mild-to-moderate AC were included in the study and subjected to one single session of PDT. After occlusion with the Alacare patch for 4 h, the AC lesions were illuminated for 10 min with red light at a dose of 37 J/cm2 . All patients received local anaesthesia prior to illumination. Additionally, all lesions were cooled during PDT with a cold air blower. PDT-induced pain and skin phototoxicity were monitored during and up to 7 days after PDT. Clinical assessment of efficacy, cosmetic outcome and global patient satisfaction was performed at 3, 6 and 12 months after treatment. RESULTS: Nineteen patients completed the study. Three months after PDT, 17 patients (89.5%) had achieved complete remission. Of these, one patient presented with recurrence of AC at the 6-month follow-up, whereas all other patients remained in remission until the end of the observation period. The complete clinical cure rate at 1 year after a single Alacare patch PDT thus was 84.2%. Pain during illumination and the phototoxic skin reaction were in general mild to moderate. The cosmetic outcome was excellent. CONCLUSION: The present prospective study on Alacare patch PDT for AC confirms its high clinical efficacy, good tolerability and favourable cosmetic effects. Alacare patch PDT should be considered as a valid treatment option for patients with AC.

Serum levels of folate, 25-hydroxyvitamin D3 and cobalamin during UVB phototherapy: findings in a large prospective trial.

BACKGROUND: Narrowband UVB phototherapy (NB-UVB) is a mainstay in the treatment of numerous inflammatory dermatoses. Whereas, a wealth of studies has shown that NB-UVB treatment increases 25-hydroxyvitamin D3 (25(OH)D) levels, only sparse and controversial data exist on its effect on serum folate and cobalamin. OBJECTIVES: To determine whether exposure to NB-UVB alters serum folate or cobalamin levels. METHODS: A single-centre, prospective, open observational study on 101 patients subjected to NB-UVB phototherapy between late fall and early spring. Serum folate, 25(OH)D and cobalamin levels were measured after 0, 12, 24 and 36 NB-UVB exposures. RESULTS: After 12 NB-UVB exposures a significant decrease of mean serum folate (-1.0 nmol/L; P = 0.03) and cobalamin (-14.5 pmol/L, P = 0.03) levels was observed whereas serum levels of 25(OH)D showed a significant increase (35.4 nmol/L, P < 0.0001). CONCLUSIONS: A standard course of NB-UVB induces a small but significant decrease of serum folate and cobalamin levels.

The frequency of photosensitizing drug dispensings in Austria and Germany: a correlation with their photosensitizing potential based on published literature.

BACKGROUND: Drug-induced photosensitivity refers to the development of cutaneous adverse events due to interaction between a pharmaceutical compound and sunlight. Although photosensitivity is a very commonly listed side-effect of systemic drugs, reliable data on its actual incidence are lacking so far. OBJECTIVES: A possible approach to evaluate the real-life extent of drug-induced photosensitivity would be an analysis of the frequency of exposure to a given photosensitizing drug combined with an indicator of its photosensitizing potential. This could serve as a basis for developing a pharmaceutical 'heatmap' of photosensitivity. METHODS: The present study investigated the number of reimbursed dispensed packages of potentially photosensitizing drugs in Germany (DE) and Austria (AT) between 2010 and 2017 based on nationwide health insurance-based databases. In addition, an indicator for the photosensitizing potential was established for each drug based on the number of reports on photosensitivity in the literature. RESULTS: This analysis includes means of 632 826 944 (+/-14 894 918) drug dispensings per year in DE and 113 270 754 (+/-1 964 690) in AT. Out of these, the mean percentage of drugs that enlist photosensitivity as a potential side-effect was 49.5% (±0.7) in DE and 48.2% (±1.2) in AT. When plotting the number of reimbursed dispensed packages vs. the number of reports on photosensitivity, two categories of drugs show high numbers for both parameters, that is diuretics and non-steroidal anti-inflammatory drugs (NSAIDs). CONCLUSIONS: Diuretics and NSAIDs appear to be responsible for the greatest part of exposure to photosensitizing drugs with potential implication on public health.

Clinical use of dimethyl fumarate in moderate-to-severe plaque-type psoriasis: a European expert consensus.

Fumaric acid esters (FAEs) are a group of small molecules that were first investigated for the treatment of psoriasis in 1959. The first fumarate-based drug - Fumaderm® - was approved in Germany in 1994 for severe psoriasis and then in 2008, the label was expanded to include moderate psoriasis. Fumaderm is a combination of different FAEs: dimethyl fumarate (DMF), which is regarded as the main active component, plus calcium, magnesium and zinc salts of monoethyl fumarate (MEF). FAEs are the most frequently used first-line systemic psoriasis treatment in Germany, with an overall treatment experience comprising more than 220 000 patient-years. FAEs have demonstrated good, sustained clinical efficacy with an acceptable safety profile for the long-term treatment of patients with moderate-to-severe psoriasis. Indeed, the European S3-Guideline on the systemic treatment of Psoriasis vulgaris recommends FAEs for induction and long-term treatment. Until recently, FAEs were only licensed (for the psoriasis indication) in Germany, but were imported to many other European countries, such as The Netherlands, UK, Ireland, Austria and Italy, for the treatment of psoriasis. In 2017, the European Medicines Agency (EMA) approved Skilarence® , a new oral formulation of DMF, for the treatment of adult patients with moderate-to-severe chronic plaque psoriasis in need of systemic therapy. Skilarence only contains DMF and is the first FAE for the treatment of psoriasis that has been approved by the EMA. This approval has given rise to a new oral treatment option for patients with moderate-to-severe plaque psoriasis across Europe. Here, we report the results of an expert meeting which was convened to deliver clinician-agreed consensus and real-world guidance on the clinical use of DMF in moderate-to-severe chronic plaque psoriasis. Guidance on appropriate patient selection, DMF dosage considerations, monitoring and side-effect management is offered based upon available evidence and collective real-world clinical experience.

Fumaric acid esters in combination with a 6-week course of narrowband ultraviolet B provides an accelerated response compared with fumaric acid esters monotherapy in patients with moderate-to-severe plaque psoriasis: a randomized prospective clinical study.

BACKGROUND: Fumaric acid esters (FAE) are safe and effective in patients with moderate-to-severe psoriasis but have a slow onset of action. A short-term combination with narrowband ultraviolet B (NB-UVB) may substantially accelerate the therapeutic response in the induction phase of treatment. OBJECTIVES: To assess the synergistic effect of a 6-week course of NB-UVB phototherapy in addition to FAE in adults with moderate-to-severe plaque psoriasis. METHODS: In this randomized, assessor-masked trial, patients with a Psoriasis Area and Severity Index (PASI) of ≥ 10 and a body surface area affected of ≥ 10 were randomized either to monotherapy with FAE (n = 16) or a combination of FAE with NB-UVB (n = 14). The primary outcome parameter of the study was the mean PASI reduction after 6 weeks of treatment. In addition, the PASI 75 response (≥ 75% improvement from baseline PASI), the Psoriasis Log-based Area and Severity Index (PLASI) and the Dermatology Life Quality Index (DLQI) were assessed as secondary outcome measures. RESULTS: In total, 30 patients (19 men, 11 women; median age 52 years, interquartile range 36-56) were analysed. The mean reduction in PASI after 6 weeks was significantly greater with the combination treatment than with FAE monotherapy (P = 0·016). This was paralleled by a much faster improvement in the DLQI in the combination group than in the FAE-monotherapy group. CONCLUSIONS: Adding a 6-week course of NB-UVB to FAE both accelerates and augments the therapeutic response during the early phase of treatment and increases quality of life in patients with moderate-to-severe plaque psoriasis.

European Dermatology Forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 1: localized scleroderma, systemic sclerosis and overlap syndromes.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities, which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 1 of this guideline provides clinicians with an overview of the diagnosis and treatment of localized scleroderma (morphea), and systemic sclerosis including overlap syndromes of systemic sclerosis with diseases of the rheumatological spectrum.

European dermatology forum S1-guideline on the diagnosis and treatment of sclerosing diseases of the skin, Part 2: Scleromyxedema, scleredema and nephrogenic systemic fibrosis.

The term 'sclerosing diseases of the skin' comprises specific dermatological entities which have fibrotic changes of the skin in common. These diseases mostly manifest in different clinical subtypes according to cutaneous and extracutaneous involvement and can sometimes be difficult to distinguish from each other. The present guideline focuses on characteristic clinical and histopathological features, diagnostic scores and the serum autoantibodies most useful for differential diagnosis. In addition, current strategies in the first- and advanced-line therapy of sclerosing skin diseases are addressed in detail. Part 2 of this guideline provides clinicians with an overview of the diagnosis and treatment of scleromyxedema, scleredema (of Buschke) and nephrogenic systemic sclerosis (nephrogenic fibrosing dermopathy).

Quality of life and comorbidities in palmoplantar pustulosis - a cross-sectional study on 102 patients.

BACKGROUND: Association of palmoplantar pustulosis (PPP) with metabolic and autoimmune diseases has been reported in mostly small case series or anecdotal cases. OBJECTIVE: To assess health-related quality of life and prevalence of comorbidities in a large cohort of PPP patients. METHODS: We conducted a cross-sectional study on patients with either active or past PPP. Disease severity was measured by the Palmoplantar Pustulosis Area and Severity Index (ppPASI). Quality of life was assessed by the Dermatology Life Quality Index (DLQI). Comorbidities were evaluated by medical history, blood examination, stool testing for Helicobacter pylori antigen and screening tools for depression and psoriatic arthritis. RESULTS: A total of 102 patients (87 women, 15 men) with a mean age of 52.6 ± 14.1 years were evaluated. The mean DLQI was 7 ± 6. Comorbidities were frequent and consisted of hypercholesterolaemia (38%), hypertension (32%), obesity (27%), metabolic syndrome (26%), depression (24%), diabetes (19%), autoimmune thyroiditis (16%) and psoriatic arthritis (16%). CONCLUSION: Patients with PPP have an impaired quality of life and a broad range of comorbidities. Contrary to other reports, our investigation failed to show an association between PPP and coeliac disease or H. pylori infection.

Randomized controlled trial comparing 35% trichloroacetic acid peel and 5-aminolaevulinic acid photodynamic therapy for treating multiple actinic keratosis.

BACKGROUND: Photodynamic therapy (PDT) and chemical peels with trichloroacetic acid (TCA) can be applied to large skin areas and thus are suitable treatment options for patients with multiple actinic keratosis (AK). However, despite its long use, TCA has been investigated only rarely in this indication. OBJECTIVES: This randomized, observer-blinded, intrapatient comparative study sought to investigate the efficacy and safety of 35% TCA vs. aminolaevulinic acid 20% (ALA) PDT in patients with extensive field cancerization and multiple AKs in the face or on the scalp. METHODS: Twenty-eight patients with at least five AKs in two comparable anatomical areas on the head were treated with 35% TCA and ALA PDT randomly assigned to each area. Their therapeutic efficacy, adverse events and cosmetic outcome were assessed by a blinded investigator at 1, 3, 6 and 12 months after treatment. RESULTS: After 12-months' follow-up TCA and ALA PDT reduced the total lesion count, the primary outcome, by 31% and 58%, respectively (P = 0·006). Complete clearance of pre-existing AKs were 49% for TCA and 74% for ALA PDT (P = 0·011). Treatment failure (number of AKs greater than 50% of the baseline count) was observed in seven patients (25%) after TCA and in two patients (7%) after PDT treatment. Treatment-related pain was significantly higher for ALA PDT (visual analogue scale 7·5 ± 2·3 vs. TCA: 5·1 ± 2·6; P = 0·04), whereas scarring (n = 6, 21%) was seen only in TCA treated patients. CONCLUSIONS: ALA PDT provided better clinical results than TCA in the treatment of patients with extensive field cancerization and multiple AKs.

Guidelines for the management of vitiligo: the European Dermatology Forum consensus.

The aetiopathogenic mechanisms of vitiligo are still poorly understood, and this has held back progress in diagnosis and treatment. Up until now, treatment guidelines have existed at national levels, but no common European viewpoint has emerged. This guideline for the treatment of segmental and nonsegmental vitiligo has been developed by the members of the Vitiligo European Task Force and other colleagues. It summarizes evidence-based and expert-based recommendations (S1 level).