EuroGuiderm guideline on lichen sclerosus-introduction into lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

EuroGuiderm guideline on lichen sclerosus-Treatment of lichen sclerosus.

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

Impact of off-label use regulations on patient care in dermatology - a prospective study of cost-coverage applications filed by tertiary dermatology clinics throughout Germany.

BACKGROUND: In dermatology, a medical speciality with a relatively high number of rare diseases, physicians often have to resort to off-label treatment options. To avoid claims, physicians in Germany can file a cost-coverage request (off-label application, OL-A). OBJECTIVES: Our aim was to investigate the extent to which the current regulations affect patient care. MATERIAL AND METHODS: Prospective cohort study among tertiary dermatology clinics throughout Germany, consecutively including OL-As (05/2019-09/2020) and assessing the follow-up correspondence. We modelled regressions to assess factors associated with cost-coverage decisions and the time needed by health insurers to process the OL-As. RESULTS: Thirteen clinics provided data on 121 OL-As, two of which applied for on-label treatments. Of the remaining 119 OL-As, 70 (58.8%) were immediately approved and 44 (37.0%) rejected. Including cases with one or more appeals, 87 of 119 OL-As (73.1%) were finally approved and 26 (21.9%) rejected. There was an association of the final approval rate with (1) the class of medication/treatment, with approval rates being significantly lower for JAK inhibitors than for biologics (OR 0.16, 95%-CI: 0.03-0.82); (2) German state, with approval rates being lower in eastern than in western states (OR 0.30, 95%-CI 0.12-0.76); and (3) cost of the intervention (no linear trend). However, none of these predictors was significant in our multiple logistic regression models. The median health insurer's processing time (first response) was 29 days (IQR 22-38). Our analyses showed no evidence of an association with the predictors we assessed. In cases approved, the median time from the decision to file an OL-A to the actual initiation of the treatment was 65.5 days (IQR 51-92). CONCLUSIONS: Our study points to substantial delays and inequalities in the provision of timely health care for dermatological patients with rare diseases, often involving treatments for which there is no adequate approved therapy.

[Current dermatology guidelines in Germany and Europe : A selection of clinically relevant recommendations]. / Aktuelle dermatologische Leitlinien in Deutschland und Europa : Eine praxisorientierte Übersicht ausgewählter Empfehlungen.

Clinical practice guidelines are systematically developed decision aids for specific medical conditions. In Germany, national dermatology guidelines are developed chiefly under the aegis of the German Dermatological Society in collaboration with the Professional Association of German Dermatologists. European and international dermatological guidelines also exist and are developed by a range of organisations, such as the European Centre for Guidelines Development, which was founded by the European Dermatology Forum in 2018. In the years 2019 and 2020, new or updated German national guidelines were published on topics such as pathological scars (hypertrophic scars and keloids), cutaneous lupus erythematosus, pyoderma grangrenosum, anal pruritus, anal eczema, anal canal and anal rim carcinomas, as well as the prevention of HPV-associated neoplasms through vaccination, syphilis and the systemic treatment of neurodermitis. A new European guideline on lichen planus closes a gap in the spectrum of guidelines available in Germany. Key recommendations and relevant changes in the guidelines are presented in this article.

2019 IUSTI-Europe guideline for the management of anogenital warts.

This guideline is an update of the 2011 European Guideline for the Management of Anogenital Warts. It is intended to support best practice in the care of patients with anogenital warts by including evidence-based recommendations on diagnosis, treatment, follow-up and advice to patients. It is intended for use by healthcare professionals in sexual healthcare or dermato-venereology clinics in Europe but may be adapted for use in other settings where the management of anogenital warts is undertaken. As a European guideline, recommendations should be adapted according to national circumstances and healthcare systems. Despite the availability of vaccine to prevent HPV types 6 and 11, the cause of >95% anogenital warts, they remain an important and frequent health problem. The previous systematic review of randomized controlled trials for anogenital warts was updated. The changes in the present guideline include the following: Updated background information on the prevalence, natural history and transmission of human papillomavirus (HPV) infection and anogenital warts. Key recommendations for diagnosis and treatment have been graded according to the strength of the recommendation and the quality of supporting evidence. 5-fluorouracil, local interferon and photodynamic therapy have been evaluated and included as potential second-line treatment options. Evidence of the impact of HPV vaccination on the incidence of anogenital warts has been updated.

Prioritizing topics in guideline development: results of a two-phase online survey of dermatologist members of the EADV.

BACKGROUND: Most clinical guidelines in dermatology are encyclopaedic, covering a disease and its aetiology, diagnosis, treatment and prevention in their entirety. The usability and uptake of guideline recommendations might be improved by guidelines that are more concise and address specific questions ranked by users according to their perceived importance. OBJECTIVE: To survey the largest association of dermatologists in Europe, identify which questions in their everyday practice they felt would benefit from short, evidence-based guidance and rank these systematically. METHODS: A two-phase online survey using a structured ranking approach and the members directory of the European Academy of Dermatology and Venereology (EADV). RESULTS: The first survey yielded 265 suggestions, indicating a response rate of 3.7%. We grouped all responses according to themes and subsequently combined these into a list of 35 broader topics. These were presented to all members of the EADV in the second survey (response rate: 9.7%), which yielded a list of the top 10 topics participants felt were most in need of guidance. The first three were 'Systemic drug treatment in dermatology during pregnancy and for women wishing to have children in the near future', 'alopecia areata' and 'interpretation of laboratory results in connective tissue diseases'. CONCLUSION: Our two-phase survey of EADV members and a structured ranking process were practical to implement and yielded a list of the top 10 topics in dermatology and venereology for guideline development. Guideline dissemination needs to be improved, and practical, more concise guidelines may facilitate efforts to do so.

The EAACI/GA²LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria.

This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Topical treatments for scalp psoriasis: summary of a Cochrane Systematic Review.

People with chronic plaque psoriasis often have lesions on the scalp that are difficult to treat. This report is a summary of a Cochrane review on the efficacy and safety of topical treatments for scalp psoriasis. For quality-of-evidence assessment, we used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach. Only randomized controlled trials (RCTs) were eligible for inclusion. We searched the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS; ongoing trials; indexes of included studies and screened abstracts of six psoriasis-specific conferences up to August 2015. We included 59 RCTs, with 11 561 participants overall. Most findings were limited to short-term treatments (< 6 months). According to the clinician and patients' self-assessment, a corticosteroid-vitamin D combination (e.g. betamethasone dipropionate plus calcipotriol) and corticosteroids of high and very high potency were better than vitamin D. The two-compound combination was superior to the corticosteroid alone, but the additional benefit was small. Reporting of quality-of-life data was insufficient. The two-compound combination and corticosteroids caused fewer withdrawals due to adverse events than vitamin D. There was no difference between the two-compound combination and corticosteroid monotherapy concerning this outcome. Overall the evidence was of moderate quality. Evaluation of other topical treatments was limited. Given the comparable safety profile and only slim benefit of the two-compound combination over the corticosteroid alone, monotherapy with generic topical corticosteroids of high and very high potency may be fully acceptable for short-term therapy. More quality-of-life data and long-term assessments are needed.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction in the incidence of postherpetic neuralgia (PHN) and other complications. The guideline development followed a structured and pre-defined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence-Based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this second part of the guideline, therapeutic interventions have been evaluated. The expert panel formally consented recommendations for the treatment of patients with HZ (antiviral medication, pain management, local therapy), considering various clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 1: Diagnosis.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction of the incidence of postherpetic neuralgia and other complications. The guideline development followed a structured and predefined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this first part of the guideline, diagnostic means have been evaluated. The expert panel formally consented recommendations for the management of patients with (suspected) HZ, referring to the assessment of HZ patients, considering various specific clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

Report from the kick-off meeting of the Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN).

A major obstacle of evidence-based clinical decision making is the use of nonstandardized, partly untested outcome measurement instruments. Core Outcome Sets (COSs) are currently developed in different medical fields to standardize and improve the selection of outcomes and outcome measurement instruments in clinical trials, in order to pool results of trials or to allow indirect comparison between interventions. A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The international, multidisciplinary Cochrane Skin Group Core Outcome Set Initiative (CSG-COUSIN) aims to develop and implement COSs in dermatology, thus making trial evidence comparable and, herewith, more useful for clinical decision making. The inaugural meeting of CSG-COUSIN was held on 17-18 March 2015 in Dresden, Germany, as the exclusive theme of the Annual Cochrane Skin Group Meeting. In total, 29 individuals representing a broad mix of different stakeholder groups, professions, skills and perspectives attended. This report provides a description of existing COS initiatives in dermatology, highlights current methodological challenges in COS development, and presents the concept, aims and structure of CSG-COUSIN.

The quality of European dermatological guidelines: critical appraisal of the quality of EDF guidelines using the AGREE II instrument.

Clinical practice guidelines are systematically developed tools to assist clinicians and health policy makers in decision making for clearly defined clinical situations. In the light of the demand for evidence-based medicine and quality in health care and the increasing methodological requirements concerning guidelines development, it is important to evaluate existing practice guidelines to systematically identify strengths and weaknesses. Currently, the most accepted tool for the methodological evaluation of guidelines is the Appraisal of Guidelines for Research & Evaluation (AGREE) Instrument. Intention of this assessment is to identify and critically appraise clinical practice guidelines commissioned by the European Dermatology Forum (EDF). A quality assessment of a predefined set of guidelines, including all available clinical practice guidelines published on the EDF guidelines internet site, was performed using the AGREE II instrument. To assure an objective assessment, four independent assessments were performed by evaluators situated in different European countries. Twenty-five EDF guidelines covering different dermatological topics were identified and evaluated. The assessment included seven guidelines developed on the highest methodological standard (systematic literature search and structured consensus conference, S3). Eighteen guidelines were identified that were based on either a structured consensus process (S2k), a systematic literature assessment (S2e) or on informal consensus only (S1). The methodological and reporting quality among the evaluated guidelines was heterogeneous. S3 guidelines generally received the highest scores. The domains 'clarity of presentation' and 'scope and purpose' achieved the highest mean ratings within the different domains of assessment, whereas the domains of 'applicability', 'stakeholder involvement' and 'editorial independence' scored poorly. Considering the large variations in the achieved scores, there is need for methodological harmonization within the EDF guidelines to achieve comparable methodological standards.

[Current guidelines in dermatology : A selection of clinically relevant recommendations]. / Aktuelle dermatologische Leitlinien : Eine praxisorientierte Übersicht ausgewählter Empfehlungen.

Guidelines are systematically developed decision aids for specific medical conditions. The German Dermatological Society, together with the German Professional Association of Dermatologists, takes the lead in the development of the guidelines for dermatology in Germany. In addition to national guidelines, European and international guidelines also exist. In 2014 and 2015 German guidelines on the following topics were newly developed or updated: cutaneous larva migrans, anticoagulation during dermatosurgery, pemphigus vulgaris and bullous pemphigoids, Mohs surgery, anal dysplasia, and anal carcinoma in HIV-infected patients. European guidelines on psoriasis vulgaris and hand eczema were updated among others. An international guideline on actinic keratosis was also published. The guidelines are available at www.awmf.org and www.euroderm.org .

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

The natural history of actinic keratosis: a systematic review.

Knowledge about the development of untreated actinic keratosis (AK) and risk of progression into squamous cell carcinoma (SCC) is important. Therefore, we set out to synthesize primary data on the natural history of AK. We carried out a systematic literature search (Medline, Medline in Process, Embase, Cochrane) of studies on the natural course of AK, regarding (i) progression and regression rates per lesion-year, (ii) changes in total lesion counts over time, and (iii) spontaneous field regression and recurrence rates, taking into account studies on participants without immunosuppression and history of skin cancer, immunosuppressed patients and participants with a history of skin cancer and sunscreen use. Twenty-four eligible studies were identified providing data on at least one of the outcomes. Progression rates of AK to SCC ranged from 0% to 0·075% per lesion-year, with a risk of up to 0·53% per lesion in patients with prior history of nonmelanoma skin cancer. Rates of regression of single lesions ranged between 15% and 63% after 1 year. The data available on recurrence rates of single lesions 1 year after regression indicate a recurrence rate of 15-53%. Data on the relative change of total AK count over time are heterogeneous, and range from -53% to +99·1%. Spontaneous complete field regression rates range from 0% to 21%, with recurrences in 57%. In general, the available data are limited. Important methodological limitations apply. Currently, no reliable estimates concerning the frequency of AK developing into invasive carcinoma can be given, and further studies are needed.