Alexander Nast

European S3‐Guidelines on the systemic treatment of psoriasis vulgaris

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

European Evidence‐based (S3) Guidelines for the Treatment of Acne

Subcommittee Members: Dr. Alexander Nast, Berlin (Germany) Dr. Cristina Oprica, Stockholm (Sweden) Prof. Dr. Brigitte Dreno, Nantes (France) Mrs. Stefanie Rosumeck, Berlin (Germany) Dr. Vincenzo Bettoli, Ferrara (Italy) Prof. Dr. Berthold Rzany, Berlin (Germany) Prof. Dr. Klaus Degitz, Munich (Germany) Dr. Adel Sammain, Berlin (Germany) Mr. Ricardo Erdmann, Berlin (Germany) Dr. Thierry Simonart, Brussels (Belgium) Prof. Dr. Andrew Finlay, Cardiff (United Kingdom) Dr. Niels Kren Veien, Aalborg (Denmark) Prof. Dr. Ruta Ganceviciene, Vilnius (Lithuania) Dr. Maja Vurnek fivkovi , Zagreb (Croatia) Dr. Alison Layton, Harrogate (United Kingdom) Prof. Dr. Christos Zouboulis, Dessau (Germany) Dr. Jose Luis Lopez Estebaranz, Madrid (Spain) Prof. Dr. Falk Ochsendorf, Frankfurt (Germany) Prof. Dr. med. Harald Gollnick, Magdeburg (Germany)

S3 – Guidelines on the treatment of psoriasis vulgaris (English version). Update

Psoriasis vulgaris is a common and often chronic inflammatory skin disease. The incidence of psoriasis in Western industrialized countries ranges from 1.5% to 2%. Patients afflicted with severe psoriasis vulgaris may experience a significant reduction in quality of life. Despite the large variety of treatment options available, surveys have shown that patients still do not received optimal treatments. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologi sche Gesellschaft (DDG) and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence‐based guidelines for the management of psoriasis. They were first published in 2006 and updated in 2011. The Guidelines focus on induction therapy in cases of mild, moderate and severe plaque‐type psoriasis in adults including systemic therapy, UV therapy and topical therapies.

European S3-Guidelines on the systemic treatment of psoriasis vulgaris - Update 2015 - Short version - EDF in cooperation with EADV and IPC

European S3-Guidelines on the systemic treatment of psoriasis vulgaris – Update 2015 – Short version – EDF in cooperation with EADV and IPC A. Nast,* P. Gisondi, A.D. Ormerod, P. Saiag, C. Smith, P.I. Spuls, P. Arenberger, H. Bachelez, J. Barker, E. Dauden, E.M. de Jong, E. Feist, A. Jacobs, R. Jobling, L. Kem eny, M. Maccarone, U. Mrowietz, K.A. Papp, C. Paul, K. Reich, S. Rosumeck, T. Talme, H.B. Thio, P. van de Kerkhof, R.N. Werner, N. Yawalkar Division of Evidence Based Medicine, Department of Dermatology, Charit e – Universit€ atsmedizin Berlin, Berlin, Germany Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy Department of Dermatology, Aberdeen Royal Infirmary, Aberdeen, UK Service de Dermatologie, Hôpital Ambroise Par e Universit e Paris V, Boulogne, France Clinical Lead for Dermatology, St Johns Institute of Dermatology, St Thomas’ Hospital, London, UK Department of Dermatology, Academic Medical Center, Amsterdam, The Netherlands Third Faculty of Medicine, Department of Dermatology, Charles University, Prague, Czech Republic Department of Dermatology, Hôpital Saint-Louis, Paris, France St. Johns Institute of Dermatology, St. Thomas’ Hospital, London, UK Hospital Universitario de la Princesa, Madrid, Spain University Medical Center Nijmegen St Radboud, Nijmegen, The Netherlands Medizinische Klinik mit Schwerpunkt Rheumatologie u. klinische Immonologie, Charit e – Universit€atsmedizin Berlin, Berlin, Germany Cambridge, UK SZTE Borgyogyaszati Klinika, Szeged, Hungary Roma, Italy Department of Dermatology, Psoriasis-Center University Medical Center Schleswig Holstein, Kiel, Germany Waterloo, Canada Department of Dermatology, Paul Sabatier University, Toulouse, France Dermatologikum Hamburg, Hamburg, Germany Section of Dermatology and Venereology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden Department of Dermatology, Erasmus University, Rotterdam, The Netherlands Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands Department of Dermatology, Inselspital, Universit€ atsklinik f€ ur Dermatologie, Bern, Switzerland *Correspondence: A. Nast. E-mail: alexander.nast@charite.de Received: 22 June 2015; Accepted: 7 July 2015

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.

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).

Efficacy and safety of systemic treatments for moderate‐to‐severe psoriasis: meta‐analysis of randomized controlled trials

Dermatologists may choose from various conventional and biological systemic agents to treat patients with moderate‐to‐severe psoriasis. We set out to analyse systematically the efficacy and tolerability of approved treatments for moderate‐to‐severe psoriasis. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) investigating the efficacy of systemic treatment approved for moderate‐to‐severe psoriasis. Efficacy was assessed as the proportion of participants with 75% improvement in Psoriasis Area and Severity Index at primary efficacy measurement (week 8–16). Safety was summarized as rates of adverse events and withdrawals. Direct and indirect comparative efficacy was assessed by random effects meta‐analysis of risk differences (RDs). In total, 48 eligible RCTs totalling 16 696 patients (11 178 randomized to biologics, 1888 to conventional treatments) were identified. In placebo‐controlled trials, infliximab was the most efficacious [RD 76%, 95% confidence interval (CI) 73–79%]. Adalimumab (RD 61%, 95% CI 56–67%), and ustekinumab 45 mg (RD 63%, 95% CI 59–66%) and 90 mg (RD 67%, 95% CI 60–74%) each had similar efficacy. These biologics are more effective than etanercept and all conventional treatments. Head‐to‐head trials indicate the superiority of adalimumab and infliximab over methotrexate (MTX), the superiority of ustekinumab over etanercept, the nonsignificant superiority of ciclosporin over MTX, and the dose‐dependent efficacy of etanercept and ustekinumab. Fumaric acid is as efficacious as MTX. Safety of treatments could not be pooled due to a lack of standardization in reporting across trials. In conclusion, the qualitative and quantitative evidence is much stronger for biological interventions than for conventional treatments.

The Diagnosis and Treatment of Oral Cavity Cancer

BACKGROUND About 10,000 persons are diagnosed as having carcinoma of the oral cavity or the throat in Germany every year. Squamous-cell carcinoma accounts for 95% of cases. METHODS We systematically reviewed the pertinent literature on predefined key questions about these tumors (which were agreed upon by a consensus of the investigators), concerning imaging, the removal of cervical lymph nodes, and resection of the primary tumor. RESULTS 246 clinical trials were selected for review on the basis of 3014 abstracts. There was only one randomized, controlled trial (evidence level 1-); the remaining trials reached evidence levels 2++ to 3. Patients with mucosal changes of an unclear nature persisting for more than two weeks should be examined by a specialist without delay. The diagnosis is made by computed tomography or magnetic resonance imaging along with biopsy and a standardized histopathological examination. Occult metastases are present in 20% to 40% of cases. Advanced disease (stages T3 and T4) should be treated by surgery followed by radiotherapy, with or without chemotherapy. 20% of the patients overall go on to have a recurrence, usually within 2 to 3 years of the initial treatment. The 5-year survival rate is somewhat above 50%. Depending on the radicality of surgery and radiotherapy, there may be functional deficits, osteoradionecrosis, and xerostomia. The rate of loss of implants in irradiated bone is about 10% in 3 years. CONCLUSION The interdisciplinary planning and implementation of treatment, based on the patients individual constellation of findings and personal wishes, are prerequisites for therapeutic success. Reconstructive measures, particularly microsurgical ones, have proven their usefulness and are an established component of surgical treatment.

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

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.

A consensus report on appropriate treatment optimization and transitioning in the management of moderate-to-severe plaque psoriasis.

There is limited information on systemic and biological treatment optimization and transitioning in routine clinical practice.