A.D. Ormerod

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.

British Association of Dermatologists’ guidelines for biologic interventions for psoriasis 2009

St John’s Institute of Dermatology, King’s College London and Guy’s and St Thomas’ NHS Foundation Trust, London SE1 9RT U.K. *Department of Dermatology, Royal Gwent Hospital, Newport NP20 2UB, U.K. Department of Dermatology, Western Infirmary, Glasgow G11 6NT, U.K. The Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester M6 8HD, U.K. §Psoriasis and Psoriatic Arthritis Alliance, PO Box 111, St Albans AL2 3JQ, U.K. –Department of Dermatology, Cardiff University, School of Medicine, Heath Park, Cardiff CF14 4XN, U.K. **Royal National Hospital for Rheumatic Diseases, Bath BA1 1RL, U.K. Department of Dermatology, Belfast City Hospital, Belfast BT9 7AB, U.K. Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, U.K. §§Department of Dermatology, Aberdeen Royal Infirmary, Foresterhill, Aberdeen AB9 2ZB, U.K.

British Association of Dermatologists guidelines for use of biological interventions in psoriasis 2005

Psoriasis is a common, persistent, relapsing inflammatory skin disease that can be associated with significant morbidity. Quality of life studies in psoriasis reveal a negative impact on patients comparable with that seen in cancer, arthritis and heart disease.1–5 Patients with severe disease constitute approximately 20–30% of all patients with psoriasis, often require systemic treatment, and represent a major economic burden to the Health Service. All standard systemic therapies for severe disease are associated with the potential for major long-term toxicity, many are expensive, and a proportion of patients has treatmentresistant disease.6 Biological therapies or ‘biologics’ describe agents designed to block specific molecular steps important in the pathogenesis of psoriasis and have emerged over the last 3–5 years as potentially valuable alternative therapeutic options. Currently, biological therapies for psoriasis comprise two main groups: (i) agents targeting the cytokine tumour necrosis factor (TNF)-a (e.g. etanercept, infliximab, adalimumab) and (ii) agents targeting T cells or antigen-presenting cells (e.g. efalizumab, alefacept). Two of these, etanercept (Enbrel) and efalizumab (Raptiva) were licensed in 2004 in the U.K. for patients with moderate to severe psoriasis.

Guideline for the diagnosis and management of vitiligo

This detailed and user‐friendly guideline for the diagnosis and management of vitiligo in children and adults aims to give high quality clinical advice, based on the best available evidence and expert consensus, taking into account patient choice and clinical expertise.

The European baseline series in 10 European Countries, 2005/2006 : results of the European Surveillance System on Contact Allergies (ESSCA)

Background: Continual surveillance based on patch test results has proved useful for the identification of contact allergy.

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Drug survival reflects a drugs effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.

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

Detection of nitric oxide and nitric oxide synthases in psoriasis

Biopsies from psoriasis lesions and clinically uninvolved skin of eight patients and five normal subjects were studied by immunocytochemistry with computerized image analysis for the presence of endothelial, neuronal and inducible isoforms of nitric oxide synthase. Endothelial nitric oxide synthase was expressed in the endothelium and weakly in some keratinoctyes. Its expression was not significantly different in psoriasis. Inducible nitric oxide synthase, however, was absent from normal skin but was significantly upregulated in psoriatic lesional skin, focally in keratinocytes but to the greatest extent in the papillary dermis and to a lesser extent in clinically uninvolved psoriatic skin. Inducible nitric oxide synthase staining was greatest in the more severe lesions and correlated with the inflammatory infiltrate (CD3-positive cells) and with keratinocyte proliferation (Ki-67-positive cells). In normal skin, neuronal nitric oxide synthase was expressed only in keratinocytes in the granular layer and eccrine sweat glands. However, in psoriasis and clinically uninvolved skin the neuronal form was present through all levels of the epidermis. Direct measurement of nitric oxide production from the skin surface revealed a tenfold increase in the lesions of 16 psoriatic patients compared with their nonlesional skin, and this nitric oxide production was inhibited by topical betamethasone.

Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens

Aims: Nitric oxide is generated from sweat nitrite in the acidic environment of the skin surface and is thought to contribute to protection against infection. This study examined the sensitivity of Trichophyton mentagrophytes, T. rubrum, Candida albicans, Streptococcus pyogenes, Staphylococcus aureus and Propionibacterium acnes to acidified nitrite.

Topical tacrolimus and pimecrolimus and the risk of cancer: how much cause for concern?

Both tacrolimus and pimecrolimus are immunosuppressive calcineurin inhibitors which lead to plausible increased risks of cancer when administered systemically. The biological risks from these drugs have been verified in humans following oral therapy for transplantation in the case of tacrolimus and in animal models for both compounds. Therefore, there is theoretical concern that topical application of these compounds might similarly increase the risk to patients. This risk has led to the institution of long-term cohort studies and increased pharmocovigilance. The U.S. Food and Drug Administration (FDA) has regularly met to monitor the worldwide evidence of a signal for increased risk and following a meeting in February this year took the step of applying black box warnings to these products. The decision to do so was prompted by indiscriminate off-label usage in the U.S.A., particularly in the under 2-year age group where systemic absorption may be more significant and the immune system is still developing. Further, this was prompted by animal data showing increased risk with increased exposure. The FDA advised weighing up the risks of treatment against the benefits and stressed that approval was for short-term intermittent treatment of patients unresponsive or intolerant to other agents, using the minimal amount required to control eczema. They also indicated that patients should not use these agents if their immune system was already compromised. Under freedom of information legislation the data considered and the recommendations made are freely available on the FDA website and many of the data for this report are taken from there.