​Author(s): Jabbar-Lopez Z.K.; Smith C.H.; Yiu Z.Z.N.; Warren R.B.; Ward V.; Exton L.S.; Mohd Mustapa M.F.; Samarasekera E.; Burden A.D.; Murphy R.; Owen C.M.; Parslew R.; Venning V.
Source: Journal of Investigative Dermatology; Dec 2017; vol. 137 (no. 12); p. 2644-2646
Publication Date: Dec 2017
Publication Type(s): Article
Database: EMBASE
 

Author(s): Smith C.H.; Jabbar-Lopez Z.K.; Peleva E.; MacMahon E.; Nelson-Piercy C.; Yiu Z.Z.; Warren R.B.; Bale T.; Burden A.D.; Coates L.C.; Cruickshank M.; Pottinger E.; Samarasekera E.J.; Hadoke T.; Strudwicke C.; Murphy R.; Owen C.M.; Parslew R.; Stoddart J.; Venning V.A.; Exton L.S.; Mohd Mustapa M.F.

Source: British Journal of Dermatology; Sep 2017; vol. 177 (no. 3); p. 628-636
Publication Date: Sep 2017

Publication Type(s): Article
​
Available  at British Journal of Dermatology -  from Wiley Online Library Medicine and Nursing Collection 2017 - NHS

Database: EMBASE

Author(s): Jabbar-Lopez Z.K.; Yiu Z.Z.N.; Warren R.B.; Ward V.; Exton L.S.; Mohd Mustapa M.F.; Samarasekera E.; Burden A.D.; Murphy R.; Owen C.M.; Parslew R.; Venning V.; Smith C.H.

Source: Journal of Investigative Dermatology; Aug 2017; vol. 137 (no. 8); p. 1646-1654

Publication Date: Aug 2017

Publication Type(s): Article

Abstract:Multiple biologic treatments are licensed for psoriasis. The lack of head-to-head randomized controlled trials makes choosing between them difficult for patients, clinicians, and guideline developers. To establish their relative efficacy and tolerability, we searched MEDLINE, PubMed, Embase, and Cochrane for randomized controlled trials of licensed biologic treatments for skin psoriasis. We performed a network meta-analysis to identify direct and indirect evidence comparing biologics with one another, methotrexate, or placebo. We combined this with hierarchical cluster analysis to consider multiple outcomes related to efficacy and tolerability in combination for each treatment. Study quality, heterogeneity, and inconsistency were evaluated. Direct comparisons from 41 randomized controlled trials (20,561 participants) were included. All included biologics were efficacious compared with placebo or methotrexate at 3-4 months. Overall, cluster analysis showed adalimumab, secukinumab, and ustekinumab were comparable in terms of high efficacy and tolerability. Ixekizumab and infliximab were differentiated by very high efficacy but poorer tolerability. The lack of longer term controlled data limited our analysis to short-term outcomes. Trial performance may not equate to real-world performance, and so results need to be considered alongside real-world, long-term safety and effectiveness data. These data suggest that it is possible to discriminate between biologics to inform clinical practice and decision making (PROSPERO 2015:CRD42015017538).Copyright © 2017 The Authors
​
Database: EMBASE

Author(s): Iskandar I.Y.K.; Ashcroft D.M.; Warren R.B.; Evans I.; McElhone K.; Griffiths C.E.M.; Owen C.M.; Burden A.D.; Smith C.H.; Reynolds N.J.

Source: British Journal of Dermatology; May 2017; vol. 176 (no. 5); p. 1297-1307

Available in full text at British Journal of Dermatology -  from John Wiley and Sons

Abstract:Background: Treatment modifications, including dose escalations, dose reductions, switches, discontinuations and restarts of biologics may be necessary in the management of psoriasis but the patterns of usage are incompletely defined. Objectives: To examine the treatment utilization patterns of adalimumab, etanercept and ustekinumab among biologic-naive and non-naive patients with psoriasis enrolled in the British Association of Dermatologists Biologic Interventions Register (BADBIR). Methods: The study cohort included adults with chronic plaque psoriasis who were followed up for >= 12 months. Treatment modifications were assessed during the first year of therapy. The time-trend method, comparing the cumulative dose (CD) patients received with the recommended cumulative dose (RCD), was used to assess dosing patterns. Concomitant use of other systemic treatments was also examined. Results: In total, 2980 patients (adalimumab: 1675; etanercept: 996; ustekinumab: 309) were included; 79.2% were biologic-naive. Over 12 months, 77.4% of patients continued the biologic, 2.6% restarted therapy after a break of >= 90 days, 2.5% discontinued, and 17.5% switched biologic therapy. Most patients (85.7%) received the RCD of the biologic, although 8.1% were exposed to a higher CD. In total, 749 (25.1%) patients used conventional systemic therapies concomitantly with a biologic at some stage; methotrexate was used most commonly (458; 61.2%). Of those using combination therapy, 454 (60.6%) continued the use of the conventional systemic therapy for > 120 days after the start of the biologic. Conclusions: More than one-third of patients experienced treatment modifications within the first year of initiating a biologic. Conventional systemic therapies, particularly methotrexate, were commonly used concurrently, which should be considered when evaluating treatment response and adverse events to biologics in real-world observational studies.Copyright © 2016 British Association of Dermatologists
​
Database: EMBASE

Author(s): Shah M.

Source: Clinical and Experimental Dermatology; 2017

Available in full text at Clinical and Experimental Dermatology -  from John Wiley and Sons

Abstract:It is important to assess outcomes for medical interventions in order to focus scarce resources on outcomes with a known positive benefit. An open, observational study was performed to assess the clinical outcomes of 600 male patients with a genital skin problem attending a specialist secondary care dermatology facility. Patients were mainly referred by general practitioners and genitourinary medicine physicians. Outcome was measured at 3 and 6 months, and was determined by clinical examination and assessment of patient symptoms. The mean age of the group was 45.3 years. The commonest diagnoses were lichen sclerosus (30.5%), balanitis (17.3%), eczema (12.8%), lichen planus (7.3%), psoriasis (7.2%) and benign lesions (5.5%). The commonest presenting symptoms were genital rash (43%), genital soreness, pain or burning (17.5%), and penile lesions (15.7%). Lichen sclerosus and all forms of balanitis were more common in uncircumcised patients, whereas lichen planus was more common in circumcised males. Short-term outcome was excellent, with 11.5% of patients being reassured and discharged on their first visit, and after 6 months 58% of all patients were clear and 12% had improved. Only 4.5% reported no improvement in symptoms. Diagnostic biopsy demonstrated malignant or premalignant lesions in nearly a fifth of those having a procedure. Close working with urological and genitourinary medicine colleagues is important to manage the various aspects of male health.Copyright © 2017 British Association of Dermatologists.
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Database: EMBASE

Author(s): Collier, Nicholas J; Chaing, Nicole Y Z; Coulson, Ian H

Source: Journal of the American Academy of Dermatology; Feb 2017; vol. 76 (no. 2); p. e43

Publication Date: Feb 2017

Publication Type(s): Journal Article
​
Database: Medline

Author(s): Singh M.; Calonje E.; Farquharson N.; Owen C.; Howat A.J.; Singh S.; Francis N.

Source: Clinical and Experimental Dermatology; 2017

Publication Date: 2017

Publication Type(s): Journal: Article In Press

Available in full text at Clinical and Experimental Dermatology -  from John Wiley and Sons

Abstract:Morphoea (localized scleroderma) is a cutaneous inflammatory condition characterized by the development of indurated and discoloured plaques. The histological features of morphoea typically include a superficial and deep perivascular and periadnexal chronic inflammatory infiltrate associated with variable degrees of dermal and/or subcutaneous sclerosis. The infiltrate is typically composed of lymphocytes, macrophages and conspicuous plasma cells. The early stages of morphoea may have a very prominent inflammatory infiltrate associated with subtle sclerosis. In addition, the inflammatory infiltrate may show a perineural and rarely intraneural distribution. We report two cases of morphoea that histologically showed plasma cell endoneuritis associated with subtle dermal sclerosis. These two cases highlight the potential for diagnostic confusion with infectious and inflammatory diseases, particularly leprosy and lupus. Copyright © 2017 British Association of Dermatologists.
​
Database: EMBASE

​Source: Contact Dermatitis; Sep 2016; vol. 75 ; p. 104

Publication Type(s): Journal: Conference Abstract

Author(s): Johnston G.; Exton L.; Mohd Mustapa M.F.; Coulson I.; English J.; Bourke J.

Abstract:The British Association of Dermatologists (BAD) is one of only a few specialist societies that fund independently produced guidelines with a qualified information technology team. In the speciality of contact dermatitis it is recognized that evidence may be lacking or of poor quality, and so employing a robust methodology is important in developing guidance even in areas where the evidence base is weak.

The Grading of Recommendations Assessment, Development and Evaluation (GRADE) is the gold-standard methodology for developing systematic reviews and clinical guidelines. It offers a transparent process from evidence to recommendations, with set criteria to guide the guideline development group (GDG) in formulating a recommendation and determining its strength, with clear, pragmatic interpretation of strong vs. weak recommendations for clinicians and patients. It also acknowledges patient values and preferences. The new BAD guidelines adopted this system for contact dermatitis. The GDG specified key clinical questions to form the basis of the guideline using the PICO method. This technique frames and answers a clinical question and considers the patient population, an intervention, a comparator and the outcome. Literature searches covering the PICO questions were run across multiple databases.

The GDG then identified all possible outcomes of interest and of importance to patients, and ranked them by those that were (i) critical for decision making, (ii) important but not critical for decision making and (iii) not important for decision making. Those outcomes agreed as critical for decision making determined the overall quality of the evidence. Unlike previous systems where each study is assessed and graded individually, GRADE assesses the quality of evidence per comparison (intervention vs. comparator/control), per outcome and then across all the studies (i.e. for the body of evidence) that report that comparison and that outcome. Evidence from randomized controlled trials would be graded initially as 'high' quality, and observational studies would start with 'low' quality ratings due to inherent selection bias, and then be upgraded or downgraded depending on the quality of the study. An overall quality rating of the evidence was then obtained for each outcome.

​A GRADE evidence summary table, which displays the quality assessments, study features and summary of findings and a template for linking the evidence to the recommendations, was used to formulate evidence. Statements/summaries, recommendations and their grading were produced 'live' during meetings following discussion of the synthesized evidence. The authors suggest that all GDGs adopt a systematic approach to investigation, management and treatment of contact dermatitis.

Source: Contact Dermatitis; Sep 2016; vol. 75 ; p. 53

Publication Type(s): Journal: Conference Abstract

Author(s): Johnston G.; Slack J.; Exton L.; Mohd Mustapa M.F.; Coulson I.; English J.; Bourke J.

Abstract:The Grading of Recommendations Assessment, Development and Evaluation (GRADE) process is now the gold-standard methodology for developing systematic reviews and clinical guidelines. The British Association of Dermatologists contact dermatitis Guidelines Development Group (GDG) is the first to adopt the GRADE methodology for the assessment of the investigation and treatment of contact dermatitis. The process commenced by establishing clinical questions, in three categories and relevant to the scope of the guideline, which asked the following questions in patients with contact dermatitis. (i) Diagnosis. Which allergens and how much should be used in tests? When should tests be carried out? Does increasing the number of allergens tested improve diagnosis? (ii) Prevention. Does education improve or prevent hand dermatitis? Do barrier creams improve hand dermatitis? (iii) Treatment. Does topical treatment work? Does systemic treatment work? Do soap substitutes improve contact dermatitis? Does education as a treatment work? Does phototherapy work?

​The GDG also established a set of outcome measures of importance to patients (prevention and treatment), graded from 1 (least important) to 9 (most important) according to the GRADE methodology, data on which were extracted from included studies. These measures are (i) return to/remain in work (9), (ii) improvement of quality of life (8), (iii) improvement or clearance of dermatitis (8), (iv) treatment tolerability (5), (v) prevention of dermatitis (5) and (vi) side-effects of interventions (4). The following recommendations were agreed by the GDG and patient representatives. (i) Diagnosis. Offer patients with contact dermatitis a patch-test technique based on the availability of resources. In identifying allergens in patients with contact dermatitis, consider testing for additional series dependent on allergen exposure. Consider additional readings at day 6 or 7 if the results are unexpectedly negative at day 4. (ii) Prevention. Consider skin-care and skin-protection creams in preventing occupational dermatitis. (iii) Treatment. Offer topical tacrolimus to patients with contact dermatitis where topical steroids are unsuitable. Offer alitretinoin to patients with moderate-to-severe chronic hand eczema. Consider psoralen-ultraviolet A therapy for treating patients with chronic hand eczema. Consider patient education in occupational contact dermatitis. There was insufficient evidence to determine the efficacy of systemic immunosuppressive treatment specifically for contact dermatitis. 'Offer' was used where evidence was of good quality and 'consider' was used where evidence was of lower quality. As a result of the GRADE process the GDG also recommended that reporting of results of future patch-test studies should be standardized and that high-quality studies are needed to address the efficacy of interventions for contact dermatitis.

​Citation: The Journal of investigative dermatology, Aug 2016, vol. 136, no. 8, p. 1584-1591, 1523-1747 (August 2016)
 
Author(s): Yiu, Zenas Z N, Exton, Lesley S, Jabbar-Lopez, Zarif, Mohd Mustapa, M Firouz, Samarasekera, Eleanor J, Burden, A David, Murphy, Ruth, Owen, Caroline M, Parslew, Richard, Venning, Vanessa, Ashcroft, Darren M, Griffiths, Christopher E M, Smith, Catherine H, Warren, Richard B
 
Abstract: A comprehensive evaluation of the risk of serious infections in biologic therapies for psoriasis is lacking. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective cohort studies reporting serious infections in people taking any licensed biologic therapy for psoriasis compared with those taking placebo, nonbiologic therapy, or other biologic therapies. The quality of the studies was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. No significant heterogeneity was detected in data from 32 RCTs (n = 13,359 participants) and one cohort study (n = 4,993 participants). In adults, low- to very-low-quality RCT data showed no significant difference between any biologic therapy and placebo at weeks 12-16 (overall pooled Peto odds ratio = 0.71, 95% confidence interval = 0.36-1.41) and weeks 20-30 (odds ratio = 2.27, 95% confidence interval = 0.45-11.49). No significant differences were found in any of the other comparisons in underpowered RCT data. Prospective cohort study data of low quality suggests that only adalimumab (adjusted hazard ratio [adjHR] = 2.52, 95% confidence interval = 1.47-4.32) was associated with a significantly higher risk of serious infection compared with retinoid and/or phototherapy in adults. No association between biologic therapies and serious infections in patients with psoriasis who were eligible for RCTs was detected. Further observational studies are needed to inform the uncertainty around this risk in the real world. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
 
Source: Medline
 

Citation: The British journal of general practice : the journal of the Royal College of General Practitioners, Mar 2016, vol. 66, no. 644, p. e222., 1478-5242 (March 2016)
 
Author(s): Spencer, Stephen, Buhary, Thajunnisha, Coulson, Ian, Gayed, Sedki
 
Source: Medline
 
Full Text:
Available in British Journal of General Practice

​Citation: Clinical and experimental dermatology, Jan 2016, vol. 41, no. 1, p. 60-63 (January 2016)
 
Author(s): Rajkomar, V, Hannah, M, Coulson, I H, Owen, C M
 
Abstract: Orf is caused by a parapoxvirus. In adults, it is commonly associated with specific occupations, whereas cases in children tend to be associated with household or recreational exposure. Spontaneous recovery usually occurs within 6 weeks. Infection in humans is believed to be through exposure to an infected animal or fomite. We present a case of a 13-month-old boy who was exposed to orf through his mother, a farmer, who had contracted the disease through administering medication to an infected animal. We believe that this may represent only the fifth case of human to human transmission of orf reported in the literature. ©2015 Crown Copyright. Clinical and Experimental Dermatology © British Association of Dermatology.
 
Source: Medline

Citation: International Journal of Dermatology, July 2015, vol./is. 54/7(827-829), 0011-9059;1365-4632 (01 Jul 2015)

Author(s): Aslam A., Savage D.B., Coulson I.H.

Country of Publication: United Kingdom

Publisher: Blackwell Publishing Ltd

CAS Registry Number: 283182-39-8 (adiponectin), 9004-10-8 (insulin)

Publication Type: Journal: Article

Source: EMBASE

Citation: British Journal of Dermatology, July 2015, vol./is. 173/(11-12), 0007-0963 (July 2015)

Author(s): Warren R., Smith C., Yiu Z., Ashcroft D., Barker J., Burden D., Lunt M., McElhone K., Ormerod A., Owen C., Reynolds N., Griffiths C.E.M.

Abstract: Persistence with therapy is a surrogate marker of drug effectiveness, safety and tolerability. We assessed the persistence of four biologics used to treat psoriasis in a large prospective pharmacovigilance cohort (British Association of Dermatologists' Biologic Interventions Register, BADBIR) in the U.K. and Ireland. Persistence rates for the first course of biologics for 3523 biologicnaive patients with chronic plaque psoriasis were compared, using survival analysis techniques, from a data extract up to August 2014. An a priori list of baseline covariates was deter mined to address potential predictors of discontinuation. These were analysed using multivariate Cox proportional hazard models for discontinuations: (i) overall, (ii) due to ineffectiveness and (iii) due to adverse events. Data for patients on adalimumab (n = 1879), etanercept (n = 1098), infliximab (n = 96) and ustekinumab (n = 450) were available. The median (interquartile range) duration of follow-up for patients receiving adalimumab was 1.3 (1.6) years, etanercept 1.5 (2.0) years, infliximab 1.2 (1.6) years and ustekinumab 1.2 (0.9) years. The overall persistence rate in the first year for adalimumab was 79%, etanercept 70%, infliximab 65% and ustekinumab 89%. Ustekinumab had the lowest first-year discontinuation rate due to ineffectiveness (4%) and adverse events (4%), while etanercept had the highest first-year discontinuation rate due to ineffectiveness (20%) and infliximab had the highest first-year discontinuation rate due to adverse events (16%). Multivariate analysis for discontinuations overall showed that female sex [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, while having psoriatic arthritis (HR 0.82, 95% CI 0.71-0.96) was a predictor for persistence. Overall, 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, while patients on ustekinumab were more likely to persist with therapy (HR 0.48, 95% CI 0.37-0.62). Patients on ustekinumab were also more likely to continue therapy compared with those on adalimumab in the models for discontinuation due to ineffectiveness (HR 0.37, 95% CI 0.25-0.57) and for adverse events (HR 0.60, 95% CI 0.39-0.92). After accounting for relevant covariates, ustekinumab had the highest overall persistence with therapy and adalimumab had the highest persistence with therapy among the tumour necrosis factor inhibitors. These data, derived from the largest published independent dataset, involving 151 dermatology centres in the U.K. and Ireland, may contribute to the decision-making process when choosing treatment for biologic-naive patients with psoriasis. BADBIR receives funding from Pfizer, Janssen and AbbVie. Decisions concerning analysis and interpretation are made autonomously of any industrial contribution.

Conference Information: 95th Annual Meeting of the British Association of Dermatologists Manchester United Kingdom. Conference Start: 20150707 Conference End: 20150709

Publisher: Blackwell Publishing Ltd

Publication Type: Journal: Conference Abstract

Source: EMBASE

Citation: Journal of the American Academy of Dermatology, May 2015, vol./is. 72/5 SUPPL. 1(AB87), 0190-9622 (May 2015)

Author(s): Shah M., Maleki N., Edward S.

Abstract: Background: Zoon's or plasma cell balanitis is an idiopathic inflammatory dermatosis affecting the glans penis and foreskin. The nonspecific histologic finding of plasma cells in biopsy specimens from penile lesions may lead pathologists and clinicians into a false sense of security. This may result in a failure to look for subtle histologic signs of another underlying condition and the failure to consider other important clinical diagnoses. Methods: A retrospective study of 23 cases labelled as Zoon's balanitis or plasma cell balanitis taken from the histopathology database. Slides were reviewed by two pathologists and were assessed for the classical features of the condition, plus other histologic features that have been described in studies of Zoon's balanitis. Results: The average age of the patients was 56.3 years. The histologic features between cases were highly variable. Four cases were diagnosed as Zoon's despite the complete absence of epidermis. In the epidermis, the following histologic features were noted in specimens: lozenge keratinocytes (78%), acanthosis (48%), spongiosis (56%), lichenoid infiltrate of lymphocytes (43%), basal cell hydropic degeneration (43%), superficial erosions (30%), neutrophilic infiltrate (26%), atrophy (26%) and parakeratosis (9%). There was no dysplasia. In the dermis, histologic features were: vascular proliferation (87%), dense plasma cell infiltrate (83%), vertical orientation of dermal vessels (69%), hemosiderin deposition (17%), erythrocyte extravasation (13%) and fibrosis (4%). There was no homogenization of collagen or atypical cells. Conclusions: There were a variety of histopathologic features in the 23 patients surveyed, suggesting Zoon's does not delineate a single condition. In some cases, the features were masking another underlying inflammatory disorder. Zoon's balanitis is a term used loosely by pathologists to describe a number of similar pathologic features, usually (but not always) with a dense plasmacytic infiltrate, but should be regarded as a nonspecific reactive pattern and not as a distinct clinical and histopathologic diagnosis. Clinicians and pathologists should look hard to exclude other underlying dermatoses and dysplasia. The term Zoon's balanitis may now be outdated as this entity seems to be a nonspecific inflammatory disorder.

Publication Type: Journal: Conference Abstract

Source: EMBASE