Caroline M. Owen

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.

British Association of Dermatologists guidelines for biologic therapy for psoriasis 2017

The overall aim of the guideline is to provide evidence-based recommendations on the use of biologic therapies (adalimumab, etanercept, infliximab, ixekizumab, secukinumab and ustekinumab) in adults, children and young people for the treatment of psoriasis; consideration is given to the specific needs of people with psoriasis and psoriatic arthritis. Biologic therapies have now been in use for over 10 years, and with accrued patient-years exposure and clinical experience, many areas that were covered in previous versions of the guideline are now part of the Summary of Product Characteristics (SPC) and/or routine care so that specific recommendations are redundant (see Toolkit A: Summary of licensed indications and posology for biologic therapy, in Supporting information 2). Therefore, in this update we focus on areas where there has been a major change in the evidence base or clinical practice, where practice is very varied and/or where clear consensus or guidelines are lacking (see section 3.1 in Supporting information 1).

Quantitative Evaluation of Biologic Therapy Options for Psoriasis: A Systematic Review and Network Meta-Analysis

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).

Real-life experience of managing vulval erosive lichen planus: a case-based review and U.K. multicentre case note audit

Summary Background  There is a lack of published evidence for treatment and outcome measures for vulval erosive lichen planus (ELPV).

Risk of Serious Infections in Patients with Psoriasis on Biologic Therapies: A Systematic Review and Meta-Analysis

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.

A case of human to human transmission of orf between mother and child

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.

Morphoea with prominent plasma cell endoneuritis

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.

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trait. Thiopurine methyl transferase activity was normal. Azathioprine 50 mg daily was commenced as a steroidsparing agent. The prednisolone was slowly tapered with only occasional new small blister formation. The patient was taking prednisolone and azathioprine when she made a trip to Saudi Arabia to undertake the Umrah. The following month at a routine follow-up visit she was noted to have an eosinophilia of 1 7 9 10 cells L 1 (normal range 0–0 4 9 10 cells L ). She denied any fever, abdominal symptoms or urticaria-like eruptions. Four weeks later her asymptomatic eosinophilia had deteriorated to 1 9 9 10 cells L . Her S. stercoralis serology was repeated and was positive. Strongyloidiasis was highly likely given her eosinophilia and previous negative serology. Stool microscopy was not performed. She was treated with ivermectin 200 lg kg 1 on two consecutive days and this was repeated 14 days later. Her eosinophilia resolved after the first two doses. The S. stercoralis serology was negative when repeated 6 months after ivermectin treatment, and her eosinophil count has continued to be normal. The differential diagnosis of eosinophilia is wide, and eosinophilia may be associated with PV. However, in migrants and returning travellers other causes may need to be considered. In a study of asymptomatic travellers returning to the U.K., 8% had an eosinophilia. The clinical guidelines of the British Infection Society state that all returning travellers and migrants with eosinophilia should have concentrated stool microscopy and Strongyloides serology performed. Strongyloides stercoralis is a nematode with a widespread tropical, subtropical and temperate distribution. It has a life cycle that includes a soil phase; however, autoinfection (without the soil phase) can occur and may cause persistent infection many years after the individual has left an endemic area. It may also cause hyperinfection in immunosuppressed patients. Strongyloides hyperinfection is often fatal due to secondary Gram-negative septicaemia. The hyperinfection syndrome is particularly common in individuals taking corticosteroids, but human T-lymphotropic virus 1 infection is also a risk factor, and there are occasional reports of hyperinfection complicating HIV. Other immunosuppressants, including biological agents, may also predispose to hyperinfection. Interestingly, rituximab, which is increasingly used to manage PV, was implicated in the death of a Brazilian patient with Strongyloides hyperinfection. Asymptomatic patients who may be at risk of strongyloidiasis should be screened using serological testing prior to immunosuppression. In those in whom it is not possible to wait for the results, and who are felt to be at significant risk, it is worth considering empirical treatment with ivermectin. This case highlights the importance of recognizing this pathogen, which is uncommon in patients managed in the U.K., but which may have severe and potentially life-threatening implications for those who are immunosuppressed. It also highlights the importance of taking a detailed travel history and understanding the altered risk profile of immunosuppressed patients who travel. S .L . WALK ER T .A .N. MANN London School of Hygiene and Tropical Medicine, Keppel St, London WC1E 7HT, U.K. Department of Dermatology, North Middlesex University Hospital NHS Trust, London, U.K. E-mail: drstevewalker@hotmail.com

Intentional and unintentional medication non-adherence in psoriasis: the role of patients’ medication beliefs and habit strength

Medication non-adherence is a missed opportunity for therapeutic benefit. We assessed “real-world” levels of self-reported non-adherence to conventional and biologic systemic therapies used for psoriasis and evaluated psychological and biomedical factors associated with non-adherence using multivariable analyses. Latent profile analysis was used to investigate whether patients can be categorized into groups with similar medication beliefs. Latent profile analysis categorizes individuals with similar profiles on a set of continuous variables into discrete groups represented by a categorical latent variable. Eight hundred and eleven patients enrolled in the British Association of Dermatologists Biologic Interventions Register were included. Six hundred and seventeen patients were using a self-administered systemic therapy; 22.4% were classified as “non-adherent” (12% intentionally and 10.9% unintentionally). Patients using an oral conventional systemic agent were more likely to be non-adherent compared to those using etanercept or adalimumab (29.2% vs. 16.4%; P ≤ 0.001). Latent profile analysis supported a three-group model; all groups held strong beliefs about their need for systemic therapy but differed in levels of medication concerns. Group 1 (26.4% of the sample) reported the strongest concerns, followed by Group 2 (61%), with Group 3 (12.6%) reporting the weakest concerns. Group 1 membership was associated with intentional non-adherence (odds ratio = 2.27, 95% confidence interval = 1.16−4.47) and weaker medication-taking routine or habit strength was associated with unintentional non-adherence (odds ratio = 0.92, 95% confidence interval = 0.89−0.96). Medication beliefs and habit strength are modifiable targets for strategies to improve adherence in psoriasis.

Mid-face toddler excoriation syndrome (MiTES): a new paediatric diagnosis

Chronic ulcerating lesions on the face are rarely seen in toddlers. Blistering disease, vasculitis, infections and self‐mutilation due to neurometabolic disease can usually be excluded on clinical and histological grounds. In the absence of identifiable disease, such lesions are sometimes attributed to child abuse or fabricated illness. We describe three toddlers with chronic mid‐face erosions, two from India and one from the UK. One had moderate developmental delay and one had had seizures. The lesions appeared to be self‐inflicted, no underlying disease was identified and there was no suspicion of child abuse. Recognition of the same disease pattern in different continents implies a distinct pathological entity. The pattern closely resembles that seen in some patients with mutations in the pain‐insensitivity genes PRDM12 and SCN11A. We suggest the term ‘mid‐face toddler excoriation syndrome’ (MiTES) to acknowledge the existence of this condition, encourage further reports and help clarify the pathogenesis.