Methotrexate and liver fibrosis in people with psoriasis: a systematic review of observational studies

Methotrexate (MTX) is an effective treatment for psoriasis but concerns regarding the development of liver fibrosis prevent optimal use. The primary objective of this systematic review was to assess whether MTX use increases the risk of developing fibrosis in people with psoriasis. Searches were performed on Medline, Embase, the Cochrane Database and Clinical Trials Register from inception until September 2013 for studies including at least two liver biopsies in people with psoriasis. Double extraction using predefined data fields was performed. Randomized controlled trials and observational studies were considered. Statistical analysis was performed using Review Manager 5. Quality of observational studies was assessed using a study quality bias checklist. Eight observational studies met the inclusion criteria (n = 429 patients). The pooled risk difference (RD) of developing significant liver fibrosis was 0·09 [95% confidence interval (CI) ?0·03 to 0·20]. The RD for developing ‘any fibrosis’ was 0·22 (95% CI 0·04–0·41). The RD for cirrhosis was 0·04 (95% CI 0·02–0·07). There was no clear association between cumulative dose of MTX and fibrosis. Obesity, diabetes and alcohol use were under‐reported. The quality of the included studies was weak and the degree of selection bias means the results are not generalizable to all patients with psoriasis taking MTX. High‐quality, population‐based studies that consider potential confounders common in psoriasis population are justified for better prediction of the subset of patients at risk of liver fibrosis. In this highly selected review population, MTX use appears to contribute to the development of ‘any’ fibrosis without clear evidence of risk stratifiers.     

A systematic review of pharmacogenetic studies on the response to biologics in patients with psoriasis

Psoriasis is a common skin disease in which the body produces too much of a protein called ‘tumour necrosis factor alpha’ (TNF‐alpha) which in turn causes inflammation. Biologics are relatively new, powerful drugs used for treating moderate to severe psoriasis due to their ability to reduce the activity of TNF‐alpha. There are several different types of biologic and finding the best one for the individual patient is a process of trial and error, which may lead to a long period with treatment not working as well as hoped and unnecessary costs. Different people's genes (genetic variants) might explain why not everyone responds the same way to a biologic, and might also help predict whether a specific biologic is likely to be successful for a patient. This area of medicine is known as pharmacogenetics. This study, from the Netherlands, is a review of other published studies, looking at the association between genetic variants and effectiveness of treatment with the different biologics. 26 studies were included in the review, looking at the biologics dalimumab, etanercept, infliximab and ustekinumab. No studies on two other biologics, secukinumab or ixekizumab, were identified. Many of the studies focused on variants in genes related to the working mechanisms of TNF‐alpha. Associations between some variants of TNF‐alpha and biologics were found in some studies, but often these results were conflicting in other studies. The authors conclude that pharmacogenetic studies in psoriasis have differing results. The genetic variant HLA‐Cw6 may be promising as a predictor for efficacy of ustekinumab, but larger studies are needed to confirm this. Large scale searches for genetic biomarkers are needed to uncover the complete genetic background of biologics treatment outcome.     

Adherence to medication in patients with psoriasis: a systematic literature review

Psoriasis is associated with considerable physical and psychological morbidity. Optimal use of psoriasis treatments can limit the physical manifestations of psoriasis and help improve quality of life, but nonadherence is common. Smoking, obesity and excessive alcohol consumption are prevalent in this population. A systematic review of adherence to medication and recommendations for lifestyle change in psoriasis was undertaken, with a critical appraisal of the quality of the selected studies. Electronic searches from inception to March 2012 (PubMed, Web of Science and Embase) were conducted. Twenty‐nine studies were included; however, none examined adherence to advice about lifestyle change. Studies using a dichotomous classification of adherence tended to report suboptimal adherence, with 21·6–66·6% of patients classed as adherent. No consistent pattern of results emerged for sociodemographical, disease and lifestyle factors as determinants of adherence. However, some treatment factors were associated with adherence. While mixed findings were reported for quality of life as a determinant of adherence, psychological factors (psychological distress and patient satisfaction with care and therapy) were associated with adherence. Only tentative conclusions can be made for determinants of adherence because the methodological quality of many of the included studies limits conclusions. There is a need for improved quality of research and reporting in this area, and this review provides a platform from which future research within this area should progress, along with suggested research recommendations.     

A systematic review showing the lack of diagnostic criteria and tools developed for lower-limb cellulitis

Cellulitis is a common skin infection seen in the UK, with most cases affecting the lower limbs. However, diagnosing lower limb cellulitis can at first be challenging as there is no diagnostic checklist available in the UK. This study aimed to identify what tools or checklists have been developed to help diagnose lower limb cellulitis. The authors, based in the UK, carried out a review of existing research and found eight studies that looked at patient features, blood tests, scans and an algorithm to help diagnosis. There was variation in the types of tools used, and the quality of the studies. The present study found insufficient evidence to support any current tools or checklists that have been developed to help diagnose lower limb cellulitis. Future work should focus on speaking to patients with cellulitis and health care professionals to better understand what should be included in a diagnostic tool/checklist.     

The prevalence of anxiety in patients with psoriasis: a systematic review of observational studies and clinical trials

Psoriasis and anxiety are chronic conditions with significant morbidity and there is evidence that they may exacerbate one another. There is little data on the prevalence of anxiety in psoriasis and the effect of psoriasis treatment on comorbid anxiety. The objective of this study was to perform a systematic review of the literature to describe the prevalence and severity of clinical anxiety disorders or anxiety symptoms among adult patients with psoriasis and characterize the effect of anti‐psoriatic interventions on clinical anxiety disorders or anxiety symptoms. We searched PubMed, EMBASE, and the Cochrane Database using search terms ‘psoriasis’ and ‘anxiety’. Results were tabulated and verified by two independent reviewers. Meta‐analyses were not performed due to heterogeneity of data. Of 213 publications identified, 938 194 patients from 15 papers were included. The mean age ranged from 31.9–59.4 years old, with a mean PASI score of 7.65–22.8 (reported by nine studies) and a body surface area involvement of 25.9–39.8% (reported by two studies). The prevalence of anxiety in patients with psoriasis was 7–48%, which was significantly higher than healthy controls in two of three studies (HR 1.29–1.31, P = 0.001 and OR 2.91 [95% CI, 2.01–4.21], P < 0.001). Four of five studies (n = 2029) demonstrated an improvement in anxiety symptoms with psoriasis treatment. This review demonstrates a high prevalence of anxiety of adult patients with psoriasis suggesting that patients would benefit from systematic screening. Although the data suggest that anxiety may be improved through various psoriasis treatments, larger prospective randomized trials are needed to confirm this effect.     

环孢素维持治疗银屑病随机对照研究的文献分析

检索MEDLINE、Embase、Cochrane图书馆、SinoMed、CNKI和万方数据库中1974年1月1日至2018年7月1日环孢素维持治疗银屑病的随机对照临床研究,评价不同环孢素给药方案治疗银屑病的疗效和安全性。共纳入9篇随机临床对照试验文献,均报道环孢素治疗银屑病有效,其中2篇文献研究发现连续治疗方案在长达24周的维持治疗期内是安全有效的,2篇发现间断治疗比连续治疗更安全有效。     

Quality of life in patients with psoriasis: a systematic literature review

Data on physical, psychological, and social functioning of patients with psoriasis have been presented in many studies. The introduction of quality-of-life questionnaires has made it possible to systematically compare these data across studies. The aim of this study was to present an overview of quality-of-life data and to describe the relationship between demographic and clinical variables and quality of life in patients with psoriasis. Computerized bibliographic databases were screened for publications from January 1966 to April 2000. Predefined selection criteria were used to identify quality-of-life studies in psoriasis. Two investigators independently assessed and, subsequently, agreed on inclusion. Data were extracted on the objectives, methods, sample characteristics, and results of the studies. A total of 118 publications were found. Seventeen studies met the inclusion criteria. Patients with psoriasis reported physical discomfort, impaired emotional functioning, a negative body and self-image, and limitations in daily activities, social contacts and (skin-exposing) activities, and work. More severe psoriasis was associated with lower levels of quality of life. There was a tendency that higher age was associated with slightly lower levels of physical functioning and slightly higher levels of psychological functioning and overall quality of life. Sex and quality of life were found to be unrelated.     

Use of topical therapies for pediatric psoriasis: A systematic review

Psoriasis is one of the most common chronic skin diseases, affecting 1%‐3% of the general population. It can have a significant negative impact on a patient's quality of life, and in approximately 30% of patients first symptoms can be traced back to childhood. We have performed a comprehensive literature search using the MEDLINE database in order to ascertain the efficacy and adverse reactions of topical treatments in pediatric psoriasis. A total of 13 relevant articles were identified on the following topical agents: corticosteroids, calcineurin inhibitors, vitamin D analogs, and dithranol. Corticosteroids achieved clearance in 72.7% of patients. Calcitriol lead to a 57.2%‐100% mean improvement in severity, and calcipotriol to 52%‐64%. Combination of calcipotriol and corticosteroids achieved an improvement in mean severity ranging between 32.1% and 80%. Treatment with tacrolimus lead to an >50% improvement. Finally, short contact dithranol lead to a variable response in clearance between different studies, ranging between 3.7% and 81%. No serious adverse reactions were documented, the most common local reaction being irritation. Pediatric psoriasis is a common and challenging condition with no easy and definitive solution. Topical agents are safe, easy to use, readily available and cheap. However, they need to be applied repeatedly, may cause skin irritation, and can be messy. Based on the results presented above, we recommend utilizing all the available topical options before escalating to systemic treatments.     

Topical herbal medicine combined with pharmacotherapy for psoriasis: a systematic review and meta-analysis

This systematic review examines the current state of the evidence for the efficacy and safety of herbal medicines (HMs) used topically in conjunction with anti-psoriatic pharmacotherapy (APP) in the treatment of psoriasis. Searches were conducted in September 2012 of PubMed, EMBASE, Cochrane Library, two Chinese databases (China National Knowledge Infrastructure and Chinese Scientific Journals Full Text Database) and of article reference lists. We included randomized controlled trials published in English, Chinese or Japanese that investigated topical HM combined with APP used systemically and/or topically compared to pharmacotherapy alone. Studies employing phototherapy were excluded. Two authors conducted searches, extracted data on study characteristics and outcomes, and assessed Risk of Bias. Disagreements were resolved by discussion with a third author. Eight studies met the inclusion criteria. All used multi-herb formulae, four in herbal baths, three in herbal ointments or creams, and one as herbal steam. The pooled data indicated a benefit for the add-on effect of herbal therapy to APP. Adding these topical HMs to conventional pharmacotherapy appeared to produce short-term additional clinical benefits. No serious adverse events were reported. Experimental studies suggest that some of the herbs possess anti-inflammatory, anti-pruritic, and/or anti-proliferative activities. However, these results need to be interpreted with caution due to methodological weaknesses and the lack of replicated studies. Studies that address the identified methodological deficiencies are required to further investigate the efficacy and safety of these HMs as adjunct therapies for psoriasis.     

Topical preparations for the treatment of psoriasis: a systematic review

Summary Background There is clinical uncertainty about the appropriate use of first‐line topical treatments for psoriasis. Objectives To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. Methods All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo‐controlled trials of topical treatments for psoriasis; and (2) randomized head‐to‐head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)‐controlled trials and 4898 patients randomized in 28 head‐to‐head studies. Results There was a significant benefit in favour of active treatments against vehicle, SWMD: ?1·06 (95% confidence interval [CI]: ?1·26 to ?0·86), approximately a 2‐point improvement on a 12‐point TSS after 6–8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: ?1·51 (95% CI: ?1·76 to ?1·25), approximately a 3‐point improvement on a 12‐point TSS. Head‐to‐head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D₃ derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0·42 (95% CI: 0·12–0·72) approximately a 0·8‐point improvement on a 12‐point TSS. No important differences in withdrawal or reporting of adverse events were identified. Conclusions Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long‐term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.     

Topical preparations for the treatment of psoriasis: a systematic review

BACKGROUND: There is clinical uncertainty about the appropriate use of first-line topical treatments for psoriasis. OBJECTIVES: To assess the relative effectiveness and tolerability of topical treatments for psoriasis suitable for use both in primary and secondary care. METHODS: All major medical databases of published literature were searched electronically; references of trial reports and recent reviews were searched; authors and companies were contacted for missing data from published reports. The study selection comprised: (1) randomized placebo-controlled trials of topical treatments for psoriasis; and (2) randomized head-to-head studies of the new vitamin D3 derivative treatments for psoriasis that reported clinical outcome using a Total Severity Score (TSS), Psoriasis Area Severity Index or Investigator Assessment of Global Improvement. Eligibility and validity were assessed and data extracted independently by two authors. Clinical outcomes were pooled using a random effect standardized weighted mean difference (SWMD) metric, including 3380 patients randomized in 41 placebo (vehicle)-controlled trials and 4898 patients randomized in 28 head-to-head studies. RESULTS: There was a significant benefit in favour of active treatments against vehicle, SWMD: -1.06 (95% confidence interval [CI]: -1.26 to -0.86), approximately a 2-point improvement on a 12-point TSS after 6-8 weeks of treatment. The only significantly different benefit was for very potent corticosteroids: SWMD: -1.51 (95% CI: -1.76 to -1.25), approximately a 3-point improvement on a 12-point TSS. Head-to-head studies support these findings, except that calcipotriol was estimated to be more effective than dithranol, coal tar and other vitamin D3 derivatives. Polytherapy, using a potent steroid and calcipotriol, was more effective than calcipotriol alone: SWMD 0.42 (95% CI: 0.12-0.72 ) approximately a 0.8-point improvement on a 12-point TSS. No important differences in withdrawal or reporting of adverse events were identified. CONCLUSIONS: Trials of short duration neither adequately inform the management of chronic disease nor describe the sequelae of treatment. The evidence base for long-term care, reflecting the disease pathway, should be improved. Combination therapy with topical vitamin D analogues and steroids, and maintenance therapy following treatment response merit further investigation.     

Ustekinumab治疗中重度斑块状银屑病的系统评价

银屑病是一种慢性复发性炎症性皮肤病,在我国患病率约0.123％［１］,因其慢性、顽固难愈、复发率高,成为皮肤科领域重点研究防治的疾病之一。Ustekinumab在2009年获准治疗中重度斑块状银屑病,它可与人体白介素12/白介素23的p40亚单位结合,抑制其生物活性,达到治疗银屑病的作用［2］,但其疗效结论尚不统一,且缺乏长期有效性及安全性评价［3］。我们检索文献,对Ustekinumab治疗中重度斑块状银屑病的疗效和安全性进行系统评价……     

A systematic review of adverse effects associated with topical treatments for psoriasis

Mild to moderate psoriasis is a disease that can often be treated with topical medications. The diversity of topical therapies and their disparate side effects complicates treatment planning. Our purpose is to compare the rates of adverse events associated with different topical psoriasis treatments. A review of medical literature from 1996 to March, 2002 was conducted using guidelines set by QUORUM statement criteria. In monotherapy studies, corticosteriods caused fewer adverse reactions compared to vitamin D analogues and tazarotene. In combination studies adverse event rates were higher than in monotherapy studies, except for the combination of topical steroid and calcipotriene which decreased irritation. Irritant contact dermatitis was the main side effect with vitamin D analogues, tazarotene, dithranol or coal tar, while side effects of topical corticosteriods included headache, viral infection and skin atrophy. Topical agents for psoriasis are usually well-tolerated without severe side effects. Formulating a patient's medication regimen should take into account the needs for short-term management and long-term control of psoriasis. Since clearance is not a realistic expectation, reasonable goals should be set as excessive use of topical treatments may increase the risk of both cutaneous and systemic side effects.     

Phenotypic switch to eczema in patients receiving biologics for plaque psoriasis: a systematic review

The use of biologic therapies for the treatment of chronic plaque psoriasis has been linked to the development of atopic eczema, amongst other cutaneous adverse events. This can cause diagnostic confusion and create difficulty in the management of patients with plaque psoriasis. The main objective of this systematic review was to review all cases of eczema, including atopic eczema, reported in patients treated with biologics for chronic plaque psoriasis. PubMed, Medline and Embase databases were used to identify studies reporting eczema in patients treated with biologic therapy for chronic plaque psoriasis. A total of 92 patients were identified from 24 studies, with patients treated with either: adalimumab; etanercept; infliximab; ixekizumab; secukinumab; or ustekinumab. Factors common to some reported cases include: a prior history of atopy; eosinophilia; raised serum immunoglobulin E. Twenty-three had documented treatment outcomes; 14 had biologic therapy discontinued or switched. Management strategies included topical or oral corticosteroids, and treatment with alternative systemic agents such as ciclosporin or apremilast. This adverse event occurred in 1.0–12.1% of patients within trial data and observational studies. This review demonstrates that there are consistent reports of a switch to an atopic eczema phenotype from psoriasis in patients taking biologics inhibiting tumour necrosis factor alpha and the interleukin (IL)-17/IL-23 axis. The majority stopped the implicated biologic, but conservative management was successful in some cases. Those with an atopic diathesis may be more at risk. Elucidation of mechanisms and risk factors would contribute to optimal therapy selection for individual patients.