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Systematic review

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Journal The Cochrane database of systematic reviews
Year 2022
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BACKGROUND: Eczema is a common skin condition. Although topical corticosteroids have been a first-line treatment for eczema for decades, there are uncertainties over their optimal use. OBJECTIVES: To establish the effectiveness and safety of different ways of using topical corticosteroids for treating eczema. SEARCH METHODS: We searched databases to January 2021 (Cochrane Skin Specialised Register; CENTRAL; MEDLINE; Embase; GREAT) and five clinical trials registers. We checked bibliographies from included trials to identify further trials. SELECTION CRITERIA: Randomised controlled trials in adults and children with eczema that compared at least two strategies of topical corticosteroid use. We excluded placebo comparisons, other than for trials that evaluated proactive versus reactive treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, with GRADE certainty of evidence for key findings. Primary outcomes were changes in clinician-reported signs and relevant local adverse events. Secondary outcomes were patient-reported symptoms and relevant systemic adverse events. For local adverse events, we prioritised abnormal skin thinning as a key area of concern for healthcare professionals and patients. MAIN RESULTS: We included 104 trials (8443 participants). Most trials were conducted in high-income countries (81/104), most likely in outpatient or other hospital settings. We judged only one trial to be low risk of bias across all domains. Fifty-five trials had high risk of bias in at least one domain, mostly due to lack of blinding or missing outcome data. Stronger-potency versus weaker-potency topical corticosteroids Sixty-three trials compared different potencies of topical corticosteroids: 12 moderate versus mild, 22 potent versus mild, 25 potent versus moderate, and 6 very potent versus potent. Trials were usually in children with moderate or severe eczema, where specified, lasting one to five weeks. The most reported outcome was Investigator Global Assessment (IGA) of clinician-reported signs of eczema. We pooled four trials that compared moderate- versus mild-potency topical corticosteroids (420 participants). Moderate-potency topical corticosteroids probably result in more participants achieving treatment success, defined as cleared or marked improvement on IGA (52% versus 34%; odds ratio (OR) 2.07, 95% confidence interval (CI) 1.41 to 3.04; moderate-certainty evidence). We pooled nine trials that compared potent versus mild-potency topical corticosteroids (392 participants). Potent topical corticosteroids probably result in a large increase in number achieving treatment success (70% versus 39%; OR 3.71, 95% CI 2.04 to 6.72; moderate-certainty evidence). We pooled 15 trials that compared potent versus moderate-potency topical corticosteroids (1053 participants). There was insufficient evidence of a benefit of potent topical corticosteroids compared to moderate topical corticosteroids (OR 1.33, 95% CI 0.93 to 1.89; moderate-certainty evidence). We pooled three trials that compared very potent versus potent topical corticosteroids (216 participants). The evidence is uncertain with a wide confidence interval (OR 0.53, 95% CI 0.13 to 2.09; low-certainty evidence). Twice daily or more versus once daily application We pooled 15 of 25 trials in this comparison (1821 participants, all reported IGA). The trials usually assessed adults and children with moderate or severe eczema, where specified, using potent topical corticosteroids, lasting two to six weeks. Applying potent topical corticosteroids only once a day probably does not decrease the number achieving treatment success compared to twice daily application (OR 0.97, 95% CI 0.68 to 1.38; 15 trials, 1821 participants; moderate-certainty evidence). Local adverse events Within the trials that tested 'treating eczema flare-up' strategies, we identified only 26 cases of abnormal skin thinning from 2266 participants (1% across 22 trials). Most cases were from the use of higher-potency topical corticosteroids (16 with very potent, 6 with potent, 2 with moderate and 2 with mild). We assessed this evidence as low certainty, except for very potent versus potent topical corticosteroids, which was very low-certainty evidence.  Longer versus shorter-term duration of application for induction of remission No trials were identified. Twice weekly application (weekend, or 'proactive therapy') to prevent relapse (flare-ups) versus no topical corticosteroids/reactive application Nine trials assessed this comparison, generally lasting 16 to 20 weeks. We pooled seven trials that compared weekend (proactive) topical corticosteroids therapy versus no topical corticosteroids (1179 participants, children and adults with a range of eczema severities, though mainly moderate or severe). Weekend (proactive) therapy probably results in a large decrease in likelihood of a relapse from 58% to 25% (risk ratio (RR) 0.43, 95% CI 0.32 to 0.57; 7 trials, 1149 participants; moderate-certainty evidence). Local adverse events We did not identify any cases of abnormal skin thinning in seven trials that assessed skin thinning (1050 participants) at the end of treatment. We assessed this evidence as low certainty. Other comparisons  Other comparisons included newer versus older preparations of topical corticosteroids (15 trials), cream versus ointment (7 trials), topical corticosteroids with wet wrap versus no wet wrap (6 trials), number of days per week applied (4 trials), different concentrations of the same topical corticosteroids (2 trials), time of day applied (2 trials), topical corticosteroids alternating with topical calcineurin inhibitors versus topical corticosteroids alone (1 trial), application to wet versus dry skin (1 trial) and application before versus after emollient (1 trial). No trials compared branded versus generic topical corticosteroids and time between application of emollient and topical corticosteroids. AUTHORS' CONCLUSIONS: Potent and moderate topical corticosteroids are probably more effective than mild topical corticosteroids, primarily in moderate or severe eczema; however, there is uncertain evidence to support any advantage of very potent over potent topical corticosteroids. Effectiveness is similar between once daily and twice daily (or more) frequent use of potent topical corticosteroids to treat eczema flare-ups, and topical corticosteroids weekend (proactive) therapy is probably better than no topical corticosteroids/reactive use to prevent eczema relapse (flare-ups). Adverse events were not well reported and came largely from low- or very low-certainty, short-term trials. In trials that reported abnormal skin thinning, frequency was low overall and increased with increasing potency. We found no trials on the optimum duration of treatment of a flare, branded versus generic topical corticosteroids, and time to leave between application of topical corticosteroids and emollient. There is a need for longer-term trials, in people with mild eczema.

Systematic review

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Authors Wang TS , Tsai TF
Journal American journal of clinical dermatology
Year 2017
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BACKGROUND: Scalp psoriasis is commonly the initial presentation of psoriasis, and almost 80 % of patients with psoriasis will eventually experience it. OBJECTIVE: Although several systematic reviews and guidelines exist, an up-to-date evidence-based review including more recent progress on the use of biologics and new oral small molecules was timely. METHODS: Of the 475 studies initially retrieved from PubMed and the 845 from Embase (up to May 2016), this review includes 27 clinical trials, four papers reporting pooled analyses of other clinical trials, ten open-label trials, one case series, and two case reports after excluding non-English literature. RESULTS: To our knowledge, few randomized controlled trials (RCTs) are conducted specifically in scalp psoriasis. Topical corticosteroids provide good effects and are usually recommended as first-line treatment. Calcipotriol-betamethasone dipropionate is well tolerated and more effective than either of its individual components. Localized phototherapy is better than generalized phototherapy on hair-bearing areas. Methotrexate, cyclosporine, fumaric acid esters, and acitretin are well-recognized agents in the treatment of psoriasis, but we found no published RCTs evaluating these agents specifically in scalp psoriasis. Biologics and new small-molecule agents show excellent effects on scalp psoriasis, but the high cost of these treatments mean they may be limited to use in extensive scalp psoriasis. CONCLUSIONS: More controlled studies are needed for an evidence-based approach to scalp psoriasis.

Systematic review

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Authors Malecic, Nina
Journal Psoriasis: Targets and Therapy
Year 2016
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Psoriasis affects 1%-3% of the population in the United Kingdom and can convey significant detriment to the physical and mental health of sufferers. Plaques of psoriasis typically affect the extensor skin surfaces and scalp. Less frequently inverse psoriasis can affect more sensitive skin such as the face, genitals, and intertriginous areas. Psoriasis is incurable, but there are a range of treatment modalities that can be used to manage the condition. Treatment options include topical preparations, phototherapy, systemic therapy, and biological agents. Tacrolimus is a macrolide calcineurin inhibitor licensed for immunosuppression in transplant patients and topical administration in atopic dermatitis. Tacrolimus administered orally and in topical form has been shown to produce successful outcomes in patients with psoriasis. Topical tacrolimus is particularly effective for inverse psoriasis, which is likely to be due to the reduced level of induration seen in these psoriatic lesions, which allows greater skin penetrance, compared with hyperkeratotic plaques of psoriasis on the body. It is also notable that the areas affected by inverse psoriasis are more susceptible to adverse effects of topical corticosteroid therapy, and thus a topical preparation without the risk of skin atrophy, telangiectasia, and striae could be a valuable addition to current topical treatment options. Oral tacrolimus has shown efficacy in the treatment of severe, refractory psoriasis. Compared to ciclosporin, systemic tacrolimus may be more suited to a patient population with increased cardiovascular risk. This review will draw together the current literature on topical and oral tacrolimus for the treatment of psoriasis. Efficacy and safety have been evaluated by case reports and randomized controlled trials and comparisons have been made between tacrolimus therapy and standard treatment. © 2016 Malecic and Young.

Systematic review

Unclassified

Journal Cochrane Database of Systematic Reviews
Year 2016
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BACKGROUND: People with chronic plaque psoriasis often have lesions on the scalp. Hair makes the scalp difficult to treat and the adjacent facial skin is particularly sensitive to topical treatments. OBJECTIVES: To assess the efficacy and safety of topical treatments for scalp psoriasis. SEARCH METHODS: We searched the following databases up to August 2015: the Cochrane Skin Group Specialised Register, CENTRAL (2015, Issue 7), MEDLINE (from 1946), EMBASE (from 1974) and LILACS (from 1982). We also searched five trials registers, screened abstracts of six psoriasis-specific conferences and checked the reference lists of included studies for further references to relevant randomised controlled trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) with a parallel-group, cross-over or within-patient design of topical treatments for people of all ages with scalp psoriasis. DATA COLLECTION AND ANALYSIS: Two authors independently carried out study selection, data extraction and 'Risk of bias' assessment. Disagreements were settled by reference to a third author.To assess the quality of evidence, we focused on the following outcomes: 'clearance' or 'response' as assessed by the investigator global assessment (IGA), improvement in quality of life, adverse events requiring withdrawal of treatment and 'response' as assessed by the patient global assessment (PGA).We expressed the results of the single studies as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes, and mean differences (MD) with 95% CI for continuous outcomes. If studies were sufficiently homogeneous, we meta-analysed the data by using the random-effects model. Where it was not possible to calculate a point estimate for a single study, we described the data qualitatively. We also presented the number needed to treat to benefit (NNTB).We categorised topical corticosteroids according to the German classification of corticosteroid potency as mild, moderate, high and very high. MAIN RESULTS: We included 59 RCTs with a total of 11,561 participants. Thirty studies were either conducted or sponsored by the manufacturer of the study medication. The risk of bias varied considerably among the included studies. For instance, most authors did not state the randomisation method and few addressed allocation concealment. Most findings were limited to short-term treatments, since most studies were conducted for less than six months. Only one trial investigated long-term therapy (12 months). Although we found a wide variety of different interventions, we limited the grading of the quality of evidence to three major comparisons: steroid versus vitamin D, two-compound combination of steroid and vitamin D versus steroid monotherapy and versus vitamin D.In terms of clearance, as assessed by the IGA, steroids were better than vitamin D (RR 1.82; 95% CI 1.52 to 2.18; four studies, 2180 participants, NNTB = 8; 95% CI 7 to 11; moderate quality evidence). Statistically, the two-compound combination was superior to steroid monotherapy, however the additional benefit was small (RR 1.22; 95% CI 1.08 to 1.36; four studies, 2474 participants, NNTB = 17; 95% CI 11 to 41; moderate quality evidence). The two-compound combination was more effective than vitamin D alone (RR 2.28; 95% CI 1.87 to 2.78; four studies, 2008 participants, NNTB = 6; 95% CI 5 to 7; high quality evidence).In terms of treatment response, as assessed by the IGA, corticosteroids were more effective than vitamin D (RR 2.09; 95% CI 1.80 to 2.41; three studies, 1827 participants; NNTB = 4; 95% CI 4 to 5; high quality evidence). The two-compound combination was better than steroid monotherapy, but the additional benefit was small (RR 1.15; 95% CI 1.06 to 1.25; three studies, 2444 participants, NNTB = 13; 95% CI 9 to 24; moderate quality evidence). It was also more effective than vitamin D alone (RR 2.31; 95% CI 1.75 to 3.04; four studies, 2222 participants, NNTB = 3; 95% CI 3 to 4; moderate quality evidence).Reporting of quality of life data was poor and data were insufficient to be included for meta-analysis.Steroids caused fewer withdrawals due to adverse events than vitamin D (RR 0.22; 95% CI 0.11 to 0.42; four studies, 2291 participants; moderate quality evidence). The two-compound combination and steroid monotherapy did not differ in the number of adverse events leading withdrawal (RR 0.88; 95% CI 0.42 to 1.88; three studies, 2433 participants; moderate quality evidence). The two-compound combination led to fewer withdrawals due to adverse events than vitamin D (RR 0.19; 95% CI 0.11 to 0.36; three studies, 1970 participants; high quality evidence). No study reported the type of adverse event requiring withdrawal.In terms of treatment response, as assessed by the PGA, steroids were more effective than vitamin D (RR 1.48; 95% CI 1.28 to 1.72; three studies, 1827 participants; NNTB = 5; 95% CI 5 to 7; moderate quality evidence). Statistically, the two-compound combination was better than steroid monotherapy, however the benefit was not clinically important (RR 1.13; 95% CI 1.06 to 1.20; two studies, 2226 participants; NNTB = 13; 95% CI 9 to 26; high quality evidence). The two-compound combination was more effective than vitamin D (RR 1.76; 95% CI 1.46 to 2.12; four studies, 2222 participants; NNTB = 4; 95% CI 3 to 6; moderate quality evidence).Common adverse events with these three interventions were local irritation, skin pain and folliculitis. Systemic adverse events were rare and probably not drug-related.In addition to the results of the major three comparisons we found that the two-compound combination, steroids and vitamin D monotherapy were more effective than the vehicle. Steroids of moderate, high and very high potency tended to be similarly effective and well tolerated. There are inherent limitations in this review concerning the evaluation of salicylic acid, tar, dithranol or other topical treatments. AUTHORS' CONCLUSIONS: The two-compound combination as well as corticosteroid monotherapy were more effective and safer than vitamin D monotherapy. Given the similar safety profile and only slim benefit of the two-compound combination over the steroid alone, monotherapy with generic topical steroids may be fully acceptable for short-term therapy.Future RCTs should investigate how specific therapies improve the participants' quality of life. Long-term assessments are needed (i.e. 6 to 12 months).

Systematic review

Unclassified

Authors Yan R , Jiang S , Wu Y , Gao XH , Chen HD
Journal Indian journal of dermatology, venereology and leprology
Year 2016
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Topical calcipotriol/betamethasone dipropionate ointment/gel has been commonly used for the treatment of psoriasis vulgaris. However, the efficacy of this combination needs to be consolidated. We aimed to assess the effects and safety profile of calcipotriol/betamethasone dipropionate for the treatment of psoriasis vulgaris, using evidence based approach. Randomized controlled trials on the treatment of psoriasis vulgaris with calcipotriol/betamethasone dipropionate were identified by searching PubMed, China National Knowledge Infrastructure and the Cochrane Library. The primary outcome measure was the Psoriasis Area and Severity Index (PASI) score. Ten randomized controlled trials involving 6590 participants were included. The methodologies of the studies were generally of moderate to high quality. These trials used topical calcipotriol/betamethasone dipropionate for 4 or 8 weeks, and were compared with topical calcipotriol or betamethasone. The results showed that calcipotriol/betamethasone dipropionate was more effective than controls. A four-week treatment with calcipotriol/betamethasone dipropionate did not show any significant difference between the once-daily or twice-daily regimen. The adverse events of calcipotriol/betamethasone dipropionate were tolerable and acceptable. The reports included in this review are heterogenous and have limitations. Topical application of calcipotriol/betamethasone dipropionate once daily is an efficacious treatment for psoriasis vulgaris and is associated with few side effects.

Systematic review

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Journal The Journal of clinical endocrinology and metabolism
Year 2015
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OBJECTIVE: We aimed to estimate pooled percentages of patients with adrenal insufficiency after treatment with corticosteroids for various conditions in a meta-analysis. Secondly, we aimed to stratify the results by route of administration, disease, treatment dose and duration. METHODS: We searched seven electronic databases (PubMed, MEDLINE, EMBASE, COCHRANE, CENTRAL, Web of Science and CINAHL/Academic Search Premier) in February 2014 to identify potentially relevant studies. Original articles testing adult corticosteroid users for adrenal insufficiency were eligible. RESULTS: We included 74 articles with a total of 3753 participants. Stratified by administration form, percentages of patients with adrenal insufficiency ranged from 4.2% for nasal administration (95% CI: 0.5-28.9) to 52.2% for intra-articular administration (95% CI: 40.5-63.6). Stratified by disease, percentages ranged from 6.8% for asthma with inhalation corticosteroids only (95% CI: 3.8-12.0) to 60.0% for haematological malignancies (95% CI: 38.0-78.6). The risk also varied according to dose from 2.4% (95% CI: 0.6-9.3) (low dose) to 21.5% (95% CI: 12.0-35.5) (high dose), and according to treatment duration from 1.4% (95% CI: 0.3-7.4) (<28 days) to 27.4% (95% CI: 17.7-39.8) (>1 year) in asthma patients. CONCLUSIONS: 1) Adrenal insufficiency after discontinuation of glucocorticoid occurs frequently; 2) there is no administration form, dosing, treatment duration, or underlying disease for which adrenal insufficiency can be excluded with certainty, although higher dose and longer use give the highest risk; 3) the threshold to test corticosteroid users for adrenal insufficiency should be low in clinical practice, especially for those patients with nonspecific symptoms after cessation. Strengths and limitations of this study This is the first meta-analysis providing a broad view on the risk of adrenal insufficiency after use of various types of corticosteroids in several underlying diseases. Studies displayed heterogeneity in the type of corticosteroid used, underlying condition, treatment dose, treatment duration, and route of administration, thereby reflecting clinical practice. Our results were stratified by these factors. As no individual data were available, risk stratification at the level of the individual patient was not possible. Many articles with high level of bias were included in this meta-analysis, as there were only few articles with low level of bias available. This may have affected the results.

Systematic review

Unclassified

Journal Journal of Cosmetics, Dermatological Sciences and Applications
Year 2015
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Patients with scalp psoriasis suffered from a lower quality of life relating to the highly visible site of their psoriatic lesions. In consequence this fact stimulates investigations involving treatments of this dermatologic disease. The aim of this review is to evaluate the topical treatments for scalp psoriasis compared with placebos. Methods: A systematic review was performed using searches in the database LILACS, MEDLINE, Cochrane Library, and Embase. As selection criteria were chosen eligible publications involving randomized controlled trials, patients with scalp psoriasis diagnosed clinically or by biopsy, interventions with topical treatments for scalp psoriasis compared with placebo. Outcome related to the reduction in severity of psoriasis of the scalp, assessed by physicians and patients, and assessment of adverse effects that required discontinuation of treatment. The results have shown that the patients were aged 12 to 97 years, including 3441 patients. Ten of the fifteen studies included reported gender data. Patients were mostly female. Twelve studies were about psoriasis’s severity. These studies in which the severity has been described, the classification of severity was mild (0 study), mild to moderate (1 study), moderate to severe (11 studies) and severe (0 study). In conclusion, topical corticosteroids, calcipotriol, ciclopirox olamine and associations between them are effective in the treatment of scalp psoriasis. Clobetasol propionate (0.05%) was the most effective active ingredient in several vehicles in the induction treatment of scalp psoriasis.

Systematic review

Unclassified

Journal Phytotherapy research : PTR
Year 2015
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Aloe vera L., is a plant used worldwide as folk remedy for the treatment of various ailments, including skin disorders. Its gel is present in cosmetics, medicinal products and food supplements. Psoriasis, an immune-mediated chronic inflammatory disease, involving mainly the skin, affects about the 2-3% of general population. Conventional pharmacological treatments for psoriasis can have limited effectiveness and can cause adverse reactions. For this reason often psoriatic patients look for alternative treatments based on natural products containing Aloe vera. We conducted a systematic review of clinical trials assessing effectiveness and safety of aloe for the treatment of psoriasis. Clinical studies published in English were considered; a total of four clinical trials met inclusion criteria. Studies were also evaluated by using the Jadad scale and Consort Statement in Reporting Clinical trials of Herbal Medicine Intervention. Quality and methodological accuracy of considered studies varied considerably, and some crucial information to reproduce clinical results was missing. We conclude that administration of aloe as cutaneous treatment is generally well tolerated, as no serious side effects were reported. Results on the effectiveness of Aloe vera are contradictory; our analysis reveals the presence of methodological gaps preventing to reach final conclusions.

Systematic review

Unclassified

Journal Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
Year 2014
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BACKGROUND: Current data from daily practice show that vitamin D₃ analogues, corticosteroids and their fixed combination products are used heterogeneously for topical long-term treatment of psoriasis. AIM: To evaluate scientific evidence about topical long-term therapy with vitamin D3 analogues, corticosteroids and their two-compound-products in psoriasis vulgaris and scalp psoriasis and to develop daily practice recommendations. METHODS: Systematic literature review via PubMed and Embase and informal expert consensus. RESULTS: The search strategy identified 21 relevant clinical trials. Best evidence regarding topical long term treatment was available for the two-compound-formulation containing calcipotriene and betamethasone. In a comparative trial in psoriasis vulgaris the two-compound-formulation showed superior tolerability and cost effectiveness compared to monotherapy. In scalp psoriasis the two-compound-gel was superior compared to calcipotriene monotherapy. Standardized and simplified treatment application modes resulted in a better clinical outcome comparing to on-demand therapies. DAILY PRACTICE RECOMMENDATIONS: Patients should be proactively involved in the choice of treatment, formulation and mode of application. Besides long-term treatment with the two-compound-formulation other treatment regimens including calcipotriene monotherapy can also be considered. Due to a favorable risk-benefit ratio in maintenance trials and due to better cost-effectiveness the application of two-compound-products once or twice a week after initial therapy is recommended.

Systematic review

Unclassified

Authors Deng S , May BH , Zhang AL , Lu C , Xue CC
Journal Phytotherapy research : PTR
Year 2014
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This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the topical use of multi-herbal formulations for the management of psoriasis vulgaris. Studies were identified from PubMed, Cochrane library, EMBASE, and the Chinese databases CNKI and CQVIP. Methods were according to the Cochrane Handbook and meta-analyses used RevMan 5.1. Nine studies met the inclusion/exclusion criteria. The comparisons were with placebo and/or anti-psoriatic pharmacotherapy (APP) with two studies having three arms. The pooled meta-analysis data indicated the topical herbal formulae improved overall clinical efficacy (defined as 50% improvement or greater) when compared with: topical placebo (plus oral herbal co-intervention); topical APP alone; and topical APP (plus pharmaceutical co-intervention). Improvement was evident in Modified Psoriasis Area and Severity Index (PASI) score when topical herbal formula was compared to placebo (plus oral herbal co-intervention). No serious adverse events were reported. The most commonly used herbs were Sophora flavescens root and Lithospermum erythrorhizon root. Experimental studies reported that these herbs and/or their constituents have anti-inflammatory, anti-proliferative, anti-angiogenic, and tissue repair actions. These actions may at least partially explain the apparent benefits of the topical multi-herbal formulations in psoriasis. Copyright © 2013 John Wiley & Sons, Ltd.