Strategies for using topical corticosteroids in children and adults with eczema.

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.

Phototherapy for atopic eczema.

BACKGROUND: Atopic eczema (AE), also known as atopic dermatitis, is a chronic inflammatory skin condition that causes significant burden. Phototherapy is sometimes used to treat AE when topical treatments, such as corticosteroids, are insufficient or poorly tolerated. OBJECTIVES: To assess the effects of phototherapy for treating AE. SEARCH METHODS: We searched the Cochrane Skin Specialised Register, CENTRAL, MEDLINE, Embase, and ClinicalTrials.gov to January 2021. SELECTION CRITERIA: We included randomised controlled trials in adults or children with any subtype or severity of clinically diagnosed AE. Eligible comparisons were any type of phototherapy versus other forms of phototherapy or any other treatment, including placebo or no treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. For key findings, we used RoB 2.0 to assess bias, and GRADE to assess certainty of the evidence. Primary outcomes were physician-assessed signs and patient-reported symptoms. Secondary outcomes were Investigator Global Assessment (IGA), health-related quality of life (HRQoL), safety (measured as withdrawals due to adverse events), and long-term control. MAIN RESULTS: We included 32 trials with 1219 randomised participants, aged 5 to 83 years (mean: 28 years), with an equal number of males and females. Participants were recruited mainly from secondary care dermatology clinics, and study duration was, on average, 13 weeks (range: 10 days to one year). We assessed risk of bias for all key outcomes as having some concerns or high risk, due to missing data, inappropriate analysis, or insufficient information to assess selective reporting. Assessed interventions included: narrowband ultraviolet B (NB-UVB; 13 trials), ultraviolet A1 (UVA1; 6 trials), broadband ultraviolet B (BB-UVB; 5 trials), ultraviolet AB (UVAB; 2 trials), psoralen plus ultraviolet A (PUVA; 2 trials), ultraviolet A (UVA; 1 trial), unspecified ultraviolet B (UVB; 1 trial), full spectrum light (1 trial), Saalmann selective ultraviolet phototherapy (SUP) cabin (1 trial), saltwater bath plus UVB (balneophototherapy; 1 trial), and excimer laser (1 trial). Comparators included placebo, no treatment, another phototherapy, topical treatment, or alternative doses of the same treatment. Results for key comparisons are summarised (for scales, lower scores are better): NB-UVB versus placebo/no treatment There may be a larger reduction in physician-assessed signs with NB-UVB compared to placebo after 12 weeks of treatment (mean difference (MD) -9.4, 95% confidence interval (CI) -3.62 to -15.18; 1 trial, 41 participants; scale: 0 to 90). Two trials reported little difference between NB-UVB and no treatment (37 participants, four to six weeks of treatment); another reported improved signs with NB-UVB versus no treatment (11 participants, nine weeks of treatment). NB-UVB may increase the number of people reporting reduced itch after 12 weeks of treatment compared to placebo (risk ratio (RR) 1.72, 95% CI 1.10 to 2.69; 1 trial, 40 participants). Another trial reported very little difference in itch severity with NB-UVB (25 participants, four weeks of treatment). The number of participants with moderate to greater global improvement may be higher with NB-UVB than placebo after 12 weeks of treatment (RR 2.81, 95% CI 1.10 to 7.17; 1 trial, 41 participants). NB-UVB may not affect rates of withdrawal due to adverse events. No withdrawals were reported in one trial of NB-UVB versus placebo (18 participants, nine weeks of treatment). In two trials of NB-UVB versus no treatment, each reported one withdrawal per group (71 participants, 8 to 12 weeks of treatment). We judged that all reported outcomes were supported with low-certainty evidence, due to risk of bias and imprecision. No trials reported HRQoL. NB-UVB versus UVA1 We judged the evidence for NB-UVB compared to UVA1 to be very low certainty for all outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physician-assessed signs after six weeks (MD -2.00, 95% CI -8.41 to 4.41; 1 trial, 46 participants; scale: 0 to 108), or patient-reported itch after six weeks (MD 0.3, 95% CI -1.07 to 1.67; 1 trial, 46 participants; scale: 0 to 10). Two split-body trials (20 participants, 40 sides) also measured these outcomes, using different scales at seven to eight weeks; they reported lower scores with NB-UVB. One trial reported HRQoL at six weeks (MD 2.9, 95% CI -9.57 to 15.37; 1 trial, 46 participants; scale: 30 to 150). One split-body trial reported no withdrawals due to adverse events over 12 weeks (13 participants). No trials reported IGA. NB-UVB versus PUVA We judged the evidence for NB-UVB compared to PUVA (8-methoxypsoralen in bath plus UVA) to be very low certainty for all reported outcomes, due to risk of bias and imprecision. There was no evidence of a difference in physician-assessed signs after six weeks (64.1% reduction with NB-UVB versus 65.7% reduction with PUVA; 1 trial, 10 participants, 20 sides). There was no evidence of a difference in marked improvement or complete remission after six weeks (odds ratio (OR) 1.00, 95% CI 0.13 to 7.89; 1 trial, 9/10 participants with both treatments). One split-body trial reported no withdrawals due to adverse events in 10 participants over six weeks. The trials did not report patient-reported symptoms or HRQoL. UVA1 versus PUVA There was very low-certainty evidence, due to serious risk of bias and imprecision, that PUVA (oral 5-methoxypsoralen plus UVA) reduced physician-assessed signs more than UVA1 after three weeks (MD 11.3, 95% CI -0.21 to 22.81; 1 trial, 40 participants; scale: 0 to 103). The trial did not report patient-reported symptoms, IGA, HRQoL, or withdrawals due to adverse events. There were no eligible trials for the key comparisons of UVA1 or PUVA compared with no treatment. Adverse events Reported adverse events included low rates of phototoxic reaction, severe irritation, UV burn, bacterial superinfection, disease exacerbation, and eczema herpeticum. AUTHORS' CONCLUSIONS: Compared to placebo or no treatment, NB-UVB may improve physician-rated signs, patient-reported symptoms, and IGA after 12 weeks, without a difference in withdrawal due to adverse events. Evidence for UVA1 compared to NB-UVB or PUVA, and NB-UVB compared to PUVA was very low certainty. More information is needed on the safety and effectiveness of all aspects of phototherapy for treating AE.

Perspectives of community pharmacy staff on commonly encountered skin conditions and the key challenges towards enhancing their role in dermatology.

This research letter discusses the perspectives of community pharmacy staff on commonly encountered skin conditions and the key challenges towards enhancing their role in this area. A mixed methods online survey was created, and a total of 174 community pharmacy staff completed the survey. The results highlight the range of conditions currently encountered in community pharmacy and the breadth of challenges facing community pharmacy staff, in particular challenges surrounding providing a differential diagnosis. Community pharmacies are an integral part of the NHS and have a key role in managing skin conditions; however, in order to optimise this role, the perspectives of staff discussed in this letter need to be further explored and addressed.

How can community pharmacists be supported to manage skin conditions? A multistage stakeholder research prioritisation exercise.

OBJECTIVE: To establish research priorities which will support the development and delivery of community pharmacy initiatives for the management of skin conditions. DESIGN: An iterative, multistage stakeholder consultation consisting of online survey, participant workshops and prioritisation meeting. SETTING: All data collection took place online with participants completing a survey (delivered via the JISC Online Survey platform, between July 2021 and January 2022) and participating in online workshops and meetings (hosted on Microsoft Teams between April and July 2022). PARTICIPANTS: 174 community pharmacists and pharmacy staff completed the online survey.53 participants participated in the exploratory workshops (19 community pharmacists, 4 non-pharmacist members of pharmacy staff and 30 members of the public). 4 healthcare professionals who were unable to attend a workshop participated in a one-to-one interview.29 participants from the workshops took part in the prioritisation meeting (5 pharmacists/pharmacy staff, 1 other healthcare professional and 23 members of the public). RESULTS: Five broad areas of potential research need were identified in the online survey: (1) identifying and diagnosing skin conditions; (2) skin conditions in skin of colour; (3) when to refer skin conditions; (4) disease-specific concerns and (5) product-specific concerns.These were explored and refined in the workshops to establish 10 potential areas for research, which will support pharmacists in managing skin conditions. These were ranked in the prioritisation meeting. Among those prioritised were topics which consider how pharmacists work with other healthcare professionals to identify and manage skin conditions. CONCLUSIONS: Survey responses and stakeholder workshops all recognised the potential for community pharmacists to play an active role in the management of common skin conditions. Future research may support this in the generation of resources for pharmacists, in encouraging public take-up of pharmacy services, and in evaluating the most effective provision for dealing with skin conditions.

The long-term safety of topical corticosteroids in atopic dermatitis: A systematic review.

Background: Topical corticosteroids (TCS) are a first-line treatment for eczema, but there are concerns about their safety when used long-term. Objectives: To systematically review adverse effects associated with longer-term use of TCS for eczema. Methods: Randomised controlled trials (RCTs), cohort and case-control studies reporting adverse effects of TCS (comparators: no TCS treatment, other topicals) in patients with eczema were identified. Included studies had greater than one year of follow-up, minimum cohort size of 50 participants, or minimum 50 per arm for RCTs. Evidence was GRADE-assessed. Prospero registration CRD42021286413. Results: We found seven studies (two randomised, five observational); two RCTs (n = 2570, including 1288 receiving TCS), two cohort (all received TCS n = 148) and three case-control studies (cases n = 10 322, controls n = 12 201). Evidence from two RCTS (n = 2570, children, three and five years' duration) comparing TCS to topical calcineurin inhibitors found intermittent TCS use probably results in little to no difference in risk of growth abnormalities, non-skin infections, impaired vaccine response and lymphoma/non lymphoma malignancies. The five-year RCT reported only one episode of skin atrophy (n = 1213 TCS arm; mild/moderate potency), suggesting TCS use probably results in little to no difference in skin thinning when used intermittently to treat flares. No cases of clinical adrenal insufficiency were reported in 75 patients using mild/moderate TCS in the three-year RCT. Small associations between TCS and type-2 diabetes and lymphoma were identified in two case-control studies compared to no TCS, but the evidence is very uncertain. No long-term studies concerning topical steroid withdrawal or eye problems were identified. Conclusion: This review provides some reassuring data on growth and skin thinning when TCS are used intermittently for up to 5 years, but many knowledge gaps remain.

Agreement and Correlation Between Different Topical Corticosteroid Potency Classification Systems.

Importance: Topical corticosteroids (TCSs) are available in multiple potencies that alter their effectiveness and safety. Pharmacoepidemiologic studies on TCSs are hampered by the absence of a universal potency classification system, limiting comparisons across studies, robust exposure classification, and clinical interpretation. Objective: To classify TCSs into 3 commonly used potency classification systems and evaluate the agreement and correlation between the 3 systems. Design, Setting, and Participants: In this classification study, a comprehensive list of TCS formulations was compiled using sources identified in the literature, the Ontario Drug Benefit Formulary, a recent Cochrane review on the use of TCSs in people with eczema, and the Anatomical Therapeutic Classification (ATC) of the World Health Organization from August 11, 2021, to January 6, 2022. Topical corticosteroid potency classifications were assigned and compared using the 7-category US classification system, a 4-category classification from a recent Cochrane review largely based on the UK formulary, and the 4-category ATC classification. To facilitate comparisons across systems, the 7-category US system was consolidated into 4 categories. Main Outcomes and Measures: Cohen weighted κ (κw) and Spearman rank correlation coefficients (r) were computed to examine agreement and correlation between the classification systems. Results: A total of 232 unique TCS formulations (ATC, n = 231; US classification, n = 232; Cochrane review, n = 89) were included. Overall, there was low-to-moderate agreement but strong correlation between the classification systems. The US classification had weak agreement with the ATC system (κw, 0.53; 95% CI, 0.45-0.60) and moderate agreement with the Cochrane review classification (κw, 0.60; 95% CI, 0.48-0.73); there was weak agreement between the ATC and Cochrane review classifications (κw, 0.58; 95% CI, 0.46-0.71). The US classification strongly correlated with the ATC system (r, 0.77; 95% CI, 0.71-0.82) and Cochrane review classification (r, 0.74; 95% CI, 0.62-0.82). There was also a strong correlation between the Cochrane review and ATC classifications (r, 0.71; 95% CI, 0.58-0.80). Conclusions and Relevance: This classification study used multiple resources to classify 232 TCS formulations into 3 potency classifications. Because these systems are often incongruent, they may yield different results in pharmacoepidemiologic studies; investigators need to be transparent in their classification approach and consider alternative potency definitions in sensitivity analyses.