Abstract: We included 36 RCTs (2706 participants), of which 31 examined topical steroids; seven, calcineurin inhibitors; and three, lithium salts. The comparative interventions included placebo, azoles, calcipotriol, a non-steroidal anti-inflammatory compound, and zinc, as well as different anti-inflammatory treatments compared against each other. Our outcomes of interest were total clearance of symptoms, erythema, scaling or pruritus scores, and adverse effects. The risk of bias in studies was most frequently classified as unclear, due to unclear reporting of methods. Steroid treatment resulted in total clearance more often than placebo in short-term trials (four weeks or less) (relative risk (RR) 3.76, 95% confidence interval (CI) 1.22 to 11.56, three RCTs, 313 participants) and in one long-term trial (lasting 12 weeks). Steroids were also more effective in reducing erythema, scaling, and pruritus. Adverse effects were similar in both groups. There may be no difference between steroids and calcineurin inhibitors in total clearance in the short-term (RR 1.08, 95% 0.88 to 1.32, two RCTs, 60 participants, low-quality evidence). Steroids and calcineurin inhibitors were found comparable in all other assessed efficacy outcomes as well (five RCTs, 237 participants). Adverse events were less common in the steroid group compared with the calcineurin group in the short-term (RR 0.22, 95% CI 0.05 to 0.89, two RCTs, 60 participants). There were comparable rates of total clearance in the steroid and azole groups (RR 1.11, 95% CI 0.94 to 1.32, eight RCTs, 464 participants, moderate-quality evidence) as well as of adverse effects in the short-term, but less erythema or scaling with steroids. We found mild (class I and II) and strong (class III and IV) steroids comparable in the assessed outcomes, including adverse events. The only exception was total clearance in long-term use, which occurred more often with a mild steroid (RR 0.79, 95% CI 0.63 to 0.98, one RCT, 117 participants, low-quality evidence). In one study, calcineurin inhibitor was more effective than placebo in reducing erythema and scaling, but there were similar rates in total clearance or adverse events for short-term treatment. In another study, calcineurin inhibitor was comparable with azole when erythema, scaling, or adverse effects were measured for longer-term treatment. Lithium was more effective than placebo with regard to total clearance (RR 8.59, 95% CI 2.08 to 35.52, one RCT, 129 participants) with a comparable safety profile. Compared with azole, lithium resulted in total clearance more often (RR 1.79, 95% CI 1.10 to 2.90 in short-term treatment, one RCT, 288 participants, low-quality evidence). Topical steroids are an effective treatment for seborrhoeic dermatitis of the face and scalp in adolescents and adults, with no differences between mild and strong steroids in the short-term. There is some evidence of the benefit of topical calcineurin inhibitor or lithium salt treatment. Treatment with azoles seems as effective as steroids concerning short-term total clearance, but in other outcomes, strong steroids were more effective. Calcineurin inhibitor and azole treatment appeared comparable. Lithium salts were more effective than azoles in producing total clearance. Steroids are similarly effective to calcineurin inhibitors but with less adverse effects. Most of the included studies were small and short, lasting four weeks or less. Future trials should be appropriately blinded; include more than 200 to 300 participants; and compare steroids to calcineurin inhibitors or lithium salts, and calcineurin inhibitors to azoles or lithium salts. The follow-up time should be at least one year, and quality of life should be addressed. There is also a need for the development of well-validated outcome measures.

Plain-language summary: We included 36 randomised controlled trials with 2706 participants, examining the effect of anti-inflammatory treatments on seborrhoeic dermatitis. These trials were short-term; most of them lasting four weeks or less. Topical steroid treatment (such as hydrocortisone and betamethasone), topical calcineurin inhibitor treatment (such as tacrolimus and pimecrolimus), and topical lithium salts all reduced the symptoms of seborrhoeic dermatitis when compared with placebo treatment. Mild (such as hydrocortisone 1%) and strong (such as betamethasone) steroid compounds were comparable in short-term follow up. Short-term total clearance was achieved with antifungal azole treatment (such as ketoconazole and miconazole), as well as with steroids. Strong steroids were better than azole treatment in reducing erythema, scaling, and pruritus, and were comparable in terms of safety. Steroids were also as effective as calcineurin inhibitors, but side-effects occurred more often with calcineurin inhibitors. We found no differences between calcineurin inhibitors and azole treatments in effectiveness or side-effects. Lithium was more effective than azoles but had a similar frequency of side-effects (one study). The most common side-effects were burning, itching, erythema, and dryness in all treatment groups. Topical anti-inflammatory agents are useful in treating seborrhoeic dermatitis. Steroids are the most investigated anti-inflammatories. We still do not know the effects and safety of topical anti-inflammatory treatments in long-term or continuous use. This is regrettable as the disease is chronic in nature. Furthermore, there are no data concerning the effects of different treatments on quality of life.