Topical Tacrolimus for Seborrhoeic Dermatitis: A Systematic Review of Efficacy and Indirect Malignancy Evidence

Seborrhoeic dermatitis (SD) is a chronic inflammatory skin disorder.Topical corticosteroids are effective for flares, but repeated facial use may thin the skin and cause telangiectasia or steroid-related facial eruptions.Topical tacrolimus is approved for atopic dermatitis (AD) in US and UK product labeling and is used off-label for SD.Its steroid-sparing potential must therefore be considered alongside the US Food and Drug Administration (FDA) boxed warning concerning a theoretical malignancy risk.This systematic review evaluates the long-term efficacy, safety, and patient-reported outcomes associated with topical tacrolimus in SD, with particular focus on steroid-refractory and immunocompromised populations.Six databases were searched for English-language reports published from January 1, 2003, through June 5, 2025.Risk of bias was assessed using RoB 2, the Newcastle-Ottawa Scale (NOS), National Heart, Lung, and Blood Institute tools, or A MeaSurement Tool to Assess systematic Reviews (AMSTAR) 2 according to study design.Clinical and methodological heterogeneity precluded a defensible new metaanalysis, so results were synthesized narratively.Twenty-one reports were included: 8 direct SD reports, 10 indirect primary safety, pharmacokinetic, or skin structure reports, and 3 prior systematic reviews.Maintenance evidence was more consistent than induction evidence.In the largest SD maintenance trial, relapse occurred in 12 of 57 tacrolimus recipients and 23 of 57 ciclopiroxolamine recipients (hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.89).Transient burning or tingling was the principal adverse effect.No included SD study was large or long enough to assess malignancy.In AD, the largest synthesis reported a tacrolimus-specific odds ratio for any cancer of 0.99 (95% credible interval: 0.89-1.09),although some observational cohorts reported cutaneous T-cell lymphoma (CTCL) signals.Protopathic bias, disease severity, and surveillance are plausible explanations but do not exclude a causal association.Topical tacrolimus appears useful for selected patients with facial SD, with the strongest direct evidence supporting twice-weekly maintenance after disease control.Long-term malignancy conclusions remain indirect for SD and should be communicated with appropriate uncertainty.Patient-preference and qualityof-life evidence is insufficient for firm conclusions.