Isotretinoin for rosacea: A systematic review

Graphical abstract

To the Editor: Rosacea is a chronic inflammatory dermatosis affecting 10% of the population worldwide.Although global guidelines recommend using oral antibiotics combined with topical anti-inflammatory agents as first-line management for moderate-to-severe disease, recalcitrance is common, requiring off-label therapeutic approaches such as low-dose isotretinoin (LDI).Herein, a systematic review was performed to assess the current level of evidence supporting LDI for rosacea, with focuses on dosages utilized, treatment duration, and efficacy achieved.
Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessments was performed using PubMed and MEDLINE, with search terms including ''Rosacea AND Isotretinoin.''Study selections were exclusive to randomized clinical trials, retrospective studies, case reports, and case series.
Of 34 studies identified, 14 studies (n ¼ 1320; mean age, 36 years [range 18-66 years]; 61% females; Table I) evaluated use of LDI (0.1-0.5 mg/kg/d or fixed doses of 10-20 mg/d) for moderate-to-severe and recalcitrant rosacea for an average treatment duration of 16-weeks or longer.Commonly affected sites among all patients included the cheeks, nose, and forehead.Reductions in total number of papules, pustules, and erythema ranged from 71% to 83% to complete resolution.Increased tolerability was observed at 10 mg/d (n ¼ 556), but disease remission periods varied, influenced by use of additional therapies.
One retrospective study (n ¼ 52) assessing openlabel LDI treatment for 57-weeks (initial dose of 20 mg/d, with dose adjustments made accordingly with responses) in patients with mild-to-moderate rosacea yielded significant improvement.Moreover, 91% of patients experienced complete clearance of papulopustules and/or 75% to 99% reduction of papulopustules. 1 Although a patient's treatment was individualized by altering LDI dosages to specifically control their symptoms and any concomitant diseases (acne and/or seborrheic dermatitis), 71% of patients reduced their isotretinoin dose to 10 mg thrice weekly within 3 months of starting therapy, which they continued for 1 year. 1 Another comparative study (n ¼ 76) evaluated efficacy of once weekly administration of LDI (20 mg/ wk) versus minocycline (100 mg/d) for mild-tomoderate rosacea and LDI (40 mg/wk) for severe rosacea for a 7-month duration. 2Despite appreciable improvement in all treated cases, 20 mg/wk isotretinoin achieved a statistically significant higher mean global improvement scale score when compared with 100 mg/d minocycline ( global improvement scale, 2.8 vs 2.3, respectively; P \.05) but minimal differences between complete response rates (10.7% vs. 8.3%, respectively; P ¼ .77).Patients treated for severe rosacea demonstrated a complete response rate of 62.5% and a mean global improvement scale of 3.7. 2 An additional study (n ¼ 22) used continuous isotretinoin microdosing (0.03-0.17 mg/kg/d) following isotretinoin 10 to 20 mg/d that also was promising. 3ll evaluated studies supported treatment of rosacea with isotretinoin.Isotretinoin can reduce sebaceous gland size and activity and even induce apoptosis and downregulate pattern recognition receptor expression implicated in disease pathophysiology conferring anti-inflammatory activity (Fig 1). 2,4,5Given that the selected studies primarily encompassed randomized clinical trials, each having marginal risk of biases, demonstrating consistency, and generating similar clinical outcomes, these findings confer a moderate-to-strong level of evidence supporting isotretinoin effectiveness to treat recalcitrant rosacea.However, routine LDI implementation is limited by lack of standardized protocols thus warranting additional long-term, high-powered studies to guide future directions and consensus on optimal dosages and treatment intervals needed to maintain disease clearance.JAAD INT

Table I .
Summary of grade of evidence for low-dose isotretinoin in the treatment of rosacea