Systemic treatment of cutaneous leishmaniasis: A systematic review and meta-analysis.

BACKGROUND

Cutaneous leishmaniasis (CL) is increasingly reported in previously non-endemic European countries. Although often self-limiting or amenable to topical therapy, systemic treatment is indicated in specific situations. Evidence guiding systemic therapies remains limited and heterogeneous.

OBJECTIVES

This systematic review and meta-analysis aimed to synthesize available evidence on systemic treatment regimens for CL.

METHODS

MEDLINE/PubMed and Embase were searched for clinically and/or parasitologically confirmed CL receiving systemic monotherapy with meglumine antimoniate (MA), miltefosine, azoles, pentamidine, or liposomal amphotericin B (L-AmB) until February 2026. Primary outcome was clinical cure assessed 2-7.5 months after treatment initiation. Pooled cure rates were estimated using random-effects meta-analysis. Subgroup analyses were performed for Old World (OWCL) and New World (NWCL) CL, and by Leishmania species.

RESULTS

Eighty-three studies comprising 96 treatment arms and 4603 patients with OWCL and NWCL were included. Overall, study quality was moderate (per JBI checklist). MA, long regarded as standard of care in many countries, had a pooled cure rate of 59% (95% CI 52%-66%). Higher rates were observed with L-AmB (77%; 95% CI 56%-90%), followed by miltefosine (75%; 95% CI 69%-81%), itraconazole (70%; 95% CI 65%-76%), and fluconazole (62%; 95% CI 16%-93%). Lower rates were obtained with pentamidine (55%; 95% CI 42%-67%) and ketoconazole (36%; 95% CI 7%-82%). Species- and region-specific sub-analyses indicated miltefosine highly effective for OWCL (particularly L. major) and NWCL (L. braziliensis, L. guyanensis, L. panamensis). Head-to-head comparisons of miltefosine and MA showed no statistically significant difference. L-AmB was similarly effective in NWCL (particularly L. braziliensis), with lack of evidence for other species.

CONCLUSIONS

Systemic treatment options for CL show variable efficacy. Despite the promising cure rates for miltefosine and L-AmB, comparative evidence remains insufficient to support therapy recommendations. Confirmation in adequately powered, high-quality RCTs, ideally stratified by species, is warranted to strengthen the evidence base.