Liposomal amphotericin B in travelers with cutaneous and muco-cutaneous leishmaniasis: Not a panacea

Background: Complex cutaneous and muco-cutaneous leishmaniasis (CL and MCL) often requires systemic therapy. Liposomal amphotericin B (L-AmB) has a strong potential for a solid clinical benefit in this indication. Methods: We conducted a retrospective analysis of data from a French centralized referral treatment program and from the “LeishMan” European consortium database. All patients with parasitologically proven CL or MCL who received at least one dose of L-AmB were included. Positive outcome was based on ulcer closure as per recent WHO workshop guidelines. Results: From 2008 through 2016, 43 travelers returning from 18 countries (Old World n = 28; New World n = 15) were analyzed with a median follow-up duration of 79 days [range 28–803]. Main clinical forms were: localized CL with one or multiple lesions (n = 32; 74%) and MCL (n = 8; 19%). As per published criteria 19 of 41 patients (46%) were cured 90 days after one course of L-AmB. When the following items -improvement before day 90 but no subsequent follow-up, delayed healing (>3 months) and healing after a second course of L-AmB- were included in the definition of cure, 27 of 43 patients (63%) had a positive outcome. Five patients (MCL = 1; CL = 4) experienced a relapse after a median duration of 6 months [range 3–27] post treatment and 53% of patients (23/43) experienced at least one adverse event including severe hypokalaemia and acute cardiac failure (one patient each). In multivariate analysis, tegumentary infection with L. infantum was associated with complete healing after L-AmB therapy (OR 5.8 IC 95% [1.03–32]) while infection with other species had no impact on outcome. Conclusion: In conditions close to current medical practice, the therapeutic window of L-AmB was narrow in travellers with CL or MCL, with the possible exception of those infected with L. infantum. Strict follow-up is warranted when using L-AmB in patients with mild disease. Author summary: Cutaneous and muco-cutaneous leishmaniasis (CL/MCL) are disfiguring diseases caused by a worldwide distributed parasite called Leishmania and its 20 species. Clinical manifestations span a wide continuum from single nodular lesion to disseminated form with mucosal involvement. Though local treatment with cryotherapy and intralesionnal antimony or topical formulations of paromomycin is generally adequate in most of situations, some patients with complex CL/MCL require systemic therapy. No convenient regimen has been proved to be safe and effective for all infecting species, all clinical forms and all patients (e.g. children, pregnant women, adults with comorbidities or immunosuppression). In this study, the authors examined in returning travelers with CL/MCL the effectiveness of an antifungal agent “liposomal amphotericin B” (L-AmB), which is highly effective in visceral leishmaniasis. Surprisingly, rates of healing were lower than in previous reports in this unselected population that reflects clinical practice in non-endemic countries. The observations also suggest that some Leishmania species (namely, L. infantum) may be more susceptible to L-AmB than others. Occurrence of adverse events should raises the question of the benefit-risk balance of L-AmB in CL/MCL. Careful attention to comorbidities and adoption of strict protocols for administration are pre-requisites for the use of L-AmB in patients with CL/MCL.