Treatment of cutaneous leishmaniasis (CL) is complex, and depends on the Leishmania species, the site of inoculation, the clinical presentation, and the patient's age. Parenterally administered drugs, mainly pentavalent antimonials administered intravenously or intramuscularly, are generally reserved for complex forms or immunocompromised patients. Local treatments are the most commonly used, and include intralesional pentavalent antimonials, thermotherapy, and cryotherapy. These therapies can be very painful, have serious potential adverse effects, and can be less effective in children.1 Miltefosine, an oral agent with recognized efficacy for the treatment of leishmaniasis, may be a good option in these cases.

A 10-year-old boy (35kg) of Moroccan origin, with no relevant medical history, was seen for a painful skin lesion on the arm that had appeared 6 months earlier, 1 week after traveling to Morocco. Physical examination revealed a crusted, exudative, erythematous violaceous plaque measuring 8×6cm (Fig. 1A). Biopsy showed a lymphohistiocytic infiltrate with intracellular amastigotes (Leishman-Donovan bodies) in the dermis, based on which the patient was diagnosed with CL. Due to the child's age, his poor tolerance for medical procedures, the potential adverse effects of intralesional pentavalent antimonials, and their reduced efficacy in children aged less than 12 years,2 it was decided to begin treatment with miltefosine (75mg/d) for 28 days. The results of laboratory tests performed before and during treatment, including a complete blood count and kidney and liver function profiles, were normal. After 2 weeks of treatment the patient no longer presented pain, and after 4 weeks a marked clinical improvement was observed, with the presence of residual hyperpigmentation. At follow-up 6 months later, the patient remained asymptomatic, with a residual plaque on the arm (Fig. 1B).

Figure 1.

Childhood cutaneous leishmaniasis. A, Very painful crusted, exudative, erythematous violaceous plaque (8×6cm) on the arm of a 10-year-old boy. B, Lesion control achieved 6 months after treatment with oral miltefosine. Residual brownish plaque on the arm. The patient remained asymptomatic.

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Treatment of leishmaniasis in children can be difficult: they present a higher percentage of facial lesions, have a significantly lower response rate to antimonials than adults, have poorer adherence to injectable treatments, and are more susceptible than adults to potential systemic toxicity associated with standard treatments1 (Table 1).

Miltefosine is an alkylphosphocholine that was initially developed as an antitumor agent, after which its anti-Leishmania activity was discovered. In 2014 it was approved by the Food and Drug Administration (FDA) for the treatment of visceral, cutaneous, and mucocutaneous leishmaniasis in patients aged ≥12 years (≥30kg), and is currently the only authorized oral drug for this indication.3 Adverse effects occur in more than half of all patients, but are predominantly mild and well tolerated. Almost 90% of adverse effects are grade 1, consisting mainly of diarrhea, vomiting, transient increases in transaminase levels, and mild renal dysfunction, and do not usually require treatment interruption1,4 (Table 2). Multiple clinical trials have demonstrated a high response rate to miltefosine in patients with visceral and cutaneous leishmaniasis. A recent meta-analysis reported similar responses in CL patients infected with Leishmania braziliensis treated with either miltefosine or antimonials, but found that miltefosine was significantly superior in patients infected with parasite species other than L. braziliensis.5 Another recent meta-analysis evaluating CL treatments in children aged ≤12 years found a satisfactory response in 68% to 82.6% of CL cases treated with miltefosine.6 A randomized clinical trial conducted in Colombia included 116 CL patients aged 2–12 years, who were treated with intramuscular meglumine antimoniate (20mg/kg/d for 20d) or oral miltefosine (1.8–2.5mg/kg/d for 28d).7 Miltefosine showed a response rate of over 80%, which was noninferior to that of meglumine antimoniate, and a lower rate of adverse effects. Numerous clinical cases and case series have demonstrated the utility of miltefosine for the treatment of Old World CL,8,9 although there are limited pediatric data available.

Miltefosine is detectable in cells and plasma up to 1 and 6 months after treatment, respectively.4 This may explain why the clinical response progressively improves after discontinuation of treatment. Some studies have shown that children may have lower plasma and intracellular concentrations of miltefosine than adults,4 which may influence the therapeutic response.

Despite being the only oral agent approved for the treatment of leishmaniasis, its good efficacy and safety profile, and its inclusion in the World Health Organization's list of essential drugs, miltefosine is considered an orphan drug given its limited availability worldwide. In Europe, it is registered only in Germany (in Spain it must be requested as a foreign medication), and constitutes a high cost for health systems.3 In Spain it costs approximately €2600 (56 hard 50-mg capsules), which is significantly more expensive than imiquimod, daylight photodynamic therapy, and intralesional antimonials. However, it could be cost-effective when considering adherence, efficacy, the indirect costs of lost time, adverse events, and direct costs to the patient.10 The fact that miltefosine is no longer patent-protected should facilitate the development of lower-cost generic products.

Daylight photodynamic therapy is another therapeutic alternative for childhood CL. A novel study reported a high response rate when the product was applied by the patient (or their relatives) once per week until clinical resolution, with minimal adverse effects.11

Children may show poorer adherence to standard CL therapy, which can have potentially serious adverse effects in these patients. Miltefosine can be a useful alternative for the treatment of leishmaniasis in these cases owing to its high efficacy, oral route of administration, and low toxicity.