Treatment of Tegumentary Forms of Leishmaniasis

Abstract

Choosing a treatment regimen of tegumentary leishmaniasis is influenced by the size, number and location of the lesion(s) but mainly determined by the infecting Leishmania species.

Before treatment, all lesions have to be well documented (measuring the diameter of the ulcer and of the complete lesion plus photo documentation). Since mucosal spread may affect the nasal as well as the oral mucosa, an ear-nose-throat (ENT) examination is indicated and the possibility of CL being part of visceral leishmaniasis (VL) has to be considered.

Treatment options include systemic treatment with antileishmanial drugs, local topical treatment with antileishmanial ointments/creams, local intralesional injection of antileishmanial drugs and local physical treatment (cryotherapy, thermotherapy).

The decision on systemic or local treatment depends on the species, the size, the numbers and the location of the lesions as well as comorbidities. The available antileishmanial drugs, including their dosing, mode of action, mechanism of elimination, adverse effects/toxicity profile and recommendations for treatment monitoring.

Treatment suggestions for cutaneous leishmaniasis are presented for each species. The treatment of mucosal leishmaniasis and leishmaniasis in pregnant women, children and patients with immunosuppression is discussed separately.

Appendix: Properties of drugs used for both visceral leishmaniasis and tegumentary forms of leishmaniasis

Drug	Administration	Dosage and duration	Half-life	Mode of action	Metabolic and elimination pathways
Systemic pentavalent antimonials	IM/IV	CL old world: 20 mg/kg of Sb5 base equivalent: 10–20 days	~2 h and 33–76 ha	Not fully understood	Renal excretion
		CL new world: 20 mg/kg of Sb5 base equivalent: 20 days		Interference with energy production of Leishmania amastigotes and with parasitic DNA topoisomerase I
		ML: 20 mg/kg of Sb5 base equivalent 28 days
		VL immunocompetent: 20 mg Sbv/kg/day for 28 days
		VL immunosuppressed: same
		VL prophylaxis in HIV+: 850 mg Sbva for adults every 3–4 weeks
Pentamidine	IV (IM)	CL: 4 mg/kg base: 3–4× within 7 days	~ 9–13 h and ~28 da	Interference with the synthesis of Leishmania DNA acting on the kinetoblast and on the mitochondrial membrane	Small extent renal excretion (4–17% in 24 h)
		ML: not indicated
		VL immunocompetent 4 mg/kg every other day or three times per week for ~15–30 doses
		VL immunosuppressed: same
		VL prophylaxis in HIV+: 4 mg/kg/day every 2–4 weeks
Miltefosine	Oral	CL: 3 × 50 mg (children:2–2.5 mg/day) for 28 days (Blum et al. 2014)	7 d and 31 da	Not fully understood	Metabolic pathway mediated by phospholipases
		ML3 × 50 mg (children:2–2.5 mg/day) for 28 days (Blum et al. 2014)		Apoptosis and disturbance of lipid dependant cell signalling pathways	Excretion with urine <0.2%
		VL immunocompetent 30–44 kg, 50 mg bid for 28 days; if ≥45 kg, 50 mg tid for 28 days		Antitumor effects
		VL immunosuppressed: same
		VL prophylaxis: no data
Ketoconazole	Oral	CL: 600 mg/day for 28 days	2 h and 8 ha	Inhibition of the cytochrome P 450 mediated 14α- demethylation of lanosterol, blocking ergosterol synthesis, and causing accumulation of 14α—methyl sterols	Hepatic; mainly biliary excretion
		Not indicated for ML and VL
Fluconazole	Oral	CL: 400 mg/day for 6 weeks	30 h		Hepatic; mainly renal excretion
		Not indicated for ML and VL
Liposomal Amphotericin B	IV	CL: 3 mg/kg/day: day 1–5,10; 18 mg/kg total dose equivalent	Terminal: 152 h	Polyenic antibiotic, targets ergosterol in the surface membrane of promastigotes and amastigotes, leading to increased permeability and the influx of ions	No extensive metabolism; very little renal and biliary excretion
		ML: 3–4 mg/kg/day: day 1–5,10; 17, 24, 31, 38: 18 30 (max 40 mg) mg/kg total dose equivalent
		VL immunocompetent 3 mg/kg/day on days 1–5, 14, and 21 (total dose 21 mg/kg)
		VL immunosuppressed 4 mg/kg/day on days 1–5, 10, 17, 24, 31, and 38 (total dose 40 mg/kg)
		VL prophylaxis: amphotericin B lipid complex (iv) 3–5 mg/kg/day every 3 weeks
15% paromomycin/ 12% methylbenzethonium chloride	Local	CL old world twice daily during 10–20 days		Broad spectrum aminoglycoside antibiotic	–
		CL new world twice daily during 20–30 days
Intralesional antimonials and cryotherapy (Figs 9.1 and 9.2)	Local	Two to ten times at 2–8 day intervals		Not fully understood
				Interference with energy production of Leishmania amastigotes and with parasitic DNA topoisomerase I

1. ^aBiphasic elimination, typically relating to the distribution and elimination phase of the drug