Effective treatment of cutaneous leishmaniasis caused by Leishmania tropica with topical photodynamic therapy

Cutaneous leishmaniasis (CL) is a parasitic disease of the skin caused by the protozoan Leishmania. Presenting a major health problem with increasing incidence, CL can be geographically divided into “Old World” CL and “New World” CL [1]. Cutaneous leishmaniasis is transmitted by the bite of an infected female sand fly of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. The various species have been divided into the two major subgenera Leishmania (L.) viannia and Leishmania leishmania [2]. This article focuses on CL caused by Leishmania tropica (subgenus Leishmania leishmania), which is by far the most common species in Syria (Old World) besides L. major [3]. Cutaneous leishmaniasis lesions are typically located on exposed areas of the skin such as the face, arms, and lower legs [4]. Leishmania parasites are characterized by a digenetic lifecycle, alternating between promastigotes in sand flies and amastigotes that replicate within phagocytes of the host [5]. After an incubation period of up to three months, the initial lesion is a small papule at the site of the sand fly bite, which subsequently transforms into a plaque or nodule that may potentially ulcerate [4]. Even though several therapeutic guidelines exist, there is no consistent approach, as many treatment modalities lack an evidence base. This presents a challenge with respect to selecting a suitable therapeutic strategy [4, 6]. According to recommendations issued by the Societies of Tropical Medicine (DTG), Chemotherapy (PEG), and Dermatology (DDG), no severe complications are to be expected following infection with “Old World” CL caused by L. tropica [4]. Moreover, spontaneous resolution within 10–15 months has been described in 50 % of cases, however, sequelae include disfiguring scars as well as hypoand hyperpigmentation [4, 6]. With respect to uncomplicated CL lesions caused by L. tropica, sole topical treatment with perilesional pentavalent antimonies, for example, sodium stibogluconate in combination with cryotherapy, thermotherapy, or topical paromomycin in an appropriate formulation for L. major represents an adequate therapeutic option. For complex lesions (for example, more than three infected lesions, infections in functionally or cosmetically critical areas such as the face or hands, lymphangitis), treatment of first choice includes imidazole (ketoconazole) and triazole (itraconazole, fluconazole); second-line treatment consists of antimony preparations with allopurinol. Photodynamic therapy (PDT) is at best considered acceptable as treatment of third choice, primarily due to lack of randomized controlled trials [4, 7–9]. A safe and noninvasive therapeutic option with predominantly mild to moderate side effects, PDT is marked by excellent cosmetic results. The exact underlying mechanisms with respect to its effects on CL is largely unknown, especially since L. amazonensis, and probably most other species, lack enzymes of heme synthesis. Data shows that the amount of protoporphyrin IX that one amastigote is able to accumulate is 500 times lower than the amount required for killing one metacyclic parasite. The good clinical outcome is therefore unlikely to involve direct lethal effects on Leishmania by ALA-PDT [5, 10]. One known side effect of PDT is local heating of the skin, which may play a role, given that hyperthermia treatment of leishmaniasis has been described as an effective therapeutic option [4].