Clinical healing of antimony-resistant cutaneous or mucocutaneous leishmaniasis following the combined administration of interferon-γ and pentavalent antimonial compounds

In an open trial, longer courses of pentavalent antimonials (Sbv) at sub-optimal doses (10 mg/kg body weight), in association with recombinant human interferon-gamma (IFN-gamma) (100 micrograms/m2 of body surface area) were administered, by daily intramuscular injections, to 13 patients with diagnoses of cutaneous or mucocutaneous leishmaniasis unresponsive to Sbv. Four patients presented with large skin ulcers, and 9 had mucosal involvement as the main manifestation, the latter affecting the nose (3 cases), nose and septum (2 cases), nose and oral cavity (1 case), and nose, pharynx and larynx (3 cases). Except for one case with severe involvement of the upper respiratory tract, the lesions were fully resolved by the end of therapy (mean duration 40 +/- 12 [SD] d, range 30-60 d) in the 11 patients who completed therapy. The main side effects were headache and fever (7 cases), together with leucopenia and eosinophilia (4 cases). It is concluded that combined administration of low doses of Sbv plus IFN-gamma may provide a novel therapeutic approach for the treatment of antimony-resistant cutaneous or mucocutaneous leishmaniasis. The possible mechanisms by which IFN-gamma contributes to resolution of the disease are discussed.