4. Post kala-azar dermal leishmaniasis

Abstract

Post kala-azar dermal leishmaniasis (PKDL) is increasingly recognized in Sudan as a complication of visceral leishmaniasis (VL), occurring in c. 55% of patients after, or during treatment of, VL. The development of PKDL seems to be restricted to parasites of the Leishmania donovani sensu stricto cluster; no particular zymodeme has been found to be associated with it. In contrast to PKDL in India, PKDL in Sudan occurs within 0–6 months after treatment for VL. The rash may be macular, maculo-papular or nodular, and spreads from the perioral area to other parts of the body, depending on grade of severity. Young children are particularly at risk of developing more severe disease. In 16% of PKDL patients, parasites can be demonstrated by microscopy in lymph node or bone marrow aspirates and, with the aid of the polymerase chain reaction (PCR), in lymph nodes of 81% of patients, possibly indicating persistent visceralized infection. Diagnosis can be made by demonstration of parasites in skin smears or biopsies in 20–30% of cases; newer techniques, using PCR with skin smears, have higher sensitivity (83%). Monoclonal antibodies against L. donovani can detect parasites in 88% of biopsies. Serological tests are of limited value. The leishmanin skin test is positive in 50–60% of cases; there is an inverse relationship between the skin test result and severity of PKDL. In differential diagnosis, miliaria rubra is the most common problem; differentiation from leprosy is the most difficult. In biopsies, hyperkeratosis, parakeratosis, acanthosis, follicular plugging and liquefaction degeneration of the basal layer may be found in the epidermis; in the dermis there are varying intensities of inflammation with scanty parasites and mainly lymphocytes; macrophages and epithelioid cells may also be found. In 20% of cases discrete granulomas may be found. After VL, the immune response shifts from a Th 2-type to a mixed Th 1/Th 2-type. High levels of interleukin-10 in skin biopsies as well as in peripheral blood mononuclear cells and plasma in patients with VL predict the development of PKDL. Treatment is needed only for those who have severe and prolonged disease; sodium stibogluconate (20 mg/kg/d for 2 months) is usually sufficient. (Liposomal) amphotericin B is effective, whereas ketoconazole, terbinafine and itraconazole are not.