Hypokalaemia-Induced Rhabdomyolysis after Treatment of Post-Kala-azar Dermal Leishmaniasis (PKDL) with High-Dose AmBisome in Bangladesh—A Case Report

Post-kala-azar dermal leishmaniasis (PKDL) is a macular, papular, and/or nodular skin rash that can appear as a sequel of visceral leishmaniasis (VL) caused by Leishmania donovani. In Bangladesh, it occurs in around 10% of VL patients, leading to high prevalences of 6/10,000–21/10,000 population in endemic regions [1], [2]. Over 95% of lesions are macular and cause no or little physical discomfort to patients. However, Leishmania parasites can been found in PKDL lesions, and there is (sparse) evidence that they are infective to sandflies [3], [4], [5]. It is generally assumed that PKDL patients form an infectious reservoir and should be treated in order to achieve disease control. There are no evidence-based treatments for PKDL. Therefore, treatment can be considered experimental, and treatment choices are “best guesses” based on good results in small clinical studies and clinical experience in the field. Medecins Sans Frontieres provides treatment for VL and PKDL in Fulbaria, a highly endemic subdistrict of Mymensingh in Bangladesh. Active case finding is undertaken, and free-of-charge short-course treatment with liposomal amphotericin B (L-AMB) (AmBisome, Gilead, United States) is provided for both VL and PKDL. L-AMB was designated by the World Health Organization (WHO) as the safest and most effective treatment for VL in the Indian subcontinent [6]. The optimal treatment for PKDL has not been established by clinical trials. Based on the safety and efficacy of L-AMB given in high total cumulative doses (50–90 mg/kg) for treatment of PKDL in small patient cohorts in East Africa [7], [8], a regimen was chosen with a total cumulative dose of 30 mg/kg, divided into six doses of 5 mg/kg L-AMB, given over a period of 3 weeks on an ambulatory basis. This dose and frequency were chosen to minimise the impact on patients' daily lives. L-AMB is known to be a safe treatment for VL in similar doses [9]. It was expected that L-AMB in this dose regimen would cause minimal adverse effects in otherwise healthy PKDL patients. PKDL was diagnosed by clinical evaluation of lesions. More than 1,300 PKDL patients have been treated to date. Unexpectedly, we encountered hypokalaemia-induced rhabdomyolysis during or following treatment. Here, we present six confirmed cases and one presumed case of this rare adverse event that occurred in the period from October to December of 2011. After three cases of confirmed rhabdomyolysis, further enrolment of PKDL patients was stopped. Patients still under treatment were closely monitored for the occurrence of hypokalaemia. Presentation of Cases Case 1 An 18-year-old female returned to the clinic 2 days after her fifth dose of L-AMB, unable to walk, sit up unaided, or even hold her head up due to severe muscle pain and weakness, predominantly in the proximal muscles. We were unable to perform biochemical assays. The patient improved gradually, and her symptoms resolved completely.