PKDL and Other Dermal Lesions in HIV Co-infected Patients with Leishmaniasis: Review of Clinical Presentation in Relation to Immune Responses

Abstract

BackgroundCo-infection of leishmaniasis and HIV is increasingly reported. The clinical presentation of leishmaniasis is determined by the host immune response to the parasite; as a consequence, this presentation will be influenced by HIV-induced immunosuppression. As leishmaniasis commonly affects the skin, increasing immunosuppression changes the clinical presentation, such as in post-kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL); dermal lesions are also commonly reported in visceral leishmaniasis (VL) and HIV co-infection.MethodsWe reviewed the literature with regard to dermal manifestations in leishmaniasis and HIV co-infection, in three clinical syndromes, according to the primary presentation: PKDL, VL, or CL.ResultsA wide variety of descriptions of dermal leishmaniasis in HIV co-infection has been reported. Lesions are commonly described as florid, symmetrical, non-ulcerating, nodular lesions with atypical distribution and numerous parasites. Pre-existing, unrelated dermal lesions may become parasitized. Parasites lose their tropism and no longer exclusively cause VL or CL. PKDL in HIV co-infected patients is more common and more severe and is not restricted to Leishmania donovani. In VL, dermal lesions occur in up to 18% of patients and may present as (severe) localized cutaneous leishmaniasis, disseminated cutaneous leishmaniasis (DL) or diffuse cutaneous leishmaniasis (DCL); there may be an overlap with para-kala-azar dermal leishmaniasis. In CL, dissemination in the skin may occur resembling DL or DCL; subsequent spread to the viscera may follow. Mucosal lesions are commonly found in VL or CL and HIV co-infection. Classical mucocutaneous leishmaniasis is more severe. Immune reconstitution disease (IRD) is uncommon in HIV co-infected patients with leishmaniasis on antiretroviral treatment (ART).ConclusionWith increasing immunosuppression, the clinical syndromes of CL, VL, and PKDL become more severe and may overlap. These syndromes may be best described as VL with disseminated cutaneous lesions (before, during, or after VL) and disseminated cutaneous leishmaniasis with or without visceralization.

Immune Activation and Bacterial Translocation: A Link between Impaired Immune Recovery and Frequent Visceral Leishmaniasis Relapses in HIV-Infected Patients

“…infantum to unexpected sites and the appearance of atypical clinical features. In this scenario, amastigotes have been recovered from skin [20,21] and from gut-associated lymphoid tissue (GALT) [22,23]. …”

Para-kala-azar dermal leishmaniasis in a patient in Brazil: a case report

“…However, there are no consistent of infiltrates in PKDL lesions. The clinical manifestations of PKDL are immunologically mediated with features of a Th2 response in the skin and a systemic Th1 response, resulting in skin abnormalities in patients who are otherwise well without features of systemic leishmanial infection [5][6][7][8][9][10]11 . In this patient, the clinical progression from visceral disease with subsequent relapses to para-kala-azar dermal leishmaniasis and later isolated (post-kala-azar) lymphadenopathy without obvious clinical evidence of visceral disease suggests a similarly developing, but abnormal and inadequate systemic immune response [11][12][13] .…”

“…In immunosuppressed patients, in particular those who are HIVinfected, relapses are common, as some degree of developing antileishmanial immunity is needed to prevent a relapse of VL. With each relapse, the treatment becomes more difficult 5 . This patient had a similar clinical syndrome, which justified the decision for maintenance treatment that to date seemed to be successful.…”

“…In recent years, the disease has spread to all regions and emerged in urban areas 2 . In Latin America, cutaneous manifestations in leishmaniasis are related to Leishmania from the subgenus Viannia 3 ; however, there are reports of cutaneous lesions similar to those observed in post-kala-azar dermal leishmaniasis (PKDL), caused by Leishmania infantum, mainly in human immunodeficiency virus (HIV)-infected patients 4,5 . In addition, L. infantum can cause atypical cutaneous leishmaniasis in Central America unrelated to VL 6 .…”

Visceral leishmaniasis: a forgotten epidemic

“…Dermal lesions are common that resemble PKDL 77. Clinical suspicion may be low as certain manifestations can be explained by HIV related disease or antiretroviral treatment such as fever, hepatosplenomegaly, lymphadenopathy and pancytopenia78 (box 2).…”