PKDL and other dermal lesions in HIV co-infected patients with Leishmaniasis: review of clinical presentation in relation to immune responses

Abstract

Background: Co-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.

Methods: We 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.

Results: A 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).

Conclusion: With 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.

Figure 1. Classical PKDL from Sudan showing a papular rash on the face.

The identity of the photographer was known to the patient, who gave permission. (Further images of PKDL can be found in the WHO PKDL atlas: A manual for health workers .)

Figure 2. A simplified, theoretical presentation of the relationship between Th1 and Th2 responses, and parasite load, with the influence of HIV and antileishmanial and antiretroviral treatment on cutaneous leishmaniasis (CL), post-kala-azar dermal leishmaniasis (PKDL), diffuse cutaneous leishmaniasis (DCL) and visceral leishmaniasis (VL).

The Th17 response is not shown but is similar in polarity to the Th1 response. Mucocutaneous leishmaniasis (MCL) and leishmaniasis recidivans (LR) are indicated as reference points.

Figure 3. Immune (re-)constitution and post-kala-azar dermal leishmaniasis (PKDL).

Panel A: Immune constitution in PKDL in immunocompetent patients. Theoretical relationship between changes in parasite load and immune response as the result of antileishmanial treatment, with associated clinical syndromes (visceral leishmaniasis [VL], PKDL) Panel B: Immune reconstitution in HIV infection. Theoretical relationship between changes in viral load and CD4 count as a result of antiretroviral therapy, with examples of associated immune reconstitution disease (cryptococcal meningitis, Kaposi's sarcoma, tuberculosis). Panel C: Theoretical overlap in mechanisms of PKDL occurring during VL and HIV co-infection treated with combined antileishmanial and antiretroviral therapy.

Figure 4. Diffuse or disseminated cutaneous leishmaniasis in an HIV-positive patient from Rajasthan, India (endemic for CL, not VL).

There are florid nodules mainly on the face and on the extremities and back; oral and nasopharyngeal infiltrations were also found. There was no previous ulcer nor were there signs of visceralization. The parasite was not typed. Reproduced with permission from Chaudhary et al., the Indian Journal for Dermatology, Venereology and Leprology .