Visceral and cutaneous leishmaniasis in a person living with HIV

Introduction

Leishmaniasis is the third most common parasitic infection in patients living with HIV, with diverse clinical presentations ranging from cutaneous, mucocutaneous, to visceral forms. Visceral leishmaniasis (VL), also known as kala-azar, is primarily caused by the Leishmania donovani complex.^1,2 This case report describes a patient living with HIV presenting with multiple concurrent infections, including visceral and mucocutaneous leishmaniasis, where the diagnostic and therapeutic approach posed a significant challenge.

Case report

A 24-year-old male, experiencing homelessness, with a diagnosis of HIV stage C3/AIDS and a CD4+ T-lymphocyte count of 3 cells/mm³, presented to the emergency department with somnolence and a Glasgow Coma Scale score of 10/15. His past medical history included HIV diagnosis 3 months prior to hospitalization, combined with cerebral toxoplasmosis and herpes virus retinitis, for which he was receiving antiretroviral therapy with dolutegravir 50 mg daily and tenofovir/emtricitabine (300/200 mg) orally once daily. Upon further inquiry, it was reported by a shelter that the patient had discontinued his prescribed medical management following discharge. His vital signs upon admission were within normal limits. Contrast-enhanced cranial computed tomography (CT) and brain magnetic resonance imaging (MRI) were consistent with active cerebral toxoplasmosis.

During the diagnostic protocol, a chest CT revealed tree-in-bud infiltrates, and the Xpert MTB/RIF® assay detected Mycobacterium tuberculosis without rifampicin resistance. Consequently, treatment with rifampicin, isoniazid, pyrazinamide, and ethambutol was initiated for 2 months, followed by a weight-adjusted bi-conjugate regimen of pyrazinamide and ethambutol for 4 months. During hospitalization, the patient developed erythematous ulcers with scalloped borders and a clean base, located in the testicular, bilateral inguinal, and anal regions (Image 1). Dermatology consultation considered an HSV or CMV as a possibility and started treatment with ganciclovir 5 mg/kg/day but did not biopsy the lesion. Persistent pancytopenia with elevated ferritin levels raised suspicion for infectious myelophthisis, leading to a bone marrow biopsy and aspiration. Myelogram immunohistochemistry revealed the presence of amastigotes consistent with Leishmania spp. (Image 2), prompting a 14-day course of liposomal amphotericin B at a dosage of 4 mg/kg/day. Subsequently, treatment with miltefosine was initiated at a dosage of 50 mg orally twice daily for 28 days, resulting in significant clinical improvement and healing of the genital ulcers (Image 3).OPEN IN VIEWER

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Image 2.

Bone marrow biopsy with Giemsa stain revealing amastigotes of Leishmania spp. (40X).

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Image 3.

Healed ulcers in the inguinal region following amphotericin B treatment.

Discussion

Leishmaniasis, a parasitic disease with global distribution, exhibits increased prevalence in immunosuppressed individuals, including those living with HIV.^3,4 While localized cutaneous leishmaniasis (LCL) typically presents with characteristic skin lesions, atypical manifestations are frequently observed in patients living with HIV with low CD4+ counts, such as genital involvement, as seen in this case, or as part of the immune reconstitution inflammatory syndrome (IRIS). ⁵ A study of HIV-leishmaniasis cutaneous co-infection in Brazil reported a high prevalence of mucosal (80%), cutaneous (73%), disseminated (60%), and genital (27%) lesions. ² In contrast to typical LCL, our patient presented with an active ulcer surrounded by achromic scars, a feature suggestive of leishmaniasis recidivans (LR), which is more commonly associated with different Leishmania species in Brazil and Ecuador. ²

In Colombia, a total of 5755 cases of Leishmania spp. infection were registered in 2022, with the cutaneous form being the most prevalent (98.2%) and the visceral form the least (0.2%). At our institution, this diagnosis is exceedingly rare, as nationally, no cases of visceral leishmaniasis were reported in the Valle del Cauca department, where the hospital is located, during the same year. Regarding Leishmania/HIV co-infection, robust epidemiological studies are lacking, highlighting a likely underdiagnosed public health issue within the Colombian territory. ⁶

The gold standard for diagnosing cutaneous leishmaniasis involves parasite identification through biopsy and staining, culture, serology (with limited sensitivity and specificity), and polymerase chain reaction (PCR), which is more sensitive but not routinely used in our institution. The Montenegro skin test demonstrates high positive predictive value. ⁷ In this case, the diagnosis of leishmaniasis was established based on the identification of amastigotes in the bone marrow and the clinical response to treatment, given the constraints in obtaining direct lesion biopsies or utilizing molecular diagnostic tests.

Visceral leishmaniasis (VL) results from the invasion of the reticuloendothelial system by the parasite, leading to bone marrow suppression and cytopenias. ⁸ Anemia (typically normocytic normochromic, 83–97%) and thrombocytopenia (40–92%) are common hematological findings.^9,10 Our patient presented with anemia upon admission and developed transient thrombocytopenia. The observed pancytopenia is a recognized manifestation of VL due to bone marrow infiltration, predisposing to opportunistic infections, ¹¹ underscoring the importance of bone marrow examination. The identification of amastigotes in bone marrow smears stained with Wright-Giemsa is crucial for VL diagnosis. ¹²

The co-infection of HIV and Leishmania has shown an increasing trend since the 1990s, particularly in Europe, and remains a significant concern in Latin America. ¹³ In immunocompromised individuals, the classic triad of VL (fever, splenomegaly, pancytopenia) may be absent or modified, with cytopenias being more prevalent, ¹⁴ as observed in our patient where atypical hematological and cutaneous manifestations complicated the initial clinical diagnosis. HIV-induced immunosuppression facilitates parasite proliferation by reducing CD4+ T-lymphocyte counts. Parasite persistence is associated with CCR5 overexpression on infected cells and impaired T-lymphocyte renewal. ¹⁵

Treatment guidelines for HIV-Leishmania co-infection are not well-standardized. Amphotericin B and its liposomal formulations demonstrate efficacy, although data in immunosuppressed patients are limited. Oral miltefosine improves adherence but carries a risk of relapse. Pentavalent antimonials are generally less favored in patients living with HIV due to increased toxicity and mortality (16). Our patient exhibited a positive response to both liposomal amphotericin B and miltefosine, with a notable improvement in genital ulcers after the first week of amphotericin B, suggesting a concurrent, resolving cutaneous leishmaniasis (Image 3). This case underscores the unusual presentation of leishmaniasis in a person living with HIV and highlights the necessity of considering this co-infection in the differential diagnosis of atypical ulcers and pancytopenia, even in the absence of travel history to endemic areas, contrasting with typical leishmaniasis presentations described in the literature.