Abstract
We describe the case of a HIV-positive patient treated for visceral leishmaniasis who developed uveitis as part of a leishmaniasis immune reconstitution syndrome. Visceral leishmaniasis is increasingly found in HIV-positive adults. Its ophthalmic manifestations can range from relatively minor to complicated anterior uveitis, leading to secondary glaucoma and loss of vision. Clinicians caring for people living with HIV should be alert to the complications of leishmaniasis that can occur before and during treatment.
Introduction
Visceral leishmaniasis (VL) is increasingly seen throughout Europe due to travel. It is transmitted by female phlebotomine sandflies. In endemic areas it causes mainly asymptomatic infection. However, symptomatic infection is increasingly found in HIV-positive adults. 1 It can affect the bone marrow, spleen, liver, gastric mucosa, biliary tract and kidneys. To the best of our knowledge, only three cases of uveitis secondary to leishmaniasis in HIV-positive patients have been reported in the literature to date. We present this unusual case of uveitis as part of a leishmaniasis immune reconstitution inflammatory syndrome (IRIS) in a person living with HIV.
Case report
Pathology results.
Computed tomography scanning of his abdomen and pelvis revealed hepatosplenomegaly and widespread lymphadenopathy. Renal ultrasound showed enlarged hyperechoic kidneys. Inguinal lymph node (LN) biopsy showed infiltration of lymphoid tissue by large histiocytes containing abundant intracytoplasmic Leishman-Donovan bodies. A Leishmania direct antiglobulin test (DAT) result was reported as positive at a titre equal to or greater than 1 in 102,400, and Leishmania donovani complex DNA was detected by PCR performed on blood samples, confirming the diagnosis of VL caused by Leishmania donovani.
He received a blood transfusion, intravenous frusemide and liposomal amphotericin B (4 mg/kg on days 1–5 and then on days 10, 17, 24 and 38).
A post-treatment inguinal LN biopsy showed persistence of Leishmania amastigotes, which prompted a further treatment cycle with liposomal amphotericin B. Inguinal LN biopsy following the second cycle of treatment was negative for leishmaniasis on microscopy.
The patient was referred to the ophthalmologists five months after his negative LN biopsy when the community optometrist noted raised areas on the iris. Ophthalmic examination showed prominent bilateral iris granulomata (Figure 1). Anterior chamber cells and flare were noted. The rest of the ophthalmic examination, including dilated fundus examination and intraocular pressure measurements, were within normal limits. His best corrected visual acuity was 6/4 in both eyes. It was noted that the patient’s CD4 count had risen from 69 cells/mm3 to 288 cells/mm3. A diagnosis was made of uveitis due to IRIS following successful treatment of VL. The patient responded to twice daily topical dexamethasone 0.1%. On follow-up slit lamp biomicroscopy one month later, his iris nodules had resolved and his iritis settled. His renal function and pancytopaenia continue to improve, his CD4 count is now 348 cells/mm3 (19%) and he remains on maintenance treatment with monthly liposomal amphotericin.
Iris granuloma
Discussion
Leishmaniasis is predominantly a tropical disease. Except for travel cases, VL secondary to L. donovani is seen mainly in Africa and Asia, while L. infantum is found in the Mediterranean region. 2 In this patient, L. donovani complex was detected by PCR; however, his travel history excluded Africa and Asia. The patient had taken frequent holidays to Spain in the preceding three years and this was felt to be the likely place of acquisition of the infection. VL is endemic in Mediterranean countries. Its incidence is increasing in Spain due to HIV-related cases. 1 The protozoan parasite is transmitted by the bite of female phlebotomine sandflies. Diagnosis can be by PCR, isoenzyme analysis, serology or light microscopy. 2 Traditionally treatment consisted of pentavalent antimonials. Nowadays liposomal amphotericin B is the preferred treatment option for VL due to toxicity and resistance associated with antimonials. 2
The presence of Leishmania spp. and associated ocular signs has been documented in canines 3 and humans.4–6 Uveitis has been described in association with post-kala-azar dermal leishmaniasis, after a symptom-free period following VL treatment. 7 Another case described bilateral granulomatous uveitis caused by immune reconstitution following successful treatment of leishmania resulting in scleral necrosis and enucleation of one eye with successful treatment of the other with dexamethasone eye drops. 8 The mechanism of this immune reconstitution-like syndrome is presumed to be related to a lack of peripheral blood mononuclear cells targeting Leishmania antigens or a skewed response with Th2 predominance. 9 As a result of the combined antileishmanial and antiretroviral therapy a shift from a predominantly Th2 to a Th1 response may occur, thereby causing the inflammatory ocular changes. 9
The ophthalmic manifestations of leishmaniasis range from relatively minor lid and conjunctival involvement mimicking chalazia to complicated anterior uveitis leading to secondary glaucoma and loss of vision. 10 Clinicians caring for persons living with HIV should be alert to the complications of VL that can occur before and during treatment.
Footnotes
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.