Fulminant ocular leishmaniasis in an HIV-1-positive patient

There is increasing evidence that the eye can be involved in Leishmania infection, especially in immunocompromised individuals. We report a HIV-positive Eritrean man, who was referred to our ophthalmology department after corticosteroid therapy had failed for a serious bilateral sight-threatening inflammation, which had been attributed to immune recovery syndrome (IRS). In 1999, after settling in the Netherlands, highly active antiretroviral therapy (HAART) had been initiated upon testing HIV positive with a low CD4 cell count (60 × 106 cells/l). Progressive weight loss and visceral complaints developed in 2000–2001. Serological tests and polymerase chain reaction (PCR) were positive for Leishmania donovani, and amastigotes were demonstrated in bone marrow aspirate and duodenal biopsies. One month into therapy with intravenous sodium stibogluconate, PCR had become negative in the bone marrow and peripheral blood, and secondary prophylaxis been initiated on a weekly basis. During this regimen, the immunological and virological parameters as well as the clinical condition had improved substantially. Secondary prophylaxis was withdrawn in December 2001 (CD4 cell count 740 × 106 cells/l). Visual complaints, caused by persistent bilateral active uveitis, started in January 2002 after a transient acute episode of malaise, fever and lymphadenopathy. There were no signs of recurrent Leishmania, and tuberculosis cultures, syphilis tests and Leishmania PCR in the peripheral blood remained repeatedly negative. Because there was no evidence of an infectious origin, the uveitis was attributed to IRS, and local and systemic corticosteriods were administered without success. The patient was referred to our ophthalmology department in November 2002, visual acuity being no more than light perception in both eyes. On admission, slit-lamp examination revealed serious bilateral uveitis, with dense keratic precipitates, massive granulomas, nodules and a mixed hypopion. The anterior segment of the left eye was completely destroyed: the pupil could hardly be distinguished and the lens was not visible. The ocular fundus could not be visualized by fundoscopy. Leishmania DNA was demonstrated in the aqueous humour; PCR for tuberculosis, cytomegalovirus, and Toxoplasma gondii was negative. All cultures were also negative. In an attempt to save the right eye, intravenous natriumstibogluconate was reinitiated in combination with intravenous fluconazole. HAART was switched after genotyping had demonstrated resistance for two mutations on the reverse transcriptase gene. On this therapy the ocular condition of the right eye stabilized. The remaining vision of this eye was finger counting (1/60). The left eye was enucleated. Histopathological examination showed massive granulomatous infiltrates throughout the whole eye. The lens had totally vanished, the iris was necrotic. Iris pigments had diffusely spread, and it was not possible to distinguish between iris pigment and amastigotes in the specimens. PCR analysis was positive for L. donovani in the aqueous humour of both eyes, in the vitreous fluid of the enucleated left eye, and in the cerebrospinal fluid (CSF). Cultures and PCR analyses for tuberculous and non-tuberculous Mycobacteriae, T. gondii, and cytomegalovirus were negative. Ocular involvement in Leishmania is rare [1]. Blanche et al. [2] described a similar case in a patient with AIDS. Severe granulomatous anterior uveitis appeared several months after the initiation of HAART. They attributed the ocular picture to Leishmania major as part of HAART-induced IRS. Gontijo et al. [3] reported simultaneous cutaneous, visceral and ocular involvement during Leishmania braziliensis in an immunosuppressed transplant patient. The same species of Leishmania was isolated from all tissues involved. Central nervous system involvement with detectable amastigotes in the CSF was reported in 1996 by Prasad and Sen [4]. Garcia-Alonso et al. [5] reported detectable anti-Leishmania IgG in both the aqueous humour and CSF during Leishmania infections in dogs. IRS, considered a HAART-induced syndrome in which T-cell reactivity against opportunistic pathogens occurs, has been described early after the initiation of antiretroviral therapy. In the eye, IRS is usually a mild to moderate inflammatory reaction, hardly obscuring fundoscopic examination, and usually responds well to topical steroids [6]. Extensive granulomas are seldom seen. In our patient the uveitis occurred 26 months later, and 9 months after a substantial increase in the CD4 cell count had been achieved. This makes the diagnosis of IRS less likely. Moreover, the deterioration after corticosteroids is not in favour of this diagnosis, and rather points towards an infectious aetiology. The development of such a devastating ocular disease when there was no evidence of reactivation of the visceral infection may seem remarkable. However, organ systems such as the eye and brain often behave as rather circumscript and isolated body compartments. In such compartments, inflammatory processes can develop locally, without systemic signs and symptoms. Physicians dealing with HIV-infected patients should be aware of uncommon manifestations of rare co-infections. This is of growing importance, because of the increased migration of individuals from countries where such infections are endemic.