Uveitis Due toLeishmania majoras Part of HAART‐Induced Immune Restitution Syndrome in a Patient with AIDS

Although it is not an AIDS-defining illness, visceral leishmaniasis (VL) is a severe opportunistic infection in HIV-infected patients. VL is common in southern Europe [1]. Most reported cases of HIV-VL coinfection involve Leishmania infantum and generally occur when the patient's CD4 cell count is µ200 cells/mm3. Leishmania amastigotes are found in atypical locations (mostly in the gastrointestinal and respiratory tracts) in severely immunocompromised patients [2]. Cutaneous lesions in patients with VL are being reported with increasing frequency; however, exclusively cutaneous leishmaniasis has remained rare in patients with HIV infection [3]. We describe a patient with AIDS and diffuse cutaneous and ganglionary leishmaniasis, without visceral involvement, due to Leishmania major. The patient developed isolated severe uveitis due to leishmaniasis while receiving highly active antiretroviral therapy (HAART), which led to the loss the right eye, despite the administration of antiparasital therapy. In September 1997, an HIV-infected, 34-year-old man from Burkina Faso (CD4 cell count, 4 cells/mm3; plasma virus load, 381,000 RNA copies/mL) had diffuse cutaneous and ganglionary leishmaniasis diagnosed by means of culture of several cutaneous and ganglionar biopsy smears. The results of cultures of blood, bone marrow, and gastrointestinal tract samples were negative. PCR amplification of a repetitive noncoding sequence and additional molecular typing by sequence analysis contributed to the diagnosis of Leishmania major zymodene MON-26 infection—the second case reported in a patient from Burkina Faso and the second case reported in association with HIV infection [4]. Treatment with amphotericin B (50 mg/day given iv for 28 days) led to complete regression of the patient's lesions. The patient received primary prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX; 80/400 mg/d) and secondary prophylaxis with meglumine antimoniate (1200 mg im per month). Two weeks after he started receiving therapy, cultures of blood and bone marrow samples were positive for Mycobacterium avium, and treatment with clarithromycin (1 g/day), ethambutol (1200 mg/day), and rifabutin was started. The patient began to receive HAART in November 1997. Since January 1998, his plasma virus load has been µ50 copies/mL. Bilateral granulomatous anterior uveitis appeared in March 1998, when the patient's CD4 cell count was 91 cells/mm3. Rapid resolution of the inflammation in the left eye occurred after the patient was treated with topical dexamethasone. Mild uveitis persisted in the right eye. Rifabutin-induced uveitis was suspected. In May 1998, despite an interruption in rifabutin therapy, visual acuity of the right eye quickly worsened to light perception and pain became intense. Slit-lamp examination revealed granulomatous uveitis with diffuse dense mutton-fat keratic precipitates, anterior chamber cell reactions (3+ [severe]), and flair reactions (3+). Intraocular pressure increased to 40 mm Hg, and examination of the fundus of the eye became impossible. A nodule was also noted in the iris and resected. No other trouble was noted. Despite receiving treatment with IFN-γ (75 µg/day) and daily doses of lipidassociated amphotericin B (150 mg/day), the patient's uveitis worsened, with extension of the inflammation to the orbit and scleral necrosis. This led to enucleation in December 1998, when the patient's CD4 cell count was 198 cells/mm3. Pathological examination of the resected nodule and the resected eye showed inflammation that contained the amastigot form of Leishmania, but the results of cultures for Leishmania species remained negative. Three weeks later, treatment with lipid-associated amphotericin B and IFN-γ was stopped. Clarithromycin and ethambutol were stopped in October 1998 without relapse of mycobacterial infection. TMP-SMX was stopped in October 2000. No relapse of uveitis or dermatitis occurred during a 38-month follow-up period, during which time the patient was receiving HAART, IL-2 (started in February 2000), and meglumine antimoniate (1200 mg per month). In November 2000, the patient's CD4 cell count was 528 cells/mm3. The HAART-induced immune restitution syndrome, in which CD4 T cell reactivity against opportunistic pathogens occurs, has been described even in severely immunosuppressed patients. Short-term complications include flare-up of hepatitis B preceding seroconversion, atypical mycobacterial lymphadenitis [5], and CNS cryptococcosis. Delayed-occurrence complications include cytomegalovirus vitritis, cryptococcal lymphadenitis [6], Graves' disease, mixed cryoglobulinemia, and sarcoidosis [7], and post—kala-azar dermal leishmaniasis was recently added to this list [8]. To the best of our knowledge, only 7 reported cases of uveitis have been considered to be post—kala-azar-ocular leishmaniasis [9]. We report the first case of uveitis due to leishmaniasis in a patient with AIDS that occurred as part of HAART-induced immune restitution syndrome. We confirm the possibility of long-term remission of leishmaniasis in patients receiving HAART. Even if patients are receiving HAART, interruption of secondary prophylaxis is not yet recommended in cases of leishmaniasis [10].