A case of panuveitis with hypopyon due to presumed ocular leishmaniasis in a HIV patient
© Couture et al.; licensee Springer. 2014
Received: 12 June 2014
Accepted: 15 July 2014
Published: 29 August 2014
Post-kala-azar dermal leishmaniasis is a well-known immunologic cutaneous reaction. There are few case reports of ocular leishmaniasis. It is a sight-threatening condition that needs to be rapidly recognized and treated to avoid permanent visual loss. Ocular leishmaniasis panuveitis can present with severe inflammation in patients with highly active anti-retroviral therapy (HAART)-induced immune reconstitution syndrome.
A case of a 40-year-old man, human immunodeficiency virus (HIV) positive on HAART, with a presumed diagnosis of ocular leishmaniasis, is presented. He had a past history of visceral leishmaniasis and was referred to the uveitis service with rapidly worsening panuveitis and counting fingers vision in both eyes. On empirical anti-leishmania therapy and systemic steroids, the visual acuity of the left eye improved to 6/9 but remained poor in the right eye. Based on the medical history, improvement with therapy and the exclusion of other common infections, a presumed diagnosis of ocular leishmaniasis-related panuveitis was made.
A major immune reaction against lingering parasites may play a key role in the pathogenesis of this sight-threatening and rapidly progressive condition. Both the infection and the immune reaction should be treated.
KeywordsOcular leishmaniasis Granulomatous panuveitis Immune reconstitution uveitis HIV
Leishmaniasis is caused by Leishmania parasites transmitted by sandflies to mammalian hosts. It is most commonly found in rural impoverished areas of the Far and Middle East; Central, Western and Eastern Europe; Africa; Asia; and Central and South America . There are about two million new cases per year . Three clinical syndromes have been described: the cutaneous disease, the mucocutaneaous disease and the visceral disease, also named kala-azar . The cutaneous form is the commonest form. Visceral leishmaniasis (VL) is the most severe and may have a 75% to 95% mortality rate within the first 2 years if left untreated.
Post-kala-azar dermal leishmaniasis is an immunologic and cutaneous reaction in patients treated for visceral leishmaniasis . In human immunodeficiency virus (HIV)-positive patients, the development of this cutaneous condition has been reported as a manifestation of immune reconstitution syndrome .
Ocular leishmaniasis has rarely been reported in the literature -. The pathogenesis of ocular leishmaniasis remains unclear. It is a sight-threatening condition, which needs to be rapidly recognized and treated to prevent permanent visual loss. Ocular leishmaniasis panuveitis has been postulated to be a part of highly active anti-retroviral therapy (HAART)-induced immune reconstitution syndrome in a co-infected HIV patient .
Written informed consent was obtained from the patient for the publication of this report and any accompanying images. Our patient was originally from Eritrea. He immigrated to the UK in 2005. He had been found to be HIV-1 positive in 2008 when he presented with VL. He then had good viral load suppression with anti-retroviral therapy, but his maximum CD4 count was only 120 cells/mm3 (baseline 55 cells/mm3 at diagnosis); he had not suffered opportunistic infections. However, his VL recurred in June 2012 with a relapsing course requiring five admissions despite appropriate prophylaxis with miltefosine and/or pentamidine. He had a classical presentation of VL with fever, fatigue, anorexia, weight loss, skin rash and splenomegaly. Amastigotes of Leishmania donovani were found on biopsy of split skin smear, and he responded to prolonged treatment with liposomal amphotericin B.
Microbiological analysis from vitreous biopsy was unremarkable and negative for microorganisms, including Leishmania, toxoplasmosis, syphilis, tuberculosis, herpes simplex virus (HSV), varicella-zoster virus (VZV) and cytomegalovirus (CMV). As the patient was showing signs of systemic and ocular improvement, he was kept on anti-leishmania therapy plus oral and topical steroids.
On the last follow-up examination in November 2013, the inflammation improved with the visual acuity improving to counting fingers and 6/24 in the right and left eyes, respectively (Figure 4B). Anterior segment examination revealed resolution of inflammation with presence of posterior synechiae and posterior subcapsular cataract in the right eye. He was maintained on sodium stibogluconate and a tapering dose of oral corticosteroids, and his vision continued to improve to 6/9 in the left eye. The ultrasound of the posterior segment showed a complete involution of the sessile nodular granulomatous swelling in both eyes (Figure 5B). Unfortunately, after the last follow-up, the patient expired due to his systemic illness and concurrent infections.
Visceral leishmaniasis (VL) may range from asymptomatic to a disseminated form. Patients with VL and HIV co-infection usually have a CD4 count less than 200 cells/μl, may have involvement of atypical sites, like the eye, and are prone to a relapsing VL course despite appropriate treatment ,. Leishmaniasis can present with severe fulminant uveitis in patients with highly active anti-retroviral therapy (HAART)-induced immune reconstitution syndrome . HAART has resulted in decrease in incidence of VL especially in the Mediterranean . The recent studies have implicated the inadequacy of the current treatment modality for HIV-associated visceral leishmaniasis . Lifelong prophylaxis is reported to be necessary for HIV-associated visceral leishmaniasis .
Ocular leishmaniasis has been described in the literature as chronic blepharo-conjunctivitis and panuveitis -. However, the pathogenesis of this condition is not well established. El Hassan et al. published a short series of six patients with presumed post-kala-azar ocular leishmaniasis with two cases having severe granulomatous panuveitis . None of the cases were confirmed microbiologically. All patients responded to systemic anti-leishmania therapy plus topical steroids. Another series published by Khalil et al. reported five cases of ocular leishmaniasis panuveitis . In this series, two patients lost their sight permanently, but three were successfully treated with oral and topical corticosteroids along with anti-leishmania treatment.
A case of fulminant ocular leishmaniasis in an HIV-positive patient was reported in 2004. This HIV-positive patient on HAART for 2 years was previously diagnosed and treated for VL. He also presented with a severe bilateral granulomatous panuveitis with hypopyon. However, in this case, leishmaniasis was confirmed by positive PCR analysis in the aqueous humour and the cerebrospinal fluid .
Another similar HIV-positive case was also reported in 2002. The patient had an initially low CD4 count and lost his only eye despite anti-leishmania therapy. The parasite was not identified until the enucleated eyeball showed severe inflammation containing leishmania amastigotes. This situation was reported as a HAART-induced immune restitution syndrome due to leishmaniasis .
Like other cases reported in the literature, our patient with ocular leishmaniasis also has relapsed VL. Though there was no further evidence of leishmanial infection, he responded well to anti-leishmania therapy. The rationale for giving concurrent oral corticosteroid therapy was possible immune reconstitution response as our patient was on HAART therapy. Well known in CMV retinitis, an immune restitution phenomenon has also been described in other conditions. Mycobacterium avium subclinical infection has been associated with fever, leucocytosis and lymphadenitis after initiation of HAART . Meningitis has also been reported in patients with latent cryptococcal infection of the central nervous system after starting HAART . Biswas et al. have earlier reported a single case report of macular haemorrhage in both eyes of an immunocompetent patient who was having opportunistic infection with leishmania . In our case, the initial CD4 count was low (117 cells/μl) when the first and mild ocular symptoms were reported. A few months later, subsequent CD4 count increase to 330 cells/μl with concomitant severe granulomatous panuveitis. Systemic corticosteroids were necessary to control the inflammation. Hence, the possibility of immune reconstitution syndrome could not be ruled out in our case, which is quite extensively reported in the literature . Biswas et al. have also reported a case of immune reconstitution in an immune-compromised individual after initiating protease inhibitors . Based on the patient response to treatment, empirical anti-leishmania therapy and systemic corticosteroid may have contributed to prevent ocular morbidity.
The diagnosis of ocular leishmaniasis-related panuveitis is difficult and requires a high index of suspicion with good knowledge of the past medical history. A bilateral and severe granulomatous uveitis in an HIV-positive patient with previous history of visceral leishmaniasis should make the clinician suspicious of ocular leishmaniasis. Prompt intervention with systemic therapy is necessary to optimize the outcome. A major immune reaction against lingering parasites might play a key role in the pathogenesis of this rapidly sight-threatening condition. Both the infection and the immune reaction should be kept in mind and targeted when treatment is planned.
- cerebral CT:
cerebral computed tomography
highly active anti-retroviral therapy
human immunodeficiency virus
herpes simplex virus
magnetic resonance imaging
optical coherence tomography
polymerase chain reaction
SC is supported in part by the Canadian National Institute for the Blind (CNIB) Baker Grants and Fellowships. RA is supported by NMRC, MOH, Singapore overseas research training fellowship. This work was supported by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health.
- Control of the leishmaniases WHO Technical Report Series 949 World Health Organization, Geneva; 2010, 1–186. [http://whqlibdoc.who.int/trs/WHO_TRS_949_eng.pdf] http://whqlibdoc.who.int/trs/WHO_TRS_949_eng.pdf
- McGwire BS, Satoskar AR: Leishmaniasis: clinical syndromes and treatment. QJM 2013,107(1):7–14. 10.1093/qjmed/hct116PubMed CentralView ArticlePubMedGoogle Scholar
- Zijlstra EE, Musa AM, Khalil EA, el Hassan IM, el Hassan AM: Post-kala-azar dermal leishmaniasis. Lancet Infect Dis 2003,3(2):87–98. 10.1016/S1473-3099(03)00517-6View ArticlePubMedGoogle Scholar
- Antinori S, Longhi E, Bestetti G, Piolini R, Acquaviva V, Foschi A, Trovati S, Parravicini C, Corbellino M, Meroni L: Post-kala-azar dermal leishmaniasis as an immune reconstitution inflammatory syndrome in a patient with acquired immune deficiency syndrome. Br J Dermatol 2007,157(5):1032–1036. 10.1111/j.1365-2133.2007.08157.xView ArticlePubMedGoogle Scholar
- El Hassan AM, Khalil EA, el Sheikh EA, Zijlstra EE, Osman A, Ibrahim ME: Post kala-azar ocular leishmaniasis. Trans R Soc Trop Med Hyg 1998,92(2):177–179. 10.1016/S0035-9203(98)90736-2View ArticlePubMedGoogle Scholar
- Khalil EA, Musa AM, Younis BM, Elfaki ME, Zijlstra EE, Elhassan AM: Blindness following visceral leishmaniasis: a neglected post-kala-azar complication. Trop Doct 2011,41(3):139–140. 10.1258/td.2011.110058View ArticlePubMedGoogle Scholar
- Meenken C, van Agtmael MA, Ten Kate RW, van den Horn GJ: Fulminant ocular leishmaniasis in an HIV-1-positive patient. AIDS 2004,18(10):1485–1486. 10.1097/01.aids.0000131348.83913.72View ArticlePubMedGoogle Scholar
- Blanche P, Gombert B, Rivoal O, Abad S, Salmon D, Brezin A: Uveitis due to Leishmania major as part of HAART-induced immune restitution syndrome in a patient with AIDS. Clin Infect Dis 2002,34(9):1279–1280. 10.1086/338720View ArticlePubMedGoogle Scholar
- Alvar J, Aparicio P, Aseffa A, Den Boer M, Cañavate C, Dedet JP, Gradoni L, Ter Horst R, López-Vélez R, Moreno J: The relationship between leishmaniasis and AIDS: the second 10 years. Clin Microbiol Rev 2008,21(2):334–359. 10.1128/CMR.00061-07PubMed CentralView ArticlePubMedGoogle Scholar
- Desjeux P, Alvar J: Leishmania /HIV co-infections: epidemiology in Europe. Ann Trop Med Parasitol 2003,97(Suppl 1):3–15. 10.1179/000349803225002499View ArticlePubMedGoogle Scholar
- Bernier R, Barbeau B, Tremblay MJ, Olivier M: The lipophosphoglycan of Leishmania donovani up-regulates HIV-1 transcription in T cells through the nuclear factor-kappaB elements. J Immunol 1998,160(6):2881–2888.PubMedGoogle Scholar
- Villanueva JL, Alarcón A, Bernabeu-Wittel M, Cordero E, Prados D, Regordán C, Alvar J: Prospective evaluation and follow-up of European patients with visceral leishmaniasis and HIV-1 coinfection in the era of highly active antiretroviral therapy. Eur J Clin Microbiol Infect Dis 2000,19(10):798–801. 10.1007/s100960000364View ArticlePubMedGoogle Scholar
- Jarvis JN, Lockwood DN: Clinical aspects of visceral leishmaniasis in HIV infection. Curr Opin Infect Dis 2013,26(1):1–9. 10.1097/QCO.0b013e32835c2198View ArticlePubMedGoogle Scholar
- Race EM, Adelson-Mitty J, Kriegel GR, Barlam TF, Reimann KA, Letvin NL, Japour AJ: Focal mycobacterial lymphadenitis following initiation of protease-inhibitor therapy in patients with advanced HIV-1 disease. Lancet 1998, 351: 252–255. 10.1016/S0140-6736(97)04352-3View ArticlePubMedGoogle Scholar
- Woods ML, MacGinley R, Eisen DP, Allworth AM: HIV combination therapy: partial immune restitution unmasking latent cryptococcal infection. AIDS 1998,12(12):1491–1494. 10.1097/00002030-199812000-00011View ArticlePubMedGoogle Scholar
- Biswas J, Mani B, Bhende M: Spontaneous resolution of bilateral macular haemorrhage in a patient with kala-azar. EYE 2000, 14: 244–246. 10.1038/eye.2000.64View ArticlePubMedGoogle Scholar
- Biswas J, Choudhry S, Kumarasamy N, Solomon S: Immune recovery vitritis presenting as panuveitis following therapy with protease inhibitors – a case report. Indian J Ophthalmol 2000,48(4):313–15.PubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.