Sir,

Opportunistic infections increase morbidity and mortality in human immunodeficiency virus (HIV)-positive patients. Prophylaxis, including Hepatitis A vaccination (HAV), is recommended for all HIV-positive/Hepatitis A virus seronegative patients.1, 2 Here we describe the occurrence of unilateral autoimmune retrobulbar optic neuritis after HAV in a HIV-infected patient on anti-retroviral therapy (ART) with immune recovery.

Case report

Our patient is a 39-year-old HIV-infected Chinese male on ART (Lamivudine and Efavirenz). His CD4 count was 471 cells/mm3 (range 500–1600 cells) 3 weeks before receiving the first dose of attenuated HAV. He had not received any previous vaccinations after being diagnosed to be HIV positive. He found his vision in the left eye brighter than his right, 6 days after receiving HAV. This persisted until he developed sudden decreased central vision in his left eye, 12 days after vaccination. There was no associated pain on eye movements. Vision in the affected eye was counting fingers closely with a left relative afferent pupillary defect (RAPD), defective colour vision (0/15 Ishihara colour plates), and a central scotoma. There was no associated uveitis or optic disc swelling. Magnetic resonance imaging revealed left optic nerve enhancement with no compressive lesions (Figure 1). Infective (opportunistic) and autoimmune workup were negative. Lumbar puncture showed lymphocytic pleocytosis with otherwise no evidence of tuberculosis, syphilis, cryptococcus, or viral infection. He was treated with intravenous methylprednisolone for 3 days, with improvement of visual acuity (6/60) and colour vision (6/15 Ishihara plates) by day 3 of treatment. This was followed by a tapering course of oral prednisolone over 2 weeks with further improvement of visual acuity to 6/15 by 1 week and subsequently to 6/9, colour vision (15/15 Ishihara plates), and significant resolution of the central scotoma by 3 weeks (Figures 2 and 3). He has remained stable after a 14-month period of observation with a residual mild left RAPD, interval development of mild temporal disc pallor, and final visual acuity of 6/12. His CD4 counts remained stable at 444 cells/mm3 after 1 year.

Figure 1
figure 1

MRI of brain using gadolinium; T1-weighted image showing enhancement of the intra-conal segment of the left optic nerve, sparing the pre-chiasmal portion.

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Figure 2
figure 2

HVF at presentation showing a dense scotoma.

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Figure 3
figure 3

HVF 3 weeks post-treatment showing significant resolution.

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Comment

This is the first report in published literature of optic neuritis after HAV in a HIV-positive patient. Antibody response after vaccination is reduced in HIV-infected patients.1, 3 ART-induced increase in CD4 counts has resulted in improved vaccination response rates.4 Higher CD4 counts and lower viral load at the time of vaccination have been associated with higher rates of antibody response and seroconversion after vaccination.1, 5 The immunological recovery also means an increased predisposition to immune-mediated reactions.

Considerable controversy surrounds the question of the presence of a causal link between vaccinations and the development of multiple sclerosis (MS) or optic neuritis, and many differing opinions have been heard. Post-vaccination optic neuritis has been reported with vaccination against influenza, hepatitis B, anthrax, and meningococcus infection in non-HIV-infected patients as case reports.6, 7, 8, 9, 10, 11 It is, however, difficult to distinguish a coincidental temporal association from a true causal association merely based on individual case reports. A multicenter, randomised, double-blind, placebo-controlled trial of influenza vaccination in patients with MS found no increased exacerbation rate, nor a change in disease course over a period of 6 months post-vaccination.12 Payne et al13 reported no statistically significant association between optic neuritis and vaccination against anthrax, influenza, hepatitis B, or smallpox in his study of 1131 cases and 3393 controls. A case–control study published in 2001 found no association between hepatitis B vaccination and the development of MS.14 However, the study was limited to cohorts of nurses making the findings only applicable to women. A retrospective case–control study15 published by Destefano et al in 2003 refuted the causal association between vaccination against hepatitis B, influenza, tetanus, measles, or rubella and the development of multiple sclerosis or optic neuritis. The authors attempted to minimise the limitations of its retrospective study by modifying inclusion criteria to reduce recall bias and by using data analysis to reduce the error that may result from their differential participation rates of case subjects and controls. In conflict, a more recent prospective case–control study published in 2004 in Neurology, involving 163 cases of MS and 1604 controls, reported an increased risk of MS associated with recombinant hepatitis B vaccination.16 No increased risk was found with influenza or tetanus vaccinations in the study.

To date, there have been no case–control study or randomised trial with regard to HAV in HIV-infected patients. The workup for opportunistic infection in our patient was negative. He responded well to steroid therapy, with a rapid course of recovery beginning from day 3 of treatment and achieving significant visual improvement by 1 week. The marked response to steroids lends weight to an immune-mediated aetiology as the underlying cause. Although immunologically mediated conditions are usually bilateral, up to 20% have a unilateral presentation in previously reported cases of post-vaccination optic neuritis.11 The course of steroid therapy (initial intravenous with subsequent oralisation) did not result in exacerbation of the HIV infection and had no adverse effect on CD4 counts. The ART regimen that he was on (lamivudine and efavirenz) has no reported causal association with optic neuritis.

The aetiology of the optic neuritis cannot be conclusively determined, but the temporal relationship between the HAV and the development of optic neuritis suggests a possible association. Systemic steroid therapy was useful in achieving prompt recovery of vision and optic nerve function, and did not exacerbate HIV infection or lead to progression to clinical AIDS.

Conflict of interest

The authors declare no conflict of interest.