Bonus online case: Cytomegalovirus immune recovery uveitis in AIDS

A patient with AIDS and subacute monocular vision deterioration.


The patient

A 40-year-old man with AIDS presented with subacute monocular vision deterioration. His symptoms started two weeks prior to presentation with sudden appearance of numerous small “dark spots” in his left eye. Two months prior, he had been diagnosed with AIDS. At the time, he had a CD4 count of 39 cells/µL and a viral load of 35,000 copies/mL, as well as cachexia, oral candidiasis, and Campylobacter enteritis. He was started on antiretroviral therapy (ART) and trimethoprim-sulfamethoxazole prophylaxis for opportunistic infection. He reported adhering to these therapies.

On admission, his vitals were normal and he reported no eye pain. External and visual acuity examination of the left eye showed scleral injection, a minimally reactive pupil, and decreased visual acuity in the superior visual fields. A slit lamp exam revealed corneal precipitates, anterior chamber debris, and vitreous haze. A retinal exam revealed a white, necrotizing, inferotemporal lesion. He had a normal right eye exam. A complete neurologic, head, and neck exam was normal. A skin examination was notable for diffuse lesions consistent with molluscum contagiosum.

Labs were significant for a CD4 count of 150 cells/µL, and HIV viral load was undetectable. The cytomegalovirus (CMV) viral load in the vitreous fluid was 440,000 copies/mL (reference range, 0 copies/mL). The patient was treated with steroid eyedrops, intravitreal foscarnet, and systemic valganciclovir with rapid visual improvement.

The diagnosis

This patient's diagnosis is CMV immune recovery uveitis (IRU). CMV IRU is a recognized subtype of the immune reconstitution inflammatory syndrome (IRIS). IRIS occurs following ART initiation as the result of an expanding population of CD4 cells responding to specific opportunistic infections and causing pathologic inflammation. The hallmarks of IRIS include clinical deterioration following ART initiation; reduction in HIV viral load following ART initiation; and an inability to attribute symptoms to medication effect, treatment failure, nonadherence, or a previously recognized and successfully treated infection. IRIS has been described in patients with mycobacterial, CMV, cryptococcal, pneumocystis, and toxoplasmosis infections.

CMV retinitis is an AIDS-defining illness common in patients with advanced HIV (CD4 count <50 cells/µL). CMV infection is necessary for a patient to be at risk for CMV IRU after initiation of ART. It is estimated that up to 38% of patients with healed CMV retinitis will develop CMV IRU after initiation of ART. CMV retinitis that improves initially with treatment but then worsens with successful ART is termed “paradoxical” CMV IRU. In patients who show no evidence of CMV infection on initial presentation but subsequently develop ocular CMV, the infection is described as “unmasked” CMV IRU. Paradoxical and unmasked CMV IRU are much less common forms of this condition and have only been described in case series.

While ocular CMV infections generally present as retinitis with blurry vision, field defects, floaters, or discomfort, CMV IRU can present with necrotizing retinitis or any ocular inflammation, including anterior uveitis, vitritis, papillitis, cystoid macular edema, and epiretinal membranes. CMV IRU can resolve completely with early treatment, but delay can lead to severe, chronic sight-threatening damage from development of cystoid macular edema or epiretinal membranes.

Treatment of both CMV retinitis and CMV IRU includes a systemic antiviral such as valganciclovir, which is generally continued until CD4 cell count is greater than 200 cells/µL for three or more months. In primary CMV retinitis, steroid therapy is contraindicated as it may worsen the CMV infection through further immune suppression. Conversely, in CMV IRU, topical ophthalmic steroids are an integral part of treatment to mitigate the inflammatory response causing the ocular damage. Because topical ocular steroids have adverse effects such as glaucoma and cataracts, patients with CMV IRU receiving steroid eyedrops require frequent ophthalmologic monitoring to minimize the dosing and duration of steroid treatments. Adjuvant eyedrops are recommended as prophylaxis against glaucoma and bacterial superinfections.

Pearls

  • CMV IRU is a recognized subtype of IRIS and can present with necrotizing retinitis or any ocular inflammation, including anterior uveitis, vitritis, papillitis, cystoid macular edema, and epiretinal membranes.
  • The treatment of CMV IRU includes systemic antivirals to treat the CMV infection and topical ophthalmic steroids to mitigate the destructive host inflammatory response.

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