Cytomegalovirus Retinitis in a Patient Taking Tocilizumab: A Case Report

Introduction

Tocilizumab is a humanized immunoglobulin G1 kappa monoclonal antibody that blocks human interleukin-6 (IL-6) receptor. ¹ It was approved in the United States in 2010 for treatment of rheumatoid arthritis, and later in 2017 for maintenance and remission of giant cell arteritis (GCA). ² In the present study, we report what we believe is the first case of cytomegalovirus (CMV) retinitis in a patient taking tocilizumab for GCA.

Methods

Case Report

A 78-year-old African American woman with no significant past medical history and an ocular history of primary open-angle glaucoma presented to the retina clinic with vitritis in the right eye. She had been diagnosed with biopsy-proven GCA 4 months earlier, when she developed an anterior ischemic optic neuropathy resulting in count fingers vision of the right eye. She was taking 30 mg of prednisone daily and 162 mg tocilizumab subcutaneously weekly. On presentation to the retina specialist, she had a visual acuity of 1/200 OD and 20/32 OS, keratic precipitates, and flare in the anterior chamber with trace cells. Her intraocular pressures (IOPs) were right eye 20 mm Hg and left eye 19 mm Hg. She had moderate debris and cells in the vitreous, with retinitis noted in the superior and inferior periphery (Figure 1). She was started on topical steroids, which improved anterior segment inflammation, but developed an IOP of 30 mm Hg in the right eye. She was then referred to her rheumatologist, who found no evidence of systemic infection and was hesitant to stop the prednisone or tocilizumab, given the risk of recurrent GCA.

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Figure 1.

Fundus photo of the right eye exhibiting retinitis with moderate debris and cells in the vitreous.

The patient received a diagnostic vitrectomy with polymerase chain reaction of the vitreous and was started empirically on valacyclovir for suspected herpes retinitis associated with acute retinal necrosis. The results from the polymerase chain reaction were negative for herpes simplex and zoster, but positive for CMV. The tocilizumab was immediately discontinued and she was switched to valganciclovir by mouth. She was tested for HIV and this was negative. Over the next 3 months, her retinitis gradually resolved on the valganciclovir, with no recurrence 4 months after discontinuing the valganciclovir (Figure 2). Her GCA has been controlled following gradual tapering of the oral prednisone for more than 1 year from 30 mg, down to 8 to 10 mg per day.

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Figure 2.

Interval improvement of retinitis of the right eye after 3 months of treatment with valganciclovir.

Results

Our case describes CMV retinitis occurring in an otherwise immunocompetent patient taking tocilizumab and prednisone for GCA. CMV retinitis can result in a posterior uveitis, but this usually occurs in severely immunocompromised individuals. However, it has been reported in immunocompetent patients, sometimes in the setting of recent intravitreal steroid injection. ^3,4 CMV viremia has in fact been reported in several cases of patients taking tocilizumab for uncontrolled rheumatoid arthritis. ^5,6 To our knowledge, CMV retinitis has not been described in the setting of tocilizumab use for GCA. Although the patient was also on oral prednisone, this relatively standard dosage and treatment has not been reported to result in CMV retinitis.

IL-6 signaling has been implicated in releasing acute-phase responses that drive inflammatory mediators of GCA. Tocilizumab inhibits signaling by binding to the α-chain of human IL-6 receptor, and has been shown to successfully induce and maintain GCA remission, thereby allowing faster tapering of concurrent corticosteroid use. ² In May 2017, tocilizumab was approved for the treatment of GCA. In a 2016 clinical trial, Villiger et al found tocilizumab to be effective in the induction and maintenance of remission in patients with GCA. ² In the tocilizumab group, 3 patients (15%) experienced serious adverse gastrointestinal events, compared to the placebo group, in which 1 patient (10%) experienced such events. In the tocilizumab group, 1 patient (5%) experienced an eye infection due to Moraxella catarrhalis and herpes, whereas no patient in the placebo group experienced such infection. ²

Interestingly, IL-6 has been shown to play a role in CMV infection, possibly through protein kinase signaling on dendritic cell differentiation to promote CMV reactivation. ⁷ Tocilizumab has been shown to selectively bind soluble and membrane-bound IL-6 receptors but not other IL-6 family cytokines. It is possible that nontargeted IL-6 receptors are upregulated as a result of tocilizumab inhibition. ¹

Conclusions

We report the first case of CMV retinitis following treatment with tocilizumab for GCA. Though initially thought to be herpetic, vitreous biopsy was diagnostic and the patient was able to receive the appropriate treatment and resolution. Clinicians should therefore be aware of this potential ocular complication because tocilizumab is now increasingly prescribed for several different diseases associated with impaired regulation of IL-6.