Anterior uveitis can be associated with infectious or noninfectious etiologies, and timely diagnosis is essential to guide appropriate treatment and minimize the potential for systemic morbidity, particularly in cases where non-ophthalmic findings develop [3, 4]. Our patient was undergoing workup for inflammatory bowel disease and arthritis and was treated initially with oral corticosteroids, which may have contributed her protracted disease course. Anterior uveitis is deemed to be idiopathic in approximately 50% of cases and often does not require extensive workup, particularly for the first episode of anterior uveitis; however, a viral etiology (i.e. varicella zoster, herpes simplex, cytomegalovirus, or rubella) should be strongly considered in the differential diagnosis when uveitis is accompanied by ocular hypertension or iris atrophy, both of which were observed in our patient’s case .
VZV-associated anterior uveitis varies in spectrum and appropriate antiviral therapy with corticosteroid may lead to disease resolution in some patients following its acute presentation. However, in other patients, chronic or recurrent disease may develop and require long-term prophylactic antiviral therapy. Complications can include iris atrophy, pupillary abnormalities (i.e. posterior synechiae, pupillary dysmotility from sphincter dysfunction and atrophy), acute IOP elevation, and glaucomatous optic neuropathy. Because of the diffuse and severe iris atrophy, we deemed the mydriasis in our patient to have occurred due to iris sphincter damage. A thalamic stroke extending to the brainstem may also lead to pupillary abnormalities; however, no evidence of brainstem ischemia was observed and the pupillary abnormalities were consistent with the local iris atrophic changes observed. Interestingly, our patient did not show typical cutaneous manifestations and presented at a younger age than most individuals, as VZV anterior uveitis is more commonly observed in elderly patients. Even in the absence of a history of herpetic zoster ophthalmicus, clinical suspicion for a viral process should remain high in patients with characteristic ophthalmic findings including hypertensive anterior uveitis, particularly in conjunction with sectoral iris atrophy . PCR of aqueous humor is a highly sensitive test to confirm the diagnosis following aspiration of intraocular fluid, which can be performed in the ophthalmic clinic setting .
After presenting with anterior uveitis, the patient developed a stroke, which was consistent with CNS vasculopathy previously described with VZV. Prior studies show an up to 10-fold increased stroke risk in patients with VZV as a result of viral infection in the arterial wall of cerebral vasculature. VZV vasculopathy was historically associated with large-vessel stroke and acute hemiplegia, but the clinical spectrum of VZV vasculopathies can include transient ischemic attacks, ischemic and hemorrhagic stroke involving both small and large vessels, aneurysm, cranial neuropathies, and venous sinus thrombosis. While VZV vasculopathy is treatable, this diagnosis is often missed and no antiviral treatment is administered, as one-third of patients have no documented history of a zosteriform rash, and many patients may have normal CSF findings [1, 6, 7, 9]. It is notable that the patient developed CNS vasculopathy despite valacyclovir therapy. Immunohistochemical studies have shown VZV antigen within the adventitial layer of arteries early during infection. Downstream mechanisms in the pathogenesis of vasculopathy include disruption of internal elastic lamina, thickening intima composed of myofibroblasts, potentially contributing to luminal occlusion, and a paucity of smooth muscle cells with subsequent loss of vessel integrity . CD4+ and CD8+ T-cells, CD68+ macrophages, and CD20+ B-cells have also been observed in the adventitia and intima, indicating a role for inflammatory pathways in this disease process. Thus, while appropriate antiviral therapy is paramount to limit viral replication, a number of other disease processes may have contributed to the patient’s unusual disease course .
The differential diagnosis of the combination of anterior uveitis and stroke includes both infectious and noninfectious conditions. These include viral etiologies (VZV, HSV), tuberculosis, syphilis, sarcoidosis, granulomatous polyangiitis, and neuro-Behcet’s disease. Systemic lupus erythematosus and rheumatoid arthritis are less commonly associated with anterior uveitis, and more often associated with scleritis as their predominant ocular inflammatory disease finding, but still warrant consideration in patients with typical systemic findings. Our patient’s treatment of her stroke included empiric intravenous acyclovir by the treating facility given her recent uveitis diagnosis. Ultimately, the patient’s neurologic symptoms and disease findings abated.
The initial diagnosis of VZV-associated hypertensive anterior uveitis, diffuse iris atrophy with pigment release, and disease course was atypical in the patient’s age, degree of pigment change, and the potentially debilitating stroke. Few cases have been reported of a stroke following diagnosis of ocular VZV . However, recognition of the relationship between the ophthalmic and CNS manifestations was important for delivery of multidisciplinary care. In addition, this case emphasizes the importance of differentiating between infectious and noninfectious etiologies of uveitis, as there were additional concerns about VZV persistence and potential disease recurrence in the eye with corticosteroid in the absence of appropriate antiviral or other immunosuppressive medications (i.e. disease-modifying anti-rheumatic drugs targeting uveitis associated with collagen vascular disease). Besides the potential of exacerbating anterior uveitis with immunosuppression, individuals with viral anterior uveitis may also develop sight-threatening retinitis (i.e. acute retinal necrosis) in the setting of delayed diagnoses leading to a resultant delay in antiviral therapy. The recognition of ocular VZV was instrumental for prompt antiviral therapy and identifying the underlying cause of stroke.