Relapse of Birdshot Uveitis after Stopping Immunosuppressive Treatment and Starting Immune Checkpoint Inhibitors for Lung Cancer

Abstract

A 56-year-old Caucasian woman with birdshot uveitis had to stop immunosuppressive treatment with adalimumab due to metastatic squamous lung carcinoma. She was subsequently treated with chemotherapy and pembrolizumab, an immune checkpoint inhibitor (ICI). After stopping adalimumab and starting pembrolizumab, the patient had an inflammatory relapse of birdshot uveitis with macular oedema. Birdshot uveitis is triggered by an unknown antigen presented on the HLA-A29 molecule which activates cytotoxic T-cells. Although immunosuppressive therapy effectively stabilizes birdshot uveitis, it might induce a higher risk of developing cancer. Treatment with ICIs, on the other hand, might exacerbate birdshot uveitis by increasing anti-tumoural immune reaction and inducing off-target autoimmunity.

Diagnosing and Managing Uveitis Associated with Immune Checkpoint Inhibitors: A Review

“…In a small retrospective study involving mostly melanoma patients, age and sex were not found to be significant risk factors, although premenopausal women (under age 52) were more likely to develop higher severity IRAEs and have their ICI treatment Few reports of birdshot-like uveitis induced by ICI therapy exist: our literature review yielded two case reports [157,158]. In the first instance, preexisting BU relapsed during pembrolizumab therapy-a 56-year-old Caucasian female, in the context of a new NSCLC diagnosis, had to discontinue her existing immunosuppressive therapy [158]. Eight months later, her ophthalmologist documented an increase in cystoid macular edema.…”

“…Few reports of birdshot-like uveitis induced by ICI therapy exist: our literature review yielded two case reports [157,158]. In the first instance, preexisting BU relapsed during pembrolizumab therapy-a 56-year-old Caucasian female, in the context of a new NSCLC diagnosis, had to discontinue her existing immunosuppressive therapy [158]. Eight months later, her ophthalmologist documented an increase in cystoid macular edema.…”

“…In some patients with ocular or systemic comorbidities, systemic corticosteroids are not recommended, which limits the treatment choice. Antimetabolites such as azathioprine, mycophenolate mofetil, cyclosporine C, and methotrexate seem to yield good results [68,158]. These molecules are already used in the treatment of chronic ocular inflammatory diseases such as juvenile idiopathic arthritis-associated uveitis.…”