Non-arteritic anterior ischemic optic neuropathy in a patient with xiap deficiency: Expanding the inflammatory ocular findings in x-linked lymphoproliferative disorders

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Conference Proceeding

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Journal of Clinical Immunology


Background: X-linked inhibitor of apoptosis protein (XIAP) deficiency is due to pathologic variants in XIAP/BIRC4, and is most often associated with hemophagocytic lymphohistiocytosis and inflammatory bowel disease. Non-arteritic anterior ischemic optic neuropathy (NAION) is an ophthalmologic condition characterized by idiopathic ischemic infarction of the optic nerve head. It typically presents in older patients with risk factors for vascular disease. In those situations it does not respond to immunomodulatory agents. Although other inflammatory ocular manifestations of XIAP deficiency, such as uveitis, have been documented, this is the first described case of NAION in this disease spectrum.

Case: We report a 51 year-old man who presented with painless, unilateral vision loss in the right eye in 2012, at 44 years of age. Serial visual field testing demonstrated inferior field vision loss. Fundoscopic exam initially revealed a swollen right optic disc. Optical coherence tomography (OCT) demonstrated marked retinal nerve fiber layer thinning in the superior retina, consistent with the known inferior visual field defect, both findings characteristic of NAION. Treatment with IV steroids produced little improvement in vision, but there was no further progression. Two years later the patient began experiencing recurrent high fevers and developed splenomegaly. Elevated transaminases and concern for lymphoproliferative disease prompted a splenectomy and liver biopsy. Both the spleen and liver biopsy were positive for EBV but were negative for malignancy. Bone marrow biopsy was unrevealing. Genetic testing identified a pathogenic variant in XIAP/ BIRC4 (1141C>T), and the patient was treated with high dose oral steroids resulting in an improvement in symptoms. Subsequently, therapy with anakinra was started and steroids were tapered. During the steroid taper, he noticed a change in the vision of his left eye consistent with NAION, as well as worsening of his colitis. There was loss of the inferior visual field and fundoscopic exam was significant for left optic disc swelling. OCT noted superior retinal nerve fiber layer thinning. Oral steroids were restarted with improvement in optic disc swelling, but without improvement or change in vision. As of his most recent exam, the patient has persistent bilateral inferior visual field defects with segmental optic nerve atrophy typical of NAION. He has continued therapy with anakinra, and subsequently tapered off of prednisone; though he remains on a physiologic dose of hydrocortisone.

Conclusions: This case demonstrates an unreported ocular manifestation in a patient with XIAP deficiency, which clinically appeared sensitive to immunomodulation. Our patient is an unusual candidate for NAION due to his young age, the average age of onset being the mid to late 60s, and lack of vascular risk factors.We hypothesize that his hyper-inflammatory condition contributed to irreversible vascular damage in the optic nerve head, resulting in NAION. Therefore, it may be useful to consider the involvement of systemic inflammatory and immune dysregulatory conditions when treating patients with atypical NAION. Additionally, NAION should be considered in patients with XIAP deficiency and sudden unilateral vision loss.



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