Orbitally Vexed

Update Item Information
Identifier walsh_2024_s1_c2
Title Orbitally Vexed
Creator Blake Colman; Rogan Fraser; Evelyn Perry; Prashanth Ramachandran; Shivanand Sheth; Neil Shuey; Subahari Raviskanthan
Affiliation (BC) Alfred Health, Royal Victorian Eye and Ear Hospital, Monash University; (RF) (SS) (NS) (SR) Royal Victorian Eye and Ear Hospital; (PR) St Vincents Hospital
Subject Optic Perineuritis; 3rd Nerve Palsy; 4th Nerve Palsy; 6th Nerve Palsy; Chemosis
Description An 84-year-old independent retiree presented with a three-day history of a painful, red, watery eye associated with horizontal binocular diplopia. His ocular history included bilateral intraocular lens replacement several years prior. Examination revealed mild left proptosis with marked periorbital oedema, chemosis and conjunctival injection. A small left esotropia was seen at primary with significant limitation of left ductions in all directions. The remainder of the anterior and posterior examination was normal with no afferent visual defect, nor additional cranial neuropathy observed. He remained systemically well without an intercurrent infective illness or constitutional symptoms. A mild pancytopenia was seen, though serum inflammatory makers were within normal limits and an extensive infective screen was unrevealing. A Bscan demonstrated left posterior globe thickening and a positive ‘T-sign', while an MRI of the brain and orbits revealed a diffusely thickened left optic nerve sheath with enhancement from the orbital apex to the posterior globe, lacking extension into the optic canal or chiasm. Investigation into his background revealed an 8-year history of relapsing polychondritis associated with mild cytopenias, fevers, joint pain and one previous episode of periorbital oedema. His regular medication included tocilizumab and oral prednisolone. A bone marrow biopsy taken a year earlier demonstrated moderately hypercellular marrow with dysplastic tri-lineage haematopoiesis and prominent vacuolation of both erythroid and myeloid precursors. A diagnostic test had been performed on his biopsy to confirm the cause of his relapsing condition with management of his current presentation guided by this result.
History Genetic testing had revealed a Mel41Val missense mutation in a gene located in the UBA1 gene on the X- chromosome, in keeping with a diagnosis of VEXAS syndrome. Pulsed intravenous methylprednisolone resulted in rapid improvement of symptoms with only mild abduction restriction, temporal conjunctival injection and subtle inferior chemosis persisting after 48 hours and complete resolution observed by day four post treatment. VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a newly characterised title for a group of adult-onset, treatment-refractory multi-system inflammatory diseases with haematological abnormalities. First reported in 2020, VEXAS occurs through recurrent and inactivating somatic mutations in the ubiquitin activating enzyme 1 (UBA1) gene in haematopoietic progenitor stem cells. Though phenotypical heterogeneity exists, VEXAS is recognised as a progressive and fatal systemic disease that mimics a number of rheumatological conditions and results in bone marrow failure and haematological malignancy. Missense mutations involving methionine at codon-41 on the X-chromosome are common, though additional mutations have been reported. True prevalence of the disease is likely under-appreciated due to clinical variability though population prevalence has been estimated as 1:4269 in men aged greater than 50 years . A history of relapsing polychondritis with macrocytosis or thrombocytopenia is thought to predict a risk of VEXAS with 100% sensitivity and 96% specificity. Common manifestations include recurrent fevers and fatigue, relapsing polychondritis, neutrophilic dermatosis, pulmonary infiltrations and various forms vasculitis [6]. Ocular involvement has been described in up to 40% of cases, with episcleritis, uveitis and scleritis the most frequently reported. Orbital myositis, superior orbital fissure syndrome and optic perineuritis have also been rarely identified in individual case reports. Corticosteroids are temporarising and used to obtain initial disease control, however patients typically become therapy refractory over time and considerable morbidity and mortality exists through myeloid- driven autoinflammation, progressive bone marrow failure or infective complications.
Disease/Diagnosis Acute orbital manifestations of an underlying haematoinflammatory disorder, VEXAS syndrome.
Date 2024-03
References 1. Grayson P, Patel BA, Young NS. ‘VEXAS syndrome'. Blood. Jul 2021. doi: 10.1182/blood.2021011455 2. Beck et al. ‘Somatic mutations in UBA1 and severe adult-onset autoinflammatory disease'. NEJM. Dec 2020. doi: 10.1056/NEJMoa2026834. 3. Ferrada et al. ‘Somatic mutations in UBA1 define a distinct subset of relapsing polychondritis patients with VEXAS'. Arthritis and Rheumatology. Oct 2021. doi: 10.1002/art.41743. 4. Kucharz EJ. ‘VEXAS syndrome: A newly discovered systemic rheumatic disorder'. Reumatologia. 2023. doi: 10.5114/reum/163090 5. Beck et al. 'Estimated prevalence and clinical manifestations of UBA1 variants associated with VEXAS syndrome in a clinical population'. JAMA. 2023. doi: 10.1001/jama.2022.24836
Language eng
Format video/mp4
Type Image/MovingImage
Source 2024 North American Neuro-Ophthalmology Society Annual Meeting
Relation is Part of NANOS Annual Meeting 2024
Collection Neuro-Ophthalmology Virtual Education Library: Walsh Session Annual Meeting Archives: https://novel.utah.edu/Walsh/
Publisher North American Neuro-Ophthalmology Society
Holding Institution Spencer S. Eccles Health Sciences Library, University of Utah
Rights Management Copyright 2024. For further information regarding the rights to this collection, please visit: https://NOVEL.utah.edu/about/copyright
ARK ark:/87278/s6es2vys
Setname ehsl_novel_fbw
ID 2592815
Reference URL https://collections.lib.utah.edu/ark:/87278/s6es2vys
Back to Search Results