Title : Epstein–barr virus-associated autonomic neuropathy presenting as isolated severe orthostatic hypotension
Abstract:
Background: Orthostatic hypotension is commonly attributed to volume depletion, medication effect, cardiac disease or endocrine dysfunction. However, persistent orthostatic hypotension after correction of reversible causes should prompt consideration of cardiovascular autonomic failure. Acute or subacute autonomic neuropathy is uncommon and is frequently idiopathic, although post-infectious and immune-mediated mechanisms are increasingly recognised. Epstein–Barr virus (EBV)-associated autonomic neuropathy is rarely reported and usually presents with multi-domain dysautonomia.1,2
Clinical Case: A gentleman in his early 60s with Rheumatoid Arthritis and Raynaud’s phenomenon treated with Methotrexate and Amlodipine respectively, presented after an unwitnessed fall preceded by dizziness and light-headedness, sustaining a left clavicular fracture. He also reported a one-month history of progressive fatigue, dizziness, sore throat, night sweats and 5kg weight loss. Shortly before admission, he had been reviewed in Haematology clinic because of these constitutional symptoms with accompanying lymphocytosis, which persisted on his admission blood tests. This prompted investigations for infective and haematological causes; a Monospot test was positive with raised immunoglobulins. Clinical examination on admission was grossly unremarkable, bar an initial blood pressure assessment which demonstrated marked orthostatic hypotension, falling from 90/63 mmHg to 70/52mmHg.
Amlodipine was discontinued and repeated intravenous fluid challenges were trialled without sustained improvement. Formal head-up tilt-table testing confirmed severe progressive orthostatic hypotension, with blood pressure falling from 108/69 mmHg to 45/33 mmHg within 8 minutes, reproducing symptoms of light-headedness and visual disturbance. Given the positive Monospot test and persistent lymphocytosis, EBV PCR was performed and returned positive at 96,079.5 copies/mL, log 4.98, supporting recent or reactivated EBV infection. Extensive investigations did not identify an alternative cardiac, endocrine, autoimmune, paraneoplastic, malignant or large-fibre neurological cause. CT thorax demonstrated bilateral ground-glass change, small pulmonary nodules and mediastinal/hilar lymphadenopathy, considered inflammatory or reactive.
The patient was treated with fludrocortisone and midodrine, titrated to symptomatic response. Serial follow-up demonstrated falling EBV viral load in parallel with haemodynamic recovery, PCR decreased from log 4.98 during the index admission to log 3.4 by Month 5, by which point clinically significant orthostatic hypotension had resolved. Thoracic imaging abnormalities seen during admission also improved, with later resolution of pulmonary nodules and reduction in mediastinal lymphadenopathy.
Conclusion: This case describes suspected EBV-associated autonomic neuropathy presenting predominantly as cardiovascular autonomic failure. The near-isolated orthostatic hypotension and serial EBV PCR correlation distinguish it from previously reported EBV-associated dysautonomia, where multi-domain autonomic involvement is more typical.
