P027 Infliximab in the treatment of cerebral tuberculosis paradoxical reactions with vasculitis
Authors: Ko Ho Juen , Fatima Anees , Sivagnanaratnam Aravinth , McGregor Alastair , Hamdulay Shahir 
Published: April 2024

Abstract

Background/Aims
Tuberculosis meningitis (TBM) is associated with high morbidity and mortality. Up to 25% of patients may experience paradoxical reactions (PR) after commencing anti-TB therapy, which are exaggerated inflammatory reactions resulting in parenchymal inflammation, tuberculomas and secondary vasculitis. PR are minimised with steroid co-treatment, and relapsing disease often requires escalating steroid therapy. High levels of CSF TNFα have been shown in TBM with PR and immunosuppressants such as thalidomide, azathioprine and mycophenolate have been used with limited success. Herewith we describe a patient with TBM and PR with secondary vasculitis and consequent stroke treated successfully with infliximab.

Methods
A 55-year-old man presented with collapse, drowsiness, anergia and lateral gaze nystagmus. He was diagnosed with MDR TB-meningitis 3 months earlier and treated with cycloserine, clofazimine, moxifloxacin, bedaquiline, linezolid and dexamthasone.

Results
Prior to this presentation there had been recurring headaches after weaning dexamathasone to cessation. Two days into admission, he developed an unsteady gait with bilateral intention tremor, bi-directional nystagmus and left upper limb dysdiadochokinesia. An MRI brain showed new intraparenchymal and meningeal lesions suggestive of tuberculomas with acute infarcts involving both thalami and the left external capsule with hydrocephalus. Intracranial CT angiogram showed irregular posterior cerebral arteries indicative of arteritis. Findings were characteristic for TB paradoxical reactions with a secondary vasculitis. Dexamethasone was recommenced at 6mg BD and weaned to 3mg over a one month period. Mycophenolate was commenced as a steroid sparing agent for PR and up-titrated to 1000mg BD over four weeks. There was minimal improvement in the patient’s neurological state and repeat MRI showed some improvement in tuberculomas, but new infarcts within the right globus pallidus and left thalamus. As there was minimal progress and high steroid dependence the patient was loaded with infliximab (5mg/kg) over the next 8 weeks. An MRI done after three infusions showed significant improvement in tuberculomas, resolution of arteritis and residual meningeal disease which correlated with clinical improvement. As progress was improving infliximab was stopped after six infusions, and both mycophenolate and prednisolone weaned to cessation. At six months of follow-up the patient has made a full neurological recovery.

Conclusion
TBM and PR are associated with significant morbidity and disability. There are no evidence based treatments for PR and corticosteroids remain the mainstay of treatment. Several case series have suggested a role for anti-TNF agents and our described case contributes to the role of anti-TNF in treating patients with TB PR with secondary vasculitis.

Disclosure
H. Ko: None. A. Fatima: None. A. Sivagnanaratnam: None. A. McGregor: None. S. Hamdulay: None.