P24 The successful use of anakinra to control protracted immune reconstitution inflammatory syndrome in HIV associated tuberculosis: a report of two cases

Abstract

Background: Paradoxical inflammatory reactions are well known to complicate tuberculosis (TB) and are observed with greater frequency in patients who are co-infected with HIV. Immune reconstitution inflammatory syndrome (IRIS) is a paradoxical inflammatory reaction following early immune system recovery after initiation of antiretroviral therapy. IRIS complicates one in five cases of HIV-associated TB. Most cases of IRIS respond to short courses of corticosteroids; however, morbidity and mortality is increased in central nervous system TB or with protracted reactions. There are no evidence-based treatment guidelines but montelukast, thalidomide and anti-tumour necrosis factor agents have been used to treat protracted paradoxical TB IRIS. Interleukin-1 mediated inflammation has been implicated in TB IRIS. We describe two cases using anakinra (recombinant human interleukin-1 receptor inhibitor) to control protracted, life-threatening inflammation in HIV associated TB. Methods: The cases are presented in the results section. Results: Case 1: A 33-year-old female from Ethiopia presented with sub-acute onset of fever, malaise with massive abdominal and thoracic lymphadenopathy. She was diagnosed with HIV (CD4=60 cells/mm3) and fully sensitive TB from lymph node aspirate. Despite two courses of TB treatment she developed a 3-year protracted IRIS with fevers, malaise and multiple cold abscesses and was unable to wean below 20mg prednisolone. AA amyloidosis developed with nephrotic range proteinuria and renal amyloid deposition on biopsy. Inflammation failed to respond to montelukast or colchicine, prompting anakinra initiation (100mg daily) with rapid clinical response, resolution of proteinuria, normalisation of inflammatory markers and successful weaning of corticosteroids. She is maintained on 100mg alternatedaily anakinra having failed an attempt to withdraw the treatment at seven years. Case 2: A 41-year-old Zimbabwean teacher with HIV (stable on antiretroviral therapy, complete viral suppression, CD4=245 cells/ mm3) presented with one month of fever, weight-loss and headache with no neurological deficit. He was diagnosed with isoniazid monoresistant miliary TB with tuberculomata in his medulla, pons and both cerebral hemispheres on magnetic resonance imaging (MRI). Following initiation of TB treatment, he developed worsening headaches, left sided weakness and dysphasia with increasing size and surrounding oedema of his tuberculomata on brain MRI. Brain biopsy demonstrated necrotic granulomatous inflammation with visible acidfast bacilli but no mycobacterial growth, compatible with paradoxical inflammation. He required protracted and high dose dexamethasone. After 18 months without successfully weaning steroids, with cognitive and functional impairment and unstable tuberculomata on serial brain MRI, anakinra was initiated with significant clinical, functional and radiological improvement. He is maintained steroid-free on 100mg alternate-daily anakinra at four years. Conclusion: This is the first published report using anakinra to control severe and life-threatening protracted paradoxical inflammation and reduce steroid exposure in HIV-associated tuberculosis.