USE OF INFLIXIMAB AS THERAPEUTIC OPTION FOR STEROID-RESISTANT PARADOXICAL REACTION IN TB

Abstract

SESSION TITLE: TB and TB-Involved Case PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/17/2022 12:15 pm - 01:15 pmINTRODUCTION: Paradoxical reaction (PR) is an immune-mediated disease exacerbation precipitated by initiation of antitubercular therapy (ATT). Unlike IRIS (immune reconstitution inflammatory syndrome), a hyperinflammatory response to HIV/AIDS treatment, PR is independent of antiretroviral therapy (ART). Standard guideline therapy for PR is limited, with glucocorticoids as a standard of care. We describe a case of steroid-resistant tuberculin PR that improved with experimental Infliximab therapy.CASE PRESENTATION: 42-year-old HIV negative female with a history of rheumatoid arthritis on methotrexate and ovarian cancer on chemotherapy, presented with dyspnea and left-sided weakness. Chest imaging demonstrated a diffuse miliary pattern (image 1). QuantiFERON testing was positive. Cerebrospinal fluid studies, bronchoalveolar lavage and sputum cultures detected Mycobacterium tuberculosis (TB). Cultures demonstrated no antimicrobial resistance. Magnetic Resonance Imaging demonstrated lesions favoring CNS tuberculomas (image 2).There was transient clinical improvement with expanded ATT (Rifampin, Isoniazid, Pyrazinamide, Levofloxacin, Linezolid, Dexamethasone) but the disease continued to worsen despite increasing dosage of the glucocorticoid. Emergent salvage therapy with Infliximab significantly improved the intracranial and respiratory disease burden (image 3) with near resolution of clinical findings.DISCUSSION: An overexaggerated cell-mediated immune response against killed or damaged mycobacterium results in PR [1]. Moreover, granulomatous host response to TB may sequester the organism from administered antitubercular treatment [2]. Manipulation of immunomodulation by targeting tumor necrosis factor alpha (TNF alpha) is a proposed potential therapeutic option for PR [2] as it can decrease inflammation and disrupt granulomatous formations.CONCLUSIONS: There are only handful case reports exploring alternatives for steroid resistant PR. TNF-a inhibition is a potential valid treatment option in such cases [2].Reference #1: Blackmore, T. K., Manning, L., Taylor, W. J., & Wallis, R. S. (2008). Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clinical Infectious Diseases, 47(10), e83–e85. https://doi.org/10.1086/592695Reference #2: Briner, M., Oberholzer, M., Chan, A., & Wagner, F. (2021). Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system. BMJ Case Reports, 14(8), e235511. https://doi.org/10.1136/bcr-2020-235511DISCLOSURES: No relevant relationships by Nicholas KlimbergNo relevant relationships by Pallabi ShresthaNo relevant relationships by Sarah UpsonNo relevant relationships by Kenji Yoshino SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Paradoxical reaction (PR) is an immune-mediated disease exacerbation precipitated by initiation of antitubercular therapy (ATT). Unlike IRIS (immune reconstitution inflammatory syndrome), a hyperinflammatory response to HIV/AIDS treatment, PR is independent of antiretroviral therapy (ART). Standard guideline therapy for PR is limited, with glucocorticoids as a standard of care. We describe a case of steroid-resistant tuberculin PR that improved with experimental Infliximab therapy. CASE PRESENTATION: 42-year-old HIV negative female with a history of rheumatoid arthritis on methotrexate and ovarian cancer on chemotherapy, presented with dyspnea and left-sided weakness. Chest imaging demonstrated a diffuse miliary pattern (image 1). QuantiFERON testing was positive. Cerebrospinal fluid studies, bronchoalveolar lavage and sputum cultures detected Mycobacterium tuberculosis (TB). Cultures demonstrated no antimicrobial resistance. Magnetic Resonance Imaging demonstrated lesions favoring CNS tuberculomas (image 2). There was transient clinical improvement with expanded ATT (Rifampin, Isoniazid, Pyrazinamide, Levofloxacin, Linezolid, Dexamethasone) but the disease continued to worsen despite increasing dosage of the glucocorticoid. Emergent salvage therapy with Infliximab significantly improved the intracranial and respiratory disease burden (image 3) with near resolution of clinical findings. DISCUSSION: An overexaggerated cell-mediated immune response against killed or damaged mycobacterium results in PR [1]. Moreover, granulomatous host response to TB may sequester the organism from administered antitubercular treatment [2]. Manipulation of immunomodulation by targeting tumor necrosis factor alpha (TNF alpha) is a proposed potential therapeutic option for PR [2] as it can decrease inflammation and disrupt granulomatous formations. CONCLUSIONS: There are only handful case reports exploring alternatives for steroid resistant PR. TNF-a inhibition is a potential valid treatment option in such cases [2]. Reference #1: Blackmore, T. K., Manning, L., Taylor, W. J., & Wallis, R. S. (2008). Therapeutic Use of Infliximab in Tuberculosis to Control Severe Paradoxical Reaction of the Brain and Lymph Nodes. Clinical Infectious Diseases, 47(10), e83–e85. https://doi.org/10.1086/592695 Reference #2: Briner, M., Oberholzer, M., Chan, A., & Wagner, F. (2021). Potential disease trigger as a therapeutic option: infliximab for paradoxical reaction in tuberculosis of the central nervous system. BMJ Case Reports, 14(8), e235511. https://doi.org/10.1136/bcr-2020-235511 DISCLOSURES: No relevant relationships by Nicholas Klimberg No relevant relationships by Pallabi Shrestha No relevant relationships by Sarah Upson No relevant relationships by Kenji Yoshino