ACTIVE TB AFTER THE USE OF TOCILIZUMAB FOR COVID-19 INFECTION

TOPIC: Chest Infections TYPE: Fellow Case Reports INTRODUCTION: Tocilizumab is a humanized anti-IL-6 receptor antibody and inhibits the binding of IL-6 to its receptors, associated with Th17 and Th22 cell differentiation which is critical for anti-mycobacterial activity. It is commonly used in patients with active rheumatoid arthritis. During the COVID-19 pandemic, tocilizumab has been widely used in severe COVID-19 infection with elevated markers of systemic inflammation. We report a case of active tuberculosis after the use of tocilizumab for COVID-19 pneumonia. CASE PRESENTATION: An 80-year-old Asian female with hypertension, coronary artery disease presented to the emergency department(ED) due to a one-day duration of fever, cough, and altered mental status. About three months prior to presentation, she had COVID-19 pneumonia requiring prolong hospitalization which was complicated by acute respiratory distress syndrome. She received tocilizumab, remdesivir, steroids and hydroxychloroquine for COVID-19 infection. Following the hospital stay, she was discharged to a long-term acute care facility, and then went home. She is originally from China and moved to the United States 50 years ago. In the ED she was febrile (100.4°F) and hypoxemic, subsequently placed on 4L of nasal cannula. The laboratory data was remarkable for leukocytosis and lactic acidosis. The chest radiograph showed bilateral reticular nodular patchy opacities. The patient was admitted and empiric antibiotics were started for possible pneumonia. Despite this treatment, her respiratory status deteriorated and she was intubated on day 4, with CT chest (figure1) revealing innumerable bilateral micronodules with centrilobular distribution and tree-in-bud opacities. There were also 2 large cavitary lesions in the right upper lobe. The sputum specimen was sent, which returned positive for Acid-Fast Bacillus. In addition, Mycobacterium tuberculosis PCR on sputum was positive. Therefore, the first-line anti-tuberculosis agents including rifampin, isoniazid, pyrazinamide, and ethambutol were started. The Mycobacterium tuberculosis Complex was isolated on sputum 3 weeks later. DISCUSSION: The data from clinical trials indicate that the use of tocilizumab is associated with a very low or absent risk of tuberculosis reactivation. However, this case highlights the judicious use of tocilizumab in patients who are at high risk of exposure or reactivation such as immigrants from endemic regions, IV drug users and health care workers, etc. In our case, the patient had other factors including severe COVID-18 infection, use of steroids, prolonged hospital stay, and malnutrition which might compromise the immune system, and predispose to active tuberculosis. CONCLUSIONS: We suggest that tests be performed to rule out latent tuberculosis in selected patients prior to tocilizumab use and monitor all patients for active tuberculosis during treatment. REFERENCE #1: Scriba TJ, Kalsdorf B, Abrahams DA, Isaacs F, Hofmeister J, Black G, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180(3):1962-70. REFERENCE #2: Cantini F, Nannini C, Niccoli L, Petrone L, Ippolito G, Goletti D. Risk of Tuberculosis Reactivation in Patients with Rheumatoid Arthritis, Ankylosing Spondylitis, and Psoriatic Arthritis Receiving Non-Anti-TNF-Targeted Biologics. Mediators Inflamm. 2017;2017:8909834. REFERENCE #3: Koike T, Harigai M, Inokuma S, Ishiguro N, Ryu J, Takeuchi T, et al. Postmarketing surveillance of tocilizumab for rheumatoid arthritis in Japan: interim analysis of 3881 patients. Ann Rheum Dis. 2011;70(12):2148-51. DISCLOSURES: No relevant relationships by Goutham Dronavalli, source=Web Response No relevant relationships by Sungryong Noh, source=Web Response