Successful management of infection and macrophage activation syndrome patient using low-dose etoposide: A case report

Macrophage activation syndrome (MAS), a sub-type of hemophagocytic lymphohistiocytosis (HLH) secondary to autoimmune rheumatic diseases, is a critical and potentially fatal condition characterized by an excessive inflammatory response. Despite the established efficacy of the HLH-2004 guideline in diagnosing and treating HLH over the years, ongoing discussion persists regarding its application, especially for HLH secondary to complicated conditions, such as autoimmune rheumatic diseases combined with severe infection. Etoposide (VP-16), a topoisomerase II inhibitor that effectively induces DNA damage and subsequent apoptosis in hyperactivated immune cells, has been widely used for the treatment of HLH. However, its suppressive effect on immune system may also cause potential exacerbation of infection in autoimmune rheumatic disease-induced HLH patients complicated with severe infection. Therefore, the use of VP-16 in such cases was inconclusive. In this case study, we propose a potentially effective strategy for managing a patient diagnosed with secondary HLH complicated with systemic lupus erythematosus (SLE) and chronic coronavirus disease 2019 infection. Our approach involves early administration of low-dose VP-16 (100 mg twice a week, 300 mg in total), combined with methylprednisolone, cyclophosphamide, and cyclosporine A. The administration of etoposide effectively led to improvements in various indices of HLH. Low dose etoposide proves to be an effective approach in alleviating HLH while mitigating the risk of infection.