DAIR to Be Different: Successful Use of DAIR Regimen, a Novel Treatment Combination for EBV-induced HLH

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by uncontrolled immune activation and hemophagocytosis. In adults, Epstein-Barr virus (EBV) infection is a known trigger. This report describes a novel approach to treating EBV-induced HLH in a 29-year-old female, avoiding the potential toxicities of chemotherapy-based regimens, such as infertility. The patient presented febrile, tachycardic, and hypotensive following a week of high fever, bilious emesis, and diarrhea. Laboratory results showed elevated AST and ALT, hyperbilirubinemia, leukopenia, thrombocytopenia, and hyperferritinemia. Imaging revealed splenomegaly, and a positive mononucleosis rapid test confirmed EBV infection. Based on her clinical presentation, laboratory findings, and a bone marrow biopsy showing phagocytic histiocytes, she was diagnosed with EBV-induced HLH, fulfilling 7 of the 8 diagnostic criteria (5 required). The patient was started on the DAIR regimen two days after transfer. DAIR combines dexamethasone for its potent anti-inflammatory properties (used in HLH-94/HLH-2004), anakinra to control the cytokine storm, IVIG for passive immune support and antiviral action, and rituximab to target EBV-infected B cells. The patient responded well to treatment. EBV became undetectable within three weeks, and by seven weeks, blood counts, liver function, ferritin, triglycerides, and fibrinogen levels had normalized. Ten weeks after symptom onset, she returned to work and is now pregnant, with no signs of relapse. This case demonstrates the effectiveness of DAIR as a chemotherapy-free alternative for EBV-induced HLH, offering a targeted approach to the syndrome's complex pathogenesis while achieving sustained remission.