Trial of Anakinra in Secondary Hemophagocytic Lymphohystiocytosis

Background: Hemophagocytic lymphohystiocytosis (HLH) is is an uncommon yet potentially devastating systemic disease, arising from uncontrolled activation of the immune system. Secondary HLH can be triggered by malignancy, metabolic disease and infection. Use of the IL-1 receptor antagonist, anakinra, has shown some promise in the treatment of this disorder. Interleukin-1 receptor antagonists such as anakinra have been used effectively in the treatment of pediatric rheumatoid arthritis. We hypothesize that this immunomodulator can also successfully treat patients with secondary HLH. This case series describes the diagnosis, progression, and therapy of three patients at Cook Children’s Medical Center with secondary HLH. Case Information: Three patients within the Cook Children’s network were diagnosed with HLH between 2014 and 2016 and treated per HLH-2004 protocol. The 1st patient, diagnosed with HLH at age 10, sustained relapse after five weeks of therapy with etoposide and dexamethasone, requiring reintensification. Thereafter, she developed fever, body aches and cytopenias with eventual diagnosis of juvenile rheumatoid arthritis, treated with prednisone and Anakinra, leading to remission. Thereafter, she was treated with tociluzumab, progressively weaned and now discontinued for several months, given continued remission. The 2nd patient, 16-year-old male, completed treatment for HLH followed by rising levels of ferritin generalized erythematous rash, swollen right elbow with erythema and pain. At that time, he was diagnosed with systemic rheumatoid arthritis and treated with Anakinra daily. He is currently in remission while continuing Anakinra for 10 months. The 3rd patient, 12-year-old female with past medical history of type 1 diabetes and idiopathic juvenile arthritis, was diagnosed with EBV driven HLH, treated with dexamethasone, etoposide, and rituximab. As part of workup, she was found to have depressed NK cell activity. She presented a year later with symptoms concerning for recurrence of HLH. Given her history of juvenile idiopathic arthritis, she was treated with Anakinra with resolution of her symptoms. She remains in remission for over two years. Conclusions: The diagnosis of HLH can be elusive and is often accompanied with multiple systemic manifestations. For those patients with a concurrent diagnosis of Juvenile Rheumatoid Arthritis, the introduction of anakinra has shown significant improvement in both arthritic symptoms and HLH markers.