Fatal primary dengue-induced Haemophagocytic Lymphohistiocytosis (HLH) in a returning traveller from India treated with anakinra for the first time

Abstract

Abstract Background Dengue fever is an arthropod-borne flavivirus infection that is highly prevalent in the tropics. A proportion of clinical cases develop severe dengue, defined by life-threatening complications including haemorrhage, capillary leak and multi-organ failure. Recently there has been increasing recognition that some cases of severe dengue may be a consequence of HLH. To our knowledge, this is the first report of treatment with Anakinra for dengue-induced HLH. Case report We report a case of Dengue fever triggering HLH in an eighteen-year-old female returning traveller from India, diagnosed with systemic lupus erythematosus (SLE) two months prior to presentation. The patient initially presented to a district general hospital emergency department (ED) with a three-day history of flu-like symptoms, fever, erythematous rash, widespread joint pain, nausea and chills. Acute Dengue virus infection was confirmed with serum polymerase chain reaction (PCR) testing. On day two, she was admitted to intensive care for multi-organ support necessitated by refractory hypotension, oligo-anuric severe acute kidney injury (AKI), acute liver failure with lactataemia and type one respiratory failure. The possibility of Dengue-induced HLH was considered early with multiple criteria for diagnosis met including hyperferritinaemia, pancytopenia, lipaemia and a marked transaminitis. HLH-directed therapy was commenced with intravenous immunoglobulins (IVIG), intravenous methylprednisolone (IVMP) and Anakinra. Subsequent bone marrow biopsy analysis demonstrated clear evidence of HLH, in the context of a persistent and marked Dengue viraemia. We observed resolution of HLH markers as well as reducing requirements for multi-organ support after initiation of Anakinra therapy. During her recovery, the patient unexpectedly developed focal neurology; intracranial imaging demonstrated widespread, discreet parenchymal lesions thought to be haemorrhagic in nature, which were deemed too severe an insult to recover from. On day 19, the difficult decision of withdrawing care after deep discussion with the family was reached, soon after which the patient passed away. A post-mortem examination was not arranged.