Cloak and dagger ‐ secondary hemophygocytic lymphohistiocytosis caused by intravenous autoinfection

We herein report on a 28-year-old, Caucasian, female patient presenting with high fever spurts and abdominal pain. After intensive work-up and exclusion of common differential diagnosis, the working diagnosis was fever of unknown origin (FUO). Blood cultures positive for unusual fecal bacteria led to the suspicion of a secondary hemophagocytic lymphohistiocytosis (sHLH) upon repeated autoinfection with feces due to an underlying psychiatric disease. The patient presented to the emergency department due to acute abdominal pain and a history of fever spurts. Initial physical examination and laboratory tests revealed a cardiopulmonary and abdominal status without pathological findings. From her past medical history, the patient reported juvenile idiopathic arthritis (low disease activity), ulcerative colitis (in remission) and an acute pancreatitis 2 years ago. Based on the clinical presentation and past medical history, the initial differential diagnosis included among others acute pancreatitis, nephrolithiasis, and cholecystitis. Initial laboratory analyses revealed elevated transaminases and alkaline phosphatase with ALT 90 U/L (reference range 10-50 U/L), AST 95 U/L (10-50 U/L), gamma-GT 199 U/L (6-42 U/L), AP 299 U/L (35-105 U/L), increased lipase activity 796 U/L (13-60 U/L) and a significantly increased C-reactive protein (CRP) of 10.64 mg/ dL (<0.5 mg/dL). The blood count showed hemoglobin, leukocytes and thrombocytes within normal ranges. Abdominal sonography and magnetic resonance imaging (MRI) showed signs of pancreatitis as well as a splenomegaly (20 cm) but no evidence of acute cholecystitis or nephrolithiasis was found. Subsequently, the diagnosis acute pancreatitis was made. Consecutively, fluid replacement, analgesics and antibiotics were initiated, causing pain reduction and normalization in lipase. However, before discharge, fever recurred (up to 41.3°C) accompanied by severe pain, chills, tachycardia and erysipelas, around a peripherally inserted venous catheter on the patient's forearm (Figure 1A). Despite multiple adaptations of the antibiotic therapy, recurrent fever episodes persisted (Figure 1B). In the light of her past medical history, adult onset Still's disease was suspected, and treatment with anakinra (4 x 100 mg per day) was commenced. However, treatment with this interleukin-1 inhibitor was unsuccessful and fever episodes persisted. After exclusion of endocarditis by trans-esophageal echocardiography and exclusion of tuberculosis, her fever persisted and the diagnosis fever of unknown origin (FUO) was made. Due to a newly developed bicytopenia (leukopenia and anemia), a bone marrow aspirate was performed, showing hyperplasia of the myeloid linage with depressed erythropoiesis, increased megakaryocytes and macrophages with hemophagocytosis (Figure 2). Worsening anemia and thrombocytopenia, as well as hypertriglyceridemia (263 mg/dL), hypofibrinogenemia (176 mg/dL) and elevated s-IL2 R (>20 ng/mL) are suggestive for sHLH. Together with pyrexia, splenomegaly, hemophagocytosis, and elevated GOT, those Andreas Pircher and Stefan Koeck contributed equally to this work. Received: 10 November 2019 Revised: 10 December 2019 Accepted: 12 December 2019