Hemophagocytic Lymphohistiocytosis in a Fatal Case of Severe Fever with Thrombocytopenia Syndrome

Abstract

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease caused by a novel Bunyavirus with a high mortality rate. We herein report a fatal case of an 86-year-old woman with SFTS complaining of a fever, fatigue, and bicytopenia. Her condition deteriorated with rapid progression of bleeding tendency, disturbance of consciousness, and multiple organ failure leading to death on Day 6 of her illness. The histopathological findings in the autopsy revealed marked infiltration of macrophages with hemophagocytosis in the bone marrow, liver, and spleen leading to a diagnosis of hemophagocytic lymphohistiocytosis (HLH). HLH might be a critical pathogenesis in fatal cases of SFTS.

Keywords: Bunyavirus; SFTS; hemophagocytic lymphohistiocytosis; tick-borne infectious disease.

Figure 1.

Bone marrow aspirate showed hypocellular marrow (absolute nuclear cell count 1.1×10⁹ cells/L) with increased proportions of macrophages, up to 13.6%. The macrophages engulfed red blood cells, thrombocytes, and nuclear cells. Original magnification, 1,000×.

Figure 2.

The tick that bit the patient on the back was identified as a semi-engorgedAmblyomma testudinarium nymph.

Figure 3.

Clinical course in this case. The symptoms, WBC count, Hb level, platelet count, and the levels of AST, LDH, and CK are shown. The definite diagnosis of SFTS, accompanied by DIC and HLH, was made on Day 5, and she was treated with ribavirin, methylprednisolone (mPSL), and fresh frozen plasma (FFP). Her condition deteriorated rapidly, and she died on Day 6. APTT: activated partial thromboplastin time, CMZ: cefmetazole, CPFX: ciprofloxacin, GI: gastrointestinal, γ-glb: γ-globulin, MINO: minocycline, PZFX: pazufloxacin, RCC: red cell concentrate

Figure 4.

Histopathological findings in the autopsy. (A) Bone marrow: Increased numbers of macrophages with active hemophagocytosis were seen in the bone marrow (Hematoxylin and Eosin (H&E) staining). (B) Liver: CD68-positive macrophages with hemophagocytosis were seen in the sinusoids and around focal necrosis. (a) H&E staining and (b) CD68 stain. (C) Spleen: CD68-positive macrophages with hemophagocytosis were seen in the red pulp. (a) H&E staining and (b) CD68 stain. Original magnification, 400×.

Figure 5.

SFTSV was detected in the cytoplasm of the macrophages in the bone marrow (A), liver (B), and spleen (C). SFTSV protein was detected by immunohistochemistry (IHC) (left panel) and SFTSV RNA byin situ hybridization AT tailing (ISH-AT) (right panel). Original magnification, 400×.