A previously healthy 27-year-old man presented with skin ulceration and exudation in January 2022. He received antibiotics. Three months later, fever, generalized body swelling, and fatigue were experienced by the patient. The laboratory data revealed abnormal liver functions, with an alanine aminotransferase (ALT) level of 92 units/L (normal: 7-40 units/L), aspartate aminotransferase (AST) level of 181.3 units/L (normal: 13-35 units/L), and total bilirubin (TBil) level of 73 micromol/L (normal: 0-23 micromol/L). The laboratory data also revealed thrombocytopenia with a platelet (PLT) count of 24 x 109/L ( Figure 1A ). The level of haemoglobin (HGB) was 74 g/L. His ferritin level was 13504 ng/ml (normal: 23.9-336.2 ng/ml), and triglyceride (TG) level was 3.61 mmol/L (normal: 0-1.7 mmol/L) ( Figure 1C, D ). He had severe hypoalbuminemia (20 g/L). Epstein-Barr virus (EBV)-DNA in blood plasma was 3.46 x 103 copies/ml (normal: < 400 copies/ml). The level of soluble CD25 (sCD25) was 12062 pg/ml (normal: <= 6000 pg/ml) ( Figure 1C ). The patient tested negative for human immunodeficiency virus (HIV). He denied a personal and family history of haematological pathologies, specifically HLH.
The patient's symptoms worsened, as evidenced by deteriorated coagulopathy with a prothrombin time (PT) of 25.5 s (normal: 10.4-12.7 s) and an active thromboplastin time (APTT) of 102 s (normal: 22.3-32.5 s) ( Figure 1B ). The fibrinogen level was only 0.41 g/L (normal: 1.8-3.5 g/L) ( Figure 1D ). Bone marrow aspiration and biopsy demonstrated inflammatory changes and an increase in the number of macrophages and histiocytes with intense haemophagocytosis. Therefore, the patient fulfilled 7 of 8 diagnostic criteria for HLH ( Table 1 ). NK-cell activity was not analysed due to the lack of availability in Shanghai during the pandemic.
The patient experienced extreme fatigue, severe oedema, persistent high fever, and large skin ulcerations with exudation. He became expressionless and unresponsive. We decided to start with RUX 15 mg twice daily plus dexamethasone (DXM) 10 mg/m2/day per HLH-94 dosing, not only because of his poor performance status (PS) and progressive deterioration of liver function but also because of the short supply of blood products, including red blood cells and platelets, at specific periods in Shanghai. Fourteen days later, DXM was reduced to 5 mg/m2/day. Broad-spectrum antibiotics, fibrinogen, prothrombin complex, and immunoglobulin were also given. The patient had no fever on Day 3 (Day 0 corresponds to RUX initiation). Eighty percent of skin ulcers were healed on Day 7. Oedema and fatigue symptoms were significantly relieved. The TBil level dropped to 58 micromol/L. After two weeks of therapy, the PLT count recovered to 136 x 109/L ( Figure 1A ). The fibrinogen level, PT, and APTT improved ( Figure 1B, D ). The sCD25 level decreased to 7238 pg/ml ( Figure 1C ). The patient achieved a partial response (PR) according to the response criterion described in previous studies. He underwent two skin biopsies and a cervical lymph node biopsy by a core needle, but all were negative for lymphoma. The histopathology of the excised right inguinal lymph node indicated an NK/T-cell lymphoma on Day 22. The pegaspargase + Gemox regimen was started on Day 23. He developed a fever again on Day 28. The levels of C-reactive protein (CRP, 97 mg/L) and ferritin (10532 ng/ml) were all elevated ( Figure 1A, C ). The values of PLT (31 x 109/L) and fibrinogen (0.80 g/L) were reduced again ( Figure 1A, D ). The pulmonary computed tomography (CT) scan suggested pneumonia. The result of alveolar lavage fluid culture was Pseudomonas aeruginosa. Although broad-spectrum antibiotics were administered according to the drug susceptibility, the patient died on Day 33 with incomplete induction chemotherapy.