A 58-year-old man who had been experiencing chills, fatigue, and recurring fever for 10 days visited our hospital. He had been diagnosed to have AIDS, non-tuberculous mycobacteria (NTM) infection, and infection with Talaromyces marneffei 3 months ago. Since then, he had received highly active antiretroviral therapy, anti-NTM therapy, and antifungal medication. Furthermore, he had a 10-year history of diabetes and had no personal or family history of HLH. The patient claimed to have lost 10 kg in the previous 6 months. After being admitted, the patient experienced frequent episodes of high fever, with a maximum temperature of 39.8 C, ongoing chest pressure, and low mental well-being. He was found to have neutropenia (neutrophil count: 0.84 x 109/L), anemia (hemoglobin level: 78 g/L), and severe thrombocytopenia (platelet count: 7 x 109/L) ( Figure 1A-C ). The levels of IL-6, IL-10, and IFN-gamma were markedly high ( Figure 2B-D ). His triglyceride, fibrinogen, ferritin and D-dimer levels were 3.63 mmol/L, 0.91 g/L,6070 ng/mL, and 32960 microg/L, respectively ( Figures 1D, E  and  Figure 2A ). Moreover, he had severe hypoalbuminemia, a CD4+ lymphocyte count of just 8/microl, and renal failure ( Table 1 ). Hepatosplenomegaly was detected on an abdominal CT. Importantly, bone marrow aspiration testing revealed hemophagocytosis. Based on HLH-2004 diagnostic criteria, the patient's symptoms were compatible with those of HLH. We were unable to determine the cause of the infection at first because the blood bacterial culture was negative. However, the next-generation sequencing (NGS) revealed the herpes virus 4 (EBV)as a culprit. EBV-DNA was 835000 copies/ml. We believe that the patient had an outbreak of HLH due to EBV activation on the basis of poor immune reconstitution.
In light of the patient's extremely poor immune status and renal failure, ruxolitinib 15 mg PO bid was started, and empiric antibiotics were started to manage any potential pathogen infections along with continuous administration of cART, anti-NTM therapy, and antifungal medication. After 3 days of ruxolitinib treatment, he no longer had a fever, and his strength and appetite had started to return. His neutrophil and platelet counts improved to 2.34 x 109/L and 27 x 109/L ( Figure 1A, C ), respectively, and CRP level decreased to 34.3 mg/ml. His ferritin level dropped to 3062 ng/mL, fibrinogen level was 2.24 g/L, and D-dimer level was 7350 microg/L after 6 days of treatment. After therapy for 14 days, his hemoglobin level and platelet count increased to 108 g/l and 66 x 109/L, respectively, and neutrophil count, kidney function, and triglyceride level normalized ( Figure 1 ). The levels of HLH-related cytokines IL-6, IL-10, and IFN-gamma decreased to 29.85, 10.7, and 29.85 pg/ml, respectively ( Figure 2 ). Furthermore, ultrasound showed that hepatosplenomegaly resolved (thickness of 3.5cm). After the cART regimen was modified and the patient's indicators markedly improved, the patient was discharged in a stable condition 21 days after being admitted ( Table 1 ). Antifungal and anti-NTM medications were continued while ruxolitinib was gradual tapered and discontinued after 4 weeks. No signs of recurrence were observed at 3 months after discharge from the hospital.