The patient, a previously healthy 14-year-old Chinese boy who was born to nonconsanguineous parents, presented with intermittent low fever and skin rash of two weeks’ duration and continuing high fever and malaise that had developed subsequently. His parents were healthy and had no family history of rheumatic and haematological diseases. Physical examination revealed scattered, slightly raised round erythaematous lesions and shoulder joint pain without splenomegaly or hepatomegaly. Laboratory tests revealed a white blood cell count of 22.9×109/L, haemoglobin 13.4 g/dL, platelets 302×109/L, C-reactive protein (CRP) 20 mg/L, erythrocyte sedimentation rate 32 mm/1 hr, ferritin 3,289 ng/mL, fibrinogen 3.8 g/L, and triglycerides 1.5 mmol/L. AST, ALT, echocardiography and bone marrow aspiration seemed to be normal. The findings of serologic tests for Epstein Barr virus, cytomegalovirus, human immunodeficiency virus, viral hepatitides and Group A streptococcal infections were negative, as were serial blood and urine cultures. Therefore, according to ILAR criteria [2], sJIA was diagnosed. Treatment with intravenous methylprednisolone (2 mg/kg.day), ibuprofen and MTX resulted in initial improvements in clinical and laboratory parameters. However, upon tapering of the methylprednisolone dosage, spiking fever, rash and arthralgia relapsed. To improve disease control and glucocorticoid withdrawal, we started TCZ treatment (8 mg/kg), leading to complete improvement in clinical and laboratory parameters. After 4 days of TCZ treatment with oral prednisolone (1 mg/kg.day), the patient developed a fever and acute dyspnoea. He was urgently admitted to the Paediatric Intensive Care Unit (PICU), where inotropic and vasoactive support were maximized and conventional mechanical ventilation started soon thereafter. Physical examination revealed coarse breath sounds, and wet rales were observed in both lungs. The chest X-ray showed a diffuse exudative lesion (Fig. 1A). Echocardiography revealed a slightly enlarged heart and decreased diastolic function with normal myocardial enzymes. His platelet counts decreased from 265×109/L to 87×109/L in two days, and his serum ferritin increased to 18,573 ng/mL. AST increased to 216 IU/L, and fibrinogen decreased to 890 mg/dl. His laboratory data met the PRINTO diagnostic criteria for MAS 2016[3]. The patient was treated with pulse methylprednisolone therapy followed by 10 mg/kg.day. His blood pressure was as low as 70/42 mmHg, and could not be maintained even after the application of five various drugs, including cardiotonics and vasopressors. The chest X-ray still showed a diffuse exudative lesion (Fig. 1B) Unfortunately, 12 h of life support still failed to maintain normal blood pressure, and then VA-ECMO was initiated. Starting 36 h later, blood pressure was maintained with fewer vasoactive drugs, and the patient underwent multiple follow-up chest radiographs (Fig. 1C). The pulmonary oedema gradually improved; therefore, ECMO support was gradually decreased, and the patient was definitively weaned off on Day 2.5 (60 h). Clinical testing showed improvement in MAS markers and chest X-ray (Fig. 1D). Then, the patient was discharged from the PICU. To improve disease control and glucocorticoid withdrawal, we tried TCZ again 14 days after the first infusion. However, 30 min after the second infusion of TCZ, the patient experienced acute anaphylaxis, including palpitations and chest stuffiness. We immediately stopped the TCZ infusion, and the patient recovered quickly with normal MAS markers. With full concurrence of the patient's family, we decided to add cyclosporine A. With a reduction of prednisolone dosage, the patient improved and was discharged after one mouth in the hospital. The correlation between clinical aspects, laboratory tests and treatment of sJIA-related MAS was summarized in Fig. 2. Currently, he has been in clinical remission on medication for nearly 9 months, with regular outpatient follow-up for gradual prednisolone reduction.
Capture next-generation sequencing (CNGS) was performed to detect the genetic basis. Genetic analysis revealed a mutation in the NLRP1 gene [c. (1175C > T) p.(Pro392Leu)] in heterozygosis, reported in sJIA [4].