A 69-year-old man reported recurrent fever and arthralgias without other accompanied symptom for 1 year. His C-reactive protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and serum ferritin (SF) levels were strikingly high, but evaluations for infectious (such as tuberculosis) or rheumatic conditions (such as giant cell arteritis) were unrevealing (Table 1). Peripheral blood analyses demonstrated macrocytic anemia (Hb 92 g/L and MCV 112.8 g/L) and mild thrombocytopenia (Plt 76*109/L). Bone marrow (BM) examination showed no myelodysplasia but presence of +8. Additionally, a next-generation sequencing panel for autoinflammatory diseases was performed and found a heterozygous NLRP3 R675Q missense mutation. Family history was unremarkable. This mutation of NLRP3 was not reported to be pathogenic previously and identified as uncertain significance. Bioinformatics protein function prediction indicated this mutation was benign. A working diagnosis of autoinflammatory syndrome with trisomy 8 was established and the patient has a prompt response to dexamethasone 10 mg per day. Methotrexate 10 mg per week was subsequently added to facilitate glucocorticoids (GCs) tapering. However, fever and CRP resurged during reduction of GCs. Methotrexate was stopped and a therapeutic trial of tofacitinib 5 mg twice daily was initiated at the treatment of 25 mg prednisone per day, after discussion and agreement achieved with the patient. During the following 16-month follow up, tofacitinib was titrated to 15 mg/day and prednisone reduced to 15 mg per day as maintenance. Attempts to reduce either tofacitinib or prednisone to a lower dosage incurred flare of symptom or inflammatory markers. The patient remained stable and underwent regular follow up to date (Figure 1A).