A 4-year-old girl (height 110 cm, weight 20 kg) presented with chief complaints of fever and polyarticular swelling and pain. In October 2019, the patient developed chills and fever with temperature of up to 39.5°C, which was treated with intermittent oral dexamethasone tablets. The fever resolved but recurred after discontinuation of the drug. Unfortunately, over the next 3 months, the patient attempted to discontinue dexamethasone, but her condition deteriorated rapidly, with persistent high fever and concurrent symmetric polyarticular swelling and pain involving almost all the joints of the body. Polyarticular swelling and pain were mainly reported in the bilateral proximal interphalangeal joints, bilateral metacarpophalangeal joints, bilateral wrists, bilateral elbows, bilateral knees, bilateral ankles, and bilateral metatarsal toes, with morning stiffness lasting more than 4 hours. The patient's daily life was severely affected, wherein she was unable to walk and required others’ support. In February 2020, she visited several hospitals and received various treatments, such as ibuprofen suspension (3 ml/3 times/day, orally), dexamethasone injection (3 mg, intramuscularly, once), traditional Chinese medicine, and etanercept (12.5 mg, subcutaneously, twice), but her fever and arthritis symptoms showed little improvement.
Due to recurrent fever and persistent polyarticular swelling and pain, the patient was admitted to our department in June 2020. Physical examination showed swelling and tenderness in the proximal interphalangeal, metacarpophalangeal, wrist, elbow, knee, ankle, and metatarsophalangeal joints, and she was uncooperative with the Patrick’s test. Laboratory tests revealed a white blood cell count of 15.32 × 109/L, haemoglobin level of 91.8 g/L, platelet count of 676.8 × 109/L, serum ferritin level of 1,103.8 U/L, erythrocyte sedimentation rate (ESR) of 85.00 mm/h, c-reactive protein (CRP) level of 146.00 g/L, significantly elevated cytokine IL-6 level at 287.95 pg/ml, alanine transaminase level of 53.3 U/L, and albumin level of 26 g/L. Blood creatinine level was within normal ranges. Results for rheumatoid factor, antinuclear antibody, anti-cyclic citrullinated peptides, and human leukocyte antigen B27 were negative. Joint ultrasound suggested effusion in both the wrist joints and knee joints, synovial hyperplasia, and thickening of articular cartilage in both the knee joints as well as enlarged lymph nodes in the bilateral neck and groin. The patient was diagnosed with sJIA after infection, tumour, and other febrile diseases were ruled out, with a 27-joint Juvenile Arthritis Disease Activity Score (JADAS-27) of 56.5, indicating high disease activity. After obtaining parental consent, the patient was started on a regimen including TCZ (8 mg/kg/2 weeks, IV), ibuprofen suspension (4 ml/three times/day, orally), and methotrexate (7.5 mg/week, orally). After 1 day of treatment, the patient's fever subsided, and arthritis symptoms improved.
Thereafter, the patient received TCZ once every 2 weeks, and her condition continued to improve, with no recurrence of fever and steady improvement in her arthritic symptoms. However, repeat laboratory tests in September 2020 (after six infusions of TCZ) suggested that some cytokines remained at high levels( Tab.)and that the CRP level was elevated (14.1 mg/L, normal: < 6 mg/L). At this point, the patient was more resistant to repeated intravenous infusions, and her parents indicated that financial constraints might prevent them from continuing to afford TCZ treatment. We considered JAK inhibitors, which have the effect of inhibiting multiple cytokines including IL-6 and which have been shown to be effective in the treatment of adult rheumatoid arthritis (RA). Therefore, we chose the more economical and convenient tofacitinib (2.5 mg/twice/day) to replace the TCZ, whereas the other treatment regimens remained unchanged. After 5 months, the patient's arthritic symptoms disappeared, and the levels of acute phase reactants and cytokines decreased to normal ranges, indicating complete remission based on the JADAS-27(Fig. 1A and B and C).
The patient subsequently presented with mild swelling and pain in some joints in May 2021 due to upper respiratory tract infection. Laboratory tests revealed increased levels of acute phase reactants (ESR: 50 mm/h, CRP: 127 mg/L) and increased cytokine levels (IL-6: 39.29 pg/ml; sIL-2R: 1,714 pg/ml). However, after hospitalisation and one intravenous dose of TCZ and switch to oral tofacitinib, the patient's symptoms resolved rapidly, and her condition was stable at follow-up as of March 2022. Overall, the efficacy of sequential tofacitinib treatment after TCZ was remarkable in this patient.