Relapse of Systemic Juvenile Idiopathic Arthritis after Influenza Vaccination in a Patient Receiving Tocilizumab

Abstract

We report the case of a patient with systemic juvenile idiopathic arthritis (s-JIA) receiving tocilizumab (TCZ) who experienced relapses of s-JIA after receiving influenza vaccination. Systemic symptoms of s-JIA might be masked during TCZ therapy. Careful observation with the monitoring of serum interleukin (IL)-18 and IL-6 levels may be useful. CASE REPORTA 3-year-old girl was initially diagnosed with systemic juvenile idiopathic arthritis (s-JIA) on the basis of the presence of spiky fever, a salmon-colored erythematous rash, polyarthritis, and leukocytosis (white blood cell count [WBC], 14,700/l) as well as elevated serum levels of C-reactive protein (CRP; 5.38 mg/ dl), matrix metalloprotease-3 (MMP-3; 626.4 ng/ml), and interleukin (IL)-18 (2,230 pg/ml). Her clinical symptoms improved rapidly after the administration of prednisolone (PSL; 1 mg/kg of body weight/day). After tapering the PSL dosage (0.6 mg/kg/day), the first relapse of s-JIA occurred, manifesting as high fever and polyarthralgia. The patient again responded to steroid therapy, but frequent relapses occurred when the PSL dosage was decreased. Treatment with tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, was initiated, and long-term remission (7 months) was achieved along with a decrease in PSL dosage (0.4 mg/kg/day). Laboratory findings showed normal serum levels of MMP-3 (41.8 ng/ml), IL-18 (675 pg/ml), and IL-6 (Ͻ3 pg/ml). The girl subsequently received a 0.2-ml subcutaneous injection of commercially available inactivated influenza vaccine on her left upper arm; the vaccine was approved for use in the 2010 to 2011 season in Japan (Kaketsuken, Kumamoto, Japan) ( Fig. 1 and Table 1). Seven days later, she abruptly developed pain and limitation of the motion of her left arm, without accompanying fever or rash. Laboratory findings revealed leukocytosis (WBC, 10,880/l) and elevated serum levels of MMP-3 (146.1 ng/ml), IL-6 (110 pg/ml), and IL-18 (4,800 IU/ml). However, her serum CRP level was normal (0.0 mg/dl). Computed tomography imaging of her left shoulder showed synovitis with effusion. After ad- ministration of a methylprednisolone pulse, treatment with PSL (0.6 mg/kg/day) and methotrexate (4 mg/week) was initiated. The girl responded to the therapy, and her clinical symptoms improved rapidly. Four weeks after the first vaccination, she received another subcutaneous injection of inactivated influenza vaccine according to the schedule previously followed in Japan (patients aged 1 to Ͻ6 years of age were inoculated twice with a dose of 0.2 ml at intervals of 1 to 4 weeks). Seven days later, pain and swelling of her left ankle joint developed, but fever and rash were absent. Laboratory findings revealed leukocytosis (WBC, 12,810/l) and elevated serum levels of MMP-3 (223.3 ng/ml), IL-6 (284 pg/ml), and IL-18 (24,000 IU/ml). However, the serum CRP level remained normal (0.0 mg/dl). Magnetic resonance imaging of her left ankle showed synovitis with effusion. After administration of a methylprednisolone pulse, her clinical s...

Vaccinations in Paediatric Rheumatology: an Update on Current Developments

“… No increase in disease activity after vaccination. Shimizu et al [ 57 ] 1 soJIA 1 anti-IL6 3 – Case report of disease flare after influenza vaccination. Shinoki et al [ 42 ] 27 soJIA 17 HC 27 anti-IL6 24 GC (mean dose 7.3 mg/day) 2B Seroconversion, seroconversion and GMT were similar to healthy controls.…”

“…These studies reported a stable disease activity over time or similar flare rates before and after vaccination (Table 2 ). One case report described a systemic onset JIA (soJIA) patient on anti-IL6 who received two seasonal influenza vaccines and had a disease flare after both vaccinations [ 57 ]. In contrast, a study in 27 soJIA patients using anti-IL6 receiving a seasonal influenza vaccine did not show any exacerbations [ 42 ].…”

“…Seven reports including 499 patients studied a non-adjuvanted non-live vaccine [ 24 , 25 , 31 , 32 , 36 , 56 , 58 ]. It was unclear whether the vaccine was adjuvanted in eight reports [ 19 , 22 , 23 , 40 , 42 , 55 , 57 , 61 ]. No marked increase in disease activity was seen in the patients receiving an adjuvanted vaccine compared to the patients who received an unadjuvanted dead composite vaccine.…”

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“…In that study, no severe adverse events or disease exacerbation was recorded after the influenza vaccination [53]. However, one case of disease exacerbation after influenza vaccination was reported in a single patient with systemic JIA receiving tocilizumab [54].…”