Tocilizumab-induced inflammatory flare in Takayasu arteritis: a case report with exploratory mechanistic findings of Fcγ receptor involvement.

To report a refractory Takayasu arteritis (TAK) patient who developed a severe inflammatory flare after tocilizumab (TCZ) therapy and explore the underlying mechanism. A 21-year-old female with active TAK received TCZ after insufficient response to prednisone. TCZ was temporarily withheld then re-added at 400 mg due to disease relapse. After TCZ reintroduction, the patient developed worsening vascular pain, new abdominal pain, dizziness, fever, and markedly elevated inflammatory markers. Imaging showed worsened arteritis and new superior mesenteric arteritis. Methylprednisolone pulse and infliximab failed to control the flare, but tofacitinib achieved complete symptom resolution and normalized inflammatory markers within one month. Peripheral blood samples of the patient were collected and peripheral blood mononuclear cells (PBMCs) Fcγ receptor (FcγR) expression and downstream signaling were assessed upon TCZ stimulation. In vitro studies showed that increasing TCZ concentrations were associated with enhanced FcγRIIA, FcγRIIB, and FcγRI expression, along with increased spleen tyrosine kinase (SYK) phosphorylation in the patient's PBMCs. TCZ can paradoxically trigger an inflammatory flare in refractory TAK, with exploratory evidence suggesting possible involvement of excessive FcγR activation. Non-antibody-based Janus kinase (JAK) inhibitors like tofacitinib may be effective rescue therapy in such cases.