Antithyroid arthritis syndrome caused by methimazole in a patient with Graves’ disease

SUMMARY: This is a report on antithyroid arthritis syndrome (AAS) which is a rare adverse effect of antithyroid agents. AAS presents with severe symptoms including myalgia, arthralgia, arthritis, fever, and skin eruption due to the use of antithyroid agents. We encountered a 55-year-old woman with severe pain in the hand and forearm and arthralgia in multiple joints, including the knee, ankle, hand, and wrist on day 23 after initiation of methimazole (MMI) for Graves’ disease. Blood tests revealed elevated inflammation markers such as C-reactive protein and interleukin-6, and magnetic resonance imaging of the hands confirmed inflammation findings. After withdrawing MMI on day 25, symptoms showed a tendency toward improvement. Afterwards, inflammation markers also dropped to an almost normal range. In addition to the above findings, the absence of anti-neutrophil cytoplasmic antibodies and most vasculitis symptoms such as nephritis, skin, or pulmonary lesions led to the diagnosis of AAS. A resolution of symptoms, except for mild arthralgia in the second to fourth fingers of the right hand, was observed 61 days after discontinuation of MMI. Although the pathogenesis is unclear, the positive drug lymphocyte stimulation test for MMI and the several weeks before the onset of AAS suggested involvement of a type IV allergic reaction. Based on a discussion of definitive treatment for Graves’ disease, radioactive iodine ablation with (131)I, which was selected by the patient, was performed and improved her thyroid function. Our case demonstrates the importance of awareness regarding AAS, which is a rare and under-recognized, but life-threatening adverse effect of antithyroid agents. LEARNING POINTS: Clinicians should be aware of the possibility of developing antithyroid arthritis syndrome (AAS) in patients treated with antithyroid medications, which can lead to severe migratory polyarthritis. Prompt cessation of the antithyroid agent is essential for the resolution of AAS. Anti-neutrophil cytoplasmic antibody (ANCA) negativity is needed to differentiate from antithyroid agent-induced ANCA-associated vasculitis, which shows arthritis similar to AAS.