A Curious Case of Periodic Fevers, Avascular Necrosis and Inflammatory Nodules

We report a case of a 16-year-old Caucasian female with the explosive onset of fevers, arthralgias and refractory urticaria. Her history was signifi-cant for avascular necrosis of her wrists and feet four years prior to her presentation. Her clinical symptoms were associated with a marked inflammatory response but without serological evidence of autoimmunity. Her condition was initially responsive to colchicine and prednisolone, however, within a period of a few months became refractory. During this time, she developed unusual inflammatory nodules arising from her extensor digitorum, which became a feature of each clinical episode consisting of a tetrad of fevers, arthralgias, urticaria and tendon nodules. She had no evidence of uveitis or gut involvement. Her clinical phenotype suggested autoinflammatory disease but targeted gene sequencing did not reveal a known syndrome. Her family history was remarkable only for a brother with self-limiting erythema nodosum and a maternal grandmother with Crohns disease. Her clinical course has remained stormy but eventually she entered remission on a regimen of methotrexate 20 mg weekly and tocilizumab 400 mg monthly. The proband and her family have since undergone whole genome sequencing at the Centre for Personalised Immunology, which has provided insight into her diagnosis. Our patient demonstrates molecular and clinical features compatible with a recently described autoinflammatory syndrome; however, her presentation extends the described phenotype. This syndrome and potential pathogenic mechanisms will be discussed.