Developing of Granulomatosis with Polyangiitis during Etanercept Therapy

We describe a 67-year-old woman who developed c-ANCA positive vasculitis with involvement in eyes, skin, kidney, peripheral nerves, and upper and lower airway during treatment with etanercept therapy for rheumatoid arthritis. A diagnosis of Granulomatosis with Polyangiitis was done. Thus, anti-TNF therapy may be associated with the development of ANCA positive vasculitis. 1. Introduction The tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of many inflammatory and autoimmune conditions as rheumatoid arthritis (RA) and inflammatory bowel disease among others. Several anti-TNF-α biological agents have been approved for the management of RA [1]. The most frequent adverse events related to anti-TNF-α therapies are infectious diseases, malignancies, demyelinating diseases, and drug-induced lupus [2, 3]. In addition, treatment with etanercept has been associated with the development of diverse granulomatous diseases such as sarcoidosis [4–6], granulomatous hepatitis [7], granulomatous thyroiditis [8], and Wegener’s granulomatosis (now denoted as Granulomatosis with Polyangiitis-GPA-) [9]. Here, we report a new case of GPA developing in a patient with RA treated with etanercept. 2. Case Report A 67-year-old woman was admitted in our service by a clinical picture of two weeks of new onset-very painful and erythematous nodules in lower limbs that were followed by ulceration. She additionally manifested constitutional symptoms, conjunctive injection, nasal congestion, paresthesia, and paresia in the lower limbs associated with peripheral neuropathy and polyarthritis. She had a 2-year history of RA refractory to treatment with prednisolone (10？mgr/day) and methotrexate (15？mgr/weekly). After 8 months of this treatment and because of high activity disease score, a treatment with subcutaneous etanercept (50？mg weekly) was initiated three months before admission. The physical examination at admission revealed bilateral conjunctive injection, and the ophthalmologic exam showed bilateral scleritis. Deformity in hands with synovitis and nodules in the right elbow extensor aspect was also observed. Ulcerated lesions with necrotic center in lower limbs were evident (Figure 1). Laboratory test showed normal hemoglobin (13？g/dL), high WBC, and platelets count (18,000/mL and 542,000/mL, resp.). No lymphopenia was found. Acute phase reactants were elevated, with an erythrosedimentation rate of 111？mm/hour and C-reactive protein of 15.3？mg/dL (normal <0.5？mg/dL). Renal and liver functions were normal. The autoantibodies profile