Cutaneous Vasculitis Induced by Etanercept and Tocilizumab

Abstract

Biological disease modifying anti-rheumatic drugs (bDMARDs) have improved outcome of rheumatoid arthritis (RA). Tocilizumab (TCZ) is a monoclonal humanized anti-interleukin-6 receptor (IL6-R) which is indicated in case of inadequate response to one or more DMARDs or other biological treatment. Vasculitis has been reported with anti-TNF (Tumor Necrosis Factor) agents among more than 140 cases according to the BIOGEAS study group ( a Study Group on Autoimmune Diseases of the Spanish Society of Internal Medicine) but only in two cases with TCZ. We report the first case of cutaneous vasculitis occurring under both anti-TNF therapy and TCZ. Keywords:Cutaneous vasculitis; Anti-rheumatic drugs; Autoimmune diseases Case ReportA 60-year-old woman was followed-up for seropositive and erosive RA fulfilling ACR 1987 criteria's. She was initially treated by methotrexate then associated to sulfasalazine without any significant benefits. Leflunomide was introduced for a period of 4 months with a prompt response. However, a generalized cutaneous rash appeared two weeks after initiating this treatment and disappeared at interruption. The patient was treated by infliximab (3 mg/kg/8weeks) with a good initial response because of active disease; methotrexate was maintained (10 mg/week). Then a secondary failure was observed although rising dose treatment and shortening time between perfusions (5 mg/kg/ 6weeks). After 7 months, we switched to etanercept (ETN) 50 mg/ week. At the third week of treatment, the patient noticed a cutaneous ecchymotic rash of her legs, appearing few hours after the injection and disappearing spontaneously. She was hospitalized after 8 weeks of treatment, no skin lesions were found and the disease remains active. Ninth ETN injection was administrated under close monitoring. So she developed the same lesions described and respiratory distress. Steroids were administrated with a good outcome. Since a major averse effect occurred under anti-TNF therapy we decided to switch the biological agent to TCZ (8 mg/kg/4weeks). After the second perfusion, identical skin lesion she acquired under ETN occurred, appeared few hours after infusion and cleared one week later (Figure1). A skin biopsy was performed showing leucocytoclasic vasculitis with a perivascular inflammatory infiltration. Laboratory tests showed normal peripheral eosinophil and lymphocyte counts. Test for antinuclear antibodies, Antineutrophil cytoplasmic antibody (ANCA) and cryoglobulinemia were negative. Complement levels were normal. TCZ was associated with a good response for RA activity. Considering cutaneous vasculitis as a minor side effect and after discussion with the patient and pharmacovigilance expert, we decided to continue this therapy with tight control. Every infusion was preceded with antihistamine drugs and steroid pulse. Till this day, the patient has received 7 perfusions. Skin lesions still appear at the same time and in the same places and disappear soon without others cutaneous or respiratory outcomes. DiscussionCutaneous...