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To the Editor: We read with great interest the article by Mohan, et al 1 , describing a series of 35 patients with leukocytoclastic vasculitis (LV) possibly related to tumor necrosis factor-α (TNF-α ) blocking agents. The information is significant because a great number of patients presented unusual manifestations that were not observed during premarketing studies. We would also like to describe a patient who presented some special manifestations that might complete the facts of the above series. At the same time, we would like to learn more about Mohan's group of patients. Our patient was a 60-year-old man with a 10-year history of seroposi-tive and erosive rheumatoid arthritis (RA), who had been treated with gold salts and chloroquine, which were withdrawn because of inefficiency, and methotrexate, which was also withdrawn because the patient developed pulmonary fibrosis. In November 2002, because of the bad clinical evolu-tion, etanercept 25 mg twice a week was added to his regular treatment of deflazacort 7.5 mg, calcium 500 mg, vitamin D 400 IU, and indomethacin 50-100 mg daily. At that time, laboratory examination showed antinuclear antibody (ANA) titer of 1/40; rheumatoid factor (RF) 315 IU/ml; negative dsDNA, anti-Sm, anti-SSA, anti-SSB, and ribonucleoprotein RNP anti-bodies; and complement levels within normal limits. He improved marked-ly, but in July 2003 he developed a red rash on his legs, diagnosed as LV. ANA titer was over 1/320, other immunological findings were normal, and RF was 320 IU/ml. Etanercept treatment was continued because of the pos-itive evolution of the RA and with the patient's agreement. His vasculitis was treated by adding leflunomide 20 mg daily, without any other change in medication. The rash clearly improved 4 weeks after leflunomide was begun and remitted after 3 months. His RA continued to improve, with ANA titer 1/160. On followup 9 months after leflunomide was introduced, the patient did not present any skin reaction and continued to receive his usual treatment, with acceptable control of his RA. LV has been described as a side effect associated with etanercept, relat-ed or unrelated to ANA, that does not occur in systemic lupus erythematosus 2-4 . On the other hand, etanercept has been successfully tried in different vasculitic syndromes 5 . Although we consider that our patient's LV etiology may be caused by etanercept, RA and other medicines cannot be ruled out as factors. The increased ANA titers seem to be related to etanercept. His resolved rash and laboratory data seem to be linked to the lefluno-mide treatment. We decided to continue with etanercept because of the patient's very positive clinical response. Administration of infliximab was not considered because it could not be prescribed at the same time as the methotrexate, due to prior lung fibrosis in this patient. Further, adalimum-ab was not commercially available in Spain. Leflunomide was adminis-tered at the same time because it was thought to have possible therapeutic and synergistic effects in vasculitis 6 . Further, leflunomide has also been associated with vasculitis as a side effect 7 . Indeed, LV has been described in association with etanercept in patients who received leflunomide at the same time 4 . So leflunomide cannot be used preventively as a TNF-α block-ing agent. The positive clinical response in our patient suggests lefluno-mide as a possible therapeutic resource against vasculitis for this kind of patient. It also seems reasonable that the TNF-α blocking agent need not always be withdrawn when this kind of side effect occurs. We have not found previous reports of improved vasculitis associated with treatment with TNF-α blocking agent except when treatment is stopped. In our patient, we ascribe improvement to leflunomide. Mohan, et al describe a patient whose skin lesions disappeared when etanercept was decreased to once a week dosing and worsened when the dosing was increased to twice a week.We believe that the clinical course of our patient adds interesting data to those presented by Mohan, et al. We would like to know if the TNF-α blocking agent in any patient in this series was not withdrawn. We also wonder which patients were taking leflunomide in combination with TNF- blocking agent at the time that the LV appeared. ANTONIO JUAN, MD, Department of Rheumatology, Hospital Son Llatzer; BARTOLOMÉ RIBAS, MD, Department of Rheumatology, Hospital San Juan de Dios; CRISTINA NADAL, MD, Department of Dermatology, Hospital Son Llatzer; IMNACULADA ROS, MD, Department of Rheumatology, Hospital Son Llatzer, Palma de Mallorca, Spain. 1. Mohan N, Edwards ET, Cupps TR, et al. Leukocytoclastic vasculitis associated with tumor necrosis factor-alpha blocking agents. J Rheumatol 2004;31:1955-8. 2. Shakoor N, Michalska M, Harris CA, Block JA. Drug-induced systemic lupus erythematosus associated with etanercept therapy. Lancet 2002;359:579-80. 3. Galaria NA, Werth VP, Schumacher HR. Leukocytoclastic vasculitis due to etanercept. J Rheumatol 2000;27:2041-4. 4. Jarrett SJ, Cunnane G, Conaghan PG, et al. Anti-tumor necrosis factor-alpha therapy-induced vasculitis: case series. J Rheumatol 2003;30:2287-91. 5. Tan AL, Holdsworth K, Pease C, Emery P, McGonagle D. Successful treatment of resistant giant cell arteritis with etanercept. Ann Rheum Dis 2003;62:373-4. 6. Metzler C, Fink C, Lamprecht P, Gross WL, Reinhold-Keller E. Maintenance of remission with leflunomide in Wegener's granulomatosis. Rheumatology Oxford 2004;43:315-20.7. Macdonald JA, Zhong T, Lazarescu A, Gan BS, Harth M. Vasculitis associated with the use of leflunomide. J Rheumatol 2004;31:2076-78. |
