Systemic lupus erythematosus induced by anti-tumour necrosis factor alpha therapy: a French national survey

Abstract

The development of drug-induced lupus remains a matter of concern in patients treated with anti-tumour necrosis factor (TNF) alpha. The incidence of such adverse effects is unknown. We undertook a retrospective national study to analyse such patients.Between June and October 2003, 866 rheumatology and internal medicine practitioners from all French hospital centres prescribing anti-TNF in rheumatic diseases registered on the website of the 'Club Rhumatismes et Inflammation' were contacted by email to obtain the files of patients with TNF-induced systemic lupus erythematosus. Twenty-two cases were collected, revealing two aspects of these manifestations. Ten patients (six patients receiving infliximab, four patients receiving etanercept) only had anti-DNA antibodies and skin manifestations one could classify as 'limited skin lupus' or 'toxidermia' in a context of autoimmunity, whereas 12 patients (nine patients receiving infliximab, three patients receiving etanercept) had more complete drug-induced lupus with systemic manifestations and at least four American Congress of Rheumatology criteria. One patient had central nervous system manifestations. No patients had lupus nephritis. The signs of lupus occurred within a mean of 9 months (range 3–16 months) in patients treated with infliximab and within a mean of 4 months (range 2–5 months) in patients treated with etanercept. In all cases after diagnosis was determined, anti-TNF was stopped and specific treatment introduced in eight patients: two patients received intravenous methylprednisolone, four patients received oral steroids (15–35 mg/day), and two patients received topical steroids. Lupus manifestations abated within a few weeks (median 8 weeks, standard deviation 3–16) in all patients except one with longer-lasting evolution (6 months). At that time, cautious estimations (unpublished data from Schering Plough Inc. and Wyeth Inc.) indicated that about 7700 patients had been exposed to infliximab and 3000 to etanercept for inflammatory arthritides in France. It thus appears that no drug was more implicated than the other in lupus syndromes, whose incidence was 15/7700 = 0.19% with infliximab and 7/3800 = 0.18% with etanercept.Clinicians should be aware that lupus syndromes with systemic manifestations may occur in patients under anti-TNF alpha treatment.

The Pathogenesis and Therapeutic Implications of Tubulointerstitial Inflammation in Human Lupus Nephritis

“…These four patients did experience an increase in dsDNA titers but this did not correspond to increased disease activity. Anti-TNF therapies are well known to be associated with the development of autoantibodies and SLE-like manifestations including pericarditis, neuritis, and nephritis 91, 92 . Therefore, more clinical studies are needed to define which lupus patients might benefit from anti-TNF therapy.…”

Cardiac Tamponade as a Presenting Manifestation of Infliximab-Induced Lupus in Patient Treated for Crohn's Disease

“…Although there is no recognized criteria for drug-induced lupus, criteria for the diagnosis of DILE in patients previously treated with anti-TNF therapy have been proposed 8. The inclusion criteria include one of the following: 1) anti-TNF-α treatment for inflammatory arthritis, 2) a temporal relationship between clinical manifestations and anti-TNF-α treatment, or 3) the presence of at least four American Congress of Rheumatology criteria of SLE 8.…”

“…The inclusion criteria include one of the following: 1) anti-TNF-α treatment for inflammatory arthritis, 2) a temporal relationship between clinical manifestations and anti-TNF-α treatment, or 3) the presence of at least four American Congress of Rheumatology criteria of SLE 8. However, inflammatory bowel disease (IBD) patients often do not fulfill the American College of Rheumatology criteria for SLE.…”

Infliximab-Induced Lupus-Like Syndrome in a Female Patient With Rheumatoid Arthritis (A Case Report): An Accident or Regularity?

“…ЭТЦ [14][15][16][17][18][19][20] и АДА [21,22], по-явившиеся позже ИНФ, также индуцируют ВИИФНОα. Обследование всех французских центров, применяющих ингибиторы ФНОα для лечения ревматических заболева-ний, выявило 22 больных с ВИИФНОα [23]. У 10 из них развилась изолированная кожная волчанка с антителами к двуспиральной ДНК (дсДНК), и у 12 была «полноцен-ная» (full-blown) ВИЛП с наличием не менее 4 из 11 диаг-ностических критериев СКВ [6,7].…”