Aortic thrombosis in young women with Crohnʼs disease receiving adalimumab: Report of two cases

Tumor necrosis factor-alpha (TNF-α) blockers are being increasingly used in the treatment of severe, active Crohn's disease (CD). Adalimumab, a fully human TNF antagonist, is indicated after failed corticosteroid and/or an immunosuppressant therapy but may be associated with serious adverse events. We report the first two cases of aortic mural thrombosis in young women with CD treated with adalimumab (40 mg, 2 weeks), initially referred to our hospital for severe bowel flare. A 25-year-old woman with CD, treated with adalimumab and methotrexate for 3 months, reported on admission severe pain in the left leg. The left dorsalis pedis artery pulse was absent. A computed tomography (CT) scan revealed an acute embolic occlusion of the popliteal and crural arteries related to a mural thrombosis of the abdominal aorta. After failure of an anticoagulation therapy and a surgical thromboembolectomy, revascularization surgery was performed. IgG anticardiolipin antibodies was detected at 69 units, whereas other coagulation screening tests were negative (Table 1). Antineutrophil cytoplasmic antibodies (ANCAs) were detected by indirect immunofluorescence. A diagnosis of anti-TNF-α-induced antiphospholipid syndrome was suspected and treatment with adalimumab was suspended. On admission of a 24-year-old woman with CD, treated with adalimumab for 18 months, an abdominal CT was performed and showed a mural nonocclusive thrombosis of the abdominal aorta with extension to the inferior mesenteric artery origin. Complete resolution of the thrombus was achieved with intravenous heparin therapy. All investigations were negative (Table 1). Characteristics of the Subjects and Results of Investigations Characteristics of the Subjects and Results of Investigations In inflammatory bowel diseases (IBD), although the risk of venous thromboembolism is recognized, the risk of arterial thrombotic events (ATE) remains a matter of debate.1,–4 Two large recent case–control studies reported an increased incidence of ATE after adjusting for other risk factors for atherosclerosis.3, 4 Aortic thrombosis are unusual complications of IBD and only case reports have been reported, mostly concerning young women with associated risk factors (postoperative status, history of smoking, oral contraceptive, systemic aspergillosis) and a severe inflammatory syndrome.3,–5 The occurrence of aortic thrombosis is unusual in CD. Such an event has not yet been reported in patients receiving adalimumab and we think that its role needs to be discussed. Although neutralizing and nonneutralizing autoantibodies may appear following the administration of anti-TNF agents, and may be associated with the occurrence of associated autoimmune diseases, their production does not correlate with the occurrence of clinical features, suggesting that the autoimmune diseases in this context may be rather associated than induced.6, 7 In addition, the development of antinuclear antibodies (ANA) and anti-DNA antibodies in adalimumab-treated patients occurred at lower frequency than patients treated with infliximab or etanercept.7 Limited data of the induction of antiphospholipid antibodies during TNF-α blocking treatment have been reported.7 We can suppose that adalimumab may have played a role in the occurrence of aortic thrombosis in the first woman, whereas its relative contribution in the second case is less pertinent since she was taken estroprogestative contraception. ATEs are associated with high morbidity/mortality and curative anticoagulant therapy may have deleterious consequences in patients with IBD. Whereas the clinical efficacy and cost-effectiveness of a systematic venous thrombolism prophylaxis in nonhospitalized IBD patients during flares is discussed and requires investigation,8 the present cases support the need for a prevention and an early identification of risk factors for thrombosis at the individual level. We think that oral contraceptives with an estrogenic component must be avoided in young women and progestogens must be preferred. In addition, since TNF blockers are being used with increasing frequency in IBD, often in diseases displaying a high degree of inflammation, monitoring the autoantibodies may help to discuss a long-term preventive anticoagulation or a specific clinical supervision level.