Development of Crohn's disease following anti-tumour necrosis factor therapy (etanercept)

Division of Rheumatology, Department of Internal Medicine, Medical School, Akdeniz University, Antalya, Turkey.
Colorectal Disease (Impact Factor: 2.35). 03/2008; 10(9):953-4. DOI: 10.1111/j.1463-1318.2008.01490.x
Source: PubMed


Inhibition of tumour necrosis factor (TNF)-alpha is effective in the treatment of rheumatoid arthritis and other inflammatory rheumatic diseases. Anti-TNF antibodies such as infliximab, etanercept and adalimumab are commonly used. There are structural and functional differences among these agents. We describe development of Crohn's disease in a patient with ankylosing spondylitis receiving anti-TNF therapy. This case suggests that the appearance of gastrointestinal symptoms in patients on anti-TNF therapy must be evaluated to find out whether this is a new onset or an exacerbation of underlying inflammatory bowel disease.

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    • "The acute inflammatory response, dependent on the acute release of proinflammatory cytokines, is important for the clearance of bacteria and fecal material from the tissues, which takes place over a few hours. The lack of TNF after the administration of therapeutic antagonists for the treatment of other chronic inflammatory diseases has been reported to precipitate the development of CD (Charach et al., 2008; Yazisiz et al., 2008). "
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    ABSTRACT: The cause of Crohn's disease (CD) remains poorly understood. Counterintuitively, these patients possess an impaired acute inflammatory response, which could result in delayed clearance of bacteria penetrating the lining of the bowel and predispose to granuloma formation and chronicity. We tested this hypothesis in human subjects by monitoring responses to killed Escherichia coli injected subcutaneously into the forearm. Accumulation of (111)In-labeled neutrophils at these sites and clearance of (32)P-labeled bacteria from them were markedly impaired in CD. Locally increased blood flow and bacterial clearance were dependent on the numbers of bacteria injected. Secretion of proinflammatory cytokines by CD macrophages was grossly impaired in response to E. coli or specific Toll-like receptor agonists. Despite normal levels and stability of cytokine messenger RNA, intracellular levels of tumor necrosis factor (TNF) were abnormally low in CD macrophages. Coupled with reduced secretion, these findings indicate accelerated intracellular breakdown. Differential transcription profiles identified disease-specific genes, notably including those encoding proteins involved in vesicle trafficking. Intracellular destruction of TNF was decreased by inhibitors of lysosomal function. Together, our findings suggest that in CD macrophages, an abnormal proportion of cytokines are routed to lysosomes and degraded rather than being released through the normal secretory pathway.
    Full-text · Article · Sep 2009 · Journal of Experimental Medicine
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    ABSTRACT: Ankylosing spondylitis (AS) is a systemic inflammatory rheumatic disease responsible for back pain, stiffness and progressive loss of functional capacity with limited therapeutic options. Regular physical exercises together with the use of nonsteroidal antiinflammatory drugs are the two recognized treatment options in AS. Infliximab is a chimeric anti-tumor necrosis factor-α monoclonal antibody that has been demonstrated to be highly effective in the treatment of AS, providing clinical amelioration at both axial and peripheral skeleton. Infliximab also improves quality of life, function, biological parameters (acute phase reactants) and inflammatory lesions of the spine as detected by magnetic resonance imaging. It is given at a 5 mg/kg dosage, as an infusion at weeks 0, 2, 6, and every 6 to 8 weeks after. Open-label and placebo-controlled trials have well demonstrated its high level of efficacy, with an improvement of the disease activity of at least 50% in 60%-80% of patients. In a large placebo-controlled trial, Assessment in Ankylosing Spondylitis Response Criteria (ASAS20) responders were observed in 61.2% of patients receiving infliximab compared to 19.2% of patients under placebo. Long-term efficacy is maintained when infliximab is administered every 6-8 weeks. Consensus international guidelines for the initiation and the use of this expensive treatment are available. Some questions remain, including the long-term safety, in particular the risk of lymphoma, and the potential influence of infliximab on radiological progression which is not currently demonstrated. Despite these concerns, infliximab has revolutionized the management of AS and represents a considerable therapeutic advancement in this disabling disease. © 2009 Toussirot et al, publisher and licensee Dove Medical Press Ltd.
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