Development of Crohn's disease following anti-tumour necrosis factor therapy (etanercept).
ABSTRACT 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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ABSTRACT: In the past, there has been considerable focus on a host of drugs and chemicals that may produce colonic toxicity. Now, a variety of new biological monoclonal antibody agents, usually administered by infusion, have appeared in the clinical realm over the last decade or so to treat different chronic inflammatory or malignant disorders.For some of these agents, adverse effects have been documented, including apparently new forms of immune-mediated inflammatory bowel disease. In some, only limited symptoms have been recorded, but in others, severe colitis with serious complications, such as bowel perforation has been recorded. In others, adverse effects may have a direct vascular or ischemic basis, while other intestinal effects may be related to a superimposed infection. Some new onset cases of ulcerative colitis or Crohn's disease may also be attributed to the same agents used to treat these diseases, or be responsible for disease exacerbation. Dramatic and well documented side effects have been observed with ipilimumab, a humanized monoclonal antibody developed to reduce and overcome cytotoxic T-lymphocyte antigen 4, a key negative feedback regulator of the T-cell anti-tumor response. This agent has frequently been used in the treatment of different malignancies, notably, malignant melanoma. Side effects with this agent occur in up to 40% and these are believed to be largely immune-mediated. One of these is a form of enterocolitis that may be severe, and occasionally, fatal. Other agents include rituximab (an anti-CD20 monoclonal antibody), bevacizumab (a monoclonal antibody against the vascular endothelial growth factor) and anti-tumor necrosis factor agents, including infliximab, adalimumab and etanercept.World Journal of Gastroenterology 04/2012; 18(16):1871-4. · 2.55 Impact Factor
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ABSTRACT: Dysregulated inflammation in the gut, designated clinically as inflammatory bowel disease (IBD), is manifested by the prototypic phenotypes of an Arthus-like reaction restricted to the mucosa of the colon, as in ulcerative colitis, or a transmural granulomatous reaction, as in Crohn's disease, or an indeterminate form of the two polar types. That the inflammation of IBD can trespass the boundaries of the bowel has long been known, with articular, ophthalmologic, cutaneous, hepatobiliary or other complications/associations - some autoimmune and others not - affecting significant numbers of patients with IBD. Also notable is the frequency of diagnosis of IBD-type diseases on a background of systemic, (mostly myelo-hematological) disorders, associated with alterations of either (or both) innate or adaptive arms of the immune response. Finally, cases of IBD are reported to occur as an adverse effect of TNF inhibitors. Bone marrow transplant has been proven to be the only curative measure for some of the above cases. Thus, in effect, the IBDs should now be regarded as a systemic, rather than bowel-localized, disease. Genome-wide association studies have been informative in consolidating the view of three phenotypes of IBD (ulcerative colitis, Crohn's disease and mixed) and, notably, are revealing that the onset of IBD can be linked to polymorphisms in regulatory miRNAs, or to nucleotide sequences coding for regulatory lymphokines and/or their receptors. At the effector level, we emphasize the major role of the Th17/IL-23 axis in dictating the perpetuation of intestinal inflammation, augmented by a failure of physiological control by regulatory T-cells. In conclusion, there is a central genesis of the defects underlying IBD, which therefore, in our opinion, is best accommodated by the concept of IBD as more of a syndrome than an autonomous disease. This altered mindset should upgrade our knowledge of IBD, influence its medical care and provide a platform for further advances.Expert review of gastroenterology & hepatology 06/2011; 5(3):401-10.
- Journal of clinical rheumatology: practical reports on rheumatic & musculoskeletal diseases 09/2012; 18(6):325. · 1.19 Impact Factor