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Paradoxical inflammation induced by anti-TNF agents in patients with IBD

Abstract

Anti-TNF antibodies have acquired a prominent place in the management of IBD (including Crohn's disease and ulcerative colitis), rheumatologic conditions (such as rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis) and psoriasis. They have a good safety profile, especially when contraindications such as demyelinating disease, active infections and/or abscesses are ruled out, and when necessary precautions to prevent reactivation of tuberculosis are taken. However, with increasing use of these agents, paradoxical adverse events have been reported. Some of these features are shared with the underlying disease for which these drugs are given, making management of these conditions challenging. For example, anti-TNF therapy is used for the treatment of psoriasis, but psoriasiform lesions are sometimes observed in patients receiving therapy. Similarly, anti-TNF therapy is used for the treatment of rheumatologic diseases, but arthralgias and arthritis are sometimes observed in patients receiving anti-TNF agents. We review the paradoxical inflammation induced by anti-TNF agents in patients with IBD, provide hypotheses for the occurrence of this paradoxical inflammation and give practical advice on how to manage these patients.

Key Points

  • Paradoxical adverse effects involving the skin, joints and lungs have been described with all anti-TNF agents

  • Skin manifestations are the most common adverse event and occur in 20–25% of patients receiving anti-TNFs

  • The outcome for skin manifestations is generally favourable with the implementation of preventive measures and topical therapy

  • Paradoxical reactions to anti-TNF agents may necessitate cessation of therapy in 5–10% of patients depending on the underlying reaction and its severity

  • The mechanisms by which adverse events to anti-TNF agents occur are not understood and more effort should be made to dissect the underlying pathways

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Figure 1: Distribution of type of skin lesions in the Leuven cohort.52
Figure 2: Examples of anti-TNF induced skin lesions.
Figure 3
Figure 4
Figure 5: Example of anti-TNF induced alopecia areata (courtesy of S. Segaert).
Figure 6: Genetic predisposition to anti-TNF skin lesions.52

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Both authors contributed equally to all aspects of this manuscript.

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Correspondence to Séverine Vermeire.

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Severine Vermeire is on the speakers bureau and receives grant/research support from Abbott, Centocor, MSD and UCB. Isabelle Cleynen declares no competing interests.

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Cleynen, I., Vermeire, S. Paradoxical inflammation induced by anti-TNF agents in patients with IBD. Nat Rev Gastroenterol Hepatol 9, 496–503 (2012). https://doi.org/10.1038/nrgastro.2012.125

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