Review Paradoxical immune-mediated inflammation in inflammatory bowel disease patients receiving anti-TNF-α agents Gionata Fiorino a , Silvio Danese a, ⁎, Benjamin Pariente b , Matthieu Allez b a IBD Center, IRCCS Istituto Clinico Humanitas, Rozzano, Milan, Italy b Service de Gastroentérologie, INSERM unit U940 (Avenir), Hôpital Saint-Louis, APHP, Université Denis Diderot, Paris 7, Paris, France abstract article info Available online 15 June 2013 Keywords: Paradoxical reactions Autoimmunity Anti-TNF IBD Reports of autoimmune diseases, including psoriasis- and dermatitis-like skin reactions with anti-tumor necrosis factor-α (TNF-α), are increasing, likely a reflection of the growing use of these agents. This paradoxical phenom- enon can no longer be considered rare, with some studies providing incidence estimates of greater than 10%. This paradoxical inflammation has been reported in patients receiving treatment with anti-TNF-α agents for a variety of inflammatory conditions, including inflammatory bowel disease, psoriasis and rheumatoid arthritis and ap- pears to be a class effect. Moreover, there have recently been reports of autoimmune arthralgia occurring in pa- tients receiving anti-TNF-α agents. Further studies are necessary to determine the true incidence of this phenomenon and to identify those patients most likely to be at risk. © 2013 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2. Paradoxical skin lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2.1. Incidence and characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2.2. Therapeutic strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 2.3. Pathogenic mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3. Paradoxical joint inflammation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.1. Therapeutic strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3.2. Pathogenic mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. De Novo IBD in patients receiving anti-TNF . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4.1. Pathogenic mechanisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5. Other IMIDs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5.1. Ocular manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 5.2. Neurological manifestations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 5.3. Sarcoidosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 6. Autoimmune diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 7. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 1. Introduction Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that plays a key role in inducing inflammatory response to injuries. Its role in triggering inflammation has been clearly established in immune- mediated diseases, including rheumatoid arthritis, spondylarthritis, inflammatory bowel diseases (IBD) and psoriasis, although some TNF- α-Amediated pathways remain unknown [1]. The pharmacological blockade of TNF-α with selective monoclonal antibodies has revolu- tionized the management of patients with immune-mediated inflam- matory disorders (IMID) [2]. There is substantial evidence supporting the overall good safety profile of the anti TNF-α agents, particularly the lack of any significant increase in risk of serious infections or cancer [3]. However, there are Autoimmunity Reviews 13 (2014) 15–19 ⁎ Corresponding author at: IBD Center, Division of Gastroenterology, IRCCS Istituto Clinico Humanitas ICH 20089, Rozzano, Milan, Italy. E-mail address: sdanese@hotmail.com (S. Danese). 1568-9972/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.autrev.2013.06.005 Contents lists available at ScienceDirect Autoimmunity Reviews journal homepage: www.elsevier.com/locate/autrev