Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease

Abstract

The treatment of inflammatory bowel disease (IBD) has been revolutionised over the past decade by the increasing use of immunomodulators. With such immunomodulation, the potential for opportunistic infection is a key safety concern for patients with IBD. Opportunistic infections pose particular problems for the clinician: they are often difficult to recognise and are associated with appreciable morbidity or mortality, because they are potentially serious and hard to treat effectively. This led the European Crohn's and Colitis Organisation (ECCO) to update the previous Consensus meeting on opportunistic infections in IBD. To organise the work, infections were classified into six major topics. Guideline statements of 2009 were analysed systematically by the chairs and the working parties. In parallel, the working parties performed a systematic literature search of their topic with the appropriate key words using Medline/Pubmed and the Cochrane database, as well as their own files. The evidence level (EL) was graded according to the 2011 Oxford Centre for Evidence-Based Medicine (http://www.cebm.net/index.aspx?o=5653). Provisional update guideline statements were then posted on a weblog. Discussions and exchange of the literature evidence among the working party members was then performed on the weblog. The working parties then met in Lille on the 15th–16th of November 2012 to agree on the statements. Consensus was defined as agreement by > 80% of participants, termed a Consensus Statement and numbered for convenience in the document. This paper is the product of work by gastroenterologists, infectious disease experts and pediatricians. It provides guidance on the prevention, detection and management of opportunistic infections in patients of all age categories with IBD. After a section on definitions and risk factors for developing opportunistic infection, there are five sections on different infectious agents, followed by a section on information and guidance for patients with IBD travelling frequently or to less economically developed countries. In the final section, a systematic work up and vaccination programme is proposed for consideration in patients exposed to immunomodulator therapies. The final document on each topic was written by the workgroup leader and their working party. Statements are intended to be read in context with qualifying comments and not read in isolation. The final text was edited for consistency of style by JF Rahier, F Magro, R Eliakim and JF Colombel before being circulated and approved by the participants. In some areas the level of evidence is generally low, which reflects the paucity of randomised controlled trials. Consequently expert opinion is included where appropriate. An immunocompromised host has an alteration in phagocytic, cellular, or humoral immunity that increases the risk of an infectious complication or an opportunistic process. Patients may also be immunocompromised if they have a breach of their skin or mucosal defense barriers that permits microorganisms to cause either local or systemic infection.1 There is no clearcut definition of an immunocompromised state. Three categories are recognised by the Centers for Disease Control,2 depending on the severity of immunosuppression: Persons who are severely immunocompromised not as a result of HIV infection: Severe immunosuppression can be the result of congenital immunodeficiency, leukemia, lymphoma, generalised malignancy or therapy with alkylating agents, antimetabolites, radiation, or high doses of corticosteroids (2 mg/kg body weight, or > 20 mg/day of prednisolone, Section 2.4.1) Persons with HIV infection Persons with conditions that cause limited immune deficits (e.g. hyposplenism and renal failure) An opportunistic infection may be defined as a usually progressive infection by a microorganism that has limited (or no) pathogenic capacity under ordinary circumstances, but which is able to cause serious disease as a result of the predisposing effect of another disease or of its treatment.3 Patients with IBD should not be routinely considered to have altered immunocompetence [EL5] per se, despite evidence of impaired innate mucosal immunity. Different immunomodulators may alter immune responsiveness by different mechanisms and to varying degrees, but there is currently no single method of evaluating the effects of immunosuppression on the immune system [EL5] From genome wide association studies there is increasing evidence of an aberrant immune response in IBD.4 Susceptibility loci involve both the innate and adaptive immune response towards a diminished diversity of commensal microbiota.5 Description of the numerous mechanisms contributing to this dysimmunity is beyond the scope of this article. Despite evidence of defective mucosal immunity, there is no proof of a systemic immune defect in patients with IBD in the absence of concomitant immunomodulator therapy. Patients with IBD are therefore rendered immunoco