The First European Evidence-based Consensus on Extra-intestinal Manifestations in Inflammatory Bowel Disease
This is the first European Crohn’s and Colitis Organisation [ECCO] consensus guideline that addresses extra-intestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. It has been drafted by 21 ECCO members from 13 European countries. Although this is the first ECCO consensus guideline that primarily addresses EIMs, it is partly derived from, updates, and replaces previous ECCO consensus advice on EIMs, contained within the consensus guidelines for Crohn’s disease 1 [CD] and ulcerative colitis 2 [UC]. The strategy to define consensus was similar to that previously described in other ECCO consensus guidelines [available at www.ecco-ibd.eu ]. Briefly, topics were selected by the ECCO guidelines committee [GuiCom]. ECCO members were selected to form working groups. Provisional ECCO Statements and supporting text were written following a comprehensive literature review, then refined following two voting rounds which included national representative participation by ECCO’s 35 member countries. The level of evidence was graded according to the Oxford Centre for Evidence-based Medicine [www.cebm.net]. The ECCO Statements were finalised by the authors at a meeting in Vienna in October 2014 and represent consensus with agreement of at least 80% of participants. Complete consensus [100% agreement] was reached for most statements. The supporting text was then finalised under the direction of each working group leader [VA, SV, FC, MH] before being integrated by the two consensus leaders [MH, FC]. This consensus guideline is pictorially represented within the freely available ECCO e-Guide [http://www.e-guide.ecco-ibd.eu/]. Up to 50% of patients with inflammatory bowel disease [IBD] experience at least one extra-intestinal manifestation [EIM], which can present before IBD is diagnosed. 34,5,6 EIMs adversely impact upon patients’ quality of life and some, such as primary sclerosing cholangitis [PSC] or venous thromboembolism [VTE], can be life-threatening. The probability of developing EIMs increases with disease duration and in patients who already have one EIM. 7 EIMs are more common in CD than UC, 7,8 particularly in patients with colonic CD; some EIMs, such as iritis/uveitis, are more common in women whereas PSC and ankylosing spondylitis are more common in males. 3 Most EIMs run in parallel with intestinal disease activity, 4 with the exception of ankylosing spondylitis and uveitis and with uncertainty regarding PSC and pyoderma gangrenosum [PG]. 9 The management of complex EIMs should be discussed in a multidisciplinary team meeting. Both peripheral and axial arthropathies occur in UC and CD, and belong to the spondyloarthritis [SpA] group of conditions (evidence level 2 [EL2]). They should be distinguished from arthralgia, which is more common. The prevalence of axial disease is equal between sexes and forms of IBD, but peripheral arthropathies are more common in CD [particularly affecting the colon] and in females [EL3] Diagnosis of axial SpA is based on the clinical feature of inflammatory low back pain associated with magnetic resonance imaging [MRI ]or radiographic features of sacroiliitis [EL 2]. Human leukocyte antigen B27 [HLA-B27] is associated with axial arthritis, but it has a lower prevalence than in idiopathic ankylosing spondylitis, making it unreliable as a diagnostic test in IBD [EL2] Radiological evidence of sacroiliitis occurs in 20–50% of patients with UC and CD, but progressive ankylosing spondylitis occurs in only 1–10% of patients [EL2]. MRI may identify early sacroiliitis in symptomatic patients with normal plain radiology [non-radiographic SpA] [EL2] Arthropathies associated with IBD belong to the SpA group of conditions. According to the Assessment in Spondyloarthritis International Society [ASAS] classification of 2009, 10 SpA are divided into axial and peripheral SpA, depending on the predominant symptoms. Diagnosis of axial SpA is based on magnetic resonance imaging [MRI] or radiographic features of sacroiliitis associated with clinical features of inflammatory low back pain. Radiological evidence of sacroiliitis is common in both UC and CD, occurring in 20–50 % of patients, 11,12,13 but progressive AS with syndesmophytes occurs in only 1–10 % of patients. 14,15,16 Early assessment using T1-weighted spin-echo [TISE], short tau inversion recovery [STIR], and fat-saturated T2-weighted sequences, are recommended for patients aged less than 40 years with inflammatory back pain lasting more than 3 months, to identify non-radiographic sacroiliitis. 17,18 Human leukocyte antigen [HLA]-B27 is found in 25–75% of patients with IBD and AS 11,19,20,21 but only in 7–15% of patients with isolated sacroiliitis. HLA-B27 positive IBD patients seem to be at risk for the development of AS 21 but, due to a lower prevalence than in idiopathic AS, it is unreliable as a diagnostic test in IBD. 22,23 Diagnosis of peripheral arthropathy and/or enthesitis associated with IBD is based on signs of inflammation and exclusion of other specific forms of arthritis [EL3]. Type I is an acute pauciarticular arthritis, affecting large joints, and is usually associated with active IBD. Type II is polyarticular, affecting a larger number of peripheral joints, and is independent of IBD activity [EL4] The peripheral arthritis of IBD is an inflammatory arthropathy but, unlike psoriatic arthritis and other inflammatory arthropathies, it is generally non-erosive. The ASAS guidelines for peripheral SpA included only six patients with IBD, 24 so the clinical classification of IBD-related peripheral arthropathies is usually based on a larger study of IBD patients. 25 On the basis of articular involvement and natural history, two different have been Type 1 is as pain with evidence of or affecting than joints, the large of the lower The are usually acute and than 10 and usually with IBD Type 2 more than joints, has a and the for or independent of IBD Diagnosis is on clinical based on features of inflammation and exclusion of other specific forms of in to arthritis, and peripheral arthritis has to be from may to and and have been less in IBD. inflammation at the of a to the to and and or is of SpA, with a prevalence of in IBD. arthritis in IBD is usually and and more common in CD, particularly in with colonic may that of bowel it usually with or the of IBD. prevalence in IBD from to in UC and in the of peripheral arthritis is only and in a of patients. The of axial involvement is less and is to the of AS, and the of IBD. AS is a progressive with and affecting patients’ quality of It is to identify early axial SpA, to the to radiographic axial SpA that occurs in % by 2 years in with an or with active inflammation on The of IBD in the of SpA is by the that sacroiliitis and spondylitis occur in to of patients with IBD, whereas to of patients with AS or SpA have evidence of only The of HLA-B27 with AS is in IBD, but to a than in idiopathic AS This may to the between the of AS and IBD. and have more than for IBD in an and in IBD and of for AS were by IBD with a that and to the to the and and to a common the complex with axial SpA should be with and are [EL but with is recommended [EL2]. [EL2] and [EL2] are of early is the for or to [EL2] of inflammation is to peripheral arthritis or symptomatic are [EL but should be as as arthritis, [EL2] and [EL4] may have a is and in [EL2] for the of IBD-related arthropathy are based on in SpA, in IBD have been only or are with axial SpA should be with of the disease the of and in axial but with is in IBD. Although the risk for a larger study CD patients and UC patients that with low of was of was associated with disease activity with Crohn’s but this was by a in disease The of such as and may be with a lower risk of disease than and in are of is the in patients or to on the of on radiographic are less may of early axial SpA, of large are of inflammation is to peripheral is for the of and for symptomatic Although and are or only in ankylosing spondylitis, a 2014 of in patients with peripheral and recommended the for patients with short disease duration and a in that was to study the that be an in SpA patients with peripheral are with seem to can be in has been to be in 35 in patients with disease on quality of pain is common in IBD and may be associated with the of or the of associated with is associated with and usually the first 3 of to is usually Diagnosis of in is from a on radiographic is a risk for and patients who should [EL2] and are common in and patients with IBD disease or low activity, and The of in is based on assessment of by is as a at least lower than the for the between and risk is and to the has been should be as for and the for in the of risk low previous IBD is to and so can be to and peripheral and are and recommended as for IBD patients from for the and are based on risk such as 3 months, of and have been recommended in in the of risk the the for with patients at risk for of the and peripheral should the risk increases for each in the have been in patients with both and normal the that is the risk for in patients with IBD. between and risk The of is a previous by of the is in the of patients with IBD, who are patients aged between and 40 of patients have with a and has been in of IBD patients. of IBD patients can 3 years in a have in with have that in are similar in IBD to in the The of each risk to be has been of the of can be a of IBD. is common in IBD patients, and so may to risk of IBD. study a for in IBD women in a lower risk of CD and UC than in are with previous a in disease to a of and [EL2] are in should and for for the duration of is a for and are recommended the is less than patients, a of should for more [EL4] of disease activity is particularly in the in women or with previous of and other can [EL2] should be in patients with low and/or risk such as which risk in the of a of may be in who has been in IBD in aged to to and/or should be or and and from and/or should be should be in the recommended this usually at a of or should be only is with and increases in patients with IBD. large study in CD that of disease activity and of and were associated with a in of 4 The of and in has been in patients with IBD, in or is common in patients with IBD and should be as should and for that are for the of low in IBD and the risk of but and can be recommended for in IBD patients. to the of a for with is in women or of the is a and should be in patients with or patients, a before be are and have using or as are associated with only increases in and in is evidence that or other peripheral The evidence for and of in patients is patients with active disease should be according to guidelines with to and inflammatory activity, in to or should be in patients with IBD before can be an risk for patients with with more should be to a to an This should be from uveitis and based upon the of and this is or in patients with manifestations and patients should be by an with in inflammatory disease uveitis and are the most common manifestations of IBD. manifestations in IBD can be to and/or of the intestinal disease The classification of uveitis has been in the of guidelines 1 ]. of The most manifestations are or and or uveitis are more to be are occurring in less than but may to of uveitis a of 13 a of features from to to disease activity in the bowel and other extra-intestinal uveitis can be independent of bowel and other EIMs and may the of bowel symptoms. of involvement with to and may be with and and and may as to which is is less common but has more to CD, uveitis is in and acute uveitis with may of a of the features of and The of to of should to an with in the management of and the of and the and the between and pain associated with of the and to be from to or other involvement should for using a to for the of inflammatory and/or both the guidelines and of the International are in disease assessment may be in and of the of manifestations from of IBD in some this to of is to be to of patients in are study of only that patients with IBD are more to of with and and inflammatory disease as EIMs of IBD represent associated with and of both and into the or this may be associated with with and supporting in uveitis with and on I and are by may or or can be for symptomatic for or uveitis should be by an and or and [EL4] a is the of most is may be with following management of the bowel and to the of and uveitis should be with and uveitis and other the level of evidence with the evidence for of being in patients with uveitis but IBD. of and or have been from 3 or 4 the of and in uveitis and but is based upon evidence from the of only a IBD. and have each been to be in CD and or It is associated with disease and has a CD involvement of and associated with UC, have been has been described in with IBD, particularly in patients with UC, and may be due to by T2-weighted is a disease that in and that to It can be associated with IBD. 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