Crohn??s Disease Patients Carrying Nod2/CARD15 Gene Variants Have an Increased and Early Need for First Surgery due to Stricturing Disease and Higher Rate of Surgical Recurrence

Álvarez-Lobos, Manuel; Aróstegui, Juan I.; Sans, Miquel; Tàssies, Dolors; Plaza, Susana; Delgado, Salvadora; Lacy, Antonio M.; Piqué, Josep M.; Yagüe, Jordi; Panés, Julián

doi:10.1097/01.sla.0000186173.14696.ea

Cited by 169 publications

(116 citation statements)

References 44 publications

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“…It is also possible that different defensins may be specific to CD and UC variations [17] . These observations demonstrate the fine-tuning of [18] . Despite the well-demonstrated and replicated role of CARD15 mutations in the susceptibility for CD in the majority of Caucasian populations [19][20][21][22][23] , no mutations have been found in Asian [24][25][26][27] and in several European populations.…”

Section: Introductionsupporting

confidence: 53%

Contribution of genetics to a new vision in the understanding of inflammatory bowel disease

Peña¹

2006

WJG

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Inflammatory bowel diseases (IBD), such as Crohn' s d i s e a s e ( C D ) a n d u l c e ra t i v e c o l i t i s ( U C ) , a r e chronic inflammatory autoimmune conditions of the gastrointestinal tract. Other organs, such as the eyes, skin and articulations, are often affected and IBD may be accompanied by other diseases of autoimmune origin. There is no single etiological factor responsible for the onset of IBD. Recent advances in genetics and in the molecular mechanisms of the proteins coded by these genes have given rise to a new vision in understanding these complex diseases. Activation of specific genes that affect antigen presentation and the handling of cells by innate immunity may lead to autoimmunity with the consequent activation of the major histocompatibility complex (MHC) and multiple cytokines involved in the regulation of acquired immunity. In this review IBD is described as a constellation of diseases that can best be classified as barrier diseases. This vision, developed by Kiel in Germany, includes the idea that changes in our environment due to the westernization of civilization have not been met with adaptation of the innate immune system, and this has given rise to autoimmune diseases. These diseases affect 1-5 of 1000 individuals and represent a major burden on the national health systems of many countries on different continents. On a world scale, a major challenge is to generate interventions to prevent the development of these diseases in Asia, Latin America and Africa.

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Section: Introductionsupporting

confidence: 53%

Contribution of genetics to a new vision in the understanding of inflammatory bowel disease

Peña¹

2006

WJG

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“…earlier need for first surgery and reduced postoperative disease-free interval [42][43][44] . Some studies have also tried to identify genetic factors associated with response to treatment.…”

Section: Genetic Predictors Of CD Coursementioning

confidence: 99%

Clinical, serological and genetic predictors of inflammatory bowel disease course

Beaugerie¹

2012

WJG

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Patients with extensive or complicated Crohn's disease (CD) at diagnosis should be treated straightaway with immunosuppressive therapy according to the most recent guidelines. In patients with localized and uncomplicated CD at diagnosis, early use of immunosuppressive therapy is debated for preventing disease progression and limiting the disabling clinical impact. In this context, there is a need for predictors of benign or unfavourable subsequent clinical course, in order to avoid over-treating with risky drugs those patients who would have experienced spontaneous mid-term asymptomatic disease without progression towards irreversible intestinal lesions. At diagnosis, an age below 40 years, the presence of perianal lesions and the need for treating the first flare with steroids have been consistently associated with an unfavourable subsequent 5-year or 10-year clinical course. The positive predictive value of unfavourable course in patients with 2 or 3 predictors ranges between 0.75 and 0.95 in population-based and referral centre cohorts. Consequently, the use of these predictors can be integrated into the elements that influence individual decisions. In the CD postoperative context, keeping smoking and history of prior resection are the strongest predictors of disease symptomatic recurrence. However, these clinical predictors alone are not as reliable as severity of early postoperative endoscopic recurrence in clinical practice. In ulcerative colitis (UC), extensive colitis at diagnosis is associated with unfavourable clinical course in the first 5 to 10 years of the disease, and also with long-term colectomy and colorectal inflammation-associated colorectal cancer. In patients with extensive UC at diagnosis, a rapid step-up strategy aiming to achieve sustained deep remission should therefore be considered. At the moment, no reliable serological or genetic predictor of inflammatory bowel disease clinical course has been identified.

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“…Studies of genotype-phenotype relationship suggest that these variants are associated with ileal location and the development of intestinal strictures. In a study evaluating the influence of NOD2/CARD15 variants on CD outcomes including 170 patients (70 of who had been operated on), Alvarez-Lobos and co-workers found that those patients carrying gene variants had a higher risk of surgical POR [21] . Recently, in another Mediterranean area study including a total of 110 patients, although these findings were not completely reproduced, those patients the L1007fs mutation also had higher rates of reoperation [22] .…”

Section: Patient and Disease Characteristicsmentioning

confidence: 99%

Postoperative Crohn’s disease recurrence: A practical approach

Nos¹,

Domènech²

2008

WJG

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risk patients. Nitroimidazolic antibiotics, although efficient, are associated with a high rate of intolerance and might induce irreversible side effects when used for a long-term. Thiopurines are not widely used after ileocecal resection, maybe because some concerns in giving immunomodulators in asymptomatic patients still remain. In the era of biological agents and genetic testing, a well-established preventive strategy for POR is still lacking, and larger studies to identify good clinical, serological, and genetic predictors of early POR as well as more effective drugs (or drug combinations) are needed.

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Crohn??s Disease Patients Carrying Nod2/CARD15 Gene Variants Have an Increased and Early Need for First Surgery due to Stricturing Disease and Higher Rate of Surgical Recurrence

Abstract: Nod2/CARD15 variants are associated with early initial surgery due to stenosis and with surgical recurrence in Crohn's disease. Patients with these variants could benefit from preventive and/or early therapeutic strategies.

Cited by 169 publications

References 44 publications

Contribution of genetics to a new vision in the understanding of inflammatory bowel disease

Contribution of genetics to a new vision in the understanding of inflammatory bowel disease

Clinical, serological and genetic predictors of inflammatory bowel disease course

Postoperative Crohn’s disease recurrence: A practical approach

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