CARD15 Mutations and Perianal Fistulating Crohn’s Disease: Correlation and Predictive Value of Antibiotic Response

Abstract

Background CARD15 mutations alter bowel immunity and increase susceptibility to Crohn 0 s disease (CD). However, the relation between these mutations and Crohn 0 s perianal fistulas has not been fully clarified. Aims To assess whether CARD15 mutations are associated with risk of developing Crohn's perianal fistulas and whether these mutations are predictors of the response of perianal fistulas to antibiotics. Methods CARD15 mutations were investigated in 203 consecutive CD patients. Presence/absence of history of perianal fistula was recorded. Patients with history of perianal fistula were divided into two groups (with/without CARD15 mutations), and response to antibiotics was evaluated in both groups. Results Of the 203 patients, 60 (29.6%) showed at least one CARD15 mutation and 55 (27.1%) had history of perianal fistula. History of perianal fistula was identified in 13 (21.7%) patients with mutations and in 42 (29.4%) patients without mutations (P = 0.260). Mean age at diagnosis of first perianal fistula was similar in patients with/without CARD15 mutations (28.7 ± 9.8 versus 29.7 ± 10.1 years, P = 0.758). Average time between disease onset and diagnosis of first perianal fistula was also similar in the two groups (4.6 ± 5.1 versus 5.0 ± 5.9 years, P = 0.816). Response of perianal fistulas to antibiotics (metronidazole alone or combined with ciprofloxacin) was significantly higher in patients without CARD15 mutations (7.7% versus 40.5%, P = 0.041). Conclusions In CD, CARD15 mutations are not associated with risk of developing perianal fistulas or with time of their outbreak. Nevertheless, patients with perianal fistulas and CARD15 mutations showed worse response to antibiotics.

Perianal Crohn’s Disease: Predictive Factors and Genotype-Phenotype Correlations

“…Our study confirms previous reports implicating CARD15/NOD2 and IL-23r SNPs as risk factors for CD [5,6]; however, we found no relationship between minor alleles in the CARD15/NOD2 and IL-23r genes and the incidence of PCD, coinciding with previous work by Freire et al [15] and Karban et al [16]. …”

“…Two years later, Vermiere et al [14]proposed that variants in the OCTN1 gene, which is located within the IBD5 gene cluster, are involved in the phenotypic expression of PCD, but not in CD susceptibility itself. Freire et al [15] noted that CARD15/NOD2 mutations did not predispose to perianal fistulization. Similarly, Karban et al [16]did not find CARD15/NOD2 or OCTN to be a risk factor for PCD in a cohort of non-Ashkenazi Jews with CD.…”

Prognostic factors affecting outcomes in fistulating perianal Crohn’s disease: a systematic review

“…All studies took place in the USA ( n = 3) [ 23 , 27 , 30 ]) or Europe (Germany ( n = 3) [ 22 , 25 , 28 ], France ( n = 2) [ 32 , 34 ], the UK ( n = 1) [ 24 ], the Netherlands ( n = 1) [ 31 ], Austria ( n = 1) [ 29 ], Spain ( n = 1) [ 26 ], and Portugal ( n = 1) [ 33 ]). The institutional setting was a teaching hospital in all cases.…”

Viruses, Autophagy Genes, and Crohn’s Disease

“…The answer to this question has practical implications for the use of antibiotics to treat inflammatory bowel disease. There is already evidence that genotype can alter responsiveness to antibiotics during recurrent Crohn’s disease [192]. …”