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CARD15 mutations and perianal fistulating Crohn's disease: correlation and predictive value of antibiotic response
Paulo Freire1, Francisco Portela, Maria M Donato
1Department of Gastroenterology, Coimbra University Hospital, Avenida Bissaya Barreto, 3000, Coimbra, Portugal. pauloavfreire@gmail.com
Insights
CARD15 mutations do not increase the risk of developing Crohn's disease perianal fistulas. However, patients with these mutations experience a poorer response to antibiotic treatment for fistulas.
Area of Science:
- Gastroenterology
- Immunogenetics
- Surgical Gastroenterology
Background:
- CARD15 mutations are linked to altered bowel immunity and increased Crohn's disease (CD) susceptibility.
- The precise relationship between CARD15 mutations and the development of CD-related perianal fistulas remains unclear.
Purpose of the Study:
- To investigate the association between CARD15 mutations and the risk of developing Crohn's perianal fistulas.
- To determine if CARD15 mutations predict the efficacy of antibiotic treatment for perianal fistulas in CD patients.
Main Methods:
- Genotyping for CARD15 mutations in 203 consecutive CD patients.
- Recording the history of perianal fistulas in the study cohort.
- Evaluating antibiotic treatment response in fistula patients stratified by CARD15 mutation status.
Main Results:
- No significant association was found between CARD15 mutations and the risk or timing of perianal fistula development in CD patients.
- Patients with CARD15 mutations and perianal fistulas demonstrated a significantly lower response rate to antibiotic therapy compared to those without mutations (7.7% vs. 40.5%).
Conclusions:
- CARD15 mutations are not associated with an increased risk or earlier onset of perianal fistulas in Crohn's disease.
- The presence of CARD15 mutations correlates with a diminished response to antibiotic treatment for established perianal fistulas in CD patients.
Background:
CARD15 mutations alter bowel immunity and increase susceptibility to Crohn's disease (CD). However, the relation between these mutations and Crohn'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.
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