Katherine Hanigan

Crohn's disease and smoking: Is it ever too late to quit?

BACKGROUND Smoking increases CD risk. The aim was to determine if smoking cessation at, prior to, or following, CD diagnosis affects medication use, disease phenotypic progression and/or surgery. METHODS Data on CD patients with disease for ≥5 yrs were collected retrospectively including the Montreal classification, smoking history, CD-related abdominal surgeries, family history, medication use and disease behaviour at diagnosis and the time when the disease behaviour changed. RESULTS 1115 patients were included across six sites (mean follow-up-16.6 yrs). More non-smokers were male (p=0.047) with A1 (p<0.0001), L4 (p=0.028) and perianal (p=0.03) disease. Non-smokers more frequently received anti-TNF agents (p=0.049). (p=0.017: OR 2.5 95%CI 1.18-5.16) and those who ceased smoking prior to diagnosis (p=0.045: OR 2.3 95%CI 1.02-5.21) progressed to complicated (B2/B3) disease as compared to those quitting at diagnosis. Patients with uncomplicated terminal ileal disease at diagnosis more frequently developed B2/B3 disease than isolated colonic CD (p<0.0001). B2/B3 disease was more frequent with perianal disease (p<0.0001) and if i.v. steroids (p=0.004) or immunosuppressants (p<0.0001) were used. 49.3% (558/1115) of patients required at least one intestinal surgery. More smokers had a 2nd surgical resection than patients who quit at, or before, the 1st resection and non-smokers (p=0.044: HR=1.39 95%CI 1.01-1.91). Patients smoking >3 cigarettes/day had an increased risk of developing B2/B3 disease (p=0.012: OR 3.8 95%CI 1.27-11.17). CONCLUSION Progression to B2/B3 disease and surgery is reduced by smoking cessation. All CD patients regardless of when they were diagnosed, or how many surgeries, should be strongly encouraged to cease smoking.

Genetic susceptibility in IBD: Overlap between ulcerative colitis and Crohn's disease

Background:The etiology of ulcerative colitis (UC) and Crohns disease (CD) involves both genetic and environmental components. Multiple UC and CD susceptibility genes have been identified through genome-wide association studies and subsequent meta-analyses. These studies have also highlighted the presence of genes common to both diseases, and shared with several other autoimmune disorders. The aim of this study was to identify single nucleotide polymorphisms (SNPs) recently identified by the International IBD Genetics Consortium (IIBDGC) demonstrating that highly significant associations with CD could also confer genetic susceptibility to UC. Methods:Statistical modeling was performed on 29 CD-associated SNPs. The study comprised of 1652 UC cases from the Australia and New Zealand IBD Consortium and 2363 Australian population-based controls. Results:After adjustment for multiple comparisons, only one SNP, rs3024505, was significantly associated with UC (P = 0.001). Independent chi-square analyses identified odds ratios of 2.22 (1.48–3.37) for the rare homozygous genotype, and 1.20 (1.06–1.35) for the minor allele. Five other SNPs demonstrated moderate to weak associations with UC. Conclusions:Of the 29 SNPs conferring high genetic susceptibility to CD, 28 were not associated with UC, thus indicating that for this SNP set there is a low level of overlap between the two major forms of IBD. Only one SNP, rs3024505 (Chr 1q32.1, upstream of IL10), was associated with susceptibility to UC. The identification of this SNP replicates a finding from Franke et al (2008), where the rs3024505 SNP was strongly associated with UC across multiple European populations.

Protective effects of Helicobacter pylori for IBD are related to the cagA-positive strain

We read with interest the article by Castano-Rodriguez et al ,1 describing the role of Helicobacter pylori and Campylobacter spp in inflammatory bowel disease (IBD). While H. pylori infection has been shown to be protective against IBD, there is some ambiguity about the biological underpinnings of this effect. There is a spectrum of H pylori exposure across Caucasian populations with lower rates identified in Australian and USA studies.2 Importantly, Australia and other ‘new world’ regions such as the USA currently have some of the highest published incidence and prevalence rates for IBD.3–5 Multiple strains of H. pylori are observed, most notably, those with an active cytotoxin-associated gene A ( cagA ) and those without. The prevalence of the cagA gene in H. pylori is reported to be between 60% and 100% in western and eastern populations, respectively,6 potentially confounding any analysis on the …

A rolling phenotype in Crohn's disease

Background and aim The Montreal classification of disease behaviour in Crohns disease describes progression of disease towards a stricturing and penetrating phenotype. In the present paper, we propose an alternative representation of the long-term course of Crohn’s disease complications, the rolling phenotype. As is commonly observed in clinical practice, this definition allows progression to a more severe phenotype (stricturing, penetrating) but also, regression to a less severe behaviour (inflammatory, or remission) over time. Methods All patients diagnosed with Crohns Disease between 01/01/1994 and 01/03/2008, managed at a single centre and observed for a minimum of 5 years, had development and resolution of all complications recorded. A rolling phenotype was defined at each time point based on all observed complications in the three years prior to the time point. Phenotype was defined as B1, B2, B3, or B23 (penetrating and stenotic). The progression over time of the rolling phenotype was compared to that of the cumulative Montreal phenotype. Results 305 patients were observed a median of 10.0 (Intraquartile range 7.3–13.7) years. Longitudinal progression of rolling phenotype demonstrated a consistent proportion of patients with B1 (70%), B2 (20%), B3 (5%) and B23 (5%) phenotypes. These proportions were observed regardless of initial phenotype. In contrast, the cumulative Montreal phenotype progressed towards a more severe phenotype with time (B1 (39%), B2 (26%), B3(35%) at 10 years). Conclusion A rolling phenotype provides an alternative view of the longitudinal burden of intra-abdominal complications in Crohns disease. From this viewpoint, 70% of patients have durable freedom from complication over time (>3 years).

Sa1194 Consistently High C Reactive Protein Is Associated With Subsequent Development of Perianal Fistulae in Patients With Crohn's Disease

in the use of systemic steroids. Conclusions: At the moment of diagnosis of CD, smoking, abdominal pain, diarrhea, lower hemoglobin values and higher CPR, ESR or platelet values, as well as ileocolonic location of the disease, penetrating or stricturing disease, and perianal involvement are associated with a subsequent surgical outcome. The early recognition of these features in newly diagnosed patients should be seriously taken into account when deciding for more aggressive medical treatments, such as immunosuppressors or biological agents, in order to defer the more invasive surgical procedures.

Su1335 A Novel Description of Longitudinal Phenotype in Patients With Crohn's Disease

BACKGROUND: The Montreal classification for patients with Crohns disease describes disease phenotype in a hierarchy: B1 (Inflammatory), B2 (Stricturing), B3 (Internal Penetrating). It does not make allowance for description of resolution, or of repeated development, of internal penetrating or stricturing complications (IPSC). It therefore always observes increasing severity of disease phenotype over time, and does not accurately represent the burden of IPSC later in the disease course. AIM: To describe a novel classification of longitudinal disease phenotype in Crohns disease, which allows description of both resolution and repeated development of IPSC. METHODS: Patients diagnosed at a tertiary referral centre (Brisbane, Australia) with Crohns disease between 1st Jan 1994 and 1st March 2008, with more than five years of clinical follow-up, had all objective clinical data recorded in a longitudinal database. Temporal evidence of presence of IPSC was obtained from the following: computed tomographic enterography (CTE), magnetic resonance enterography (MRE), ileocolonoscopy, gastroscopy, findings at abdominal surgery and examination of macroscopic surgical specimens. Disease phenotype at each time point was classified as the presence or absence of IPSC over the previous three years of disease course. Longitudinal disease phenotype was compared to progressive Montreal phenotype. Subgroup analysis was performed for patients with B1, B2 or B3 Montreal phenotype within one year of diagnosis. RESULTS: 316 patients with a median follow-up of 10.0 years (interquartile range (IQR) 6.81 13.67) were analyzed. Mean age at diagnosis was 27.4 years and 55% were female. Montreal location classification at diagnosis was L1 (131 patients), L2 (58) and L3 (117). Progressive Montreal phenotype was comparable to published cohorts.1 In comparison longitudinal phenotype classification demonstrated a predominance of stricturing complications. Stricturing complications predominated regardless of Montreal phenotype within the first year (graphs not shown). The steep slope in all lines at 3 years represents patients with an isolated IPSC at presentation regressing to a less severe classification. CONCLUSION: B2 (Stricturing) complications make up the bulk of recurring or non-resolving IPSC in patients with Crohns disease, regardless of Montreal phenotype within one year of diagnosis. This is not evident when disease classification is observed using the Montreal classification system alone. 1: Tarrant KM, Barclay ML, Frampton CMA, Gearry RB. Perianal disease predicts changes in Crohns disease phenotype-results of a population-based study of inflammatory bowel disease phenotype. Am J Gastroenterol. 2008 Dec;103(12):3082-93.

Su1336 The Pre-Diagnosis Inflammatory Signature of Patients With Inflammatory Bowel Disease

BACKGROUND: The Montreal classification for patients with Crohns disease describes disease phenotype in a hierarchy: B1 (Inflammatory), B2 (Stricturing), B3 (Internal Penetrating). It does not make allowance for description of resolution, or of repeated development, of internal penetrating or stricturing complications (IPSC). It therefore always observes increasing severity of disease phenotype over time, and does not accurately represent the burden of IPSC later in the disease course. AIM: To describe a novel classification of longitudinal disease phenotype in Crohns disease, which allows description of both resolution and repeated development of IPSC. METHODS: Patients diagnosed at a tertiary referral centre (Brisbane, Australia) with Crohns disease between 1st Jan 1994 and 1st March 2008, with more than five years of clinical follow-up, had all objective clinical data recorded in a longitudinal database. Temporal evidence of presence of IPSC was obtained from the following: computed tomographic enterography (CTE), magnetic resonance enterography (MRE), ileocolonoscopy, gastroscopy, findings at abdominal surgery and examination of macroscopic surgical specimens. Disease phenotype at each time point was classified as the presence or absence of IPSC over the previous three years of disease course. Longitudinal disease phenotype was compared to progressive Montreal phenotype. Subgroup analysis was performed for patients with B1, B2 or B3 Montreal phenotype within one year of diagnosis. RESULTS: 316 patients with a median follow-up of 10.0 years (interquartile range (IQR) 6.81 13.67) were analyzed. Mean age at diagnosis was 27.4 years and 55% were female. Montreal location classification at diagnosis was L1 (131 patients), L2 (58) and L3 (117). Progressive Montreal phenotype was comparable to published cohorts.1 In comparison longitudinal phenotype classification demonstrated a predominance of stricturing complications. Stricturing complications predominated regardless of Montreal phenotype within the first year (graphs not shown). The steep slope in all lines at 3 years represents patients with an isolated IPSC at presentation regressing to a less severe classification. CONCLUSION: B2 (Stricturing) complications make up the bulk of recurring or non-resolving IPSC in patients with Crohns disease, regardless of Montreal phenotype within one year of diagnosis. This is not evident when disease classification is observed using the Montreal classification system alone. 1: Tarrant KM, Barclay ML, Frampton CMA, Gearry RB. Perianal disease predicts changes in Crohns disease phenotype-results of a population-based study of inflammatory bowel disease phenotype. Am J Gastroenterol. 2008 Dec;103(12):3082-93.