A rolling phenotype in Crohn's disease

Irwin, James; Ferguson, E. E.; Simms, Lisa A.; Hanigan, Katherine; Carbonnel, Franck; Radford‐Smith, Graham

doi:10.1371/journal.pone.0174954

Cited by 12 publications

(19 citation statements)

References 22 publications

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“…The dominant observed complication in this study was bowel stenosis. The absolute rate and relative proportion of intra-abdominal stenosis, perforation, and fistula formation in our cohort is similar to published cohorts when represented by cumulative Montreal phenotype classification [ 5 , 7 , 31 , 34 ]. We believe that this is representative of the spectrum of long-term complications suffered by patients with Crohn’s disease, and that therapy initiated with the goal of preventing the development of long-term complications would be given predominantly to prevent bowel stenosis.…”

Section: Discussionsupporting

confidence: 86%

A Method Using Longitudinal Laboratory Data to Predict Future Intestinal Complication in Patients with Crohn’s Disease

et al. 2022

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Background Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn's disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes. Aims To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn's disease. Methods An observational cohort of patients with Crohn's disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to represent longitudinal laboratory data. Cox regression was used to identify laboratory variables independently associated with the development of a subsequent complication. A clinical scoring tool was designed. Results In 246 patients observed over a median of 5.72 years, 134 complications occurred. Minimum or maximum value in a preceding window period of one year was most strongly associated with subsequent complication. A Longitudinal Laboratory score of ≥ 2 (maximum albumin level < 39 g/L = 1, maximum mean cell volume < 88 fL = 1, minimum platelet count > 355 × 10 9 /L = 1, minimum C reactive protein > 5 mg/L = 1) was 62% sensitive and 91% specific in identifying patients who develop a subsequent complication. Conclusion A consistent reduction in serum albumin and mean cell volume, and a consistent increase in platelet count and C reactive protein were associated with a subsequent complication in patients with Crohn's disease. Longitudinal laboratory tests may be used as described in this paper to provide a rational for earlier escalation of therapy.

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Section: Discussionsupporting

confidence: 86%

A Method Using Longitudinal Laboratory Data to Predict Future Intestinal Complication in Patients with Crohn’s Disease

et al. 2022

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“…The observed strong association between a stenotic segment and a penetrating course of the disease is supported by both clinical experience and published pathology literature [4,27] and was also found on cross-sectional imaging in pediatric patients [28]. Previous reports have shown a lower association between penetrating Crohn's disease and stenoses, with reported simultaneous occurrence in 25% and 47.1% of patients, respectively [29,30]. This lower association may be related to the fact that the evaluation criteria were not exclusively based on radiological evidence.…”

Section: Discussionsupporting

confidence: 67%

Crohn’s disease: prevalence, MR features, and clinical significance of enteric and colonic sinus tracts

et al. 2020

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Objectives Enteric and colonic sinus tracts are inflammatory complications that precede intestinal fistulas in patients with Crohn’s disease (CD). The aim of this study was to retrospectively determine the prevalence, morphologic features, and outcome of sinus tracts using MR imaging. Methods A consecutive cohort of 642 patients with known CD, referred for MR enterography or MR enteroclysis (study period 01/2014–09/2019), was evaluated retrospectively for the presence of sinus tracts, their locations, presence and length of coexisting strictures, bowel wall thickness, CDMI score, upstream dilation, and bowel distension. Clinical outcome was assessed using medical records. For metric data, means and standard deviation, as well as one-way ANOVA and Pearson’s correlation coefficient, were calculated. Results In 36/642 patients with CD undergoing MRE, 49 sinus tracts (forty in small intestine, nine in left-sided colon) were detected with a prevalence of 6.9% in patients with MR-visible signs of CD (n = 519, overall prevalence of 5.6%). Mean segmental bowel wall thickness was 8.9 mm, and mean CDMI score was 9.3. All sinus tracts were located within a stenotic segment, showing mesenteric orientation within the small bowel and upstream dilation in 13 patients. Of 36 patients, 19 underwent immediate surgery and seven developed clinical progression within the segment containing the sinus tract. Conclusions Sinus tracts occur in 6.9% of patients with visible signs of CD. They are located within stenotic, severely thickened bowel segments with high MR inflammation scores. Their detection is clinically important, because they indicate a more aggressive phenotype and, if left untreated, may show severe progression. Key Points • Sinus tracts occur in 6.9% of patients with MR-visible signs of Crohn’s disease. • Sinus tracts are a radiological indicator of early penetrating Crohn’s disease, with a high risk of progression, and require dedicated treatment. • Sinus tracts can be recognized by characteristic findings and typically occur in stenotic, severely thickened bowel segments with high MR inflammation scores.

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“…as well on data availability in the SIBDC database [ 39 ]. In detail, we included the following patient parameters: history of intestinal surgery, steroid-dependent/steroid-refractory disease or at least 6 months continuous treatment with corticosteroids (prednisone, prednisolone, cortisol), use of at least two anti-TNF antibodies, pancolitis in UC patients or the presence of L4, B2 or B3 according to disease location involvement (L1:ileal, L2:colonic, L3:ileocolonic, L4: upper gastrointestinal) and disease behavior (B1:inflammatory, B2:stricturing, and B3:penetrating–both internal and perianal) based on Montreal classification in CD patients as well as hospitalization due to IBD [ 40 – 42 ]. A mild disease course was defined by the absence of any of those clinical criteria and a severe disease course was defined by the presence of at least one of those clinical criteria.…”

Section: Methodsmentioning

confidence: 99%

The presence of genetic risk variants within PTPN2 and PTPN22 is associated with intestinal microbiota alterations in Swiss IBD cohort patients

et al. 2018

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BackgroundGenetic risk factors, intestinal microbiota and a dysregulated immune system contribute to the pathogenesis of inflammatory bowel disease (IBD). We have previously demonstrated that dysfunction of protein tyrosine phosphatase non-receptor type 2 (PTPN2) and PTPN22 contributes to alterations of intestinal microbiota and the onset of chronic intestinal inflammation in vivo. Here, we investigated the influence of PTPN2 and PTPN22 gene variants on intestinal microbiota composition in IBD patients.MethodsBacterial DNA from mucosa-associated samples of 75 CD and 57 UC patients were sequenced using 16S rRNA sequencing approach. Microbial analysis, including alpha diversity, beta diversity and taxonomical analysis by comparing to PTPN2 (rs1893217) and PTPN22 (rs2476601) genotypes was performed in QIIME, the phyloseq R package and MaAsLin pipeline.ResultsIn PTPN2 variant UC patients, we detected an increase in relative abundance of unassigned genera from Clostridiales and Lachnospiraceae families and reduction of Roseburia when compared to PTPN2 wild-type (WT) patients. Ruminoccocus was increased in PTPN22 variant UC patients. In CD patients with severe disease course, Faecalibacterium, Bilophila, Coprococcus, unclassified Erysipelotrichaeceae, unassigned genera from Clostridiales and Ruminococcaceae families were reduced and Bacteroides were increased in PTPN2 WT carriers, while Faecalibacterium, Bilophila, Coprococcus, and Erysipelotrichaeceae were reduced in PTPN22 WT patients when compared to patients with mild disease. In UC patients with severe disease, relative abundance of Lachnobacterium was reduced in PTPN2 and PTPN22 WT patients, Dorea was increased in samples from PTPN22 WT carriers and an unassigned genus from Ruminococcaceae gen. was increased in patients with PTPN2 variant genotype.ConclusionsWe identified that IBD-associated genetic risk variants, disease severity and the interaction of these factors are related to significant alterations in intestinal microbiota composition of IBD patients.

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A rolling phenotype in Crohn's disease

Cited by 12 publications

References 22 publications

A Method Using Longitudinal Laboratory Data to Predict Future Intestinal Complication in Patients with Crohn’s Disease

A Method Using Longitudinal Laboratory Data to Predict Future Intestinal Complication in Patients with Crohn’s Disease

Crohn’s disease: prevalence, MR features, and clinical significance of enteric and colonic sinus tracts

The presence of genetic risk variants within PTPN2 and PTPN22 is associated with intestinal microbiota alterations in Swiss IBD cohort patients

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