Assessing fatigue in inflammatory bowel disease: comparison of three fatigue scales.

BACKGROUND: Fatigue is commonly reported by patients with inflammatory bowel disease (IBD), both in quiescent and active disease. Few fatigue scales have been tested in IBD. AIM: To assess three fatigue assessment scales in IBD and to determine correlates of fatigue. METHODS: Potential participants (n = 2131) were randomly selected from an IBD organisation's members' database; 605 volunteered and were posted three fatigue scales: Inflammatory Bowel Disease Fatigue scale, Multidimensional Fatigue Inventory and Multidimensional Assessment Fatigue scale and questionnaires assessing anxiety, depression, quality of life (QoL) and IBD activity. The questionnaires were tested for stability over time with another group (n = 70) of invited participants. Internal consistency was measured by Cronbach's alpha and test-retest reliability by the intraclass correlation coefficient (ICC). RESULTS: Four hundred and sixty-five of 605 (77%) questionnaires were returned; of 70 invited, 48/70 returned test (68.6%) and 41/70 (58.6%) returned retest. The three scales are highly correlated (P < 0.001). Test-retest suggests reasonable agreement with ICC values between 0.65 and 0.84. Lower age, female gender, IBD diagnosis, anxiety, depression and QoL were associated with fatigue (P < 0.001) on univariable analysis. However, on multivariable analysis only depression and low QoL were consistently associated with fatigue, while female gender was associated on most scales. IBD diagnosis, age and other factors were not consistently associated with severity or impact of fatigue once other variables were controlled for. CONCLUSIONS: All three fatigue scales are likely to measure IBD fatigue adequately. Responsiveness to change has not been tested. Depression, poorer QoL and probably female gender are the major associations of fatigue in IBD.

Use of sirolimus (rapamycin) to treat refractory Crohn's disease.

We present the case of a 37-year-old woman with severe refractory colonic and perianal Crohn's disease who had lost response to second-line, steroid-sparing treatments azathioprine, methotrexate and infliximab. For many such patients extensive surgery has often been considered the only option. New insights provided by the results of genome-wide association scanning in Crohn's disease highlight autophagy, a cellular process implicated in the clearance of intracellular bacteria, as a key process in Crohn's disease pathogeneses. Sirolimus (rapamycin) is a drug used to upregulate autophagy in cell culture in the laboratory, and in clinical practice to prevent rejection following organ transplantation due to independent immunosuppressive action. Our patient was treated with sirolimus for 6 months at a dose that maintained serum trough levels of 5 ng/ml. There was marked and sustained improvement in Crohn's disease symptoms with the Harvey-Bradshaw index falling from 13 to 3, in serum markers of inflammation (C-reactive protein fell from 79 to 2) and endoscopic appearance. This is the first reported case of the use of sirolimus to treat Crohn's disease.

Evidence for association of OCTN genes and IBD5 with ulcerative colitis.

BACKGROUND AND AIMS: Genetic association between Crohn's disease (CD) and OCTN1 (SLC22A4) C1672T/OCTN2 (SLC22A5) G-207C variants in IBD5 has recently been reported. These genes encode solute carriers and the association was suggested to be distinct from the background IBD5 risk haplotype. There have been conflicting reports of the association between markers in the IBD5 region and ulcerative colitis (UC) and interaction (epistasis) between this locus and CARD15. Our aim was to ascertain the contribution of OCTN variants to UC and CD in a large independent UK dataset, to seek genetic evidence that the OCTN association is distinct from the IBD5 risk haplotype and to identify interactions between the IBD5 and CARD15 loci. METHODS: A total of 1104 unrelated Caucasian subjects with inflammatory bowel disease (IBD) (496 CD, 512 UC, 96 indeterminate) and 750 ethnically matched controls were genotyped for three single nucleotide polymorphisms (SNPs) in the CD associated genes (OCTN1+1672, OCTN2-207, and IGR2230), and two flanking IBD5 tagging SNPs, IGR2096 and IGR3096. Data were analysed by logistic regression methods within STATA. RESULTS: OCTN variants were as strongly associated with UC and IBD overall as they were with CD (p = 0.0001; OR 1.3 (95% confidence interval 1.1-1.5)). OCTN variants were in tight linkage disequilibrium with the extended IBD5 risk haplotype D' 0.79 and 0.88, and r2 = 0.62 and 0.72 for IGR2096 and 3096, respectively. There was no deviation from a multiplicative model of interaction between CARD15 and IBD5 on the penetrance scale. CONCLUSIONS: The OCTN variants were associated with susceptibility to IBD overall. The effect was equally strong in UC and CD. Although OCTN variants may account for the increased risk of IBD associated with IBD5, a role for other candidate genes within this extended haplotype was not excluded. There was no statistical evidence of interaction between CARD15 and either OCTN or IBD5 variants in susceptibility to IBD.