Introduction

Metastatic Crohn’s disease (MCD), also known as cutaneous Crohn’s disease is one of the rarest cutaneous lesions in IBD. It is defined by granulomatous lesions infiltrating the skin that are discontinuous from the affected GI tract. In most occasions, MCD occurs parallel to the course of a well-establish GI disease, but occasionally it can precede the GI manifestations from months to years. Studies addressing the therapeutic approach to MCD are limited. Ustekinumab is licenced for Crohn`s disease and also for skin disorders including psoriasis. We report our experience in managing MCD in a tertiary IBD centre.

Aims & Methods

This is a single centre retrospective review of biopsy proven cutaneous Crohn’s disease. Patient details obtained from patient records included demographic data, previous failure to biologics and/or IMS, response and time to response to Ustekinumab and therapeutic drug monitoring.

Results

A retrospective review of patients with cutaneous Crohn’s disease was performed. All patients had undergone a skin biopsy for histologically confirmation. Ten patients were included (Males: Females 5:5). Median age was 53 years (IQR 24-67). The most common location was the perianal area often preceded by a surgical wound from a proctectomy and 2 patients had peristomal skin affected. Ninety- percent of patients had failed antiTNF therapy and 6 out of 10 had failed to both Infliximab and Adalimumab, one of them had also lost response to Vedolizumab. All patients received ustekinumab with median follow up since initiation of 45 months (IQR 27-60). All patients noticed improvement since initiation of Ustekinumab with a median time to response of 10 weeks (IQR 4-28). Four out of 10 patients achieved a complete healing of the skin lesions while rest of patients reported a partial response. Most patients had therapeutic or supratherapeutic Ustekinumab level ranging from 2 to 6 mg/L. Dose escalation was done in 8 patients.

Conclusion

Metastatic Crohn’s disease is a rather uncommon entity with different clinical manifestations. Our series report satisfactory response to ustekinumab in MCD. Larger studies are required to confirm these findings.

Introduction

Despite being a frequent step in clinical practice, there is little real world evidence supporting the benefit of optimizing mesalamine in ulcerative colitis (UC) patients who have a mild to moderate flare. The aim of this study was to assess the role of optimizing 5-ASA in patients in clinical remission (CR) who suffer clinical relapse.

Aims & Methods

Patients in CR who developed a mild to moderate flare treated with 5-ASA optimization from 2015 to 2023 were included. Patients under immunosuppression were excluded, as well as flares treated with oral or topical corticosteroids (CS). The primary outcome was corticosteroid-free clinical remission (CFCR) at six months. Secondary outcomes were need for CS at six months and deep remission (DR) defined as fecal calprotectin <250 ug/g or Mayo endoscopic score of 0.

Results

From 908 UC patients screened, 116 flares met the inclusion criteria. The average disease duration was 9.1±7.0 years. The majority were under oral therapy (91%), 6% topical therapy and the remainder combined therapy. Most flares were mild (81.9%). Optimization of 5-ASA recaptured CR in 72.4% and 37.1% of those were in DR at six months. Around 15% required CS at six months. The absence of a flare in the previous year (OR 13.5; p<0.01) and lower PRO-2 score (OR 2.07; p=0.020) were identified as predictive factors for CFCR at six months, as well as both DR and need for CS at six months. Non-extensive UC (E1/E2) was also a predictive factor for DR and need for CS at six months (p<0.05). The type or formulation of 5-ASA (granules vs tablet), pre-flare or optimized 5-ASA dose were not associated with primary or secondary outcomes.

Conclusion

Optimizing 5-ASA therapy recaptured CR in a significant number of patients. Those with extensive UC, previous flares and with higher symptom burden should be closely monitored.

Disclosure

The authors declare that there are no conflicts of interest related to this study.

Introduction

High-definition anorectal manometry (HD-ARM), balloon expulsion test (BET) and magnetic resonance defecography (MR-defecography) are important tools in studying constipation.

Aims & Methods

Evaluate the prevalence of functional defecation disorders and structural anorectal alterations in patients with constipation and compare the findings of HD-ARM and BET with MR-defecography.
Retrospective cohort study including patients with functional constipation (FC) or irritable bowel syndrome with constipation (IBS-C) submitted to HD-ARM, BET and MR-defecography. Patients were divided into three groups: 1) normal anorectal evacuation pattern in HD-ARM and BET; 2) abnormal anorectal evacuation pattern and BET; 3) normal anorectal evacuation pattern and abnormal BET, or abnormal anorectal evacuation pattern and normal BET.

Results

A total of 64 patients were included, 49 with FC (76.6%) and 15 with IBS-C (23.4%). There were 20 patients in group 1 (31.3%), 11 in group 2 (17.2%) and 33 in group 3 (51.5%). In MR-defecography, 47 patients had relevant structural anorectal alterations (73.4%) and 15 had an abnormal contraction of the puborectalis during the defecatory maneuver (23.4%).
Nineteen patients were diagnosed with dyssynergic defecation (29.7%). These patients had significantly higher residual anal pressure and lower percentage of anal relaxation during defecation (109.6±43.2 vs 85.8±29.7 mmHg, p=0.038 and 9% vs 24%, p=0.018, respectively), as well as a lower differential of rectoanal pressure (-32.2±31.4 vs 3.0±29.6 mmHg, p<0.001).
Patients with structural anorectal alterations had a significantly higher body mass index (BMI) (27.4±4.5 vs 23.5±3.3, p=0.002), and all obese patients had structural alterations.
Comparing the findings of HD-ARM and BET with MR-defecography: in group 1, 15 patients had structural alterations (75.0%); in group 2, 8 patients had structural alterations (72.7%); in group 3, 22 patients only had structural alterations (66.7%), 6 only had dyssynergic defecation (18.2%), 2 patients had both (6.0%) and 3 did not have any findings (9.1%). In 24.2% of patients with inconclusive findings in HD-ARM and BET, MR-defecography allowed the diagnosis of dyssynergic defecation.

Conclusion

Patients with structural anorectal alterations had a significantly higher BMI. Almost three quarters of patients with FC and IBS-C had relevant structural anorectal alterations and one third had dyssynergic defecation. Therefore, it is important to combine MR-defecography with HD-ARM and BET in the study of constipation.

Introduction

Nutritional deficiencies are common in IBD patients and have been widely reported in Crohn's disease (CD) patients in particular. Nonetheless micronutrient screening is not routine in all centres in the UK. Body Mass Index (BMI) is widely used for detecting malnutrition in clinical practice but it is not sensitive marker of muscle mass. Hand grip strength (HGS) is quick to perform and may be an effective parameter to predict muscle function and health in IBD patients in busy outpatient settings. Different cut points are used in clinical practice to determine muscle weakness and may yield different results.

Aims & Methods

The aims of this study were (1) To examine micronutrient status (2) To establish the incidence of over- and under-weight and (3) To measure hand grip strength to determine the frequency of dynapenia in stable patients with IBD referred to specialist dietitian clinic for advice.
A baseline micronutrient screen including 9 vitamin and minerals (Vitamins A,D, E, folate, B12, ferritin, selenium, copper and zinc as well as haemoglobin) was performed on all consenting patients at initial dietitian appointment. Inflammatory marker, C reactive protein, was also checked. Patients with raised CRP, were excluded from the micronutrient analysis. All patients were weighed, height measured and BMI calculated. Hand grip strength was measured using Marsden hand grip dynamometer. The maximum result of 6 trials was recorded and its corresponding percentile (1). Dynapenia was defined as HGS<16kg for females and <27kg for males (2) . Results of Ulcerative colitis (UC) and Crohn’s disease (CD) patients were compared.

Results

A total of 292 consecutive patients, (108m, 184 f) referred for dietitian input from April 2023 to March 2025 were included. Mean age was 45 years (SD18). 201 patients with CD and 91 with UC were included. Results are presented in Table 1. No difference in micronutrient status was found between CD and UC patients apart from vitamin D where a higher incidence of deficiency was found in UC compared with CD patients (p=0.045). Contrary to widespread belief incidence of underweight was low in both CD and UC with a higher incidence of obesity in both groups than underweight. Over a quarter of the IBD population had muscle weakness defined by both Dodds et al (2014) and Cruz-Jentofft et al (2019) which is concerning (1,2).

Conclusion

Vitamin D status in particular should be monitored in all stable patients with IBD. A high proportion of both UC and CD patients were found to have weak muscle strength. HGS is a readily obtainable measure quick to perform and could be easily incorporated into routine clinical practice. Further research is needed to establish its clinical significance for stable IBD patients.

References

1. Dodds RM, Syddall HE, Cooper R, Benzeval M, Deary IJ, Dennison EM, Der G, Gale CR, Inskip HM, Jagger C, Kirkwood TB, Lawlor DA, Robinson SM, Starr JM, Steptoe A, Tilling K, Kuh D, Cooper C, Sayer AA. Grip strength across the life course: normative data from twelve British studies. PLoS One. 2014 Dec 4;9(12):e113637. doi: 10.1371/journal.pone.0113637. PMID: 25474696; PMCID: PMC4256164.
2. Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyère O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169. Erratum in: Age Ageing. 2019 Jul 1;48(4):601. doi: 10.1093/ageing/afz046. PMID: 30312372; PMCID: PMC6322506.

Disclosure

No conflict of interest to disclose

Introduction

Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disorder of the bile ducts, associated with significant morbidity and an increased risk of malignancy. Preclinical studies in mice deficient in the multidrug resistance protein 2 (Mdr2−/−) have demonstrated that the integrin αvβ6 plays a critical role in biliary fibrosis by activating latent transforming growth factor (TGF)-β1, the main profibrotic cytokine in the liver. Moreover, several studies have shown that autoantibodies against integrin αvβ6 exhibit good diagnostic accuracy in ulcerative colitis (UC). The aim of this meta-analysis is to evaluate the diagnostic performance of anti-integrin αvβ6 autoantibodies in PSC.

Aims & Methods

A systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Four electronic databases (PubMed, Scopus, ScienceDirect, and the Cochrane Library) were systematically searched up to February 2025. Eligible studies included those involving patients with PSC as well as non-PSC control groups, in which the overall sensitivity and specificity of serum anti-integrin αvβ6 autoantibodies for the diagnosis of PSC were reported. Pooled sensitivity, specificity, and area under the curve (AUC) were calculated using a random-effects model. Subgroup analyses were conducted based on the presence or absence of concomitant UC. Meta-analyses were performed using RevMan version 5.4.

Results

Four studies, comprising a total of 1,228 participants, met the predefined eligibility criteria. All studies defined the positivity threshold as the mean value in control groups plus three standard deviations (SD). The pooled sensitivity and specificity for the diagnosis of PSC were 0.679 (95% CI: 0.670–0.689) and 0.940 (95% CI: 0.939–0.941), respectively, with high heterogeneity (I² = 99%).
In the subgroup analysis, the sensitivity and specificity of the test for diagnosing PSC in the absence of concomitant UC were 0.075 (95% CI: 0.071–0.080) and 0.940 (95% CI: 0.939–0.941), respectively. In contrast, in the subgroup of patients with both PSC and UC, sensitivity reached 0.960 (95% CI: 0.959–0.961), while specificity was 0.720 (95% CI: 0.713–0.727).
Sensitivity analyses performed to explore the observed heterogeneity revealed that exclusion of one study (Bloeman, 2024) significantly improved diagnostic performance across all subgroups, with a pooled sensitivity of 0.831 (95% CI: 0.8236–0.8384) and specificity of 0.946 (95% CI: 0.9451–0.9468).

Conclusion

Serum anti-integrin αvβ6 autoantibodies demonstrate diagnostic value in PSC, with consistently high specificity across all patient groups and notably high sensitivity in those with concomitant ulcerative colitis. The high specificity supports a strong negative predictive value. Given the supporting preclinical evidence, integrin αvβ6 warrants further investigation not only as a diagnostic biomarker but also as a potential therapeutic target.

Disclosure

​No conflict of ​Interest