Introduction

Graves’ disease (GD) and ulcerative colitis (UC) are two distinct autoimmune disorders with increasing evidence of shared pathophysiological mechanisms. While previous epidemiological studies have reported a higher risk of IBD among individuals with GD, the association between GD and UC specifically remains controversial. In particular, the causal direction, genetic liability, and molecular mediators underlying this relationship are not well defined.

Aims & Methods

We conducted a multi-layered investigation to clarify the relationship between GD and UC. First, a large-scale prospective analysis using the UK Biobank cohort was performed to assess the association between GD and subsequent UC risk, with adjustments for demographic, lifestyle, and clinical covariates utilizing COX proportional hazard models. Second, two-sample Mendelian randomization (MR) analyses were conducted using publicly available genome-wide association study (GWAS) datasets to infer potential causal links. Finally, we performed protein mediation analysis integrating plasma proteomic data to identify potential intermediate proteins and pathways mediating the effect of GD on UC.

Results

Observational analysis revealed that patients with GD had a significantly elevated risk of developing UC. Stratified analysis further revealed that this association was more pronounced among male and obese individuals. The association remained significant even after adjusting for key covariates including medication use, psychological disorders, air pollution exposure, and sunlight exposure. Genetic-level analysis using Mendelian randomization confirmed a potential causal relationship between AITD and UC. This association was independently validated in MR sensitivity analyses. Through mediation analysis based on plasma proteomic data, 28 UC-related proteins were identified as potential mediators of the AITD–UC relationship. Among them, proteins such as Arachidonate 15-lipoxygenase B (ALOX15B) were significantly enriched in the high-risk group. Collectively, six pathways likely represent the core signaling axes through which GD promotes UC pathogenesis, highlighting potential targets for mechanistic and therapeutic exploration.

Conclusion

This study provides robust clinical, genetic, and molecular evidence for a link from GD to UC, mediated through specific immunopathogenic proteins and pathways. These findings offer novel insights into shared autoimmunity and may inform biomarker-driven strategies for early identification and targeted prevention of UC in patients with GD.

References

Ferrari SM. The association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series. Autoimmun Rev. 2019 Mar;18(3):287-292.
Ordás I. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19.
Xian W. Graves Disease and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization. J Clin Endocrinol Metab. 2023 Apr 13;108(5):1075-1083.
Burisch J. Incidence of Immune-Mediated Inflammatory Diseases Among Patients With Inflammatory Bowel Diseases in Denmark. Clin Gastroenterol Hepatol. 2019 Dec;17(13):2704-2712.e3.

Disclosure

The authors declare no conflicts of interest.

Clinical Case Summary

A 42-year-old male patient was admitted to our department due to a chronic abdominal pain and symptoms of gut-brain dysfunction (bloatedness, belching, stomach fullness and mixed bowel habits) that lasted for years. He also suffered of ventricular extrasystoles that were more prominent during stomach fullness and for which he underwent two ablation procedures. Five years prior to hospitalization extensive outpatient assessment was performed (laboratory check-up, gastroscopy, abdominal ultrasound, esophageal manometry, 24h pH-metry, occult blood testing, microbiome testing), but, except for insufficient cardia and reduced biodiversity, there were no other pathological findings. The symptomatic therapy was given, but yielded inadequate relief. Due to severe insomnia and worsening of aforementioned symptoms, the patient underwent cognitive behavioural therapy. Although insomnia improved, bloatedness and postprandial pain persisted. At that point, patient contacted our department and was subsequently hospitalized. Extensive laboratory check-up was redone, as well as functional tests, MR enterography and CT scan of the thorax, abdomen and pelvis. Except for distal esophageal spasm and defecatory dyssynergia, findings were normal. Finally, we decided to perform an abdominal vascular ultrasound. An impression in the celiac trunk was noted - especially prominent during the expiration with a peak systolic velocity of 3m/s. Based on the ultrasound finding and clinical scenario, the diagnosis of mean arcuate ligament syndrome (MALS) was established. Surgical decompression procedure was performed and the patient reported improvement in postprandial pain and cessation of bloatedness. Having given the diagnosis, the patient finally entered the way to recovery. However, the issue of determining the optimal timing for integrating symptoms of gut-brain interaction into the framework of rare diagnoses and for modifying the diagnostic approach remains unresolved.

References

1. Image of vascular ultrasound performed prior to decompression procedure
2. Image of postoperative vascular ultrasound - performed 3 months postoperatively

Disclosure

The Authors have nothing to disclose.

Introduction

Functional and organic bowel diseases in children often present with gastrointestinal (GI) symptoms, yet systematic data on symptom profiles at first presentation limited. Functional bowel disorders (FBD) are common and often require costly and invasive diagnostic procedures. The Pediatric Structured Assessment of Gastrointestinal Symptoms (pSAGIS) is a validated tool that facilitates structured and standardized symptom assessment in pediatric outpatient settings (1).

Aims & Methods

We aimed to compare GI symptoms at first presentation in children with subsequently diagnosed functional (FD), any organic bowel disease (aOD), and specifically inflammatory bowel disease (IBD) using the pSAGIS. The diagnosis of FD was based on the Rome IV criteria (2). From 2016 and 2023, 1550 children completed the pSAGIS questionnaire at their first outpatient visit at St. Anna Children’s Hospital, Vienna. The tool assesses 21 GI symptoms (five grades, from no problem (0) to very severe (4)), grouped into five domains: abdominal pain, dyspepsia, diarrhea, constipation, and dysphagia/nausea. Symptom severity scores (0–12 to 20, depending on the number of items in each domain) were analyzed using median ± SD; p < 0.05 was considered significant.

Results

Of all patients (n=1550), 17.7% (n=274) were excluded due to non-gastroenterological diagnoses. 28.7% (n=445) were diagnosed with FD and 53.6% (n=831) with aOD, including 7.2% (n=111) with IBD. The number of symptoms rated as present (mild to very severe) was 6.4±3.0 SD (FD) vs. 4.8±2.9 SD (aOD) vs. 4.3±2.5 SD (IBD) (FD vs. aOD and vs. IBD: p<0.001). The number of symptoms rated as moderate to very severe was 4.3±3.7 SD (FD) vs. 2.2±3.2 SD (aOD) vs. 2.0±3.1 SD (IBD) FD vs. aOD and vs. IBD: p<0.001).

Symptom scores in all five domains were significantly higher in the functional group:

Conclusion

Children with functional bowel disorders report significantly higher symptom burden at first presentation compared to those with organic disease, including IBD. In addition to its role in long-term monitoring of treatment outcomes, pSAGIS may support early symptom-based differentiation. This could support more targeted diagnostic pathways and inform timely therapeutic decisions in pediatric gastroenterology.

References

(1) Hammer J et al, JPGN 2023; (2) Hyams JS et al, Gastroenterology 2016.

Introduction

Confocal microscopy through VivaScope offers real-time, high-resolution virtual imaging of fresh tissue, allowing a rapid histopathological diagnosis. This study evaluates the performance of virtual diagnosis using VivaScope in comparison with standard pathological diagnosis for biopsies obtained during endoscopic ultrasound (EUS)-guided fine-needle biopsy (FNB) of suspected malignancy.

Aims & Methods

This prospective study included consecutive patients undergoing EUS-FNB for tumor evaluation were included . Two passes were made using 22-gauge FNB needles and their adequacy was established by macroscopic assessment (> 4 mm in length). Two diagnosis groups were analyzed: the virtual diagnosis group from the VivaScope confocal microscopyvirtual images of the first EUS-FNB pass, interpreted independently by two experienced pathologists and the final diagnosis was based on the both EUS-FNB passes introduced in formalin and analyzed pathologically (H&E staining and immunohistochemistry) by other two pathologists blinded from the virtual analysis and independent between them. The concordance and interobserver agreement between the virtual and final diagnosis were assessed.

Results

Fifty-two patients undergoing EUS-FNB were included. The final histological diagnoses ware: 37 malignant lesions (23 pancreatic adenocarcinomas, 3 cholangiocarcinomas, 2 pancreatic neuroendocrine tumors, and 9 other malignancies) and 15 with benign pathology (14 chronic pancreatitis, 1 schwannoma). All the samples were adequate for pathological assessment. VivaScope evaluation showed high interobserver agreement, with a Cohen’s kappa of 0.95 and 98% concordance (51/52 cases). Standard pathological diagnosis showed perfect agreement (100%) between observers. In 12 (23%) cases the immediate management of the patient was changed after the VivaScope result, especially regarding the management of obstructive jaundice.
There was one false negative result on VivaScope: a lesion interpreted as benign, which was later confirmed to be a pancreatic adenocarcinoma on final histology. Additionally, three false positive cases were identified — all were initially interpreted as pancreatic neuroendocrine tumors using VivaScope but were ultimately diagnosed as chronic pancreatitis.

Conclusion

VivaScope confocal microscopy provides rapid and reliable on-site diagnostic assessment during EUS-guided biopsies, with excellent interobserver agreement and strong concordance with classical histology. However, care must be taken when interpreting suspected pancreatic neuroendocrine tumors on VivaScope, as confocal features may overlap with chronic inflammatory changes such as those seen in chronic pancreatitis. VivaScope is a valuable adjunct tool that may enhance clinical decision-making in gastrointestinal oncology.