Introduction

Disorders of Gut-Brain Interactions (DGBIs), such as functional dyspepsia (FD) or Irritable Bowel Syndrome (IBS) are common in patients with Hypermobile Ehlers-Danlos Syndrome/Hypermobile Spectrum Disorder (hEDS/HSD)¹. Healthcare utilisation (HCU) is high in DGBIs but no study to date has looked at HCU or healthcare costs (HCC) in patients with hEDS/HSD and these DGBIs.

Aims & Methods

To calculate the healthcare costs associated with patients with hEDS/HSD and FD and/or IBS.
A cross-sectional study was performed. Patients completed a ROME IV, SF6 (quality of life questionnaire) and HCU questionnaire. The latter was adapted from the IBD Boost study² and included consultations, admissions, clinically assisted nutrition and hydration (CANH), medications and personal expenses over 6 months. Costs were calculated based on the National Schedule of NHS Costs³ and NHS Business Services Authority Prescription Cost Analysis⁴. Patients were grouped based on ROME IV diagnoses of FD and IBS. Chi-squared was used for categorical data. The Kruskal-Wallis test was used for continuous variables. A multivariate regression analysis was performed to see what healthcare characteristics were the strongest predictors of rising HCCs. In view of the multiple comparisons p<0.005 was considered significant.

Results

660 hEDS/HSD patients completed the study; 92.9% were female, median age 39 years. 90(13.2%) had IBS only, 197(29.0%) had FD only, 212(31.2%) had both FD and IBS and 161(23.7%) had neither IBS nor FD. Table 1 describes and compares HCU across the 4 groups. There were significantly more outpatient visits, admissions and CANH use in patients with FD±IBS. Total HCC per patient was significantly higher in patients with both FD and IBS (£3622.15) and FD only (£3782.82) compared to IBS only (£1610.12,p<0.001) and neither IBS nor FD (£1376.34,p<0.001). Consultations and admissions contributed to the majority of total HCC (31.3% and 27.4% respectively). Rheumatology and Gastroenterology were the commonest secondary/tertiary services used. CANH was used in 37.6% of patients with FD only and 29.2% of patients with both FD and IBS and accounted for 11% and 7% of total HCC in these DGBI groups respectively. The 10 highest HCCs (£21,653.80-£99,983.90) were in patients with FD±IBS, and they all required an inpatient admission.
The average SF6 in patients with FD±IBS (0.253) was significantly lower than in patients with IBS only (0.511,p<0.001) or those with neither IBS nor FD (0.519,p<0.001). 22.0% of the entire cohort had a score less than 0, which is a quality of life worse than death.
The adjusted R² value of the regression model used to determine what factors independently correlated with rising HCCs was 0.527. The variables significantly predicted rising HCCs, F(31,557)=3.775, p<0.001. 'Polypharmacy' and 'Employment Status' were the greatest predictors of rising healthcare costs (β=-0.209, p<0.001 and β=-0.121,p=0.003 respectively).

Table 1: Comparison of HCU in hEDS/HSD with and without FD and IBS over 6 months.

	Neither IBS nor FD (n=161)	IBS only (n=90)	FD only (n=197)	Both FD and IBS (n=212)	p-value (comparing differences across all groups)
Median number of outpatients visits per patient(range)	4(0-104)	7.5(0-84)	9(0-135)	9(0-102)	<0.001
Number(%) with ≥1 admission	8(5)	2(2.2)	33(16.8)	26(12.3)	<0.001
The median number of investigations per patient(range)	2(0-12)	3(0-8)	2(0-10)	2.5(0-11)	0.742
Number(%) on CANH	16(9.9)	8(8.9)	74(37.6)	62(29.2)	<0.001
The median number of medications per patient(range)	6(0-18)	7(1-17)	6(1-17)	7(1-23)	0.132

Conclusion

In hEDS/HSD patients, those with FD±IBS had the highest HCU and HCC highlighting the need to prioritise the development of cost-effective services for those with foregut disorders.

References

¹Lam et al. Clinical Gastroenterology and Hepatology 2021;19(2)
²Roukas et al. Frontline Gastroenterology 2022;14(1)
³England N. 2019/20 National Cost Collection Data Publication 2022
⁴NHSBSA. Prescription Cost Analysis – England 2020/21 2021

Introduction

Patients with Hypermobile Ehlers Danlos Syndrome (hEDS) have a high prevalence of Disorders of Gut-Brain Interaction (DGBI) and pose complex nutritional challenges in gastroenterology clinic. Despite this, little is known regarding nutrient intake and adequacy in hEDS.

Aims & Methods

Our aim was to assess nutrient intake and adequacy of patients with hEDS, as well as to determine which factors, including co-existent DGBI, are associated with poor intake. We conducted a cross sectional survey of patients with hEDS from two tertiary neurogastroenterology clinics as well as the Ehlers-Danlos Support UK. Inclusion criteria were adults with hEDS, exclusion criteria were those currently or previously using artificial nutrition. Patients completed the validated semi-quantitative Scottish Collaboration Group Food Frequency Questionnaire (FFQ) alongside questionnaires characterising: demographics, DGBIs (Rome IV), gastrointestinal, mood, somatic and autonomic symptoms, past history of eating disorders and screen for Avoidant Restrictive Food Intake Disorder (ARFID) using the Nine Item Avoidant-Restrictive Scale (NIAS). Nutrient intake was calculated from the FFQ and nutrient adequacy was calculated by comparison with UK daily reference values (DRVs) for age and sex. Unpaired t-tests were performed to compare nutrient intakes among patients with and without comorbidities, including the most common DGBIs.

Results

425 participants were included in the final analysis (mean: 41 years, 96% female). Only 48.5% reported BMI in the normal range, whereas 5.2% were underweight (BMI <18.5 kg/m²)and46.4% were overweight/obese (BMI >25 kg/m²). Only one third met their estimated average requirements (EAR) for energy (kcal/d). The majority met their reference nutrient intake (RNI) for protein (87.3%) and fat (72.5%), in contrast to only 21.2% for carbohydrate. Fibre intakes were very low (AOAC mean 23.7g/day (SD: 12.7) with only 24.7% meeting the RNI of 30 g/d. More than 58% of participants met/exceeded their DRV for micronutrients (zinc, magnesium, copper, manganese and selenium) and >95% for vitamins. Patients with functional nausea (n=157) were less likely to meet their protein requirements compared to those without (82.2% vs. 90.3%, p=0.015) and also had lower intakes for sodium (p=0.02), magnesium (p=0.02), calcium (p=0.01), zinc (p=0.002), selenium (p=0.03), folic acid (p=0.02) and vitamin C (p=0.05). Patients with previous eating disorders were less likely to meet nutrient requirements for thiamine (p=0.01) and vitamin B12 (p=0.04). Patients with ARFID (n=110) were less likely to meet requirements for all nutrients (except fat, calcium, vitamin D, vitamin B12) compared to patients without.

Conclusion

Patients with hEDS are rarely underweight and tend to consume high protein, high fat diets that are low in fibre. Functional nausea is the single most important DGBI impacting nutrient intake, as well as previous eating disorders and disordered eating (ARFID). These factors should be considered by clinicians and dietitians when assessing nutrient intake in this complex patient group.

Disclosure

RT, AF and QA have received a grant from EDS-UK to conduct this study. AF undergoes consulting work for Abbvie.
KW has received research funding from Almond Board of California, Danone, International Nut & Dried Fruit Council, and has a patent for volatile organic compounds in the detection and management of IBS.
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.

Introduction

Patients with Hypermobile Ehlers Danlos Syndrome (hEDS) have a high prevalence of Disorders of Gut-Brain Interaction (DGBI) and pose complex nutritional challenges in gastroenterology clinic. Despite this, little is known about their dietary patterns and whether this is associated with relevant clinical characteristics.

Aims & Methods

Our aim was to identify dietary patterns in hEDS, phenotype patients according to their dietary patterns and determine whether these patterns are associated with gastrointestinal or other factors. We conducted a cross sectional survey of patients with hEDS from two tertiary neurogastroenterology clinics as well as the Ehlers-Danlos Support UK. Patients completed the validated semi-quantitative Scottish Collaboration Group Food Frequency Questionnaire (FFQ) alongside questionnaires characterising: demographics, DGBIs (Rome IV), past history of Postural orthostatic Tachycardia Syndrome (PoTS) or Mast Cell Activation Syndrome (MCAS), somatic and autonomic symptoms, anxiety and depression, gastrointestinal specific anxiety, Restrictive Food Intake Disorder (ARFID) screen, artificial nutrition use, nutritional supplement use and previous dietetic consultation. The 169 food items on the FFQ were consolidated into 49 food groups and principal components analysis (PCA) was used to derive dietary patterns. Cluster analysis was then used to classify patients into dietary groups. Clinical characteristics were compared between clusters using the Chi-square test, analysis of variance (ANOVA) and Kruskal-Wallis test as appropriate.

Results

470 patients were included in the final analysis, of which four clusters were identified: cluster 1 (n=169) - low energy intake; cluster 2 (n=62) - vegetarian / health conscious; cluster 3 (n=133) - prudent / low residue and cluster 4 (n=106) - refined / highly processed food. Patients in the low energy intake group (cluster 1) were most likely to attend the tertiary neurogastroenterology clinic (p=0.002), have a dietetic consultation (p=0.02) and report previous or current use of artificial nutrition (p=0.03) compared to the other clusters. Patients in the vegetarian / health conscious group (cluster 2) had the lowest depression scores (p=0.03), lowest GI specific anxiety (p=0.005) and interestingly, were most likely to take nutritional supplements (p=0.04). Patients in the prudent / low residue group (cluster 3) and the refined / highly processed food group (cluster 4) had the highest body mass index (p=0.003). Patients in the refined / highly processed food group (cluster 4) were youngest (p<0.001), had higher scores for depression (p=0.03), higher scores for GI specific anxiety (p=0.005) and higher scores for ARFID (p=0.007). They were also least likely to take nutritional supplements (p=0.04) and least likely to attend the tertiary neurogastroenterology clinic (p=0.002). Interestingly, there was no significant association between dietary patterns and PoTS, MCAS or DGBIs.

Conclusion

This is the first study to identify dietary patterns in patients with hEDS. The most common dietary cluster was lower energy intake and this was most likely to be seen in those attending tertiary clinics and utilising artificial nutrition. Whereas those who are on a refined / highly processed food diet tend to be younger and have more psychopathology. Further research is needed to establish how these associations could best be utilised in clinical practice.

Disclosure

RT, AF and QA have received a grant from EDS-UK to conduct this study. AF undergoes consulting work for Abbvie.
KW has received research funding from Almond Board of California, Danone, International Nut & Dried Fruit Council, and has a patent for volatile organic compounds in the detection and management of IBS.
QA undergoes consulting work for Takeda Pharmacueticals, and Classado Biosciences Ltd.

Introduction

Hypermobile Ehlers-Danlos syndrome (hEDS) is a hereditary non-inflammatory disorder of connective tissue laxity characterized by joint hyperextensibility in association with musculoskeletal symptoms. The prevalence of gastrointestinal (GI) symptoms, such as abdominal pain, nausea, and constipation is high in hEDS. Research on the relationship between EDS and GI symptoms has mostly been restricted to disorders of the gut-brain axis, whereas the relationship between hEDS and GI dysmotility remains to be clarified.

Aims & Methods

This study aimed to explore antro-duodenal manometry (ADM) patterns in patients with hEDS presenting with GI symptoms.

In a prospective open-label study, patients with hEDS and GI symptoms presumed to be the results of GI dysmotility underwent a 6-hour high resolution ADM. The manometry tracings were analyzed by two investigators (KS and JC) independently. Antral contraction frequency (contractions per minute) < 1.0 was considered as antral hypomotility. Pylorospasm was defined as isolated pyloric pressure waves within 60 minutes postprandial. The following neuropathic enteric patterns were scored: presence of retrograde peristalsis, bursts, clustered contractions, and absence of phase III contractions. Abnormal ADM was defined as having antral hypomotility and/ or pylorospasm and/ or neuropathic enteric patterns.

Results

Fifty patients (48 women, mean age 30.4 ± 11.1 yrs.) were included. At baseline, 74% of patients were dependent on enteral feeding and the mean BMI was 20.4 ± 4.4 kg/m².
Overall, ADM tracings with one or more abnormal patterns were identified in 53% of patients. Antral hypomotility and pylorospasm were detected in 29% and 15% of patients, respectively. Neuropathic enteric patterns were only seen in 17% of patients. In all cases, no more than one neuropathic pattern was identified. Among the observed neuropathic enteric patterns, 15% of patients showed retrograde peristalsis, 13% absence of phase III contractions, and 2% bursts. Clustered contractions were not identified in this cohort.

Conclusion

Hypermobile Ehlers-Danlos patients presenting with gastrointestinal symptoms showed low numbers of abnormal ADM patterns. In particular, enteric dysmotility was observed in only a small minority of cases. Antroduodenal dysmotility therefore does not appear to be a principle pathomechanism in the majority of hEDS cases studied. Further research is needed to understand the mechanisms that underlie GI symptom generation in this population.

Introduction

Ehlers–Danlos syndrome (EDS) is a connective tissue disorder characterized by a non-inflammatory nature. Hypermobility EDS (hEDS) accounts for 80–90% of all EDS cases‎^‎1.
Over the past two decades, studies have reported a high prevalence of gastrointestinal (GI) symptoms among hEDS patients, including abdominal pain, bloating, constipation, diarrhea, nausea, vomiting, and reflux disease.

Aims & Methods

To characterize the GI symptoms in patients with hEDS and to explore the potential contribution of functional and anatomical abnormalities to the GI manifestations observed in this population.
We conducted a retrospective cohort study of patients diagnosed with hEDS who were evaluated at both the EDS and Gastroenterology clinics. Eligible patients had a clinical diagnosis of hEDS based on the Brighton criteria. Patients with a documented diagnosis of inflammatory bowel disease (IBD) were excluded. Demographic data, GI symptoms, and results from diagnostic evaluations—including anorectal manometry, balloon expulsion test, defecography, gastric emptying scans, transit studies, and endoscopic procedures—were collected and analyzed.

Results

A total of 76 patients with hEDS were included with a median age of 33.7 years. Common comorbidities included endometriosis (43.5%), fibromyalgia (36.8%). Macrophage activation syndrome was diagnosed in 2.6%.
Upper GI symptoms were frequently reported, with heartburn (31.6%), postprandial pain (30.3%), early satiety (25%), epigastric pain unrelated to meals (22.4%), and dysphagia (13.2%) being the most prevalent.
Lower GI complaints were even more common: constipation affected 64.5% of patients, bloating 57.9% and chronic diarrhea 40.8%. Notably, 19.7% experienced both constipation and diarrhea.
Among 32 patients who underwent colonoscopy, 30 had normal findings.
Anorectal manometry revealed hyposensitivity in 54% of constipated patients and hypersensitivity in 54% of diarrhea patients. Squeeze pressure was low in 38% of diarrhea patients. Balloon expulsion failure occurred in ~50% of patients across groups.
Defecography demonstrated a high prevalence of anatomical abnormalities: rectocele (67–78%), enterocele (47–78%), and rectal prolapse (53–78%). Gastroparesis was identified in 45–60% of patients undergoing gastric emptying scans due to lower GI complaints. Prolonged colonic transit was found in 25–50% of those evaluated.

Conclusion

Patients with hEDS commonly experience a broad range of upper and lower GI symptoms, often presenting with multiple overlapping complaints. Functional and structural abnormalities—such as rectal hyposensitivity, pelvic floor dysfunction, rectocele, and enterocele—were frequently identified and may underlie these symptoms. Notably, gastroparesis was prevalent, highlighting the widespread impact of EDS on GI motility. These findings underscore the importance of comprehensive GI assessment in EDS patients, integrating both functional testing and imaging to guide appropriate management.

References

1. Tinkle B, Castori M, Berglund B, Cohen H, Grahame R, Kazkaz H, Levy H. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): Clinical description and natural history. Am J Med Genet C Semin Med Genet. 2017 Mar;175(1):48-69. doi: 10.1002/ajmg.c.31538. Epub 2017 Feb 1. PMID: 28145611

Introduction

Functional Constipation (FC) and Constipation-predominant Irritable Bowel Syndrome (IBS-C) are two common disorders of gut-brain interaction (DGBI) which can often present overlapping symptoms, thus making difficult to distinguish them. ​

Aims & Methods

This study aims to determine whether the demographic and clinical profiles of consecutive patients diagnosed with FC and IBS-C differ in real-world clinical practice.
Demography and clinical information from the first clinical consultation where the diagnosis was made by a single consultant using a standardized clinical letter were retrospectively collected from January 2016 to March 2025 at a single tertiary care neurogastroenterology clinic in the UK Data were collected using a standardised template and were reported as median [interquartile range (IQR)] or frequency (%), and compared using the Chi-square test or Mann-Whitney U test.

Results

	FC (n= 88)	IBS - C (n=257)	p-value
Demography and general characteristics
Male, n (%) Age (years), median (IQR) Duration of symptoms (year),median (IQR)	24 (27%) 47 (25) 12,5 (17)	42 (16%) 32 (26) 5 (10)	0.036 0.0001 0.0001
Total number of concomitant medical condition, median (IQR) Chronic pain, n (%) Abdominal surgeries, n (%)	1 (2) 12 (14%) 24 (27%)	4 (4,5) 66 (26%) 112 (44%)	0.001 0.02 0.01
Total number of hospital admissions, median (IQR)	1 (2)	1 (5)	1.0
Total number of previous diagnostic investigation at first consultation, median (IQR)	1 (2)	1 (2)	1.0
Concomitant medications
Total number of concomitant medications, median (IQR) Tricyclic antidepressant, n (%) Selective Serotonin Reuptake Inhibitor, n (%) Serotonin-norepinephrinereuptake inhibitors, n (%) Opioids n, (%) Laxatives n, (%) Antispasmodics n, (%)	3 (4,5) 12 (14%) 12 (14%) 8 (9%) 13 (15%) 61 (70%) 3 (3%)	4 (4,5) 44 (18%) 39 (15%) 13 (5%) 82 (31%) 116 (45%) 42 (16%)	0.001 0.550 0.859 0.268 0.003 0.0001 0.003
Gi symptoms
Nausea, n (%) Early satiety n, (%) Vomiting, n (%) Post pandrial fulness, n (%) Heartburn, n (%) Abdominal pain, n (%)	16 (19%) 6 (7%) 7 (8%) 8 (9%) 13 (15%) 9 (10%)	93 (37%) 56 (21%) 45 (17%) 53 (20%) 52 (19%) 234 (91%)	0.002 0.002 0.04 0.02 0.330 0.0001

A total of 88 FC and 257 IBS-C consecutive patients were diagnosed according to Rome IV criteria. FC patients were older and most frequently males, with a longer duration of symptoms. Abdominal pain was largely absent in FC patients and when present this was not related to defecation but reported as result of long-lasting lack of bowel movement. Upper gastrointestinal symptoms were more frequent in IBS-C compared to FC. Comorbidities, particularly chronic pain syndromes, and abdominal surgeries were more frequently reported by IBS-C patients. in addition, IBS-C patients were more frequently on pain medications, while FC on laxatives. Table 1 summarizes the data collected in both groups.

Conclusion

This real-world study suggests that FC and IBS-C patients differ in demographic, clinical profile and comorbidities. IBS-C patients report a more severe clinical picture despite FC patients and had a longer duration of symptoms.

References

Bharucha AE, Sharma M. Painful and Painless Constipation: All Roads Lead to (A Change in) Rome. Dig Dis Sci. 2018 Jul;63(7):1671-1674. doi: 10.1007/s10620-018-5027-2. PMID: 29564675; PMCID: PMC6293467.
Bouchoucha M, Devroede G, Mary F, Bon C, Bejou B, Benamouzig R. Painful or Mild-Pain Constipation? A Clinically Useful Alternative to Classification as Irritable Bowel Syndrome with Constipation Versus Functional Constipation. Dig Dis Sci. 2018 Jul;63(7):1763-1773. doi: 10.1007/s10620-018-4995-6. Epub 2018 Feb 28. PMID: 29492744.