A Prospective Evaluation of Undiagnosed Joint Hypermobility Syndrome in Patients With Gastrointestinal Symptoms

doi:10.1016/j.cgh.2014.01.014

Clinical Gastroenterology and Hepatology

Volume 12, Issue 10, October 2014, Pages 1680-1687.e2

Preliminary data from this study have been presented as abstracts at international meetings in 2012.

https://doi.org/10.1016/j.cgh.2014.01.014 Get rights and content

Background & Aims

The Joint Hypermobility Syndrome (JHS) is a common connective tissue disorder characterized by joint hyperflexibility, dysautonomia, and chronic pain. Gastrointestinal (GI) symptoms are reported in JHS patients attending rheumatology clinics, but the prevalence and symptom pattern of previously undiagnosed JHS in GI clinics are unknown.

Methods

By using validated questionnaires, a prospective cross-sectional study in secondary care GI clinics estimated the prevalence of JHS in new consecutively referred patients, compared GI symptoms in patients with and without JHS, and by using multiple regression determined whether the burden of GI symptoms in JHS patients was dependent on chronic pain, autonomic, psychological, and medication related factors. A positive control group consisted of JHS patients referred from rheumatology clinics with GI symptoms (JHS-Rh).

Results

From 552 patients recruited, 180 (33%) had JHS (JHS-G) and 372 did not (non-JHS-G). Forty-four JHS-Rh patients were included. JHS-G patients were more likely to be younger, female with poorer quality of life (P = .02) than non-JHS-G patients. After age and sex matching, heartburn (odds ratio [OR], 1.66; confidence interval [CI], 1.1–2.5; P = .01), water brash (OR, 2.02; CI, 1.3–3.1; P = .001), and postprandial fullness (OR, 1.74; CI, 1.2–2.6; P = .006) were more common in JHS-G vs non-JHS-G. Many upper and lower GI symptoms increased with increasing severity of JHS phenotype. Upper GI symptoms were dependent on autonomic and chronic pain factors.

Conclusions

JHS is common in GI clinics, with increased burden of upper GI and extraintestinal symptoms and poorer quality of life. Recognition of JHS will facilitate multidisciplinary management of GI and extra-GI manifestations.

Section snippets

Objectives and Hypotheses

Our aims were to determine (1) the prevalence and phenotypic severity of JHS in GI clinics; (2) whether in this setting, JHS is associated with a particular or excessive GI symptom burden and reduced quality of life (QOL) compared with patients without JHS; and (3) whether GI symptoms in JHS are interdependent with other patient characteristics previously associated with JHS (autonomic dysfunction, chronic pain, somatization, and psychopathology).

Study Design, Cohort Selection, and Setting

A prospective cross-sectional study design was used to address our aims.

The main study cohort was derived from consecutive new patients with GI symptoms (but without prior JHS diagnosis), aged 16–70 years, who were attending general gastroenterology clinics at a large university teaching hospital in London between April 2010 and April 2012. After hypermobility assessment, patients were categorized as JHS (JHS-G) or non-JHS (non-JHS-G). An additional smaller sample of consecutive new patients

Unselected cohort

Two thousand four hundred one new patients referred from primary care to GI clinics and unaware of their hypermobility status were invited to participate, and 723 consented to take part. Of these, 144 did not complete their questionnaires, 16 did not undergo a full examination, and 11 did not meet the inclusion criteria, leaving 552 patients who were included in the study (Figure 1).

Positive control group

Fifty-four consecutive patients referred from specialist rheumatology clinics with a known diagnosis of JHS

Discussion

This is a comparative study of GI symptoms in patients with and without JHS in a prospective unselected (unbiased) cohort attending secondary care GI clinics. The main findings were (1) approximately one-third of unselected patients attending GI clinics have undiagnosed JHS based on validated clinical criteria; however, the phenotype is less severe than that observed in selected patients from rheumatology clinics; (2) undiagnosed JHS is significantly associated with increased reflux and

Conclusion

JHS is common and present in approximately one-third of patients attending GI clinics, albeit of a less marked phenotype than JHS-Rh in terms of hypermobility features, autonomic symptoms, chronic pain measures, and GI symptoms. Dyspepsia and reflux are significantly increased in these patients, and the mechanism for these symptoms remains to be elucidated, although it would seem that autonomic and pain/hypersensitivity factors are involved. Although future studies will examine the specific

Acknowledgments

The authors thank Dr Hanadi Kazkaz, MBBS, University College Hospital London, for assistance with the rheumatological aspects of the study; and Dr Neel Sharma, MBBS, for assistance with the collection of part of the data. They also thank Professor David Alpers (Centre for Human Nutrition) and Professor David Rampton (Queen Mary University London) for critical appraisal of the manuscript.

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These associations are drastically reduced when controlling for somatic symptoms, suggesting that they are a relevant confounder toward GI illness behavior in this patient group. Our findings corroborate with the published literature regarding the high prevalence of FGIDs in HSD/hEDS, although previous studies have been limited to case series, cohort studies, and small secondary care case-control studies.2-12 Notably, 2 national cohort studies, comprising 134 EDS societal members from France and more than 1000 EDS societal members in the United States, reported that 84% and 93% qualified for at least 1 FGID based on the Rome III criteria, respectively.11,12
Individuals with hypermobility spectrum disorder or hypermobile Ehlers-Danlos Syndrome (HSD/hEDS) are increasingly encountered by gastroenterologists and pose complex clinical challenges. Uncontrolled studies have found functional gastrointestinal disorders (FGIDs) to be common in patients with HSD/hEDS. Some patients have somatic symptoms (medically unexplained symptoms) that might affect FGIDs. We performed a case–control study to determine the prevalence of and factors associated with Rome IV FGIDs in subjects with HSD/hEDS compared with age- and sex- matched population-based controls.
An online general health survey was completed by 603 individuals with HSD/hEDS in October 2018 (cases) and 603 matched individuals from the population of the United Kingdom (controls) in 2015. The mean participant age was 39 yrs, and 96% were women. The survey included questions about Rome IV FGIDs, non-GI and non-musculoskeletal somatic symptoms (maximum number, 10), quality of life, medical history and healthcare use. The prevalence of FGIDs was compared between cases and controls, with subsequent logistic regression models - adjusting for the number of somatic symptoms - used to determine the associations for FGIDs in HSD/hEDS compared with controls.
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Thus, we used both cutoff values. The necessary sample size was determined based on a previous study in children with functional GI pain disorders and an adult study of patients with IBS.14,16 The studied sample size was adequate to detect a difference in Beighton score between children with IBS/FAP and healthy control children with a P value of <.05 and a power of 0.95 and for detecting a difference in the proportion of children with/without joint hypermobility (cutoff of 6) with a P value of <.05 and a power of 0.95.
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: Conflicts of interest The authors disclose no conflicts.

: Funding Supported by a charitable grant from the Pseudo-obstruction Research Trust, as well as a grant from Bowel and Cancer Research and Ehlers-Danlos Syndrome Support UK.

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Original articleAlimentary tractA Prospective Evaluation of Undiagnosed Joint Hypermobility Syndrome in Patients With Gastrointestinal Symptoms

Background & Aims

Methods

Results

Conclusions

Section snippets

Objectives and Hypotheses

Study Design, Cohort Selection, and Setting

Unselected cohort

Positive control group

Discussion

Conclusion

Acknowledgments

Gen Hosp Psychiatry

Am J Med

Mayo Clin Proc

Systematic review: pathophysiology and management of gastrointestinal dysmotility in systemic sclerosis (scleroderma)

Aliment Pharmacol Ther

The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome)

Am J Med Genet A

Tenascin-X deficiency is associated with Ehlers-Danlos syndrome

Nat Genet

The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS)

J Rheumatol

Hypermobility scoring

Br J Rheumatol

Ehlers-Danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations

ISRN Dermatol

The frequency of hypermobility and its relationship with clinical findings of fibromyalgia patients

Clin Rheumatol

Original article
Alimentary tract
A Prospective Evaluation of Undiagnosed Joint Hypermobility Syndrome in Patients With Gastrointestinal Symptoms