Functional gastrointestinal disorders are associated with the joint hypermobility syndrome in secondary care: a case-control study

Fikree A, Aktar R, Grahame R, Hakim AJ, Morris JK, Knowles CH, Aziz Q; 2015 Neurogastroenterol 27: (569-579).

Ann Dunbar PT, DPT, MS, WCS

June 3, 2015

Introduction

• Functional gastrointestinal disorders (FGID) account for 40% of visits to GI clinics.
• Despite increasing focus on research, diagnostic biomarkers and etiology are not well established.
• It is well established that inflammatory connective tissue disorders are associated with GI dysfunction and evidence is increasing that non-inflammatory disorders (such as joint hypermobility disorders) may also be related.
• Due to lack of distinct biomarker, current gold standard for diagnosing joint hypermobility syndrome (JHS) is 1998 Brighton classification for JHS (see Table 1 in article).
• It has been recognized more recently that JHS is a disorder of multiple systems (eg chronic pain syndromes, dysautonomia, urinary symptoms, GI symptoms, and anxiety disorders). GI sx such as globus, bloating, reflux, postprandial fullness, and early satiety have a high prevalence in rheumatology and genetics clinics. In GI clinics, 1/3 of pts have undiagnosed JHS suggesting association between GI symptoms and this syndrome however, conclusive evidence is limited due to lack of controlled studies.

Aims

Primary:  Determine using case controlled design, whether JHS is associated with FGID compared with GI disorders among patients referred to secondary care GI clinics.

Secondary:  Characterize the association and determine whether JHS is associated with FGID Rome III subcategories and whether presence of JHS in FGID is associated with reduced QOL and increased comorbidity. (Note: the Rome Process is an international effort to create and use scientific data to aid in the diagnosis and treatment of FGID).

Study Design:  Case control study design

Methods:

• Consecutive new pts ages 18-70 in GI clinics in large university teaching hospital in East London participated.
• Pts completed questionnaires to assess GI sx, psychopathology, autonomic symptoms, somatic sx, and QOL.
• Pts underwent interviews and exams performed by lead author to diagnose JHS; author was blinded to results of questionnaires and any diagnosis.
• Presence of fibromyalgia determined using 1990 Wolfe criteria
• An independent GI physician, blinded to hypermobility status assessed, investigated and diagnosed the GI patient. If given more than 1 diagnosis, they used the diagnosis more relevant to the presenting complaint.
• Based on primary diagnosis, pts were broadly placed into either functional or organic disorder categories. FGID categories also separated into Rome III subtypes. Diagnosis of dysmotility required confirmation from further GI testing (eg colonoscopy).
• Data analysis and statistics described in article.              

Results

• Cohort of consented, eligible subjects = 688; 47 did not receive a GI dx so they were excluded from analysis leaving cohort of 641 pts where 59.1% were female, mean age 42.0 years;  54.2% were functional dx (patients) and 47.6% were organic diagnosis (controls).
• Significantly more females in FGID group 65.5% vs 52.1% (p<0 .001="" 2="" 40.1="" 44.0="" amongst="" and="" comparable="" compared="" controls="" distribution="" ethnic="" groups.="" o:p="" p="" patients="" to="" vs="" was="" were="" younger="">

Prevalence of JHS in cases (FGID) and controls (organic GI dz)

• Significantly higher prevalence of JHS in FGID group. See Table 2 (p=0.002). After adjusting for age and gender, significant association between JHS and FGID remained compared to organic GI group (ORadj:1.51, CI 1.07-2.12, p=0.02)  

• Prevalence of JHS in specific organic GI disorders
• When grouped into various categories (Table 3), high prevalence of JHS in reflux disorders (38.6%) and erosive reflux dz (36.1%). Lower prevalence of JHS observed in organic dysmotility (15.4%), ulcerative colitis (21.0%) and other inflammatory dz (21.8%). See Table 4.
• Prevalence of JHS in specific FGID subtypes
• 75.9% of subjects completed questionnaire (in entirety), so researchers were able to categorize cohort into Rome III functional subtypes
• Found no significant difference in the prevalence of those with JHS with either single FGID or overlapping disorders (Table 5)
• Found significant association between JHS and functional gastroduodenal disorders (44.1%; ORadj: 2.08, CI: 1.25-3.46, p=0.005).
• Anorectal disorders and functional bowel disorders were more prevalent amongst JHS cohort but did not reach significance.
• Postprandial distress syndrome (epigastric discomfort after eating) was associated with JHS after adjusting for gender and age (ORadj: 1.99, CI: 1.06-3.76, p=0.03)
• Comorbidity and QOL in FGID patients with and without JHS
• Considering age, gender, or likelihood of overlapping functional disorders , there were no differences in patients with or without JHS (p>0.05, See Table 5) however JHS had significantly more chronic pain measures and higher incidence of more widespread, chronic pain (p=0.01), fibromyalgia (p=0.01)  and greater likelihood of presence of tender points (p=0.002).
• JHA patients also had greater somatic sensitivity (p=0.001), higher urinary autonomic scores (p=0.03), but no differences in vasomotor, syncope, or orthostatic scores.
• JHS patients also had worse QOL scores related to pain (p=0.004) and role-limiting emotional scores (p=0.01). Depression scores did not differ between groups however, anxiety scores were higher in JHS groups (p=0.01).

Discussion

• This is first large comparative study examining whether JHS is associated with FGID in people with no prior hypermobility dx. Main findings:
• Statistically significant that JHS is present in approximately 40% of new patients given dx of FGID compared with 27% of pts given an organic dx
• JHS is specifically associated with functional gastroduodenal disorders, specifically postprandial distress syndrome
• Among FGID pts, those with JHS syndrome have more somatic sensitivity, chronic pain, anxiety and poorer QOL compared to those without JHS.
• Because pts with established JHS were excluded, this may have accounted for lack of association between IBS-constipation and JHS (where earlier JHS dx could indicate more ‘severe phenotype’).  On the other hand, JHS has been found to be associated with rectal evacuatory dysfunction, and rectal abnormalities and authors note this deserves further study.
• Post hoc analysis demonstrated significant association between JHS and reflux disorders (ORdj:1.89, CI: 1.03-3.45, p=0.04). Authors suggest this requires validation with larger sample size.
• Study demonstrates that JHS pts have multiple comorbidities: chronic pain, fibromyalgia, somatic symptoms, anxiety, and urinary autonomic symptoms and that JHS is associated with both GERD and functional dyspepsia. These GI dysfunctions have detrimental effect on QOL highlighting importance of identifying associations between otherwise unrelated sx.
• Strength of study design: reduced selection and response bias (studied previously undiagnosed pts), reduced performance and recall bias (use of prospective design); case-control design strengthened findings that JHS in GI clinics is associated with FGID more than organic dz.
• Limitations: Use of Brighton classification relies on some subjective clinical criteria rather than a biomarker.  Also, this study was powered to look at differences in large groups so results from smaller groups (specific GI disorders) should be interpreted with caution.  Lastly, authors used original Wolfe criteria to dx fibromyalgia which was what was available to use at time of application for ethics approval and now newer criteria are available.
• Results suggest autonomic dysfunction, sensorimotor abnormalities and psychopathology may be factors implicated in the patho-etiology of GI sx.  More research needed for this and to fill the ‘knowledge gaps’ regarding the role of connective tissue in the gut.

Summary

This research suggests that JHS is significantly associated with FGID and this subgroup of patients have decreased QOL and increased comorbidity.

 Clinical Application: 

1—How often do you use the Beighton Scale of hypermobility in your musculoskeletal screening?

3---Do any of these findings fit your clinical experience?   

2—The authors suggest that because of the multiple symptom impact of JHS, patients may benefit from a more ‘holistic multisciplinary management [approach].’ Will the findings in this study change the way you practice or provide care for your patients with functional GI disorders? 

 

Other References

Functional GI Disorders

http://www.iffgd.org/

International Foundation for Functional Gastrointestinal Disorders

“Functional gastrointestinal (GI) and motility disorders are the most common GI disorders in the general population.  Estimates vary, but about 1 in 4 people or more in the U.S. have one of these disorders. The conditions account for about 40% of GI problems seen by doctors and therapists.

The term "functional" is generally applied to disorders where the body's normal activities in terms of the movement of the intestines, the sensitivity of the nerves of the intestines, or the way in which the brain controls some of these functions is impaired. However, there are no structural abnormalities that can be seen by endoscopy, x-ray, or blood tests. Thus it is identified by the characteristics of the symptoms and infrequently, when needed, limited tests. The Rome diagnostic criteria categorize the functional gastrointestinal disorders and define symptom based diagnostic criteria for each category.”  http://www.iffgd.org/

 Rome III Criteria

“The Rome process is an international effort to create scientific data to help in the diagnosis and treatment of functional gastrointestinal disorders.” (Wikipedia) The first set of criteria were issued in 1989. Utilizing the Delphi method (expert consensus building process) they have been modified several more times with the most recent being 2006, the latter also including pediatrics.

The adult categories are as follows:

• Esophageal (Category A)
• Gastroduodenal (Category B)
• Bowel (Category C)
• Functional disorders include: irritable bowel syndrome (C1); functional bloating (C2); functional constipation (C3); functional diarrhea (C4)

• Functional Abdominal Pain Syndrome (Category D)
• Biliary (Category E)
• Anorectal  (Category F)

Components of the Brighton classification: see Table 1 in study

Components of the Beighton scale of hypermobility:

	LEFT	RIGHT
1. Passive dorsiflexion and hyperextension of the fifth MCP joint beyond 90°	1	1
2. Passive apposition of the thumb to the flexor aspect of the forearm	1	1
3. Passive hyperextension of the elbow beyond 10°	1	1
4. Passive hyperextension of the knee beyond 10°	1	1
5. Active forward flexion of the trunk with the knees fully extended so that the palms of the hands rest flat on the floor	1	1
TOTAL	/ 9