1. Clinicians should be aware of the observed associations between hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSDs) and postural orthostatic tachycardia syndrome (POTS) and/or mast cell activation syndrome (MCAS) and their overlapping GI) manifestations; while theoretical explanations exist, experimental evidence of the biological mechanisms that explain relationships is limited and evolving.
2. Testing for POTS/MCAS should be targeted to patients presenting with clinical manifestations of POTS/MCAS, but universal testing for POTS/MCAS in all patients with hEDS/HSDs is not supported by the current evidence.
3. Gastroenterologists seeing patients with DGBI should inquire about joint hypermobility and strongly consider incorporating the Beighton score for assessing joint hypermobility into their practice as a screening tool; if the screen is positive, gastroenterologists may consider applying 2017 diagnostic criteria to diagnose hEDS (https://www.ehlers-danlos.com/wp-content/uploads/2017/05/hEDS-Dx-Criteria-checklist-1.pdf) or offer appropriate referral to a specialist where resources are available.
4. Testing for POTS through postural vital signs (eg, symptomatic increase in heart rate of 30 beats/min or more with 10 minutes of standing during an active stand or head-up tilt table test in the absence of orthostasis) and referral to specialty practices (eg, cardiology or neurology) for autonomic testing should be considered in patients with hEDS/HSDs and refractory GI symptoms who also report orthostatic intolerance after exclusion of medication side effects and appropriate lifestyle or behavioral modifications (eg, adequate hydration and physical exercise) have been attempted but is not required for all patients with hEDS/HSDs who report GI symptoms alone.
5. In patients presenting to gastroenterology providers, testing for mast cell disorders including MCAS should be considered in patients with hEDS/HSDs and DGBI who also present with episodic symptoms that suggest a more generalized mast cell disorder (eg, visceral and somatic pain, pruritus, flushing, sweating, urticaria, angioedema, wheezing, tachycardia, abdominal cramping, vomiting, nausea, diarrhea, urogynecological and neurological complaints) involving 2 or more physiological systems (eg, cutaneous, GI, cardiac, respiratory, and neuropsychiatric), but current data do not support the use of these tests for routine evaluation of GI symptoms in all patients with hEDS/HSDs without clinical or laboratory evidence of a primary or secondary mast cell disorder.
6. If MCAS is suspected, diagnostic testing with serum tryptase levels collected at baseline and 1–4 hours following symptom flares may be considered by the gastroenterologist; increases of 20% above baseline plus 2 ng/mL are necessary to demonstrate evidence of mast cell activation.
7. If a diagnosis of MCAS is supported through clinical and/or laboratory features, patients should be referred to an allergy specialist or mast cell disease research center where additional testing (eg, urinary N-methylhistamine, leukotriene E4, 11β-prostaglandin F2) may be performed.
8. Diagnostic evaluation of GI symptoms consistent with DGBI in patients with hEDS/HSDs and comorbid POTS and/or MCAS should follow a similar approach to the evaluation of DGBI as in the general population including the use of a positive symptom-based diagnostic strategy and limited noninvasive testing.
9. Testing for celiac disease may be considered earlier in the diagnostic evaluation of patients with hEDS/HSDs who report a variety of GI symptoms and not only limited to those with diarrhea. There is insufficient research to support routine testing for disaccharidase deficiencies or other diet-mediated mechanisms as causes of GI symptoms in hEDS/HSDs.
10. Diagnostic testing for functional defecation disorders with anorectal manometry, balloon expulsion test, or defecography should be considered in patients with hEDS/HSDs and lower GI symptoms such as incomplete evacuation given the high prevalence of pelvic floor dysfunction, especially rectal hyposensitivity, in this population.
11. In patients with hEDS/HSDs and comorbid POTS who report chronic upper GI symptoms, timely diagnostic testing of gastric motor functions (eg, measurement of gastric emptying and/or accommodation) should be considered after appropriate exclusion of anatomical and structural diseases, as abnormal gastric emptying may be more common than in the general population.
12. Medical management of GI symptoms in hEDS/HSDs and POTS/MCAS should focus on treating the most prominent GI symptoms and abnormal GI function test results. In addition to general DGBIs and GI motility disorder treatment, management should also include treating any symptoms attributable to POTS and/or MCAS.
13. Treatment of POTS may include increasing fluid and salt intake, exercise training, and use of compression garments. Special pharmacological treatments for volume expansion, heart rate control, and vasoconstriction with integrated care from multiple specialties (eg, cardiology, neurology) should be considered in patients who do not respond to conservative lifestyle measures.
14. When MCAS is suspected, patients can benefit from treatment with histamine receptor antagonists and/or mast cell stabilizers, in addition to avoiding triggers such as certain foods, alcohol, strong smells, temperature changes, mechanical stimuli (eg, friction), emotional distress (eg, pollen, mold), or specific medications (eg, opioids, nonsteroidal anti-inflammatory agents, iodinated contrast).
15. Besides general nutritional support, special diets including a gastroparesis diet (ie, small particle diet) and various elimination diets (eg, low fermentable carbohydrates, gluten- or dairy-free, low-histamine diets) can be considered for improving GI symptoms. Dietary interventions should be delivered with appropriate nutritional counseling or guidance to avoid the pitfalls of restrictive eating.
16. Management of chronic GI symptoms in patients with hEDS/HSDs who do not exhibit symptoms consistent with POTS or MCAS should align with existing approaches to management of DGBI and GI motility disorders in the general population, including integrated multidisciplinary care involving multiple specialties, where appropriate (eg, cardiology, rheumatology, dietician, psychology).
