Evidence‑Based Specialist Referral Guidelines for Hypermobile Ehlers‑Danlos Syndrome (hEDS)

Gastroenterology Referral Criteria

In patients with hEDS, chronic gastrointestinal symptoms consistent with disorders of gut‑brain interaction are present in >60 % of cases, warranting gastroenterology evaluation. 1
When upper‑GI symptoms persist after exclusion of structural disease, timely diagnostic testing of gastric motor function is recommended. 2
Lower‑GI complaints such as incomplete evacuation often reflect a high prevalence of pelvic‑floor dysfunction, particularly rectal hyposensitivity, in the hEDS population. 2
The presence of episodic, generalized symptoms beyond isolated GI complaints should prompt assessment for mast‑cell activation syndrome (MCAS). 2

Referral to an allergy specialist or mast‑cell disease center is indicated when clinical and laboratory findings (e.g., baseline tryptase and post‑flare levels collected 1–4 h after symptoms) support a diagnosis of MCAS. 2
Patients exhibiting episodic systemic symptoms suggestive of a generalized mast‑cell disorder, not limited to the gastrointestinal tract, also merit allergy/immunology evaluation. 2

Formal autonomic testing should be considered for hEDS patients who demonstrate orthostatic intolerance manifested by palpitations, dizziness, presyncope, syncope, or light‑headedness. 3
Clinical features that improve when the patient is seated or supine, or that worsen with food intake, physical exertion, or heat exposure, further support the need for autonomic assessment. 3
Standing‑induced tachycardia or palpitations are additional indications for formal testing. 3
When refractory GI symptoms coexist with orthostatic intolerance after exclusion of medication side‑effects and implementation of lifestyle modifications, autonomic evaluation is advised. 3
Universal screening for postural orthostatic tachycardia syndrome (POTS) in all hEDS patients is not supported by current evidence. 3

Brain‑gut behavioral therapies are recommended because studies show increased rates of anxiety and psychological distress among individuals with hypermobility. 2

Do not perform universal autonomic testing; limit testing to patients with symptomatic orthostatic intolerance. 3
Do not delay celiac disease testing in hEDS patients presenting with diverse GI symptoms; early testing is advised. 2
Avoid routine opioid prescriptions for pain‑predominant features of hEDS; prioritize non‑opioid pain management strategies. 2