Can Eosinophilic Gastroenteritis Cause Autonomic Dysfunction?
Yes, eosinophilic gastroenteritis (and eosinophilic gastrointestinal disorders more broadly) can be associated with autonomic dysfunction, particularly postural orthostatic tachycardia syndrome (POTS), with a prevalence 5-10 fold higher than the general population. 1
Evidence for the Association
The most direct evidence comes from a retrospective cohort study demonstrating that the prevalence of POTS in patients with eosinophilic gastrointestinal disorders (EGIDs) was 1.25% compared to 0.17% in the general population, representing a 5-10 fold increased risk. 1 Among seven identified patients with both EGID and autonomic dysfunction:
- All had POTS, with 71% being female and 100% Caucasian 1
- Two patients (29%) also had gastroparesis 1
- Onset of autonomic symptoms coincided with EGID symptom onset in 43% of cases or with acute EGID flares in another 43% 1
- Two subjects (29%) had comorbid Ehlers-Danlos syndrome and mast cell activation syndrome 1
Clinical Implications and Mechanism
The underlying mechanism linking eosinophilic gastroenteritis to autonomic dysfunction remains unclear, but the temporal relationship suggests a potential pathophysiologic connection. 1 Importantly, successful control of EGID did not lead to improvement of autonomic symptoms in any cases, suggesting that once autonomic dysfunction develops, it may become independent of the underlying eosinophilic process. 1
Eosinophils release highly cytotoxic granular proteins that cause severe tissue damage, and they accumulate through a complex molecular network involving Th2 cells, various cytokines (including IL-3, IL-5), and chemokines. 2 This inflammatory cascade could theoretically affect autonomic nerve fibers within the gastrointestinal tract.
Diagnostic Considerations
Providers should maintain a high index of suspicion for comorbid autonomic dysfunction in EGID patients, particularly when symptoms persist despite adequate treatment of the eosinophilic disease. 1 Key clinical features to assess include:
- Orthostatic intolerance symptoms (lightheadedness, palpitations, fatigue upon standing) 1
- Gastroparesis symptoms (early satiety, nausea, vomiting) that may overlap with EGID manifestations 1
- Temporal relationship between EGID flares and autonomic symptoms 1
- Presence of other associated conditions such as Ehlers-Danlos syndrome or mast cell activation syndrome 1
Broader Context of Eosinophilic Disorders and Systemic Manifestations
While the guidelines focus primarily on eosinophilic esophagitis, hypereosinophilic syndromes (HES) can affect multiple organs including the gastrointestinal tract, heart, skin, lungs, and nervous system, with up to 38% of HES patients experiencing gastrointestinal symptoms. 3, 4 This demonstrates that eosinophilic disorders can have systemic neurologic manifestations beyond the gut.
In patients presenting with esophageal symptoms and hypereosinophilia (absolute eosinophil count >1500 cells/μL), further screening for non-EoE eosinophilic gastrointestinal disease and monitoring for other organ involvement should be considered. 3 This broader evaluation may help identify patients at risk for autonomic complications.
Important Caveats
- The association is based on a single retrospective cohort study with a small number of cases (n=7), limiting the strength of conclusions 1
- The mechanism remains speculative, and causality cannot be definitively established 1
- Treatment of the underlying EGID does not appear to reverse autonomic dysfunction once established 1
- Overlap with other conditions (Ehlers-Danlos syndrome, mast cell activation syndrome) suggests shared pathophysiology or common predisposing factors 1