Overlap In Gastrointestinal Manifestations Among Small Fiber Neuropathy, Postural Tachycardia Syndrome, Ehlers-Danlos Syndrome, And Mitochondrial Disease Adult Patients

INTRODUCTION: Small fiber neuropathy (SFN) is characterized by damage to thinly myelinated A-delta and/or unmyelinated C-fibers in the peripheral nervous system; these fibers regulate automatic functions, including digestion. SFN is known to cause abnormalities in the neural control of smooth muscle, however, the gastrointestinal (GI) manifestations of these abnormalities have not been reported. Structural and functional small fiber abnormalities are common in patients with postural tachycardia syndrome (POTS), Ehlers-Danlos syndrome (EDS), and mitochondrial disease (MD), and clinicians frequently see overlapping GI manifestations in these patient populations. METHODS: Among adult (ages 18–74) patients, we examined the relative GI manifestations of SFN, POTS, EDS, and MD to determine whether these diseases have unique GI phenotypes. We conducted a retrospective cohort analysis of SFN (N = 506, 75.5% female), POTS (N = 255, 90.1% female), EDS (N = 413, 87.1% female), and MD (N = 175, 68.0% female) patients reporting GI symptoms presenting to an academic medical center between 2004 and 2019. Patient diagnoses were categorized by symptom clusters: esophageal, gastric, lower GI, and abdominal pain with examination of the frequency of individual diagnoses as well. RESULTS: Overall, GI diagnoses were common and most frequent in MD (92.0%) relative to POTS (86.7%), EDS (81.1%), and SFN (70.4%). Abdominal pain was common among all conditions, led by MD (69.1%) and POTS (61.2%) (Table 1). There were significant differences in symptom distribution across all disease groups (Figure 1): there was a relatively-even distribution of diagnoses in SFN, gastric diagnoses were most common in POTS (65.1%), esophageal diagnoses most common in EDS (43.8%), and esophageal diagnoses (70.9%) and lower GI diagnoses (69.1%) most common in MD. Among individual diagnoses, >50% of patients with POTS experienced nausea/vomiting, constipation, and abdominal pain and >50% of MD patients experienced GERD, nausea/vomiting, constipation, and abdominal pain. CONCLUSION: Despite similar demographics and chronic GI complaints, GI phenotypes differed significantly between patients with SFN, POTS, EDS, and MD. Patients with MD and POTS were most likely to present with GI complaints, with abdominal pain the most common manifestation among all of the disorders.Table 1.: Characteristics of adults patients diagnosed with SFN, POTS, EDS, or MD. Note. SFN = small fiber neuropathy; POTS = postural tachycardia syndrome; EDS = Ehlers-Danlos syndrome; MD = mitochondrial disease. 1. Continuous variables analyzed with ANOVA and categorical variables analyzed with Chi-Square TestFigure 1.: Overall prevalence of GI diagnoses in SFN, POTS, EDS, and MD patients. Note. Patients may have more than one diagnosis.