Hypermobile Ehlers-Danlos syndrome (hEDS) and hypermobility spectrum disorder (HSD) are increasingly recognized among orthopedic physicians to cause joint instability, frequent dislocation, and chronic musculoskeletal pain. Yet, patients with these disorders frequently have coexisting conditions, such as postural tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), autoimmune and allergic disease, and neuropsychiatric conditions including anxiety, depression, ADHD, and autism. These comorbidities complicate diagnosis and treatment, therefore potentially decreasing the overall quality of care these patients receive. Despite the clinical relevance of comorbidities, the extent of research linking hypermobility disorders to these conditions has not been comprehensively examined. A bibliometric analysis was conducted using the Web of Science Core Collection to identify articles and journals related to the topic. Articles with hEDS and hypermobility spectrum disorder (HSD) as the main topic and addressing at least one of the four comorbidity domains (orthopedic, autonomic, immunologic, or neuropsychiatric) were included without restriction on the type of document. The trend in the year of publication was graphed using the Web of Science Analyze results tool, while the collected bibliographic data was analyzed using VOSviewer to assess the coauthorship network and keyword co-occurrence patterns. Microsoft Excel was also utilized to visualize the articles with the most citations. Between 1967 and June 18, 2026, 1,281 publications were published, with 97.1% in English. About 65.8% of the articles were published within the last ten years, showing the rapid growth of research in this field. The country with the highest number of publications was the United States (482, 37.6%), followed by England (223, 17.4%) and Italy (114, 8.9%). The organization contributing the greatest number of articles in the dataset was the University of London, with 97 articles. Isolated author collaboration networks were observed, featuring small clusters with rare interactions, typically separated by country. Research connecting hEDS and HSD to their orthopedic, autonomic, immunologic, and neuropsychiatric comorbidities has expanded rapidly over the past decade, driven largely by a few geographically isolated research clusters. Despite this growth, the immunologic and mast cell activation literature remains substantially underdeveloped, and collaboration across these research groups remains limited. Future efforts should prioritize cross-disciplinary and cross-national collaboration, with particular attention to expanding research on the immunologic and mast cell activation dimensions of hypermobility disorders.

Hyperadrenergic and neuropathic features have been described in postural tachycardia syndrome (POTS). This study describes the prevalence, autonomic testing characteristics, and symptom severity of individuals with hyperadrenergic and neuropathic features in a laboratory-diagnosed POTS cohort. We performed a cross-sectional study of individuals with a laboratory diagnosis of POTS. Hyperadrenergic POTS (HyperPOTS) features were defined as an upright norepinephrine level of > 600 pg/mL and/or > 3 times their respective supine norepinephrine. Neuropathic POTS (NeuroPOTS) features were defined by a CASS ≥ 2 and/or ≥ 1 sudomotor abnormalities. Autonomic symptom severity was determined by the Composite Autonomic Symptom Score (COMPASS-31). Other standard autonomic reflex testing components, including heart rate response to deep breathing (HRDB), Valsalva, and 10-min head-up tilt testing, were also performed. Of the 223 participants (mean age 31.6 years; female 89%), 161 (41%) had HyperPOTS features, 113 (29%) exhibited NeuroPOTS features, and 40 (18%)/48 (22%) demonstrated neither or both, respectively. NeuroPOTS features were associated with higher supine HR and rates of abnormal HRDB than those without NeuroPOTS. No significant differences in COMPASS-31 scores were found between all groups studied. HyperPOTS and NeuroPOTS are common, co-occurring features in adults with POTS. Autonomic symptom burden did not differ significantly between phenotypes, likely reflecting insensitivity of the COMPASS-31 to phenotype-specific domains. NeuroPOTS was associated with impaired cardiovagal function, consistent with involvement in cardiac postganglionic parasympathetic pathways, though this is partly confounded by HRDB's inclusion in our NeuroPOTS definition. These findings support the concept that POTS phenotyping may aid in therapy selection, and the need for phenotype-sensitive symptom instruments.

Patients with severe manifestations of disorders of gut-brain interaction (DGBI) have higher rates of concomitant Orthostatic Intolerance (OI) and Postural Orthostatic Tachycardia Syndrome (POTS). These conditions diminish quality of life and increase health care use. We conducted a systematic review to assess OI and POTS prevalence in patients with DGBI. Databases were searched through January 2026 for articles reporting the prevalence of OI and POTS among patients with DGBI. Pooled prevalence rates, odds ratios (ORs), and confidence intervals (CIs) were calculated using a random-effects model. Thirteen studies included 869 patients with DGBI and 1951 controls. OI prevalence in DGBI patients was DGBI (PP=50.0%, 95% CI: 35.0-64.9). The odds of OI in patients with DGBI were significantly higher compared with controls (OR=5.17, 95% CI: 1.73-15.50, P=0.003). Pediatric patients with DGBI had a higher prevalence of OI (59.7%, 95% CI: 36.4-79.3) than adults (32.5%, 95% CI: 19.3-49.4). The prevalence of OI in patients with DGBI was significantly higher when diagnosed using the Rome IV criteria (66.1%, 95% CI: 43.3-83.3) compared with the Rome III criteria (30.6%, 95% CI: 21.4-41.6). The prevalence of OI in DGBI was higher with questionnaire-based diagnosis (54.5%, 95% CI: 9.7-93.0) compared with physician-based diagnosis (48.8%, 95% CI: 35.2-62.7). Finally, POTS was prevalent in 31.5% (95% CI: 17.3-50.2) of patients with DGBI. OI is more prevalent in patients with DGBI as compared with controls without DGBI. POTS occurs in over one-third of patients with DGBI. While OI and DGBI are associated, clinical heterogeneity suggests low-quality evidence, warranting cautious interpretation.

Lyme disease, caused by Borrelia burgdorferi sensu lato, may lead to persistent complications, including autonomic nervous system dysfunction. Although postural orthostatic tachycardia syndrome is frequently associated with orthostatic intolerance in Lyme disease, broader autonomic impairment remains insufficiently characterized. This cross-sectional study included 324 participants: 233 patients with late-stage Lyme disease and 91 healthy controls. All participants underwent cardiovascular autonomic reflex testing, beat-to-beat heart rate variability analysis, baroreflex assessment, 24-hour Holter electrocardiography, and ambulatory blood pressure monitoring. Compared with controls, patients with Lyme disease demonstrated significantly higher rates of sympathetic and parasympathetic dysfunction (p<0.05). Heart rate variability spectral parameters, including very low frequency, low frequency, and high frequency components, were significantly reduced, while baroreflex sensitivity and baroreflex effectiveness index were also impaired (p<0.05). Holter monitoring additionally revealed reduced time-domain heart rate variability parameters and an elevated low-frequency/high-frequency ratio, suggesting relative sympathetic predominance in patients with Lyme disease (p<0.05). These findings support the presence of cardiovascular autonomic dysfunction in patients with late-stage Lyme disease and highlight the importance of comprehensive autonomic evaluation in this population. Keywords: Autonomic Dysfunction; Lyme disease; Heart rate variability; Neurocardiology.

There is a growing body of literature evaluating both postural orthostatic tachycardia syndrome (POTS) and Ehlers-Danlos syndrome (EDS). We conducted a systematic review to evaluate what is currently known about the co-existence of both conditions. A search of MEDLINE and EMBASE was performed in December 2025 and data were collected in tables and pooled to determine the prevalence of POTS in EDS and EDS in POTS. A total of 30 studies were included with 8421 patients with EDS and 12,983 patients with POTS. The average age across 16 studies that reported mean age was 33.3 years. POTS in patients with EDS ranges from 17.5% to 92.7% depending on the population. EDS in patients with POTS ranges from 17.9% to 50.0% depending on the population. One study suggested that patients with EDS and POTS had greater medication use, pain medications and greater number of clinic visits compared to POTS alone while another suggests that these patients have greater gastrointestinal symptoms and the odds were greatest for postprandial distress syndrome, chronic nausea and vomiting syndrome, vomiting and post-prandial fullness. We conclude that EDS and POTS frequently co-occur, and proportions of patients with POTS and EDS depends on the population evaluated. Overall, more research is needed to better understand how to effectively manage patients living with both EDS and POTS.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating form of orthostatic intolerance that predominantly (∼90%) affects young women, leading to diminished quality of life. Challenges associated with POTS are compounded by lengthy diagnostic delays on the order of years, repeated visits to multiple physicians, and misdiagnoses. Fundamental criteria for diagnosing POTS are (1) experiencing orthostatic symptoms (eg, lightheaded, dizzy, nausea, and heart palpitations) that improve with recumbency for at least 3–6 months and (2) a sustained increase in heart rate (HR) of ≥30 beats/min within 5–10 minutes of standing in the absence of hypotension (≥40 beats/min for people younger than 19 years). Given the nonspecific nature of patients’ symptomology, orthostatic tachycardia in the absence of hypotension is heavily relied on for diagnosis. However, inconsistency of HR responses to orthostatic stress tests conducted in clinical settings may contribute to diagnostic delays and misdiagnoses experienced by many individuals. To characterize this variability, we conducted 2 supine-to-stand tests to assess the test-retest reliability (ie, consistency) of HR responses to clinical orthostatic stress tests in people with POTS.

To report the prevalence of endometriosis among female patients with postural orthostatic tachycardia syndrome (POTS) and determine which condition is more commonly diagnosed first. In a retrospective case-control analysis, we reviewed medical records for patients with POTS who presented to our autonomic center from 2018 to 2024. POTS was defined by symptoms of orthostatic intolerance accompanied by a heart rate increase of ≥30 beats per minute within the first 10 min of head-up tilt table testing. Endometriosis diagnoses were determined using surgical pathology when available or clinical documentation by a gynecologic specialist. Among 1322 female patients with POTS, 229 (17.3%) had a diagnosis of endometriosis, a prevalence significantly higher than the prevalence of 10% observed in the general female population (p < 0.001) and higher than the prevalence of 10.2% observed in our tilt-negative cohort (p < 0.001). For patients with both diagnoses, endometriosis was diagnosed before POTS in 156 patients (68%), and POTS was diagnosed first in 73 patients (32%). Endometriosis is significantly more prevalent in female patients with POTS than in the general population, with endometriosis more likely to be diagnosed first. Clinicians should be aware of the high co-occurrence and consider further workup for endometriosis in patients with POTS presenting with pelvic pain or dysmenorrhea, and vice versa.