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  1. K. Mathias1,
  2. A. Mantha2,
  3. L. Mathias3,
  4. D. Arkfeld3
  1. 1University of Chicago, Internal Medicine, Chicago, United States of America
  2. 2USC Keck School of Medicine, Internal Medicine, Los Angeles, United States of America
  3. 3USC Keck School of Medicine, Rheumatology, Los Angeles, United States of America


Background: Patients with hypermobile Ehlers-Danlos syndrome (hEDS) often report symptoms of cutaneous flushing, pruritis, vomiting, diarrhea and anaphylactoid responses to environmental, food, and mechanical stimuli. There is a growing body of literature investigating the possible link between disorders of mast cell regulation including mast cell activation syndrome (MCAS) and connective tissue disorders including hEDS. The evidence for such a relationship, however, remains limited1.

Objectives: We aimed to evaluate the association between hEDS and MCAS among hospitalized patients using a nationally representative cohort.

Methods: Hospitalized patients with a diagnosis of hEDS or MCAS were identified in the 2016-2018 National Inpatient Sample (NIS) using the International Classification of Diseases 10 system (ICD-10). The NIS is an all-payer inpatient database that estimates over 37 million annual U.S. hospitalizations and is maintained by the Healthcare Cost and Utilization Project. The primary outcomes were prevalence of EDS and MCAS among hospitalized patients. Secondary outcomes included cause of admission, mortality, length of stay, and cost of care. Multivariate hierarchical regression analysis was using adjusting for demographics, hospital factors, and comorbid conditions.

Results: Among 37,665 patients identified in this study, 35,115 (95.9%) patients had hEDS and 3,630 (9.6%) patients had MCAS. 1080 patients had concomitant diagnosis of hEDS (3.1%) and MCAS (29.8%), of whom 555 (51.4%) were diagnosed in 2018 compared with 100 (9.3%) patients in 2016 (P<0.001). The mean age of patients with both conditions was significantly lower than those diagnosed with hEDS (29.5 vs 36.6 years, P<0.001) or MCAS (29.5 vs 39.8 years, P<0.001) alone. Those with comorbid hEDS and MCAS were more likely female (95.8% vs 84.5%, P<0.001), had private insurance (67.6% vs 52.4%, P<0.001) and were among the highest income quartile (47.4% vs 31.9%, P<0.001). There were no significant differences in mortality or overall comorbidity burden. Patients with hEDS and MCAS had higher adjusted hospitalization charges ($64,445 vs $54,782, β=0.15, P<0.05) and longer adjusted lengths of stay (6.4 vs 4.9 days, IRR 1.35, P<0.001).

Conclusion: Nearly 1 in 3 patients diagnosed with MCAS have comorbid diagnosis of hEDS. This association appeared to increase over time with the increasing diagnosis of MCAS. Social determinants of disease such as health insurance status and income appeared to be associated with the identification of the overlap syndrome. These findings merit further investigation into the co-occurrence of these disease entities and development of consistent clinical diagnostic criteria.

References: [1]Kohn A, Chang C. The Relationship Between Hypermobile Ehlers-Danlos Syndrome (hEDS), Postural Orthostatic Tachycardia Syndrome (POTS), and Mast Cell Activation Syndrome (MCAS). Clin Rev Allergy Immunol. 2020;58(3):273-297. doi:10.1007/s12016-019-08755-8

Disclosure of Interests: None declared

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