Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature.

Ehlers-Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS.

The psychological burden associated with Ehlers-Danlos syndromes: a systematic review.

CONTEXT: Ehlers-Danlos syndromes (EDS) are disorders of connective tissue that lead to a wide range of clinical presentations. While we are beginning to understand the association between EDS and psychological manifestations, it is critical that we further elucidate the relationship between the two. Understanding the correlation between EDS and mental health will better ensure swift diagnosis and effective treatment for patients. OBJECTIVES: This study aims to systematically examine and report the prevalence of psychiatric disorders in the EDS population. METHODS: The PubMed database was searched on June 14, 2021 for articles published from January 2011 to June 2021. We included original, evidence-based, peer-reviewed journal articles in English that reported information on psychiatric disorders among EDS patients. Psychiatric disorders and psychological conditions were limited to those included in the "psychology" and "mental disorders" Medical Subject Headings (MeSH) search terms defined by the National Library of Medicine. Publications identified utilizing this search strategy by M.K. were imported into the Covidence system, where they first underwent a title and abstract screening process by three independent reviewers (M.K., K.L., H.G.). During the full-text review, two independent reviewers read the full text of the questionable articles to assess their eligibility for inclusion. Studies were excluded if they did not meet our target objective or if they were not in English or if they were opinion pieces, conference abstracts, or review articles. Data were extracted from the shortlisted studies by reviewers. During the data extraction phase, the quality and risk of publication bias were assessed by two independent reviewers utilizing the National Institutes of Health (NIH) Study Quality Assessment Tools. Any disagreements in study selection, data extraction, or quality assessment were adjudicated via discussion between the two reviewers, utilizing a third reviewer as a decider if necessary. RESULTS: Out of 73 articles identified, there were no duplicates. A total of 73 records were screened, but only 40 articles were assessed in full text for eligibility. A total of 23 articles were ultimately included, which collectively discussed 12,298 participants. Ten (43.5%) of the included studies were cross-sectional in design, three (13.0%) were case reports, and three (13.0%) were retrospective chart reviews. The remaining seven (30.4%) articles were either case-control, cohort, qualitative, controlled observational, or validation studies. Twelve (52.2%) of the studies reported data on depression disorders, six of which reported prevalence data. Nine (39.1%) of the studies reported data on anxiety disorders, five of which reported prevalence data. Studies that reported nonprevalence data presented odds-ratio, mean scores on psychiatric evaluations, and other correlation statistics. Psychiatric disorders that were most reported in these articles were mood disorders (n=11), anxiety disorders (n=9), and neurodevelopmental disorders (n=7). Although the reports varied, the highest psychiatric prevalence reports in EDS patients involved language disorders (63.2%), attention-deficit/hyperactivity disorder (ADHD) (52.4%), anxiety (51.2%), learning disabilities (42.4%), and depression (30.2%). CONCLUSIONS: Although mood disorders were cited in more articles, the highest reported prevalence was for language disorders and ADHD. This discrepancy highlights the importance of performing more research to better understand the relationship between EDS and psychiatric disorders.