Multidisciplinary Approach to Treating Chronic Pain in Patients with Ehlers–Danlos Syndrome: Critically Appraised Topic

Abstract

The Ehlers–Danlos syndromes (EDS) are a group of 13 related connective tissue disorders with a combined prevalence of 1 in 5000 people, with the most common noted as hypermobile EDS (hEDS). The EDS genetic condition is thought to affect both males and females equally, although most symptomatic patients are female. EDS causes a myriad of symptoms, including skin hyperextensibility and fragility, easy bruising and bleeding, joint hypermobility, subluxation, dislocation, and chronic pain. Pain is one of the most common symptoms of EDS, leading to disability and decreased quality of life. Current guidelines for treating chronic pain in EDS are lacking. Clinicians focus on a conservative multidisciplinary approach in patients with EDS, which avoids surgical interventions and its accompanying risks of morbidity and mortality. The multidisciplinary approach includes physiotherapy, occupational therapy, cognitive behavioral therapy, and pharmacologic interventions to decrease pain. This review identifies literature examining the components of this conservative multidisciplinary approach and their effectiveness across the PubMed, EMBASE, CINAHL, Web of Science, and Trip databases, using the terms “Ehlers-Danlos Syndrome AND Pain Management” that was then subsequently evaluated. The evaluation of this current literature provides weak evidence to support the efficacy of the individual components of the conservative multidisciplinary approach. Lack of alternative approaches leaves medical providers with little choice but to suggest these pain control methods, despite low-grade evidence of weak evidence of their efficacy. More research into the pathophysiology of chronic pain in EDS could help identify additional modes and rationales for therapy.

Clinical-Genomic Analysis of 1261 Patients with Ehlers–Danlos Syndrome Outlines an Articulo-Autonomic Gene Network (Entome)

“…This holistic approach could validate as pathophysiologic rather than psychogenic [ 95 ] the stress, anxiety, and joint-muscle pain [ 96 ] of EDS patients, enable many effective therapies [ 1 , 6 , 7 , 14 , 47 , 77 , 97 , 98 ] before the pain becomes programmed to persist [ 99 ], and promote an EDS genetics that matches advances in genomic technology with the advantages of patient-informed experience.…”

Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome

“…Concerning pain associated with malfunction of the ECM, the contribution of TNX-deficient clEDS and COL5A1 haploinsufficiency-related classical EDS to the development of neuropathic pain has been revealed by using a murine EDS model. Patients with EDS take large amounts of medications such as acetaminophen, non-steroid anti-inflammatory drugs (NSAIDs), anticonvulsants, antidepressants, opioids, and lidocaine; however, current managements are inadequate ( Demes et al, 2020 ; Whalen and Crone, 2022 ). Interestingly, mechanical allodynia in Tnxb −/− mice was inhibited by the anticonvulsant drug gabapentin and the mu-opioid agonist [D-Ala 2 , N-MePhe 4 , Gly-ol 5 ]-enkephalin (DAMGO) but not by the NSAID indomethacin ( Okuda-Ashitaka et al, 2020 ).…”

A gene network implicated in the joint-muscle pain, brain fog, chronic fatigue, and bowel irregularity of Ehlers-Danlos and “long” COVID19 syndromes

“…Many genes like FLNC in Table 4 are associated with cardiomyopathy and muscle weakness, reflecting overlap of proteins in cardiac, skeletal, and probably intestinal smooth muscle (possibly contributing to the 92% of EDs patients with bowel dysmotility in S1 Table). Further study of musculoskeletal and mitochondrial dysfunction [140–141] in EDS and acute/long COVID19 could justify trials of promising dietary [31], physical therapy [18, 142] and exercise [75, 121, 143] protocols in both disorders. Important objectives regarding long COVID19 are to associate symptom frequencies and outcome measures with defined post-infection time periods, then determine whether the genes influencing COVID19 infectious (S5 Table) also influence the duration and disability of its post-infectious phases.…”

“…These considerations make one gene-one type/disease matches [6][7] unlikely and molecular diagnoses without clinical correlation [92] ). Further study of musculoskeletal and mitochondrial dysfunction [140][141] in EDS and acute/long COVID19 could justify trials of promising dietary [31], physical therapy [18,142] and exercise [75, 121,143] protocols in both disorders.…”

“…Collaborative interpretations of variant diagnostic utility-disease relevance by molecular geneticists and appropriate physician subspecialists ). Further study of musculoskeletal and mitochondrial dysfunction [140][141] in EDS and acute/long COVID19 could justify trials of promising dietary [31], physical therapy [18,142] and exercise [75,121,143] protocols in both disorders.…”