Fatigue in Hypermobility: How Common Is It?

Fatigue is one of the most frequently reported and consistently under-recognised features of hypermobility spectrum disorders (HSD) and hypermobile Ehlers-Danlos syndrome (hEDS). Studies using standardised fatigue measures find that 60–90% of patients with these conditions report fatigue that is significantly above population norms, and for many — particularly those with more severe musculoskeletal involvement or comorbid dysautonomia — fatigue is the most limiting symptom, surpassing pain in its impact on quality of life, occupational function, and social participation. Yet the mechanism linking connective tissue laxity to fatigue is not immediately obvious and is frequently overlooked in clinical assessments that focus primarily on the pain and joint instability aspects of hypermobility.

Mechanisms of Fatigue in Hypermobility

Several distinct but interacting mechanisms contribute to chronic fatigue in hypermobility. The first is the metabolic cost of continuous muscular stabilisation. As discussed in previous articles, the nervous system responds to joint instability by maintaining a state of tonic muscle co-contraction throughout daily activity. This is energetically expensive — muscles that are never fully releasing at rest or during sleep consume ATP at a higher baseline rate than muscles in individuals with normal joint stability. Over the course of a day, the cumulative energy cost of this persistent low-grade muscle activation is substantial, and many hypermobile individuals describe feeling exhausted by tasks (prolonged standing, cooking, typing) that non-hypermobile individuals find effortless. This is not deconditioning in the traditional sense — it is an inherently elevated metabolic cost of ordinary physical existence.

The second mechanism is poor sleep quality. Hypermobile individuals have higher rates of sleep disturbance than the general population, driven by multiple factors: nocturnal pain from joints that lack passive stability and are vulnerable to compression in sustained positions, restless legs and peripheral dysaesthesia (common in hEDS), and the chronic sympathetic activation that accompanies persistent pain and proprioceptive uncertainty. Non-restorative sleep compounds the muscular fatigue and lowers the pain threshold, creating a self-perpetuating cycle.

Dysautonomia and POTS: Postural orthostatic tachycardia syndrome (POTS) — a form of dysautonomia in which heart rate increases excessively on standing due to failure of the normal venous return and sympathetic compensation mechanisms — is significantly more prevalent in hypermobility spectrum disorders than in the general population, with rates estimated at 25–50% in hEDS cohorts. POTS produces profound fatigue, particularly after standing, exercise, or any activity involving upright posture. In any hypermobile patient presenting with unexplained fatigue and exercise intolerance, POTS should be formally screened for with an active stand test or tilt-table test.

The third mechanism is mast cell activation, which is increasingly recognised as a common comorbidity in hypermobility spectrum disorders. Mast cells in connective tissue contain and release a variety of proinflammatory and neuromodulatory mediators including histamine, prostaglandins, and cytokines. Dysregulation of mast cell activation — producing disproportionate mediator release in response to minor stimuli — generates a low-grade systemic inflammatory state associated with fatigue, cognitive impairment ("brain fog"), gastrointestinal symptoms, and widespread pain sensitisation. The pathological link between connective tissue abnormalities and mast cell dysregulation is under active investigation.

Management of Fatigue in Hypermobility

Management of chronic fatigue in hypermobility requires a multifaceted approach. Energy conservation and pacing — understanding and working within individual energy envelopes, avoiding the boom-bust cycle of overdoing activity on good days followed by prolonged setbacks — is fundamental. Graduated exercise, beginning at a very low level and increasing extremely slowly, improves mitochondrial function, reduces the metabolic cost of stabilisation as muscles become stronger, and has evidence for improving fatigue in hypermobility. Sleep hygiene and management of nocturnal pain (appropriate positioning, supporting cushions, and where indicated, pharmacological management) improves restorative sleep and directly reduces daytime fatigue. Screening and management of dysautonomia — increased salt and fluid intake, compression garments, and in some cases pharmacological management — can dramatically improve fatigue in patients with POTS. Manual therapy reducing the acute muscular load allows greater tolerance for exercise and daily activity.

References & Further Reading

  1. Castori M, et al. Management of pain and fatigue in joint hypermobility syndrome. Ther Adv Musculoskelet Dis. 2012;4(6):437–453.
  2. De Wandele I, et al. Dysautonomia and its underlying mechanisms in the hypermobility type of EDS. Semin Arthritis Rheum. 2014;44(1):93–100.
  3. Tinkle BT, et al. Hypermobile connective tissue disorders: Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017;175(1):48–69.