Can a patient with Ehlers-Danlos (Ehlers-Danlos syndrome) hypermobility type experience shortness of breath despite normal chest X-ray findings and should they undergo further testing?

Dyspnea in Ehlers-Danlos Hypermobility Type Despite Normal Chest X-Ray

Yes, patients with hypermobile Ehlers-Danlos syndrome (hEDS) commonly experience shortness of breath despite normal chest X-ray findings, and further diagnostic testing is warranted to identify the underlying mechanism. 1, 2

Why Normal Chest X-Rays Don't Rule Out Respiratory Problems in hEDS

Dyspnea is a prevalent symptom in hEDS and generalized hypermobility spectrum disorder, affecting a substantial proportion of patients, yet chest radiographs typically appear normal because the underlying mechanisms are functional rather than structural. 1, 2

The etiologies of dyspnea in hypermobile and classical EDS are wide-ranging and frequently coexist in the same patient, including:

• Respiratory muscle weakness - a known contributor that won't show on chest X-ray 1, 2
• Upper and lower airway collapse - dynamic obstruction during breathing that requires specialized testing to detect 1, 3
• Chest wall abnormalities - including skeletal defects like pectus excavatum that may be subtle on plain films 4
• Asthma or exercise-induced bronchoconstriction - requires pulmonary function testing for diagnosis 1
• Obstructive sleep apnea syndrome - has high prevalence in non-vascular EDS 1

Essential Further Testing Algorithm

First-Line Pulmonary Testing

Perform spirometry with detailed pulmonary examination to determine whether shortness of breath is associated with restrictive lung conditions, skeletal defects (pectus excavatum), diaphragmatic paralysis, or interstitial fibrosis. 4

Measure maximal inspiratory pressure (MIP) and assess diaphragmatic thickening fraction using ultrasound to evaluate for respiratory muscle weakness, which is a known contributor to dyspnea in hEDS. 2

Consider cardiopulmonary exercise testing to determine whether exercise-induced dyspnea and hyperventilation are masquerading as other conditions, especially given the high prevalence of deconditioning in hEDS patients. 4

Cardiovascular Evaluation

Obtain echocardiography to evaluate for:

• Aortic root dilation (occurs in 25-33% of hypermobile and classic EDS cases) 5
• Mitral valve prolapse or regurgitation 5
• Elevated pulmonary pressures 5
• Impaired left ventricular relaxation 5

Measure postural vital signs with active stand test - a heart rate increase ≥30 beats/min in adults (≥40 beats/min in adolescents) within 10 minutes of standing without orthostatic hypotension indicates postural orthostatic tachycardia syndrome (POTS), which commonly coexists with hEDS and causes dyspnea. 6

Upper Airway Assessment

Refer to appropriate specialists (cardiologist or pulmonologist) to perform cardiopulmonary testing when breathlessness might be caused by conditions other than exercise-induced bronchoconstriction. 4

Consider flexible laryngoscopy during exercise if inspiratory stridor is present, as laryngeal hypermobility can cause life-threatening upper airway obstruction in EDS patients. 3

Additional Considerations

Screen for obstructive sleep apnea given its high prevalence in non-vascular EDS, which contributes to daytime dyspnea and fatigue. 1

Evaluate for gastroesophageal reflux disease (GERD) as it affects up to 98% of hEDS patients and can contribute to respiratory symptoms. 6

Critical Pitfalls to Avoid

Do not dismiss dyspnea based solely on normal chest X-ray findings - the mechanisms causing breathlessness in hEDS are predominantly functional (muscle weakness, airway collapse, autonomic dysfunction) rather than structural parenchymal disease visible on plain radiographs. 1, 2

Do not assume asthma without objective testing - perform spirometry and bronchoprovocation challenges rather than empiric therapeutic trials, as exercise-induced dyspnea in hEDS has multiple non-asthmatic causes. 4

Recognize that multiple mechanisms frequently coexist in the same patient, requiring a systematic evaluation of respiratory muscle function, airway dynamics, cardiovascular status, and autonomic function. 1

Consider referral to a pulmonologist experienced with connective tissue disorders if initial testing doesn't identify a clear mechanism, as specialized assessment may be needed to differentiate between respiratory muscle weakness, airway collapse, and other contributors. 4