Laryngological Symptomatology in Patients with Ehlers–Danlos Syndrome
Editor's Note: This Manuscript was accepted for publication on June 13, 2023.
The authors have no other funding, financial relationships, or conflicts of interest to disclose.
Abstract
Laryngological manifestations of connective tissue diease with hypermobility such as ehlers-danlos syndrome (EDS) are not well defined in the literature. EDS is an inherited, hetrogeneous, connective tissue disorder characterized by joint hypermobility, skin extensibility, and joint dislocations. A case series of 9 patients is presented with varying laryngological complaints. Common comorbities include postural orthostatic tachycardia syndrome (POTS), fibromyalgia, irritable bowel syndrome (IBS), and gastroesophageal reflux disease (GERD)/laryngopharyngeal reflux disease (LPRD). Six patients were singers. Videostroboscopic parameters and treatment courses are described. It may be beneficial to view patients with EDS and laryngological complaints through a holistic lens as many may need interdisciplinary assessment and management. Laryngoscope, 134:894–896, 2024
INTRODUCTION
Ehlers–Danlos Syndrome (EDS) is an inherited connective tissue disorder characterized by joint hypermobility, skin extensibility, and tissue fragility.1 On rare occasions, EDS has been shown to present with laryngological findings, including hoarseness, dysphonia, dysphagia, and vocal fold hemorrhage.2 In this case series, we examine the presenting laryngological complaints, comorbidities, and videostroboscopy findings among 9 patients with EDS referred to our otolaryngology clinic at a single institution.
CASE REPORT
A retrospective chart review of patients with EDS presenting to our clinic with laryngological complaints from 2019 to 2022 was conducted. The study was approved by the Cleveland Clinic Institutional Review Board (IRB 20-215).
Nine patients were identified, of whom eight had hypermobile EDS. Mean age at presentation was 33 years old, with a range of 22–50 years old. Eight out of nine patients were female. Six out of the nine patients were singers, and one reported having high voice demands as a mental health counselor. The most common presenting complaint was dysphonia (eight out of nine patients), followed by dysphagia (five patients) and laryngospasm (three patients).
EDS has been associated with several gastrointestinal (GI) conditions, cardiovascular, musculoskeletal, and neuropsychiatric conditions, including gastroesophageal reflux disease (GERD) and postural orthostatic tachycardia syndrome (POTS).1, 3 Table I shows the most common comorbidities seen in this cohort.
| Patient | Fibromyalgia | Postural Orthostatic Tachycardia Syndrome (POTS) | Reflux: Gastroesophageal Reflux Disease/Laryngopharyngeal Reflux (GERD/LPR) | Vagal Nerve Sensitivity | Chronic Cough | Migraine | Irritable Bowel Syndrome (IBS) |
|---|---|---|---|---|---|---|---|
| 1 | X | X | X | X | X | ||
| 2 | X | ||||||
| 3 | X | X | X | X | X | ||
| 4 | X | X | X | X | X | ||
| 5 | X | X | X | X | X | X | X |
| 6 | X | X | X | X | X | ||
| 7 | X | X | X | X | X | X | |
| 8 | X | X | X | ||||
| 9 | X |
All but one patient underwent videostroboscopy. Table II outlines the findings from videostrobsocopy.
| Patient and Presenting Complaint | Glottic Closure | Vocal Fold Mobility | Vocal Fold Amplitude | Mucosal Edge | Mucosal Wave | Periodicity | Supraglottic compression |
|---|---|---|---|---|---|---|---|
| Patient 1: dysphonia | Complete in modal; Hourglass in loft | WNL | WNL | Bilateral midcord swellings | Symmetric | Periodicity | A-P |
| Patient 2: dysphonia, dysphagia | Incomplete | WNL | Decreased right | Edema right | Symmetric | Periodicity | A-P |
| Patient 3: laryngeal spasm, chronic cough; globus sensation | Posterior glottal chink in modal; Splinting in loft | WNL | WNL | WNL | Symmetric | Periodicity | L-M |
| Patient 4: dysphonia, dysphagia | Posterior glottal chink | WNL | WNL | Bilateral midcord swellings | Symmetric | Periodicity | Absent |
| Patient 5: dysphonia, throat tightness, laryngospasm, chronic cough | Incomplete hourglass | WNL | Decreased bilaterally | Bilateral midcord swellings | Symmetric | Periodicity | L-M |
| Patient 6: dysphonia, dysphagia, globus sensation, laryngospasm | Complete | WNL | WNL | WNL | Symmetric | Periodicity | A-P |
| Patient 7: dysphonia, chronic cough | Complete | WNL | WNL | WNL | Symmetric | Periodicity | Present |
| Patient 8: Dysphonia, chronic cough | Complete | WNL | WNL | WNL | Symmetric | Periodicity | Present |
| Patient 9: Dysphagia, Hyoid dislocation | NA | NA | NA | NA | NA | NA | NA |
- A-P = Anterior—Posterior; L-M = Lateral-Medial; WNL = Within normal limits.
Dysphonia
Eight patients presented with dysphonia (most commonly hoarseness and straining of the voice), four of whom had abnormal findings on videostroboscopy involving the mucosal edge. Three patients had bilateral mid-fold swellings, and one had vocal fold edema. All four of these patients were professional voice users.
The patient with vocal fold edema had a history of bilateral vocal cord nodules treated via microsurgical excision of the nodules. However, her hoarseness persisted post-surgery. Voice therapy and two rounds of steroid injections were then pursued, yielding a mild improvement in phonation.
All other patients were diagnosed with muscle tension dysphonia and improved after several sessions of voice therapy. However, one patient with muscle tension dysphonia was doing well until she suddenly lost her voice again 3.5 months after initiation of voice therapy.
Dysphagia
Dysphagia was reported in five patients, most commonly as a secondary or tertiary complaint.
Four patients with dysphagia underwent modified barium swallow studies, revealing normal swallow function. Two patients underwent swallowing therapy and showed improvement in function. The remaining two patients were found to have an underlying functional GI pathology; one patient had an esophagram showing a hiatal hernia and Schatzki ring, and another was found to have esophageal spasm on manometry. Both were referred to gastroenterology for further management.
One patient presented with dysphagia and episodes of hyoid bone dislocation, endorsing painful “popping” and “dislocating” episodes in her throat provoked by yawning or laughing. She was referred to speech-language pathology (SLP) to work on potential laryngeal stabilization strategies.
Laryngospasm
Three patients presented with laryngospasm. Two of these patients were diagnosed with vagal nerve sensitivity and chronic cough and were treated with superior laryngeal nerve (SLN) blocks consisting of 1 mL of 40 mg triamcinolone approximately every 2 months. One patient developed low ACTH and cortisol levels after receiving five doses of the nerve block and was diagnosed with adrenal sufficiency, at which point this treatment was discontinued. They were referred to endocrinology, and voice therapy was initiated. One patient who presented with dysphagia, laryngospasm, and throat tightness was managed successfully with voice and swallowing therapy.
DISCUSSION
Our case series of nine patients demonstrates a broad range of laryngeal presentations among individuals with EDS. While there are certain rare laryngological complaints that seem to be more common in patients with EDS (e.g., hyoid bone dislocation due to hypermobility) than in the general population, most patients with EDS may present very similarly to others in the laryngology clinic.2 Comparing the prevalence of laryngological complaints among EDS patients versus the general population may be an area for further research.
The pathophysiology of the laryngeal manifestations of EDS has yet to be fully described. Previously proposed theories include damage to the vocal folds due to collagen abnormalities, lack of coordination or mobility of the vocal folds, reduced mobility of the cricoarytenoid joints, and hypermobility of the hyolaryngeal complex.2, 4 Our findings suggest that the presence of EDS may accelerate the development of common laryngological complaints rather than lead to unique pathologies. On videostroboscopy, all patients had vocal fold mobility within normal limits and symmetric mucosal wave. While four patients did present with vocal fold lesions, all were professional singers. It is difficult to ascertain to what extent this finding is related to their high voice demands versus potential collagen abnormalities underlying EDS that may make patients more prone to phonotrauma. However, most of these patients also presented with signs of vocal hyperfunction. One theory that has not been previously discussed to our knowledge is that the need to stabilize the hyolaryngeal complex in patients with hypermobility may result in a compensatory muscle tension dysphonia.
In addition, this case series highlights the need to more critically examine the interplay between laryngological symptoms and other comorbidities in patients with EDS. For example, dysphagia has been reported as a common symptom in EDS in previous case studies, though in our series, all patients had normal oropharyngeal swallowing function. Thus, it is important to rule out esophageal etiologies when assessing dysphagia in patients with EDS.2 Furthermore, our series is the first to our knowledge to include patients treated with SLN blockade for laryngospasm. Both patients also had a history of POTS. Given the association of EDS with disorders of autonomic regulation, including POTS, it is important to consider vagal nerve sensitivity as a potential cause of laryngospasm in patients with EDS.
CONCLUSION
Recent years have seen an increase in reports on the laryngeal manifestations of Ehlers–Danlos Syndrome. Here, we attempt to view patients with EDS from a holistic lens, highlighting the need for interdisciplinary assessment and management between physicians, SLPs, and other healthcare professionals to maximize quality of life.
ACKNOWLEDGMENTS
We thank Lydia DeAngelo and Julia Maxwell for their help with data collection.
