A review of respiratory manifestations and their management in Ehlers-Danlos syndromes and hypermobility spectrum disorders

Abstract

Background: Ehlers-Danlos Syndromes (EDS) and Hypermobility Spectrum Disorders (HSD) are a heterogeneous group of heritable genetic connective tissue disorders with multiple characteristics including joint hypermobility, tissue fragility, and multiple organ dysfunction. Respiratory manifestations have been described in EDS patients, but have not been systematically characterized. A narrative review was undertaken to describe the respiratory presentations and management strategies of individuals with EDS and HSD. Methods: A broad literature search of Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL was undertaken from inception to November 2020 of all study types, evaluating EDS/ HSD and pulmonary conditions. This narrative review was limited to adult patients and publications in English. Results: Respiratory manifestations have generally been described in hypermobile EDS (hEDS), classical and vascular EDS subtypes. Depending on EDS subtype, they may include but are not limited to dyspnea, dysphonia, asthma, sleep apnea, and reduced respiratory muscle function, with hemothorax and pneumothorax often observed with vascular EDS. Respiratory manifestations in HSD have been less frequently characterized in the literature, but exertional dyspnea is the more common symptom described. Respiratory symptoms in EDS can have an adverse impact on quality of life. The respiratory management of EDS patients has followed standard approaches with thoracotomy tubes and pleurodesis for pleural manifestations, vocal cord strengthening exercises, continuous positive pressure support for sleep apnea, and exercise training. Reduced respiratory muscle function in hEDS patients responds to inspiratory muscle training. Conclusion: Respiratory symptoms and manifestations are described in EDS and HSD, and have generally been managed using conservative non-surgical strategies. Research into the prevalence, incidence and specific respiratory management strategies in EDS and HSD is needed to mitigate some of the associated morbidity.

Haploinsufficiency of Col5a1 causes intrinsic lung and respiratory changes in a mouse model of classical Ehlers‐Danlos syndrome

“…Heterozygous pathogenic variants in type III collagen cause vEDS, a severe type of EDS characterized by tissue fragility affecting arteries and hollow organs. In vEDS, respiratory complications have been documented and often required clinical intervention (Chohan et al, 2021 ; Parducci, 2021 ). This is likely due to the deleterious effects of type III collagen mutations on blood vessels, airways, and lung parenchyma although investigations on the respiratory consequences of vEDS have not been conducted.…”

“…The respiratory manifestations in EDS have recently been reviewed (Chohan et al, 2021 ; Parducci, 2021 ) and were described in patients affected with vEDS, cEDS and hEDS (hypermobile) types. Respiratory abnormalities may be associated with significant morbidity and may be under‐recognized in EDS (Chohan et al, 2021 ; Parducci, 2021 ).…”

“…The respiratory manifestations in EDS have recently been reviewed (Chohan et al, 2021 ; Parducci, 2021 ) and were described in patients affected with vEDS, cEDS and hEDS (hypermobile) types. Respiratory abnormalities may be associated with significant morbidity and may be under‐recognized in EDS (Chohan et al, 2021 ; Parducci, 2021 ). Importantly, although connective tissue laxity is a prominent feature of EDS, its effects at the level of the lung tissue and on the respiratory function of patients with EDS have not been described.…”

The Mystery of Ehlers-Danlos Syndrome: An Autobiographical Case Report

“…The diagnosis of vEDS was made on average seven years after arterial or intestinal complications [ 5 ]. For those with recurrent pneumothoraces, bullectomy, pleural rubbing, and chemical pleurodesis are indicated [ 6 ].…”

CRD editor’s corner archive: July-September

“…Helping people with rare diseases is always a challenge because individual physician experience of the syndrome in question will inevitably be limited and treatment strategies are often untested. In the journal this month Chohan and colleagues 6 provide a comprehensive review of respiratory symptoms, organ pathology and management in Ehlers-Danlos syndrome and broader hyper-mobility syndromes. Although data is limited in many areas, it’s clear how burdensome respiratory symptoms are for many such patients.…”