What disease is characterized by a collagen defect causing cystic bronchiectasis?

Ehlers-Danlos Syndrome: The Disease with Collagen Defect Causing Cystic Bronchiectasis

Ehlers-Danlos syndrome (EDS) is the primary disease characterized by a collagen defect that causes cystic bronchiectasis, particularly the vascular type (vEDS) which involves defects in type III collagen. 1, 2

Pathophysiology of Bronchiectasis in Ehlers-Danlos Syndrome

• EDS is a heritable connective tissue disorder caused by defects in collagen synthesis, structure, or processing, with vascular EDS specifically involving mutations in the COL3A1 gene encoding type III collagen 2, 3
• The collagen defect in EDS leads to weakened bronchial walls that are susceptible to permanent dilation (bronchiectasis) due to reduced structural integrity of the airways 1, 4
• Neutrophilic inflammation contributes to the destruction of bronchial walls through the action of neutrophil elastase and collagenase, further degrading the already defective collagen 4
• The bronchiectasis in EDS is often cystic in nature and may have a central distribution pattern 5

Clinical Features and Diagnosis

• Patients with EDS typically present with hyperextensible skin, joint hypermobility, and easy bruising alongside respiratory symptoms 2, 3
• Respiratory manifestations include recurrent pneumothorax, cough, sputum production, and recurrent respiratory infections 2, 1
• High-resolution CT (HRCT) is essential for diagnosing bronchiectasis in EDS, showing abnormal dilation of bronchi 4, 6
• Key radiological features include:
  • Enlarged internal bronchial diameter (signet ring sign) 6
  • Failure of airways to taper while progressing to the lung periphery 5
  • Possible air-fluid levels in dilated airways 5

Diagnostic Approach

• Genetic testing for COL3A1 mutations confirms the diagnosis of vascular EDS 2, 3
• Approximately 50% of patients with classic EDS have mutations in COL5A1 and COL5A2 genes 3
• Most mutations result in haploinsufficiency of type V collagen or production of functionally defective collagen protein 3
• Comprehensive evaluation should include assessment for other manifestations of EDS, including vascular complications which can be life-threatening 2

Management Considerations

• Airway clearance techniques are strongly recommended for patients with bronchiectasis associated with EDS 7
• Pulmonary rehabilitation should be offered to patients with impaired exercise capacity 7
• Long-term macrolide treatment is recommended for patients at high risk of exacerbations 7
• For patients with chronic Pseudomonas aeruginosa infection, long-term inhaled antibiotics are strongly recommended 7
• No specific treatment for the underlying collagen defect is currently available 3

Clinical Significance and Prognosis

• Early diagnosis and intervention are important to potentially prevent progression of bronchiectasis 4, 5
• Vascular complications represent the most serious risk in vEDS, with potential for arterial or organ rupture leading to early mortality 2
• Inter- and intrafamilial phenotypic variability is observed, but no clear genotype-phenotype correlations have been established 3
• Preventive guidelines should be implemented to reduce the risk of trauma and complications 3

Other Collagen Disorders Associated with Bronchiectasis

• Marfan syndrome (affects fibrillin-1) can cause bronchiectasis in approximately 28% of patients 1
• Cutis laxa (defective elastin) may also present with bronchiectasis 1
• Rheumatoid arthritis, which can affect collagen metabolism, is associated with bronchiectasis in 2-5% of cases 1

Pitfalls and Caveats

• Bronchiectasis may be the presenting feature of EDS before other systemic manifestations become apparent 2
• The diagnosis of EDS may be missed if clinicians focus solely on the respiratory manifestations without considering the systemic nature of collagen disorders 2
• Patients with EDS and bronchiectasis are at increased risk for pneumothorax and should be monitored closely 2
• The presence of atypical cystic changes on chest CT in young patients should prompt consideration of underlying connective tissue disorders 2