Orphanet Journal of Rare Diseases | CT and Pathological Characteristics of Vascular Ehlers-Danlos Syndrome Presenting with Hemoptysis

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This study systematically reviewed 9 cases of vascular Ehlers-Danlos syndrome (vEDS) presenting primarily with hemoptysis, summarizing their clinical features, CT findings, and pathological changes, thus providing evidence for early diagnosis of vEDS.

 

Literature Overview
This article, titled 'Pulmonary vascular Ehlers-Danlos syndrome with hemoptysis as the main manifestation: CT and histologic findings of lung parenchymal damage', was published in the Orphanet Journal of Rare Diseases. It retrospectively summarizes clinical data, imaging features, and genetic testing results of 9 vEDS patients treated at the First Affiliated Hospital of Guangzhou Medical University between May 2017 and December 2024. The study highlights that vEDS is often misdiagnosed as infectious diseases in clinical practice and suggests early genetic testing for young male patients presenting with recurrent hemoptysis and abnormal CT findings to improve diagnostic accuracy.

Background Knowledge
Ehlers-Danlos syndrome (EDS) is a group of rare hereditary connective tissue disorders. Vascular EDS (vEDS), caused by mutations in the COL3A1 gene, primarily affects the synthesis of type III collagen, leading to increased fragility of blood vessels and organs, and a higher risk of rupture or hemorrhage. Common pulmonary manifestations in vEDS patients include spontaneous pneumothorax and hemothorax, while hemoptysis is rare and often misdiagnosed due to lack of specific clinical and imaging features. Diagnosis of vEDS currently relies on clinical manifestations, imaging features, and COL3A1 genetic testing. However, due to the similarity between pulmonary features of vEDS and infectious diseases, early diagnosis remains challenging. Therefore, this study aims to summarize the imaging and pathological features of vEDS patients presenting primarily with hemoptysis, offering more accurate diagnostic strategies for clinicians.

 

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Research Methods and Experiments
The study enrolled patients suspected of pulmonary vEDS at the First Affiliated Hospital of Guangzhou Medical University between May 2017 and December 2024. All patients met the following criteria: (1) presented with hemoptysis, with or without pneumothorax or hemopneumothorax; (2) underwent chest CT imaging, including non-contrast, contrast-enhanced scans, pulmonary artery CTA, and bronchial artery CTA; and (3) tested positive for COL3A1 mutations. Clinical data were reviewed using the electronic medical record system. CT images were interpreted by a radiologist with 15 years of experience in pulmonary vascular imaging, documenting lesion distribution, morphology, and changes during follow-up. Pathological specimens were analyzed by a pathologist with 15 years of experience in pulmonary pathology, including HE staining and immunohistochemical staining results.

Key Findings and Insights

• Of the 9 patients, 8 were male and 1 was female, with a mean age of 22.22 ± 5.72 years. All presented with recurrent hemoptysis, including 7 with blood clots and 2 with blood-streaked sputum.
• CT imaging showed patchy ground-glass opacities, fibrous bands, nodules, and cavity shadows in all patients, predominantly located in the bilateral lower lobes.
• Pathological analysis in 5 patients showed diffuse red blood cell exudation in alveolar spaces and increased hemosiderin-laden macrophages, supporting the diagnosis of pulmonary hemorrhage.
• Initially, 8 patients were misdiagnosed with infectious diseases, and 4 received anti-tuberculosis treatment, indicating insufficient awareness of vEDS in clinical practice.
• 18FDG-PET/CT showed maximum SUV values of 3.9–9.2 in the lesions but no evidence of neoplastic diseases.
• Ground-glass opacities and nodules were found to be dynamic during follow-up, whereas fibrous bands and calcified nodules remained relatively stable.

Significance and Future Directions
This study emphasizes the lack of specificity in pulmonary manifestations of vEDS, which often leads to misdiagnosis as infection or neoplasm-related diseases. For young male patients presenting with recurrent hemoptysis and CT abnormalities, vEDS should be considered and COL3A1 genetic testing should be performed early. Future multi-center studies may further analyze the phenotypic differences associated with various COL3A1 mutations across populations, providing evidence for early diagnosis and personalized treatment of vEDS.

 

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Conclusion
Through a retrospective analysis of 9 vEDS patients presenting with hemoptysis as the main symptom, this study found that clinical and imaging features are often non-specific and easily misdiagnosed as infectious diseases. It is recommended that clinicians consider vEDS when young males present with recurrent hemoptysis and CT findings such as multiple ground-glass opacities, nodules, and fibrous bands unresponsive to anti-infective treatment, and perform COL3A1 genetic testing as early as possible. Early diagnosis not only helps prevent severe vascular or organ rupture events but also provides a basis for genetic screening of the patient’s family members, offering significant clinical guidance.

 

Yongxia Lei, Gengfeng Chen, Tao Chen, Yu Deng, and Xinchun Li. Pulmonary vascular Ehlers-Danlos syndrome with hemoptysis as the main manifestation: CT and histologic findings of lung parenchymal damage. Orphanet Journal of Rare Diseases.