• Rare lung diseases
• Imaging/CT MRI etc
• Bronchoscopy
• Histology/Cytology

A 17-year-old male patient presented with a 2-year history of intermittent self-resolving left or right pleuritic chest pain, radiating to the back and with variable duration from several minutes to days. He was a non-smoker and had no known medical or family history. Physical examination was remarkable for hypermobility of small joints (figure 1A) and translucent skin with visible veins (figure 1B). Two chest CT scans, separated by 2 years, revealed waxing and waning bilateral multiple nodules and cavities with surrounding ground glass opacity (figure 1C–F). Absence of aortic and arterial aneurysms was revealed by the enhanced CT. Pulmonary function tests revealed restrictive ventilation dysfunction and no diffusion impairment. Bronchoscopy showed visible tortuous mucosal vessels (figure 1G,H) and multiple telangiectasias-like and haemorrhagic foci (figure 1I) on the smooth mucosal surface of the trachea and bilateral bronchus. Bronchoalveolar lavage fluid (BALF) was haemorrhagic and showed a large number of haemosiderin-laden macrophages, as demonstrated by Prussian blue staining (figure 1J). The rheumatology-associated antibody titres were negative, including the antinuclear, anti-dsDNA, anti-neutrophil cytoplasmic and antiglomerular basement membrane antibody. Echocardiography was normal. A de novo pathogenic heterozygous splice-site variant (c.690+1G>T) located in intron 8 of the COL3A1 gene (NM_000090.3) was identified in the patient by whole-exome sequencing and was verified with Sanger sequencing. He was diagnosed with vascular Ehlers-Danlos syndrome (vEDS). vEDS is a rare autosomal dominantly inherited type III collagen disorder leading to vessel and organ fragility. Pulmonary complications, of which the most common presentation is spontaneous pneumothorax and/or haemopneumothorax, are reported in 16% of patients with vEDS.1 Although uncommon, they appear to occur as an early or the first onset manifestation in the course of the disease, preceding the intestinal perforation and arterial rupture.2 Approximately half of patients with vEDS, including clinically asymptomatic patients, demonstrate lung CT abnormalities. The most common CT feature is emphysema.1 The present case showed an unusual pattern of vEDS with pulmonary involvement characterised by spontaneous intrapulmonary haemorrhage. These nodules and cavities with surrounding ground glass opacities mimicked infection or vasculitis. Clinicians should consider intrapulmonary haemorrhage caused by vEDS as a differential diagnosis especially in adolescent or young adult patients. vEDS with pulmonary involvement as an early manifestation is usually not suspected or diagnosed prior to surgical histopathological examinations. It is reported that intraluminal and interstitial haemosiderosis is an important component of vEDS on histological examination of lung surgical samples, probably due to vascular disruption and/or alveolar capillary haemorrhage.1 3 Therefore, the BALF haemosiderosis in our case suggests that it is a useful and less traumatic examination for vEDS, although it is not specific. In addition, the mucosal lesions seen in the bronchoscopy of our case, to our knowledge, have never been reported. We believe that endobronchial lesions are not coincidental and are a complication of vEDS. These characteristic radiological and bronchoscopic findings of intrapulmonary haemorrhage should lead to an investigation of other vEDS features such as translucent skin with visible veins, small joints hypermobility, bruising or tissue fragility, and subsequent genetic testing to achieve an early diagnosis and avoid unnecessary lung biopsy.

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Figure 1

Vascular Ehlers-Danlos syndrome in a 17-year-old man: (A, B) Hypermobility of interphalangeal joints and translucent skin with visible veins. (C, D) Chest CT scans taken 2 years before the present admission revealed multiple nodules and cavities in both lungs. (E, F) Chest CT scans taken at the present admission showed the nodules and cavities in the previous CT had disappeared and new nodules and cavities with surrounding ground glass opacity had developed. (G–I) Visible tortuous mucosal vessels and multiple telangiectasias-like and haemorrhagic foci on the smooth mucosal surface of the trachea and bilateral bronchus were noted on bronchoscopy (arrows and asterisk, respectively). (J): Cytological examination of bronchoalveolar lavage fluid showed a large amount of haemosiderin-laden macrophages (prussian blue staining, overall magnification ×200).