Application of contrast-enhanced ultrasound in hemothorax of hereditary hemorrhagic telangiectasia: A case report and literature review

Abstract

Hereditary hemorrhagic telangiectasis (HHT) is an autosomal dominant hereditary disease, which can lead to abnormal angiogenesis. We performed contrast-enhanced ultrasound (CEUS) in a patient with HHT represented with hemothorax. After targeted embolization, the condition of hemothorax improved. In this case, we explore the use of CEUS to locate the responsible vessel of hemothorax, and found that CEUS could be used as a complementary preoperative method of localization with computed tomography angiography (CTA).

Keywords

Contrast-enhanced ultrasound hereditary hemorrhagic telangiectasis hemothorax

1 Introduction

Hereditary hemorrhagic telangiectasis (HHT) is an autosomal dominant hereditary disease with an estimated prevalence of approximately 1 in 5000, which can lead to significant vascular malformations [1, 2]. Epistaxis is the most common symptom of HHT and standard laser treatment of epistaxis is widely used, while nasal spray may be helpful when used additionally [3]. Mucocutaneous telangiectasia the most common sign and HHT is also often complicated by the presence of arteriovenous malformations (AVMs) of the brain, lung, gastrointestinal tract and liver [4]. The diagnosis of HHT is based on clinical criteria whereby the presence of at least three of the following four criteria establishes a definite diagnosis of HHT: recurrent epistaxis, multiple characteristic telangiectasias, visceral vascular malformations, and a first-degree relative meeting the diagnostic criteria of HHT. Pulmonary arteriovenous malformations (PAVMs) are the most common pulmonary manifestation of HHT and only rarely occur sporadically in patients without HHT [5]. The main complications of PAVM result from intrapulmonary shunt and include stroke, brain abscess, and hypoxemia. Local pulmonary complications include PAVM rupture leading to life-threatening hemoptysis or hemothorax [6]. PAVMs can be diagnosed using both contrast-enhanced and unenhanced chest CT because of the characteristic feeding artery and draining vein [7]. The new ultrasonic imaging technology, contrast-enhanced ultrasound (CEUS), makes it possible to display microvascular [8]. Studies have shown that CEUS can provide additional microvascular information in the diagnosis of solid lesions [9 –11]. In the current study, a case of a female patient represented with hemothorax with a history of HHT was diagnosed using CEUS which was helpful to locate the bleeding site was reported.

2 Case presentation

A 61-year-old female patient presented with chest pain, and shortness of breath for half a month. Bloody pleural effusion was found while drainage tube indwelled for 4 days. She had a history of hereditary hemorrhagic telangiectasis (HHT) for 6 years and accepted no special treatment. Laboratory tests showed that the hemoglobin ranged from 73 to 59 to 53 g/L. The right thoracentisis continued to elicit a large amount of bloody pleural fluid, which was difficult to remove. Computed tomography angiography (CTA) revealed multiple arteriovenous malformations in both lungs, right pleural effusion, right lung atelectasis, and suspicious lesions of tortuous dilated blood vessels near mediastinum in the pleura of right anterior chest wall. CTA indicated that right internal mammary arteriovenous malformation is more likely to be the responsible vessel (Fig. 1).

Fig. 1

(A), (B) CTA showing multiple arteriovenous malformations in both lungs (yellow arrow and white arrow), atelectasis of the right lung, and pleural effusion. Ruptured PAVM and (supposedly) pulled towards the pleura (yellow arrow), which indicated that the right internal mammary arteriovenous malformation is more likely to be the responsible vessel.

Conventional ultrasound revealed a large amount of pleural effusion. A hypoechoic vascular mass (4.4 cm×2.6 cm) was found near the right anterior wall pleura and the lateral pericardium in the mediastinum, with surrounding pulsation (Fig. 2). Color Doppler showed no obvious blood flow signal.

Fig. 2

(A), (B) Ultrasound scan near the pleura of the right anterior wall and the lateral pericardium in the mediastinum showing a hypoechoic vascular mass (4.4 cm×2.6 cm). (B) Color Doppler showing no obvious blood flow signal.

CEUS with an intravenous bolus of 2.4 mL Sonovue revealed that the hypoechoic structure began to increase rapidly in the arterial phase at approximately 11 sec and faded slowly; it still showed strong enhancement in the venous phase, with multiple flaky nonenhanced areas and large supply vessels. And at 14 sec, the whole course of the vessel between the pleura and the mass was shown. As a result, CEUS suggested that the mass was one of the arteriovenous of this HHT patient, and the supply vessel may have derived from the right chest wall vessel located in intercostal (Fig. 3).

Fig. 3

CEUS findings of the above mass of arteriovenous. (A) Microbubbles were first detected at 10 sec of the mass and the responsible vessel. (B) More microbubbles were found in the mass and the responsible vessel. (C) The whole course of the responsible vessel was seen, and more microbubbles went into the mass. (D) The mass faded slowly at 45 sec.

Subsequently, the patient underwent digital subtraction angiography (DSA). During the operation, abnormally twisted vessels at the distal end of internal mammary and the intercostal artery were found, and arterial embolization was performed (Fig. 4). After the targeted embolotherapy of abnormally twisted internal mammary and the intercostal artery, the respiratory symptoms of the patient such as shortness of breath improved, and the pleural drainage fluid continued to decrease. The drainage tube was removed successfully. Reexamination with chest computed tomography (CT) and conventional ultrasound showed that the right pleural effusion was significantly reduced, and the right lower lung had been recruited. The patient improved and was discharged from the hospital.

Fig. 4

(A) (B) DSA showing abnormally twisted vessels at the distal end of internal mammary and the intercostal artery.

3 Discussion

HHT is an autosomal dominant genetic disease, with an estimated prevalence of approximately 1/5000. In clinical practice, it is often accompanied by arteriovenous malformations of brain, lung, gastrointestinal tract and liver [4]. PAVMs are found in up to half of patients with HHT and can lead to fatal embolic and hemorrhagic complications, from symptomatic hypoxemia to paradoxical thromboembolism, and hemoptysis or hemothorax [5, 12]. The thin-walled PAVM aneurismal sac may also rupture. In the cases of potential life-threatening hemoptysis/hemothorax and neurological signs, most of the PAVMs have a subpleural localization [13]. Spontaneous rupture of PAVMs can result in hemothorax and has been estimated to affect between 4.4% patients of PAVMs [14]. So, it is clear that PAVM hemorrhage leading to hemothorax can be fatal but is a relatively rare feature of PAVMs and the two main exceptions are if the patient is pregnant or if PAVMs are perfused at systemic pressures for example due to pulmonary hypertension or systemic arterial supply (from bronchial or nonbronchial systemic arteries) to PAVM sacs [15].

PAVMs are more likely to occur in patients with mutations in the ENG gene, and PAVMs are more likely to be multiple than in patients with mutations in the ACVRL1 gene [16, 17]. PAVM diagnosis is mainly based upon CT scanner examination. PAVMs are classified as simple, complex, diffuse, or telangiectatic. Simple PAVMs are characterized as having one feeding artery that typically leads to a venous sac with a single draining vein [7]. Enhancing, lobulated, serpiginous subpleural structure is suggesting PAVMs in CTA, feeding arteries and a large and convoluted AVM sac might be visible [18, 19]. Morphology and organ involvement of hereditary vascular malformations is also well delineated by magnetic resonance imaging [20].

For the hemothorax cases of PAVMs, percutaneous image-guided embolotherapy used to disrupt the flow through PAVMs via transcatheter embolization is nowadays first line treatment in most disease cases. This avoids major surgery, general anesthesia, and loss of pulmonary parenchyma function [5 , 21]. The aim of transcatheter embolization is to occlude all the PAVMs feeding arteries by a selective catheterization of pulmonary arteries by using a coaxial system, via a percutaneous femoral approach. Surgery was once the most important treatment method [22], and now is still in consideration while percutaneous image-guided embolotherapy is not helpful. Embolization has been shown to be efficacious and to have a good safety profile, with rare complications during 5–10 years follow-up [4]. In the short term, these studies showed very high rates of significant improvement in oxygenation.

To undergo an effective embolization, it is critical to localizing the supply the responsible vascular correctly before the operation, while CTA plays a significant role. In the haemothorax patients, imaging features such as the “anomalous bulge” sign of CTA is helpful for confirming PAVMs rupture. “Anomalous bulge” sign on CTA is vessel wall of ruptured PAVM and pulled towards the pleura by the negative intrathoracic pressure [14]. In our case, CTA indicated that right internal mammary arteriovenous malformation was likely to be the responsible vessel. At the same time, CEUS found that the supply vessel might derive from the right chest wall vessel located in intercostal. Subsequently, the DSA confirmed the result of both CTA and CEUS, and the two locations were embolized in the embolotherapy surgery. In published articles, the present study was the first case study to locate the feeding artery of HHT patients with hemothorax. CEUS has been used to evaluate the characteristics of hepatic artery blood flow perfusion in patients of HHT in publication [23]. Compared with CT and other examination methods, CEUS has the advantages of low cost, radiation protection, repeatability and accessibility, good safety and intravenous tolerance [8, 24]. Studies showed that high-flow and slow-flow vascular malformations had statistically significant differences when measured by CEUS [25]. Another modern ultrasound method, elastography, quantitative Acoustic Radiation Force Impulse (ARFI) may be a tool for therapy planning, and for monitoring sclerotherapy outcome as well as the effect of sclerosing agents on malformation and surrounding tissue in patients with venous malformations [26]. CEUS combined with elastography can be used for optimization of curative surgery, such as liver and pancreas [27, 28].

CEUS is also used to diagnose active bleeding in other parts of the body, but few case reports have explored to locate the feeding vessel of ruptured vessel represented with hemothorax in HHT patients, the following cases were situations when CEUS performed in the active bleeding to find the responsible vessels. Tombesi P [29] et al. reported a case of spontaneous active bleeding in the thoracoacromial artery; Francesca DV [30] et al. reported a case of postinterventional hematoma; and Jiaojiao M [31] et al. reported a case of active bleeding of the brachial artery.

Hemothorax caused by HHT is rare in the general population, mostly occur with PAVMs. This case reported that CEUS can provide information about responsible vessels to locate the feeding vessel correctly. CEUS can be used as a complementary preoperative localization method with CT, aimed to make correct decisions before embolotherapy.

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