Hereditary hemorrhagic telangiectasia with pulmonary hypertension: a report of three cases

Abstract

Background: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant genetic disorder characterized by multisystem vascular malformations, with a low prevalence worldwide. Pulmonary hypertension (PH), a grave complication of HHT, is associated with a poor prognosis. At present, an agreed approach to the management of HHT in patients with PH is not available. The report herein details the diagnostic and therapeutic processes of three patients with HHT complicated by PH, with the aim of providing clinical insights for practitioners.

Case description: The following report details three cases of HHT with PH. All three patients had a history of recurrent epistaxis, as well as dilated blood vessels in the skin and mucous membranes. Consequently, all patients underwent right heart catheterisation (RHC), a procedure that confirmed the diagnosis of PH in all cases. Following diagnosis, Case 1 received treatment consisting of bevacizumab in conjunction with tadalafil and macitentan, Case 2 was treated with thalidomide in combination with sildenafil and macitentan, and Case 3 received a combination of sildenafil and ambrisentan. A family history of disease was identified in all three cases, with Case 1 and Case 2 exhibiting a family history of mutations in the ACVRL1 gene. Patients were followed over a period of six months, resulting in a variety of clinical outcomes, with Case 3 succumbing during the follow-up period. These cases underscore the challenges in diagnosis and the necessity of diverse therapeutic approaches for the management of HHT-PH.

Conclusions: The combination of HHT and PH is associated with a poor prognosis and limited treatment options. For patients who do not respond well to targeted drug therapy, the administration of antiangiogenic drugs in combination is recommended. It is imperative for healthcare professionals to exercise heightened suspicion of the diagnosis in patients with PH and telangiectasia of the skin and mucous membranes, and to undertake a comprehensive investigation into the family history. The implementation of genetic testing is crucial to mitigate the occurrence of missed diagnoses and misdiagnoses of this disease.

Keywords: Hereditary hemorrhagic telangiectasia (HHT); case report; drug therapy; pulmonary hypertension (PH).

Figure 1

Mucocutaneous telangiectasia on the lips, mucous membranes, and fingertips of Case 1 (A,B). This image is published with the patient’s consent.

Figure 2

Right ventricular angiography and portal vein ultrasound findings from Case 1. (A) Right ventricular angiography showed several bubbles in the left heart. (B) Portal vein ultrasound revealed significantly increased hepatic artery velocity.

Figure 3

Pulmonary artery CT, vascular reconstruction, and abdominal enhanced CT findings from Case 1. (A) Pulmonary artery CTA indicated that the main pulmonary artery was dilated. (B) Vascular reconstruction revealed pulmonary vascular malformations (indicated by arrows). (C) Abdominal enhanced CT showed that the liver exhibited diffuse nodular vascular malformations, consistent with hepatic vascular abnormalities. CT, computed tomography; CTA, computed tomography angiography.

Figure 4

Diffuse capillary telangiectasia of the bilateral nasal mucosa.

Figure 5

Pulmonary artery CT and abdominal enhanced CT findings of Case 2. (A) Pulmonary artery CT revealed findings suggestive of pulmonary hypertension. (B) Abdominal enhanced CT indicated hepatic arteriovenous fistulae, characterized by multiple tortuous vascular clusters within the liver. CT, computed tomography.

Figure 6

Hepatic arterioportal fistula.

Figure 7

Pulmonary artery CTA of Case 3. Curved pulmonary veins with an anomalous connection to the azygos vein and thickening of the three hepatic veins and dilation of the inferior vena cava. CTA, computed tomography angiography.

Figure 8

Family pedigree of the three cases. HHT-PH, hereditary hemorrhagic telangiectasia with pulmonary hypertension.