A Rare Case of Hereditary Hemorrhagic Telangiectasia: A Case Report

Abstract

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a very rare autosomal dominant genetic disorder that leads to abnormal blood vessel formation in the skin, mucus membranes (called telangiectasia), and organs such as the lung, liver, and brain. It occurs due to a mutation in one of the ACVRL1 , ENG , and SMAD4 genes, which code for the formation of blood vessels. The most common symptom is recurring nosebleed (epistaxis; due to rupture of nasal mucosal telangiectasia), which begins in childhood and affects about 90-95% of people with HHT. Other common signs and symptoms include punctate, linear, or splinter-like telangiectasias on the upper body, oral mucosa, or nail beds, gastrointestinal bleeding, and iron deficiency anemia. The diagnostic criteria currently in use are the Curaçao criteria. The diagnosis is made by clinical screening (e.g., history and physical exam), baseline investigations (complete blood count, hemoglobin, hematocrit, and ferritin level), genetic testing, and detailed medical imaging to detect visceral arteriovenous malformations (AVMs) such as esophagogastroduodenoscopy, colonoscopy, multiphase contrast CT, computed tomography angiography (CTA or CT Angio), magnetic resonance angiography (MRA), chest X-ray, Doppler ultrasonography, liver biopsy, and cerebral angiography. Management includes intravenous iron therapy or blood transfusion, antifibrinolytics (e.g tranexamic acid), ablation therapies (e.g. laser treatment, radiofrequency ablation, electrosurgery, sclerotherapy, and argon plasma coagulation), and systemic anti-angiogenic agents (e.g. thalidomide, bevacizumab). In this report, we present the case of a 22-year-old man from Swabi, Pakistan, with a history of recurrent epistaxis (nosebleed) from childhood, who presented with multiple episodes of melena (blood in stool), fatigue, palpitation, and iron deficiency anemia for five years. Multiple esophagogastroduodenoscopies (OGDs) and colonoscopies were done over the years, which showed AVM in the antrum and fundus of the stomach, duodenum, and colon, and a diagnosis of HHT was made. CTA and exploratory laparotomy showed ileal loop hemangiomas. He was managed with multiple blood transfusions, argon plasma coagulation (APC) for the AVMs, oral thalidomide, and steroids. Despite therapy, the patient had intermittent episodes of blood in stool and low blood counts. During his stay in Hayatabad Medical Complex (HMC), the patient was managed with high-frequency blood transfusion and bevacizumab (systemic anti-angiogenic agent). A dramatic reduction in the number of required transfusions and improvement in the patient's bloodlines and symptoms was noted. This case highlights the importance of endoscopic methods for the timely diagnosis of HHT and its management with intravenous bevacizumab.

A neglected cause of anaemia: hereditary hemorrhagic telangiectasia

“…1,8 Diagnosis of HHT is based on Curaçao's diagnostic criteria established in 1999 June which includes 4 domains-epistaxsis, telangiectasia, visceral telangiectasia and a positive family history. 3 Presence of 3 out of the 4 domains confirms the diagnosis. Genetic testing plays an important role for asymptomatic children of an affected parent.…”

“…1 Epistaxis occurs in about 90% of affected individuals. 2,3 Gastrointestinal mucosal telangiectasias lead to hemorrhages in the form of melena, hematemesis and hematochezia. 1 Hepatic vascular dysplasias, though asymptomatic in most cases, can cause portal hypertension and cholestatic jaundice due to pressure over bile ducts.…”

The ENG/VEGFα Pathway Is Likely Affected by a Nonsense Variant of Endoglin (ENG)/CD105, Causing Hereditary Hemorrhagic Telangiectasia Type 1 (HHT1) in a Chinese Family

“…Therefore, ENG-pathway genes could be used as the therapeutic targets for HHT1 [ 47 ]. Interestingly, great progress has been made in developing drugs that target VEGF and the angiogenic pathway, for example, the anti-VEGF antibody bevacizumab [ 48 , 49 , 50 ].…”

A case of hereditary hemorrhagic telangiectasia treated with cryotherapy

“…However, it requires preprocedural application of local anesthesia, is more invasive, and is a less feasible option for cutaneous lesions. 2 Cryotherapy is a more acceptable treatment because of its safety, affordability, speed of application, and effectiveness in treating mucocutaneous telangiectasias.…”