hereditary hemorrhagic telangiectasia

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disorder that affects the blood vessels in the body. It is characterized by the formation of abnormal, fragile blood vessels called telangiectasias and arteriovenous malformations (AVMs), which can lead to excessive bleeding and other complications [9].

The main symptoms of HHT include:

• Severe nosebleeds
• Strokes or ischemic events due to AVMs in the brain
• Bleeding in the digestive tract
• Anemia due to chronic blood loss

Other symptoms may include: * Blue discoloration of the skin (cyanosis) * Coughing up blood (hemoptysis) * Fatigue * Headaches [6]

HHT is an autosomal dominant disorder, meaning that a single copy of the mutated gene is enough to cause the condition. It is caused by mutations in the ACVRL1, ENG, and SMAD4 genes [10].

The disorder can affect various parts of the body, including the skin, mucous membranes, lungs, brain, liver, and gastrointestinal tract. Treatment options for HHT include surgical removal of AVMs, embolization to block blood flow to affected areas, and other interventions to manage symptoms and prevent complications [8].

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder that affects the blood vessels, leading to various signs and symptoms. Here are some of the common symptoms associated with HHT:

• Nosebleeds: Nosebleeds are one of the most common symptoms of HHT, often starting in childhood and recurring throughout life [1]. They can be spontaneous or triggered by minor trauma to the nose.
• Abnormal blood vessels: Small abnormal blood vessels within the inside layer of the nose can cause frequent nosebleeds [2].
• Dizziness, double vision, seizures, and strokes: If HHT affects blood vessels in the brain, it can lead to dizziness, double vision, seizures, and even strokes [3].
• Nosebleeds as a family trait: Since HHT is a hereditary disease, nosebleeds often run in families affected by this condition [4].
• Recurring nosebleeds: Some people with HHT experience recurring nosebleeds that can be heavy enough to require medical attention [5].
• Anemia and related symptoms: Blood loss from nasal and/or gastrointestinal bleeding can lead to anemia, causing fatigue, shortness of breath, chest pain, or lightheadedness [6][8].

It's essential for individuals with suspected HHT to consult a healthcare professional for proper diagnosis and treatment. Early detection and management can help alleviate symptoms and prevent complications.

References: [1] Dec 28, 2022 [2] Jun 18, 2024 [3] What are the symptoms of hereditary hemorrhagic telangiectasia (HHT)? [4] Nose. Nosebleeds are a common symptom of HHT, and can be spontaneous (without an obvious cause) and recurring. [5] Fatigue, shortness of breath: Some people with HHT may experience these symptoms because they have anemia — due to blood loss from nasal and/or gastrointestinal bleeding. [6] Symptoms of hereditary hemorrhagic telangiectasia (HHT) include nosebleeds and arteriovenous malformation (AVM). [7] Signs of bleeding include blood in the stool (black or bloody stools) and anemia.

Hereditary Hemorrhagic Telangiectasia (HHT) can be diagnosed through a combination of clinical evaluation, imaging tests, and genetic testing.

Clinical Evaluation A physical examination by a doctor may reveal signs and symptoms associated with HHT, such as: * Multiple telangiectasias (small dilated blood vessels) * Arteriovenous malformations (AVMs) in various organs * Recurrent nosebleeds or bleeding from other sites

Imaging Tests Imaging tests can help identify AVMs and other vascular abnormalities associated with HHT. These may include: * Contrast echocardiography to visualize the heart and blood vessels * MRI of the brain to detect AVMs in the brain * Transthoracic contrast echocardiography as an initial imaging test

Genetic Testing Genetic testing can confirm a diagnosis of HHT by identifying mutations in genes associated with the disorder. This may involve: * DNA extraction from a small sample (e.g., blood or saliva) * Next-generation sequencing to detect single nucleotide and copy number variants in 12 genes * Genetic testing as a primary tool for confirming HHT and guiding further screening

SMAD4 Testing In individuals with suspected HHT, SMAD4 testing can be considered as a first test when clinical findings suggest juvenile polyposis.

Genetic Testing Limitations It's essential to note that negative genetic test results do not always mean the disorder is not present. A positive genetic test can confirm HHT, but further evaluation and imaging tests may still be necessary to determine the extent of vascular abnormalities.

References: * [1] Dec 28, 2022 — Your doctor may diagnose HHT based on a physical examination, results of imaging tests and a family history. * [2] by SE OLITSKY · 2010 · Cited by 59 — Screening should include contrast echocardiography and MRI of the brain. * [3] Sep 19, 2023 — SMAD4 testing can be considered as a first test in individuals with suspected HHT and clinical findings suggestive of juvenile polyposis. * [4] Jun 18, 2024 — HHT can be diagnosed by performing genetic testing. * [5] Genetic Testing for HHT​​ A positive genetic test can confirm HHT. However, negative genetic test results do not always mean the disorder is not present. * [6] Genetic testing is a type of laboratory test used to diagnose inherited diseases like HHT. * [7] Genetic testing is a primary tool for confirming HHT and helping to identify those who should receive further screening for arteriovenous malformations (AVMs), ... * [8] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 12 genes associated with hereditary hemorrhagic telangiectasia. * [9] If HHT is suspected—or if you have determined that you have HHT through genetic testing—we will order imaging tests, which will help locate AVMs and determine ...

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare genetic disorder characterized by the formation of abnormal blood vessels in various parts of the body, leading to recurrent episodes of bleeding and other complications. While there is no cure for HHT, various drug treatments have been explored to manage its symptoms.

Current Treatment Options

According to recent studies [1], hormone therapy, including antiestrogen therapy with tamoxifen, has shown good responses in treating epistaxis (nosebleeds) due to HHT. Additionally, iron salts, estrogen-based formulations, antifibrinolytics, and immunomodulators have been considered as potential treatment agents when necessary [2].

Emerging Therapies

Recent clinical trials have investigated the efficacy of pomalidomide in treating HHT. A randomized, placebo-controlled trial found pomalidomide to be safe and effective for treating this rare vascular disorder [3]. Another study reported a positive outcome from an NIH-supported clinical trial, which was the first positive trial for treatment of hereditary hemorrhagic telangiectasia [4].

Future Directions

While these findings are promising, further research is required to fully understand the potential benefits and risks of these treatments. As noted in one review article, "no mechanism-based targeted therapy has been developed" for HHT, highlighting the need for continued investigation into effective treatment options [5].

In summary, while there is no FDA-approved drug specifically for treating HHT, various medications have shown promise in managing its symptoms. Ongoing research aims to identify more effective and targeted treatments for this rare condition.

References:

[1] May 6, 2024 — Hormone therapy, including antiestrogen therapy with tamoxifen, for the treatment of epistaxis due to HHT has produced good responses, though ...

[2] by C Grigg · 2017 · Cited by 42 — Although initial reports suggest that intranasal bevacizumab is an effective agent, further research is required.

[3] by F Robert · 2020 · Cited by 123 — Presently, the therapeutic treatments for HHT are intended to reduce the symptoms of the disease. However, no mechanism-based targeted therapy ...

[4] Sep 18, 2024 — NIH-supported clinical trial is the first positive trial for treatment of hereditary hemorrhagic telangiectasia.

[5] by H Al-Samkari · 2024 · Cited by 2 — We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT.

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder characterized by the formation of abnormal blood vessels, leading to bleeding and other complications. When it comes to differential diagnosis, several conditions can be considered in the process of ruling out HHT.

• Ataxia-Telangiectasia: This is a rare genetic disorder that affects the nervous system, immune system, and other bodily systems. While it shares some similarities with HHT, such as telangiectases (dilated blood vessels), it is not directly related to HHT.
• CREST Syndrome: A condition characterized by calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia. While CREST syndrome shares some clinical features with HHT, such as telangiectases, it is a distinct entity.
• Pediatric Syphilis: This condition can present with various symptoms, including skin lesions and telangiectases. However, the presence of syphilis-specific antibodies and other laboratory findings would help differentiate it from HHT.
• Rosacea: A chronic skin condition characterized by inflammation, redness, and telangiectasia. While rosacea shares some clinical features with HHT, such as telangiectases, it is not directly related to the vascular malformations seen in HHT.
• Rothmund-Thomson Syndrome: A rare genetic disorder that affects the skin, hair, and eyes. While it can present with telangiectasia, it is a distinct entity from HHT.

The differential diagnosis of HHT is typically not broad, as clinical findings and history are all-important in making an accurate diagnosis [2]. The Curaçao criteria, which include recurrent epistaxis (nosebleeds), cutaneous/mucosal telangiectases, visceral lesions, and a family history of HHT, can be used to diagnose HHT with high accuracy [4][5][6].

In conclusion, while several conditions share some clinical features with HHT, the differential diagnosis is typically focused on ruling out these entities based on clinical findings and history. A thorough evaluation by a healthcare professional is necessary to make an accurate diagnosis.

References: [1] May 6, 2024 — Differential Diagnoses. [2] The differential diagnosis of hereditary hemorrhagic telangiectasia (HHT) is typically not broad. [3] by SE OLITSKY · 2010 · Cited by 59 — HHT can be diagnosed using the Curaçao criteria or by identifying a causative mutation. [4] The clinical diagnosis is based on having at least three of the four Curaçao criteria: recurrent epistaxis, cutaneous/mucosal telangiectases, visceral lesions, and a family history of HHT. [5] by A Kritharis · 2018 · Cited by 207 — The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria.