Makindo Medical Notes

About

• Hereditary Haemorrhagic Telangiectasia (HHT): Also known as Osler-Weber-Rendu disease.
• A rare autosomal dominant genetic disorder that results in abnormal blood vessel formation (telangiectasia).
• Telangiectasia typically found on the skin and mucous membranes, but also in the lungs, liver, and brain.
• Most cerebral arteriovenous malformations (AVMs) in HHT patients are symptomatic.
• Family history often includes a parent, sibling, or child with the same condition.

Studies show the prevalence of brain AVMs in HHT patients to be 10.4%, with no significant difference between males and females.

Aetiology

• A disorder of angiogenesis, leading to the development of fragile blood vessels.
• Mutations in the ACVRL1, ENG, and SMAD4 genes are commonly associated with HHT.
• Patients with HHT1 are more likely to have brain AVMs compared to those with HHT2.

Aetiology of Stroke in HHT

• Bleeding from a cerebral vascular malformation (AVM).
• Paradoxical embolism through a pulmonary AVM (rare).
• The vessels in HHT lack contractile elements, so bleeding from telangiectases can be severe, especially in gastrointestinal bleeds (GI bleeds).

Most individuals with pulmonary arteriovenous malformations (PAVMs) have HHT.

Clinical Features

• Epistaxis (nosebleeds) is common in most individuals by adulthood.
• GI bleeding, haematemesis, melaena, and iron deficiency anaemia often occur in patients over the age of 50.
• Haemorrhagic stroke is a risk due to cerebral AVMs.
• Mucocutaneous lesions are found on the skin, in the oral cavity, and in the nose.
• Embolic stroke may occur via paradoxical embolism through a pulmonary AVM.
• Pulmonary AVMs can rupture, leading to haemoptysis (coughing up blood).

Clinical Signs

Types of HHT

• Type 1: Caused by mutations in the ENG gene, associated with a 13.4% prevalence of brain AVMs.
• Type 2: Caused by mutations in the ACVRL1 gene, associated with a 2.4% prevalence of brain AVMs.
• Juvenile Polyposis/HHT Syndrome: Caused by mutations in the SMAD4 gene.

Differential Diagnosis

• Vasculitis rash.
• Thrombocytopenia.
• Telangiectasia in chronic liver disease, which appear as spider-like with a central core and radiating small vessels.

Diagnostic Clinical Criteria

Diagnostic Clinical Criteria

Epistaxis: Spontaneous and recurrent nosebleeds. Mucocutaneous Telangiectasia: Multiple telangiectasias at characteristic sites (lips, oral cavity, fingers, and nose). Lesions are blanchable, pink-red, and range from pinpoint to pinhead in size. Occasionally, they appear as 2-5 mm macules or “spidery” purple lesions. Visceral AVMs: Pulmonary Cerebral Hepatic GI Spinal Family History: A first-degree relative with a confirmed HHT diagnosis.

The clinical diagnosis of HHT is considered:

• Definite: When three or more criteria are present.
• Possible or Suspected: When two criteria are present.
• Unlikely: When fewer than two criteria are present.

Note: These diagnostic criteria were established for adults and may be misleading when applied to children.

Investigations

• Full blood count (FBC) to exclude iron deficiency anaemia from GI blood loss.
• Ferritin and iron studies, ESR, CRP, U&E, LFTs, B12, and folate levels.
• Brain imaging (CT/MRI/MRA) if stroke is suspected.
• Chest X-ray or lung CT to identify any pulmonary AVMs.
• Cerebral angiography for suspected AVMs. The Spetzler-Martin grade for HHT-related lesions is 2 or lower in nearly 90% of patients.
• Bubble echocardiogram for screening pulmonary AVMs, followed by a CT pulmonary angiogram if positive.
• Colonoscopy and upper endoscopy +/- capsule endoscopy to investigate GI bleeding. Patients with SMAD4 mutations may also be screened for polyps.
• Molecular genetic testing to confirm the genetic subtype of HHT in affected individuals and family members, allowing for appropriate screening and preventive treatment.

Management

• ABC protocol and stroke management for haemorrhagic stroke.
• Acute management of upper GI bleeding, with transfusion if necessary.
• ENT referral for epistaxis management, typically treated with laser ablation for mild to moderate cases.
• Gastroenterology consultation for GI bleeds and iron replacement therapy for anaemia.
• Avoid antithrombotic drugs. Antifibrinolytic drugs such as tranexamic acid may be used in select patients.
• Genetic counselling for affected families.
• Management of cerebral AVMs based on individual cases. Surgical and nonsurgical treatments may have similar long-term outcomes.
• Interventional neuroradiology for closure of pulmonary AVMs. PAVMs with a feeding artery greater than 1-3 mm should be considered for treatment via transcatheter embolization.

References

• Prevalence and characteristics of brain arteriovenous malformations in hereditary haemorrhagic telangiectasia: A systematic review and meta-analysis
• MR of hereditary haemorrhagic telangiectasia: Prevalence and spectrum of cerebrovascular malformations
• Surgical vs. nonsurgical treatment for brain AVMs in hereditary haemorrhagic telangiectasia
• Hereditary haemorrhagic telangiectasia: Diagnosis, management, and pathogenesis