Hereditary Haemorrhagic Telangiectasia Flashcards
HHT - Example Question
A 47-year-old lady presented with shortness of breath and a nosebleed. She had been experiencing heavy nosebleeds over the past fifteen years and had twice required cauterization. On this admission she felt very tired, with shortness of breath and chest pain on minimal exertion.
Aside from nosebleeds she had a past medical history of hypertension and hypothyroidism. She had recently consulted a cosmetic surgeon privately as she had spider veins over her lips which she wished to have removed.
She lived with her husband who had been diagnosed with multiple sclerosis and her 18-year-old son who had learning difficulties and epilepsy. She reported that her mother and sister also experienced frequent nosebleeds.
On examination there was conjunctival pallor. The lung fields were clear on auscultation and both heart sounds were present with a systolic murmur audible over the aortic region. The abdomen was soft and non-tender with no palpable masses or organomegaly. On inspection of the skin there was a bruise in the left antecubital fossa and no rashes.
What is the most likely unifying diagnosis?
Von Willebrand disease Wegeners granulomatosis Von Hippel Lindau disease Idiopathic Thrombocytopaenic Purpura > Hereditary haemorrhagic telangiectasia
Hereditary haemorrhagic telangiectasia (HHT), also known as Osler Weber Rendu syndrome, is an autosomal dominant disorder leading to abnormal blood vessel formation in the skin, mucous membranes, liver, lungs and brain. In this case, both the patients mother, sister and son are also affected indicating a likely autosomal dominant inheritance. Telangiectasia, such as the ones on this patients lips, are found on mucosal surfaces and in the gastrointestinal tract. These can cause nosebleeds and this is the most common presentation of HHT. Nosebleeds and bleeding from telangiectasia in the gastrointestinal tract can lead to an iron deficiency anaemia which explains the shortness of breath, pallor, chest pain and flow murmur in this case. Other manifestations of HHT occur secondary to the formation of arteriovenous malformations (AVMs) and include haemoptysis, portal hypertension and oesophageal varices, congestive cardiac failure, headache, intracerebral haemorrhage and seizures. Treatment is largely symptomatic and anaemia is treated with transfusions and iron replacement.
Von Willebrand disease can present with nosebleeds and may be inherited in an autosomal dominant fashion. However, this diagnosis would not account for the severe symptomatic anaemia, telangiectasia or the neurological features in this patients son. Other features of von Willebrands disease include bleeding gums and purpura.
Wegeners granulomatosis is a form of vasculitis that can cause nosebleeds. It is not a genetic condition and other clinical manifestations include haemoptysis, rapidly progressive glomerulonephritis, arthritis and a purpuric rash.
Von Hippel Lindau disease is a rare autosomal dominant condition which is associated with many tumour types including haemangioblastomas, neuroendocrine tumours and renal cell carcinoma. It can present with walking difficulties, headaches and hypertension in addition to other symptoms and signs however nosebleeds are not a commonly recognised feature of this disease.
Idiopathic Thrombocytopaenic Purpura (ITP) is an autoimmune condition which can present with easy bruising, purpura and nosebleeds. In patients with ITP there is usually no family history and the condition does not cause telangiectasia.
Hereditary Haemorrhagic Telangiectasia
Also known as Osler-Weber-Rendu syndrome, hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant condition characterised by (as the name suggests) multiple telangiectasia over the skin and mucous membranes. Twenty percent of cases occur spontaneously without prior family history.
There are 4 main diagnostic criteria. If the patient has 2 then they are said to have a possible diagnosis of HHT. If they meet 3 or more of the criteria they are said to have a definite diagnosis of HHT:
- epistaxis : spontaneous, recurrent nosebleeds
- telangiectases: multiple at characteristic sites (lips, oral cavity, fingers, nose)
- visceral lesions: for example gastrointestinal telangiectasia (with or without bleeding), pulmonary arteriovenous malformations (AVM), hepatic AVM, cerebral AVM, spinal AVM
- family history: a first-degree relative with HHT
HHT - Example Question
A 25 year old Caucasian male presents with his first ever episode of witnessed generalised seizure, with witnessed jerking of his right arm and leg, lasting for 4 minutes terminated by benzodiazepines administered by paramedics. There is no other past medical history and documentation of head injuries. His past medical history includes recurrent epistaxes since childhood and current treatment for a left calf deep vein thrombosis, provoked following two recent long-haul flights from Australia. A thrombophilia screen has subsequently been negative. Family history is unavailable.
On examination, the patient is confused post-ictally and is uncooperative with examination. You note that his pupils are equal and reactive, he is moving all 4 limbs with no obvious focal neurology. There appears to be no visual or sensory neglect. A urinary toxscreen is negative.
His blood tests and arterial blood gas are as follows:
Hb 17.5 g/dl MCV 87 fl Platelets 223 * 109/l WBC 9.2 * 109/l Urea 6.6 mmol/l Creatinine 64 µmol/l CRP 24 mg/l
pH 7.32 PaO2 9.1 kPa PaCO2 4.2 kPa Lactate 4.2 mmol/l Bicarbonate 16 mmol/l
With sedation, the patient undergoes a CT head, which demonstrates an arterio-venous fistula in his right parietal lobe.
The patient remains an inpatient while discussed for management with neurosurgeons and returns to baseline with no focal neurological deficits. At 48 hours after admission, he develops sudden onset left face, arm and leg weakness and loss of sensation, with flaccid tone, downgoing plantars. A repeat CT head confirms a right middle cerebral artery ischaemic stroke.
What is the unifying diagnosis?
Malignancy of unclear primary > Haemorrhagic hereditary telangectasia Saddle pulmonary embolus Polycythaemia rubra vera Paroxysmal nocturnal haemoglobinuria
This is a difficult question: the patient has an intracerebral arterio-venous fistula and likely at least another in his pulmonary vasculature, resulting in a chronic hypoxaemia (note normal bicarbonate and secondary polycythaemia), ruling out an acute pulmonary embolus and likely resulting in a paradoxical stroke. Primary polycythaemia rubra vera should not result in hypoxaemia. There does not appear to be an underlying prothrombotic element: his current DVT is uncommon but appears provoked with a negative thrombophilia. There is little to suggest malignancy.
A previous history of epistaxis is also suggestive of haemorrhagic hereditary telangectasia (HHT), which appears to be the most common and earliest clinical feature. Diagnosis is clinched by the consensus Curacao criteria, requiring the following 4 features to be investigated in this case: spontaneous or recurrent epistaxis, multiple cutaneous telangectasia (a full dermatological examination is essential), visceral involvement (in this case, pulmonary and cerebral AVMs) and a first-degree relative with HHT (family history is required). Meeting at least 3 features produces a definite diagnosis while 2 of 4 features suggests ‘suspected’ diagnosis.
HHT Example Question
A 24 year-old gentleman is referred for your opinion from the Emergency Department. He presented with his first tonic-clonic seizure. A CT scan of his head shows a contrast enhancing lesion in the left frontal lobe. On taking a history you elicit that he has been having recurrent nosebleeds and dark stools for the past 12 months.
What is the likely unifying diagnosis?
Peutz Jeghers syndrome > Hereditary haemorrhagic telangiectasia Tuberous sclerosis Von Willebrand disease Neurofibromatosis - type 2
This young gentleman is likely to have a diagnosis of hereditary haemorrhagic telangiectasia (HHT). The contrast enhancing lesion on the CT scan represents an arterio-venous malformation. The history of recurrent nosebleeds and melena is typical of HHT and are secondary to telangiectasia on the nasal and gastrointestinal mucosa.
