Hereditary hemorrhagic telangiectasia - Clinicals, Diagnosis, and Management

Cardiovascular

Clinicals - History

Fact Explanation
Positive family history Hereditary hemorrhagic telangiectasia (HHT) or Rendu–Osler–Weber disease, is an autosomal dominant disorder, which affects the blood vessels causing abnormal connections between arterioles and veins. This results in increased risk of bleeding. There are two types of disease presentation named HHT1 and HHT2. Curaçao criteria are used to establish the diagnosis. Presence of family history, recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations are the diagnostic criteria. If any three out of above four are present the definitive diagnosis can be made. If two criteria are present diagnosis is considered as possible. Positive family history
Hereditary hemorrhagic telangiectasia (HHT) or Rendu–Osler–Weber disease, is an autosomal dominant disorder, which affects the blood vessels causing abnormal connections between arterioles and veins. This results in increased risk of bleeding. There are two types of disease presentation named HHT1 and HHT2. Curaçao criteria are used to establish the diagnosis. Presence of family history, recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations are the diagnostic criteria. If any three out of above four are present the definitive diagnosis can be made. If two criteria are present diagnosis is considered as possible.
Asymptomatic Some patients with involvement of the central nervous system and visceral organs can be asymptomatic. Asymptomatic
Some patients with involvement of the central nervous system and visceral organs can be asymptomatic.
Mucocutaneous telangiectasia Subcutaneous bleeding and mucosal bleeding is one of the characteristic presentation of the HHT. Mucocutaneous telangiectasia
Subcutaneous bleeding and mucosal bleeding is one of the characteristic presentation of the HHT.
Epistaxis This is one of the symptoms in the classic triad of presentation of HHT. Spontaneous and recurrent episodes of epistaxis is a common presentation. Epistaxis
This is one of the symptoms in the classic triad of presentation of HHT. Spontaneous and recurrent episodes of epistaxis is a common presentation.
Positive family history This is an autosomal dominant disorder. Every off springs of the affected person is having the disease. Positive family history
This is an autosomal dominant disorder. Every off springs of the affected person is having the disease.
Symptoms of pulmonary arterio-venous malformations (AVM) Patients with pulmonary AVMs may present with dyspnea and reduced exercise tolerance. Large AVMs result in significant right to left shunt and may lead to cyanosis. Symptoms of pulmonary arterio-venous malformations (AVM)
Patients with pulmonary AVMs may present with dyspnea and reduced exercise tolerance. Large AVMs result in significant right to left shunt and may lead to cyanosis.
Gastrointestinal bleeding Hematemesis and malena are due to gastrointestinal bleeding from the AVMs. Hepatic involvement may result in bleeding from esophageal varices. Gastrointestinal bleeding
Hematemesis and malena are due to gastrointestinal bleeding from the AVMs. Hepatic involvement may result in bleeding from esophageal varices.
Symptoms of anemia Some patients may present with symptoms of anemia due to occult gastrointestinal bleeding. Patients complain of fatigue, palpitations, dyspnea on exertion and increased sleepiness. Symptoms of anemia
Some patients may present with symptoms of anemia due to occult gastrointestinal bleeding. Patients complain of fatigue, palpitations, dyspnea on exertion and increased sleepiness.
Migraine Patients can present with migraine and it is commonly seen in patients with pulmonary AVMs. Migraine
Patients can present with migraine and it is commonly seen in patients with pulmonary AVMs.
Stroke or transient ischemic attacks Pulmonary AVMs can cause emboli in the cerebral circulation resulting in ischemic stroke or transient ischemic attacks. Stroke or transient ischemic attacks
Pulmonary AVMs can cause emboli in the cerebral circulation resulting in ischemic stroke or transient ischemic attacks.
Symptoms of cerebral abscess Pulmonary AVMs can cause septic emboli in the cerebral circulation and development of cerebral abscesses. Some patients may present with recurrent episodes of cerebral abscess. Patients complain of prolonged fever, headache and focal neurological signs. Symptoms of cerebral abscess
Pulmonary AVMs can cause septic emboli in the cerebral circulation and development of cerebral abscesses. Some patients may present with recurrent episodes of cerebral abscess. Patients complain of prolonged fever, headache and focal neurological signs.
Acute paraplegia Acute paraplegia occurs due to spinal AVMs which is rare presentation but common in children. Acute paraplegia
Acute paraplegia occurs due to spinal AVMs which is rare presentation but common in children.
Abdominal pain Abdominal pain is seen in patients with visceral AVMs due to emboli in the mesenteric arteries. Abdominal pain
Abdominal pain is seen in patients with visceral AVMs due to emboli in the mesenteric arteries.
Symptoms of hepatic involvement Right upper quadrant pain and jaundice can be presenting complains of hepatic involvement. Hepatic AVMs are commoner in HHT2 patients than in patients with HHT1. Symptoms of hepatic involvement
Right upper quadrant pain and jaundice can be presenting complains of hepatic involvement. Hepatic AVMs are commoner in HHT2 patients than in patients with HHT1.
Visual disturbances Ocular hemorrhages, migrainous aura and transient cerebral ischemia (due to embolization) can result in visual disturbances. Visual disturbances
Ocular hemorrhages, migrainous aura and transient cerebral ischemia (due to embolization) can result in visual disturbances.
Hematuria AVMs in the bladder can cause hematuria. Hematuria
AVMs in the bladder can cause hematuria.

Clinicals - Examination

Fact Explanation
Telangiectases Telangiectases often appear about one year after patient presents with epistaxis. Mucosal involvement is seen in almost all patients. Skin lesions are pulsatile and measure about 1 to 3mm. they blanch with pressure. Similar lesions are seen in mucosal membranes and conjunctiva as well. Telangiectases
Telangiectases often appear about one year after patient presents with epistaxis. Mucosal involvement is seen in almost all patients. Skin lesions are pulsatile and measure about 1 to 3mm. they blanch with pressure. Similar lesions are seen in mucosal membranes and conjunctiva as well.
Cyanosis Patients with pulmonary AVMs and large right to left shunts can have cyanosis. Cyanosis
Patients with pulmonary AVMs and large right to left shunts can have cyanosis.
Polycythemia Prolong hypoxemia can result in secondary polycythemia. Polycythemia
Prolong hypoxemia can result in secondary polycythemia.
Jaundice Jaundice is seen in patients with hepatic involvement. Jaundice
Jaundice is seen in patients with hepatic involvement.
Signs of pulmonary hypertension Some patients may develop pulmonary hypertension and have palpable second heart sound and loud pulmonary component of the second heart sound. Signs of pulmonary hypertension
Some patients may develop pulmonary hypertension and have palpable second heart sound and loud pulmonary component of the second heart sound.
Continuous thoracic bruit This is due to large pulmonary AVMs. Continuous thoracic bruit
This is due to large pulmonary AVMs.
Focal neurologic signs Focal neurologic signs can be detected in patients with stroke. Focal neurologic signs
Focal neurologic signs can be detected in patients with stroke.
Evidence of hyperdynamic circulation Anemia and large right to left shunts cause high output cardiac failure. Bounding pulse, aortic flow murmur can be detected. Peripheral edema, pulmonary crackles, and cardiomegaly are signs of heart failure. Evidence of hyperdynamic circulation
Anemia and large right to left shunts cause high output cardiac failure. Bounding pulse, aortic flow murmur can be detected. Peripheral edema, pulmonary crackles, and cardiomegaly are signs of heart failure.
Fundoscopic examination Retinal telangiectasias, retinal hemorrhages, dilated and tortuous retinal vessels can be seen. Fundoscopic examination
Retinal telangiectasias, retinal hemorrhages, dilated and tortuous retinal vessels can be seen.

Investigations - Diagnosis

Fact Explanation
Full blood count Hemoglobin is low with reduced mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with iron deficiency anemia. Hemoglobin is elevated in patients with secondary polycythemia. White blood cells can be elevated in the presence of concurrent infection. Full blood count
Hemoglobin is low with reduced mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with iron deficiency anemia. Hemoglobin is elevated in patients with secondary polycythemia. White blood cells can be elevated in the presence of concurrent infection.
Pulse oximetry Detects oxygen saturation. Especially useful in patients with pulmonary AVMs. Pulse oximetry
Detects oxygen saturation. Especially useful in patients with pulmonary AVMs.
Chest X-ray In pulmonary AVMs the dilated vessels are seen as enlarged masses. But chest X-ray is less sensitive in detecting AVMs. Chest X-ray
In pulmonary AVMs the dilated vessels are seen as enlarged masses. But chest X-ray is less sensitive in detecting AVMs.
Echocardiogram Contrast echocardiography can demonstrate the shunt of blood from right heart to the left due to arteriovenous malformations. However in order to make the definitive diagnosis of pulmonary involvement a CT scan is necessary. Echocardiogram
Contrast echocardiography can demonstrate the shunt of blood from right heart to the left due to arteriovenous malformations. However in order to make the definitive diagnosis of pulmonary involvement a CT scan is necessary.
Endoscopy Nodular angiomas are seen in the intestinal mucosa. Esophageal varices can also be detected in patients with portal hypertension. Endoscopy is the gold standard in diagnosing gastrointestinal involvement of HHT. Endoscopy
Nodular angiomas are seen in the intestinal mucosa. Esophageal varices can also be detected in patients with portal hypertension. Endoscopy is the gold standard in diagnosing gastrointestinal involvement of HHT.
CT Chest CT can diagnose pulmonary AVMs. Abdominal CT can detect hepatic and renal involvement. A high resolution CT is more sensitive in detecting pulmonary AVMs. CT
Chest CT can diagnose pulmonary AVMs. Abdominal CT can detect hepatic and renal involvement. A high resolution CT is more sensitive in detecting pulmonary AVMs.
MRI MRI has high sensitivity in detecting pulmonary AVMs. MRI
MRI has high sensitivity in detecting pulmonary AVMs.
Genetic tests Identifies specific genetic mutations in the endoglin gene (chromosome 9) activin receptor like kinase type I gene (chromosome 12). Genetic tests
Identifies specific genetic mutations in the endoglin gene (chromosome 9) activin receptor like kinase type I gene (chromosome 12).
Angiography Useful in detecting AVMs. Vessels are 3mm or more in diameter. Intrahepatic shunting can be seen in hepatic AVMs. Angiography
Useful in detecting AVMs. Vessels are 3mm or more in diameter. Intrahepatic shunting can be seen in hepatic AVMs.
Indocyanine Green Chorioangiography (ICG) ICG is helpful in visualizing ophthalmic involvement in HHT. Dilatated and tortuos choroidal vessels can be seen extending from the peripapillary area. Indocyanine Green Chorioangiography (ICG)
ICG is helpful in visualizing ophthalmic involvement in HHT. Dilatated and tortuos choroidal vessels can be seen extending from the peripapillary area.

Investigations - Management

Fact Explanation
Full blood count Patients with iron deficiency anemia need regular follow up of hemoglobin levels. Full blood count
Patients with iron deficiency anemia need regular follow up of hemoglobin levels.
Serum ferritin Serum ferritin is low in iron deficiency anemia. Serum ferritin
Serum ferritin is low in iron deficiency anemia.
Chest X-ray Chest X-ray is done at least once during childhood, puberty, and before pregnancy. Thereafter it is repeated in 10-year intervals. Chest X-ray
Chest X-ray is done at least once during childhood, puberty, and before pregnancy. Thereafter it is repeated in 10-year intervals.
Arterial blood gas analysis Presence of low oxygen saturation which cannot be corrected with breathing 100% oxygen is suggestive of pulmonary AVM. Arterial blood gas analysis
Presence of low oxygen saturation which cannot be corrected with breathing 100% oxygen is suggestive of pulmonary AVM.
CT Chest CT is recommended to follow up patients after occlusion of pulmonary AVMs. CT
Chest CT is recommended to follow up patients after occlusion of pulmonary AVMs.
Magnetic resonance angiogram As for the CT scan, magnetic resonance angiogram is recommended to follow up patients after occlusion of pulmonary AVMs. Magnetic resonance angiogram
As for the CT scan, magnetic resonance angiogram is recommended to follow up patients after occlusion of pulmonary AVMs.
Liver function test Evaluation of hepatic enzymes, prothrombin time and serum bilirubin levels reflects the degree of hepatic involvement in HHT. Liver function test
Evaluation of hepatic enzymes, prothrombin time and serum bilirubin levels reflects the degree of hepatic involvement in HHT.
Pulse oxymetry Reduced oxygen saturation despite breathing 100% oxygen is seen in the presence of pulmonary AVMs. Pulse oxymetry
Reduced oxygen saturation despite breathing 100% oxygen is seen in the presence of pulmonary AVMs.
Contrast enhanced echocardiogram Contrast enhanced echocardiography and CT are considered as the gold standards in detecting pulmonary artery AVMs. Contrast enhanced echocardiogram
Contrast enhanced echocardiography and CT are considered as the gold standards in detecting pulmonary artery AVMs.
Helical CT Useful in detecting pulmonary AVMs. This is considered as the gold standard in detecting pulmonary AVMs. Helical CT
Useful in detecting pulmonary AVMs. This is considered as the gold standard in detecting pulmonary AVMs.
Contrast-enhanced MRI Like the CT this is a good screening option to screen for pulmonary and cranial AVMs. Contrast-enhanced MRI
Like the CT this is a good screening option to screen for pulmonary and cranial AVMs.
Prenatal diagnosis Genetic testing can be done to detect the presence of genetic mutations in the fetus. However since all the genetic abnormalities have not been detected genetic testing cannot accurately confirm or exclude the risk of HHT. Prenatal diagnosis
Genetic testing can be done to detect the presence of genetic mutations in the fetus. However since all the genetic abnormalities have not been detected genetic testing cannot accurately confirm or exclude the risk of HHT.

Management - Supportive

Fact Explanation
Health education Patients should be educated about the genetic basis of the disease and the risk of transmission to subsequent generations. Female patients in child bearing age should be adequately counseled about the risk of transmission to the fetus. They should be advised to seek immediate health care once a significant bleeding episode is present. Health education
Patients should be educated about the genetic basis of the disease and the risk of transmission to subsequent generations. Female patients in child bearing age should be adequately counseled about the risk of transmission to the fetus. They should be advised to seek immediate health care once a significant bleeding episode is present.
Basic life support Some patients can present with shock due to hemorrhage. Assessment of airway, breathing and circulation should be done first. Airway patency should be maintained in unconscious patients with oropharyngeal airway or with tracheal intubation. Oxygen should be administered if oxygen saturation is low. Blood should be sent to the emergency grouping and crossmatching as soon as possible. Crystalloids are the intravenous fluid of choice for the initial resuscitation followed by colloids till blood is available for the transfusion. Basic life support
Some patients can present with shock due to hemorrhage. Assessment of airway, breathing and circulation should be done first. Airway patency should be maintained in unconscious patients with oropharyngeal airway or with tracheal intubation. Oxygen should be administered if oxygen saturation is low. Blood should be sent to the emergency grouping and crossmatching as soon as possible. Crystalloids are the intravenous fluid of choice for the initial resuscitation followed by colloids till blood is available for the transfusion.
Hematinic Patients with iron deficiency anemia due to recurrent bleeding benefit from supplementation of hematinic. Hematinic
Patients with iron deficiency anemia due to recurrent bleeding benefit from supplementation of hematinic.
Antibiotic prophylaxis Antibiotic prophylaxis is indicated in all patients with pulmonary AVMs before surgical or dental procedures to minimize the risk of septicemia and septic embolization. Antibiotic prophylaxis
Antibiotic prophylaxis is indicated in all patients with pulmonary AVMs before surgical or dental procedures to minimize the risk of septicemia and septic embolization.
Management of cerebral abscess Patients with cerebral abscess are treated with antibiotics and surgical drainage of the abscess where possible. Management of cerebral abscess
Patients with cerebral abscess are treated with antibiotics and surgical drainage of the abscess where possible.

Management - Specific

Fact Explanation
Conservative management Patients with mild HHT and who are stable may not need specific treatment. Conservative management is also indicated during pregnancy. Conservative management
Patients with mild HHT and who are stable may not need specific treatment. Conservative management is also indicated during pregnancy.
Management of skin lesions Cauterization, hypertonic saline sclerotherapy, or dye laser treatment are useful in managing skin lesions. Management of skin lesions
Cauterization, hypertonic saline sclerotherapy, or dye laser treatment are useful in managing skin lesions.
Management of epistaxis Humidification of inspired air, nasal packing, antifibrinolytics can be used in emergencies. Topical estrogen therapy, endoscopic ablation (electrocautery and argon beam ablation) nasal septum skin transplants are used for the treatment of recurrent epistaxis. Management of epistaxis
Humidification of inspired air, nasal packing, antifibrinolytics can be used in emergencies. Topical estrogen therapy, endoscopic ablation (electrocautery and argon beam ablation) nasal septum skin transplants are used for the treatment of recurrent epistaxis.
Management of gastrointestinal bleeding Endoscopic ligation, photoablation, electrocautery, endo clot or sclerosant injection are endoscopic treatment options. Aminocaproic acid and bevacizumab are also used. Surgical resection of the affected segment is also done if the above measures fail. Management of gastrointestinal bleeding
Endoscopic ligation, photoablation, electrocautery, endo clot or sclerosant injection are endoscopic treatment options. Aminocaproic acid and bevacizumab are also used. Surgical resection of the affected segment is also done if the above measures fail.
Management of pulmonary AVMs Selective embolization, silicone balloon tamponade or surgical resection are done to control symptomatic pulmonary AVMs. Ablation of pulmonary AVMs will help in minimizing the risk of cerebral emboli as well. Management of pulmonary AVMs
Selective embolization, silicone balloon tamponade or surgical resection are done to control symptomatic pulmonary AVMs. Ablation of pulmonary AVMs will help in minimizing the risk of cerebral emboli as well.
Management of hepatic AVMs Patients may benefit from selective embolization. In the presence of hepatic dysfunction and congestive cardiac failure liver transplantation can be done. Management of hepatic AVMs
Patients may benefit from selective embolization. In the presence of hepatic dysfunction and congestive cardiac failure liver transplantation can be done.
Management of cranial AVMs Neurosurgical resection can be attempted for selected accessible cranial lesions. Management of cranial AVMs
Neurosurgical resection can be attempted for selected accessible cranial lesions.

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