True statement regarding hereditary hemorrhagic telangiectasia:
Ans: B (Associated with cerebral arteriovenous malformation) Ref: Robbins Pathologic Basis of Disease. 5th edition, WB Saunders 1994:509 and Medscape & Begbie ME, Hereditary Haemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome): A view from the 21st century. Postgrad Med J. Jan 2003;79(927):18- 24Explanation:"Skin lesions begin as dark red lines or as punctate, pulsating vascular papules the size of match heads. These may be found on the skin, oral mucosa, nasal mucosa and conjunctiva." Ref: Robbins"Most common presenting feature is Epistaxis (90% cases)""Cerebral Arteriovenous malformations in 10% cases.""In severe cases of HHT. recurrent epistaxis refractory to ablative treatment is treated surgically with nasal septum skin transplants by using skin taken from the tower trunk. Severe cases of HHT may respond to estrogen therapy."* Though estrogen is indicated in severe cases of HHT, it is not the first line treatment.Hereditary Hemorharqic Telangiectasia I Osler-Weber-Rendu Disease (OWRD)Autosomal dominant disorder.Generalized vascular dysplasia affecting blood vessels throughout the body.Increased tendency for bleeding.Four major clinical diagnostic criteria (Curagao criteria) are:o Epistaxis.o Telangiectasias.o Visceral lesions.o Family history (a first-degree relative with HHT).The HHT diagnosis is classified as definite if 3 or 4 criteria are present, possible or suspected if 2 criteria are present, and unlikely if fewer than 2 criteria are present.HHT has been classified into the following 4 types:o HHT type 1o HHT type 2o HHT type 3o HHT-juvenile polyposis overlap syndrome (JPHT).HHT is attributed to genetic mutations that involve signaling of TGF-p.Defects in at least 4 genes are implicated in its development:o Mutations of ENG (encoding endoglin) - These characterize HHT type 1 and involve chromosome 9.o Mutations of ALK1 (encoding ALK-1), also called ACVRL1 (activin A receptor kinase type II-like 1) - These are implicated in HHT type 2 and involve chromosome 12.o Mutations of chromosome 5 (5q31.1 -32) - These are distinct from hereditary benign telangiectasia (HBT), a gene defect in RASA1 (chromosome 5q14).o Mutations of SMAD4/MADH4 (encoding Smad4) - These are described in JPHT, which is also autosomal dominant, involves chromosome 18, and combines clinical manifestations of HHT and juvenile polyposis.The first 2 (HHT types 1 and 2) account for approximately 85% of cases.Clinical FeaturesClassic triad of Osler-Weber-Rendu diseaseo Telangiectases of the skin and mucous membranes,o Epistaxis.o Positive family history.Visceral and central nervous system (CNS) involvement.Cerebral AVMs in 10% cases.Most common presenting complaint - Epistaxis (90% cases).Second Most common presenting complaint - Skin telangiectases - 75% cases.Hepatic or pulmonary involvement - Arteriovenous malformations seen in 30% cases.Gastrointestinal Symptomso Gastrointestinal (Gl) bleeding in 15% cases. The risk of Gl tract bleeding increases at approximately 50 years of age.o Recurrent painless Gl bleeding occurs in 10-40% of patients,o Visceral AVMs.o Abdominal pain due to thrombosis of Gl AVMs.Hepatic Symptomso Liver involvement (often asymptomatic) is reported in as many as 40% of patients.o Symptoms may include right upper quadrant pain, jaundice, symptoms of high-output cardiac failure, and bleeding from esophageal varices.o Cardiac failure is caused by a large teft-to-right shunt due to AV fistula.o Atypical cirrhosis.Neurologic Symptomso Migraine headaches,o Stroke and brain abscess,o Spinal AVMs in children.o Acute paraplegia due to spinal arteriovenous fistula.Misc Symptomso Iron deficiency anemia caused by recurrent blood loss, o Intraocular hemorrhage.o Bloody tears due to conjunctival telangiectases.Complicationso Brain abscess,o Hemorrhagic or ischemic stroke, o High-output congestive heart failure,o Chronic Gl bleeding and anemiao Portal hypertension with esophageal varices,o Pulmonary hemorrhage,o Liver cirrhosis.Curasao Criteria for diagnosis of HHT:o Epistaxis - Spontaneous and recurrent.o Telangiectases - Multiple characteristic sites (eg, lips, oral cavity, fingers or nose).o Visceral lesions - Gastrointestinal (GI) telangiectasia (with or without bleeding), pulmonary arteriovenous malfermation (AVM), hepatic AVM, cerebral AVM and spinal AVM.o Family history - A first-degree relative who has HHT (according to these same criteria).o HHT diagnosis is classified as definite if 3 criteria are present, possible or suspected if 2 criteria are present, and unlikely if fewer than 2 criteria are present.
GI bleeding is the major presenting feature
Associated with cerebral arteriovenous malformation
Only mucosal involvement present and skin is usually spared
Estrogen is the first line treatment
Autoimmune Skin Disorders