WBR0111

Author	[[PageAuthor::William J Gibson (Reviewed by Yazan Daaboul, M.D. and Rim Halaby, M.D. [1])]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Genetics
Sub Category	SubCategory::Dermatology, SubCategory::Hematology
Prompt	[[Prompt::A 23-year-old woman presents to her primary care physician complaining of small violaceous red lesions on her lips, nose, and fingers (shown below). The patient reports that these lesions have appeared rather suddenly, with many arising over the past year. Further history-taking reveals that since childhood, she has had frequent nosebleeds and severe gastrointestinal distress that is often accompanied by black stools. Laboratory studies reveal the following: Hemoglobin: 6.2 g/dL WBC: 2,400 /mm3 Platelets: 200,000 /mm3 Ferritin: 4.32 (13-150 ng/mL) Serum iron: 36 (50-150 ug/dL) Albumin: 3.5 g/dL INR: 1.1 What is the patient's most likely diagnosis? ]]
Answer A	AnswerA::Henoch-Schonlein purpura
Answer A Explanation	[[AnswerAExp::Henoch-Schonlein purpura (HSP) is a small-vessel vasculitis caused by IgA immune complex deposition in blood vessels. The syndrome commonly causes kidney disease, abdominal pain, joint pain, and palpable purpura commonly seen in the lower extremities. HSP is not characterized by recurrent episodes of epistaxis, or telangiectasias of the lips, nose, and fingers.]]
Answer B	AnswerB::Von-Willebrand's disease
Answer B Explanation	[[AnswerBExp::Von Willebrand’s disease is the most common hereditary coagulation abnormality. It is caused by a deficiency of von Willebrand protein, a multimeric protein required for platelet adhesion. Patients often experience recurrent episodes of epistaxis, easy bruising, and bleeding gums. Gastrointestinal bleeding or Telangiectasias of the lips, fingers, and nose are not a hallmark of this disease.]]
Answer C	AnswerC::Osler Weber Rendu syndrome
Answer C Explanation	[[AnswerCExp::Hereditary hemorrhagic telangiectasia (Osler Weber Rendu Syndrome) is an autosomal dominant disorder characterized by iron-deficiency anemia due to recurrent episodes of epistaxis and gastrointestinal bleeding, telangiectasias, and arteriovenous malformations.]]
Answer D	AnswerD::Factor VIII deficiency
Answer D Explanation	[[AnswerDExp::Factor VIII Deficiency is the cause of hemophilia A, an X-linked recessive clotting disorder. Patients with hemophilia suffer severe bleeds, such as hemarthroses. Patients will often have an increased PT, with a normal PTT and bleeding time.]]
Answer E	AnswerE::Thrombotic thrombocytopenic purpura
Answer E Explanation	[[AnswerEExp::Thrombotic thrombocytopenic purpura (TTP) is a rare coagulopathy that causes extensive microscopic clotting formation. Patients with TTP may have nosebleeds due to consumption of platelets and widespread thrombus formation. It is characterized by the pentad: Fever, thrombocytopenia, microangiopathic hemolytic anemia, renal failure, neurological symptoms. However, TTP is often sudden in onset, and does not cause telangiectasias of the lips, nose and fingers.]]
Right Answer	RightAnswer::C
Explanation	[[Explanation::Osler-Weber-Rendu syndrome or Hereditary Hemorrhagic Telangiectasia (HHT) is a rare autosomal dominant genetic disease of variable penetrance and expressivity that causes vascular dysplasia. It is caused by mutations of 2 genes, endoglin and ALK-1 that cause HH1 and HH2, respectively. Both genes encode proteins of vascular endothelial cells involved in tumor growth factor-beta (TGF-beta) signaling. HHT is characterized by iron-deficiency anemia due to recurrent nasal and gastrointestinal bleeding, mucocutaneous telangiectasia, and arteriovenous malformations that may include the pulmonary and the cerebral circulations. The patient's recurrent episodes of epistaxis, characteristic telangiectasia, and iron-deficiency anemia due to nose bleeds and gastrointestinal bleeding are highly suggestive of HHT. By the age 16 years, the majority of patients will develop signs and symptoms of HHT. Almost all patients with HHT develop symptoms by the age of 40. While typically nose bleeds start early during adolescence, cutaneous manifestations present later in life. Arteriovenous malformations are considered the most significant burden of the disease, due to the risk of hemorrhage, paradoxical embolism, and neurological complications. Recently, hepatic and cardiac involvement have been widely recognized, with signs of portal hypertension, hepatic encephalopathy, biliary disease, and high-output heart failure. Treatment focuses on reducing bleeding from blood vessel lesions, and sometimes surgery and other targeted interventions to eliminate arteriovenous malformations. Chronic bleeding often requires iron supplements and may sometimes necessitate blood transfusions. Educational Objective: Hereditary hemorrhagic telangiectasia (Osler Weber Rendu Syndrome) is an autosomal dominant disorder characterized by iron-deficiency anemia due to recurrent episodes of epistaxis and gastrointestinal bleeding, telangiectasias, and arteriovenous malformations. References: Begbie ME, Wallace GMF, Shovlin CL. Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century. Postgrad Med J. 2003;79:18-24 Ozkok A, Akpinar TS, Akkaya V. Osler-Weber-Rendu syndrome: a rare cause of iron deficiency. J Gen Intern Med. 2011;26(9):1077 First Aid 2014 page 87]]
Approved	Approved::Yes
Keyword	WBRKeyword::Bleeding, WBRKeyword::Coagulation, WBRKeyword::Coagulopathy, WBRKeyword::Telangiectasia, WBRKeyword::Genetics, WBRKeyword::Autosomal dominant, WBRKeyword::Dermatology, WBRKeyword::Skin, WBRKeyword::Epistaxis
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