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|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:<br>
|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:<br>


pH: 7.41 <br>
Hemoglobin: 6.2 g/dL <br>
WBC: 2,400 /mm3 <br>  
WBC: 2,400 /mm3 <br>  
Platelets: 200,000 /mm3 <br>
Platelets: 200,000 /mm3 <br>
Hemoglobin: 6.2 g/dL <br>
Ferritin: 4.32 (13-150 ng/mL) <br>
Ferritin: 4.32 (13-150 ng/mL) <br>
Serum iron: 36 (50-150 ug/dL) <br>
Serum iron: 36 (50-150 ug/dL) <br>
Albumin: 3.5 g/dL <br>
Albumin: 3.5 g/dL <br>
INR: 1.1 <br>


Which of the following conditions is the most likely diagnosis?
What is the patient's most likely diagnosis?


[[Image:WBR0111.jpg|600px]]
[[Image:WBR0111.jpg|600px]]
|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.




|Explanation=The patient in this vignette suffers from [[Osler-Weber-Rendu syndrome]] (also known as [[Hereditary Hemorrhagic Telangiectasia]], HHT).  Her recurrent [[epistaxis]], characteristic [[telangiectasia]], and [[anemia]] due to gastrointestinal bleeding are highly suggestive of HHT.  Hereditary hemorrhagic telangiectasia is a genetic disorder that leads to abnormal blood vessel formation in the skin, mucous membranes, and often in organs such as the lungs, liver, and brain. It may lead to [[nosebleeds]], as well as digestive tract bleeding (black stools). Treatment focuses on reducing bleeding from blood vessel lesions, and sometimes surgery or other targeted interventions to remove arteriovenous malformations in organs. Chronic bleeding often requires iron supplements and sometimes blood transfusions. HHT is transmitted in an autosomal dominant fashion, and occurs in one in 5,000 people.
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.
|AnswerA=Henoch-Schonlein purpura
|AnswerA=Henoch-Schonlein purpura
|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.
|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.
|AnswerB=Von-Willebrand's disease
|AnswerB=Von-Willebrand's disease
|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 epistaxis, easy bruising and bleeding gums. [[Telangiectasia]]s of the lips, fingers and nose are not a hallmark of this disease, nor is gastrointestinal bleeding.
|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 [[Telangiectasia]]s of the lips, fingers, and nose are not a hallmark of this disease.
|AnswerC=Osler Weber Rendu syndrome
|AnswerC=Osler Weber Rendu syndrome
|AnswerCExp=[[Hereditary hemorrhagic telangiectasia]] (Osler Weber Rendu Syndrome) is an autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and gastrointestinal bleeding.
|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.
|AnswerD=Factor VIII deficiency
|AnswerD=Factor VIII deficiency
|AnswerDExp=Factor VIII Deficiency is the cause of [[hemophilia A]], an X-linked recessive clotting disorder. Patients with hemophilia suffer severe bleeds. The patients will often have an increased [[PT]], normal [[PTT]], and [[bleeding time]].
|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]].
|AnswerE=Thrombotic thrombocytopenic purpura
|AnswerE=Thrombotic thrombocytopenic purpura
|AnswerEExp=[[Thrombotic thrombocytopenic purpura]] (TTP) is a rare disorder of the blood-coagulation system, causing extensive microscopic clots to form in the small blood vessels throughout the body. Patients with [[TTP]] may have nosebleeds due to consumption of platelets in widespread thrombus formation. However, TTP is often sudden in onset, and does not cause telangiectasias of the lips, nose and fingers.
|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.
|EducationalObjectives=[[Hereditary hemorrhagic telangiectasia]] (Osler Weber Rendu syndrome) is characterized by recurrent [[epistaxis]], telangiectasias, and gastrointestinal bleeding.
|EducationalObjectives=[[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=First Aid 2014 page 87; First Aid 2012 page 90.
|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
|RightAnswer=C
|RightAnswer=C
|WBRKeyword=Bleeding, Coagulation, Coagulopathy, Telangiectasia, Genetics, Autosomal dominant, Dermatology, Skin, Epistaxis
|WBRKeyword=Bleeding, Coagulation, Coagulopathy, Telangiectasia, Genetics, Autosomal dominant, Dermatology, Skin, Epistaxis
|Approved=Yes
|Approved=Yes
}}
}}

Revision as of 19:03, 9 September 2014

 
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
Linked Question Linked::
Order in Linked Questions LinkedOrder::