A 58-year-old Indian woman presents with a 2-year history of progressive iron deficiency anemia (Hb 7.2 g/dL) and recurrent melena. She reports a lifelong history of spontaneous recurrent epistaxis since childhood and multiple small red spots on her lips and fingertips. Upper endoscopy and colonoscopy were unrevealing. Video capsule endoscopy reveals multiple small bowel telangiectasias as shown in the diagram (marked **A**). Genetic testing confirms a heterozygous mutation in the ENG gene. Which of the following best explains the pathophysiology of the vascular lesions marked **A** in this patient?
A. Chronic portal hypertension leading to formation of portosystemic collaterals in the small bowel mucosa
B. Abnormal TGF-β signaling due to endoglin deficiency, resulting in loss of pericyte coverage and direct artery-to-vein shunting without intervening capillaries
Intestinal wall infiltration by neoplastic smooth muscle cells causing vascular compression and ischemic ulceration
C.
D. Immune-mediated destruction of the intestinal vascular endothelium with secondary fibrinoid necrosis
Explanation
Why option 1 is correct
The structure marked A represents multiple small bowel telangiectasias characteristic of Hereditary Hemorrhagic Telangiectasia (HHT). The patient's ENG gene mutation (HHT1) encodes endoglin, a co-receptor for TGF-β/BMP signaling in endothelial cells. Loss of endoglin function disrupts normal vascular wall maturation, leading to defective pericyte recruitment and smooth muscle layer development. This results in direct artery-to-vein shunting without intervening capillaries—the hallmark pathophysiology of HHT vascular dysplasia. This abnormal vascular architecture is responsible for the chronic GI bleeding and iron deficiency anemia seen in this patient (Faughnan AIM 2020 HHT Guidelines; PATH-HHT NEJM 2024).
Why each distractor is wrong
Option 2: Portal hypertension causes esophageal varices and gastric portal hypertensive gastropathy, not small bowel telangiectasias. The patient's normal upper endoscopy and colonoscopy, absence of stigmata of chronic liver disease, and genetic confirmation of ENG mutation exclude this mechanism.
Option 3: GIST tumors (marked C in the diagram) cause focal smooth muscle proliferation and ischemic ulceration, not diffuse telangiectasias. GISTs present as solitary lesions with mass effect, not the multifocal vascular dysplasia seen here.
Option 4: Immune-mediated vasculitis (e.g., Behçet's disease, vasculitis) causes fibrinoid necrosis and acute inflammation, not the chronic structural vascular dysplasia of HHT. The patient's lifelong epistaxis and family history point to an inherited vascular disorder, not autoimmune disease.
High-YieldNEET PG
HHT is a TGF-β/BMP signaling disorder (ENG or ACVRL1 mutations) causing pericyte loss and direct AV shunting—not inflammation, neoplasia, or hemodynamic disease.
