BASICS
- Dysplastic blood vessel formation within the gastrointestinal tract
- Also known as angioectasias, arteriovenous malformations (AVMs) and telangiectasias
DESCRIPTION
- Most common vascular abnormality of the GI tract
- Lesions are usually small in diameter (<1 cm).
- Angiodysplasias may be single or multiple (40-60%).
- Most commonly found in the right colon but may occur anywhere in the gastrointestinal tract
- Bleeding is often recurrent and chronic resulting in iron deficiency anemia. Bleeding can also be acute.
- Bleeding from angiodysplasias stops spontaneously in 90% of cases.
- Most common in patients >60 years of age
EPIDEMIOLOGY
Incidence
Exact incidence of angiodysplasia is unknown. á
Prevalence
- Prevalence in general population is not well studied.
- Prevalence in asymptomatic adults aged >50 years undergoing screening colonoscopy is 0.83% with no incidents of bleeding over 3-year follow-up (1).
- Angiodysplasias thought to account for 5-6% of all gastrointestinal bleeding (2).
- Upper GI bleed: 4% in one prospective study (3)
- Lower GI bleed: 3% in one prospective study (4). Systematic review with broader range of 3-40% (5)
- Obscure GI bleed: Patients >50 years old with indications for small bowel capsule endoscopy were estimated as high as 50% (6).
ETIOLOGY AND PATHOPHYSIOLOGY
- Exact pathophysiology is unknown.
- Lesions develop from chronic, low-grade obstruction of submucosal veins as a result of increased smooth muscle contractility. Subsequent capillary congestion results in formation of arteriovenous collaterals.
- Chronic obstruction leads to local hypoxia, causing induction of vascular growth factors and the development of abnormal vessels.
- Increased production of vascular endothelial growth factor (VEGF) occurs with tissue hypoxia.
- A defect (or absence) in von Willebrand factor (VWF) is associated with increased angiogenesis and increased angiodysplasia formation (7).
- Right colon, with wide diameter and high wall tension, is the most common location for lesions (62%) (8).
- Up to 23% of patients with colonic angiodysplasia also have small bowel lesions (9).
COMMONLY ASSOCIATED CONDITIONS
- Aortic stenosis (Heyde syndrome; increased mucosal hypoxia with concomitant VWF deficiency)
- von Willebrand disease (VWD)
- End-stage renal disease (ESRD; platelet dysfunction)
- Left ventricular assist devices
- Hereditary hemorrhagic telangiectasia (HHT or Osler-Weber-Rendu; increased VEGF)
DIAGNOSIS
- Often found incidentally during endoscopy
- May be found during evaluation for GI bleeding
HISTORY
- Usually asymptomatic
- May have overt rectal bleeding or melena
- May have symptoms of anemia if bleeding is recurrent or chronic (fatigue, shortness of breath)
- Bleeding is usually episodic.
- History of renal disease
- Family history of bleeding disorders or hereditary vascular malformations
PHYSICAL EXAM
- If anemic, patient may be tachycardic.
- Acute bleed; hypotension (orthostatic or general) depending on amount/rate of blood loss
- Systolic murmur of aortic stenosis
- Heme-positive stools on rectal exam
DIFFERENTIAL DIAGNOSIS
- Upper GI bleed:
- Peptic ulcer disease
- Gastritis
- Malignancy
- Lower GI bleed:
- Diverticular disease
- Malignancy
- Hemorrhoids
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- CBC: hemoglobin, hematocrit, mean corpuscular volume (MCV)
- Ferritin level and iron studies
- Fecal occult blood test
Diagnostic Procedures/Other
- Primary diagnostic tool is endoscopy.
- Multiple modalities may be required depending on lesion location and amount of bleeding.
- Upper endoscopy
- Colonoscopy
- Double-balloon enteroscopy
- Small bowel capsule endoscopy (SBCE)
- Endoscopy shows flat, red lesions on the mucosal surface with fern-like arborizations from a central vessel. May be difficult to visualize if the patient is anemic
- Sensitivity of endoscopy decreases with overinsufflation due to decreased mucosal blood flow. Opioid analgesics cause a similar phenomenon.
- Invasive angiography may be used in cases of brisk bleeding; however, endoscopy has a higher yield and a lower complication rate in initial diagnosis.
- CT angiography: detects lesions if they are bleeding at a rate of 0.5 mL/min (10)[C]. Helical CT or magnetic resonance angiography may be used in cases with active bleeding.
- CT angiography: moderate sensitivity (70%) and high specificity (100%) for diagnosis as well as a high positive predictive value (100%) when compared to angiography plus colonoscopy (11)[B].
- Tagged RBC scans detect lesions bleeding at a rate of 0.05 to 0.1 mL/min. Best used in slow bleeds that are not visualized by other methods.
- Intraoperative enteroscopy is helpful in cases with difficulty locating a bleed.
- Flexible spectral imaging color enhancement (FICE) on capsule endoscopy has higher sensitivity (91%) for detecting angiodysplasia than white light endoscopy (80%) (12)[B].
- Histology shows dilated mucosal or submucosal vessels with a single layer of surface epithelium, little or no smooth muscle and few inflammatory changes.
TREATMENT
Angiodysplasias incidentally found during gastrointestinal evaluation; for another reason, have minimal bleeding risk and should not be treated. á
MEDICATION
Several medications have been studied without confirmed efficacy in reducing GI bleeding/mortality. Endoscopic therapy remains first-line. á
First Line
Endoscopic therapy: insufficient evidence to recommend one type over another (13)[A] á
- Argon plasma coagulation (APC)
- High-frequency energy transmitted to tissue by ionized gas (limits submucosal injury)
- Most commonly used/studied treatment
- Prospective study of 100 patients with 16-month follow-up determined bleeding cessation in 77% of cohort and baseline hemoglobin increase (14)[B].
- Saline injection into the submucosa prior to APC may help protect against wall injury.
- Electrocoagulation
- High temperatures coagulate mucosal bleeding.
- Mechanical hemostasis
- Endoscopic clips or band ligations for localized lesions to avoid tissue injury (case reports)
- 36% of patients treated endoscopically experienced rebleed (15)[A].
- Rebleeding may be attributed to undiscovered angiodysplasia lesions, not failure of obliteration.
Second Line
- Thalidomide inhibits angiogenesis through suppression of VEGF. Effectiveness demonstrated in case reports/series.
- In one randomized controlled trial (open-label), thalidomide led to a response in 71% of patients versus 4% in the iron group. Treatment was notably limited by side effects (16)[B].
- Somatostatin analogs (octreotide): Retrospective cohort study demonstrated LAR octreotide significantly reduced bleeding episodes and blood transfusions in patients with long-standing disease (17)[B].
- Meta-analysis of 72 patients refractory to endoscopic therapy, showed a significant effect of somatostatin analogs, (pooled odds ratio 14.52; 95% CI 5.9-35.4) for cessation of bleeding (15)[A].
- Hormonal therapy (estrogen)
- No difference in bleeding recurrence or need for transfusion compared to placebo
- Estrogen may help control bleeding in those with VWD, HHT, or ESRD.
- Atorvastatin (high dose) has antiangiogenic properties in case reports.
- Applications and limitations:
- Data on pharmacologic management of angiodysplasia is limited to case reports and small case series. Large RCT on efficacy are lacking.
- Studies exclude patients with ESRD.
- No study involving thalidomide or octreotide has shown a mortality benefit (13)[A].
SURGERY/OTHER PROCEDURES
- Angiography with embolization can also be considered (limited data, high complication rate)
- Surgical resection should be considered in patients with life-threatening bleeding because it is definitive treatment for recurrent angiodysplastic bleeding.
- Injection sclerotherapy is not commonly used.
- Laser sclerotherapy is uncommon (complication rates).
INPATIENT CONSIDERATIONS
Must be cautious with endoscopic interventions, particularly for lesions in the right colon (thin walled-increased risk for perforation) á
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Patients may require multiple transfusions.
- Consider iron supplementation.
Patient Monitoring
Monitor for anemia: Check CBC intermittently for hemoglobin, hematocrit, and MCV. á
PROGNOSIS
- Natural history of incidentally discovered angiodysplasia in healthy individuals with no evidence of blood loss is benign with a low risk of bleeding.
- Patients with bleeding angioectasias can develop chronic blood loss. Treatment reduces rebleeding.
REFERENCES
11 Foutch áPG, Rex áDK, Lieberman áDA. Prevalence and natural history of colonic angiodysplasia among healthy asymptomatic people. Am J Gastroenterol. 1995;90(4):564-567.22 Regula áJ, Wronska áE, Pachlewski áJ. Vascular lesions of the gastrointestinal tract. Best Pract Res Clin Gastroenterol. 2008;22(2):313-328.33 Clouse áRE, Costigan áDJ, Mills áBA, et al. Angiodysplasia as a cause of upper gastrointestinal bleeding. Arch Intern Med. 1985;145(3):458-461.44 Nahon áS, Macaigne áG, Pariente áA, et al. Characteristics and prognostic factors of hemorrhagic colonic angiodysplasia: prospective multicenter study of the ANGH Group. Gastrointest Endoscop. 2010;71(5):AB194-AB195.55 Farrell áJJ, Friedman áLS. Review article: the management of lower gastrointestinal bleeding. Aliment Pharmacol Ther. 2005;21(11):1281-1298.66 Liao áZ, Gao áR, Xu áC, et al. Indications and detection, completion, and retention rates of small-bowel capsule endoscopy: a systematic review. Gastrointest Endosc. 2010;71(2):280-286.77 Starke áRD, Ferraro áF, Paschalaki áKE, et al. Endothelial von Willebrand factor regulates angiogenesis. Blood. 2011;117(3):1071-1080.88 Diggs áNG, Holub áJL, Lieberman áDA, et al. Factors that contribute to blood loss in patients with colonic angiodysplasia from a population-based study. Clin Gastroenterol Hepatol. 2011;9(5):415-420.99 Steger áAC, Galland áRB, Hemingway áA, et al. Gastrointestinal haemorrhage from a second source in patients with colonic angiodysplasia. Br J Surg. 1987;74(8):726-727.1010 Schenker áMP, Majdalany áBS, Funaki áBS, et al. ACR Appropriateness Criteria « on upper gastrointestinal bleeding. J Am Coll Radiol. 2010;7(11):845-853.1111 Junquera áF, Quiroga áS, Saperas áE, et al. Accuracy of helical computed tomographic angiography for the diagnosis of colonic angiodysplasia. Gastroenterology. 2000;119(2):293-299.1212 Nakamura áM, Ohmiya áN, Miyahara áR, et al. Usefulness of flexible spectral imaging color enhancement (FICE) for the detection of angiodysplasia in the preview of capsule endoscopy. Hepatogastroenterology. 2012;59(117):1474-1477.1313 Swanson áE, Mahgoub áA, MacDonald áR, et al. Medical and endoscopic therapies for angiodysplasia and gastric antral vascular ectasia: a systematic review. Clin Gastroenterol Hepatol. 2014;12(4):571-582.1414 Kwan áV, Bourke áMJ, Williams áSJ, et al. Argon plasma coagulation in the management of symptomatic gastrointestinal vascular lesions: experience in 100 consecutive patients with long-term follow-up. Am J Gastroenterol. 2006;101(1):58-63.1515 Jackson áCS, Gerson áLB. Management of gastrointestinal angiodysplastic lesions (GIADs): a systematic review and meta-analysis. Am J Gastroenterol. 2014;109(4):474-483.1616 Ge áZZ, Chen áHM, Gao áYJ, et al. Efficacy of thalidomide for refractory gastrointestinal bleeding from vascular malformation. Gastroenterology. 2011;141(5):1629.e4-1637.e4.1717 Nardone áG, Compare áD, Scarpignato áC, et al. Long acting release-octreotide as "rescue"Ł therapy to control angiodysplasia bleeding: a retrospective study of 98 cases. Dig Liver Dis. 2014;46(8):688-694.
ADDITIONAL READING
- Bauditz áJ, Lochs áH. Angiogenesis and vascular malformations: antiangiogenic drugs for treatment of gastrointestinal bleeding. World J Gastroenterol. 2007;13(45):5979-5984.
- Franchini áM, Mannucci áPM. Von Willebrand disease-associated angiodysplasia: a few answers, still many questions. Br J Haematol. 2013;161(2):177-182.
- Martin-Grace áJ, Tamagno áG. Somatostatin analogs in the medical management of occult bleeding of the lower digestive tract. Gastroenterol Res Pract. 2015;2015:702921.
CODES
ICD10
- K55.20 Angiodysplasia of colon without hemorrhage
- K55.21 Angiodysplasia of colon with hemorrhage
- K31.819 Angiodysplasia of stomach and duodenum without bleeding
- K31.811 Angiodysplasia of stomach and duodenum with bleeding
ICD9
- 569.84 Angiodysplasia of intestine (without mention of hemorrhage)
- 569.85 Angiodysplasia of intestine with hemorrhage
- 537.82 Angiodysplasia of stomach and duodenum without mention of hemorrhage
- 537.83 Angiodysplasia of stomach and duodenum with hemorrhage
SNOMED
- Angiodysplasia of colon
- angiodysplasia of intestine (disorder)
- Angiodysplasia of duodenum
- angiodysplasia of stomach (disorder)
CLINICAL PEARLS
- Angiodysplasias are small vascular lesions along the GI tract. Most found in the cecum and proximal ascending colon. May be the source of blood loss in cases of obscure GI bleeding
- Angiodysplasias found incidentally have a low risk of bleeding and should not be treated.
- When indicated, first-line treatment is endoscopic therapy. Pharmacologic agents may be considered in refractory cases.