Phillips first described a vascular abnormality that caused bleeding from the large bowel in a letter to the London Medical Gazette in 1839. During the 1920s, neoplasms were considered the major source of GI hemorrhage. However, in the 1940s and 1950s, diverticular disease was recognized as an important source of bleeding. In 1951, Smith described active bleeding from a diverticulum visualized through a sigmoidoscope. An association between colonic angiodysplasia and aortic stenosis was described by Heyde in 1958.
Vascular abnormalities as a source of active bleeding were controversial. In 1960, Margulis and colleagues identified a vascular malformation in the cecum of a 69-year-old woman who presented with massive bleeding. This diagnosis was accomplished with operative mesenteric arteriography.
Galdabini first used the name angiodysplasia in 1974; however, confusion about the exact nature of these lesions resulted in a multitude of terms that included arteriovenous malformation, hemangioma, telangiectasia, and vascular ectasia. These terms have varying pathophysiologies, with a common presentation of GI bleeding.
Angiodysplasia is a degenerative lesion of previously healthy blood vessels found most commonly in the cecum and proximal ascending colon. Seventy-seven percent of angiodysplasias are located in the cecum and ascending colon, 15% are located in the jejunum and ileum, and the remainder are distributed throughout the alimentary tract. These lesions typically are nonpalpable and small.
Angiodysplasia is the most common vascular abnormality of the GI tract. After diverticulosis, it is the second leading cause of lower GI bleeding in patients older than 60 years. Angiodysplasia may account for approximately 6% of cases of lower GI bleeding. It may be observed incidentally at colonoscopy in as many as 0.8% of patients older than 50 years. The prevalence for upper GI lesions is approximately 1-2%. Small bowel angiodysplasia may account for 30-40% of cases of GI bleeding of obscure origin.
Angiodysplasia may present as an isolated lesion or as multiple vascular lesions. Unlike congenital or neoplastic vascular lesions of the GI tract, this lesion is not associated with angiomatous lesions of the skin or other viscera.
Clinical presentation is usually characterized by maroon-colored stool, melena, or hematochezia. Bleeding is usually low grade but can be massive in approximately 15% of patients. In 20-25% of episodes, only tarry stools are passed. Iron deficiency anemia and stools that are intermittently positive for occult blood can be the only manifestations of angiodysplasia in 10-15% of patients. Bleeding stops spontaneously in over 90% of cases but is often recurrent.
Pathophysiology
The exact mechanism of development of angiodysplasia is not known. One prominent hypothesis accounts for the high prevalence of these lesions in the right colon and is based on the Laplace law. The Laplace law relates wall tension to luminal size and transmural pressure difference in a cylinder whereby the wall tension is equal to the pressure difference multiplied by the radius of the cylinder. In the case of the colon, wall tension refers to intramural tension, pressure difference is that between the bowel lumen and the peritoneal cavity, and cylinder radius is the radius of the right colon. Wall tension is highest in bowel segments with the greatest diameter, such as the right colon.
This theory suggests that repeated episodes of colonic distention are associated with transient increases in lumen pressure and size. This results in multiple episodes of increasing wall tension with obstruction of submucosal venous outflow, especially where these vessels pierce the smooth muscle layers of the colon. Over many years, this process causes gradual dilation of the submucosal veins and, eventually, dilation of the venules and arteriolar capillary units feeding them.
Ultimately, the capillary rings dilate, the precapillary sphincters lose their competency, and a small arteriovenous communication forms. This accounts for the characteristic early-filling vein observed during mesenteric angiography.
The developmental theory of angiodysplasia accounts for several clinical and pathologic features, including occurrence in older individuals, location in the cecum and proximal right colon, and prominent submucosal veins that dilate after traversing the muscularis propria. In addition, it also accounts for the lack of pathologic changes in arterioles supplying vascular ectasias and the absence of any mucosal lesion associated with them. Previous studies demonstrating that colonic motility, increased tension in the bowel wall, and increased intraluminal pressure can diminish venous flow lend further support to this theory. Dilated submucosal veins have been one of the most consistent histological findings and may represent the earliest abnormality in colonic angiodysplasia. This histological feature supports the theory of chronic venous obstruction in the genesis of angiodysplasia.
Of note, the aforementioned pathophysiological mechanisms responsible for the development of cecal lesions are unlikely to apply to lesions in the upper GI tract, despite being morphologically identical.
Recently, a link between a deficiency of high molecular-weight multimers of von Willebrand factor, aortic stenosis, and colonic angiodysplasia has been proposed.
Frequency
United States
The prevalence of angiodysplasia is 0.8% in healthy patients older than 50 years who are undergoing screening colonoscopy.
Foutch et al noted the prevalence of angiodysplasia to be 0.93% from 3 prospective studies in which screening colonoscopies were performed in 964 asymptomatic individuals (mean age, 61 y).
Patients with von Willebrand disease may have an increased incidence of gastrointestinal bleeding from colonic angiodysplasia.
International
No widespread studies to determine the incidence of angiodysplasia have been conducted, but the incidence probably is similar to that in the United States.
Mortality/Morbidity
- Bleeding from angiodysplasia usually is self-limited, but it can be chronic, recurrent, or even acute and life threatening.
- Approximately 90% of bleeding angiodysplasias spontaneously cease bleeding.
- Mortality is related to the severity of bleeding, hemodynamic instability, age, and the presence of comorbid medical conditions.
Race
No racial predilection exists.
Sex
Angiodysplasia occurs with equal frequency in men and women.
Age
Most patients found to have angiodysplasia are older than 60 years; of these patients, most are older than 70 years. However, case reports exist of occurrence in young people.
Treatment
Medically manage each patient in accordance with the severity of bleeding, hemodynamic stability, and recurrence of symptoms. A conservative approach to patients who are hemodynamically stable is recommended because most bleeding angiodysplasias will cease spontaneously. Treatment usually is not advocated for asymptomatic patients when angiodysplasias are found incidentally. Initially, hemodynamically stabilize all patients with active bleeding with intravenous fluid and packed red blood cells as needed. In addition, correct coagulopathies. When intervention is warranted, institute steps to control hemorrhage. Endoscopic techniques have been employed most frequently. Gastric and duodenal angiodysplastic lesions have been managed most commonly with endoscopic obliteration techniques. Rebleeding after these techniques has been attributed to other areas of bleeding angiodysplasia rather then failure of obliteration. These techniques include monopolar electrocautery, heater probe, sclerotherapy, band ligation, and argon and neodymium:yttrium-aluminum-garnet (Nd:YAG) lasers.Medical Care
Surgical resection is the definitive treatment.Surgical Care
Consultation with both a gastroenterologist and a surgeon is recommended. Interventional radiology often plays a critical role in the management of these patients. Withhold oral intake until diagnosis has been made and treatment has been initiated. Restrict activity until hemodynamic stability can be maintained.Consultations
Diet
Activity
Medication
Medical treatment has been used in active and recurrent bleeding from colonic angiodysplasia with controversial results. Hormonal treatment with estrogen and progesterone has been evaluated by randomized trials but remains controversial and is probably not effective. Octreotide, both short and long acting, has been described effective in few case reports and case series only. Other agents, such as thalidomide, remain experimental. DDAVP has also been used in specific subsets of patients. At the moment, no medical therapy has been proven to effectively treat bleeding from angiodysplasia.
Drug Category: Oral contraceptives
Only use hormonal therapy for the small subset of patients who are transfusion-dependent from bleeding angiodysplasia refractory to conservative and endoscopic therapy and who are poor surgical candidates. This is not for routine management of bleeding angiodysplasia. No large-scale, randomized, double-blinded studies have demonstrated its effectiveness.
Estrogen-progesterone therapy, previously used to treat bleeding associated with hereditary hemorrhagic telangiectasia, also has been tried in patients with GI bleeding from angiodysplasia.
Proposed mechanisms by which hormonal therapy might affect bleeding include improvement in coagulation, alterations in microvascular circulation, and improvements in endothelial integrity.
Data from a double-blinded, crossover trial using 0.05 mg ethinyl estradiol and 1 mg norethisterone administered daily to 10 elderly patients with GI ectasia (6 of the patients had hereditary hemorrhagic telangiectasia) have indicated that the combination significantly reduced bleeding and transfusion requirements. Several other small series with anecdotal success have been described, but one must be skeptical.
One study by Lewis refutes the benefits of hormonal therapy in angiodysplasia.This involved a retrospective cohort study of 64 patients. Thirty patients were administered 5-10 mg of norethynodrel with mestranol (0.075-0.15 mg) or with conjugated estrogens (0.625 mg), and the bleeding rates did not differ before and after therapy and did not differ from bleeding rates of historical controls or from patients who refused therapy. Treatment adverse effects in this study included vaginal bleeding, fluid retention, and stroke (23% of the treated patients).
Overall the current data do not support the use of hormonal therapy in patients with colonic angiodysplasia.
| Drug Name | Ethinyl estradiol and norethindrone (Ovcon 50) |
|---|---|
| Description | Suggested mechanisms by which hormonal therapy might affect bleeding include improvement in coagulation, alterations in the microvascular circulation, and improvements in endothelial integrity. One active tab contains ethinyl estradiol 0.05 mg and norethindrone 1 mg. |
| Adult Dose | 1 tab PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; thrombophlebitis; undiagnosed vaginal bleeding; pregnancy; estrogen-dependent neoplasia; severe hepatic disease; breast cancer |
| Interactions | May reduce hypoprothrombinemic effects of anticoagulants; estrogen levels may be reduced with coadministration of barbiturates, rifampin, and other agents that induce hepatic microsomal enzymes; an increase in corticosteroid levels may occur when administered concurrently with ethinyl estradiol; use of ethinyl estradiol with hydantoins may cause spotting, breakthrough bleeding, and pregnancy; increase in fluid retention caused by estrogen intake may reduce seizure control |
| Pregnancy | X - Contraindicated; benefit does not outweigh risk |
| Precautions | Cigarette smoking increases risk of serious cardiovascular adverse effects; caution in hepatic impairment, migraine, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease; associated adverse effects include GI distress, breakthrough bleeding, breast tenderness, weight change, and contact lens intolerance; in males, adverse effects include gynecomastia and decreased libido |
Drug Category: Somatostatin analogs
These agents have been reported to decrease the rate of bleeding from intestinal angiodysplasia. In our experience is usually well tolerated and may decrease the rate of chronic bleeding. Octreotide should be first choice in patients with portal hypertension.
| Drug Name | Octreotide (Sandostatin) |
|---|---|
| Description | Mechanism of action in this setting not fully understood. Used in acute variceal bleeding and for recurrent bleeding after endoscopic therapy. May reduce transfusion requirement. |
| Adult Dose | 100 mcg SC bid |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | May reduce effects of cyclosporine; patients on insulin, oral hypoglycemics, beta-blockers and calcium channel blockers may need dosage adjustments |
| Pregnancy | B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals |
| Precautions | Adverse effects primarily related to altered GI motility, and include nausea, abdominal pain, diarrhea and increased incidence of gallstones and biliary sludge; because of alteration in counter-regulatory hormones, (insulin, glucagon and GH) hypo- or hyperglycemia may be seen; bradycardia, cardiac conduction abnormalities and arrhythmias have been reported; due to inhibition of TSH secretion, hypothyroidism may also occur; exercise caution in patients with renal impairment; cholelithiasis may occur |
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