Angiodysplasia, characterized by abnormal, twisted, and enlarged small blood vessels in the gastrointestinal (GI) tract’s mucosal and submucosal layers, stands as the most prevalent vascular anomaly within this system. While frequently identifiable through colonoscopy and angiography, diagnosing angiodysplasia in pathological specimens often presents a considerable challenge. This article provides an in-depth review of Angiodysplasia Diagnosis, encompassing its evaluation, histopathology, and treatment strategies. It further elucidates the crucial role of an interprofessional team in effectively managing patients afflicted with this condition.
Objectives:
- Detail the underlying causes of angiodysplasia.
- Elucidate the histopathological characteristics of angiodysplasia and differentiate it from other similar conditions.
- Define the diagnostic evaluation process and management approaches for angiodysplasia.
- Underscore the significance of collaborative efforts and effective communication within an interprofessional healthcare team to ensure optimal patient management and improve overall outcomes in angiodysplasia cases.
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Introduction
The gastrointestinal (GI) tract is frequently affected by various abnormal blood vessels, representing deviations from the normal structure of arteries, veins, or capillaries. These vascular anomalies range from benign conditions like hemangiomas to malignant tumors such as angiosarcomas. They can also be congenital, as seen in hereditary hemorrhagic telangiectasia, or predominantly acquired, as in the case of angiodysplasia.[1] Angiodysplasia is defined by abnormal, tortuous, dilated small blood vessels situated within the mucosal and submucosal layers of the GI tract. These aberrant vessels are composed of endothelium with minimal or absent smooth muscle.[2] Angiodysplasia represents the most common cause of small bowel bleeding, previously termed obscure gastrointestinal bleeding (OGIB), particularly in patients over the age of 60.[3] Notably, angiodysplasia is not associated with hereditary, dermatological, or systemic diseases and can manifest in any segment of the GI tract.[4] Accurate angiodysplasia diagnosis is crucial for effective patient management.
Etiology
The precise cause of angiodysplasia remains elusive; however, current literature proposes several contributing factors. These include age-related degeneration of small blood vessels and the influence of cardiovascular and pulmonary diseases, which may induce microvessel hypoperfusion. This reduced blood flow could lead to ischemic necrosis of abnormal vascular lesions.[4] A recognized association exists between angiodysplasia and aortic stenosis.[5] Mucosal hypoperfusion related to cardiac disease has also been cited as a causative factor in angiodysplasia development.[6] Furthermore, bleeding from angiodysplasia lesions in both the upper and lower GI tracts has been reported in individuals with von Willebrand disease (VWD).[7] Understanding the etiology is a key step in angiodysplasia diagnosis and management.
Epidemiology
Angiodysplasia is the most common vascular abnormality in the GI tract within the general population, predominantly affecting individuals over 60 years of age.[8, 9] The prevalence of angiodysplasia escalates with age. It can manifest asymptomatically or present with GI bleeding.[10] Approximately 5% to 10% of patients experiencing non-variceal upper GI bleeding are diagnosed with angiodysplasia.[11] In patients older than 50 years, small bowel angiodysplasia is the leading cause of obscure GI bleeding (OGIB). Conversely, small bowel tumors are more frequently the cause of OGIB in patients under 50 years.[3, 12] The colon is the most common location for angiodysplasia within the GI tract.[13] Literature suggests a higher association of angiodysplasia with conditions such as end-stage renal disease (ESRD), Von Willebrand disease, left ventricular assist device (LVAD) implantation, and aortic stenosis (Heyde syndrome). Accurate epidemiological data is vital for understanding the scope of angiodysplasia diagnosis and its impact.
In End-stage renal disease, while peptic ulcer disease remains the primary cause of GI bleeding, angiodysplasia constitutes a significant proportion of both upper and lower GI bleeding cases in ESRD patients, accounting for approximately 20% to 30% respectively. Reports indicate that angiodysplasia is responsible for roughly half of recurrent bleeding episodes in patients with chronic renal failure.[14, 15]
Aortic stenosis (Heyde syndrome) – Heyde first proposed the connection between GI bleeding of unknown origin and aortic stenosis in 1958, which was later attributed to angiodysplasia. The association remains a topic of discussion, with small case-control and retrospective studies presenting mixed findings both supporting and refuting this link. Notably, some reports have documented the cessation of recurrent GI bleeding after aortic valve replacement in long-term follow-up.[16, 17, 18]
Systemic sclerosis (SSc) – Gastric antral vascular ectasia (GAVE), also known as watermelon stomach, is a vascular malformation of the gastric antral mucosa. While some consider GAVE a variant of angiodysplasia within the broader spectrum of vascular anomalies, many authors classify it as a systemic disease-related vascular ectasia, particularly associated with systemic sclerosis. Prevalence estimates of GAVE in SSc patients are around 5.7%, based on a large retrospective study.[19]
Currently, no causal link has been established between these conditions and angiodysplasia. The observed associations may be influenced by increased endoscopic investigations in these patient populations. Patients with these conditions are more susceptible to gastrointestinal bleeding due to underlying coagulopathies, such as uremic platelet dysfunction in ESRD and acquired Von Willebrand factor deficiency in aortic valve stenosis and left ventricular assist devices (LVAD).[20, 21, 22, 23] Considering these associated conditions is important in the differential angiodysplasia diagnosis process.
Pathophysiology
The precise mechanism underlying angiodysplasia remains unclear. However, a prevailing hypothesis suggests that increased contractility within the muscularis propria layer can lead to submucosal vein obstruction. Chronic obstruction of these vessels may contribute to the development of age-related angiodysplasia lesions. Capillary congestion and precapillary sphincter dysfunction can subsequently result in the formation of arteriovenous collaterals.[24]
Angiogenesis, the formation of new blood vessels, plays a crucial role in vascularity increases in response to hypoxia or ischemia. In hypoxic conditions, angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor exhibit increased expression in angiodysplasia. These factors are significant in angiodysplasia development and influence the risk of bleeding.[25, 26]
Research in endothelial cells has demonstrated that inhibiting von Willebrand factor (VWF) expression enhances proliferation mediated by VEGF and angiogenesis. This highlights a correlation between hemostasis and angiogenesis, which may be relevant in treating angiodysplasia patients with VWD.[27] Understanding the pathophysiology aids in refining angiodysplasia diagnosis and treatment strategies.
Histopathology
While angiodysplasia is often readily visualized during colonoscopy and angiography, its detection in gross pathological specimens without specialized injection techniques is frequently challenging. Vascular injection studies on resected colons have indicated that angiodysplasia develops due to intermittent partial obstruction of small veins draining the colonic mucosa and submucosa as they traverse the muscularis propria. Over time, obstruction of these penetrating veins leads to dilation and tortuosity of submucosal veins and subsequently, the venules and capillaries draining into them. Histopathological examination is a critical component of angiodysplasia diagnosis.
Angiodysplasias can be diagnostically elusive in pathological specimens. Freshly resected specimens may only exhibit subtle vascular markings and erythema, and even these signs may be absent. After formalin fixation, lesions are typically not visible on the mucosal surface. When a vascular lesion is identified, histological examination typically reveals a distinct cluster of dilated, tortuous veins and venules within the submucosa, sometimes accompanied by dilated capillaries in the overlying mucosa.[28] Detailed histopathological analysis is essential for confirming angiodysplasia diagnosis and excluding other conditions.
History and Physical
Patients with angiodysplasia can be asymptomatic or present with mild to moderate occult lower GI bleeding without abdominal pain. A thorough history should encompass the same elements as in evaluations for upper and lower GI bleeding. Patients may present with occult blood in stool and iron deficiency anemia. Physical examination in a hemodynamically stable patient may reveal signs and symptoms of anemia. The presence of a systolic ejection murmur during cardiac auscultation may raise suspicion for underlying aortic stenosis. Angiodysplasia lesions can be incidentally discovered during endoscopy performed for other indications. Orthostasis or hypotension may occur in rare instances of acute and heavy bleeding. Although bleeding often ceases spontaneously, recurrence is possible. Angiodysplasia-related GI bleeding can occur throughout the GI tract, but is more frequently observed in the cecum, rectosigmoid area, the remainder of the colon, small intestine, and stomach, in descending order of frequency.[29] A comprehensive history and physical examination are important initial steps in angiodysplasia diagnosis.
Evaluation
Angiodysplasia diagnosis frequently occurs incidentally during colonoscopy for colorectal cancer screening or when evaluating patients for acute or chronic blood loss anemia. The initial diagnostic approach depends on the bleeding characteristics and suspected source location. Slow bleeding from the stomach or small bowel may manifest as melena, whereas a colonic origin may present as fresh red blood per rectum. Clinicians should be aware that significant upper GI bleeding can also present with fresh blood per rectum. Patient evaluation should include vital sign assessment to ascertain hemodynamic stability. Initial investigations typically involve a complete blood count, liver function tests, coagulation studies, and renal function tests to assess anemia severity and identify underlying medical conditions associated with bleeding, such as end-stage renal disease or congenital/acquired coagulation disorders (e.g., cirrhosis). Given the widespread distribution of angiodysplasia throughout the GI tract, a combination of endoscopic and radiological studies may be necessary for definitive angiodysplasia diagnosis.
Upper GI endoscopy and colonoscopy are standard initial diagnostic tools. Angiodysplasia visualized directly during endoscopy or colonoscopy appears as 5 to 10 mm flat, cherry-red, fern-like projecting vessels originating from a central arteriole.[30] Colonoscopy sensitivity for angiodysplasia diagnosis is estimated at approximately 80%, with a positive predictive value around 90%.[31]
For small bowel angiodysplasia suspected as the source of obscure GI bleeding, further evaluation with wireless video capsule endoscopy or deep bowel enteroscopy (single or double-balloon enteroscopy) may be necessary if initial workup is inconclusive. These advanced endoscopic techniques play a crucial role in angiodysplasia diagnosis in challenging cases.
Radionuclide scanning is the most sensitive radiologic diagnostic modality for detecting active bleeding, capable of identifying bleeding rates as low as 0.1 to 0.5 ml/min. Two primary nuclear scans are utilized: 99m Tc pertechnetate autologous red blood cell and technetium sulfur colloid. Technetium red cell scintigraphy is now more commonly employed due to its longer half-life, enabling imaging at extended intervals up to 24 hours post-injection, thereby enhancing the detection of intermittent active bleeding compared to technetium sulfur colloid tests.[32] The primary limitation of radionuclide scanning is its generalized localization of bleeding within the abdominal region, which may not precisely pinpoint the specific bleeding site due to intestinal peristalsis. While helpful in confirming active bleeding, radionuclide scanning is often a preliminary step in angiodysplasia diagnosis.
CT angiography and magnetic resonance angiography are valuable investigative tools for further assessment when conventional methods fail to identify bleeding sources. Helical CT angiography exhibits a sensitivity of 70% and specificity of 100%. However, its efficacy is greater during active bleeding, requiring a minimum bleeding rate of 0.3 to 0.5 ml/min.[33] These imaging modalities offer more detailed anatomical information, aiding in angiodysplasia diagnosis and localization.
Angiography is typically indicated for hemodynamically unstable patients with active bleeding or when conventional diagnostic approaches fail to identify the active bleeding source. Angiography necessitates a blood loss rate of 0.5 to 1 ml/min for active bleeding source diagnosis. It also offers the advantage of simultaneous therapeutic intervention.[34] Angiography is a critical tool in both angiodysplasia diagnosis and management, particularly in acute bleeding scenarios.
Intraoperative enteroscopy is a valuable resource when both endoscopic and radiological investigations are unsuccessful in locating the bleeding source. This involves endoscopy via oral, rectal, or enterotomy routes during surgery. Diagnostic yield is estimated between 60% and 88%. Intraoperative enteroscopy is rarely used and reserved for cases with unidentified bleeding sources in actively bleeding patients. Potential complications include perforation, serosal/mesenteric/vessel tears, azotemia, and prolonged ileus.[35, 36] This invasive procedure is a last resort for angiodysplasia diagnosis when other methods are insufficient.
Angiodysplasia colonoscopy view.
Alt text: Colonoscopy image showing angiodysplasia, a vascular lesion characterized by abnormal, dilated blood vessels on the colon lining, appearing as small, reddish, fern-like projections.
Treatment / Management
Angiodysplasia is frequently diagnosed incidentally during endoscopy for unrelated reasons. Management strategies are categorized based on clinical presentation: incidental angiodysplasia, non-bleeding angiodysplasia in a patient with GI bleeding, and actively bleeding angiodysplasia with GI bleeding. Treatment decisions should be guided by these classifications and the patient’s clinical status.
Incidental angiodysplasia – Incidental angiodysplasia, discovered in the absence of GI bleeding history or unexplained iron deficiency anemia, generally does not require treatment. The long-term bleeding risk associated with incidental angiodysplasia is not well-defined, and current recommendations are primarily based on expert consensus.
Nonbleeding angiodysplasia in a patient with GI bleeding – In patients presenting with GI bleeding but non-bleeding angiodysplasia identified as a potential source, treatment is typically recommended, again guided by expert opinions.
Actively bleeding angiodysplasia – Management of actively bleeding angiodysplasia generally mirrors the approach for upper and lower GI bleeding from other causes, focusing on hemodynamic resuscitation, frequent complete blood count monitoring, and blood transfusions as needed. Treatment decisions should be tailored to hemodynamic stability and the presence of active bleeding.
Hemodynamically unstable patient – For unstable patients with active bleeding, immediate intravenous fluid resuscitation is crucial. Patients exhibiting obtundation, thready pulse, hypoxia, active hematemesis, and airway compromise necessitate intubation and intensive care unit admission for continuous CBC monitoring and blood transfusions. Endoscopy or colonoscopy should be performed if feasible; however, in cases of ongoing active bleeding, surgical or radiological intervention with angiography may be required.
Hemodynamically stable patient – In hemodynamically stable patients, endoscopy or colonoscopy should be performed within 24 hours, guided by bleeding characteristics. If these investigations do not identify a bleeding source, subsequent diagnostic modalities are selected based on the presence or absence of continued active bleeding.
Endoscopy or colonoscopy – When angiodysplasia is identified during endoscopy or colonoscopy, several techniques can be employed for treatment:
- Argon plasma coagulation ablation – This is the most frequently used intervention.[37] It delivers high-frequency energy to tissues via ionized gas. Thorough bowel preparation is essential to prevent colonic gas explosion.[38] It carries a relatively higher risk of bowel perforation in the upper GI tract.
- Electrocoagulation – This technique uses bipolar or heater probe coagulation and is more suitable for lower GI tract applications.
- Endoscopic clips and band ligation – These mechanical methods are used to treat angiodysplasia. Band ligation is an option for angiodysplasia treatment in the stomach and small bowel.
- Injection sclerotherapy – This involves injecting a sclerosant to obliterate angiodysplasia and other vascular lesions in the upper and lower GI tracts. Commonly used sclerosants include ethanolamine or sodium tetradecyl sulfate. Endoscopic ligation, endoscopic resection, and photocoagulation are also utilized endoscopically for angiodysplasia treatment.[39, 40, 41]
Endoscopy with push enteroscopy is employed to investigate and treat OGIB with endoscopic intervention.
Angiography – Angiography is typically performed in patients with active bleeding who have not responded to other treatments, are unsuitable for surgery, or to localize bleeding sites preoperatively for surgical resection. Therapeutic interventions include temporary measures with absorbable gelatin sponge, local vasopressin infusion, or permanent embolization using micro-coils, particles, or glue. Major complications include bowel ischemia or infarction, along with arteriography-related complications. Initial hemostasis success rates with embolization are reported at 95% for lower GI bleeding and 64% to 89% for upper GI bleeding.[42, 43] Rebleeding rates after lower GI bleed embolization are estimated between 22% and 48%.[44, 45]
Surgery – Surgical resection becomes necessary in patients with severe, active bleeding requiring multiple blood transfusions and failure of all other management strategies.[46] Rebleeding post-surgery may result from incomplete resection or missed lesions. Preoperative push enteroscopy, intraoperative enteroscopy, and angiography can improve bleeding site localization, reducing rebleeding risk. Preoperative endoscopy or colonoscopy can also be used to inject dye or place endoclips to demarcate lesions for better surgical localization. Intraoperative enteroscopy can further assist in localizing unidentified lesions. Aortic valve replacement in patients with associated aortic stenosis may alleviate angiodysplasia-related bleeding.[16]
Angiogenesis inhibitors – Thalidomide and bevacizumab have shown promise in treating gastrointestinal vascular malformations, including angiodysplasia.[25, 26, 47] A clinical trial reported a 71.6% effective response rate (GI bleeding cessation >50% by year-end) in the thalidomide group compared to 3.7% in the control group.[48] While thalidomide has demonstrated potential in refractory angiodysplasia-related GI bleeding and transfusion-dependent patients, its use necessitates caution due to significant side effects, including teratogenicity. Bevacizumab, a human monoclonal antibody against vascular endothelial growth factor, has been used in case reports and series for refractory GI bleeding related to angiodysplasia but should be considered a last resort due to limited data.[47]
Hormone therapy – Limited studies have assessed estrogen therapy, with or without progesterone, for chronic obscure GI bleeding.[49] However, other studies, including a randomized controlled trial, have not shown benefit from hormonal therapy in preventing angiodysplasia-related GI bleeding.[50]
Octreotide – Octreotide appears effective in treating refractory angiodysplasia-related GI bleeding, as indicated in case series and meta-analyses. Options include subcutaneous octreotide injections (50-100 mcg twice daily) and long-acting octreotide-LAR (intramuscularly once monthly). Studies evaluating octreotide demonstrated response rates of 73% to 76% in terms of bleeding events, transfusion requirements, and mean hemoglobin levels.[51, 52, 53, 54] Octreotide may be considered in patients with refractory angiodysplasia-related bleeding. A detailed understanding of treatment options is crucial for effective angiodysplasia diagnosis and management.
Differential Diagnosis
Symptomatic angiodysplasia typically presents with symptoms similar to upper and lower GI bleeding, manifesting as unexplained iron deficiency anemia or overt GI bleeding. Differential angiodysplasia diagnosis must consider common causes of both upper and lower GI bleeding:
- Peptic ulcer disease
- Diverticulosis
- Colitis (ischemic, inflammatory bowel disease, radiation-induced, infectious)
- Hemorrhoidal bleeding
- GI malignancies, such as colon and rectal cancer.[55]
Accurate differential angiodysplasia diagnosis is essential for appropriate patient care.
Prognosis
Patients with angiodysplasia generally have a favorable prognosis, as bleeding resolves spontaneously in most cases. However, patients with ten or more angiodysplasia lesions or lesions larger than 10 mm may experience a less favorable prognosis, lower hemoglobin levels, and require more blood transfusions.[56] Prognostic factors are important to consider in long-term angiodysplasia diagnosis and management.
Complications
Chronic occult bleeding and iron deficiency anemia are the most common complications and presenting symptoms of symptomatic angiodysplasia. In rare instances, symptomatic angiodysplasia can manifest as massive bleeding, leading to hemodynamic instability. Recognizing potential complications is part of comprehensive angiodysplasia diagnosis and care.
Consultations
Gastroenterologist consultation is essential for patients with symptomatic angiodysplasia to confirm the diagnosis and guide further treatment using various endoscopic techniques. Patients with symptomatic angiodysplasia and an unconfirmed bleeding source after initial investigations may require interventional radiology consultation for angiography, both for diagnosis and potential therapeutic intervention. Surgical consultation is necessary for cases with uncontrolled bleeding despite other interventions. Interdisciplinary consultations are vital for optimal angiodysplasia diagnosis and management.
Deterrence and Patient Education
Patient reassurance is recommended in most cases of incidental angiodysplasia, as it is typically asymptomatic. The decision for endoscopic therapy is usually based on clinical presentation and the presence of GI bleeding or unexplained iron deficiency anemia. Patient education and appropriate deterrence strategies are important aspects of angiodysplasia management, particularly after angiodysplasia diagnosis.
Enhancing Healthcare Team Outcomes
Most patients with bleeding angiodysplasia initially present to the emergency department. Therefore, nursing staff and triage personnel must be well-versed in managing these patients. Due to the complexity of diagnosis, a multidisciplinary team, including various specialists and healthcare providers, is often involved in patient care. Resuscitation is paramount for unstable patients. Once stabilized, imaging studies are necessary to locate angiodysplasia for definitive treatment. Acutely bleeding patients require monitoring in an intensive care setting, with awareness of potential complications.
When medical treatment is indicated, specialists should collaborate closely with a board-certified pharmacotherapy pharmacist to optimize drug selection and dosing. A gastroenterology specialty nurse can further ensure patient compliance, provide counseling, and assess therapeutic effectiveness, regardless of the chosen treatment path. Effective communication and collaboration among specialists and all interprofessional team members—including ED physicians, specialists, pharmacists, and nursing staff—are crucial for improving patient outcomes. [Level 5] This collaborative approach significantly enhances the quality of angiodysplasia diagnosis and care.
A recent case-control study involving 270 angiodysplasia patients diagnosed between 2010 and 2015 and 5594 controls identified risk factors for incidental angiodysplasia as anticoagulants, autoimmune disease, chronic obstructive pulmonary disease, male gender, and thyroid dysfunction. Risk factors for symptomatic angiodysplasia included advanced age, diabetes mellitus, hyperlipidemia, and valvular heart disease. These findings highlight that risk factors for symptomatic angiodysplasia differ from and are more significant than those for incidental angiodysplasia, which can inform tailored treatment plans for angiodysplasia patients.[57]
Angiodysplasia endoscopic view.
Alt text: Endoscopic view of angiodysplasia in the colon, displaying characteristic cherry-red, flat lesions with fern-like projections indicative of abnormal vascular formations.
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References
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Disclosure: Maryam Aghighi declares no relevant financial relationships with ineligible companies.
Disclosure: Mehran Taherian declares no relevant financial relationships with ineligible companies.
Disclosure: Ashish Sharma declares no relevant financial relationships with ineligible companies.
