Preventing Acute Bleeding Episodes in Gastric Antral Vascular Ectasia

By Tiffany Lin, MD, and Soumya Chatterjee, MD, MS, FRCP

Gastric antral vascular ectasia (GAVE) is a significant cause of recurrent gastrointestinal bleeding in patients with systemic sclerosis (SSc). Our presentation at the American College of Rheumatology’s 2015 meeting detailed the intriguing results of our small, retrospective study that may provide hope for preventing recurrent bleeding episodes in GAVE.

Current treatment landscape

GAVE is a serious complication of many conditions; available treatment modalities only address active bleeding. We used to think GAVE was a rare manifestation of SSc, but it was simply underdetected. A recent study utilizing video capsule endoscopy as a screening method revealed a prevalence of 18 percent in patients with SSc. GAVE has also been reported with hepatic cirrhosis, chronic renal failure, bone marrow transplant, diabetes mellitus and congestive heart failure.

Figure. Endoscopic view of GAVE. Gastroscopy shows longitudinal rugal folds traversing the antrum and converging onto the pylorus. Each fold contains a visible convoluted column of vessels. Histologically, GAVE is defined as the presence of dilated vessels with fibrin thrombi, fibromuscular hyperplasia of the lamina propria and fibrohyalinosis.

The current standard of care for management of GAVE involves treatment of acute episodes of bleeding with endoscopic procedures and blood transfusions. However, re-bleeding often occurs, requiring repeated treatments. Additionally, endoscopic procedures carry the risk of complications, including acute bleeding, acute perforation, antral stenosis related to scarring, and sepsis.

Building a case: Immunosuppressive therapy for GAVE

Currently, immunosuppressive therapy has no defined role in prevention of acute bleeding episodes from GAVE. However, prior case reports have shown stabilization in hemoglobin levels and reduced frequency of blood transfusions in patients with SSc who were treated with cyclophosphamide for other indications such as interstitial lung disease secondary to SSc and lymphoma. Potential toxicities related to cyclophosphamide, including severe cytopenias, infection, malignancy, hemorrhagic cystitis and infertility, preclude its use except in organ- or life-threatening disease. Other immunosuppressive therapies have better safety profiles, but despite their established use in treating other manifestations of SSc, they have not been studied in GAVE.

Based on mechanisms suggested in prior case reports, we performed a single-center retrospective study to determine whether immunosuppressive therapy, used for any indication in patients with SSc, is associated with reduced frequency of interventions needed for GAVE. We studied a cohort of 48 patients seen at Cleveland Clinic with SSc-associated GAVE.

Immunosuppressive therapy associated with fewer endoscopies

Twenty-nine of the 48 patients received immunosuppressive therapy, which included mycophenolate, glucocorticoids, hydroxychloroquine, cyclophosphamide, intravenous immunoglobulin, methotrexate and azathioprine. Immunosuppressive therapies were prescribed for a variety of indications, including cutaneous, musculoskeletal and pulmonary manifestations of SSc, and for treatment of hematologic malignancies.

Our study showed that patients receiving immunosuppressive therapy require significantly fewer therapeutic endoscopies than those not receiving immunosuppressive therapy. This decrease in frequency was even more pronounced among those receiving mycophenolate.

A potential therapy to alter natural history of GAVE

Our study suggests that immunosuppressive therapy, especially with mycophenolate, may have the potential to alter the natural history of GAVE in patients with SSc and reduce the frequency of acute episodes of gastrointestinal bleeding and anemia. Given mycophenolate’s safety profile, it may be considered in those who have refractory bleeding from GAVE that requires repeated therapeutic endoscopies

Some limitations of our study include its retrospective approach and the small number of patients from a single academic center, unknowns about the impact of antibody subtype on GAVE severity, and the presence of other organ manifestations of SSc. Nevertheless, the results of our study provide intriguing evidence that immunosuppressive therapy may have the potential to favorably alter the natural history of GAVE in patients with SSc.

Dr. Lin (lint@ccf.org; 216.444.5627) is a rheumatology fellow in the Department of Rheumatic and Immunologic Diseases.

Dr. Chatterjee directs the Scleroderma Program in the Department of Rheumatic and Immunologic Diseases.