Epidemiology and Clinical Implications of Gastrointestinal Symptoms in Systemic Amyloidosis

Abstract

Introduction: Gastrointestinal (GI) symptoms in systemic amyloidosis patients are poorly characterized. This purpose of this study is to define the epidemiology and clinical implications of such symptoms in the context of endoscopic investigation. Methods: This was a retrospective single center cohort study of 583 amyloid patients seen at a tertiary referral center from June 2008 to January 2017. Of 96 symptomatic patients, 82 received endoscopic biopsies (either esophagogastroduodenoscopy or colonoscopy), subsequently grouped into those with histologic evidence of GI amyloid (biopsy proven) versus those without (biopsy absent) (Figure 1). Analysis was done with Fisher exact test or Mann-Whitney U test with p < 0.05 denoting significance.FigureResults: 16.8% of patients had GI symptoms. 84.4% of these patients had light-chain (AL) amyloidosis, 12.5% had transthyretin (TTR) amyloidosis, and 3.1% had other types of amyloidosis. Of the 82 symptomatic patients who received endoscopy, only 37 (45%) had biopsy proven GI amyloid. The sites of highest diagnostic yield were the stomach (30.0%), duodenum (38.6%), ileum (36.4%) and colon (26.7%). The most common symptom was abdominal pain/nausea/vomiting (50.0%) followed by weight loss (40.2%) and diarrhea (26.8%). 23.2% received functional GI diagnostics, 73.2% got acid suppression, 28.0% got neuropathic or motility agents, and 7.3% got non-pharmacologic therapies (Table 1). Biopsy proven patients more often had cardiac amyloid (p < 0.005), and more often received hematologic therapy or transplant (p=0.01). Biopsy absent patients had slightly more frequent neurologic involvement (p=0.17-0.31) (Table 2). Biopsy results had no significant correlation with other organ involvement, burden of organ involvement, GI symptoms, or motility-specific management (Table 1 and 2).Table: Table. Gastrointestinal CharacteristicsTable: Table. Systemic Amyloidosis CharacteristicsConclusion: Nearly 1 in 6 amyloid patients have GI symptoms, and approximately half do not have GI amyloid as the etiology of those symptoms. Unfortunately, the type of symptom does not predict endoscopic findings. Despite the lack of an alternative etiology, most biopsy absent patients are not managed as a functional bowel disorder. Gastroenterologists may have an increased role to play in the care of systemic amyloidosis beyond performing endoscopies, such as evaluation of cardiac amyloid patients for concurrent GI amyloid or chronic management of GI dysmotility.