Amyloidosis can be acquired or genetic and is classified based on etiology of the deposited insoluble low-molecular-weight protein subunits. The most common forms of acquired amyloidosis are AL, as in our case; serum amyloid A (AA), which is an acute phase reactant and complication of chronic inflammatory disease; and β-2 microglobulin, which is dialysis related with protein accumulation due to decreased renal clearance. The continuous protein deposition and build-up damages the integrity and function of affected organs.
AL amyloidosis is caused by plasma cell dyscrasia and deposition of immunoglobulin light chains. Determining the epidemiology of AL amyloidosis is difficult due to its rarity. AL amyloidosis is also challenging to diagnose, given its various presenting clinical syndromes. American data reported in 2018 suggests the incidence and prevalence of AL amyloidosis is between 9.7 and 14.0 cases per million person-years and 40.5 cases per million, respectively [7].The majority of patients with AL amyloidosis are over 65-years-old. The most common clinical presentations of AL amyloidosis are nephrotic syndrome and restrictive cardiomyopathy [8]. Tissue biopsy stained with Congo Red showing green birefringence under polarized light is the diagnostic gold standard [2]. The sensitivity and specificity of biopsy location is variable and may involve abdominal fat pad aspiration or biopsy of the organ in which amyloid is suspected, acknowledging increased risks of hemorrhage with the latter. Rectal biopsy is another surrogate site utilized to diagnose systemic amyloidosis with a reported sensitivity of 85% but is no longer recommended as a first-line option for diagnosis due to patient discomfort, risk of complications, and low diagnostic yield in the setting of negative fat pad aspiration [9].
Treatment of AL amyloidosis aims to reduce the production of fibrils to limit deposition–and therefore damage–within amyloidogenic organs. There are many therapeutic regimens used to treat AL amyloidosis, but lack of randomized data comparing efficacy makes decisions surrounding therapy difficult. Since the underlying pathophysiology is plasma cell dyscrasia, management has similarities to that of MM. However, outcomes are better in AL amyloidosis than MM. Treatment options include autologous stem cell transplant (ASCT) and various chemotherapy regimens such as: melphalan and dexamethasone (MDex), cyclophosphamide, thalidomide and dexamethasone (CTDa), and CyBorD [2].
We performed a review of the literature regarding AL amyloidosis in the GI system. PubMed database was used. No date restrictions were used. Only English-language reports were included. Case report, retrospective chart review, and previous systemic reviews that discussed presentation, diagnosis, and management of gastrointestinal amyloidosis were included. There exists no higher-level evidence. Search Terms used: “amyloid”, “AL amyloidosis” “amyloidosis”, “gastrointestinal amyloidosis”, “endoscopy amyloidosis”. 31 results were obtained and formed the basis for this focused review. Articles were further selected based on relevance.
Previous retrospective chart reviews suggest that Gl tract involvement is uncommon in AL amyloidosis, with biopsy proven [10] and clinically apparent [11] disease in 3% and 1% of patients, respectively. The majority of patients with GI amyloid have systemic involvement [10]. There are various GI manifestations of AL amyloidosis, including weight loss, GI bleeding, heartburn, and nausea [10]. Common sites of AL amyloid infiltration include the duodenum, stomach, colorectum, and esophagus [3, 10, 12].With regards to endoscopic abnormalities in those with AL amyloidosis and GI symptoms, 50% present with GI bleeding secondary to ischemia, vascular friability, or mucosal/submucosal lesions [13]. Endoscopic appearances of GI manifestations of AL amyloidosis are highly variable, differ based on anatomic location, and are not specific to amyloidosis subtype [3]. The most common gastric findings include depressed lesions (45%), erythema (32%), edema (29%), mucosal friability (26%), and elevated lesions similar to submucosal tumors (26%); conversely, there may be no gastric findings (45%) [3].
Therapy for GI manifestations of AL amyloidosis are primarily supportive including nutritional supplementation and treatment of diarrhea or obstruction [14].There are no treatment guidelines for endoscopic management of UGIB secondary to AL amyloid disease [9]. Based on a prospective cohort, the prognosis of those with GI manifestations of AL amyloidosis is worse compared to those without GI sequelae, with median survival reported as 7.95 months and 15.84 months, respectively [15].
Recent case reports describe UGIB in patients with known multiple myeloma or monoclonal gammopathy of unknown significance [16, 17]. This case differs because the patient lacked a prior diagnosis and his presentation of recurrent UGIB led to the discovery of his underlying AL amyloidosis. Advanced and irreversible organ dysfunction often precedes the diagnosis of amyloidosis [2]. Therefore, a high index of suspicion and an accessible target organ for diagnostic examination are of utmost importance in expediting treatment and management. Overall, GI amyloidosis presenting as recurrent UGIB is a rare, but known manifestation of AL amyloid disease. This case highlights GI amyloidosis as a differential diagnostic consideration for UGIB and provides an additional example of its endoscopic appearance.