Systemic amyloidosis and the gastrointestinal tract

Abstract

Systemic amyloidosis is characterized by the extracellular deposition of protein in an abnormal fibrillar form. Several different types of amyloidosis exist, each defined by the identity of their respective fibril precursor protein. Among patients with systemic amyloidosis, histological involvement of the gastrointestinal tract is very common but is often subclinical. Conversely, primary diseases of the gastrointestinal tract can cause systemic amyloidosis; for example, AA amyloidosis can occur secondary to IBD. The presence and pattern of gastrointestinal symptoms varies substantially, not only between the different types of amyloidosis but also within them. Typical clinical presentations, most of which are nonspecific, include macroglossia, hemorrhage, motility disorders, disturbance of bowel habit and malabsorption. Endoscopic and radiological features are also nonspecific, with the small intestine most commonly affected. Currently, the aim of therapy for amyloidosis is to slow amyloid formation by reducing the abundance of the fibril precursor protein. No specific treatments for the gastrointestinal symptoms of systemic amyloidosis are available; however, case reports and small published series encourage nutritional support for patients with motility disorders and pharmacological agents for treatment of diarrhea. Surgical procedures should be contemplated only in an emergency setting because of the risk of decompensation of organs affected by amyloid deposition.

Amyloidosis of the gastrointestinal tract: a 13-year, single-center, referral experience

“…2 For dysmotility and early satiety, metoclopromide has been tried with limited success. Erythromycin, a pro-kinetic medication, was shown to have some benefit in improving delayed gastric emptying and early satiety in an ATTR patient.…”

“…1,2 Fibrils are comprised of protofilaments, made up of beta-sheet rich polypeptides. By electron microscopy, amyloid fibrils are ~10 nm in diameter; by polarized light microscopy, the regular structure of the fibris leads to apple green-birefringence following staining with Congo red dye.…”

“…2,8 GI involvement in AL amyloidosis is defined as the presence of GI symptoms with direct biopsy verification. 9…”

A rare gastrointestinal manifestation of systemic primary amyloidosis

“…However, despite attempts to treat underlying plasma cell dyscrasia and decrease light chain production, most patients are refractory to treatment. 1 The mortality associated with AL amyloidosis is high with a median survival of less than two years despite conventional treatment. 9 GI amyloidosis is not only infrequently amenable to systemic and symptomatic treatment, but has a negative impact on both quality of life and survival.…”

“…1 Of the many types of amyloidosis, amyloid light chain (AL) amyloidosis, or primary amyloidosis, is the most common form with a prevalence estimated to be 6-10 cases per million person-years. 2 AL amyloidosis is most often a manifestation of a primary plasma cell dyscrasia with 15% from multiple myeloma.…”