Gastrointestinal amyloidosis: A focused review

Table 1 Differences in systemic and localized gastrointestinal amyloidosis

Systemic gastrointestinal amyloidosis	Localized gastrointestinal amyloidosis
More common subtype	Less common subtype
Amyloid production at a remote location with subsequent deposition in the GI tract	Amyloid production in the GI tract with subsequent deposition locally
Presence of amyloid precursor proteins in the blood	Amyloid precursor proteins absent in the blood
Associated with plasma cell dyscrasia, chronic inflammatory conditions, dialysis, or hereditary conditions	Not associated with an underlying disease pathology
Amyloid precursor protein deposited include AL, AA, Aβ2M and ATTR	Amyloid precursor protein most deposited is AL
Management consists of symptomatic management and treatment of the underlying etiology	Management consists of observation or surgical excision of the localised deposition
Prognosis depends on the type and amount of amyloid deposition	Good prognosis. No transition to systemic type

AL: Monoclonal light chain; AA: Serum amyloid A; Aβ2M: β2-microglobulin amyloid; ATTR: Familial transthyretin-associated amyloidosis; GI: Gastrointestinal.

Table 2 The common forms of systemic amyloidosis with organ involvement

Type of systemic amyloidosis	Causative protein	Organ involvement
Primary systemic amyloidosis	Monoclonal light chain (AL)	Heart, Kidneys, Liver, Peripheral nervous system, Autonomic nervous system, and Gastrointestinal tract
Senile systemic amyloidosis	Wild-type transthyretin (ATTR)	Heart
Hereditary systemic amyloidosis	Mutant transthyretin (ATTR); Apolipoprotein 1 (AApoA1); Mutant fibrinogen A alpha (AFib); Lysozyme (ALys)	Heart; Heart, Kidneys, Liver, Peripheral nervous system, and Skin; Kidneys and Liver; Kidneys and Liver
Isolated Atrial Systemic Amyloidosis	Atrial natriuretic factor (AANF)	Heart
Secondary Systemic Amyloidosis	Serum amyloid A (AA)	Kidneys, Heart, and Gastrointestinal tract
Dialysis-Related Systemic Amyloidosis	β2-microglobulin (Aβ2M)	Osteoarticular tissue, Circulatory system, and Gastrointestinal tract
Finnish-type Systemic Amyloidosis	Gelsolin (AGel)	Lattice dystrophy of cornea, and Corneal neuropathy

Table 3 Management of gastrointestinal amyloidosis based on the amyloid protein

Gastrointestinal amyloidosis	AL amyloidosis	AA amyloidosis	Hereditary amyloidosis	Dialysis-related amyloidosis
Treatment strategy	Systemic: Eligible: Autologous stem cell transplantation (ASCT) for plasma cell dyscrasias. Non-eligible: No standard protocol; combination of Bortezomib, Melphalan and Dexamethasone has shown improved survival. Localized: Observation or localized surgical excision	Chronic inflammatory conditions: Biologics (anti-TNF antibodies, humanized anti-IL6 receptor antibody) and immunosuppressants. Familial mediterranean fever: Colchicine.	Liver production of transthyretin: Orthotopic liver transplantation (OLT). Disease modifying therapy: Transthyretin stabilizers (Tafamidis and Diflunisal), Doxycycline, Patisiran and Inotersen may be used on case-to-case basis	Prevention: Removal of plasmatic β2-microglobulin (Aβ2M) through hemodialysis or peritoneal dialysis. Early renal transplant