Involvement of the gastrointestinal tract in amyloidosis: when to think about it and how to diagnose
1 Klinika nefrologie 1. LF UK a VFN v Praze
Amyloidoses are disorders of diverse aetiologies in which deposits of abnormally folded proteins with fibrillar ultrastructures infiltrate the extracellular spaces of affected organs. More than 36 proteins (and many more variants) are known to be involved in amyloidosis. AL amyloidosis is the most frequent form. In this condition, amyloid deposits containing light chains (LCs) infiltrate tissues and can cause their dysfunction and failure. AA and ATTR amyloidosis are other types of systemic amyloidoses. The most frequently affected organs are the kidneys (74%), heart (60%), liver (27%), gastrointestinal tract (10–20%) and autonomous nervous system (18%). In total, 69% of patients have more than one affected organ at the time of diagnosis. Positive staining with Congo red is the dominant feature of all amyloidoses. Typing of renal or liver amyloidosis in clinical practice is typically performed by direct immunofluorescence of frozen tissue or by immunohistochemistry of fixed samples. Positivity for monoclonal LC λ or κ is detected in AL amyloidosis, while staining with antibodies against other fibrillar precursors is negative. Tissues are stained for amyloid A in AA amyloidosis and for transthyretin in ATTR amyloidosis. Gastrointestinal involvement during AL and AA amyloidosis typically manifests as dysphagia, weight loss, altered motility (gastroparesis and intestinal pseudo-obstruction), malabsorption or bleeding. Liver involvement can cause hepatomegaly with portal hypertension. Diagnosis of liver amyloidosis is confirmed when a liver biopsy is positive for Congo red staining, when the total liver span is more than 15 cm in the absence of heart failure, or when the alkaline phosphatase concentration is 1.5-fold higher than the institutional upper limit and amyloidosis is demonstrated from biopsy at an alternate site. The endoscopic findings of amyloidosis are variable and may include multiple polypoid protrusions, granular appearance of the mucosa, erosions, ulcerations and submucosal hematomas. Optimal management of patients with all types of amyloidosis requires early diagnosis, correct assessment of the type, effective treatment with supportive therapy and very careful follow-up.
KeywordsAA amyloidosis, AL amyloidosis, hepatomegaly, malabsorption syndrome, serum amyloid A, free light chains
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