Involvement of the gastrointestinal tract in amyloidosis: when to think about it and how to diagnose
Authors:
Ryšavá R.
Authors‘ workplace:
Klinika nefrologie 1. LF UK a VFN v Praze
Published in:
Gastroent Hepatol 2019; 73(2): 154-162
Category:
Chapters from Internal Medicine: Case report
doi:
https://doi.org/10.14735/amgh2019154
Amyloidózy jsou onemocnění odlišné etiologie, u kterých dochází k depozici abnormálně uspořádaných proteinů fibrilární ultrastruktury extracelulárně v postižených tkáních. V současné době rozeznáváme 36 různých typů amyloidóz (a spoustu jejich variant). AL amyloidóza je nejčastější formou a amyloidová depozita obsahující lehké řetězce imunoglobulinů (LC – light chain) infiltrují tkáně a způsobují jejich dysfunkci až selhání. AA a ATTR amyloidóza jsou další časté formy systémových amyloidóz. Mezi nejčastěji postižené orgány patří ledviny (v 74 %), srdce (60 %), gastrointestinální trakt (10–20 %), játra (27 %) a autonomní nervový systém (18 %).
Overview
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.
Conflict of Interest: Author declares that the article/manuscript complies with ethical standards, patient anonymity has been respected, and states that she has no financial, advisory or other commercial interests in relation to the subject matter.
Publication Ethics: The article/manuscript has not been published or is currently being submitted to another review.
The author agrees to publish her name and e-mail in the published article/manuscript.
Dedication: The article/manuscript is not supported by a grant nor has it been created with the support of any company.
The Editorial Board declares that the manuscript met the ICMJE „uniform requirements“ for biomedical papers.
Submitted: 27. 2. 2019
Accepted: 9. 4. 2019
Keywords:
hepatomegaly – AL amyloidosis – AA amyloidosis – free light chains – serum amyloid A – malabsorption syndrome
Sources
1. Benson MB, Buxbaum JN, Eisenberg DS at al. Amyloid nomenclature 2018: recommendations by the International Society of Amyloidosis (ISA) nomenclature committee. Amyloid 2018; 25 (4): 215–219. doi: 10.1080/13506129.2018.1549825.
2. Rysava R. AL amyloidosis: advences in diagnostics and treatment. Nephrol Dial Transplant 2018. In press. doi: 10.1093/ndt/gfy291.
3. Duhamel S, Mohty D, Magne J et al. Incidence and prevalence of light chain amyloidosis: a population-based study. Blood 2017; 130: 5577.
4. Kyle RA, Larson DR, Therneau TM et al. Long-term follow-up of monoclonal gammopathy of undetermined significance. N Engl J Med 2018; 378 (3): 241–249. doi: 10.1056/NEJMoa1709974.
5. Merlini G, Palladini G. Amyloidosis: is a cure possible? Ann Oncol 2008; 19 (Suppl 4): iv63–66. doi: 10.1093/annonc/mdn200.
6. Hazenberg BP, van Rijswijk MH. Clinical and therapeutic aspects of AA amyloidosis. Baillieres Clin Rheumatol 1994; 8 (3): 661–668.
7. Lachmann HJ, Gillmore JD, Wechalekar AD et al. A single centre 20 year case series of AA amyloidosis – changing epidemiology. XIIIth International Symposisum on Amyloidosis, Groningen 2012; OP 51.
8. Hazes, JM, Cats A. Rheumatoid arthritis. In: Klippel JH, Dieppe PA (eds). Rheumatology. Mosby-Year Book Europe Limited 1994.
9. Lachmann HJ, Goodman HJ, Gilbertson JA et al. Natural history and outcome in systemic AA amyloidosis. N Engl J Med 2007; 356 (23): 2361–2371.
10. Gillmore JD, Lovat LB, Persey MR et al. Amyloid load and clinical outcome in AA amyloidosis in relation to circulating concentration of serum amyloid A protein. Lancet 2001; 358 (9375): 24–29.
11. Sousa A, Coelho T, Barros J et al. Genetic epidemiology of familial amyloidotic polyneuropathy (FAP) -type I in Póvoa do Varzim and Vila do Conde (north of Portugal). Am J Med Genet 1995; 60 (6): 512–521.
12. Nichols WC, Dwulet FE, Liepnieks J et al. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem Biopsys Res Commun 1988; 156 (2): 762–768.
13. Benson MD, Liepnieks J, Uemichi T et al. Hereditary renal amyloidosis associated with a mutant fibrinogen alpha-chain. Nat Genet 1993; 3 (3): 252–255.
14. Merlini G. AL amyloidosis: diagnosis and prognosis. Haematologica 2007; 92 (6) (Suppl 2): 58–59.
15. Guidelines Working Group of UK Myeloma Forum, British Commitee for Standards in Haematology, British Society for Haematology. Guidelines on the diagnosis and management of AL amyloidosis. Br J Haematol 2004; 125 (6): 681–700.
16. Ryšavá R. Systémové amyloidózy a jejich léčba. Praha: Maxdorf Jessenius 2013.
17. Yadav P, Leung N, Sanders PW et al. The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease. Kidney Int 2015; 87 (4), 692–697. doi: 10.1038/ki.2014.333.
18. Bradwell AR, Carr-Smith HD, Mead GP et al. Highly sensitive, automated immunoassay for immunoglobulin free light chains in serum and urine. Clin Chem 2001; 47 (4): 673–680.
19. te Velthuis H, Knop I, Stam P et al. N Latex FLC – new monoclonal high-performance assays for the determination of free light chain kappa and lambda. Clin Chem Lab Med 2011; 49 (8): 1323–1332. doi: 10.1515/CCLM.2011.624.
20. Hutchison CA, Basnayake K, Cockwell P. Serum free light chain assessment in monoclonal gammopathy and kidney disease. Nat Rev Nephrol 2009; 5 (11): 621–628. doi: 10.1038/nrneph.2009.151.
21. Kastritis E, Papassotiriou I, Merlini G et al. Growth differentiation factor-15 is a new biomarker for survival and renal outcomes in light chain amyloidosis. Blood 2018; 131 (14): 1568–1575. doi: 10.1182/blood-2017-12-819904.
22. Gertz MA, Comenzo R, Falk RH et al. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): a consensus opinion from the 10th International symposium on amyloid and amyloidosis, Tours, France, 18–22 April 2004. Am J Hematol 2005; 79 (4): 319–328.
23. Fikrle M, Paleček T, Kuchyňka P et al. Cardiac amyloidosis: a comprehensive review. Cor et Vasa 2013; 55 (1): e60–75.
24. Maceira AM, Joshi J, Prasad SK et al. Cardiovascular magnetic resonance in cardiac amyloidosis. Circulation 2005; 111 (2): 186–193. doi: 10.1161/01.CIR.0000152819.97857.9D.
25. Hawkins PN. Serum amyloid P component scintigraphy for diagnosis and monitoring amyloidosis. Curr Opin Nephrol Hypertens 2002; 11 (6): 649–655.
26. Palladini G, Perlini S, Merlini G. Imaging of systemic amyloidosis. In: Gertz MA, Rajkumar SV (eds). Amyloidosis: diagnosis and treatment. Springer Science and Business Media, LLC 2010; 15–32. doi: 10.1007/978-1-60761-631-3_2.
27. Rapezzi C, Quarta CC, Guidalotti PL et al. Role of (99m) Tc-DPD scintigraphy in diagnosis and prognosis of hereditary transthyretin-related cardiac amyloidosis. JACC Cardiovasc Imaging 2011; 4 (6): 659–670. doi: 10.1016/j.jcmg.2011.03.016.
28. Koop AH, Mousa OY, Wang MH. Clinical end endoscopic manifestation of gastrointestinal amyloidosis: a case series. Clujul Medical 2018; 91 (4): 469–473. doi: 10.15386/cjmed-951.
29. Said SM, Sethi S, Valeri AM et al. Renal amyloidosis: origin and clinicopathologic correlation of 474 recenet cases. Clin J Am Soc Nephrol 2013; 8 (9): 1515–1523. doi: 10.2215/CJN.10491012.
30. Sethi S, Theis JD, Leung N et al. Mass spectrometry-based proteomic diagnosis of renal immunoglobulin heavy chain amyloidosis. Clin J Am Soc Nephrol 2010; 5 (12): 2180–2187. doi: 10.2215/CJN.02890310.
31. van Gameren II, Hazenberg BP, Bijzet J et al. Diagnostic accuracy of subcutaneous abdominal fat tissue aspiration for detecting systemic amyloidosis, and its utility in clinical practice. Arthritis Rheum 2006; 54 (6): 2015–2021.
32. Picken MM. Amyloidosis – where are we now and where are we heading? Arch Pathol Lab Med 2010; 134 (4): 545–551. doi: 10.1043/1543-2165-134.4.545.
33. Pika T et al. Diagnostika a léčba systémové AL amyloidózy. Transfuze Hematologie dnes 2019. In press.
34. Gertz MA, Hayman SR. Immunoglobulin light chain amyloidosis. In: Rajkumar SV, Kyle RA. Treatment of multiple myeloma and related disorders. Cambridge: Cambridge University Press 2009: 112–128.
35. Gertz MA, Merlini G. Definition of organ involvement and response to treatment in AL amyloidosis: an updated consensus opinion. Amyloid 2010; 17: 48–49.
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Paediatric gastroenterology Gastroenterology and hepatology Medical genetics Surgery Cardiology NeurologyArticle was published in
Gastroenterology and Hepatology
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