Amyloidosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]

Overview

In 1639, Nicolaus Fontanus autopsied a young man who had ascitis, jaundice, liver abscess and splenomegaly and his report has been the first description of amyloidosis.
In 1854, Rudolph Virchow introduced the term of amyloid as an macroscopic abnormality in some tissues.
In 1867, Weber reported the first case of amyloidosis associated with multiple myeloma.
In 1922, Bennhold introduced Congo red staining of amyloid that remains the gold standard for diagnosis.
In 1959, Cohen and Calkins used ultra-thin sections of amyloidotic tissues and assessed by electron microscopic examination, explained the presence of non-branching fibrils with indeterminate length and variable width.^[1]

Type	Amyloidogenic protein/ fibril	Clinical syndrome
AL (primary amyloidosis)	Light chains of immunoglobulines (most common type)	Monoclonal gammopathy
AA (secondary amyloidosis)	Serum amyloid A protein	Chronic inflammatory diseases
AF	Mutant transthyretin, A1-apolipoprotein, gelsolin, fibrinogen, etc.	Familial polyneuropathy/cardiomyopathy/nephropathy
ATTRwt	Wild-type transthyretin	Senile restrictive cardiomyopathy _ Transthyretin-related amyloidosis wild-type
AH	ß2-microglobulin	Long-term hemodialysis

Classification	subtypes	Causes	Important clinical findings
Systemic amyloidosis	Primary amyloidosis (AL)	Aggregation and deposition of immunoglobulin light chains that usually produced by plasma cell clones	Nephrotic syndrome Restrictive cardiomyopathy Peripheral neuropathy Hepatomegaly with elevated liver enzymes Macroglossia Purpura and an unexplained bleeding diathesis
	Secondary amyloidosis (AA)	Chronic inflammation (TB, familial mediterranean fever, rheumatoid arthritis and multiple myeloma)	Nephrotic syndrome Heart failure
	Hereditary amyloidosis	Amyloidogenic mutations and subsequently deposition of amyloids	Heart failure Arrhythmia
Organ-specific amyloidosis	Renal amyloidosis	Immunoglobulin light-chain amyloidosis (AL amyloidosis) Transthyretin-related amyloidosis (associated with familial/mutant or senile/wild-type TTR)	Proteinuria Nephrotic syndrome Chronic renal failure
	Cardiac amyloidosis		Systolic dysfunction Diastolic dysfunction Arrhythmia
	Hepatic amyloidosis		Hepatomegaly Elevated liver enzymes
	Amyloid neuropathy		Peripheral neuropathy and autonomic neuropathy Neurodegenerative disorders Parkinson, Alzheimer, and Huntington's disease
	Gastrointestinal amyloidosis		Nonspecific findings Dyspepsia, abdominal pain, diarrhea, malabsorption

In amyloidosis, insoluble fibrils of amyloid are deposited in body organs, causing organ dysfunction and eventually death.^[2]
In AL amyloidosis untreated individuals have the worst prognosis. In this group of patients median survival is one to two years.^[3]

In patients with amyloidosis the most frequent complications include:^[4]

In primary (AL) amyloidosis survival rate depends on:^[5]

The median survival of patients with AL amyloidosis is aproximately 3.8 years.^[6]
In primary (AL) amyloidosis 27% of patients dying within 1 year from diagnosis.
The major determinant of outcome in amyloidosis is the extent of cardiac involvement.
- Cardiac amyloidosis is the cause of death in 75% of the patients who died, including sudden death in 25%.

↑ Kyle RA (June 2011). "Amyloidosis: a brief history". Amyloid. 18 Suppl 1: 6–7. doi:10.3109/13506129.2011.574354001. PMID 21838413.
↑ Baker KR, Rice L (2012). "The amyloidoses: clinical features, diagnosis and treatment". Methodist Debakey Cardiovasc J. 8 (3): 3–7. PMC 3487569. PMID 23227278.
↑ Khan MF, Falk RH (November 2001). "Amyloidosis". Postgrad Med J. 77 (913): 686–93. PMC 1742163. PMID 11677276.
↑ Jerzykowska S, Cymerys M, Gil LA, Balcerzak A, Pupek-Musialik D, Komarnicki MA (2014). "Primary systemic amyloidosis as a real diagnostic challenge - case study". Cent Eur J Immunol. 39 (1): 61–6. doi:10.5114/ceji.2014.42126. PMC 4439975. PMID 26155101.
↑ Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, Quellard N, Lacombe C, Goujon JM, Lavergne D, Abraham J, Touchard G, Fermand JP, Jaccard A (August 2012). "Al amyloidosis". Orphanet J Rare Dis. 7: 54. doi:10.1186/1750-1172-7-54. PMC 3495844. PMID 22909024.
↑ Merlini G, Seldin DC, Gertz MA (May 2011). "Amyloidosis: pathogenesis and new therapeutic options". J. Clin. Oncol. 29 (14): 1924–33. doi:10.1200/JCO.2010.32.2271. PMC 3138545. PMID 21483018.