What is meant by amyloid?

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Amyloid is an abnormal fibrillar protein that is deposited in the extracellular tissue.
The proteins are deposited in a rigid, mesh-like, sheet structure.

What is amyloidosis or amyloid degeneration?

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Amyloidosis is a life-threatening condition in which there is deposition of abnormal fibrillar proteins known as amyloid in the extracellular tissue.

Why do amyloid deposits in chronic infection not resolve?

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Humans are susceptible to the complications of the amyloid protein because they have no enzyme that can break this structure down.

What are the common sites of amyloid deposition?

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Based on the clinical features of AL and AA amyloidosis common sites of amyloid deposition include:
Kidneys (leading to proteinuria and nephrotic syndrome)
Heart (leading to restrictive cardiac disease and arrhythmias)
Liver (Hepatomegaly)
Spleen (Splenomegaly)
Nervous System (Peripheral neuropathy, carpal tunnel syndrome, autonomic neuropathy)
Gastro-intestinal tract (Macroglossia, bleeding, poor absorption)

What are the different types of amyloid protein?

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AL protein (associated with Multiple Myeloma/Immunocyte dyscrasias, i.e., Primary amyloidosis)
AA protein (associated with Chronic inflammatory conditions e.g., T.B., Rheumatoid arthritis, Secondary amyloidosis)
β₂ or microglobulin (Aβ₂m) protein (associated with Chronic renal failure or dialysis, i.e., Hemodialysis-associated amyloidosis).
Note: Familial amyloidosis is also mentioned, caused by a mutation in transthyretin.

Which type of amyloidosis occurs in chronic inflammation?

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AA amyloidosis (or Secondary amyloidosis) occurs in chronic inflammation.
Examples of chronic inflammatory conditions include:
-Rheumatoid arthritis (commonest cause of AA amyloid in the UK)
-Inflammatory bowel disease
-Tuberculosis (T.B.)
-Bronchiectasis
-Osteomyelitis
-Renal cell carcinoma

What are the main clinical findings in amyloidosis?

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The clinical features depend on the type (AL vs. AA) and organs involved.
The patient description in your prompt suggests AL amyloidosis due to the presence of:
-Progressive ankle swelling / Pitting pedal oedema (suggests kidney/cardiac involvement)
-Frothy urine / 3+ Proteinuria (Kidney involvement: Proteinuria and nephrotic syndrome)
-Fatigue
-Numbness in his feet (Nervous system involvement: Peripheral neuropathy)
-Large, firm tongue / Macroglossia (Gastro-intestinal tract involvement)
-Hepatomegaly (Liver involvement)

How is amyloidosis classified?

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Amyloidosis is classified by the protein and the system involved.
Classification by Protein Involved (Systemic/Generalized Amyloidosis)
• AL amyloid
(Immunocyte dyscrasias with monoclonal B-cell proliferations like Multiple myeloma)
• AA amyloid
(Chronic inflammatory conditions)
• Familial amyloidosis
(Autosomal dominant disorder, commonly caused by a mutation in transthyretin)
Classification by Clinical Type
• Primary Amyloidosis:
Associated with Immunocyte dyscrasias (e.g., Multiple myeloma), involving the AL protein.
• Secondary Amyloidosis:
Associated with Chronic inflammatory conditions (e.g., T.B., bronchiectasis), involving the AA protein.
• Haemodialysis-associated amyloidosis:
Associated with Chronic renal failure or dialysis, involving the β₂-microglobulin (Aβ₂m) protein.

How to test for amyloidosis?

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Blood and urine tests may provide hints about the diagnosis, but the gold standard for detecting amyloid deposits is to perform Congo red staining on a tissue sample, which appears apple-green when viewed with a polarizing microscope. Laser microdissection followed by mass spectrometry can determine the type of amyloid in virtually 100% of cases.