Systemic Amyloidosis

A negative tissue biopsy does not rule out the diagnosis of amyloidosis as it may be patchy except for the heart, where the disease is usually widespread if there are echo changes

About

• Amyloid is a waxy substance formed by protein with a secondary structure of beta-pleated sheets
• Deposition within organs which cannot be broken down and removed leading to dysfunction
• There is usually a smaller protein molecule from which the amyloid is formed

Aetiology

• Amyloid stains with apple-green birefringence when stained with Congo red and examined under polarized light
• B2 microglobulin amyloid is associated with renal dialysis and causes carpal tunnel syndrome and osteonecrosis
• It is deposited in tissues and may cause local damage. Clinical effects may be significant.
• Difficult if not impossible for normal tissue macrophages to digest and remove.
• By electron microscopy, the fibrils are seen to be non-branching, with a consistent diameter of 7.5 to 10 nm.

Different types

Clinical Red flags to suggest Systemic Amyloidosis

• Nephrotic syndrome and Heavy proteinuria
• Autonomic neuropathy (eg, postural hypotension, diarrhoea)
• Carpal tunnel syndrome
• Peripheral sensorimotor neuropathy, Neuropathic pain or sensory disturbances
• Macroglossia, carpal tunnel syndrome, respiratory disease
• Bleeding (e.g., cutaneous, such as periorbital, gastrointestinal), malnutrition/cachexia and genetic predisposition (eg, family history, ethnicity).
• Cardiac disease, Heart failure, Syncope is common and a poor prognostic sign, Pleural and pericardial effusions and atrial arrhythmias are often

Investigations

• FBC, ESR, U&E, Calcium, ECG, CXR
• LFT: low albumin, low protein, raised bilirubin
• Myeloma screen: Plasma protein electrophoresis and Bence-Jones protein and skeletal survey or CT
• Rectal biopsy: Amyloid deposition can be found in the fat and histological examination of a sample obtained by needle aspiration of the subcutaneous abdominal fat has a high diagnostic yield. Congo red staining (leading to green birefringence with polarized microscopy)
• CT: hepatomegaly, splenomegaly
• Determination of amyloid type: Immunohistochemistry, DNA analysis, and proteomics. Protein/gene analysis: transthyretin mutations
• Echocardiogram: cardiomegaly, diastolic abnormalities, increased wall thickness, restrictive cardiomyopathy . “speckled” pattern with increased echo signal
• Nerve conduction tests and autonomic testing

Management

• Supportive and manage cause
• Primary Amyloidosis (AL): manage myeloma
• Secondary Amyloidosis (AA): manage cause
• Familial Amyloidosis (ATTR): liver transplantation considered definitive therapy
• Beta-2 Microglobulin Amyloid (B2M): renal transplantation