Amyloidosis - Summary

Group of disorders associated with extracellular deposition of fibrils formed from low-molecular-weight proteins in a B-pleated sheet configuration



Types Of Amyloidosis:

• Primary amyloid amyloidosis (AL): immunocyte dyscrasias

• Secondary amyloid A (AA) → Chronic Inflammatory Conditions (Tuberculosis, Bronchiectasis, Chronic osteomyelitis, Rheumatoid arthritis, Ankylosing spondylitis, IBD)

• Familial amyloidosis

• Senile amyloidosis

• Dialysis-related amyloidosis: (β2-microglobulin)

• Heavy-chain (AH) amyloidosis



Amyloidosis Diagnosis:

1. Clinical suspicion

2. Visualization of the protein

3. Characterization of the precursor

4. Identification of the extent of disease



Amyloidosis Clinical Manifestations:

Renal:

• Nephrotic syndrome

• Proteinuria

• Can detect early if there is a "protein-albumin" dissociation in urine

• Amyloid nephropathy is common in AA and AL

Cardiac:

• LVH, low-voltage EKG, & restrictive cardiomyopathy

GI:

• Diarrhea, malabsorption, and pseudo-obstruction

• Hepatosplenomegaly & hepatic failure

• GI bleeding

Neuro:

• Orthostatic hypotension

• Autonomic neuropathy, Peripheral neuropathy causing paresthesias, muscle wasting

Bone/Joint:

• Amyloid arthropathy

• Carpal tunnel syndrome

Muscles:

• Infiltration of muscles

Skin:

• Periorbital purpura and macroglossia

Nails:

• Dystrophy

Heme:

• ↓ activity of factor X, vascular infiltration with amyloid (AMYLOID ANGIOPATHY)



AL Protein:

Monoclonal B Cell Lymphocyte Proliferation → Increased plasma cells → Immunoglobulin light chains → AL Protein

• AL Amyloid: Immunoglobulin light chains as part of plasma-cell dyscrasias

• K or L Immunoglobulin light chain



AA Protein:

Chronic Inflammatory Conditions/Recurring Inflammation → Macrophage activation → IL-1 & IL-6 → AA Protein

• Circulating inflammatory protein



ATTR Protein:

Transthyretin TTR → Mutant TTR → ATTR Protein



When To Suspect Amyloidosis?

• Severe fatigue

• Nail dystrophy, waxy or thickened skin

• Persistent pleural effusions

• Parenchymal nodules (amyloidomas)

• Hepatomegaly: Bruising

• Primary hypoadrenalism

• Nausea/vomiting, malabsorption

• Poor appetite, unintentional weight loss

• Eyelid swelling

• Glaucoma, floaters, periorbital purpura

• Restrictive cardiomyopathy

• Conduction abnormalities, arrhythmia

• Palpable spleen

• Peripheral neuropathy: Carpal tunnel, neuropathy, orthostatic hypotension "glove and stocking" peripheral neuropathy



Amyloidosis Diagnostic Testing

Blood Tests:

• SPEP with Serum immunofixation

• Free light-chain assay, troponin, NT-proBNP

• Creatinine, albumin, alkaline phosphatase, uric acid

Urine Tests:

• UPEP with Urine Immunofixation

• Tissue biopsy-Congo red

• Amyloid typing

Cardiac Testing:

• EKG

• Echocardiogram with Doppler imaging: Normal-size ventricles with disproportionate atrial enlargement

• MRI of the heart

GI Tests:

• Diagnostic imaging of liver and spleen

• Fecal fat measurements

• Serum carotene levels

Nerve Tests:

• Nerve conduction studies

• Other: Serum amyloid P scintigraphy

Biopsies:

• (Subcutaneous fat, minor salivary glands, or rectal mucosa)

• Congo red: apple-green birefringence under polarized light microscopy

• Immunohistochemical staining: Light-chain nature of the amyloid



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