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 #Amyloidosis #Diagnosis #Amyloid
