Amyloidosis
Definition
Amyloidosis refers to a group of diseases characterized by extracellular deposition of abnormal, misfolded protein fibrils (amyloid) in various tissues and organs, impairing their function.
Classification
- 1 According to distribution
- 2 According to biochemical type (precursor protein)
Etiology
Primary (AL type)
- Clonal plasma cell disorders → overproduction of light chains.
- Example: multiple myeloma.
Secondary (AA type)
- Chronic inflammatory conditions:
- Rheumatoid arthritis.
- Chronic infections (e.g., tuberculosis, osteomyelitis).
- Inflammatory bowel disease.
Hereditary forms
- Mutations in transthyretin (ATTR).
Age-related (senile) forms
- Deposition of wild-type transthyretin in elderly.
Localized forms
- Alzheimer’s disease (Aβ in brain).
- Islet amyloid polypeptide in type 2 diabetes (in pancreatic islets).
Pathogenesis
- Chronic overproduction or misfolding of specific precursor proteins.
- These proteins aggregate into β-pleated sheet fibrils, forming amyloid.
- Amyloid deposits in extracellular spaces → tissue compression and disruption.
- Causes progressive organ dysfunction.
Clinical manifestations
General features
- Symptoms vary depending on organ involvement.
- Often present with non-specific symptoms: fatigue, weight loss.
Kidney
- Most common organ involved.
- Proteinuria → nephrotic syndrome → chronic renal failure.
Heart
- Restrictive cardiomyopathy → diastolic dysfunction, heart failure.
- Arrhythmias.
Liver and spleen
- Hepatomegaly, splenomegaly.
Gastrointestinal tract
- Malabsorption.
- Diarrhea or constipation.
- Macroglossia (especially in AL type).
Nervous system
- Peripheral neuropathy.
- Autonomic neuropathy → orthostatic hypotension, GI dysmotility.
Skin
- Purpura ("pinch purpura"), especially periorbital ("raccoon eyes").