What are the clinical features of amyloidosis?

Clinical Features of Amyloidosis

Amyloidosis is characterized by extracellular deposition of misfolded proteins in multiple organs, with the heart and kidneys being most commonly affected, leading to progressive organ dysfunction and potential failure. 1, 2

Types of Amyloidosis and Survival

• Primary (AL) amyloidosis: Most common type, involves light chain proteins

  • Cardiac involvement in up to 50% of cases
  • Median survival of 13 months (only 4 months if heart failure present)
  • Extracardiac manifestations: kidney, liver, nervous system, skin, carpal tunnel syndrome 1

• Hereditary (ATTRv) amyloidosis: Involves mutant transthyretin

  • Median survival of 70 months
  • Extracardiac manifestations: kidney, nervous system, blindness 1

• Senile (wild-type ATTR) amyloidosis: Involves transthyretin

  • Median survival of 75 months
  • Common cardiac involvement 1

• Reactive (AA) amyloidosis: Involves amyloid A protein

  • Cardiac involvement in <10% of cases
  • Median survival of 25 months
  • Extracardiac manifestations: kidney, liver 1

• Dialysis-related amyloidosis: Involves β-microglobulin 2

  • Affects joints, carpal tunnel syndrome, skeletal system 1

Organ Involvement

Cardiac Manifestations

• Increased myocardial stiffness leading to diastolic dysfunction
• Elevated filling pressures progressing to diastolic heart failure
• Restrictive cardiomyopathy phenotype
• Normal heart size with preserved systolic function initially
• Systolic dysfunction with disease progression
• Conduction abnormalities (atrioventricular block)
• Atrial tachyarrhythmias
• Reduced QRS voltage amplitude on ECG (in ~50% of cases)
• Pseudoinfarct pattern in precordial leads
• Atrial fibrillation 1, 2

Renal Manifestations

• Proteinuria (often nephrotic range)
• Progressive renal dysfunction 2

Neurologic Manifestations

• Peripheral neuropathy
• Autonomic neuropathy
• Paresthesias 2, 3

Gastrointestinal Manifestations

• Malabsorption
• Early satiety
• Weight loss
• Nausea and vomiting
• Abdominal pain
• Constipation
• Diarrhea
• Bloating 2

Hepatic Manifestations

• Hepatomegaly
• Mildly abnormal liver tests
• Elevated alkaline phosphatase (most common laboratory abnormality) 1, 2

Soft Tissue Manifestations

• Macroglossia
• Submandibular gland enlargement
• Periorbital purpura
• Coagulopathy
• Carpal tunnel syndrome 1, 2

Musculoskeletal Manifestations

• Biceps tendon rupture
• Spinal stenosis
• Arthropathy 2

Clinical Presentation and Diagnosis

Patients with amyloidosis typically present with:

• Fatigue
• Weight loss
• Edema
• Dyspnea
• Paresthesias
• Early satiety 2

The gold standard for diagnosis is tissue biopsy with Congo red staining, which can be obtained from:

• Affected organs
• Abdominal fat pad
• Rectum
• Bone marrow 2

Important Clinical Considerations

1. Amyloidosis rarely affects just one organ - patients have a median of 2 sites involved 1

2. Early recognition is crucial as treatment effectiveness depends on initiating therapy before irreversible organ damage occurs 2

3. Consider amyloidosis in patients with:

   • Unexplained heart failure with preserved ejection fraction
   • Unexplained proteinuria
   • Peripheral neuropathy of unknown origin
   • Hepatomegaly with mildly abnormal liver tests
   • Combination of autonomic symptoms with weight loss and organ dysfunction 2

4. The relentlessly progressive nature with motor, painful sensory and severe autonomic dysfunction, profound weight loss, and systemic features are distinct characteristics of amyloid neuropathy 3

5. BNP levels can help diagnose cardiac amyloidosis with sensitivity of 93% and specificity of 90%, and can predict prognosis and mortality 1

Amyloidosis is often diagnosed late due to its vague presentation that mimics other conditions, leading to delayed treatment and poorer outcomes. Maintaining a high index of suspicion in patients with multisystem involvement is essential for early diagnosis and improved survival.