Symptoms of Amyloidosis
Amyloidosis presents with a diverse range of symptoms affecting multiple organ systems, most commonly involving the heart and kidneys, with patients typically having a median of 2 sites involved. 1
Cardiac Manifestations
- Heart failure with preserved ejection fraction
- Restrictive cardiomyopathy
- Electrocardiographic abnormalities:
- Reduced QRS voltage amplitude
- Conduction abnormalities (atrioventricular block)
- Atrial tachyarrhythmias 1
Renal Manifestations
- Proteinuria (often in nephrotic range)
- Progressive renal dysfunction 1
Gastrointestinal Manifestations
- Early satiety
- Weight loss
- Abdominal pain
- Nausea
- Alternating constipation and diarrhea
- Malnutrition and wasting 2, 1
Neurological Manifestations
- Peripheral neuropathy:
- Distal sensory loss
- Numbness, pain, and weakness
- Wide-based unsteady gait 2
- Autonomic dysfunction:
- Orthostatic hypotension
- Urinary retention
- Erectile dysfunction 2
- Carpal tunnel syndrome (often precedes polyneuropathy by many years) 2
- Lumbar stenosis or lumbosacral radiculopathy 2
Hepatic Manifestations
- Hepatomegaly
- Mildly abnormal liver tests
- Elevated alkaline phosphatase 1
Soft Tissue and Other Manifestations
- Macroglossia (enlarged tongue)
- Submandibular gland enlargement
- Periorbital purpura (distinctive bruising around eyes)
- Coagulopathy
- Biceps tendon rupture
- Spinal stenosis 1
Type-Specific Presentations
Primary (AL) Amyloidosis
- Most common type
- Cardiac involvement in up to 50% of cases
- Median survival of only 13 months (4 months if heart failure present) 1
Hereditary (ATTRv) Amyloidosis
- Involves mutant transthyretin
- Median survival of 70 months
- Prominent neurologic symptoms
- Extracardiac manifestations including kidney, nervous system involvement 1
Senile (wild-type ATTR) Amyloidosis
- Common cardiac involvement
- Median survival of 75 months 1
Clinical Pearls
- Early recognition is crucial as treatment effectiveness depends on initiating therapy before irreversible organ damage occurs 1
- Consider amyloidosis in patients with unexplained heart failure with preserved ejection fraction, unexplained proteinuria, and peripheral neuropathy of unknown origin 1
- The combination of proteinuria, cardiomyopathy, hepatomegaly with mildly abnormal liver tests, peripheral/autonomic neuropathy, weight loss, and GI symptoms without clear etiology should prompt consideration of amyloidosis 1
- Amyloidosis is often underdiagnosed, with 25% of patients with AL amyloidosis dying within 6 months of diagnosis 3
Warning Signs That Should Prompt Investigation
- Unexplained heart failure with preserved ejection fraction
- Adult nondiabetic nephrotic syndrome
- Peripheral neuropathy with distal sensory symptoms
- Unexplained hepatomegaly without imaging abnormalities
- Monoclonal gammopathy with atypical clinical features 3
Remember that symptoms vary based on the type of amyloidosis and organs affected, but multisystem involvement is characteristic of this disease.