Signs and Symptoms of Amyloidosis
Amyloidosis presents with a myriad of nonspecific symptoms that vary depending on the organs involved, making early recognition challenging but crucial for preventing irreversible organ damage. 1
Clinical Manifestations by Organ System
Cardiac Manifestations
- Heart failure with preserved ejection fraction (HFpEF)
- Restrictive cardiomyopathy
- Elevated cardiac biomarkers (troponin T, NT-proBNP)
- Arrhythmias
- Orthostatic hypotension
Renal Manifestations
- Nephrotic range proteinuria
- Progressive renal dysfunction
- Albuminuria (may appear before overt nephrotic syndrome)
Gastrointestinal Manifestations
- Early satiety
- Weight loss
- Abdominal pain
- Nausea and vomiting
- Constipation or diarrhea
- Malabsorption
- GI bleeding
- Pseudo-obstruction (particularly poor prognosis) 2
Neurological Manifestations
- Peripheral neuropathy (especially small fiber involvement)
- Autonomic dysfunction
- Carpal tunnel syndrome
- Painful sensory neuropathy
- Progressive motor deficits 3
Soft Tissue/Musculoskeletal Manifestations
- Macroglossia (enlarged tongue) - particularly in AL amyloidosis
- Submandibular gland enlargement
- Periorbital purpura
- Biceps tendon rupture (more common in ATTR amyloidosis)
- Spinal stenosis (more common in ATTR amyloidosis) 1
Hepatic Manifestations
Pulmonary Manifestations
- Dyspnea
- Septal and parenchymal infiltrates
- Nodular infiltrates
- Pleural effusions
- Cysts
- Lymphadenopathy 5
Constitutional Symptoms
- Fatigue
- Weight loss
- General malaise 1
Distinguishing Features Between Types of Amyloidosis
AL Amyloidosis (Primary)
- Macroglossia and submandibular gland enlargement
- Periorbital purpura
- Coagulopathy (acquired factor X deficiency)
- Associated with monoclonal light chains in serum/urine
- 15% of patients have multiple myeloma 1, 2
ATTR Amyloidosis (Transthyretin)
- Musculoskeletal manifestations (biceps tendon rupture, spinal stenosis)
- Cardiomyopathy (especially in wild-type ATTR)
- Peripheral and autonomic neuropathy (especially in hereditary ATTR) 1
Diagnostic Challenges
The diagnosis of amyloidosis is often delayed due to:
- Nonspecific and vague symptoms
- Multiple organ involvement with varying presentations
- Symptoms that mimic more common conditions
High-risk populations who should be screened regularly include:
- Patients with monoclonal gammopathy of undetermined significance (MGUS)
- Patients with unexplained heart failure with preserved ejection fraction
- Patients with unexplained proteinuria
- Patients with peripheral neuropathy of unknown origin 1
Red Flags for Amyloidosis
Consider amyloidosis in patients presenting with:
- Proteinuria
- Cardiomyopathy
- Hepatomegaly with mildly abnormal liver tests
- Peripheral and autonomic neuropathy
- Weight loss
- GI symptoms without clear etiology 2
Early recognition and diagnosis are essential as treatment effectiveness depends on initiating therapy before irreversible organ damage occurs 1. The definitive diagnosis requires tissue biopsy with Congo Red staining, which shows characteristic apple-green birefringence under polarized light 2.