What are the symptoms of amyloidosis?

Symptoms of Amyloidosis

Amyloidosis presents with highly variable, nonspecific symptoms that depend entirely on which organs are affected, making early recognition challenging but critical since treatment is most effective before irreversible organ damage occurs.

Cardiac Manifestations

The heart is one of the two most frequently affected organs in systemic amyloidosis 1:

• Heart failure with preserved ejection fraction (HFpEF) is a hallmark presentation, often with restrictive features 1, 2
• Patients may experience dyspnea, fatigue, and exercise intolerance 1
• Volume overload can cause hepatic congestion, resulting in abdominal pain and nausea that may mimic primary gastrointestinal involvement 3

Renal Manifestations

The kidneys are the second most commonly affected organ 1:

• Nephrotic range proteinuria is characteristic, presenting as edema, foamy urine, and hypoalbuminemia 1, 2
• Patients should be screened for rising albuminuria even before overt nephrotic syndrome develops 1
• This can progress to renal failure requiring dialysis 4

Gastrointestinal Manifestations

GI involvement occurs through multiple mechanisms including mucosal involvement, autonomic neuropathy causing dysmotility, and vascular involvement 3:

• Weight loss is extremely common and often profound 1, 5
• Chronic diarrhea or alternating diarrhea and constipation, particularly night diarrhea 1, 5
• Early satiety and nausea from gastroparesis or gastric outlet obstruction 6, 3
• Abdominal pain and altered bowel habits 6, 5
• GI bleeding from mucosal involvement 1, 5
• Malabsorption leading to significant malnutrition 1, 3

Neurologic Manifestations

Peripheral and autonomic neuropathy are prominent, especially in AL and ATTRv amyloidosis 1, 7:

Peripheral Neuropathy

• Distal sensory symptoms beginning symmetrically in toes and feet: numbness, paresthesias, burning pain, and dysesthesias 1, 2
• Symptoms worsen at night or end of day 1
• Progressive weakness starting in toe extensors and ankle dorsiflexors 1
• Gait imbalance from proprioceptive loss 1
• Progresses 15-20 times more rapidly than diabetic neuropathy 1

Autonomic Dysfunction

• Orthostatic hypotension (dizziness upon standing) 1, 7
• Urinary retention and sexual dysfunction 1
• Severe autonomic symptoms are characteristic of amyloid neuropathy 7

Soft Tissue and Organ Enlargement (Primarily AL Amyloidosis)

These are highly specific but insensitive signs 1, 8:

• Macroglossia (enlarged tongue) - pathognomonic when present 1
• Submandibular gland enlargement 1
• Hepatomegaly without imaging abnormalities 1, 2
• Periorbital purpura (bruising around eyes) - highly specific 8

Constitutional Symptoms

• Profound fatigue affecting quality of life 1, 4
• Unexplained weight loss, often severe 1, 5

Key Clinical Pitfalls

The nonspecific nature of symptoms leads to frequent misdiagnosis and delayed treatment 1, 8. By the time symptoms surface, organ damage has already occurred 1. Consider amyloidosis in:

• Adult nondiabetic nephrotic syndrome 2
• HFpEF with restrictive features 2
• Peripheral neuropathy with prominent autonomic features 7, 2
• Monoclonal gammopathy of undetermined significance (MGUS) with atypical features 1, 2
• Unexplained hepatomegaly 2

High-risk populations (particularly MGUS patients) benefit from regular screening with NT-proBNP and albuminuria monitoring before overt symptoms develop 1. Early diagnosis is paramount since all forms now have approved therapies that improve survival, disability, and quality of life, but only if initiated before severe end-organ damage occurs 2.