Symptoms of Amyloidosis
Amyloidosis presents with a wide spectrum of clinical manifestations that vary depending on the type of amyloid protein and the organs involved, with the most common symptoms including fatigue, weight loss, edema, dyspnea, paresthesias, and early satiety. 1
Common Systemic Symptoms
- Fatigue and general malaise
- Unintentional weight loss
- Edema (swelling)
- Lightheadedness or syncope
Organ-Specific Symptoms
Cardiac Manifestations
- Dyspnea (shortness of breath)
- Heart failure with preserved ejection fraction
- Restrictive cardiomyopathy
- Electrocardiographic abnormalities 1
Gastrointestinal Manifestations
- Early satiety
- Nausea and vomiting
- Abdominal pain
- Constipation and/or diarrhea
- Malabsorption with bloating 2
- Hepatomegaly with right upper quadrant pain 1
Neurologic Manifestations
- Peripheral neuropathy with paresthesias (numbness and tingling)
- Autonomic neuropathy leading to:
- Orthostatic hypotension
- GI dysmotility
- Sexual dysfunction 3
- Carpal tunnel syndrome 4
Renal Manifestations
Soft Tissue and Musculoskeletal Manifestations
- Macroglossia (enlarged tongue) - particularly common in AL amyloidosis 4
- Submandibular gland enlargement
- Periorbital purpura ("raccoon eyes")
- Biceps tendon rupture
- Spinal stenosis 1
- Muscle weakness (in amyloid myopathy) 3
Clinical Presentation by Amyloidosis Type
AL Amyloidosis (Immunoglobulin Light Chain)
- Most commonly affects the heart and kidneys
- Higher frequency of macroglossia (26%) 4
- Carpal tunnel syndrome
- Purpura, particularly around the eyes
- Nephrotic syndrome
- Peripheral neuropathy 5
ATTR Amyloidosis (Transthyretin)
- Cardiac involvement with heart failure
- Peripheral and autonomic neuropathy
- GI symptoms (more common in neuropathic variants) 2
- Better survival compared to AL amyloidosis 1
Red Flags for Diagnosis
- 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 1
Important Diagnostic Considerations
The symptoms of amyloidosis are often nonspecific, leading to delayed diagnosis. Early recognition is crucial as treatment effectiveness depends on initiating therapy before irreversible organ damage occurs 1. The gold standard for diagnosis is tissue biopsy with Congo red staining, which can be obtained from affected organs or from more accessible sites like abdominal fat pad, rectum, or bone marrow 2, 1.
It's important to note that symptoms may be caused by direct amyloid infiltration of organs or by indirect effects such as autonomic neuropathy affecting organ function. For example, GI symptoms may occur even without direct mucosal deposition of amyloid fibrils 2.