What Is Amyloidosis and What Does It Do to the Body?

What Are the Early Signs and Symptoms of Amyloidosis?

Amyloidosis often presents with vague, nonspecific symptoms that can mimic those of more common conditions. This contributes to delayed diagnosis, sometimes taking years before proper identification. Early warning signs may include unexplained fatigue and weakness, which are frequently dismissed as aging or stress-related. Swelling in the ankles and legs (edema) often occurs as protein deposits affect kidney function. Weight loss without trying is another common early indicator, as is shortness of breath, particularly during physical activity.

Some patients experience carpal tunnel syndrome as an early manifestation, especially in certain types of amyloidosis. Digestive disturbances are frequently reported, including diarrhea, constipation, or alternating between both. Skin symptoms may include easy bruising, purpura (purple patches), and thickened skin. An enlarged tongue (macroglossia), difficulty swallowing, and changes in taste sensation are distinctive symptoms that should prompt medical attention. The diversity of these symptoms reflects how amyloidosis can affect multiple body systems simultaneously.

What Causes Amyloidosis?

Amyloidosis develops when proteins that normally circulate in the blood fold incorrectly and form insoluble fibrils. These misfolded proteins deposit in tissues and organs, disrupting their structure and function. Several different types of amyloidosis exist, each caused by specific protein abnormalities.

AL amyloidosis (primary amyloidosis) is the most common form in developed countries and occurs when bone marrow produces abnormal antibody light chains. This type is often associated with multiple myeloma, a blood cancer. AA amyloidosis (secondary amyloidosis) develops as a complication of chronic inflammatory conditions like rheumatoid arthritis, inflammatory bowel disease, or chronic infections. The body produces serum amyloid A protein in response to inflammation, which can then form amyloid deposits.

Hereditary amyloidosis results from genetic mutations, most commonly affecting the transthyretin protein (TTR) produced by the liver. Wild-type ATTR amyloidosis, previously called senile systemic amyloidosis, occurs when the normal TTR protein becomes unstable with aging. Dialysis-related amyloidosis can develop in people on long-term kidney dialysis when beta-2 microglobulin protein accumulates. Localized amyloidosis affects specific areas without systemic involvement, such as the skin, bladder, or airways.

How Does Amyloidosis Affect Different Organs in the Body?

Amyloid deposits can infiltrate virtually any organ system, causing progressive dysfunction as they accumulate. When amyloid infiltrates the heart (cardiac amyloidosis), it causes the heart walls to thicken and become stiff, leading to restrictive cardiomyopathy. This reduces the heart’s ability to fill with blood and pump effectively, resulting in heart failure symptoms like fatigue, shortness of breath, and fluid retention.

Kidney involvement (renal amyloidosis) damages the filtering structures, leading to protein in urine, decreased kidney function, and eventually kidney failure. In the nervous system, amyloid deposits can affect both peripheral nerves and the autonomic nervous system. Peripheral nerve damage causes numbness, tingling, or pain in the extremities, while autonomic neuropathy affects involuntary functions like blood pressure, heart rate, and digestion.

Gastrointestinal tract involvement can cause various symptoms, including diarrhea, constipation, bleeding, and malabsorption of nutrients. When amyloid affects the liver, it typically enlarges without causing significant dysfunction until advanced stages, though liver enzymes may be abnormal in blood tests. Less commonly, amyloidosis can affect the respiratory system, causing coughing and breathing difficulties, or the skin, leading to various manifestations including waxy deposits, easy bruising, and characteristic purple patches around the eyes.

What Diagnostic Methods Are Used to Identify Amyloidosis?

Diagnosing amyloidosis requires a systematic approach, typically beginning with blood and urine tests to detect abnormal proteins. Specific tests include serum and urine protein electrophoresis and immunofixation to identify monoclonal proteins, as well as free light chain assays to measure levels of kappa and lambda light chains.

Tissue biopsy remains the gold standard for diagnosis. This involves removing a small sample of affected tissue and staining it with Congo red dye, which produces a characteristic apple-green birefringence under polarized light when amyloid is present. Common biopsy sites include fat pad, rectum, kidney, heart, liver, or the specific organ showing symptoms. Mass spectrometry can then identify the specific type of amyloid protein present.

Cardiac evaluation often includes echocardiography to assess heart wall thickness and function, electrocardiogram to detect electrical abnormalities, and cardiac MRI which may show characteristic patterns. Nuclear medicine scans like technetium pyrophosphate or DPD scans can help diagnose ATTR amyloidosis. Genetic testing is essential when hereditary amyloidosis is suspected, particularly for familial ATTR variants. Comprehensive evaluation typically requires coordination between multiple specialists, including hematologists, cardiologists, nephrologists, neurologists, and geneticists.

What Treatment Options Are Available for Amyloidosis?

Treatment approaches for amyloidosis vary based on the specific type, organs affected, and disease stage. For AL amyloidosis, targeting the underlying plasma cell disorder is crucial. Chemotherapy regimens similar to those used for multiple myeloma are often employed, including proteasome inhibitors (bortezomib, carfilzomib), immunomodulatory drugs (lenalidomide, pomalidomide), and monoclonal antibodies (daratumumab). High-dose chemotherapy followed by autologous stem cell transplantation may be an option for eligible patients.

For ATTR amyloidosis, several groundbreaking treatments have emerged recently. Tafamidis stabilizes the TTR protein, preventing it from forming amyloid fibrils, and has shown survival benefits in cardiac ATTR amyloidosis. RNA-targeting therapies like patisiran and inotersen reduce TTR production in hereditary ATTR amyloidosis by interfering with gene expression in the liver. Liver transplantation may be considered for certain patients with hereditary ATTR amyloidosis to eliminate the source of mutated protein.

AA amyloidosis treatment focuses on controlling the underlying inflammatory condition. For localized amyloidosis, surgical removal of affected tissue may be sufficient. Supportive care is essential for all types of amyloidosis and includes managing symptoms and organ dysfunction. This may involve diuretics for fluid retention, blood pressure medications, pacemaker implantation for heart rhythm abnormalities, and dietary modifications. Clinical trials continue to investigate promising new therapies, including antibodies targeting amyloid deposits and gene editing approaches.

This article is for informational purposes only and should not be considered medical advice. Please consult a qualified healthcare professional for personalized guidance and treatment.