Amyloidosis

Amyloidosis is a rare disease characterized by the abnormal accumulation of amyloid proteins in organs and tissues. This buildup can disrupt normal function and lead to organ damage. Amyloidosis symptoms may include weight loss, swelling, and organ dysfunction.

Amyloidosis treatment helps to manage symptoms, slow the progression of the disease, and address underlying conditions that may contribute to amyloidosis. In this article, we will study the meaning of amyloidosis, its types, stages of development, causes, symptoms, and treatment in detail.

Amyloidosis is a rare disease that occurs when abnormal proteins, called amyloid fibrils, build up in tissue throughout the body. These deposits can affect one organ or multiple and can build up in the heart, brain, kidneys, spleen, and other parts. Amyloidosis can be primary (due to abnormal production of amyloid proteins) or secondary (resulting from chronic inflammatory conditions or other diseases). In advanced stages, amyloidosis can lead to organ dysfunction and failure, highlighting the importance of early detection and management of this condition.

The types of amyloidosis are:

Primary (AL) Amyloidosis

• Primary amyloidosis is caused by the abnormal production of immunoglobulin light chains (amyloid L or AL protein) by plasma cells in the bone marrow.
• It primarily affects the heart, kidneys, liver, nerves, and gastrointestinal tract.
• Symptoms may include heart failure, kidney dysfunction, neuropathy, and gastrointestinal disturbances.

Secondary (AA) Amyloidosis

• Secondary amyloidosis occurs as a complication of chronic inflammatory or infectious diseases, such as rheumatoid arthritis, tuberculosis, or inflammatory bowel disease.
• It is characterized by the deposition of serum amyloid A protein (SAA) derived from acute-phase reactants produced in response to inflammation.
• Secondary amyloidosis commonly affects the kidneys, liver, spleen, and adrenal glands.
• Treatment involves managing the underlying inflammatory condition.

Hereditary (ATTR) Amyloidosis

• Hereditary amyloidosis results from mutations in the transthyretin (TTR) gene, leading to the production of abnormal transthyretin protein.
• It can manifest as familial amyloid polyneuropathy (FAP), familial amyloid cardiomyopathy (FAC), or familial leptomeningeal amyloidosis (FLA).
• Symptoms vary depending on the specific mutation but commonly involve peripheral neuropathy, cardiomyopathy, and gastrointestinal dysfunction.
• Treatment may include liver transplantation, gene-silencing therapies, or TTR stabilizers.

Dialysis-Related Amyloidosis

• Dialysis-related amyloidosis occurs in individuals undergoing long-term hemodialysis or peritoneal dialysis.
• It results from the accumulation of beta-2 microglobulin protein (β2M) in joints, tendons, and bones, leading to musculoskeletal symptoms such as joint pain and stiffness.
• Treatment may involve optimizing dialysis techniques and kidney transplantation to reduce β2M levels.

Senile Systemic Amyloidosis

• Senile systemic amyloidosis primarily affects older individuals, over the age of 70.
• It is characterized by the deposition of wild-type transthyretin protein, particularly in the heart.
• Senile systemic amyloidosis may lead to heart failure with preserved ejection fraction (HFpEF) and other cardiovascular complications.

Localized Amyloidosis

• Localized amyloidosis involves the deposition of amyloid protein in specific organs or tissues, without systemic involvement.
• Examples include cerebral amyloid angiopathy (amyloid deposition in cerebral blood vessels), cutaneous amyloidosis (amyloid deposits in the skin), and laryngeal amyloidosis (amyloid accumulation in the larynx).
• Treatment varies depending on the affected organ and may include surgical excision or localized radiotherapy.

The stages of amyloidosis are:

Localized Amyloidosis

• Amyloid deposits are confined to specific organs or tissues.
• Symptoms may be mild or absent, depending on the location and extent of deposits.
• Examples include cutaneous amyloidosis (skin), laryngeal amyloidosis (larynx), and cerebral amyloid angiopathy (blood vessels in the brain).

Systemic Amyloidosis

• Amyloid deposits spread to multiple organs and tissues throughout the body.
• Commonly affected organs include the heart, kidneys, liver, nerves, and gastrointestinal tract.
• Symptoms become more widespread and may include fatigue, weight loss, edema, neuropathy, and gastrointestinal disturbances.

Organ Dysfunction

• Accumulation of amyloid deposits leads to impairment of organ function.
• Symptoms become more severe as organ dysfunction progresses.
• Heart failure, kidney failure, neuropathy, hepatomegaly, and gastrointestinal complications may occur.

End-Stage Disease

• Multiple organ failure occurs, leading to life-threatening complications.
• Patients may experience severe symptoms such as cardiomyopathy, renal failure, neuropathy, and gastrointestinal bleeding.
• Without timely intervention, end-stage amyloidosis can be fatal.

Causes of amyloidosis includes:

• Abnormal Protein Production: Primary (AL) amyloidosis occurs when abnormal plasma cells in the bone marrow produce excess immunoglobulin light chains, which form amyloid fibrils.
• Chronic Inflammatory or Infectious Conditions: Secondary (AA) amyloidosis develops in response to chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, or chronic infections like tuberculosis.
• Aging and Degenerative Disorders: Senile systemic amyloidosis is associated with aging and the accumulation of wild-type transthyretin (TTR) amyloid deposits, primarily affecting the heart.
• Long-Term Dialysis Treatment: Dialysis-related amyloidosis occurs in individuals undergoing long-term hemodialysis or peritoneal dialysis for end-stage renal disease.
• Unknown Causes (Idiopathic): Idiopathic cases may involve a combination of genetic predisposition, environmental factors, or other underlying conditions that contribute to abnormal protein folding and amyloid formation.

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Symptoms of Amyloidosis includes:

• Fatigue: Feeling tired or exhausted even after adequate rest.
• Swelling (Edema): Swelling in the ankles, legs, or other parts of the body due to fluid accumulation.
• Shortness of Breath: Difficulty in breathing, especially during physical activity or when lying down.
• Weight Loss: Due to loss of appetite or underlying organ dysfunction.
• Weakness: Reduced strength or muscle weakness, affecting daily activities.
• Numbness and Tingling: Peripheral neuropathy, causing sensations of numbness, tingling, or pain in the hands and feet.
• Orthostatic Hypotension: Drop in blood pressure upon standing, leading to dizziness or lightheadedness.
• Gastrointestinal Symptoms: Digestive issues such as diarrhea, constipation, or difficulty swallowing.
• Enlarged Organs: Enlargement of the liver (hepatomegaly) or spleen (splenomegaly), which may cause abdominal discomfort.
• Skin Changes: Changes in skin color or texture, such as easy bruising or purplish patches.
• Heart-related Symptoms: Symptoms may include palpitations, chest pain, or shortness of breath due to heart involvement.
• Kidney Problems: Proteinuria (protein in the urine), swelling (edema), or changes in urinary habits due to kidney damage.

The diagnostic methods for amyloidosis are:

• Medical history and physical examination: A doctor may inquire about symptoms and perform a physical examination to look for signs of amyloidosis.
• Blood and urine tests: These tests can detect abnormal protein levels, kidney function, and other indicators of amyloidosis.
• Biopsy: A tissue sample, from the affected organ (e.g., kidney, heart, liver), is examined under a microscope to identify amyloid deposits.
• Imaging tests: X-rays, CT scans, MRIs, or echocardiograms may be used to detect organ damage caused by amyloid deposits.
• Genetic testing: In some cases, genetic testing may be performed to identify genetic mutations associated with certain types of amyloidosis.
• Bone marrow biopsy: This test can determine if abnormal cells are producing amyloid proteins and help classify the type of amyloidosis.

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Treatment for amyloidosis depends on the form of the disease, but goals generally include slowing its progression, reducing symptoms, and extending life. Treatments may include:

• Chemotherapy: Chemotherapy medicines are often given intravenously (IV), subcutaneously, or orally. Common chemotherapy medicines for AL amyloidosis include bortezomib (Velcade), cyclophosphamide, and dexamethasone.
• Stem cell transplantation: Autologous hematopoietic stem cell transplantation is considered the most effective treatment for amyloidosis in eligible patients.
• Treating the underlying condition: For secondary amyloidosis (AA), the underlying condition must be treated. For example, eradication of infections can resolve AA lidoses.
• Medications to help with symptoms: These include painkillers, anti-sickness medicines, and diuretics.
• Kidney dialysis: If your kidneys are not working properly, you may need kidney dialysis.
• Kidney transplant or liver transplant: If these organs are damaged, you may need a kidney transplant or liver transplant.
• Supportive therapies: Treatments such as diuretics to manage fluid retention, blood thinners to reduce the risk of blood clots, and pain medications may be used to alleviate symptoms and improve quality of life.

Amyloidosis is a rare, serious disease that can be difficult to diagnose because of its varied presentation. It’s caused by the accumulation of misfolded protein aggregates in the body’s tissues, which can lead to organ dysfunction, disability, and death. Amyloidosis can affect multiple organs and has different manifestations. Diagnosis involves a combination of medical history, imaging tests, and tissue biopsy. Treatment strategies aim to reduce the production of abnormal proteins, manage symptoms, and address complications through medications, chemotherapy, stem cell transplants, and supportive therapies.

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What are the Main Causes of Amyloidosis?

The main causes of amyloidosis include abnormal protein production by the bone marrow and deposition of these proteins in tissues and organs.

What is the Life Expectancy of a Person with Amyloidosis?

The life expectancy of a person with amyloidosis varies widely depending on factors such as the type of amyloidosis, organs affected, and effectiveness of treatment, typically ranging from several months to years.

What are Warning Signs of Amyloidosis?

The warning signs of amyloidosis include fatigue, swelling (edema), unintended weight loss, and organ-specific symptoms such as difficulty breathing or irregular heartbeat.

Can Amyloidosis be Cured?

Amyloidosis can be managed and treated to improve symptoms and slow progression, but a complete cure may not always be achievable.

Which Organ is Most Affected by Amyloidosis?

The heart is often the most affected organ in systemic amyloidosis, leading to symptoms like heart failure and arrhythmias.