Journal of Clinical & Experimental Pathology
Open Access

Amyloidosis is a complex medical condition characterized by the abnormal accumulation of amyloid proteins in various tissues and organs throughout the body. These proteins can cause disruptions to normal tissue structure and function when they misfold, clump, and form insoluble fibrils. The deposition of amyloid fibrils can lead to organ dysfunction and failure, ultimately impacting multiple systems within the body. Amyloidosis can be classified into several types based on the precursor protein that forms the amyloid fibrils.

Light chain amyloidosis type occurs when the body produces abnormal antibodies called light chains, which can accumulate as amyloid fibrils. It is often associated with plasma cell disorders such as multiple myeloma. Transthyretin (ATTR) amyloidosis is a protein primarily produced in the liver. Mutations in the transthyretin gene or aging-related changes can cause it to misfold and form amyloid fibrils, leading to ATTR amyloidosis. Secondary amyloidosis type is typically associated with chronic inflammatory conditions such as rheumatoid arthritis, inflammatory bowel disease, or chronic infections. Chronic inflammation triggers the liver to produce a protein called Serum Amyloid A (SAA), which can form amyloid fibrils. Several genetic mutations can predispose individuals to amyloidosis by causing the production of abnormal proteins prone to amyloid formation. These mutations can affect various precursor proteins, including transthyretin, apolipoprotein A1, gelsolin, and others. In systemic amyloidosis, amyloid deposits can affect multiple organs and tissues throughout the body, including the heart, kidneys, liver, nervous system, and gastrointestinal tract. Amyloidosis that is localized to one particular organ or tissue, such as the skin, lungs, bladder, or central nervous system, is known as localized amyloidosis.

The symptoms of amyloidosis can vary widely depending on the organs affected and the extent of amyloid deposition. Some common symptoms include, fatigue, shortness of breath, swelling in the ankles and legs (edema), weight loss, easy bruising, numbness or tingling in the hands or feet, enlarged tongue (macroglossia), skin changes, such as purpura (purple patches caused by bleeding under the skin) or waxy deposits. Diagnosing amyloidosis can be challenging due to its diverse clinical presentations and the similarity of symptoms with other diseases. A comprehensive evaluation typically involves medical history and physical examination in which the doctor may inquire about symptoms, medical history, and family history of amyloidosis or related conditions. A physical examination may reveal signs such as organ enlargement or neuropathy. Blood and urine tests can detect abnormal levels of proteins, kidney function, and signs of inflammation. Imaging techniques such as echocardiography, MRI, CT scans, or ultrasound may be used to assess organ involvement and detect amyloid deposits. Biopsy of affected tissues (such as the abdominal fat pad, bone marrow, kidney, or affected organs) is crucial for confirming the presence of amyloid deposits and identifying the amyloid protein type. In cases of hereditary amyloidosis, genetic testing can identify specific mutations associated with the condition.

The treatment approach for amyloidosis depends on the type of amyloidosis, the organs involved, and the extent of organ damage. Treatment goals typically include reducing the production of amyloid proteins, preventing further amyloid deposition, and managing organ dysfunction. Treatment options may include, chemotherapy drugs are often used to target and suppress the underlying plasma cell or lymphocyte clone responsible for producing abnormal proteins in amyloidosis. Stem cell transplantation may be considered for eligible patients with amyloidosis to replace abnormal plasma cells with healthy ones. In ATTR amyloidosis, medications such as tafamidis and patisiran can stabilize transthyretin proteins and slow the progression of the disease. Symptomatic management may include medications to control heart failure, high blood pressure, arrhythmias, neuropathic pain, or other complications associated with amyloidosis. Liver transplantation may be considered for select patients with hereditary ATTR amyloidosis to replace the liver's source of mutant transthyretin protein. Supportive measures such as dietary modifications, physical therapy, and supportive devices (e.g., compression stockings) can help manage symptoms and improve quality of life.

The prognosis of amyloidosis varies depending on several factors, including the type of amyloidosis, extent of organ involvement, presence of underlying conditions, and response to treatment. AL amyloidosis tends to have a poorer prognosis compared to ATTR amyloidosis, primarily due to its association with plasma cell disorders and the potential for rapid disease progression. However, advancements in treatment options, including novel targeted therapies, have improved outcomes for many patients with amyloidosis. Amyloidosis is a complex group of disorders characterized by the abnormal accumulation of amyloid proteins in various tissues and organs. It can present with a wide range of symptoms and complications, making diagnosis and management challenging. A multidisciplinary approach involving hematologists, nephrologists, cardiologists, neurologists, and other specialists is often necessary to provide comprehensive care for patients with amyloidosis. With ongoing research and advances in treatment modalities, there is hope for improved outcomes and quality of life for individuals affected by this rare but serious condition.