A rare group of illnesses caused by an insoluble protein complex (amyloid) being deposited between the cells of internal organs and eventually impairing their function. Amyloidosis can rarely cause arthritis but is more often a complication of long-standing inflammatory arthritis.

Cause - Although amyloid was first described 150 years ago by the famous German pathologist R. Virchow, the proteins involved have been well characterized only in the last 30 years. The types of amyloid are named A for amyloidosis, followed by a letter or abbreviated name that represents the type of amyloid protein.

Three main types of amyloid protein cause different types of amyloidosis. In addition, there are also rare hereditary forms of amyloidosis and associations with rare diseases such as FAMILIAL MEDITERRANEAN FEVER.

1. In AA amyloidosis, a protein called serum amyloid A (SAA) is produced as part of the immune response to chronic inflammation. The condition is therefore sometimes called secondary amyloidosis. This used to be a common complication of chronic infections such as tuberculosis.

However, with the development of more effective antibiotics, it now usually results from longstanding inflammatory arthritis such as RHEUMATOID ARTHRITIS and ANKYLOSING SPONDYLITIS and a chronic inflammatory disease, familial Mediterranean fever.

Genetic factors probably affect how often amyloidosis complicates chronic arthritis. For example, in Scandinavian countries, amyloidosis complicating rheumatoid arthritis, although uncommon, occurs significantly more often than in the United States.

2. AL amyloidosis is sometimes called primary amyloidosis. It can be thought of as a type of malignancy of blood cells (plasma cells) that overproduce an amyloid protein composed of the light (L) chains of an immunoglobulin protein. AL amyloid may also occur in patients with a type of cancer called multiple myeloma that affects the plasma cells of the bone marrow.

It can occur in people with benign monoclonal gammopathy and sometimes occurs in the absence of any associated illness. In all these conditions, a type of white blood cell called plasma cells have escaped from their normal control mechanisms and produce increased amounts of the amyloid proteins.

3. Ab2M amyloidosis, or beta2-microglobulin amyloidosis, is the third type and is sometimes called dialysis-associated amyloidosis. It occurs in patients who have received hemodialysis for a long time (see DIALYSIS) and can be detected in most patients after 15 years of dialysis.

Symptoms - AA amyloidosis may not cause any symptoms and is sometimes diagnosed only after protein has been found in the urine and investigated. The amount of protein in the urine is often small initially, but it can increase and result in nephrotic syndrome. This may progress to kidney failure.

Amyloid protein can be deposited in many tissues, including the heart, but heart failure is rare. In AL amyloidosis the abnormal protein is deposited in greater quantities in organs such as the heart, liver, and tongue. Nephrotic syndrome and heart failure are common and usually have a poor outcome.

The liver may enlarge, and gastrointestinal involvement can lead to poor absorption of nutrients and GI bleeding. Arthritis occurs in less than 5 percent of patients and usually affects shoulders, knees, wrists, metacarpophalangeal (MCP) joints, and proximal interphalangeal (PIP) joints.

Amyloid can deposit in the soft tissues of the wrist and cause CARPAL TUNNEL SYNDROME. Patients on long-term dialysis who have beta2- microglobulin amyloidosis develop arthritis, tendinitis, and carpal tunnel syndrome as well as destructive bony cysts that can sometimes cause fractures.

Diagnosis - Biopsy of either an affected organ (e.g., heart or kidney) or of more easily accessible tissues (rectum or subcutaneous fat) will show the amyloid in approximately 80 percent of patients. Aspiration of fat, a test that involves drawing a small amount of abdominal fat into a syringe, is often the most convenient way to obtain a tissue sample.

The type of amyloid protein can be determined by staining the tissue with dyes that are specific for the different types of protein. If the heart is affected, echocardiography (an ultrasound of the heart) may show thickening of the walls of the ventricles and reduced contractility of the heart.

Nuclear medicine scans using various radiolabeled molecules have been useful when defining the extent of the disease and its response to treatment. However, they are not used in routine clinical care. If myeloma is suspected, examination of the bone marrow will show increased numbers of plasma cells.

Treatment and Outcome - Complications caused by amyloidosis such as heart and kidney failure are treated in the usual manner. Treatment of amyloidosis itself is directed at reducing the production of amyloid protein so that less is deposited in the tissues.

A lot of research has been directed toward developing methods to remove amyloid protein from tissues, but this is not currently possible. In AA disease, the most important aspect of treatment is to suppress the inflammation or, in chronic infections, to eliminate its cause.

If AA amyloidosis is caused by chronic inflammatory arthritis, CORTICOSTEROIDS and drugs that suppress the immune system are often used to control the inflammation. AL amyloidosis associated with myeloma or a monoclonal gammopathy is usually treated with a combination of an anticancer drug, such as melphalan, and PREDNISONE.

Some patients with AL amyloidosis have been treated with bone marrow transplantation. COLCHICINE may be helpful for patients with amyloidosis associated with familial Mediterranean fever. In patients with beta2- microglobulin amyloidosis, renal transplantation enables them to stop hemodialysis and can improve the symptoms.