Center for Amyloidosis - Diagnosis and Treatment

What is Amyloidosis?

Amyloidosis is a rare, multi-system disease (about 2,500 new cases per year in the U.S.), characterized by extracellular deposits of insoluble proteins in some organs which, over time, leads to their dysfunction.

The kidney is the organ most commonly involved in primary and secondary amyloidosis, but rarely involved in various forms of familial amyloidosis. Protein in the urine is a common expression of renal involvement and leads to nephrotic syndrome (high protein in the urine, low protein in the blood, fluid retention reflected mainly by edemas and an increase of cholesterol in the blood). Less commonly found are amyloid deposits associated with renal dysfunction as an initial manifestation of the disease.

Edema in the absence of heart failure is characteristic of nephrotic syndrome. Sudden edema or a sudden unexplained increase in elevated serum cholesterol levels indicate the need to evaluate the presence of protein in the urine and look for amyloidosis.

Amyloid infiltration of the heart causes a thickening of the ventricular septum and the development of heart failure. The rapid development of heart failure with ventricular septum thickening, with no expansion of the ventricles and with relatively preserved heart function, is a classic expression of primary cardiac amyloidosis.

In hypertension, there is a similar picture in terms of the heart but characteristically, in contrast to amyloidosis, the left ventricle of the heart is increased. Further, on ECG testing (electrical testing of the heart), large electric complexes are seen with hypertension and the amyloids are very small. A doctor who sees a patient with septum thickening in the presence of a normal-sized ventricle and small complexes on the ECG should suspect amyloidosis.

Nervous System
Even though renal or cardiac involvement is less common, small peripheral nerve damage (neuropathy) may be the initial significant finding and points to primary amyloidosis. In some cases of familial amyloidosis, neuropathy is the main expression of the disease. The initial neurological disorder is a tingling and decreased sensation in the upper and lower extremities. Subsequently, the patient can also develop a twitching or movement disorder, mainly in the palm of the hand, commonly refered to as "Carpal Tunnel Syndrome". With disease progression, damage also appears in the autonomic nervous system (does not feel/sense but controls the various body parts). Such damage is characterized by diarrhea and a drop in blood pressure on standing, which can be severe and cause recurrent episodes of fainting. In addition, men may also experience erectile dysfuntion. The central nervous system is not involved in systemic amyloidosis.

Liver and Digestive Tract
Specific hepatic involvement is common in primary and secondary amyloidosis, but is not expressed in familial amyloidosis. Hepatic involvement is usually without symptoms, despite growth (sometimes significantly) of the liver. In general, palpation of the liver where amyloid has filtered through is very hard. In laboratory tests, there is an increase in liver enzymes, sometimes to the point of liver failure. Hepatic amyloidosis appears alone only rarely and is usually associated with the involvement of organs elsewhere.

Diarrhea associated with amyloidosis is usually connected to a malfunction of the autonomic nervous system. Sometimes it is the result of amyloid deposits anywhere in the digestive tract. There may be bleeding and malabsorption of food products. Loss of taste and difficulty eating solid foods due to an enlargement of the tongue may contribute to weight loss, which may be an expression of the specific systemic disease. Patients with damage to the nerves that innervate the colon can suffer from a swallowing disorder with chest pain due to involvement of the esophagus as well as very severe constipation.

Soft Tissue and Skin
Cutaneous manifestations of primary amyloid may provide significant clues to the diagnosis, especially when other organ involvement suggests systemic disease. Cutaneous involvement is limited almost exclusively to primary amyloid. Its expression can be in part the appearance of skin nodules called amyloidomas. Purpura (blue bruises as after injury) around the eyes is the result of fragile capillaries and is in fact almost uniquely expressed in primary amyloidosis. Hemorrhages may occur as a result of coughing, sneezing or straining during bowel movement. Soft tissue penetration can cause an enlarged tongue and hoarseness despite vocal cord examination potentially shown as being normal.

Pulmonary amyloid deposits are often found in autopsies of patients with primary amyloidosis or senile amyloidosis, but rarely cause problems in a person's day-to-day life. Significant pulmonary involvement may occasionally appear in primary amyloidosis, causing a sharp decline in the ability to exchange gases. This complication occurs most often in patients with significant cardiac involvement. Effusions of fluid in the lung membrane, while quite common in patients who have heart failure as a result of amyloidosis, may indicate amyloidosis of the lung membrane itself if repeated in a disproportionate quantity to the severity of cardiac failure.

The Endocrine System
The endocrine glands also may be involved in amyloidosis, particularly the thyroid and adrenal.

The Center

Since amyloidosis is a rare disease, very few people are aware of it and currently diagnosis of the problem takes time, causing a delay in treatment. Many times the patient may find himself going from doctor to doctor without getting a concrete answer as to what is ailing him.

The Center for Amyloidosis aims to:
1. Raise Awareness of the Disease Amongst GPs and Specialists in Hospitals for Early Diagnosis:
As described, amyloidosis is a multi-system disease expressed by a wide range of clinical signs. As a result, the patient is sometimes directed to several specialists - generally a nephrologist, cardiologist or neurologist. Recent developments in treatments require accurate and early diagnosis in order for the patient to take full advantage of them. Additionally, a high level of awareness among family physicians and specialists is of great importance - currently most patients arrive a year and a half to three years after the appearance of symptoms without having been diagnosed!

2. Improving Diagnosis in Israel:
Our laboratory is currently developing a number of laboratory methods, biochemical, molecular and imaging, that should improve the chances of early diagnosis. The intention of the biochemical testing is one called NT-proBNP, an up-to-date test for the levels of free light chain, molecular tests identifying the type of amyloid (primary, secondary, familial, senile). In terms of imaging methods, there are MRI methods, echocardiography and mapping - some exist and others are being developed.

3. Patient Care with a Multi-System Perspective:
The center is a place where the amyloid patient receives treatment which addresses all the problems the disease causes. The Center will coordinate between the hematologist as team leader, a nephrologist, cardiologist, neurologist, gastroenterologist, dermatologist, pulmonologist and an endocrinologist. In addition, and if necessary, there will be assistance from a dietitian, social worker and psychologist.Treatment for the disease itself is given by hematologists. Standard treatment today is providing new drugs such as VELCADE, THALIDOMIDE, REVLIMID combined with CYCLOPHOSPHAMIDE MELPHALAN and steroids with or without bone marrow transplantation.

4. Cooperation with Amyloidosis Centers Worldwide:
Such cooperation is especially important in the subject of clinical studies that allow patients to receive important medicines that are still not found in the 'medical basket' provided by the Sick Funds/public healthcare systems. At this point, we have formed a close relationship with the Amyloidosis Centers in Boston and Italy (Prof. Falk and Professor Merlin).

Diagnostic and treatment center in the Department of Hematology;
Dr. Moshe Gatt
Hematology Clinic
Phone: 02-5842111