Multiple myeloma-associated amyloidosis is a type of systemic amyloidosis related to multiple myeloma.
Amyloidosis is a rare disorder characterized by the deposition of abnormal protein called amyloid in the body.
Amyloid is an abnormal protein built up of fibril proteins (95%), the P component and several glycoproteins. In the microscope amyloid is seen as an extracellular hyaline substance. The three common forms of amyloid are distinguished:
- AL (amyloid light chain) – consists of the light immunoglobulin chains;
- AA (amyloid-associated) produced in the liver;
- Aβ – typical for Alzheimer disease;
- ATTR – common type of amyloid seen in familial amyloidosis;
Multiple myeloma (or plasma cell myeloma) is a plasma cell cancer, a condition in which plasma cells start reproducing out of control. Plasma cells are the type of white blood cells responsible for the production of antibodies IgG or IgA. In case of multiple myeloma plasma cells produce immunoglobulin light chains which later form the amyloid (AL).
Amyloid accumulates in the heart, digestive system, kidneys and nervous system. It was estimated that AL amyloidosis represents about 85% of all the cases of amyloidosis.
Individuals who suffer from multiple myeloma are at risk of developing amyloidosis. It is suggested that amyloidosis is seen in up to 10-15% of cases of multiple myeloma.
Symptoms of amyloidosis include non-specific signs such as fatigue, weakness, poor appetite and weight loss.Amyloid deposits in various tissues result in heart insufficiency/restrictive cardiomyopathy, nephrotic syndrome, hepatosplenomegaly, carpal tunnel syndrome, macroglossia and skin lesions.
- Deposits of the abnormal protein in the heart tissue thicken and make the heart wall stiff, therefore leading to diastolic dysfunction of the heart. The heart is unable to pump the blood effectively, this disorder is known as congestive heart failure characterized by the accumulation of fluid in the pleural cavity (shortness of breath is the common sign) and blood stasis in the lower extremities (develops edema, swelling of ankles and legs). Amyloid in the myocardium (the heart muscle) blocks the conduction of the impulses in the heart and causes heartbeat irregularity.
- Involvement of the digestive system causes dysmotility which leads to early satiety, nausea, vomiting, dysphagia, gastroparesis, gastroesophageal reflux, loss of appetite, constipation, chronic intestinal pseudo-obstruction, weight loss, etc. Ulcers/erosions develop on the surface of the stomach and intestines and sometimes a bleeding occurs.
- Spleen and liver appear enlarged.This condition is called hepatosplenomegaly. This may be felt by the person and cause discomfort.
- Enlarged tongue (macroglossia) is the most common symptom of multiple myeloma-associated amyloidosis caused by the amyloid deposition in the tissues of the tongue. Big tongue interferes with swallowing and may lead to breathing problems during sleep known as sleep apnea.
- Kidney may be affected as well. In the beginning occurs proteinuria (protein in the urine), followed by the kidney failure.
- Skin lesions in amyloidosis appear as purpura, macules and papules that may affect various parts of the body. Bleeding in the periorbital area is characteristic (“raccoon eyes”).
- Nerve damage in amyloidosis results in polyneuropathy. The most common disorder is carpal tunnel syndrome: An individual experiences numbness and weakness in the hands.
Criteria for the diagnosis of AL amyloidosis
All four criteria must be met:
- Presence of an amyloid-related systemic syndrome (such as renal, liver, heart, gastrointestinal tract or peripheral nerve involvement).
- Positive amyloid staining by Congo red in any tissue (e.g. fat aspirate, bone marrow or organ biopsy).
- Evidence that amyloid is light chain-related established by direct examination of the amyloid (immunohistochemical staining, direct sequencing, etc.).
- Evidence of a monoclonal plasma cell proliferative disorder (serum or urine monoclonal protein, abnormal free light chain ratio or clonal plasma cells in the bone marrow).
The production of amyloid may be reduced by the administration of chemotherapy. High-dose melphalan and autologous peripheral blood stem cell transplantation were reported to be an effective treatment of AL amyloidosis.
Bone marrow transplantation may also be performed. Organ transplantation is a life-saving surgery in case of organ failure.
Drugs used may include:
- Melphalan of >300 mg/day;
- Cyclophosphamide as a chemotherapeutical agent;
- Thalidomide is used in combination with dexomethasone despite the side-effects for refractory patients;
- Dexamethasone (as pulsed high-dosage regimen or a modified regimen) and Prednisolone.