Basic Information: Symptoms
As many organs can be affected by multiple myeloma, its symptoms and signs vary greatly from person to person.
The symptoms of multiple myeloma can be classified in groups as follows:
- symptoms caused by cytokines produced by myeloma cells
- symptoms caused by monoclonal immunoglobulin
- symptoms caused by interference of plasma cells in physiological blood forming functions of bone marrow
- other pathophysiologic nonspecific constitutional symptoms of multiple myeloma
Clinical symptoms of multiple myeloma:
1) Bone pains caused by osteolysis
The bone pain is one of the most common symptoms due to focal osteolysis or to multiple lytic lesions.
Patients complain most often of the pain in lumbar part of the spine where highly significant bone loss of vertebras due to myeloma osteolysis is frequently observed. Additionally, pathologic compression fractures may occur in myeloma patients. The disease may result in painful osteolysis of any other bone. Punched out osteolytic lesions develop mainly in the skull.
The most common anamnestic symptom of multiple myeloma is pain in lumbar back caused by a pathologic compression fracture.
The typical X-ray picture of a myeloma patient reveals multiple lytic bone lesions and pathologic fractures. Some patients suffer only from osteoporosis without lytic lesions; in this case, only myelogram can differentiate primary osteoporosis from osteoporosis due to MM. MR imaging can be helpful in differential diagnosis of osteoporosis origin.
Consequently, every patient with persistent or worsening back pain should undergo x-ray inspection. If a patient reports skeletal pains lasting more than one month and the x-ray inspection doesn´t reveal the origin of the pain the MR imaging should be used to precise the diagnosis.
Progression of osteolysis leads to hypercalcemia.
2) Infections resulting from immunosupression
Immune system disorders and recurrent infections, longer and more severe than previously reported, may represent another typical symptom of the disease.
At early stage of the disease, B-cell immune disfunction occurs, whereas in advanced myeloma, T-cell immune disfunction is observed. T-cell immune system disorder causes the suppression of normal immunoglobulin. As the disease progress, their shortage becomes considerable. The suppression of polyclonal immunoglobulin in myeloma patient limits the production of corresponding immunoglobulin upon antigen stimulation. Patients with multiple myeloma can obtain vaccinations but its efficacy is decreased in the phase of progression of the disease. In the case of severe infections, it is necessary to administrate individualised dosage of intravenous immunoglobulin. Chronic lymphatic leukemia is associated with immunodefficiency as well.
Increaseing frequency and intensity of suffered infections should make the attending physician suspect the myeloma diagnosis. The corresponding examinations should be undergone to confirm or refute the suspicion.
3) Anemia and pancytopenia
Anemia, trombocytopenia and leucopenia with corresponding clinical symptoms can reveal multiple myeloma. They are a consequence of the overgrowth of cancerous cells and of the dysregulation of the cytokine network.
4) Sensory-motor polyneuropathy caused by monoclonal immunoglobulin
The disorder appears as diffusional pains of the limbs due to the polyneuropathy that involves peripheral nerves more than motor nerves.
5) Myeloma neuropathy
So-called "Myeloma kidney" may lead even to a serious renal insufficiency involving the necessity of chronic dialysis treatment. Chronic renal failure is due to deposition of monoclonal light chains. Free light chains have small molecules and pass easily through the glomerular basement membrane and are absorbed by the cells of the proximal tubules. In these cells, they are decomposed in amino acid and transported to the bloodstream. Elevated light chain concentration leads to injury to proximal tubule and loop of Henle. Thus, the light chain accumulation is associated with irreversible renal tubular dysfunction. This mechanism also reveals that decreased urine excretion (diuresis) and increased urine concentration in kidneys accelerates the renal failure.
Patients with increased protein concentration in urine should undergo monoclonal immunoglobulin examination. If the examination was positive, other relevant examinations confirming or refuting the diagnosis of multiple myeloma should be performed.
6) Disorder in blood platelet homeostasis
Disorder in blood platelet homeostasis can be life-threatening in case of operation or injury. Trombocytopathy occurs frequently especially in patients with elevated light chain levels. The light chain adheres on the surface of trombocytes and interferes with their functions. It is necessary to consider this risk of trombocytes aggregation in myeloma patient to correctly diagnose the trombocytopathy.
If a myeloma patient has to undergo an operation, it is necessary to examine thrombocytes aggregation, besides the standard examination such as fibrinogen, INR, APTT, TT. If these tests reported a pathologic finding, a haemocoagulation specialist should assess the risk of bleeding.
In myeloma patients, the disorder of coagulation mechanism is associated with an increased blood viscosity that result in bruising, ecchymoses, gastrointestinal bleeding or in thrombosis (for example venae centralis retinae). The hyperviskcosity is observed mostly in monoclonal IgM-gammopathy, more rarely in gammopathy IgG or IgA as a consequence of increased levels of circulating serum immunoglobulins. Its occurence is ascribed to monoclonal bands of IgA and IgG immunoglobulins.
The clinical manifestation od hyperviscosity are chiefly observed in the eyeground, the feature is called "fundus paraproteinemicus".