Multiple myeloma is a malignant disease of the plasma cells of bone marrow, accounting for 1% of all malignant disease. There is clonal proliferation of bone marrow plasma cells usually capable of producing monoclonal immunoglobulins (paraproteins), which in most cases are IgG or IgA. The paraproteinaemia may be associated with excretion of light chains in the urine (Bence Jones protein) which are either kappa or lambda; sometimes there are light chains without a paraproteinaemia.
The peak age of presentation is 60 years. There is:
■ Bone destruction - increased osteoclastic activity causes bone pain (back ache is the most common presenting symptom), osteolytic lesions, patho-logical fractures, spinal cord compression and hypercalcaemia.
■ Bone marrow infiltration with plasma cells resulting in anaemia, infec-tions and bleeding.
■ Acute kidney injury has multiple causes: deposition of light chains in the tubules, hypercalcaemia, hyperuricaemia and amyloid deposition in the kidneys.
Paraproteins may form aggregates in the blood, which greatly increase the viscosity, leading to blurred vision, gangrene and bleeding. Infections are also due to a reduction in the normal polyclonal immunoglobulin levels (immune paresis).
Two out of three diagnostic features should be present:
■ Paraproteinaemia on serum protein immunofixation or Bence Jones protein in the urine.
■ Radiological evidence (CT, MRI) of lytic bone lesions.
■ An increase in bone marrow plasma cells on bone marrow aspirate or trephine biopsy.
Other essential investigations are as follows:
■ Blood count, which may show anaemia, thrombocytopenia and leuco-penia. The ESR is almost always high.
■ Serum biochemistry may show evidence of renal failure and hyper-calcaemia. The alkaline phosphatase is usually normal.
■ Serum β2-microglobulin and albumin are used in prognosis.
With good supportive care and chemotherapy with autologous stem cell transplantation, median survival is now 5 years with some patients surviving to 10 years. Young patients receiving more intensive therapy may live longer.
Supportive therapy includes correction of anaemia with blood transfusion or erythropoietin, prompt treatment of infections, and treatment of bone pain with radiotherapy or high-dose dexamethasone. Acute kidney injury (p. 383) and hypercalcaemia (p. 651) may be corrected by adequate hydration alone. Progression of bone disease is reduced by bisphosphonates e.g. zoledronate, which inhibit osteoclastic activity. Hyperviscosity is treated by plasma-pheresis together with systemic therapy.
Specific treatment involves combination chemotherapy with melphalan (an alkylating agent), prednisolone and thalidomide. Younger patients (<65-70 years) are treated with high-dose melphalan with peripheral blood stem cell rescue. Lenalidomide, a thalidomide analogue, and bortezomib, a proteosome inhibitor, are currently used for relapsed myeloma.
Monoclonal gammopathy of undetermined sigmíicance
This is usually seen in older patients, where a raised level of paraprotein (usually IgA) is found in the blood, but without other features of myeloma. Patients are often asymptomatic and no treatment is required. Follow-up is necessary as 20-30% go on to develop multiple myeloma over a 25-year period.
1. Ethics and communication
2. Infectious diseases
3. Gastroenterology and nutrition
4. Liver, biliary tract and pancreatic disease
Liver, biliary tract and pancreatic disease
LIVER BIOCHEMISTRY AND LIVER FUNCTION TESTS
SYMPTOMS AND SIGNS OF LIVER DISEASE
NON - ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
COMPLICATIONS AND EFFECTS OF CIRRHOSIS
TYPES OF CHRONIC LIVER DISEASE AND CIRRHOSIS
PRIMARY SCLEROSING CHOLANGITIS
BUDD - CHIARI SYNDROME
LIVER DISEASE IN PREGNANCY
CARCINOMA OF THE PANCREAS
NEUROENDOCRINE TUMOURS OF THE PANCREAS
5. Haematological disease
Assessment and treatment of suspected neutropenic sepsis
INHERITED HAEMOLYTIC ANAEMIAS
ACQUIRED HAEMOLYTIC ANAEMIA
THE WHITE CELL
HAEMOSTASIS AND THROMBOSIS
6. Malignant disease
COMMON INVESTIGATIONS IN MUSCULOSKELETAL DISEASE
COMMON REGIONAL MUSCULOSKELETAL PROBLEMS
THE SERONEGATIVE SPONDYLOARTHROPATHIES
Clinical features, Investigations
INFECTION OF JOINTS AND BONES
AUTOIMMUNE RHEUMATIC DISEASES
SYSTEMIC INFLAMMATORY VASCULITIS
DISEASES OF BONE
8. Water, electrolytes and acid–base balance
WATER AND ELECTROLYTE REQUIREMENTS
BODY FLUID COMPARTMENTS
REGULATION OF BODY FLUID HOMEOSTASIS
PLASMA OSMOLALITY AND DISORDERS OF SODIUM REGULATION
DISORDERS OF POTASSIUM REGULATION
DISORDERS OF MAGNESIUM REGULATION
DISORDERS OF ACID - BASE BALANCE
9. Renal disease
INVESTIGATION OF RENAL DISEASE
URINARY TRACT INFECTION
HYPERTENSION AND THE KIDNEY
RENAL CALCULI AND NEPHROCALCINOSIS
URINARY TRACT OBSTRUCTION
ACUTE RENAL FAILURE/ACUTE KIDNEY INJURY
CHRONIC KIDNEY DISEASE
RENAL REPLACEMENT THERAPY
CYSTIC RENAL DISEASE
TUMOURS OF THE KIDNEY AND GENITOURINARY TRACT
DISEASES OF THE PROSTATE GLAND
10. Cardiovascular disease
COMMON PRESENTING SYMPTOMS OF HEART DISEASE
INVESTIGATIONS IN CARDIAC DISEASE
ISCHAEMIC HEART DISEASE
VALVULAR HEART DISEASE
PULMONARY HEART DISEASE
ARTERIAL AND VENOUS DISEASE
DRUGS FOR ARRHYTHMIAS
DRUGS FOR HEART FAILURE
DRUGS AFFECTING THE RENIN - ANGIOTENSIN SYSTEM
NITRATES, CALCIUM - CHANNEL BLOCKERS AND POTASSIUM - CHANNEL ACTIVATORS
11. Respiratory disease
12. Intensive care medicine
13. Drug therapy, poisoning, and alcohol misuse
14. Endocrine disease
PITUITARY HYPERSECRETION SYNDROMES
THE THYROID AXIS
MALE REPRODUCTION AND SEX
FEMALE REPRODUCTION AND SEX
THE GLUCOCORTICOID AXIS
THE THIRST AXIS
DISORDERS OF CALCIUM METABOLISM
DISORDERS OF PHOSPHATE CONCENTRATION
ENDOCRINOLOGY OF BLOOD PRESSURE CONTROL
DISORDERS OF TEMPERATURE REGULATION
15. Diabetes mellitus and other disorders of metabolism
16. The special senses
COMMON NEUROLOGICAL SYMPTOMS
COORDINATION OF MOVEMENT
THE CRANIAL NERVES
COMMON INVESTIGATIONS IN NEUROLOGICAL DISEASE
UNCONSCIOUSNESS AND COMA
STROKE AND CEREBROVASCULAR DISEASE
EPILEPSY AND LOSS OF CONSCIOUSNESS
NERVOUS SYSTEM INFECTION AND INFLAMMATION
HEADACHE, MIGRAINE AND FACIAL PAIN
SPINAL CORD DISEASE
DEGENERATIVE NEURONAL DISEASES
DISEASES OF THE PERIPHERAL NERVES