Rosen & Barkin's 5-Minute Emergency Medicine Consult (460 page)

• Normal cells transform into myeloma cells at the hematopoietic stem cell level.
  
• Pathologic derangements:
  
  • Tumor cells within marrow lead to bone destruction and cytopenia.
    
  • Immunodeficiency develops secondary to suppression of normal immune functions.
    
  • Myeloma proteins lead to hyperviscosity and amyloidosis.
    
  • Multifactorial renal failure
    
• Plasma cell secretions activate osteoclasts, leading to:
  
  • Bone lysis, pathologic fractures, and neurologic impairment
    
  • Hypercalcemia (exacerbated by impaired renal function)
    
• Anemia due to marrow infiltration and renal insufficiency
  
• Immunocompromised due to:
  
  • Decrease in the number of normal immunoglobulins
    
  • Qualitative and quantitative defects in T- and B-cell subsets
    
  • Granulocytopenia
    
  • Decreased cell-mediated immunity
    
• Hyperviscosity secondary to protein accumulation:
  
  • Leads to high-output congestive heart failure
    
• Myeloma light chains accumulate in the renal epithelial cells and destroy the entire nephron.
  
• Clinical signs such as anemia, renal insufficiency, or lytic bone lesions
  
• Complications:
  
  • Pathologic fractures
    
  • Hypercalcemia
    
  • Renal failure
    
  • Recurrent infection
    
  • Anemia
    
  • Spinal cord compression (10% of all multiple myeloma [MM] patients)
    

• Incidence: 4/100,000 population:
  
  • 1% of all cancers
    
  • 15% of all hematopoietic malignancies
    
  • 10,000 deaths/yr
    
• Mean age at diagnosis is 70 yr
  
• Slightly higher incidence in men and African Americans (reason unknown)
  

• Rarely seen in children.
  
• <2% in patients <40 yr of age
  

DIAGNOSIS

• Bone pain predominates (with secondary disuse or neurologic sequelae):
  
  • Ribs/sternum
    
  • Spine
    
  • Clavicle
    
  • Skull
    
  • Shoulder
    
  • Hip
    
• Constitutional symptoms:
  
  • Anemia
    
  • Weakness
    
  • Fatigue
    
  • Recurrent infection
    
  • Weight loss
    
• Asymptomatic (20%):
  
  • MM found on follow-up of routine blood screening
    
• Multiple bouts of sepsis secondary to the encapsulated organisms (
  Streptococcus pneumoniae, Haemophilus influenzae,
  and
  Staphylococcus
  ).
  

• CBC, ESR, electrolytes, BUN, creatinine, urinalysis
  
• Plain radiographs related to bone pain:
  
  • Skeletal survey: Lateral skull, AP/lateral spine, AP of pelvis, humerus, and femur
    
• CT or MRI for persistent bone pain with negative plain radiographs
  
• Confirmation of diagnosis:
  
  • Serum and urine protein electrophoresis
    
  • Serum and urine protein immunofixation (diagnostic when electrophoresis is normal or nonspecific)
    
  • Vitamin D levels
    
  • Bone marrow biopsy
    

• CBC:
  
  • Normochromic, normocytic anemia
    
  • Thrombocytopenia
    
  • Leukocytosis
    
• “Rouleaux” formation on peripheral blood smear (stacks of red blood cells)
  
• Electrolytes, BUN, creatinine, glucose:
  
  • Renal insufficiency
    
• Serum calcium:
  
  • Hypercalcemia due to bone resorption
    
• Urinalysis:
  
  • Dipstick selects for albumin and not light-chain proteinuria.
    
  • False-negative screening urinalysis for Bence Jones protein is common.
    
• Elevated erythrocyte sedimentation rate (ESR)
  
• Urinary and serum electrophoresis show a monoclonal protein spike:
  
• Quantitative screening for light chain is diagnostic.
  

• Plain radiographs demonstrate:
  
  • Lytic bone lesions
    
  • Pathologic fractures
    
• CT:
  
  • More sensitive for small lesions
    
  • Can differentiate malignant from benign vertebral compression fractures in non-MRI candidates
    
• MRI:
  
  • Preferred to detect spinal compression or soft-tissue plasmacytomas
    
• PET with MR or CT: May have future role in surveying response to treatment
  
• Technetium pyrophosphate bone scan:
  
  • Lights up bone deposition
    
  • False-negative scan with MM due to an uncoupling of bone absorption and deposition that results in a negative bone scan even when lytic lesions are present
    
• Bone marrow biopsy: Increase in plasma cells
  
• Cytogenetic screening may offer prognostic significance.
  

• Monoclonal gammopathy of undetermined significance
  
• Amyloidosis
  
• Chronic lymphocytic leukemia
  
• Non-Hodgkin lymphoma
  
• Waldenström macroglobulinemia
  
• Bone marrow plasmacytosis includes collagen vascular disease, cirrhosis, immune complex disease, viral illness, and papular mucinosis.
  

TREATMENT

Immobilize appropriately patients with MM who present with back pain or neurologic symptoms:

• Presume to have a pathologic spinal fracture
  

Recognition and treatment of:

• Hypercalcemia
  
• Renal failure
  
• Sepsis
  
• Spinal cord compression
  
• Anemia
  

• Opiate analgesics are the mainstay of therapy in ED (NSAIDS may worsen renal insufficiency).
  
• Splint pathologic fracture; immobilize pathologic spine fractures.
  
• Aggressive normal saline hydration with bisphosphonate therapy for hypercalcemia
  
• Symptomatic anemia may be managed with transfusions or erythropoietin therapy.
  
• Hematology/oncology consultation for chemotherapy—administer on inpatient/outpatient basis:
  
  • Early or asymptomatic stages do not need treatment.
    
  • Chemotherapy in early stage shows no benefit.
    
  • Melphalan and prednisone combination chemotherapy is the most common treatment:
    
    • Symptom relief and decrease in M protein levels in up to 70% of patients
      
  • Alternative chemotherapy includes cyclophosphamide with or without prednisone or VAD (vincristine, doxorubicin [Adriamycin], and dexamethasone).
    
• Prolonged melphalan use may lead to a secondary leukemia.
  
• High-dose chemotherapy with stem cell transplantation has shown promise.
  
• Thalidomide is useful for salvage therapy.
  

FOLLOW-UP

• Refractory pain requiring systemic analgesics
  
• Life-threatening complications of MM, including acute renal failure, hypercalcemia, sepsis, spinal cord compression, hyperviscosity, neutropenia, and cardiac tamponade
  

Pain controlled with oral analgesics

• Oncology referral for all patients regardless of stage of disease discovery
  
• Neurosurgery and orthopedic referral for persistent vertebral pain that may require percutaneous vertebroplasty or kyphoplasty
  

• Infectious complications are the major cause of morbidity and mortality such that febrile illness should be treated with empiric therapy for common respiratory and urinary tract infections.
  
• Consider diagnosis of multiple myeloma for any persistent neurologic complaints or unknown mobility in the elderly.
  

• Altundag K, Altundag O, Gundeslioglu O. Multiple myeloma.
  N Engl J Med
  . 2005;352:840–841.
  
• Bladé J, Rosiñol L. Complications of multiple myeloma.
  Hematol Oncol Clin North Am
  . 2007;21(6):1231–1246, xi.
  
• Cheong HW, Peh WC, Guglielmi G. Imaging of diseases of the axial and peripheral skeleton.
  Radiol Clin North Am
  . 2008;46(4):703–733, vi.
  
• Grethlein SJ, Thomas, LM. Multiple myeloma. Treatment and medication. Emedicine. Updated Nov 19, 2009. Available at
  http://emedicine.medscape.com/article/204369-treatment
  
• Raab MS, Podar K, Breitkreutz I, et al. Multiple myeloma.
  Lancet.
  2009;374(9686):324–339.
  

See Also (Topic, Algorithm, Electronic Media Element)

• Anemia
  
• Hypercalcemia
  
• Renal Failure
  
• Sepsis