Multiple Myeloma, Emergency Medicine

Basics

Description

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)

Etiology

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

Signs and Symptoms

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).

Essential Workup

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

Diagnosis Tests & Interpretation

Lab

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.

Imaging

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.

Differential Diagnosis

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

Treatment

Pre-Hospital

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

Presume to have a pathologic spinal fracture

Initial Stabilization/Therapy

Recognition and treatment of: � �

Hypercalcemia
Renal failure
Sepsis
Spinal cord compression
Anemia

Ed Treatment/Procedures

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

Disposition

Admission Criteria

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

Discharge Criteria
Pain controlled with oral analgesics � �
Issues for Referral

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

Pearls and Pitfalls

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.

Additional Reading

Altundag � �K, Altundag � �O, Gundeslioglu � �O. Multiple myeloma. N Engl J Med. 2005;352:840 " �841.
Blade � �J, Rosi � �ol � �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.

Codes

ICD9

203.00 Multiple myeloma, without mention of having achieved remission � �

ICD10

C90.00 Multiple myeloma not having achieved remission � �

SNOMED

109989006 multiple myeloma (disorder)

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