View source for Multiple myeloma

==Background==
*Malignant proliferation of plasma cells  overproduction of abnormal antibodies (paraproteins or light-chain protein)
**Osteoclasts are activated through the RANK pathway by the abnormal antibodies leading to osteolytic lesions
*Symptoms result from accumulation of plasma cells and paraproteins
*Most common primary bone malignancy
*More commonly seen in African Americans and males

==Clinical Features==
*Percentages below correspond to clinical presentations in newly diagnosed disease
*Bone (plasma cell proliferation in marrow) lesions in ~80%
**Pathologic [[fractures]]
***Due to lytic lesions and osteopenia
***”Punched-out” lytic lesion on x-ray
***Frequently involve spine, as well as ribs, skull, extremities
**Bone pain (even in absence of fracture) in ~60%<ref>Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003;78:21-33.</ref>
***Commonly in back, ribs, extremities, often worse with movement
*[[renal failure|Renal impairment]] in 20-40%<ref>Eleutherakis-Papaiakovou V, Bamias A, Gika D, et al. Renal failure in multiple myeloma: incidence, correlations, and prognostic significance. Leuk Lymphoma 2007;48:337-341.</ref>
**Ranges from mild creatinine elevation to [[ESRD]]
**Due to light-chain deposition, myeloma cast nephropathy and/or amyloidosis
**[[Hypercalcemia]] exacerbates
**Vulnerable to further damage from nephrotoxic mediations/contrast 
*Hematologic
**[[Anemia]] in ~70%<ref>Birgegard G, Gascon P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European Cancer Anaemia Survey. Eur J Haematol 2006;77:378-386.</ref>
**Due to plasma cell infiltration in marrow +/- renal failure
**[[Hyperviscosity syndrome ]]
***Increase serum viscosity due to paraproteins  poor capillary flow and organ congestion
***Cryoglobulinemic vasculitis 
****Altered mental status, syncope, stroke
**Rouleaux formation on peripheral smear 
*Neuro
**[[Spinal cord compression]] due to vertebral fracture or collapse or plasmacytoma
**Intracranial plasmacytoma (rare)
**Peripheral neuropathy, radiculopathy
*[[Hypercalcemia]]
**Due to local osteolysis 
**Though overall uncommon as first presentation finding
*[[Infection]]
**Most common cause of death in patients with multiple myeloma
**Impaired plasma cell function decreased effective antibody production
**Often on immunosuppressive chemotherapy or bone marrow transplant meds
**Splinting due to rib pain/fractures increased pneumonia risk
*Coagulopathy can occur due to dysfibrinogenemia

[[File:Lyticlesionfracture.png|thumbnail|Pathological fracture from lytic lesion]]

==Differential Diagnosis==
{{Anemia DDX}}
{{Bone tumors and their mimics DDX}}

==Evaluation==
[[File:Plasmozytom multiple Osteolysen Unterarm.png|thumb|X-ray of the forearm, with lytic lesions]]
*Definitive diagnosis is by biopsy of marrow or plasmacytoma
*CBC
*Peripheral smear- may see Rouleaux formation of RBCs, atypical plasma cells
[[File:Rouleaux.jpg|thumbnail|Roleaux formation on peripheral smear]]
*BMP, ionized Ca, Mg, phos
**Paraproteins bind calcium, so non-ionized Ca levels could be falsely elevated
**Pseudohyponatremia from paraproteinemia
**Hyperphosphatemia from increased bone turnover
*Serum and urine testing for monoclonal protein (to aid in initial diagnosis if patient not already known to have MM)
**SPEP and UPEP electrophoresis
**Urine analysis will show large, waxy, laminated casts due to monoclonal proteins known as Bence Jones proteinuria
***Urine dipstick will be negative for protein as it detects albumin rather than monoclonal proteins
*Most common monoclonal proteins in order are as follows: IgG, IgA, Kappa > lambda light chains
*Other work up contingent on presentation:
**MRI spine: low threshold if any clinical evidence of cord compression
**Plain films of suspected pathologic fractures
**Infectious work up
**ECG can show shortened QT interval secondary to hypercalcemia

==Management==
*[[analgesia|Treat pain]]
**Consider referring to [[palliative care]] if feasible (or suggesting consult to patient/inpatient team)
*Manage other complications:
**If [[fever|febrile]], get cultures, start broad-spectrum [[antibiotics]]
**Splint [[fractures]] and/or consult ortho as appropriate
**See [[Hypercalcemia]], [[Hypercalcemia of malignancy]]
***[[Prednisone]] 60mg PO daily can be helpful in addition to standard hypercalcemia treatments
**See [[Cord Compression]], [[Malignant spinal cord compression]], [[Epidural compression syndromes]]
**See [[Renal failure]]
**See [[Anemia]]
***If patient is eligible for transplant and indication equivocal, may want to avoid transfusion and/or consult oncology

==Disposition==
*Consideration for heme/onc consultation

==See Also==
*[[Oncologic emergencies]]
*[[Lymphoma]]
*[[Hypercalcemia of malignancy]]

==External Links==
*[http://emergencymedicinecases.com/tag/multiple-myeloma/ Emergency Medicine Cases Episode 33: Oncologic Emergencies]

==References==
<references/>
*Multiple Myeloma. Antonio Palumbo, M.D., and Kenneth Anderson, M.D. N Engl J Med 2011; 364:1046-1060March 17, 2011. DOI: 10.1056/NEJMra1011442

[[Category:Heme/Onc]]