Flailing at the Diagnosis: An Atypical Chest Pain Presentation of Multiple Myeloma Richard Lewis Martin III, MD, MPH

Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health

Presentation

Hospital Course

Background

References

Bone pain is the most common presentation of multiple myeloma (70-80%), and 90% of this group will present with lumbar or rib pain. Plain films are only 80-90% sensitive at detecting lytic bone lesions, due to an inability to detect lesions with less than 30-50% trabecular bone loss. By the time this degree of sternal/rib bone loss occurs, patients are at high risk for fracture, which can result in serious complications such as flail chest and acute hypoxic respiratory failure. Because early treatment with chemotherapy and zoledronic acid significantly reduces vertebral fractures and skeletal events, multiple myeloma is an important disease to keep on a differential for persistent atypical chest pain, especially in light of evolving anemia and renal injury.

Imaging Studies

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56 year old male with PMH notable for GERD, nephrolithiasis, and depression with past suicide attempt, presents seven months ago with chest pain after reaching above his head at work…

Only after ICU admission for acute hypoxic/hypercarbic respiratory failure was he found to have diffuse osteolytic lesions on CT C/A/P without contrast. Kappa free light chain 1100, beta-2 microglobulin 6.38, and bone marrow biopsy with kappa light chain producing clonal plasma cells ~10% verified multiple mye loma, f o r wh ich he rece i ved bo r tezomib and dexamethasone. After four months of ICU care, he was eventually weaned from both tracheostomy and dialysis support, transitioning to inpatient rehabilitation with good recovery.

WORKUPSYMPTOMS PLAN

7 mo

4 mo

2 mo

HgB 13.3,Cr 0.96trop, d-dimer -CXR #1, stress -

HgB 12.1Cr 1.18Ca 9.3, UA -CXR #2 -HgB 11.8Cr 1.38CXR #3: atelectesisHgB 11.2Cr 1.75UA: Hgb +, protein +

4/10 left sided, sharp,worse with cough, movements

IbuprofenTizanidineHydrocodone

Kyle RA, Gertz MA, Witzig TE, Lust JA, Lacy MQ, Dispenzieri A et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc 2003; 78: 21-33Edelstyn GA, Gillespie PJ, Grebbell FS. The radiological demonstration of osseous metastases. Experimental observations. Clini Radiol. 1967; 18: 158-162.Dimopoulos M, Terpos E, Comenzo RL, et al. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple myeloma. Leukemia. 2009; 23(9):1545-1556.

Lidocaine patchpain consultpsych consult

Diclofenac, GabapentinPhysical therapyWorkers comp

Mhaskar R, Redzepovic J, Wheatley K, Clark OA, et al. Bisphosphonates in multiple myeloma: a network meta -analysis. Cochrane Database Syst Rev. 2012; 5: CD003188

Current Guidelines

Fleegler B, Fogarty C, Owens G, Cohen E, Cassileth PA. Pathologic flail chest complicating multiple myeloma. Arch Intern Med. 1980 Mar;140(3):414-5

WBXR WBLDCT *WBMRI FDG-PETSensitivity ~80% >94% 88-94% 95%Specificity “low” 47-50% 26-58% 18-68%

Detection Rate - 1.1-1.3 1.1-1.8 1.1-1.5Advantages low cost

low radiationaxial

skeletondiffuse boneosteopenias

plasmacytomaextramedullary

Limitations false negative recurrence skull, ribs false positives

Prognostic no no yes yes

7/10 previous pain,now w/ breathing. New left back withrad. down spine

8/10 previous pain,add sternal/flank,tender to touch

1 mo

Case reports warning about delayed diagnoses of myeloma presenting as chest pain date back to 1980, yet myeloma remains the most common cancer with three or more PCP visits prior to oncology referral, in part because major review articles and guidelines by ACP, AFP, ACEP continue to minimize myeloma in the differential of musculoskeletal chest pain and because providers are unfamiliar with the limitations of plain films for detecting lytic lesions.

8/10 diffuse MSK,now with frankresting dyspnea

rheum. consultdiazepamhydrocodone

* requires contrast

1/2015

poor inspirationand atelectasis posterior left

5th rib fracture

Dual Energy PA + Lateral

A B C

CT Chest/Abdomen/Pelvic w/IV contrast

Coronal views of (A) vertebral column, (B) posterior ribs and pelvis, and (C) Sagital view of sternum and vertebral column, all showing diffuse, innumerous hypointense osteolytic lesions suggestive of metastatic disease. Atelectatic lung (*).

Differential56 year old male presents with progressive musculoskeletal chest and pelvic pain and steadily worsening anemia and renal function, concerning for… Multiple Myeloma, SLE, Met. Renal Carcinoma

Upon retrospective review of 1/2015 CXR#3, patient had fracture of posterior 5th rib

Imaging Review

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Figure is synthesis from results and figures of references 3, 8-9

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Guanqun C, Lizheng F, Guoyao Z, O’Leary CM. Discovering Multiple Myeloma Early in Ambulatory Patients With Chest Pain.Clinical Journal of Oncology Nursing. April 2013; 17 (2) 205-7.

Lyratzopoulos G, Neal RD, Barbiere JM, et al. Variation in number of general practitioner consultations before hospital referral for cancer: findings from the 2010 National Cancer Patient Experience Survey in England. Lancet Oncol. 2012; 13(4): 353-365.

Shephard EA, Neal RD, Rose P, Walter FM, et al. Quantifying the risk of multiple myeloma from symptoms reported in primary care patients: a large case-control study using electronic records. Br J Gen Pract February 2015; DOI: 10.3399/bjgp15X683545.

STRONGEST VARIABLES ASSOCIATED WITH MULTIPLE MYELOMA

HypercalcemiaRib Pain*ESR/CRPWeight Loss

Back Pain*Nosebleeds

SYMPTOMS7.7 (5.4 - 11)5.6 (4.2 - 7.1) 4.6 (4.2 - 5.0) 4.4 (3.2 - 6.0)

LR (95%CI) LABS LR (95%CI)26 (18 - 35)6.8 (6.3 - 7.4)

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MCV elevationCytopenia*

6.2 (5.3 - 7.3)5.3 (5.0 - 5.7)

Mateos MV, Hernandez MT, Giraldo P, De la Rubia J, et al. Lenalidomide plus Dexamethasone for High-Risk Smoldering Multiple Myeloma. NEJM August 2013; 369(5): 438-447.

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International Myeloma Working Group supports use of whole body low dose CT (WBLDCT) over WBXR for myeloma imaging, due to increased detection of thoracic cage (5 fold) and spine (7 fold). WBMRI can detect diffusely infiltrated non-lytic marrow in smoldering myeloma, helping identify high risk (>80%) 2 year progression to clinical myeloma which would merit treatment.

10-12

2/28/2015

Regelink JC, Minnema MC, Terpos E, et al. Comparison of modern and conventional imaging techniques in establishing multiple myeloma-relatedbone disease: a systematic review. Br J of Haem. 2013; 162: 50-61

Pianko MJ, Terpos E, Roodman GD, Divgi CR, et al. Whole-Body Low-Dose Computed Tomography and Advanced Imaging Techniques for Multiple Myeloma Bone Disease. Clin Cancer Res. December 2014;20(23) 5888-5897

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