A THICK PROBLEM
A 56-year-old man was diagnosed with immunoglobulin A (IgA) k multiple myeloma. Over the past year, he has been treated with cyclophosphamide, bortezomib, and dexamethasone (CyBorD) for six cycles, followed by autologous stem cell transplantation complicated by relapse with day +100 marrow showing a significant progression of disease with greater than 90% plasma cells. Now, he presents to the outpatient clinic with a diffuse rash comprising violaceous, reticular patches over bilateral lower extremities but sparing his groin and arms (Figure 1A). He reports a history of similar prior episodes occurring intermittently since his initial diagnosis. The rash is accompanied by blurry vision, headache, dizziness, and somnolence but no epistaxis or gait instability.
|White blood cell (WBC)||2.06 × 103/µL||3.4 - 11.2 × 103/µL|
|Hemoglobin||8.8 g/dL||11.7-5.3 g/dL|
|Platelets||121 × 103/µL||150 - 450 × 103/µL|
|Total protein||92 g/dL||81.0-100 g/dL|
|M-SPIKE||3.0 g/dL||0.2-0.5 g/dL|
|IgG||298 mg/dL||700-1600 mg/dL|
|IgA||3331 mg/dL||70-400 mg/dL|
|IgM||17 mg/dL||40-230 mg/dL|
|Free kappa light chain||10.60 mg/dL||0.33 – 1.94 mg/dL|
|Free lambda light chain||0.14 mg/dL||0.57 – 2.63 mg/dL|
|Free kappa/lambda ratio||75.71 mg/dL||0.26 – 1.65 mg/dL|
|Beta-2-microglobulin||4.8 mg/dL||0.9 – 1.7 mg/dL|
What is the best next step?
- Check serum viscosity
- Draw a serum viscosity and initiate plasma exchange
- Systemic steroids
Symptomatic hyperviscosity is a medical emergency that requires prompt therapeutic plasma exchange based on the patient's neurologic symptoms and physical findings, such as blurry vision, headache, dizziness, and somnolence. The diagnosis is based on the classical triad of neurological deficits, visual changes, and/or mucosal bleeding rather than on the magnitude of the viscosity measurement. Red blood cell transfusions should be avoided before plasmapheresis since they might further increase serum viscosity.
Hyperviscosity syndrome results from the aggregation of light chains and increased blood viscosity in type I cryoglobulinemia1 and generally manifests when the blood viscosity exceeds 4.0 centipoises (cP). Still, the turnaround time is variable, so we shouldn't wait for the results before starting treatment2.
Anticoagulation is the mainstay of treatment for antiphospholipid syndrome, but it is not indicated for hyperviscosity.
High-dose steroids are often used in conjunction with cytoreductive therapy in the treatment of multiple myeloma1. The use of systemic steroids alone is not recommended in the treatment of type I cryoglobulinemia.
- Why so thick?
The serum viscosity in this patient was too high to measure, with a recurrent comment from the lab explaining they were “unable to perform due to serum adhering to glass viscometer.” After the first plasma exchange, the viscosity was reduced to 3.0 cP. The second plasma exchange was performed the following day using one plasma-volume 5% albumin as replacement fluid. Post-procedure viscosity was measured at 1.7 cP with a resolution of the rash after plasma exchange (Figure 1B).
Serum viscosity should be measured in patients with monoclonal gammopathy and signs or symptoms suggestive of hyperviscosity syndrome, such as blurring or loss of vision requiring a prompt retinal exam, or headache, vertigo, nystagmus, dizziness, tinnitus, sudden deafness, diplopia, or ataxia3 or non-neurologic symptoms such as epistaxis, bleeding gums, heart failure, and respiratory compromise. This is a true emergency that can lead to confusion, dementia, disturbances of consciousness, stroke, or coma4. Hyperviscosity symptoms rarely occur until serum viscosity reaches >4 cP (normal value is 1.5 cP relative to water5). However, it has been shown that serum viscosity and immunoglobulin protein concentration are not always linearly related, but serum viscosity can increase with IgM levels as low as 3g/dL and, more commonly, with IgM levels of 6 g/dL, IgA greater than 6g/dL, or IgG of 10g/dL5, even though serum viscosity measurement does not always correlate with clinical symptoms.