From the Guidelines
Elevated IgM levels should be managed by treating the underlying cause, with a focus on reducing IgM levels and alleviating symptoms, particularly in cases of Waldenström macroglobulinemia, where therapies such as bortezomib-based regimens or plasmapheresis may be necessary to rapidly reduce IgM levels and prevent complications like hyperviscosity syndrome 1.
Causes and Evaluation
Elevated IgM levels can occur in various conditions, including infections, autoimmune disorders, liver diseases, and hematologic disorders like Waldenström macroglobulinemia and lymphoma. When elevated IgM is detected, further evaluation should include:
- Complete blood count
- Liver function tests
- Viral serologies
- Possibly bone marrow examination depending on clinical suspicion Management focuses on treating the underlying cause rather than the elevated IgM itself.
Treatment Approaches
For infections, appropriate antimicrobials are indicated; for autoimmune conditions, immunosuppressive therapy may be needed; and for malignancies like Waldenström macroglobulinemia, chemotherapy or targeted therapies are typically required. In cases of Waldenström macroglobulinemia with high IgM levels, bortezomib-based therapy is recommended to rapidly reduce IgM levels and prevent complications like hyperviscosity syndrome 1. Plasmapheresis can also be used to alleviate symptoms of hyperviscosity syndrome, particularly in patients with very high IgM levels (typically >4000 mg/dL) before rituximab administration 1.
Special Considerations
Specific clinical conditions may require special actions, such as:
- Elevated serum IgM arising from IgM-secreting clonal cells in the bone marrow of patients with WM, which often results in hyperviscosity syndrome
- Monoclonal IgM can cause disease-related peripheral neuropathy (PN), cryoglobulinemia, cold agglutinemia, and renal insufficiency
- Bortezomib, thalidomide, and vincristine should be avoided where PN is present in WM, and choosing alternatives (e.g., carfilzomib or combinations such as DRC or bendamustine–rituximab) may avoid symptom exacerbation 1.
From the Research
Elevated IgM Overview
- Elevated IgM levels can indicate a current or recent infection, but false-positive results can occur, leading to misdiagnoses and inappropriate therapy 2
- In the context of COVID-19, elevated SARS-CoV-2-specific IgM levels have been associated with clinically unfavorable outcomes in patients 3
Clinical Significance of Elevated IgM
- Elevated IgM levels can be seen in various infections, including Lyme disease, and can be used as a diagnostic tool, but should be interpreted with caution due to the risk of false-positive results 2, 4, 5
- In Lyme disease, elevated IgM levels can indicate early infection, but diagnosis should be based on clinical manifestations and adjunctive laboratory testing 4, 5
Treatment and Management
- Treatment of Lyme disease typically involves antibiotics, such as doxycycline or amoxicillin, and early treatment can cure most cases of early Lyme disease 4, 6, 5
- In COVID-19, the association between elevated IgM levels and poor outcomes highlights the importance of accurate diagnosis and timely treatment 3
Diagnostic Considerations
- IgM detection should not be accepted as a stand-alone test for diagnosis, and confirmation by other means, including testing of serial samples and additional test methods, is recommended 2
- In Lyme disease, diagnosis should be based on clinical manifestations, such as erythema migrans, fever, and malaise, and adjunctive laboratory testing, including IgM and IgG antibody tests 4, 5