The complete pathogenesis of HMGCR Ab-related IMNM remains blurry, but other findings (such as the presence of few infiltrating lymphocytes and membrane attack complex on non-necrotic muscle cell membranes) support the pathogenic nature of HMGCR autoantibodies.10 Also, evidence from other studies that HMGCR autoantibody levels correlate with initial elevated CPK levels and muscle weakness supports the pathogenicity of these antibodies.15,16
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Explore This IssueDecember 2017
Although HMGCR is usually not expressed on the surface of myocytes, researchers hypothesize that under different pathological conditions it can be expressed on the surfaces of different cells.17,18 This highlights a clear association between statin exposure and an antibody triggered autoimmune reaction leading to IMNM.
However, we must note that more than 33% of the patients in various study groups were statin-naive.10,11,19 The statin-naive patients with HMGCR Ab-related IMNM are relatively young and have severe disease presentation with poor response to steroids and other immunomodulatory therapy.
HMGCR Ab-related IMNM’s common presentation includes subacute to chronic, moderate to severe proximal muscle weakness, with CPK elevation higher than the levels commonly seen in other inflammatory myopathies.11 Different studies have revealed different ranges of CPK levels. For example, a study by Grable-Esposito et al reports mean CPK levels of 8,203 IU/L, but a study by Christopher-Stine et al notes higher mean CPK levels of 10,333 IU/L.
A recent NAM review showed that extra-muscular manifestations, such as ILD and cardiac involvement, occur less frequently in HMGCR Ab-related IMNM compared with other NAM subgroups.3,20 Allenbach et al report in their study that around 20% of patients with HMGCR Ab-related IMNM presented with dysphagia and respiratory muscle involvement without evidence of ILD.19 The literature doesn’t include many cases that feature HMGCR Ab-related IMNM presenting with severe respiratory muscle involvement leading to respiratory failure requiring mechanical ventilation.
HMGCR Ab-related IMNM initially shows mild to moderate response to steroids, but most patients develop progressive muscle weakness, and their high CPK levels remain, which indicates the need to step up therapy. Studies have highlighted the role of various immunomodulatory therapies, such as methotrexate, cyclophosphamide, rituximab, IVIG and azathioprine, in ameliorating symptoms in these patients.3 Further, in patients with severe disease presentation, researchers propose a role of aggressive immunomodulation with combination immunosuppressive therapy.3,19
In our case series, the first patient diagnosed with HMGCR Ab-related IMNM had moderate initial response to steroids, but he later developed rapid progression of muscle weakness with significant respiratory muscle involvement. Therefore, we added IVIG, but unfortunately, he died due to pneumococcal sepsis.