Myositis Mysteries

Prednisone remains the first-line pharmacologic therapy for PM and DM. We advocate an initial dose of 1 mg/kg/day, with a pulse of methylprednisolone (typically 1 gm) at the outset in significantly affected patients. We favor disease modifying antirheumatic drug (DMARD) initiation (most often MTX at usual rheumatologic doses of up to 25 to 30 mg/week or azathioprine at up to 2 mg/kg/day) within a month of initiating prednisone in order to avoid disease flares while attempting to taper prednisone. If prednisone taper is not tolerated with single therapy of 25 to 30 mg MTX/week or 100 to 150 mg azathioprine/day, then consider a combination of azathioprine and MTX.¹⁴ In our experience using MTX as adjunct therapy for IIM, MTX-related pulmonary toxicity has been very uncommon.

Opinions vary considerably regarding the role of IVIG in IIM treatment. A controlled clinical trial has demonstrated efficacy in treatment-resistant DM and, in an open-label study, significant muscle strength improvement was reported in treatment-refractory PM.^15,16 In our opinion, monthly IVIG infusions (1–2 gm/kg/month) should be considered for both DM and PM. Although many patients may benefit substantially, this effect often diminishes with a prolonged course of infusions. In cancer-associated myositis, when chemotherapy is used for the treatment of the tumor, IVIG can be a sensible option.

Added options in refractory DM and PM include cyclosporine and tacrolimus, particularly if there is co-existing interstitial lung disease.^17,18 Early uncontrolled reports using mycophenylate mofetil have shown mixed results and no controlled trial has been reported. Because reports of cyclophosphamide efficacy in IIM are conflicting, this medication should be reserved for cases resistant to other immunosuppressants and IVIG.¹⁹

Despite some evidence for an immune contribution to the pathogenesis of IBM, and although some patients respond transiently to conventional IIM treatment, no therapy substantially affects the progression of this disease. However, no rigorous long-term trial has been reported.²⁰ Significant improvement in dysphagia symptoms following IVIG has been reported.²¹

The role of anti–tumor necrosis factor or B cell–depleting therapies in IIM is unknown. Published uncontrolled case reports describe varied outcomes. Ongoing controlled clinical trials investigating the role of these agents in PM/DM may clarify the potential efficacy of these therapies.

Monitoring indices of active disease is important in guiding therapy and should not be limited to periodic measurement of serum muscle enzymes. The International Myositis Assessment and Clinical Studies (IMACS) international collaboration has developed a core set of three outcome measures for PM and DM: myositis disease activity, damage, and health-related quality of life.^22,23 Although developed specifically for use in PM and DM clinical trials, these outcomes measures can be useful in clinical practice. The principle of comprehensive disease assessment is also applicable to IBM.

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TABLE 3. Autoantibodies in IIM

One of the most important principles of IIM treatment is that the question, “Is this IIM?”, should not be dismissed following initial diagnosis. Maintain a high index of suspicion and reassess the question in the following settings. When in doubt, re-biopsy.

1. Persistent elevated muscle enzymes despite appropriate treatment and improving symptoms: Treat the patient, not the number! MRI can identify active inflammation in patients with conflicting indices of disease activity, such as persistent CK elevations without corresponding muscle weakness or vice versa;
2. Persistent or increasing muscle weakness with or without CK change: This could represent active IIM, but a high index of suspicion for steroid myopathy or a high degree of muscle damage must be maintained; and
3. Evolving symptoms suggestive of IBM in a patient whose muscle biopsy was read as PM: This probably is IBM, particularly in concert with appropriate clinical characteristics.

Conclusion

The IIMs are a heterogenous group of immune-mediated myopathies. Thorough consideration of the potential differential diagnosis and careful examination of a muscle biopsy are essential for accurate diagnosis and choice of appropriate therapy. Cornerstones of therapy are corticosteroids, DMARDS, and physiatry. If your myositis patient is not responding, rethink the diagnosis and consider appropriate consultations, laboratory studies, imaging, or re-biopsy.