Some patients who cannot tolerate, or are refractory to, prednisone may respond favorably to oral azathioprine with care being taken to avoid severe leukopenia. Methotrexate is currently favored by many groups over azathioprine as an adjunct to steroids (5 to 10 mg/week in 3 divided oral doses, increased by 2.5 mg/week, to a total dose of 20 mg weekly). Methotrexate or azathioprine should generally be given along with the lowest effective doses (15 to 25 mg) of prednisone. Although one study failed to show efficacy (Oddis et al), in cases that have been refractory to corticosteroids and methotrexate, we and our colleagues have had success with rituximab intravenously, 750 mg/m2, repeated in 2 weeks and sometimes required every 6 to 18 months. Some clinicians favor, from the beginning, a combination of prednisone in low dosage and one of these immunosuppressant drugs, and this approach is generally necessary when myocarditis or interstitial pneumonitis is coupled with DM. It has been suspected that patients with anti-Jo or other antibodies may respond more favorably. Mycophenolate mofetil has also been introduced and has allowed a reduction in steroid dose within several months in both PM and DM, according to a number of anecdotal reports, but has not proven clearly effective in a randomized trial; the reasons for this failure are being actively discussed and we have not abandoned its use. Cyclosporine has also been used in recalcitrant cases; it has few advantages over other immunosuppressant drugs and has a number of potentially serious side effects, including nephrotoxicity. Cyclophosphamide, which is a useful drug in the treatment of Wegener granulomatosis, polyarteritis, and other vasculitides, is said to be of lesser value in PM, but it may be useful in refractory cases and has perhaps the highest toxicity of the immunosuppressive medications that are used for inflammatory myopathies; we no longer use it with any regularity.
Except for patients with malignancy, the prognosis in adult PM and DM is generally favorable. Only a small proportion of patients with PM succumb to the disease and then usually from a secondary pulmonary complication or from myocarditis as already mentioned. Several of our patients have had severe aspiration pneumonias as a result of their dysphagia. The period of activity of disease varies considerably but is typically 2 to 3 years in both the child and adult. As indicated earlier, the majority improves with corticosteroid therapy, but many are left with varying degrees of weakness of the shoulders and hips. Approximately 20 percent of our patients have recovered completely after steroid therapy and long-term remissions have been achieved after withdrawal of medication in about an equal number. The extent of recovery is roughly proportional to the acuteness and severity of the disease and the duration of symptoms prior to institution of therapy. Patients with acute or subacute PM in whom treatment is begun soon after the onset of symptoms have the best prognosis. In the series collected by DeVere and Bradley, in which patients were treated early, there was remission in more than 50 percent of cases, whereas Riddoch and Morgan-Hughes reported a far lower rate in patients who were treated more than 2 years after onset of the disease. Those patients who have come to our attention after a long period of proximal weakness and with substantial muscle atrophy have not recovered completely, although some improvement occurred over years.
Even in patients who have a coexistent malignancy, muscle weakness may lessen and serum enzyme levels decline in response to corticosteroid therapy, but weakness returns after a few months and may then be resistant to further treatment. As already stated, if the tumor is successfully removed, muscle symptoms may remit, but this experience has not been uniform.
The overall mortality after several years of illness had in the past approximated 15 percent, being higher in childhood DM, in PM with rheumatologic diseases, and, of course, when a malignancy is found. Recent figures give more optimistic results.