Idiopathic Infl ammatory Myopathy: Treatment Options Stephen J. DiMartino, MD, PhD Corresponding author ing PM or IBM can be more diffi cult [ 2 ]. The following Stephen J. DiMartino, MD, PhD noninfl ammatory myopathies and neurologic conditions Weill Medical College, Cornell University; and Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021. can also present with proximal muscle weakness: cen- E-mail: [email protected] tral and peripheral nervous system disorders, adult-onset Current Rheumatology Reports 2008, 10: 321– 327 muscular dystrophies (eg, limb-girdle muscular dystro- Current Medicine Group LLC ISSN 1523-3774 phy, fascioscapulohumeral muscular dystrophy, Becker’s Copyright © 2008 by Current Medicine Group LLC muscular dystrophy), metabolic myopathies (eg, phospho- fructokinase defi ciency, acid-maltase defi ciency, carnitine palmityl-transferase II defi ciency, mitochondrial myopa- Idiopathic infl ammatory myopathy (IIM) comprises a thies), endocrine myopathies (eg, hypo- or hyperthyroidism, group of rare disorders in which there is an immune- Cushing’s syndrome, acromegaly), neuromuscular junction mediated attack on skeletal muscle, the consequence of disorders (eg, myasthenia gravis, Eaton-Lambert syndrome), which is muscle damage and weakness in the patient. viral myopathy, and toxic myopathy. As in other infl ammatory diseases, the general approach Today, statin myopathy is frequently considered in to therapy is use of immunosuppressive agents. the differential diagnosis of weakness or myalgia given Many options exist for IIM treatment, but therapeutic these agents’ high use in clinical practice [ 3 ]. Differen- approaches are based mostly on empirical evidence tiation among these entities often can be accomplished and small studies, many of which are uncontrolled. using a combination of clinical features, serologic studies, Recently, new agents have been designed to target electromyography, MRI, and muscle biopsy. Due to the specifi c components of the immune response, and they large differential diagnosis of myopathy, when referring offer hope for more effective or safer IIM therapy. patients for electromyography, MRI, or biopsy, it is essen- tial to work with physicians who have experience with muscular disorders. Regardless, because all of the above Introduction studies have their own limitations, even a thorough work- Idiopathic infl ammatory myopathy (IIM) comprises the up may yield an equivocal conclusion. Because the patient following entities: polymyositis (PM), dermatomyositis may be deteriorating quickly, time may be an important (DM), inclusion body myositis (IBM), juvenile DM, myo- factor, and the physician will be pressed to make a treat- sitis associated with malignancy, and myositis associated ment decision despite an unclear diagnosis. Furthermore, with systemic infl ammatory disease (overlap syndromes). PM and DM can be associated with the presence of Although these conditions are grouped together for aca- malignancy. In this scenario, the symptoms attributable demic purposes, they differ signifi cantly in their individual to myositis may precede the discovery of the malignancy. clinical and histologic features. For example, although DM Often these patients respond poorly to myositis therapy, and PM are autoimmune conditions included in the same but respond to treatment of the malignancy [4 ]. Signs family as systemic lupus erythematosus, scleroderma, and and symptoms suggestive of IIM include arthritis, rash, rheumatoid arthritis, IBM appears to be a degenerative elevated acute phase reactants, positive antinuclear anti- process [1 ]. Nevertheless, all of the IIMs share the theme body, family history of autoimmunity, lack of atrophy, of immune-mediated attack on skeletal muscle, which pro- lack of facial muscle involvement, and acute to subacute duces muscle damage and weakness in the patient. As in presentation. The presence of myositis-specifi c antibodies other infl ammatory diseases, immunosuppressive agents can suggest a defi ned clinical pattern such as the antisyn- are the general approach to therapy. However, several thetase syndrome or may predict response to therapy [5 ]. unique challenges await the physician treating IIM. The next challenge is the choice of therapy and its The fi rst challenge is making the correct diagnosis. management. Due to the rarity of IIMs, few randomized Because DM is often associated with a characteristic rash, placebo-controlled trials (RCTs) have been performed. this diagnosis is usually straightforward; however, diagnos- Most studies exploring therapeutic options for IIM 322 Infl ammatory Muscle Disease (including the RCTs) use few patients, have varied out- strength; furthermore, after disease has been controlled, come criteria, or include heterogeneous populations of a rise in muscle enzymes may predict subsequent worsen- patients with IIM, all of which make it diffi cult to draw ing of clinical status [ 8 ]. conclusions and apply the results to individual patients. Indeed, treatment approaches remain empirical. In the Corticosteroids last decade, the International Myositis Assessment and Corticosteroids were fi rst employed to treat another Clinical Studies (IMACS) Group has developed a set of autoimmune condition, rheumatoid arthritis, in 1948 outcome criteria to be used for RCTs [ 6 , 7 ]. This effort (reviewed by Neeck [ 9 ]). Since the 1950s, corticoste- should help overcome many of the limitations of previous roids have been the fi rst-line therapy for PM and DM. studies. Currently, many centers worldwide participate in IBM tends not to respond well to any therapy, but a trial observational and interventional trails. Due to the rarity early in the disease course may result in some improve- of the disease, it is important to consider every patient ment [10 ]. Although no adequate trials have compared with IIM for a clinical trial if logistically possible. different steroid treatment protocols, the recommenda- High-dose corticosteroids remain the fi rst line of tions of physicians who have treated many IIM patients therapy. Because corticosteroids cause many serious side tend to be similar. The following are three examples of effects or worsen preexisting medical problems, numerous specifi c approaches to steroid therapy that have been medical issues in addition to the myositis become active published previously. simultaneously; this requires coordination of care and good communication between several health care providers. 1. Maintain patient on approximately 1 mg/kg or Furthermore, treatment with steroids can cause myopathy, 60 mg prednisone (or equivalent steroid dose) creating a paradox unique to IIM treatment. daily in a divided dose for at least 1 month and The next challenge is to manage patients who respond until the CK has normalized. Then decrease the partially to or are refractory to therapy. Due to issues dis- dose by about 25% each month with a goal of a cussed earlier, there is no clear defi nition of when a patient once-daily maintenance dose of 5 to 10 mg per is refractory to therapy. A complete failure to respond day (by 4–6 months) [ 8 ]. or a minimal response after 4 to 6 weeks of appropriate 2. Eighty to 100 mg prednisone once daily for 3 to 4 therapy should prompt a reconsideration of the diagnosis. weeks, followed by tapering over 10 weeks to 80 to Noninfl ammatory myopathies, IBM, myositis associated 100 mg every other day. This can be accomplished with malignancy, and anti-SRP syndrome are not likely by reducing the “off day” dose by 10 mg/week (side to respond as well as PM and DM. In patients with long- effects may make a faster taper necessary) until it standing disease, it may be diffi cult to determine how is down to zero. Assuming a response, follow with much of the patient’s weakness is due to active infl am- tapering 5 to 10 mg every 3 to 4 weeks until down mation and how much is due to damage. Serum muscle to approximately 50 mg every other day. At this enzymes, MRI, or repeat muscle biopsy may help deter- point, the rate of taper is slowed even further to a mine if active infl ammation is playing a role. decrease of 2.5 mg every few months [ 11 ]. 3. One to 1.5 mg/kg per day of prednisone (maximum, 100 mg/day), changing to every other day dosing in General Approach to Therapy 2 to 4 weeks (or 2–3 months in patients with more The patient is started on a high dose of corticosteroid severe disease). This regimen is continued until the and maintained on this dose until strength improves and patient has regained normal strength or until their muscle enzyme levels decrease (approximately 4–6 weeks), strength has plateaued (approximately 4–5 months). and then the dose is slowly tapered over months. Because Then taper by 5 mg every 2 weeks until at 20 mg some patients with IIM have a monocyclic disease course, every other day; then taper by no more than 2.5 mg patients who respond well to this therapy may eventually be every 2 weeks [ 12 ]. tapered off steroids completely or may be maintained on a low dose. However, if the patient does not respond well to In a retrospective study of 113 patients with IIM, Joffe therapy or fl ares during the taper, the addition of second- et al. [ 10 ] showed that after the fi rst prednisone trial, 25% line therapies and possibly third-line therapies (discussed of patients had a complete remission, 61% of patients had later) are then considered. During treatment, patients are a partial remission, and 14% of patients had no response. usually followed closely using