Initial treatment of dermatomyositis and polymyositis in adults

INTRODUCTION — The major categories of idiopathic inflammatory myopathies (IIM) include dermatomyositis (DM), antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), and inclusion body myositis (IBM). So-called "polymyositis" has fallen out of favor as a distinct category as most cases of previously categorized PM probably had antisynthetase syndrome, IBM, IMNM, or an overlap syndrome. Defining the optimal treatment regimens for these disorders has been difficult because of their rarity, their highly complex clinical phenotypes, and the limited number of randomized, double-blind clinical trials [1-3].

Understanding of the inflammatory myopathies has evolved over the years, but disease classification schemes have not kept pace [4]. Newer classifications, based upon histologic and serologic distinctions between the different disorders, may be instrumental to defining optimal treatments for individual patients [5-7].

The initial therapy of IIM (except for IBM, for which there are no effective medical therapies) will be reviewed here. The treatment of recurrent or resistant disease, the clinical manifestations and approach to diagnosis of these disorders in adults, the management of cutaneous manifestations of DM, and issues related to IIM in children are discussed separately:

●(See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults".)

●(See "Clinical manifestations of dermatomyositis and polymyositis in adults".)

●(See "Cutaneous dermatomyositis in adults: Overview and initial management".)

●(See "Management of refractory cutaneous dermatomyositis in adults".)

●(See "Juvenile dermatomyositis and other idiopathic inflammatory myopathies: Epidemiology, pathogenesis, and clinical manifestations".)

GOALS OF THERAPY — The goals of treatment are to improve muscle strength while preventing both relapse and treatment-associated adverse events. For some patients, treatments may be selected primarily to address extramuscular disease manifestations (eg, interstitial lung disease or cutaneous disease). The approach to such patients is addressed separately. (See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Treatment' and "Interstitial lung disease in dermatomyositis and polymyositis: Treatment" and "Interstitial lung disease in dermatomyositis and polymyositis: Treatment", section on 'Approach to therapy'.)

INITIAL THERAPY

Subclinical muscle disease — For patients with clinically asymptomatic muscle disease and a creatine kinase less than five times the upper limit of normal, many experts would agree that systemic immunosuppression may not be indicated; however, it is unknown whether lack of treatment may lead to more muscle atrophy and fatty replacement over time [8]. We suggest evaluating the patient’s strength and muscle enzymes every three to six months to monitor for the development of symptomatic disease that might require treatment or further evaluation, including magnetic resonance imaging (MRI) of the muscles up to once yearly to assess for evidence of edema and progression to fatty replacement. (See 'Mild to moderate muscle disease' below.)

Patients with cutaneous dermatomyositis (DM) commonly have subclinical muscle disease. For other patients, it is important to remember that there are multiple causes of muscle enzyme elevation other than inflammatory myopathy that may need to be considered. (See "Cutaneous dermatomyositis in adults: Overview and initial management".)

Mild to moderate muscle disease

Treatment approach — For patients with clinical weakness, we suggest simultaneous treatment with systemic glucocorticoids and a conventional synthetic disease-modifying antirheumatic drug (csDMARD) such as azathioprine, methotrexate, or mycophenolate.

For patients with moderate muscle disease (ie, significant muscle weakness on examination), we suggest using higher doses of glucocorticoids (eg, prednisone 1 mg/kg daily, to a maximum dose of 80 mg) in addition to a csDMARD.

●Mild muscle disease (ie, near normal muscle strength) – We suggest treating simultaneously with glucocorticoids (eg, prednisone 0.5 mg/kg) and either methotrexate, azathioprine, or mycophenolate.

●Moderate muscle disease (ie, significant muscle weakness on examination) – We suggest using higher doses of glucocorticoids (eg, prednisone 1 mg/kg daily, to a maximum dose of 80 mg) in addition to either methotrexate or azathioprine.

The typical dose ranges are:

●Methotrexate 15 to 25 mg weekly, given orally or subcutaneously. Initial dosing and titration regimens are the same as those for rheumatoid arthritis and are outlined elsewhere. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Dose titration'.)

●Azathioprine 2 mg per kg once daily, given orally. Specifics on dosing are found elsewhere. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Dose titration and monitoring'.)

●Mycophenolate 1 g twice daily, given orally.

The rationale for starting a csDMARD with glucocorticoids, choosing between methotrexate and azathioprine, and other alternative csDMARD options are discussed below. (See 'Rationale and selection of DMARD' below.)

Rationale for glucorticoids — Despite the absence of placebo-controlled trials demonstrating their effectiveness, glucocorticoids are the cornerstone of initial therapy for DM and polymyositis (PM). Although older studies were unable to demonstrate an improvement in survival with glucocorticoids [9,10], there is a general consensus that glucocorticoid therapy improves strength and preserves muscle function [11]. In a National Institutes of Health series, for example, 39 percent of 113 glucocorticoid-treated patients had complete normalization of serum enzymes, and 25 percent regained full muscle strength [12].

Data supporting use of adrenocorticotropic hormone (ACTH) gel (80 units subcutaneous, twice weekly) in place of oral glucocorticoids for the initial management of inflammatory myopathies are limited, and we do not recommend this approach [13].

Rationale and selection of DMARD

●Methotrexate versus azathioprine – We suggest avoiding methotrexate in patients with kidney function impairment, liver disease, or interstitial lung disease. Otherwise, choosing between methotrexate and azathioprine is largely dictated by the side effects associated with each agent and patient preference. Methotrexate is more convenient than azathioprine, requiring only once-a-week administration either orally or parenterally. Patients who are deficient in thiopurine methyltransferase may not be able to tolerate azathioprine. The specific adverse effects of these agents are discussed separately. (See "Major adverse effects of low-dose methotrexate" and "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Adverse effects'.)

Efficacy data do not support one agent over the other. No placebo-controlled prospective study has been conducted in DM or PM using methotrexate. Several retrospective series have found a response to methotrexate that ranges from 71 to 82 percent, even in patients who initially failed glucocorticoids [12,14-16].

A randomized trial of 16 patients compared prednisone plus azathioprine with prednisone alone [1]. At three months, there was no difference between the treatment groups in muscle strength or creatine kinase levels. However, at three years, patients treated with combination therapy had better functional outcomes and required less prednisone for maintenance therapy (1.6 mg daily versus 8.7 mg daily) [17]. The response to azathioprine may take as long as four to six months [18,19].

●Alternatives to methotrexate and azathioprine – Alternatives to these agents include mycophenolate mofetil (1 to 1.5 g twice daily) or tacrolimus (0.1 to 0.2 mg/kg daily, in two divided doses).

Use of mycophenolate mofetil has become increasingly common, particularly for patients with DM who also have skin disease.

Tacrolimus doses should be adjusted to maintain a trough concentration between 5 to 20 ng/mL, although the optimal target concentration has not been established. Other considerations for each of these agents, including dose titration, monitoring, and adverse effects, are discussed separately. (See "Mycophenolate: Overview of use and adverse effects in the treatment of rheumatic diseases" and "Pharmacology of calcineurin inhibitors".)

Data supporting the use of mycophenolate mofetil and tacrolimus are generally limited to small studies and case series [20-23].

●Rationale for starting csDMARD with glucocorticoids – As many as 50 percent of patients with PM do not respond to glucocorticoid therapy alone [5]. Patients who do respond to glucocorticoid monotherapy are at higher risk of relapse.

Severe muscle disease — For patients with severe disease (eg, dysphagia, diaphragmatic weakness, or weakness preventing self-care), we suggest treatment with intravenous immunoglobulin (IVIG; 2 g/kg, divided over two to five days, administered monthly) and IV methylprednisolone (1 g daily for three days), followed by prednisone 1 mg/kg daily (to a maximum dose of 80 mg daily). The rationale for the use of glucocorticoids is discussed elsewhere. (See "Overview of intravenous immune globulin (IVIG) therapy" and "Overview of intravenous immune globulin (IVIG) therapy", section on 'Dosing and administration' and 'Rationale for glucorticoids' above.)

Alternatives to IVIG include IV rituximab (1 g administered two weeks apart) and oral cyclophosphamide (2 mg/kg daily for six months). These agents are more commonly used for patients with DM or AsnS associated with severe interstitial lung disease, or IMNM (particularly anti-SPR myositis). While there is no expert consensus on the order in which such agents are used for patients with concomitant interstitial lung disease and severe muscle disease, many experts would use IVIG as well as either cyclophosphamide or rituximab for patients with interstitial lung disease. (See "Rituximab: Principles of use and adverse effects in rheumatoid arthritis", section on 'Administration and dosing' and "General principles of the use of cyclophosphamide in rheumatic diseases", section on 'Daily oral cyclophosphamide' and "Interstitial lung disease in dermatomyositis and polymyositis: Treatment", section on 'Refractory disease'.)

●Intravenous immunoglobulin – In a randomized, double-blind, placebo-controlled trial of 95 patients with DM, 78.7 percent of patients responded to IVIG compared with 43.8 percent of placebo-treated patients (rate difference 35 percent, 95% CI 16.70-53.24) [24].

●Rituximab – The Rituximab in Myositis (RIM) trial is the largest randomized, double-blind, placebo-controlled trial conducted in the inflammatory myopathies [25]. RIM enrolled 75 patients with PM, 72 patients with DM, and 48 patients with juvenile DM who were randomized to receive treatment with rituximab, either at baseline or after a delay of eight weeks. By the end of the study, 83 percent of patients demonstrated clinical improvement, although there was no statistically significant difference between the two groups. A post-hoc analysis demonstrated that the fastest response to rituximab was seen among patients with antisynthetase and anti-Mi-2 autoantibodies [26].

●Cyclophosphamide – Data supporting the use of cyclophosphamide for DM or PM are predominantly limited to small series [27], and it is generally not used for muscle or skin disease in the absence of concomitant interstitial lung disease.

ASSESSING TREATMENT RESPONSE — The response to treatment should be assessed three months after the start of therapy. Failure to observe clinical or laboratory improvement after three to four months of therapy should prompt consideration of alternate treatment strategies. The management of such patients is discussed separately. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults".)

Laboratory assessment — We suggest testing muscle enzymes every two to four weeks until the muscle enzymes begin to normalize. Muscle enzymes usually begin to decline within a few weeks of treatment and generally normalize within the first six months, although persistently elevated muscle enzymes in the absence of symptoms can be observed. It is debated as to whether increasing immunosuppression to normalize the muscle enzymes is necessary. In our clinical practice, our personal practice has changed over time, and we are now more likely to try to normalize the muscle enzymes even if full strength returns. If the muscle enzymes normalize, they should continue to be monitored in three- to six-month intervals or earlier if muscle symptom worsening is noted by the patient.

Clinical assessment — We suggest testing muscle strength approximately every three months to monitor the response to therapy, especially within the first year of diagnosis or change in therapy. Muscle strength recovery lags behind the decline in muscle enzymes, and maximal recovery of strength may not occur for several months.

The clinician should test the affected muscle groups on a regular basis as the primary gauge of clinical progress. It is useful to determine which muscles are the weakest for a given patient and to test these muscles sequentially over time. Since proximal muscles are typically most involved, the following muscle groups are often tested:

●Upper extremity and neck

•Deltoids – Asking the patient to abduct the arms to 90 degrees and resist the examiner pushing down on the arms.

•Neck flexors – Asking the supine patient to push their head forward while the examiner applies reverse pressure against the forehead.

●Lower extremity

•Quadriceps – Asking the patient to extend the lower leg against resistance with the limb flexed at the hip and knee.

•Hip flexors – Asking the patient to flex the thigh against resistance with the leg flexed at the knee and hip. The examination may also be performed with the patient supine and the examiner assessing strength against resistance with the hip flexed to 60 degrees with their knee extended. We prefer to examine the hip flexors supine to better assess the presence of mild weakness. Care must be taken to examine both proximal and distal musculature, including ankle dorsiflexors and plantar flexors, which can broaden the differential diagnosis when present.

Proximal lower-extremity strength, including the quadriceps and other muscles, may also be evaluated by asking the patient to cross their arms and rise from a chair, using only the proximal leg muscles. Quantitative strength testing, such as the use of a handheld dynamometer, can be useful to further assess muscles that are in the 4 to 5 range to provide a more precise assessment of strength and can also provide more consistency between multiple providers who assess the patient, but it is likely best reserved for tertiary care settings and research studies rather than generally being recommended for clinical practice.

Other assessments — We suggest pulmonary function testing in patients with respiratory muscle weakness or interstitial lung disease. Pulmonary function tests can be assessed two to three months after initiating treatment, and in 6- to 12-month intervals thereafter. Patients with respiratory muscle involvement should experience improvements in pulmonary function testing with immunosuppression. For patients with interstitial lung disease, lack of worsening of pulmonary function tests may reflect treatment response. (See "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis", section on 'Pulmonary function tests'.)

Muscle MRI, generally performed on the bilateral thighs, can serve as an additional measure of therapeutic response, although repeat imaging and/or electromyography (EMG) is often reserved only for patients with a suboptimal response to therapy.

SUBSEQUENT THERAPY

Patients with clinical response — We suggest tapering glucocorticoids while continuing disease-modifying antirheumatic drug (DMARD) therapy to ensure disease stability. (See 'Duration of DMARD therapy' below.)

Glucocorticoid tapering — The decision to begin tapering glucocorticoids should be based on a combination of the improvement in muscle enzymes and recovery of muscle strength. We typically start a gradual glucocorticoid taper after four weeks of initial therapy to reduce the risk of developing glucocorticoid myopathy. Ideally, normalization of enzymes and complete recovery of muscle strength should occur before glucocorticoids are tapered.

The glucocorticoid dose can usually be gradually reduced over the next 9 to 12 months to the minimum dose required to maintain disease control. There is no standard tapering regimen for the inflammatory myopathies, but regimens similar to the one outlined below are often used. Assuming that a patient begins prednisone treatment at 60 mg daily and remains on this dose for six weeks, the following taper will require a total of 26 weeks to reach a daily dose of 5 mg:

●The prednisone dose should be tapered by 10 mg each week until a dose of 40 mg daily is reached.

●After one week on 40 mg daily, the prednisone dose should be tapered by 5 mg each week until the patient reaches 20 mg daily.

●After one week on 20 mg daily, the prednisone dose should be tapered by 2.5 mg each week until the patient reaches 10 mg daily.

●After one week on 10 mg daily, the prednisone dose should be tapered by 1 mg every two weeks until the patient reaches 5 mg daily.

If there are no disease flares, most patients discontinue glucocorticoids at 9 to 12 months. Some patients may be maintained on low-dose glucocorticoids (<5 mg daily) for longer periods of time if disease worsening occurs with attempted tapers, although ideally tapering off glucocorticoids completely is preferred.

●Monitoring during taper – The patient should be monitored carefully during the tapering period to watch for signs of recurrent weakness, extramuscular complications, or glucocorticoid toxicity. The recurrence of proximal muscle weakness in a patient treated for a prolonged period with glucocorticoids poses a significant clinical conundrum, as steroid myopathy also affects the proximal musculature. (See "Major adverse effects of systemic glucocorticoids".)

●Adjusting glucocorticoid taper – Deviations from this regimen may be necessary if the patient develops a glucocorticoid myopathy or experiences a disease flare. Some patients may need to remain on a low dose of prednisone (eg, 5 mg daily) to prevent disease relapse.

●Alternate-day glucocorticoid taper – Although some clinicians use alternate-day glucocorticoid tapers for the treatment of inflammatory myopathies, there is little indication that such regimens are associated with less toxicity compared with the conventional regimen outlined above.

Duration of DMARD therapy — If a patient has successfully discontinued glucocorticoids and has remained in a glucocorticoid-free remission for at least one to two years, it is reasonable to consider a gradual taper of the glucocorticoid-sparing agent. The exception to this recommendation is in patients with autoimmune necrotizing myopathies who can often reduce their immunosuppression or immunomodulator dosing but generally cannot successfully taper off immunosuppression or immunomodulators such as intravenous immunoglobulin (IVIG) without disease flares. However, there are no studies that address the question of the optimal duration of therapy. The decision to taper therapy should be based on patient preference, the presence of treatment associated adverse events, and the patient’s history of relapse.

●Tapering strategies – Tapering of conventional synthetic DMARDs (csDMARDS; eg, methotrexate, azathioprine, or mycophenolate) should be conducted gradually, with planned cessation of therapy over approximately six months or longer.

With IVIG, the dose may be reduced or the interval between infusions may be gradually increased. A suggested tapering strategy may be one of the following: If both strength and creatine kinase have normalized after five to six months of therapy, the dose may be reduced form 2 g/kg monthly to 1 g/kg monthly. This is generally continued for at least six more months, after which a further reduction can occur, but this time the reduction should be done by gradually lengthening the dosing interval by two weeks, eg, to every six weeks, for a few cycles, then every eight weeks, etc. Alternatively, the initial 2 g/kg monthly dose may be reduced by maintaining the dose but increasing the interval to six weeks and gradually lengthening the interval as above.

●Monitoring during DMARD tapering – During DMARD tapering, the patient's clinical status must be closely monitored to permit early detection of disease flares so that the disease does not require the resumption of high-dose glucocorticoids.

Patients with resistant disease — For patients who have failed to have improvement in muscle enzymes or experience worsening muscle strength following four weeks of therapy, alternate treatment approaches may be required. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults", section on 'Resistant disease'.)

OTHER MANAGEMENT RECOMMENDATIONS — In addition to drug therapy, there are a variety of other important considerations in the treatment of patients with inflammatory myopathy. These include the initiation of an exercise program under the supervision of a physical therapist, steps to prevent aspiration in patients with esophageal dysfunction, counseling about the need for patients with dermatomyositis (DM) to avoid ultraviolet light, and prophylaxis against osteoporosis and opportunistic infections.

Exercise — We suggest the following approach:

●Bedridden or chair-bound patients with severe weakness should receive passive range of motion exercises to prevent joint contractures. Careful attention to positioning reduces the risk of pressure sores.

●Isometric and resistive exercises should begin as soon as the patient has recovered enough strength to be able to participate.

●Patients with less severe weakness should be encouraged to participate in an active exercise program, progressing as tolerated from lower-level isometric exercises to more vigorous isotonic exercises [28].

Observational studies support the early introduction of physical therapy to improve muscle strength [29-31]. However, large studies of exercise for inflammatory myopathy have not been performed, and there are limited data demonstrating benefit.

Aspiration risk — For patients with dysphagia due to cricopharyngeal muscle dysfunction, we suggest the following approach:

●Speech therapy consultation for advice about aspiration risk and precautions

●Elevation of the head of the bed

●Semi-thick diets

●A nasopharyngeal or gastric feeding tube may be necessary to provide adequate nutrition and to help protect the airway in patients with severe dysphagia

In addition, patients with myositis and overlap with scleroderma may develop reflux esophagitis due to incompetence of the lower esophageal sphincter. Treatment with proton pump inhibitors decreases both the risk of stricture formation and reflux symptoms, but some patients have persistent symptoms. The treatment of refractory gastroesophageal reflux is discussed separately. (See "Approach to refractory gastroesophageal reflux disease in adults".)

Skin disease and avoidance of sunlight — The cutaneous manifestations of DM are often photosensitive, and patients should be counseled to avoid direct sun exposure. Skin manifestations can persist despite effective treatment of myositis. Pruritus is often a significant complaint and may be treated with topical agents such as menthol, camphor, antihistamines, pramoxine, and lidocaine. Systemic agents used include hydroxyzine, doxepin, and amitriptyline. The treatment of the cutaneous manifestations of DM is reviewed in detail separately. (See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Treatment'.)

Osteoporosis prevention — All patients treated with high-dose glucocorticoids are at risk for glucocorticoid-induced osteoporosis. Thus, all patients embarking upon treatment courses for inflammatory myopathy are potential candidates for antiresorptive therapy designed to prevent bone loss.

The prevention and treatment of glucocorticoid-induced osteoporosis are discussed separately. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Opportunistic infections — Because of the high-dose glucocorticoid therapy and other immunosuppressive medications used to treat inflammatory myopathy, patients with DM and polymyositis (PM) are at an increased risk for opportunistic infection, including Pneumocystis jirovecii, fungal, mycobacterial, and viral infections [32,33].

Management and prophylaxis against opportunistic infections is discussed elsewhere. (See "Evaluation and prevention of infections associated with biologic agents and JAK inhibitors in adults".)

Immunizations — We advise that patients receive appropriate immunizations prior to the institution of immunosuppressive therapies (table 1). (See "Immunizations in autoimmune inflammatory rheumatic disease in adults" and "Immunizations in autoimmune inflammatory rheumatic disease in adults", section on 'Approach to vaccination'.)

Pregnancy — We suggest delaying attempts to conceive until after disease remission has been achieved for at least three months.

The outcomes of pregnancy in patients with idiopathic inflammatory myopathies (IIM) and the influence of pregnancy on the activity of inflammatory muscle disease are both issues for which there are few data [34].

In one review of 43 pregnancies in women with inflammatory myopathy, healthy births were more likely when the myositis was inactive (73 versus 26 percent) [34].

Additional considerations regarding the use of immunosuppressive agents are discussed elsewhere. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)

PROGNOSIS — Disease severity and outcome are highly variable, ranging from mild monophasic disease readily responsive to antiinflammatory treatment to cases that follow a relentless downhill course unresponsive to treatment. Response rates to treatment and mortality rates are difficult to measure from the literature because of the lack of prospective controlled trials, variability in diagnostic criteria and treatment modalities over time, and lack of uniform response definitions.

Mortality — In a study of 107 patients diagnosed with an inflammatory myopathy, the 10-year survival rate was 71 percent [35]. Risk factors for mortality among patients with idiopathic inflammatory myopathies (IIM) include [36]:

●Increased age

●Male sex

●Interstitial lung disease

●Cancer

●Delay in diagnosis or treatment

Treatment response — In one study of 165 patients followed or a median of five years, 20 percent had monophasic course [37].

In another study of 77 patients with either DM or PM, certain demographic and clinical characteristics are associated with a poorer response to treatment and poorer outcome and include [38]:

●Older age

●Pulmonary involvement

●Dysphagia

●Underlying malignancy

●Delay in diagnosis or initiation of treatment

●Greater weakness at presentation

Some myositis-associated antibodies (MSA), such as anti-PMScl, anti-MDA-5, or anti-SRP antibodies, can be associated with a poor treatment response [39]. Patients without a detectable MSA require longer treatment courses than patients with an identified MSA [40]. A more detailed description of the MSA is presented separately. (See "Overview of and approach to the idiopathic inflammatory myopathies", section on 'Myositis-specific autoantibodies' and "Overview of and approach to the idiopathic inflammatory myopathies", section on 'Myositis-associated autoantibodies'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dermatomyositis and polymyositis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Dermatomyositis (The Basics)" and "Patient education: Polymyositis (The Basics)")

●Beyond the Basics topics (see "Patient education: Polymyositis, dermatomyositis, and other forms of idiopathic inflammatory myopathy (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Initial therapy

•Subclinical muscle disease – For patients with clinically asymptomatic muscle disease and a creatinine kinase less than 5 times the upper limit of normal, systemic immunosuppression is not indicated. (See 'Subclinical muscle disease' above.)

•Mild to moderate muscle disease – Glucocorticoids are the cornerstone of therapy for the inflammatory myopathies. For patients with symptomatic weakness, we suggest treatment with glucocorticoids and a disease-modifying antirheumatic drug (DMARD) rather than glucocorticoids alone, due to the high risk of relapse associated with glucocorticoid monotherapy (Grade 2C). The dose of glucocorticoids depends on the severity of muscle disease (ie., 0.5 mg/kg for mild muscle disease, 1 mg/kg for moderate muscle disease). We suggest the use of either methotrexate (15 to 25 mg weekly, oral or subcutaneous) or azathioprine (2 mg/kg daily) for DMARD therapy, although other alternatives exist. (See 'Mild to moderate muscle disease' above.)

•Severe muscle disease – For patients with severe disease (eg, dysphagia, diaphragmatic weakness, or weakness preventing self-care), we suggest treatment with intravenous immunoglobulin (IVIG; 2 g/kg divided over two to five days, administered monthly) and IV methylprednisolone (1 g daily for three days) rather than other combinations of immunosuppression (Grade 2C). IV methylprednisolone should be followed by prednisone 1 mg/kg daily (to a maximum dose of 80 mg daily). (See 'Severe muscle disease' above.)

●Assessing treatment response – We suggest monitoring the response to therapy by testing muscle enzymes every two weeks and muscle strength every three months. For patients with pulmonary involvement, we suggest pulmonary function testing two to three months after initiating treatment. (See 'Assessing treatment response' above.)

●Patients with clinical response – After four weeks of therapy, we suggest a gradual taper in glucocorticoid dose over the subsequent 9 to 12 months. After a patient has been in a glucocorticoid-free remission for at least one year, it is reasonable to consider a gradual taper in DMARDs, although this is an individual decision that should be based on patient preference and risk of relapse. (See 'Patients with clinical response' above.)

●Other management recommendations – All patients should have an exercise program and appropriate prophylaxis for osteoporosis and opportunistic infections. Patients at risk of aspiration and patients with cutaneous manifestations of dermatomyositis (DM) may require additional precautions. (See 'Other management recommendations' above.)

●Prognosis – Disease severity, treatment response, and mortality are highly variable. Older patients and patients with lung disease or cancer tend to have the worst outcomes. (See 'Prognosis' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Stacy Rudnicki, MD and Marc L Miller, MD, who contributed to earlier versions of this topic review.