Initial treatment of dermatomyositis and polymyositis in adults

INTRODUCTION — Dermatomyositis (DM) and polymyositis (PM) are classified as idiopathic inflammatory myopathies. Defining the optimal treatment regimens for these disorders has been difficult because of the rarity of these disorders, their highly complex clinical phenotypes, and the limited number of randomized, double-blind clinical trials [1-3].

In addition, understanding of the inflammatory myopathies has evolved over the years, but disease classification schemes have not kept pace. Newer classifications, based upon histologic and serologic distinctions between the different disorders, may help define the natural history of these diseases better, may assist in the design of well-conceived randomized clinical trials, and may lead to the development of rational therapies [4-6].

The initial therapy of DM and PM 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 DM and PM in children are discussed separately. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults" and "Clinical manifestations of dermatomyositis and polymyositis in adults" and "Cutaneous dermatomyositis in adults: Overview and initial management" and "Management of refractory cutaneous dermatomyositis in adults" and "Juvenile dermatomyositis and other idiopathic inflammatory myopathies: Epidemiology, pathogenesis, and clinical manifestations" and "Juvenile dermatomyositis and polymyositis: Treatment, complications, and prognosis".)

PROGNOSIS AND PREDICTORS OF OUTCOME — 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. Mortality rates are increased compared with individuals without inflammatory myopathy. 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. Nevertheless, some general conclusions can be made.

Certain demographic and clinical characteristics are associated with a poorer response to treatment and poorer outcome and include [7]:

●Older age

●Pulmonary involvement

●Dysphagia

●Underlying malignancy

●Delay in diagnosis or initiation of treatment

●Greater weakness at presentation

Myositis-specific and myositis-associated autoantibodies that help define certain myositis subgroups appear to also have predictive value for response to treatment [8]:

●Patients with anti-Jo-1 antibodies and anti-synthetase syndrome often have an incomplete response to treatment and worse long-term prognosis related to the presence of associated interstitial lung disease.

●Anti-signal recognition particle (SRP) antibodies are associated with immune-mediated necrotizing myositis. These patients often present with marked creatine kinase (CK) elevation and severe weakness and are less responsive to treatment.

●Patients with anti-Mi-2 antibodies have prominent dermatomyositis (DM) rashes and markedly elevated CK levels and respond well to treatment with corticosteroids and have a favorable long-term outcome.

●Myositis-associated antibodies including anti-ribonucleoprotein (RNP), anti-Ku, and anti-PM-Scl are associated with a favorable outcome, while anti-Ro52 has been associated with interstitial lung disease and poor prognosis.

A more detailed description of the myositis-specific and myositis-associated autoantibodies 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'.)

Mortality rates in DM and polymyositis (PM) are increased with cancer, pulmonary and cardiac disease, and infections accounting for the increase. Risk factors for mortality include [9]:

●Increased age

●Male sex

●Interstitial lung disease

●Cancer

●Delay in diagnosis or treatment

INITIAL THERAPY — The goals of treatment are to improve muscle strength and to avoid the development of extramuscular complications. In patients with dermatomyositis (DM), resolution of cutaneous disease manifestations is an additional goal.

Despite the absence of placebo-controlled trials demonstrating their effectiveness, glucocorticoids are the cornerstone of initial therapy for DM and polymyositis (PM). Some clinicians also begin treatment immediately with a glucocorticoid-sparing agent, generally azathioprine or methotrexate, particularly in patients who are severely ill. (See 'Glucocorticoid-sparing agents' below.)

Systemic glucocorticoids — Although older studies were unable to demonstrate an improvement in survival with glucocorticoids [10,11], there is a general consensus that glucocorticoid therapy improves strength and preserves muscle function [12]. 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 [13].

The outcome of patients in community hospital settings may be better than those presumably more ill patients in tertiary care settings. As an example, in a report of 27 patients, 17 (64 percent) had little or no weakness after glucocorticoid therapy, and 11 (41 percent) achieved prolonged remissions off all medications [14].

General approach — Clinicians should inform patients at the start of therapy that they will be on prednisone in tapering doses for approximately one year, depending upon their response to therapy and achievement of disease control. Discussion of the potential side effects of glucocorticoids is essential so that patients know what to anticipate. (See "Major adverse effects of systemic glucocorticoids".)

There is no standard glucocorticoid regimen for treating the inflammatory myopathies, but two general principles apply:

●Initiation of treatment with high doses for the first several months to establish disease control

●Slow taper to the lowest effective dose for a total duration of therapy between 9 and 12 months

Initial glucocorticoid therapy — Glucocorticoid therapy in DM or PM is typically initiated with prednisone at a dose of 1 mg/kg per day, to a maximum daily dose of 80 mg [12]. Pulse methylprednisolone (1000 mg per day for three days) may be used at the start of therapy for patients who are severely ill.

For the first four to six weeks of therapy, prednisone is continued at 1 mg/kg per day with ongoing assessment of the clinical response. Maintenance of the prednisone dose at 1 mg/kg per day beyond six weeks may increase the risk of developing glucocorticoid myopathy. (See "Glucocorticoid-induced myopathy".)

Assessing treatment response — The response to glucocorticoids should be assessed every few weeks after the start of therapy. Muscle enzymes begin to decline within a few weeks of treatment and generally normalize by about six weeks. Muscle strength recovery, however, lags behind the decline in muscle enzymes, and maximal recovery of strength may not occur until three months, although this is variable. In DM, the time courses of cutaneous responses to therapy are similar: some patients respond promptly, and, in others, improvement is more delayed.

Once treatment has begun, the clinician should select several muscle groups to test 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:

●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

Proximal lower extremity strength, including the quadriceps and other muscles, may also be evaluated by asking the patient to cross his or her arms and to rise from a chair, using only the proximal leg muscles.

●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 patient to push his or her head forward while the examiner applies reverse pressure against the forehead

Patients with respiratory muscle weakness or interstitial lung disease can be assessed with serial pulmonary function testing. It is reasonable to test at two to three months after initiating treatment.

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. Ideally, normalization of enzymes and complete recovery of muscle strength should occur before glucocorticoids are tapered, although continuation of high-dose glucocorticoids for more than six weeks may cause steroid myopathy and decline in strength. (See 'Glucocorticoid-sparing agents' below.)

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/day 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/day is reached.

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

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

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

Deviations from this regimen may be necessary if patients develop glucocorticoid myopathy or experience disease flares. Continuation of the prednisone taper can be considered if the patient has achieved and maintained good disease control. Tapering off prednisone completely should not proceed faster than 1 mg decreases every two weeks.

The patient should be monitored carefully during the tapering period and should be watched for signs of recurrent weakness, extramuscular complications of DM or PM, and signs of 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".)

Alternate-day glucocorticoid tapers — 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.

Glucocorticoid responses — Overall, more than 80 percent of patients with inflammatory myopathies improve with glucocorticoids alone. However, as many as 50 percent of patients with PM do not respond to glucocorticoid therapy alone [4]. Furthermore, among patients who do respond, the majority do not return to normal muscle strength [13].

Apparent glucocorticoid failures — In the setting of apparent failure to respond to glucocorticoids, three possibilities should be reviewed before intensifying immunosuppression:

●Alternative diagnoses such as inclusion body myositis, muscular dystrophy, or hypothyroidism should be considered. Repeat muscle biopsies may need to be performed. (See "Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults", section on 'Differential diagnosis'.)

●If the diagnosis of DM or PM is confirmed, glucocorticoid-induced myopathy should be considered if the patient remains weak or has developed recurrent weakness in the setting of normal muscle enzyme levels. (See "Glucocorticoid-induced myopathy".)

Continued evidence of fibrillation potentials and positive sharp waves on electromyography suggests active myositis [15]. Because of the patchy nature of inflammation and the fact that inactivity may cause type 2 muscle fiber atrophy, muscle biopsy may not always help in distinguishing glucocorticoid-induced myopathy from poorly controlled myositis. The potential utility of magnetic resonance imaging (MRI) to distinguish between glucocorticoid-induced myopathy and active myositis remains undefined.

An empiric trial of lowering the prednisone dose and observing the muscle strength response is a practical approach to this dilemma.

●An unrecognized malignancy associated with myositis may be a cause of failed response to glucocorticoids. Most myositis-associated malignancies are diagnosed within the two-year period before and after the development of myositis [16]. (See "Malignancy in dermatomyositis and polymyositis".)

In evaluating patients with inflammatory myopathies for potential malignancy, the recommended approach is to perform a comprehensive history and physical examination, routine laboratory testing, and a chest X-ray. Age-appropriate cancer screening is justified, but "fishing expeditions" are discouraged. A full discussion of the approach to screening patients with DM or PM for malignancy is provided separately. (See "Malignancy in dermatomyositis and polymyositis".)

Once alternative underlying diagnoses, glucocorticoid myopathy, and occult malignancy have been excluded satisfactorily, the next step is the addition of a glucocorticoid-sparing agent.

GLUCOCORTICOID-SPARING AGENTS — A glucocorticoid-sparing immunosuppressive agent is generally initiated with glucocorticoid treatment because of the potential for these medications to reduce the cumulative dose of prednisone and thereby diminish glucocorticoid-induced morbidity. For patients in whom glucocorticoids are contraindicated, these glucocorticoid-sparing agents are occasionally used as a first-line drug.

Agent selection — For the majority of patients with dermatomyositis (DM), the current first-line glucocorticoid-sparing agent is usually either azathioprine or methotrexate. However, for those who present with life-threatening manifestations of DM or polymyositis (PM), such as severe weakness or dysphagia, we suggest using intravenous immune globulin (IVIG) as the first-line glucocorticoid-sparing agent. (See 'Intravenous immune globulin' below.)

These drugs have not been compared directly in a clinical trial. Because of hepatotoxicity and pulmonary toxicity associated with methotrexate, azathioprine or mycophenolate mofetil are preferred in patients who have interstitial lung disease associated with their myositis, have underlying liver disease, or are unwilling to abstain from alcohol.

Timing of initiation — Starting a glucocorticoid-sparing agent simultaneously with prednisone may prevent intermediate and long-term side effects, particularly in patients with concomitant medical problems such as diabetes. In addition, those patients with profound weakness or significant extramuscular complications warrant treatment with two drugs from the outset. As examples, patients with interstitial lung disease or severe esophageal dysfunction are candidates for a glucocorticoid-sparing agent from the start of therapy.

Azathioprine — 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 (CK) levels. However, at three years, patients treated with combination therapy had better functional outcomes and required less prednisone as maintenance therapy (1.6 mg/day versus 8.7 mg/day) [17]. The response to azathioprine may take as long as four to six months [18,19].

Dosing and monitoring — We use an initial dose of azathioprine of 50 mg/day and obtain a complete blood count (CBC) after two weeks of therapy to assure that the counts are stable. We then increase the daily dose by 50 mg each week to 1.5 mg/kg/day. In patients with an inadequate response after three months of therapy, we increase the dose as tolerated up to as high as 2.5 mg/kg/day. Some experts do not exceed a dose of 250 mg/day. We obtain CBCs, a platelet count, and liver function tests monthly initially, and once a stable dose is achieved we perform testing every three months.

Alternative approaches, including more gradual dose escalation and more frequent monitoring, are recommended by some experts. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Dose titration and monitoring'.)

There is uncertainty regarding the benefits of routine testing for thiopurine methyltransferase (TPMT) deficiency before beginning azathioprine. Although some clinicians routinely perform TPMT testing prior to initiating azathioprine, others do not perform such testing but rather initiate therapy at a low dose with close monitoring as the dose is gradually increased. The use of TPMT testing along with other potential adverse effects are discussed in detail separately. (See "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Pharmacogenetics and azathioprine toxicity' and "Pharmacology and side effects of azathioprine when used in rheumatic diseases", section on 'Adverse effects'.)

Adverse effects — Systemic flu-like reactions associated with fever and gastrointestinal complaints develop in up to 12 percent of patients treated with azathioprine. These reactions are independent of TPMT status and require discontinuation of the drug [20]. Other side effects include bone marrow suppression, pancreatitis, and liver toxicity. Long-term side effects may include increased risk of malignancy.

Methotrexate — No placebo-controlled prospective study has been done in DM or PM using methotrexate. Several retrospective series have found response rates ranging from 71 to 82 percent, even in patients who initially failed glucocorticoids [13,21-23].

Dosing — Methotrexate has an advantage over azathioprine in convenience, requiring only once-a-week administration either orally or parenterally. Methotrexate is administered with the same dosing regimen as that used for rheumatoid arthritis, generally starting with an initial dose of 15 mg/week and increasing slowly by 2.5 mg/week every two to four weeks, if there is inadequate response to the lower dose, up to a maximum dose of 25 mg/week over two to three months. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Dosing and administration'.)

Prior to the availability of alternative therapies, higher doses of methotrexate (up to 50 mg/week) had been used for refractory or resistant disease [23]. When used in doses above 25 mg/week, oral administration of methotrexate is usually replaced by the subcutaneous, intramuscular, or intravenous route, depending upon the clinical setting. In such circumstances, higher doses of folic acid (eg, 2 or 3 mg/day) or leucovorin (folinic acid) may also be required depending on symptoms associated with methotrexate use. For leucovorin, 5 mg of leucovorin is given once weekly, 8 to 12 hours after methotrexate administration. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Folic acid supplementation' and "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults", section on 'Resistant disease'.)

Adverse effects — Methotrexate toxicity, including stomatitis, gastrointestinal symptoms, and leukopenia, can be seen with low-dose therapy. This risk can be minimized by the concurrent administration of folic acid (1 to 2 mg/day) or, in patients who do not respond completely to folic acid, by the use of leucovorin (5 mg per week, 8 to 12 hours after the methotrexate dose). (See "Major side effects of low-dose methotrexate".)

Because of potential hepatotoxicity, the use of methotrexate may be problematic in patients with a history of liver disease or in those who drink alcohol, even in modest quantities. Azathioprine is preferred in patients with liver disease and in those unwilling to abstain from alcohol, although it also can cause abnormalities in liver function. (See "Hepatotoxicity associated with chronic low-dose methotrexate for nonmalignant disease".)

There is no evidence that methotrexate pulmonary toxicity is more common in patients with myositis-associated interstitial lung disease. However, the development of methotrexate pneumonitis in a myositis patient presents diagnostic difficulties. In addition, the patient's already compromised pulmonary function increases the risk for a bad outcome. (See "Methotrexate-induced lung injury".)

Intravenous immune globulin — For patients with severe life-threatening weakness or dysphagia at risk for aspiration, we favor IVIG as the preferred glucocorticoid-sparing agent. IVIG is also effective against the cutaneous manifestations of myopathic DM and can be used in those patients with severe rash [24,25]. Some patients may eventually be able to transition from IVIG to another immunosuppressive agent. Dosing of IVIG is discussed elsewhere. (See "Management of refractory cutaneous dermatomyositis in adults", section on 'Intravenous immune globulin'.)

IVIG is favored for these indications because it may have a more rapid onset of action than glucocorticoids. However, prolonged treatment may be limited by difficulty of administration, cost, and potential toxicity.

IVIG has received US Food and Drug Administration (FDA) approval for the treatment of adults with DM. An industry-sponsored randomized trial of 95 patients with DM demonstrated that the percentage of patients who achieved at least minimal improvement based on a composite score of disease activity was higher among those who received IVIG compared with placebo (79 versus 44 percent) at 16 weeks [26]. IVIG was associated with more adverse events, including thromboembolic events.

Additional information regarding the use of IVIG for DM can be found elsewhere. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults".)

Antimalarials — Hydroxychloroquine (200 to 400 mg/day) is effective in up to 75 percent of patients in controlling skin disease but without any benefit to muscle disease [27]. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults", section on 'Refractory rash'.)

Other agents — Additional glucocorticoid-sparing therapies are discussed elsewhere. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults", section on 'Resistant disease'.)

DURATION OF THERAPY — Most patients wish to discontinue immunosuppressive therapy at some point if the disease is well-controlled. However, there are no studies that address the question of the optimal duration.

We attempt to discontinue all immunosuppressive medications after the first round of therapy, with careful monitoring by the patient and clinician for early signs of relapse.

Most patients and clinicians prefer to discontinue glucocorticoids before stopping azathioprine or methotrexate. Attempts to taper azathioprine or methotrexate gradually are reasonable in patients who have achieved remission and have discontinued glucocorticoids.

The glucocorticoid tapering regimen is described above. If there are no disease flares during the course of the taper, most patients discontinue glucocorticoids at 9 to 12 months. (See 'Glucocorticoid tapering' above.)

Tapering of azathioprine or methotrexate should be conducted at monthly intervals after the patient is in clinical remission, with planned cessation of therapy over approximately six months. The patient's clinical status must be closely monitored to permit early detection of disease flares, at a severity that does not require the resumption of high-dose glucocorticoids.

LONG-TERM FOLLOW-UP — Long-term follow-up data on patients with inflammatory myopathy are few. One study followed 165 patients for a median of five years [28]. Of the 165 patients, 157 (95 percent) were treated with glucocorticoids and 94 (57 percent) with other immunosuppressive or immunomodulating agents. Sixty percent of the patients had courses characterized as chronic, 20 percent had polycyclic disease courses, and 20 percent had monophasic courses.

Side effects of therapy included:

●Cushingoid appearance (71 percent)

●Psychological or psychiatric symptoms (35 percent)

●Osteoporosis (29 percent)

●Infections (29 percent)

Malignancy developed in five patients following the diagnosis of inflammatory myopathy. Thirty-four patients died over the course of follow-up, including 18 deaths related directly to myositis, 7 to cancer, 4 to pulmonary complications, and 4 to complications of medications.

Among the 110 patients (84 percent of the 131 survivors) re-examined after a mean of five years, 24 percent had considerable disability, 25 percent had significant muscle weakness, and 84 percent had an abnormal quality of life.

Forty-one percent of patients were still using more than 10 mg/day of prednisone or an immunosuppressive agent.

RECURRENT AND RESISTANT DISEASE — Some patients either relapse after an initial response or fail to respond to the above regimens. The management of such patients is discussed separately. (See "Treatment of recurrent and resistant dermatomyositis and polymyositis in adults".)

GENERAL MEASURES AND EXTRAMUSCULAR MANIFESTATIONS — 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 — Large studies of the role of exercise during rehabilitation for inflammatory myopathy have not been performed [29]. While strength and aerobic exercise training programs do not appear to cause harm [30], there is limited evidence to conclude that they offer benefit [31]. However, observational studies support the concept that physical therapy and rehabilitation should begin early in the course of treatment, with regimens tailored to the severity of weakness:

●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.

●Patients with mild weakness should be encouraged to continue reasonable levels of activity as tolerated [32].

Aspiration risk — Patients with dysphagia due to cricopharyngeal muscle dysfunction are at risk for aspiration. Several interventions can reduce this risk:

●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.

●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 frequently respond to the agents used to treat the associated myositis, including glucocorticoids, methotrexate, and azathioprine. However, skin manifestations can persist despite effective treatment of myositis. Therapy for cutaneous disease is usually indicated due to the presence of severe pruritus and patient distress over the appearance of skin lesions. The treatment of the cutaneous manifestations of DM is reviewed in detail separately. (See "Cutaneous dermatomyositis in adults: Overview and initial management" and "Management of refractory cutaneous dermatomyositis in adults".)

Scrupulous protection from the sun, including liberal use of sunscreens and sun-protective clothing, is important because the rashes are often related to photosensitivity. Patients can also benefit from use of topical corticosteroids. (See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Photoprotection' and "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Topical corticosteroids'.)

Antimalarial drugs can be used to treat the skin disease in patients with prominent rash or DM sine myositis (amyopathic DM). In such patients, hydroxychloroquine (HCQ) used in combination with quinacrine may be effective if HCQ alone is inadequate. In addition, topical tacrolimus can be effective for skin lesions refractory to other therapies. (See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Interventions for pruritus' and "Cutaneous dermatomyositis in adults: Overview and initial management".)

Pruritus — Pruritus is often a significant complaint. Various topical remedies used include menthol, camphor, antihistamines, pramoxine, and lidocaine. Systemic agents used include hydroxyzine, doxepin, and amitriptyline. (See "Cutaneous dermatomyositis in adults: Overview and initial management", section on 'Interventions for pruritus'.)

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. Pneumocystis jirovecii, a common pathogen in immunosuppressed hosts, may cause lethal infections, particularly in patients with interstitial lung disease. Fungal and mycobacterial infections of the lung and gastrointestinal tract and herpesvirus infections may also occur [33,34]. (See "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

Prophylaxis against pneumocystic jirovecii is thus often indicated for patients treated with high-dose glucocorticoids and/or other immunosuppressive agents. (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Prophylaxis' and "Interstitial lung disease in dermatomyositis and polymyositis: Clinical manifestations and diagnosis", section on 'Differential diagnosis'.)

A common prophylactic strategy for Pneumocystis involves the use of one double-strength tablet daily of trimethoprim-sulfamethoxazole (TMP/SMZ), which contains 160 mg of trimethoprim and 800 mg of sulfamethoxazole. Because both trimethoprim and methotrexate are folate antagonists, some have raised concerns that the use of double-strength TMP/SMZ tablets on a daily basis combined with weekly methotrexate may lead to bone marrow suppression. For myositis patients treated with methotrexate, daily single-strength TMP/SMZ (80 mg of trimethoprim and 400 mg of sulfamethoxazole) is likely to be safe.

Immunizations — We advise that patients receive appropriate immunizations prior to the institution of immunosuppressive therapies (table 1).

PREGNANCY — The outcomes of pregnancy in patients with dermatomyositis (DM) and polymyositis (PM) and the influence of pregnancy on the activity of inflammatory muscle disease are both issues for which there are few data. One summary of these issues included four cases and a review of 39 other pregnancies in a total of 33 patients [35]. In this study, there was no consistent effect of pregnancy on the mothers' disease activity. The outcomes of the pregnancies were as follows:

●Among the 29 pregnancies in 20 women with DM (including one twin pregnancy), the outcomes were:

•15 healthy full-term births

•7 miscarriages, stillbirths, or abortions

•3 premature births

•3 pregnancies with intrauterine growth retardation (IUGR)

●Among the 13 women with PM, the outcomes were:

•8 healthy infants

•2 pregnancies complicated by IUGR

•4 stillbirths or abortions (one therapeutic)

•2 premature births (one followed by neonatal death).

Healthy births appeared to be more likely when myositis is inactive than when active disease is present during pregnancy [35]. Among the 22 women with inactive disease during pregnancy, 16 (73 percent) gave births to healthy babies. In contrast, only 7 of the 27 women (26 percent) who had active disease during pregnancy delivered healthy infants.

Thus, if pregnancy is desired, disease manifestations should be controlled as well as possible before the patient attempts to conceive. Additional considerations in the treatment of pregnant women with inflammatory myopathy include:

●The use of glucocorticoids and azathioprine appears to be relatively safe during pregnancy. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)

●If teratogenic agents are necessary to control severe disease, therapeutic termination of the pregnancy should be considered, and appropriate counseling should be provided.

●Chronic use of glucocorticoids may result in suppression of the hypothalamic-pituitary-adrenal axis. Stress-dose glucocorticoids may be needed during childbirth. (See "Safety of rheumatic disease medication use during pregnancy and lactation".)

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

●Predictors of outcome – Determinants of prognosis in dermatomyositis (DM) and polymyositis (PM) include the specific type of myositis, disease severity, delay in diagnosis, the presence of selected extramuscular disease features, the presence of an underlying malignancy, and autoantibody profile. Myositis-specific and myositis-associated autoantibodies that help define certain myositis subgroups appear to have predictive value for response to treatment. (See 'Prognosis and predictors of outcome' above.)

●Initial therapy – We recommend glucocorticoids for inflammatory myopathy associated with significant muscle weakness (Grade 1B). (See 'Initial therapy' above.)

•We typically begin prednisone at a dose of 1 mg/kg per day and generally do not exceed 80 mg daily.

•For patients who are severely ill, we suggest initiating glucocorticoid therapy with an intravenous methylprednisolone pulse: 1000 mg/day for three days (Grade 2C).

•We suggest tapering prednisone to the lowest effective dose over a total of 9 to 12 months (Grade 2C). (See 'Glucocorticoid tapering' above.)

●Glucocorticoid-sparing agents – We suggest initiating a glucocorticoid-sparing agent at the same time glucocorticoids are begun (Grade 2C). The first-line glucocorticoid-sparing agents are azathioprine and methotrexate.

•Selection between azathioprine and methotrexate is guided by a variety of factors including patient preference, underlying liver or lung disease, willingness to limit alcohol intake, and deficiencies in thiopurine methyltransferase (TPMT) alleles. (See 'Glucocorticoid-sparing agents' above.)

•We suggest azathioprine in patients who have interstitial lung disease associated with their myositis, have underlying liver disease, or are unwilling to abstain from alcohol (Grade 2C).

•The usual starting dose for azathioprine is 50 mg/day. This can be increased gradually to up to 2.5 mg/kg/day. A complete blood count should be monitored within two weeks of starting azathioprine.

•The usual starting dose for methotrexate is 15 mg/week. If there is an inadequate response after two to three months, this can be increased to 25 mg/week.

Once treatment has begun, following muscle strength on serial physical examinations is a more important gauge of treatment response than are the serum concentrations of muscle enzymes.

●Duration of therapy – We suggest attempting to discontinue immunosuppressive therapy after the first round of treatment, with careful follow-up for the possibility of disease recurrence (Grade 2C). (See 'Duration of therapy' above.)

We suggest tapering glucocorticoids off before beginning to taper the glucocorticoid-sparing agent (Grade 2C). (See 'Duration of therapy' above.)

●Apparent glucocorticoid failures – In the setting of apparently resistant disease, several potential scenarios should be considered:

•The original diagnosis of DM or PM was incorrect.

•The patient may have developed a glucocorticoid-induced myopathy.

•An unrecognized malignancy associated with myositis may be the cause of the failure to respond to therapy. (See "Malignancy in dermatomyositis and polymyositis".)

These issues are discussed in further detail above. (See 'Apparent glucocorticoid failures' above.)

●General treatment measures

•Physical therapy and rehabilitation should begin early in the course of treatment, with regimens tailored to the severity of weakness.

•Aspiration precautions are advisable for patients with esophageal dysfunction. Speech therapy evaluations may be helpful for patients with esophageal disease.

•Patients with DM may be photosensitive and should, therefore, take measures to avoid ultraviolet light.

•Glucocorticoid-induced osteoporosis can be an important cause of long-term treatment-related morbidity. We recommend that measures should be taken for the prevention of glucocorticoid-induced osteoporosis (Grade 1A), which can be an important cause of long-term treatment-related morbidity. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

•For patients treated with the combination of high-dose prednisone and any other immunosuppressive agent, we suggest prophylaxis against Pneumocystis jirovecii infections (Grade 2B). (See "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Prophylaxis'.)

•For Pneumocystis prophylaxis, one appropriate regimen is a single-strength tablet of trimethoprim-sulfamethoxazole (80 mg/400 mg) each day. Daily double-strength trimethoprim-sulfamethoxazole tablets should not be used in patients treated with methotrexate.

•If a female patient desires to become pregnant, disease manifestations should be as well-controlled as possible before the patient attempts to conceive.

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