Polymyositis- Dermatomyositis

The inflammatory myopathies represent the largest group of acquired and potentially treatable causes of skeletal muscle weakness.

These disorders present as progressive and symmetric muscle weakness Patients usually report increasing difficulty with everyday tasks requiring the use of proximal muscles, such as getting up from a chair, climbing steps, stepping onto a curb, lifting objects, or combing hair. In all forms of inflammatory myopathy, pharyngeal and neck-flexor muscles are often involved, causing dysphagia or difficulty in holding up the head (head drop). Myalgia and muscle tenderness may occur. Weakness in PM and DM progresses subacutely over a period of weeks or months.

Polymyositis

The actual onset of PM is often not easily determined, and patients typically delay seeking medical advice for several weeks or even months. This is in contrast to DM, in which the rash facilitates early .PM occurs in association with a systemic autoimmune or connective tissue disease, or with a known viral or bacterial infection. Drugs, especially d-penicillamine, statins, or zidovudine (AZT), may also trigger an inflammatory myopathy similar to PM.

Dermatomyositis

DM is a distinctive entity identified by a characteristic rash accompanying, or more often preceding, muscle weakness. The rash may consist of a blue-purple discoloration on the upper eyelids with edema .DM usually occurs alone but may overlap with scleroderma and mixed connective tissue disease.

Associated Clinical Findings

Extramuscular Manifestations

These may be present to a varying degree in patients with PM or DM, and include:

  • Systemic symptoms, such as fever, malaise, weight loss, arthralgia, and Raynaud’s phenomenon, especially when inflammatory myopathy is associated with a connective tissue disorder.
  • Joint contractures, mostly in DM and especially in children.
  • Dysphagia and gastrointestinal symptoms, due to involvement of oropharyngeal striated muscles and upper esophagus, especially in DM and IBM.
  • Cardiac disturbances, including atrioventricular conduction defects, tachyarrhythmias, dilated cardiomyopathy, a low ejection fraction, and congestive heart failure, may rarely occur, either from the disease itself or from hypertension associated with long-term use of glucocorticoids.
  • Pulmonary dysfunction, due to weakness of the thoracic muscles, interstitial lung disease, or drug-induced pneumonitis (e.g., from methotrexate), which may cause dyspnea, nonproductive cough, and aspiration pneumonia. Interstitial lung disease may precede myopathy or occur early in the disease and develops in up to 10% of patients with PM or DM, most of whom have antibodies to t-RNA synthetases, as described below.
  • Subcutaneous calcifications, in DM, sometimes extruding on the skin and causing ulcerations and infections.
  • Arthralgias, synovitis, or deforming arthropathy with subluxation in the interphalangeal joints can occur in some patients with DM and PM who have Jo-1 antibodies .

Association with Malignancies

Although all the inflammatory myopathies can have a chance association with malignant lesions, especially in older age groups, the incidence of malignant conditions appears to be specifically increased only in patients with DM and not in those with PM or IBM. The most common tumors associated with DM are ovarian cancer, breast cancer, melanoma, colon cancer, and non-Hodgkin lymphoma.

Pathogenesis

An autoimmune etiology of the inflammatory myopathies is indirectly supported by an association with other autoimmune or connective tissue diseases..

Drug-Induced Myopathies

D-Penicillamine, procainamide, and statins may produce a true myositis resembling PM. Other drugs may elicit a toxic noninflammatory myopathy include cholesterol-lowering agents such as clofibrate, lovastatin, simvastatin, or provastatin, especially when combined with cyclosporine, amiodarone, or gemfibrozil. Statin-induced necrotizing myopathy or asymptomatic elevations of CK usually improve after discontinuation of the drug. “Weakness” Due to Muscle Pain and Muscle Tenderness

Diagnosis

The clinically suspected diagnosis of PM, DM, is confirmed by analysis of Serum muscle enzymes,The most sensitive enzyme is CK, which in active disease can be elevated as much as fiftyfold.Along with the CK, the serum glutamic-oxaloacetic and glutamate pyruvate transaminases, lactate dehydrogenase, and aldolase may be elevated..
EMG findings, and

Muscle biopsy—is the most sensitive and specific test for establishing the diagnosis of inflammatory myopathy and for excluding other neuromuscular diseases.

Treatment

The goal of therapy is to improve muscle strength, thereby improving function in activities of daily living, and ameliorate the extramuscular manifestations (rash, dysphagia, dyspnea, fever. Agents used in the treatment of PM and DM include the following:

Glucocorticoids. Oral prednisone is the initial treatment of choice; the effectiveness and side effects of this therapy determine the future need for stronger immunosuppressive drugs. The efficacy of prednisone is determined by an objective increase in muscle strength and activities of daily living, which almost always occurs by the third month of therapy. A feeling of increased energy or a reduction of the CK level without a concomitant increase in muscle strength is not a reliable sign of improvement. If prednisone provides no objective benefit after 3 months of high-dose therapy, the disease is probably unresponsive to the drug and tapering should be accelerated while the next-in-line immunosuppressive drug is started 2. Other immunosuppressive drugs. Approximately 75% of patients ultimately require additional treatment. This occurs when a patient fails to respond adequately to glucocorticoids after a 3-month trial, the patient becomes glucocorticoid-resistant, glucocorticoid-related side effects appear, attempts to lower the prednisone dose repeatedly result in a new relapse, or rapidly progressive disease with evolving severe weakness and respiratory failure develops.

The following drugs are commonly used

  • Azathioprine
  • Methotrexate
  • Mycophenolate mofetil
  • Tacrolimus (formerly known as Fk506) has been effective in some difficult cases of PM.

Immunomodulation. In a controlled trial of patients with refractory DM, intravenous immunoglobulin (IVIg) improved not only strength and rash but also the underlying immunopathology. The benefit is often short-lived (8 weeks), and repeated infusions every 6–8 weeks are generally required to maintain improvement

Prognosis

The 5-year survival rate for treated patients with PM and DM is 95% and the 10-year survival rate is 84%; death is usually due to pulmonary, cardiac, or other systemic complications. The prognosis is worse for patients who are severely affected at presentation, when initial treatment is delayed, and in cases with severe dysphagia or respiratory difficulties. Older patients, and those with associated cancer also have a worse prognosis. DM responds more favorably to therapy than PM and thus has a better prognosis. Most patients improve with therapy, and many make a full functional recovery, which is often sustained with maintenance therapy. Up to 30% may be left with some residual muscle weakness. Relapses may occur at any time.