Understanding Myositis

As understanding of disorders such as polymyositis has developed, classification schemes have been modified. Myositis and related disorders are now generally referred to under the rubric of inflammatory muscle diseases. As a group, they are still relatively rare and poorly understood disorders. Although there are characteristic differences, they share certain overlapping clinical features and are considered here together.

As with many inflammatory disorders of obscure cause, inflammatory muscle diseases are considered as genetically-mediated autoimmune disorders with an otherwise unknown trigger. Human leukocyte antigen (HLA)-DR3, as in many systemic rheumatic disorders, has been demonstrated to be a risk factor for inflammatory muscle disease.

Examination of muscle and sera from patients with inflammatory muscle diseases has provided evidence of both cellular and humoral responses that have been proposed as playing a role in the pathogenesis of these disorders. Muscles from patients with polymyositis are infiltrated by CD8+ T cells, most of which are cytotoxic. Analysis of T cell receptors indicate oligoclonality, suggesting at least some specificity of the response. Interestingly, in dermatomyositis, B cells are also often seen, where they are not a prominent component of the infiltrating cells in polymyositis.

Evidence to suggest a humoral role is also indirect. Specific autoantibodies are found in sera of patients with inflammatory muscle disease. Moreover, these antibodies have been shown to penetrate cell membranes and to interact with and inhibit specific enzymatic functions. How and if this relates to the development of myositis is yet to be elucidated.

The disorders considered as inflammatory muscle diseases are relatively rare. Surveys in England in the 1960s suggested a prevalence of 1 in 37,000 and an annual incidence of about 3 per million population. Comparable incidence figures were found in Tennessee over a similar time period for whites, but in black females the incidence was 18 cases per million population per year. Most studies do suggest that the disease is more common in women. Onset is bimodal, with peaks in childhood and middle age.

The most common presentation is the insidious onset of proximal muscle weakness. Patients frequently complain of increasing inability to:

Rise from a squat or from a chair Climb stairs
Get their hand over their heads to reach objects
Comb their hair.
Later in the course, distal muscles or pharyngeal muscles may become weak.

In most individuals, specific muscle group testing will establish that there is weakness in predominantly the proximal muscles. The examiner should not be misled by "give-way" weakness, which is more often due to either pain or feigned weakness. In general, muscles are not tender. Patients with dermatomyositis will have characteristic rashes, which may temporarily occur in any relationship with the muscle involvement. Gottron's papules, a pathognomonic feature of the disease, are erythematous plaques over the extensor surface of the elbows, fingers, and knees, and over the malleoli. The heliotrope rash which is a violaceous discoloration around the eyes, is also a signature finding in dermatomyositis. More nonspecific rashes are also seen, including a photosensitive erythroderma, particularly over the neck, face and upper torso. Subcutaneous calcification can be extensive and varies from an asymptomatic radiographic finding to a pruritic lesion that ulcerates through the skin.

Other organ systems are only occasionally directly involved. Arthralgias and arthritis are not uncommon. When arthritis is present, it generally is non-erosive. Pulmonary interstitial fibrosis is a worrisome finding which may be unresponsive to therapy, and presents with a dry cough and dyspnea on exertion.

Of course, individuals with extensive weakness may have problems clearing their secretions and aspiration or atelectasis due to diminished respiratory excursion. An occasional patient may have heart failure or arrythmias due to myocarditis.

Classification of inflammatory muscle diseases have historically been based on associated clinical findings (ie, idiopathic polymyositis, idiopathic dermatomyositis, juvenile myositis, myositis associated with malignancy, and overlap syndromes). As understanding of these disorders has improved, certain histologic and serologic associations have been made (see Pathogenesis and Laboratory Tests and Radiographs sections, this chapter). The difference between primary polymyositis and dermatomyositis is based on the absence or presence of the characteristic rash described above. Juvenile myositis appears to be much like the adult disease, but children are more likely to have dermatomyositis.

Patients are said to have a myositis overlap syndrome if myositis is part of another inflammatory rheumatic disease. Patients with rheumatoid arthritis, systemic lupus erythematosus, and scleroderma may have myositis as a component of their illnesses. In most patients, the muscle disease is overshadowed by the other features of their disorders.

One clinical impression is that patients with myositis are more likely to develop malignancies. For the most part, these observations were based on anecdotal reports. More recent controlled trials have yielded conflicting results, but there is a suggestion that gastric and ovarian cancers are seen more often in patients with myositis. An often recommended approach is to perform a careful examination and the routine screening tests (eg, mammograms, PAP smears, rectal exam) appropriate for an individual of that particular age. Abnormalities uncovered with these procedures should be vigorously pursued. Outcome of patients with malignancy and myositis is dependent on the outcome of the malignancy. There have been reports of the myositis improving with remission of the cancer, even when there has been surgical extirpation.

Nearly all patients with myositis will have elevation of serum concentrations of muscle cytoplasmic enzymes. Creatine kinase (CK) is the most commonly measured enzyme and is elevated in over 90% of cases. In regenerating muscle, CK-MB band may be released and detectable in the serum when there is no evidence of myocardial disease. Other muscle enzymes, including aldolase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, are frequently elevated in patients with active myositis. Other causes of elevated muscle enzymes should always be considered. Trauma, ischemia, and certain drugs may elevate serum levels. Body builders and blacks may have elevated serum levels of muscle enzymes. CK levels are often used to follow therapy, but they should not be used to the exclusion of a history and physical examination.

Other abnormal laboratory tests reflect the systemic inflammation. Erythrocyte sedimentation rate, C-reative protein, white blood cell and platelet counts may be elevated.

Antinuclear antibodies are found in the serum of about 50% or more of patients with myositis. Specific antibodies may be of some utility in defining disease subsets.

Jo-1 antibodies (directed against histidyl-tRNA synthetase) and other antisynthetase antibodies are found more often in individuals with active myositis who are also more likely to have interstitial lung disease and perhaps nonerosive arthritis.

Antibodies to Mi-2 are seen in some patients with dermatomyositis. Anti-PM-Scl, Ku, and several URNP antibodies seem to select a group of patients with a myositis scleroderma overlap syndrome.

Electromyograms (EMGs) and nerve conduction studies are useful in determining whether there is evidence of a myopathy and in helping to eliminate neuropathic causes of weakness. Typical EMG findings include insertional irritability; short, small, low amplitude polyphasic potentials; and bizarre spikes.

Electrical muscle testing is usually performed unilaterally; this aids in identifying specific muscle groups that may be abnormal. Biopsy can be undertaken on the contralateral side, since the EMG itself may induce histological changes which may be confused with myositis.

Muscle biopsies demonstrate degeneration with necrosis, regeneration, and phagocytosis. There is frequently perimysial and perivascular infiltration of mononuclear cells. An occasional biopsy may demonstrate a necrotizing vasculitis.

The diagnosis of an inflammatory myositis is readily made when a patient presents with:

Proximal muscle weakness
Elevated levels of muscle enzymes
Characteristic findings on electrical studies and on muscle biopsy
The scale of dermatomyositis.

Although developed in 1975, the criteria of Bohan and Peter (Table 9.1) are still of use when considering the diagnosis of inflammatory muscle disease.

However, most patients do not need this extensive evaluation, as a complete history and examination may lead to the discovery of other causes for the patient's weakness. Complaints of weakness are common and are confused with fatigue by many patients. In those with true weakness, it might be discovered through the history that a patient has been exposed to a toxin or used certain drugs that caused elevated muscle enzymes.

The fact of a family member with a muscle disease may lead to the diagnosis of a congenital myopathy. Signs and symptoms of hyper- or hypothyroidism may be clues to an endocrine cause of weakness. Careful neurological examination may demonstrate sensory abnormalities which would likely serve to exclude an inflammatory muscle disease. In these situations, other tests will be useful in confirming a specific diagnosis. Examples of other causes of muscle weakness are listed in the following table.

Other Causes Of Muscle Weakness

Metabolic Disorders

Mitochondrial

Enzyme deficiencies: Acid maltase, Phosphofructokinase, Carnitine palmitoyltransferase, Hyperpyrexia

Drugs/Toxins: Carbon monoxide, Clofibrate, Chloroquine, Ethanol, Penicillamine, Cimetidine, Lovastatin, Corticosteroids, Ipecac, Zidovudine, Colchicine

Neurological Disorders:

Amyotrophic lateral sclerosis
Guillain-Barré syndrome
Diabetic neuropathies
Myasthenia gravis
Endocrine
Thyroid disease (hypo- and hyper-)
Hypercortisolism
Hyperparathyroidism
Hypokalemia

Muscular Dystrophies

Oculopharyngeal
Limb-girdle
Duchenne's syndrome
Becker's disease
Fascioscapulohumeral

Cancer Related

Paraneoplastic
Hypercalcemia

Infectious

Viral:

Echovirus
Coxsackievirus

Bacterial:

Clostridia
Staphylococcic
Protozoal (eg, toxoplasmosis)
Nematodal (eg, trichinosis)
May present as myositis or myalgia

Therapy of patients with inflammatory muscle disease revolves around maneuvers leading to preservation of range of motion and muscle strength and control of inflammation. Rest and range of motion exercises are usually recommended when muscle inflammation is active. As the disease comes under control, progressive strengthening exercises can be employed.

Pharmacological Therapy

Corticosteroids remain the mainstay of pharmacological therapy of inflammatory myositis. Therapy is usually initiated with high doses of corticosteroids (1 mg/kg/d or greater of prednisone). Within 1 month of initiating therapy, muscle enzymes usually are dramatically improved. At this time, steroid tapering can begin. Many patients' myositis can eventually be controlled with alternate-day steroids; some individuals will enter apparent remissions, then steroids can be further tapered.

The role of other medications is less clear. Addition of azathioprine or methotrexate may allow for more rapid tapering of the corticosteroids. In open-label studies, cyclosporin A and cyclophosphamide have been used successfully in some patients. Intravenous immunoglobulin has also been used successfully in some patients, but the duration of the response is limited. Recent studies have further demonstrated that either a combination of azathioprine and methotrexate or high dose methotrexate with leucovorin rescue may be useful when other therapies are not effective.