Polymyositis/DermatomyositisDz

Synonyms: Idiopathic inflammatory myopathy (IIM), DM/PM, dermatopolymyositis, inflammatory myositis.

ICD-9 Code: DM, 710.3; PM, 710.4.
ICD-10 Code: PM, M33.2, DM M33.0 – M33.1

ICD-10 Code: dermatopolymyositis M33 (category). M33.0 = juvenile dermatomyositis; M33.1 = other dermatomyositis; M33.2 = polymyositis; M33.9 = dermatopolymyositis unspecified

Definition: PM and DM are types of IIM. Other less common causes of IIM, such as inclusion body myositis, are listed in Table 32. IIM is characterized clinically by proximal muscle weakness, histopathologically by inflammation and damage to skeletal muscle, and serologically by elevated concentrations of muscle-derived proteins (e.g., creatine kinase). A number of autoantibodies are associated with DM/PM.

Etiology: There is no known cause for these conditions. Somewhat distinct histopathologic findings suggest that DM, PM, and inclusion body myositis may have different causes. A number of cases of IIM, particularly DM, occur in patients with malignancies (see below).

Pathology: Histopathologic analysis of muscle tissue shows a mononuclear cell infiltrate, consisting predominantly of lymphocytes that surround or invade muscle fibers. Muscle fiber necrosis, degeneration, phagocytosis, and regeneration are also seen; atrophy, fibrosis, and fat replacement are late findings. In typical PM, the predominant cells are cytotoxic CD8+ T cells that are endomysial in location. In typical DM, the infiltrates are predominantly perimysial and consist of CD4+ T cells and B cells. Deposition of complement fragments (e.g., the membrane attack complex) in the muscle microvasculature causes vascular injury, leading to vasculitis and perifascicular atrophy. Proinflammatory cytokines IL-1a, IL-113, TNF-a, transforming growth factor-13, and chemokines monocyte migration inhibitor factor, monocyte chemoattractant protein-1, CCR2A/B are increased in PM/DM.

Genetics: Some cases of DM are associated with the major histocompatibility complex alleles HLA-DR3 and DRw52. (Note: This genotype is associated with formation of antibodies to aminoacyl-tRNA synthetase; see below.)

Demographics: The overall prevalence of PM and DM is five to 10 cases per million population. Whereas PM is more common (1.5:1) than DM in adults, the reverse is true in children. Peak incidence occurs between 40 and 60 years of age. The female:male ratio is 2:1. Familial aggregation is rare (thus, a family history of muscle problems should suggest an alternative diagnosis).

Cardinal Findings: IIM may affect skeletal muscle, skin, and other sites.
—Muscle: Most patients present with symmetric, proximal muscle weakness. Involvement of the large muscles of the legs and arms may compromise activities such as climbing stairs, getting in and out of a car, rising from the tub or toilet, and raising arms over the head. Neck weakness may cause difficulty raising the head while recumbent. Importantly, the ability to detect frank muscle weakness on physical examination depends on the severity and chronicity of the disease and the muscle bulk and strength of the patient before disease onset. Less than half of patients complain of myalgia at the onset. Pharyngeal skeletal muscle may be involved, causing upper pharyngeal dysphagia, dysphonia, nasal regurgitation, and the risk of aspiration. Some patients have involvement of the respiratory muscles (e.g., diaphragm or intercostals), which may result in dyspnea, respiratory failure, or even death.
—Skin: Patients with several characteristic cutaneous manifestations and inflammatory myositis are said to have DM. Gottron papules are raised, scaly, erythematous or violaceous, nontender lesions commonly seen over the metacarpophalangeal joints, proximal interphalangeal joints, or knees; they are seen in more than 70% of patients with DM. The heliotrope rash is a purplish (“violaceous”) rash over the eyelids, often accompanied by periorbital edema. An erythematous or violaceous “V-neck” or “shawl” pattern rash is often noted in sun-exposed areas, affecting the upper chest, upper back, and base of the neck. Periungual erythema and dilated nailfold capillaries may be seen. Nailfold capillaroscopy may show capillary dilatation or hemorrhage similar to that seen in scleroderma. “Mechanic’s hands” (hyperkeratosis and scaling over the fingers) and calcinosis (soft tissue calcification) are uncommon. Calcinosis is more common
in children.
—Other findings: Cardiac involvement (e.g., dysrhythmia, electrocardiographic changes) may be detected in 50% of patients but is infrequently symptomatic. Pulmonary involvement is less common and includes respiratory muscle weakness and interstitial lung disease. Some patients display constitutional symptoms including fever, weight loss, anorexia, and malaise.

Complications: Pulmonary involvement (aspiration pneumonia, interstitial lung disease, bronchiolitis obliterans, respiratory failure) is the most common cause of death. Cardiomyopathy is a rare but serious complication of PM/DM. Persistently active disease may cause substantial muscle loss and irreversible weakness. Patients with myositis may also develop “overlap disease” or MCTD with features of scleroderma, RA, or lupus.

Rhabdomyolysis is a potentially life-threatening complication of PM/DM but may occur as a result of trauma, hyperthermia, excessive muscle activity, hereditary muscle enzyme defects, myotoxic drugs (e.g., cocaine, statins), muscle hypoxia, metabolic and endocrine disorders, or infectious myositis. Patients often complain of muscle pain, profound weakness, and red-brown or “tea-colored” urine (from myoglobinuria) and are found to have marked muscle enzyme elevations. Early diagnosis is necessary to avoid electrolyte and renal disorders (myoglobin is toxic to renal tubules). Treatment includes aggressive hydration and mannitol diuresis, alkalinization, or dialysis.

Juvenile DM: DM is much more common (20:1) than PM in children. The peak age of onset is 5 to 14 years, and it is associated genetically with the major histocompatibility complex HLA-B8 and DR-3 alleles. Classically, the DM rash, which closely resembles rashes in the adult, precedes muscle involvement. There are several important differences between adult and childhood DM. Coexistent vasculitis, ectopic calcification of subcutaneous tissue or muscle, and lipodystrophy are more common in children with DM than adults. It has been suggested that measurements of aldolase may be more useful than creatine kinase in childhood myositis. In contrast with adult DM, childhood DM is rarely associated with malignancy. With successful therapy, children with DM return to normal strength and function more frequently than adults.

PM/DM and Malignancy: The possible association of IIM with malignancy has been debated in the medical literature for nearly a century. Studies have been mostly anecdotal, and hampered by small numbers of patients and potential bias. It has been suggested that approximately 9% of PM and >15% of DM cases are associated with malignancy. The cancer may precede, follow, or be diagnosed concurrently with the myositis. In ~20% of DM cases, the tumor behaves as a paraneoplastic syndrome, with the activities of the two conditions apparently linked. The cancers observed are the same as those seen in the general population (i.e., in the United States, lung and breast cancer; in Japan, gastric cancer), although it has been suggested that ovarian cancer is seen with greater frequency. Most investigators recommend that only a thorough, directed history, physical examination, and laboratory evaluation (appropriate for the patient’s age and gender) be performed. No evidence supports more extensive testing (e.g., imaging studies, tumor markers); such investigations are expensive and unlikely to yield useful data.

Potential autoantibody associations with cancer among DM/PM patients have been sought for years. Anti-p155/p140 antibodies (p155 = transcriptional intermediary factor 1-gamma [TIF1-gamma]/p140 = TIF1-alpha]) have been suggested to have an association with development of cancer among DM patients (although such antibodies may also be seen in juvenile DM which is rarely associated with malignancy)

Diagnostic Criteria: See Table 33.

Diagnostic Tests
—Markers of muscle damage: Elevation in serum creatine kinase reflects skeletal muscle injury; creatine kinase is the most commonly used diagnostic test in PM/DM. Its advantages include (a) sensitivity (elevations in creatine kinase are observed in at least 70%–90% of cases); (b) relative specificity for skeletal muscle (although creatine kinase is also found in brain and myocardium); (c) correlation of creatine kinase levels with disease activity (increases may be seen weeks before a clinical flare; normalization correlates with successful treatment); and (d) dynamic range (increases in creatine kinase with PM/DM are often 20–50 times normal). Note: Normal creatine kinase levels vary with gender (higher in men) and race (higher in blacks).

Other tests that reflect muscle injury include aldolase (also relatively specific), lactate dehydrogenase, aspartate aminotransferase, and, less commonly, alanine aminotransferase.

—EMG: EMG is very useful for confirming the diagnosis of PM/DM. It is abnormal in >90% of patients and can help exclude other potential causes of muscle weakness (e.g., neuropathy). EMG findings characteristic of PM/DM include myopathic motor unit potentials (small units, early recruitment), a myopathic interference pattern (full, low amplitude), and spontaneous insertional activity (fibrillations, positive sharp waves, complex repetitive discharges, but not fasciculations). Nerve conduction velocity studies should be normal. EMG is also used in longitudinal follow-up of disease activity in patients with PM/DM. It can be useful in determining whether new symptoms of weakness relate to a recurrence of inflammatory activity or some other cause (e.g., steroid myopathy). Practical considerations for EMG include (a) doing muscle enzyme determinations before EMG because the procedure may elevate them and (b) doing EMG unilaterally to allow biopsy to be done on the contralateral side.
—Muscle biopsy: Specimens may be required to confirm the diagnosis. Needle biopsies may provide sufficient tissue for examination, but definitive open surgical biopsies are commonly used. The biopsy yield may be improved by previous localization of involved muscle by EMG or MRI (see below). Proper procedures for handling the tissue should be discussed with the pathologist who will receive the specimen.
—MRI: MRI has been used in the evaluation of IIM. T1-weighted images provide detail of muscle anatomy, but T2-weighted images are better for detecting inflammation. Fat-suppressed T2 (STIR) images may also be useful. MRI is not routinely recommended in evaluating PM/DM because it is expensive, and the results have not necessarily correlated with histopathologic findings or clinical signs and symptoms.
—Autoantibodies: ANA is positive in 50% to 80% of patients with PM/DM (thus, it usually does not help in evaluating any single patient). Autoantibodies to some aminoacyl-tRNA synthetases are characteristic of some subsets of IIM; for example, anti-Jo-1 (anti-histidyl-tRNA synthetase; the most commonly detected anti-tRNA synthetase) (see also section on myositis-specific autoantibodies). Such antibodies are found in 25% to 30% of patients (more with PM than DM). Patients with the “antisynthetase syndrome” have symptoms such as interstitial lung disease, polyarticular inflammatory arthritis (particularly of the small joints of the hands), Raynaud phenomenon, fever, acute onset, and mechanic’s hands. Anti-melanoma differentiation associated protein 5 (MDA-5) have been reported to be associated with relatively mild muscle involvement, and interstitial lung disease among DM patients.
—Other tests: Acute-phase reactants (e.g., CRP and ESR) are elevated in ~50%.

Certain autoantibodies have been associated with manifestations of disease in DM/PM patients. For example autoantibodies to aminoacyl tRNA synthetase enzymes, the most common of which is Jo-1 (anti-histidyl tRNA synthetase) are associated with the “anti-synthetase syndrome” with manifestations including interstitial lung disease, mechanic’s hands, fever, Raynaud’s phenomenon and inflammatory arthritis.

Differential Diagnosis: The differential diagnosis of IIM includes various neuromuscular, metabolic, endocrinologic, infectious, and other causes of muscle weakness (Table 34). The evaluation of weakness and myopathy is discussed elsewhere.

Therapy: Early recognition and treatment of PM/DM are critical. Delays in treatment increase the chance of irreversible muscle damage and decrease the likelihood of a full recovery. Glucocorticosteroids are the mainstay of therapy. Initial doses are usually 1 to 2 mg/kg or more of prednisone (e.g., 40 mg twice daily). These high doses are used for weeks to months to achieve disease control and lower serum muscle enzyme levels. Steroids may then be tapered over the next 2 to 3 months while the patient’s symptoms (weakness) and muscle enzymes are carefully monitored. The response to steroids is often slow and may take 8 to 12 weeks. Approximately 25% of patients have a complete response, 60% a partial response, and 15% no response to an initial prednisone trial. In patients with no response or partial response to prednisone, second-line agents are commonly used to improve outcome and limit exposure to steroids. MTX (15–25 mg/wk) or azathioprine (1 to 2 mg/kg/day) are most commonly used, often in combination with prednisone initially. High-dose immunoglobulin (intravenous IgG, 2 g/kg) has been successful, but response is transient. A role for biologic therapies (i.e., anakinra, TNF inhibitors, rituximab) has not been defined in PM/DM, although there are a number of case reports.
—Steroid myopathy: Steroids can cause a myopathy, which becomes a consideration in patients receiving long-term therapy with these drugs. EMG or muscle biopsy (shows type II fiber atrophy) are often required to distinguish steroid myopathy from active IIM.
—Physical therapy: In addition to pharmacologic therapy, treatment of patients with PM/DM may include physiotherapy to improve functional status and facilitate rehabilitation.

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