Myopathies: Dermatomyositis & Polymyositis

Essentials of Diagnosis

• Bilateral proximal muscle weakness

• Characteristic cutaneous manifestations in dermatomyositis (Gottron papules, heliotrope rash)

• Elevated creatine kinase, myositis-specific antibodies, diagnostic muscle biopsy

• Increased risk of malignancy, particularly in dermatomyositis

General Considerations

• An autoimmune disease of unknown cause characterized primarily by inflammation of muscles

• Five clinically defined subsets

  • Juvenile dermatomyositis

  • Dermatomyositis

  • Polymyositis

  • Myositis associated with malignancy

  • Myositis may overlap other connective tissue diseases, especially

    • Scleroderma

    • Systemic lupus erythematosus [SLE]

    • Mixed connective tissue disease

    • Sjögren syndrome

• Malignancies most commonly associated with dermatomyositis in descending order of frequency

  • Ovarian

  • Lung

  • Pancreatic

  • Stomach

  • Colorectal

  • Non-Hodgkin lymphoma

Demographics

• Peak incidence: fifth and sixth decades

• Women are affected twice as commonly as men

Symptoms and Signs

POLYMYOSITIS

• Progressive muscle weakness of the proximal muscle groups of the upper and lower extremities as well as neck over weeks to months

• Leg weakness (eg, difficulty in rising from a chair or climbing stairs) typically precedes arm symptoms

• No facial or ocular muscle weakness

• Pain and tenderness of affected muscles (25%)

• Initiation of swallowing may be difficult

DERMATOMYOSITIS

• The characteristic rash is dusky red and may appear in malar distribution mimicking the classic rash of SLE

• Erythema also occurs over other areas of the face, neck, shoulders, and upper chest and back ("shawl sign")

• Periorbital edema and a purplish (heliotrope) suffusion over the eyelids are typical signs

• Periungual erythema, dilations of nailfold capillaries, Gottron papules (raised violaceous lesions overlying the dorsa of DIP, PIP, and MCP joints) and Gottron sign (erythematous rash on the extensor surfaces of the fingers, elbows, and knees) are highly suggestive

• A subset of patients with polymyositis and dermatomyositis develops the "antisynthetase syndrome," a group of findings including

  • Inflammatory nonerosive arthritis

  • Fever

  • Raynaud phenomenon

  • "Mechanic's hands" (hyperkeratosis along the radial and palmar aspects of the fingers)

  • Interstitial lung disease

  • Often, severe muscle disease associated with certain autoantibodies (eg, anti-Jo-1 antibodies)

Differential Diagnosis

MUSCLE INFLAMMATION

• Polymyositis

• Dermatomyositis

• SLE

• Scleroderma

• Sjögren syndrome

• Inclusion body myositis

• Statin-induced immune-mediated necrotizing myopathy

• Trichinosis

OTHER CAUSES OF PROXIMAL MUSCLE WEAKNESS

• Polymyalgia rheumatica (PMR)

  • PMR patients are age > 50 and—in contrast to patients with polymyositis—have pain but no objective weakness

• Endocrine

  • Hypothyroidism

  • Hyperthyroidism

  • Cushing syndrome

• Alcoholism

• Drugs

  • Corticosteroids

  • Alcohol

  • Hydroxychloroquine

  • Statins

  • Clofibrate

  • Colchicine

  • Chloroquine

  • Emetine

  • Aminocaproic acid

  • Bretylium

  • Penicillamine

  • Drugs causing hypokalemia

  • Immune checkpoint inhibitors

  • Tryptophan

• HIV myopathy

• Hyperparathyroidism

• Spinal stenosis

• Osteomalacia

• Mitochondrial myopathy

• Limb-girdle muscular dystrophy

• Peripheral and central nervous system disorders (eg, chronic inflammatory polyneuropathy, multiple sclerosis, myasthenia gravis, Eaton-Lambert disease, and amyotrophic lateral sclerosis) can produce similar weakness

  • However, they are distinguished from inflammatory myopathies by characteristic symptoms and neurologic signs and often by distinctive electromyographic abnormalities

Laboratory Tests

• Serum levels of muscle enzymes, especially creatine kinase and aldolase, are elevated

• Antinuclear antibodies can be present in many patients

• A number of autoantibodies are seen exclusively in patients with myositis and are associated with distinctive clinical features (Table 20–10)

  • Anti-Jo-1 antibody is seen in the subset of patients who have antisynthetase syndrome

  • Anti-Mi-2 is associated with dermatomyositis

  • Anti-SRP (anti-signal recognition particle) is associated with rapidly progressive, severe polymyositis and dysphagia

  • Anti-155/140 is strongly associated with dermatomyositis with malignancy

  • Anti-MDA5 (melanocyte differentiation-associated protein 5) is linked to dermatomyositis with cutaneous ulcerations and rapidly progressive interstitial lung disease

• CA-125 levels (and transvaginal ultrasonography) may be useful in women, given the strong association of ovarian carcinoma and dermatomyositis

Imaging Studies

• Chest radiographs are usually normal, although interstitial fibrosis is occasionally seen

• MRI can detect early and patchy muscle involvement, can guide biopsies, and often is more useful than electromyography

Diagnostic Procedures

• Biopsy of clinically involved muscle is the only specific diagnostic test

• The pathologic findings in polymyositis and dermatomyositis are distinct

  • In dermatomyositis, the cellular infiltrate is mostly perifascicular and perivascular

  • In polymyositis, the inflammatory infiltrate involves the fascicle itself

• Electromyographic abnormalities consisting of polyphasic potentials, fibrillations, and high-frequency action potentials can point toward a myopathic, rather than a neurogenic, cause of weakness

Medications

• Most patients respond to corticosteroids

  • Prednisone 40–60 mg or more orally daily is required initially

  • The dose is then adjusted downward while monitoring muscle strength and serum levels of muscle enzymes

• Immunosuppressive drugs, such as methotrexate or azathioprine, are often started to reduce cumulative steroid exposure

• Intravenous immune globulin is effective for dermatomyositis resistant to prednisone

• Mycophenolate mofetil (1.0–1.5 g twice daily orally) may be useful as a steroid-sparing agent

• Rituximab is effective in some patients with inflammatory myositis unresponsive to prednisone

• Hydroxychloroquine (200–400 mg/day orally not to exceed 5 mg/kg) can help ameliorate skin disease

Therapeutic Procedures

• Limit sun exposure for patients with rash of dermatomyositis

Follow-Up

• Up to one patient in four with dermatomyositis has an occult malignancy that may not be detected until months afterward in some cases

• Search for an occult malignancy should include age- and risk-appropriate cancer screening tests

• If these evaluations are unrevealing, then a more invasive or extensive laboratory evaluation is probably not cost-effective

Complications

• Muscle atrophy and contractures in advanced polymyositis

• Hypercapnea and respiratory failure can develop from weakness of respiratory muscles

• Rhabdomyolysis with acute kidney injury can complicate very severe muscle inflammation

Prognosis

• Patients with an associated neoplasm have a poor prognosis

  • However, remission of the myositis may follow treatment of the tumor

  • Corticosteroids may or may not be effective in these patients

When to Refer

• All patients with myositis should be referred to a rheumatologist or neurologist

• Severe lung disease may require consultation with a pulmonologist

When to Admit

• Signs of rhabdomyolysis

• New onset of dysphagia

• Respiratory insufficiency with hypoxia or carbon dioxide retention