eMedicine Specialties > Neurology > Neuromuscular Diseases

Dermatomyositis/Polymyositis

Author: Aamir Hashmat, MD, Consulting Staff, Neurology and Neurodiagnostics Lab, Department of Neurology, Jeff Anderson Regional Medical Center
Coauthor(s): Zaineb Daud, MD, Consulting Staff, Department of Neurology, Medical College of Pennsylvania Hahnemann University; Thomas H Brannagan III, MD, Associate Professor of Clinical Neurology, Weill Medical College of Cornell University; Director, Diabetic Neuropathy Research Center, Department of Neurology, New York-Presbyterian Hospital, Weill Cornell Medical Center
Contributor Information and Disclosures

Updated: Nov 14, 2006

Introduction

Background

In 1863, Wagner first recognized dermatomyositis/polymyositis. In 1891, Unverricht provided the first description of dermatomyositis. Dermatomyositis and polymyositis have been classified into the following clinical groups, as Walton and Adams originally proposed:

• Primary polymyositis (idiopathic, adult)
• Dermatomyositis (idiopathic, adult)
• Childhood dermatomyositis or myositis with necrotizing vasculitis
• Polymyositis associated with connective tissue disorder (ie, overlap syndrome)
• Polymyositis or dermatomyositis associated with neoplasia

Inflammatory myopathies are acquired muscle diseases characterized by primary muscle weakness, endomysial inflammation, and elevated levels of serum muscle enzymes. Polymyositis and dermatomyositis, along with inclusion-body myositis, are the most common diseases of the striated muscle, skin, and surrounding connective tissue that clinicians observe. Each has unique clinical and histologic features. The pathology of both polymyositis and dermatomyositis have an underlying autoimmune basis, but the mechanisms for the 2 conditions differ.

Pathophysiology

Polymyositis

Polymyositis is presumed to be an autoimmune-mediated disease secondary to defective cellular immunity, which may be due to diverse causes that may occur alone or in association with viral infections, malignancies, or connective-tissue disorders. Evidence suggests that a T cell–mediated cytotoxic process is directed against unidentified muscle antigens. Supporting this conclusion are CD8 T cells, which, along with macrophages, initially surround healthy nonnecrotic muscle fibers and eventually invade and destroy them.

The factors triggering a T cell–mediated process in polymyositis are unclear. Viruses have been implicated; however, so far, only the human retroviruses HIV and human T-cell lymphotrophic virus type I (HTLV-I), the simian retroviruses, and coxsackievirus B have been etiologically connected with the disease. These viruses may directly invade the muscle tissue, damaging the vascular endothelium and releasing cytokines, which then induce abnormal expression of the major histocompatibility complex (MHC) and which render the muscle susceptible to destruction.

An autoimmune response to nuclear and cytoplasmic autoantigens is detected in about 60-80% of patients with polymyositis and dermatomyositis. Some serum autoantibodies are shared with other autoimmune diseases (ie, myositis-associated antibodies [MAA]), and some are unique to myositis (ie, myositis-specific antibodies [MSA]). The MSA are found in approximately 40% of patients with polymyositis and dermatomyositis, whereas MAA are found in 20-50%.

Myositis-specific antibodies

The identified MSA targets include 3 distinct groups of proteins: aminoacyl–transfer RNA (tRNA) synthetases (anti-Jo-1), nuclear Mi-2 protein, and components of the signal-recognition particle (SRP).

Most of the anti-tRNA synthetase antibodies are directed toward functional and highly conserved domains of the enzyme. As many as 6 of 20 aminoacyl-tRNA synthetases have been described, but anti-histidyl-tRNA synthetase (Jo-1) is most common (20-30%). Autoantibodies directed toward the other synthetases specific for alanine (anti-PL12), glycine (anti-EJ), isoleucine (anti-OJ), threonine (anti-PL7), and asparagine (anti-KS) have been reported in only about 1% of patients. Anti-Jo-1 autoantibodies were originally described as precipitating autoantibodies in sera of patients with polymyositis. Later, the anti-Jo-1 antibodies were recognized to be specific for patients with polymyositis. The target for the anti-Jo-1 antibodies was one of a family of distinct cellular enzymes: the aminoacyl-tRNA synthetases.

The Jo-1 antigen is histidyl-tRNA synthetase. This enzyme is partially responsible for attaching tRNA to their cognate ribosomal RNA (rRNA). The Jo-1 antigen migrates as a 53-kd protein on sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE).

The presence of autoantibodies against the Jo-1 antigen has been reported in up to 23% of polymyositis patients by immunodiffusion. Anti–Jo-1 antibodies are almost completely specific for myositis and are more common in polymyositis than in dermatomyositis and rare in children. The presence of anti-Jo-1 antibodies defines a distinct group of polymyositis patients with interstitial lung disease, arthritis, and fevers. The anti–Jo-1 response appears to be self-antigen driven, having a broad spectrotype over time and undergoing isotype switching. Anti–Jo-1 antibodies also inhibit the function of histidyl-tRNA synthetase in humans more than they do in other species.

Anti-Mi-2 antibodies recognize a major protein of a nuclear complex formed by at least 7 proteins that is involved in the transcription process. Autoantibodies recognizing Mi-2 are considered specific serologic markers of dermatomyositis. They are detected in about 20% of patients with myositis and are associated with relatively acute onset, a good prognosis, and a good response to therapy.

Anti-SRP antibodies are directed towards an RNA-protein complex that consists of 6 proteins and a 300-nucleotide RNA molecule (7SL RNA). Patients with anti-SRP antibodies have acute polymyositis with cardiac involvement, a poor prognosis, and a poor response to therapy.

Myositis-associated antibodies

The MAA are found in the sera of 20-50% of patients and are commonly encountered in other connective tissue diseases. The most important antigenic targets of the MAA are the PM/Scl nucleolar antigen, the nuclear Ku antigen, the small nuclear ribonucleoproteins (snRNP), and the cytoplasmic ribonucleoproteins (RoRNP). The anti-PM/Scl autoantibodies are generally found in patients affected by polymyositis overlapping with scleroderma. Anti-Ku antibodies are found in patients with myositis overlapping with other connective tissue diseases. Antibodies directed against snRNP are frequently found in patients with myositis and in patients with connective tissue–disease overlap syndrome, whereas antibodies toward Ro/SSA 60 kd, Ro/SSA 52 kd, and La/SSB protein components of the RoRNP complex are almost exclusively found in patients with Sjögren syndrome and systemic lupus erythematosus (SLE).

Dermatomyositis

Dermatomyositis is likely the result of a humoral attack on the muscle capillaries and small arterioles. Complement c5b-9 membrane-attack complex is deposited and is needed in preparing the cell for destruction in antibody-mediated disease. B cells and CD4 (helper) cells are also present in abundance in the inflammatory reaction associated with the blood vessels. As the disease progresses, the capillaries are destroyed, and the muscles undergo microinfarction. Perifascicular atrophy occurs in the beginning; however, as the disease advances, necrotic and degenerative fibers are present throughout the muscle.

Frequency

International

The incidence of polymyositis and dermatomyositis is 5-10 cases per 100,000 individuals.

Mortality/Morbidity

The active period of the disease is approximately 2-3 years in both children and adults. The duration is greater for patients with cardiac or pulmonary complications than for others; approximately 20% of the patients recover completely. The mortality rate after several years of the disease is approximately 15%; the rate is increased in patients with dermatomyositis with connective tissue diseases and malignancy.

Race

No racial predilection is observed.

Sex

A female preponderance has been reported in all age groups, with a female-to-male ratio of 2:1.

Age

• Most patients present with polymyositis when aged 30-60 years, with a small peak in people aged 15 years.
• Dermatomyositis affects children and adults equally. The peak incidence is observed in individuals aged 45-64 years, with a small peak in children aged 5-14 years.

Clinical

History

• Polymyositis
  • Polymyositis is a disease of exclusion with acute or subacute onset. It is best defined as an inflammatory myopathy of subacute onset (ie, weeks to months) and steady progression occurring in adults who develop diffuse weakness, which is more severe proximally than distally.
  • The weakness is painless in two thirds of the patients. A rash is not present.
  • Eye muscles are not involved, and facial muscles are involved only with severe disease.
  • Family history of neuromuscular disease, endocrinopathy, or exposure to myotoxic drugs or toxins is absent.
  • The disease may exist for several months before the patient seeks medical advice, and all the muscles of the thighs, trunk, shoulders, hips, and upper arms are usually involved.
  • Symptoms include difficulty getting up from a chair, climbing steps, stepping onto a curb, lifting objects, and combing hair. Fatigue, myalgias, and muscle cramps may also be present.
  • In contrast, fine motor movements that depend on the strength of distal muscles, such as buttoning a shirt, sewing, knitting, or writing are affected only late in the disease.
• Dermatomyositis
  • Dermatomyositis occurs in children as well as adults. It is characterized by the muscle weakness.
  • Extramuscular manifestations of the disease may include the following:
    • General systemic disturbances, fever, arthralgia, malaise, weight loss, Raynaud phenomenon
    • Dysphagia, similar to that of scleroderma
    • Atrioventricular defects, tachyarrhythmias, dilated cardiomyopathies
    • Gastrointestinal (GI) ulcers and infections
    • Contracture of joints
    • Pulmonary involvement due to weakness of thoracic muscles, interstitial lung disease
    • Subcutaneous calcifications
  • Dermatomyositis in children resembles the adult form. Children commonly develop a tiptoe gait secondary to flexion contracture of the ankles in early childhood.
  • Children tend to have extramuscular manifestations, especially GI ulcers and infections, more frequently than adults do.

Physical

• Polymyositis
  • Nothing is characteristic about the muscle weakness. It is not painful, although a minority of patients report aches or cramps.
  • The weakness may fluctuate from week to week and from month to month.
  • Ocular muscles remain normal even in advanced untreated cases.
  • Facial muscles remain normal except in rare advanced cases.
  • The pharyngeal and neck flexor muscles are often involved, causing dysphagia and difficulty in holding up the head.
  • In advanced cases and rarely in acute cases, respiratory muscles are affected. Severe weakness is almost always associated with muscular wasting.
  • Sensation remains normal.
  • On occasion, the muscle may be sore to palpation and may have a nodular and grainy feel.
  • The tendon reflexes are preserved, but they may be absent in severely weakened or atrophied muscles.
  • Primary cardiac abnormalities due to myocarditis may be present in a few patients. These abnormalities mainly manifest as atrioventricular conduction defects, tachyarrhythmias, low ejection fraction, dilated cardiomyopathy, or congestive heart failure.
  • General systemic disturbances, such as fever, malaise, weight loss, arthralgia, and Raynaud phenomenon, may occur when polymyositis is associated with a connective-tissue disorder.
• Dermatomyositis
  • The rash consists of a heliotrope (ie, blue-purple) discoloration on the upper eyelids; a flat, red rash involving the face and upper trunk; and a raised, violaceous, scaly eruption on the knuckles (ie, Gottron rash).
  • The erythematous lesions may result in scaling, pigmentation, and depigmentation of the skin, producing a shiny appearance.
  • The rash may involve other body surfaces, including knees, elbows, neck, anterior chest (ie, V sign), or back and shoulders (ie, shawl sign); sun exposure can exacerbate the rash.
  • Dilated capillary loops at the base of the fingernail are characteristic of dermatomyositis. The cuticles may be irregular and thickened, and the palmar and lateral surfaces of the fingers may become rough and cracked.
  • Myopathy in dermatomyositis is more proximal than distal.
  • The degree of weakness may range from mild to moderate to severe. Sometimes, quadriparesis are observed.
  • Muscle pain and tenderness are observed early in the course of the disease.
  • Sensation is normal, and tendon reflexes are preserved unless the muscle is severely weak and atrophic.

Causes

The causes of idiopathic polymyositis and dermatomyositis are not known. An autoimmune process is implicated (as discussed above) because these conditions may be associated with other autoimmune diseases, such as myasthenia gravis, Hashimoto thyroiditis, scleroderma, Waldenström macroglobulinemia, and others and because they respond to immunosuppressive medication.

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