eMedicine Specialties > Neurology > Neuromuscular Diseases

Dermatomyositis/Polymyositis

Sushma Podila, MD, Resident Physician, Department of Neurology, Columbia Presbyterian Medical Center
Thomas H Brannagan III, MD, Associate Professor of Clinical Neurology and Director, Peripheral Neuropathy Center, Columbia University, College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus, New York

Updated: Aug 28, 2009

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

Hematoxylin and eosin paraffin section shows polymyositis. Longitudinal section shows a dense, chronic, endomysial inflammatory infiltrate. Image courtesy of Roberta J. Seidman, MD.

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 toward 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 2:1.¹

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.¹

Clinical

History

Classification criteria for polymyositis and dermatomyositis

For a diagnosis of dermatomyositis, patients must present with at least one of the skin symptoms listed in "skin lesions" and 4 of the remaining symptoms.

For a diagnosis of polymyositis, patients present with no skin symptoms and 4 of the remaining criteria.

Criteria for diagnosis (symptoms)

• Proximal muscle weakness (upper or lower extremity and trunk)
• Elevated serum CK (creatine kinase) or aldolase level
• Muscle pain on grasping or spontaneous pain
• Myogenic changes on EMG (short-duration, polyphasic motor unit potentials with spontaneous fibrillation potentials)
• Positive anti-Jo-1 (histadyl tRNA synthetase) antibody
• Nondestructive arthritis or arthralgias
• Systemic inflammatory signs (fever: more than 37° C at axilla, elevated serum CRP level or accelerated ESR [erythrocyte sedimentation rate] of more than 20 mm/h by the Westergren method)
• Pathological findings compatible with inflammatory myositis (inflammatory infiltration of skeletal evidence of active regeneration may be seen)

Skin lesions

• Heliotrope rash (red purple edematous erythema on the upper palpebra)
• Gottron's sign (red purple keratotic, atrophic erythema, or macules on the extensor surface of finger joints)
• Erythema on the extensor surface of extremity joints: slightly raised red purple erythema over elbows or knees

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 in 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 - Na et al found the frequency of subcutaneous calcifications to be significantly higher in juvenile dermatomyositis than adult dermatomyositis.¹
• 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.

Differential Diagnoses

Other Problems to Be Considered

Polymyositis is a diagnosis of exclusion.

Groups of diseases that should be excluded

Familial neuromuscular diseases
Systemic metabolic muscle diseases, eg, endocrinopathies and mitochondriopathies
Systemic medical illness, eg, malabsorption syndromes, alcoholism, cancer, vasculitis, granulomatous disease, sarcoidosis, or treatment with various known myotoxic drugs or toxins
Biochemical muscle diseases (eg, enzyme deficiencies)
Inclusion-body myositis (excluded by histologic findings)

Diseases differentiated by skin changes

The rash and subcutaneous calcifications are so characteristic of dermatomyositis that the diagnosis of dermatomyositis is very rarely in doubt. Some of the diseases from which it must be differentiated on the basis of skin changes are as follows:

SLE: The skin changes in the phalanges must be distinguished from dermatomyositis because, in SLE, the phalanges are involved and the knuckles are spared; in dermatomyositis, the reverse is true.

Eosinophilia myalgia syndrome: This was caused by the ingestion of contaminated L-tryptophan and has not been observed since the contaminated product was identified. The skin can be tight and shiny, but it is not erythematous. Joint contractures are common. Although the inflammatory process is confined mostly to the subcutaneous tissue, inflammation can spread to the muscle and cause myopathic muscle weakness.

Shulman syndrome (eosinophilic fasciitis): Patients with this syndrome present with joint contractures and thickening of the skin and subcutaneous tissue.

Other conditions

Other conditions that must be kept in mind when considering polymyositis and dermatomyositis are as follows:

Overlap syndromes: Polymyositis and, less commonly, dermatomyositis can be associated with other collagen-vascular diseases (ie, overlap syndromes). SLE, systemic sclerosis, rheumatoid arthritis, and Sjögren syndrome all may have weakness as a facet of the disease complex. Muscular weakness and atrophy are greater than what arthritis alone can account for. They are characterized by elevated titers of anti–U1/U2-ribonucleoprotein antibodies, PM-Scl antibodies or SSA antibodies in scleroderma, Sjögren syndrome, SLE, or mixed connective tissue disease. Dermatomyositis is rarely associated with other collagen-vascular diseases except for scleroderma.

Carcinoma with polymyositis or dermatomyositis: Polymyositis and especially dermatomyositis may be a part of paraneoplastic syndromes. About 10-20% of patients with dermatomyositis have neoplasms. Cancers of breast, lung, ovary, and stomach are most commonly implicated.

The risk of cancer is greater in patients with DM than PM. Other risk factors noted in individual studies include:

• Evidence of capillary damage on muscle biopsy
• DM complicated by cutaneous necrosis on the trunk
• Cutaneous leukocytoclastic vasculitis 
• Older age at diagnosis of DM or PM

Age-appropriate cancer screening tests (eg, mammography and colonoscopy) are a valuable part of the workup of a patient with DM or PM. Serum CA125, CA19-9, PSA, and stools for occult blood can be considered as part of workup. Some experts recommend screening female DM patients with a serum CA125 determination at least twice yearly, and the performance of annual pelvic and transvaginal ultrasonography for up to 5 years after the diagnosis of DM.

Workup

Laboratory Studies

• Polymyositis
  • The diagnosis of polymyositis is established by using serum enzyme levels and electromyography (EMG) studies and confirmed by means of diagnostic muscle biopsy.
  • The most sensitive enzyme is creatine kinase (CK). In the presence of disease, levels can be elevated as much as 50 times the reference level. The CK level usually parallels disease activity. In active polymyositis, it is rarely in the reference range. The level may also be in the reference range in some patients with polymyositis associated with connective-tissue disease.
  • Anti-Jo-1 antibodies are present in one fifth of patients.
  • Along with CK, levels of aldolase, serum aspartate aminotransferase (AST, or glutamic-oxaloacetic transaminase [SGOT]), serum alanine aminotransferase (ALT, or glutamic-pyruvic transaminase [SGPT]), and lactate dehydrogenase (LDH) may also be elevated. If AST levels are higher than ALT levels, a myogenic cause should be suspected.
• Dermatomyositis
  • Levels of serum CK are usually, though not always, elevated. Levels may be as high as several 100s to 1000 U/mL.
  • AST, ALT, LDH, and aldolase levels may also be elevated.
  • Cancer antigen 125 (CA125) and cancer antigen 19-9 (CA19-9) may be useful markers of the risk of tumors in patients with dermatomyositis and polymyositis. Therefore, tests of these markers should be included in the search for cancer in patients with dermatomyositis/polymyositis, especially those without interstitial lung disease

Imaging Studies

• MRI may show increased signal intensity in the affected muscles and surrounding tissues.
• Because of the lack of sensitivity and specificity, MRI is not helpful in diagnosing the disease; however, it can help in monitoring its progress, and it may be used to guide decisions regarding muscle biopsy.

Procedures

• EMG may be helpful in diagnosis, though findings can be normal in 15% of patients. It shows a typical myopathic pattern with irritability, although it is not specific for the condition. These findings are most consistently observed in weak proximal muscles. EMG also is helpful in selecting a muscle for biopsy.
• Specific findings are as follows:
  • In polymyositis, needle EMG shows myopathic potentials characterized by short-duration, low-amplitude polyphasic units on voluntary activation and increased spontaneous activity with fibrillations, complex and repetitive discharges, and positive and sharp waves, along with early recruitment.
  • In dermatomyositis, needle EMG shows myopathic features with indications of muscle irritability. The myopathic potentials are characterized by short-duration, low-amplitude, polyphasic units and increased spontaneous activity with fibrillations, complex repetitive discharges, and positive sharp waves. Recruitment pattern shows early recruitment.
• Single-fiber EMG (SFEMG)
  • In 1 study, SFEMG were recorded from the extensor digitorum communis of 34 patients with polymyositis or dermatomyositis and compared with findings on routine EMG, serum CK determination, and muscle biopsy.
  • SFEMG recordings were abnormal in all 34 patients. The prominent feature was markedly increased fiber density with normally or mildly increased jitter.
  • SFEMG is of great value in diagnosis and in evaluating the disease process to understand inflammatory myopathies in patients with clinically suspected disease but normal findings on routine EMG, CK determination, and muscle biopsy.

Histologic Findings

Polymyositis

Muscle biopsy is the definitive test not only for establishing the diagnosis of polymyositis but also for excluding other neuromuscular diseases. In polymyositis, inflammation is the histologic hallmark of the disease. The endomysial infiltrates are mostly in foci in the fascicles, initially surrounding healthy muscle fibers and finally invading these cells and resulting in phagocytosis and necrosis. Because the inflammatory infiltrates can be small and multifocal, they can be missed in a small muscle-biopsy specimen. Perifascicular atrophy or prominent perivascular infiltrates are not present, and the blood vessels are normal. When the disease becomes chronic, the connective tissue increases. The diagnosis of polymyositis is definite when a patient has subacute elevated levels of serum CK and findings on muscle biopsy consistent with the histologic features of polymyositis (see Images 1-4).

Hematoxylin and eosin paraffin section shows polymyositis. Longitudinal section shows a dense, chronic, endomysial inflammatory infiltrate. Image courtesy of Roberta J. Seidman, MD.

Hematoxylin and eosin frozen section shows polymyositis. Endomysial chronic inflammation is present among intact myofibers that are remarkable only for increased variability of fiber size. Image courtesy of Roberta J. Seidman, MD.

Hematoxylin and eosin paraffin section shows polymyositis. Patient had dense endomysial inflammation that contains an abundance of plasma cells, which can be observed in patients with chronic polymyositis. Two necrotic myofibers, characterized by dense eosinophilic staining, are observed. Focal fatty infiltration of the muscle is present in the lower left quadrant of the photomicrograph. Image courtesy of Roberta J. Seidman, MD.

Hematoxylin and eosin paraffin section shows polymyositis. Photomicrograph illustrates attack on a nonnecrotic myofiber by autoaggressive T lymphocytes. On the left, the central myofiber is intact. On the right, it is obliterated by a segmental inflammatory attack. If immunohistochemistry were performed, expected findings would include an admixture of CD8 T lymphocytes and macrophages in the inflammatory process. Image courtesy of Roberta J. Seidman, MD.

Findings on muscle biopsy can be diagnostic. Although inflammation is the histologic hallmark of dermatomyositis, polymyositis, and inclusion-body myositis, dermatomyositis is the only disease that shows perifascicular atrophy. In addition, many fibers undergo degeneration and necrosis that cause them to lose their staining ability; therefore, they are termed ghost fibers. When these changes are associated with collections of inflammatory cells around the blood vessels, the diagnosis of dermatomyositis is certain (see Images 5-7).

Hematoxylin and eosin paraffin shows dermatomyositis. In dermatomyositis, inflammation is characteristically perivascular and perimysial. Vessel oriented approximately vertically in the center has a mild perivascular chronic inflammatory infiltrate. The endothelium is plump. The wall is not necrotic. A few lymphocytes in the wall of the vessel are probably in transit from the lumen to the external aspect of the vessel. Some observers may interpret this finding as vasculitis, but it is certainly neither necrotizing vasculitis nor arteritis. Image courtesy of Roberta J. Seidman, MD.

Hematoxylin and eosin frozen section shows perifascicular atrophy in dermatomyositis. Fascicles in this sample show atrophy, predominantly at the periphery, along the connective-tissue border. Ischemia is considered to cause perifascicular atrophy. This finding is characteristic of dermatomyositis, mostly associated with the juvenile form but it is also observed in the adult form. Image courtesy of Roberta J. Seidman, MD.

Immunofluorescence for membrane attack complex of complement (MAC) in dermatomyositis. Bright ring of yellow-green fluorescence at the center represents MAC in the wall of the microvessel. Finding was not present after treatment with steroids. Image courtesy of Roberta J. Seidman, MD.

Treatment

Medical Care

The goal of therapy is to improve muscle strength to improve function in activities of daily living. Improvement in strength is usually accompanied by a decrease in the serum CK level, a change that must be interpreted with caution because most immunosuppressive therapies decrease levels of serum muscle enzymes without necessarily improving muscle strength.

Consultations

• Consultation with an occupational and rehabilitation therapist may help patients with ambulation by providing necessary equipment.
• A swallowing evaluation for dysphagia is recommended.
• Proper emotional support is also important.

Diet

Advise patients who are receiving steroid therapy to follow a strict low-salt, low-carbohydrate, and high-protein diet to avoid weight gain and hypertension.

Activity

Physical therapy helps to preserve muscle function and prevents disuse atrophy of the weak muscles or joint contractures; therefore, consider it in the initial stage of the disease.

Medication

Of all the treatments that are available, prednisone remains the drug of choice.² If treatment with steroids is not successful, other lines of treatment are considered, such as intravenous immunoglobulins (IVIG), antineoplastic agents, and antimetabolites.³

Systemic corticosteroids

Corticosteroids act as anti-inflammatory and immunosuppressive agents and are the first-line drug for treating both polymyositis and dermatomyositis.

Prednisone (Deltasone, Orasone, Meticorten)

Objective increase in muscle strength by second or third month of therapy determines efficacy.

Dosing

Adult

Usual starting dose: 1 mg/kg PO qd; length of treatment and taper individualized to clinical response and normalization of CK; general guideline: treatment for 3-4 wk, then taper slowly over 8-10 wk to 1 mg/kg qod; with continued efficacy and no serious adverse effects, reduce dosage further by 5-10 mg PO q3-4wk to lowest possible dose that controls disease; total should be 1-2 y

Pediatric

Usual starting dose: 1-2 mg/kg/d PO; not to exceed 100 mg/d; individualize taper as in adults; total treatment should be at least 1-2 y

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection; peptic ulcer disease; hepatic dysfunction; connective tissue infections; fungal or tubercular skin infections

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, hypertension, osteonecrosis, myopathy, peptic ulcer disease, cataracts, glaucoma, hypokalemia, osteoporosis, euphoria, psychosis, growth suppression, and infections may occur with glucocorticoid use; patients should be cautioned on excessive appetite, should be on a low-fat, low-carbohydrate diet; should use supplemental calcium and bisphosphonate

Antineoplastic agents

These drugs inhibit cell growth and proliferation. Cyclophosphamide has shown promising results. The drug may be helpful in a subset of patients with interstitial lung disease. Methotrexate (MTX), an antagonist of folate metabolism, has been used frequently despite disappointing results.

Cyclophosphamide (Cytoxan, Neosar)

Chemically related to nitrogen mustards. As alkylating agent, mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth and proliferation of immune cells, in turn resulting in immunosuppression.

Dosing

Adult

2-2.5 mg/kg/d PO/IV, usually 50 mg PO tid

Pediatric

Administer as in adults

Interactions

Allopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate doxorubicin-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; toxicity may increase with chloramphenicol; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia; coadministration with succinylcholine may increase neuromuscular blockade by inhibiting cholinesterase activity

Contraindications

Documented hypersensitivity; severely depressed bone marrow function

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Increases risk of neoplasia; regularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis

Methotrexate (Folex PFS, Rheumatrex)

Unknown mechanism of action in treatment of inflammatory reactions. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). May affect immune function, including inhibition of production of proinflammatory cytokines. Adjust dose gradually to attain satisfactory response. Children who do not respond to high-dose prednisone should be treated with MTX immediately.

Dosing

Adult

7.5 mg/wk PO/SC as single dose qwk; depending on clinical response, increase dose 2.5-5 mg/wk to maximum of 25 mg/wk; may also administer IV

Pediatric

Usually started with single weekly dose of 0.25 mg/kg/wk PO/SC, followed by weekly increase to maximum of 0.6 mg/kg/wk depending on clinical response or toxicity

Interactions

Concurrent PO aminoglycosides may decrease absorption and blood levels; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, can increase plasma levels; may decrease phenytoin plasma levels; may increase plasma levels of thiopurines

Contraindications

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, clinically significant anemia); renal insufficiency

Precautions

Pregnancy

X - Contraindicated; benefit does not outweigh risk

Precautions

Monitor CBC counts qmo and liver and renal function q1-3mo during therapy (more frequently during initial dosing or dose adjustments or elevated MTX is a risk [eg, in dehydration]); toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if blood counts decrease substantially; fatal reactions reported when administered concurrently with NSAIDs; adverse effects include MTX pneumonitis, stomatitis, GI symptoms, leukopenia, renal toxicity, and hepatotoxicity

Immunoglobulins

These drugs improve the clinical and immunologic aspects of the disease. May decrease autoantibody production and increase solubilization and removal of immune complexes. IVIG has been effective in dermatomyositis.⁴ Improvement is observed after the first infusion and is evident clearly by the second monthly infusion. If no improvement is observed by second or third dose, treatment is unlikely to be successful.

Danieli et al in an open study found that IVIG as an add-on treatment with mycophenolate mofetil is safe and effective in refractory myositis.⁵  

Immune globulin intravenous (Gammunex, Gammagard, Octagam)

At high doses, promising and safe choice with good benefit. Expensive and may have to be repeated q4-6wk to maintain benefit.

Dosing

Adult

0.4 g/kg/d IV for 5 d or 1 g/kg/d for 2 d

Pediatric

Not established

Interactions

Globulin preparation may interfere with immune response to live virus vaccine (MMR) and reduce efficacy (do not administer within 3 mo of vaccination)

Contraindications

Documented hypersensitivity; IgA deficiency

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Check serum IgA levels before therapy (use IgA-depleted product, eg, Gammagard S/D); infusions may increase serum viscosity and thromboembolic events; infusions may increase risk of migraine attacks, aseptic meningitis (10%), urticaria, pruritus, or petechiae (2-30 d after infusion); increases risk of renal tubular necrosis in elderly patients and in patients with diabetes, volume depletion, or preexisting kidney disease; laboratory changes associated with infusions include elevated antiviral or antibacterial antibody titers for 1 mo, 6-fold increase in ESR for 2-3 wk, and apparent hyponatremia

Immunosuppressant agents

The use of a nonsteroidal immunosuppressive drug is determined by the need for a steroid-sparing effect when (1) serious complications have developed with steroid use, (2) repeated relapses have occurred each time an attempt was made to lower a high steroid dosage, (3) prednisone did not improve strength, or (4) the patient has a rapidly progressive disease accompanied by severe weakness and respiratory failure.

Mycophenolate Mofetil (CellCept)

Metabolized in liver; CYP450, prodrug converted to mycophenolic acid. Promising drug for the treatment of dermatomyositis/polymyositis.

Dosing

Adult

2 g PO bid

Pediatric

Not established

Interactions

Combination with acyclovir or ganciclovir may increase levels for both drugs due to competition for renal tubular excretion; aluminum and/or magnesium in some antacids and cholestyramine-containing products may decrease absorption, reducing levels (do not coadminister); probenecid may increase levels; salicylates and azathioprine may increase toxicity; may decrease levonorgestrel AUC; may decrease response to live viral vaccine; may increase free fraction levels of theophylline when given in combination

Contraindications

Documented hypersensitivity; Lesch-Nyhan syndrome

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Increases risk of infection (monitor blood count); severe renal impairment (CrCl <25 mL/min) may increase adverse effects due to increased free MPA; caution in active peptic ulcer disease; incidence of malignancies and lymphoma consistent with that of other immunosuppressants (0.9%); constipation, nausea, diarrhea, urinary tract infection, and nasopharyngitis common; interstitial lung disorders, colitis, pancreatitis, intestinal perforation, GI hemorrhage, gastric ulcers, duodenal ulcers, and ileus rare; do not chew, crush, or cut Myfortic tab

Azathioprine (Imuran)

Alternative to corticosteroids. Derivative of 6-mercaptopurine. Dosages of 1.5-2 mg/kg/d PO well tolerated. Adverse effects fewer than those of other immunosuppressive agents.

Dosing

Adult

Starting dose: 50 mg/d PO; increase gradually as tolerated, monitor blood levels; effective range approximately 2-3 mg/kg

Pediatric

Administer as in adults

Interactions

Toxicity increases with allopurinol; concurrent ACE inhibitors may induce severe leukopenia; may increase levels of MTX metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Contraindications

Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

LFTs; reduce dose if platelet count <150 X 10⁹/L or total neutrophil count <1 X 10⁹/L; monitor blood parameters qwk initially, then each mo as stable dose achieved; total WBC count may be reduced to 4 X 10⁹/L, and lymphocyte count may be reduced to about 7.5 X 10⁹/L; some patients may have flu symptoms

Follow-up

Complications

• The main complications are related to involvement of organs other than the muscles, such as GI ulcerations, melena, hematemesis, or even infarctions affecting long stretches of the bowel, especially in dermatomyositis.
• A major problem with dermatomyositis can be the subcutaneous calcifications; when they protrude through the skin, they result in ulcerations, infections, and permanent disfiguring scars.
• In polymyositis, cardiac abnormalities and interstitial lung disease are common complications, especially in patients with anti–Jo-1 antibodies. Some studies have reported rates of these complications as high as 45%.

Prognosis

• The natural history of polymyositis and dermatomyositis is unknown because patients are now almost always treated with steroids.
  • Patients with interstitial lung disease may have a high mortality rate.
  • A number of patients still do not respond adequately to therapies and remain disabled.
  • Acute fulminating disease seems to be difficult to treat and resistant to therapies.
  • Patients in whom treatment is initiated soon after the onset of the symptoms have the best prognosis.
• When treatment is unsuccessful, the patient should be reevaluated and the muscle biopsy specimen reexamined.
  • A second biopsy may be considered to ensure that the diagnosis is correct.
  • The disorders most commonly mistaken for polymyositis are inclusion-body myositis and sporadic limb-girdle muscular dystrophy, which is suspected when the disease has a slow onset and progression and when the muscle-biopsy specimen does not show primary inflammatory features.

Patient Education

• The Myositis Association of America serves as a resource for patients and the medical community.
• Polymyositis/dermatomyositis at a glance
  • Polymyositis/dermatomyositis is a chronic inflammatory disease of muscle.
  • Muscle weakness is the most common symptom of polymyositis/dermatomyositis.
  • The cause of polymyositis/dermatomyositis is unknown.
  • Diagnosis of polymyositis/dermatomyositis involves physical examination of muscle strength, blood tests for muscle enzymes, electrical tests of muscle and nerves, and confirmation by muscle biopsy.
  • Treatment of polymyositis/dermatomyositis involves high doses of cortisone-related medications, immune suppression, and physical therapy.

Miscellaneous

Medicolegal Pitfalls

• The following may increase the medicolegal risk associated with the evaluation and management of this disorder:
  • Delay in diagnosis
  • Misdiagnosis
  • Failure to diagnose malignancy in dermatomyositis
  • Failure to inform patient about potential drug toxicity and medication adverse effects

Special Concerns

• Pregnancy
  • Polymyositis and dermatomyositis can occur in the last trimester of pregnancy or during puerperium; whether pregnancy is responsible for activating the disease is not known.
  • Pregnant women with dermatomyositis and polymyositis have been treated with steroids and have delivered healthy but small babies, though miscarriages and stillborn babies have also been reported.
• Overlap syndromes

Multimedia

Media file 1: Hematoxylin and eosin paraffin section shows polymyositis. Longitudinal section shows a dense, chronic, endomysial inflammatory infiltrate. Image courtesy of Roberta J. Seidman, MD.

Media file 2: Hematoxylin and eosin frozen section shows polymyositis. Endomysial chronic inflammation is present among intact myofibers that are remarkable only for increased variability of fiber size. Image courtesy of Roberta J. Seidman, MD.

Media file 3: Hematoxylin and eosin paraffin section shows polymyositis. Patient had dense endomysial inflammation that contains an abundance of plasma cells, which can be observed in patients with chronic polymyositis. Two necrotic myofibers, characterized by dense eosinophilic staining, are observed. Focal fatty infiltration of the muscle is present in the lower left quadrant of the photomicrograph. Image courtesy of Roberta J. Seidman, MD.

Media file 4: Hematoxylin and eosin paraffin section shows polymyositis. Photomicrograph illustrates attack on a nonnecrotic myofiber by autoaggressive T lymphocytes. On the left, the central myofiber is intact. On the right, it is obliterated by a segmental inflammatory attack. If immunohistochemistry were performed, expected findings would include an admixture of CD8 T lymphocytes and macrophages in the inflammatory process. Image courtesy of Roberta J. Seidman, MD.

Media file 5: Hematoxylin and eosin paraffin shows dermatomyositis. In dermatomyositis, inflammation is characteristically perivascular and perimysial. Vessel oriented approximately vertically in the center has a mild perivascular chronic inflammatory infiltrate. The endothelium is plump. The wall is not necrotic. A few lymphocytes in the wall of the vessel are probably in transit from the lumen to the external aspect of the vessel. Some observers may interpret this finding as vasculitis, but it is certainly neither necrotizing vasculitis nor arteritis. Image courtesy of Roberta J. Seidman, MD.

Media file 6: Hematoxylin and eosin frozen section shows perifascicular atrophy in dermatomyositis. Fascicles in this sample show atrophy, predominantly at the periphery, along the connective-tissue border. Ischemia is considered to cause perifascicular atrophy. This finding is characteristic of dermatomyositis, mostly associated with the juvenile form but it is also observed in the adult form. Image courtesy of Roberta J. Seidman, MD.

Media file 7: Immunofluorescence for membrane attack complex of complement (MAC) in dermatomyositis. Bright ring of yellow-green fluorescence at the center represents MAC in the wall of the microvessel. Finding was not present after treatment with steroids. Image courtesy of Roberta J. Seidman, MD.

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Keywords

dermatomyositis, polymyositis, inflammatory myopathies, primary muscle weakness, endomysial inflammation, elevated levels of serum muscle enzymes, myositis-associated antibodies, MAA, myositis-specific antibodies, MSA, muscle diseases, juvenile dermatomyositis, childhood dermatomyositis, overlap syndrome, polymyositis associated with neoplasia, polymyositis associated with connective tissue disorder, dermatomyositis associated with neoplasia, childhood dermatomyositis with necrotizing vasculitis, childhood myositis with necrotizing vasculitis

Contributor Information and Disclosures

Author

Sushma Podila, MD, Resident Physician, Department of Neurology, Columbia Presbyterian Medical Center
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas H Brannagan III, MD, Associate Professor of Clinical Neurology and Director, Peripheral Neuropathy Center, Columbia University, College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus, New York
Thomas H Brannagan III, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Peripheral Nerve Society
Disclosure: Nothing to disclose.

Medical Editor

Milind J Kothari, DO, Professor and Vice-Chair, Department of Neurology, Pennsylvania State University College of Medicine; Consulting Staff, Department of Neurology, Hershey Medical Center
Milind J Kothari, DO is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and American Neurological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Glenn Lopate, MD, Associate Professor, Department of Neurology, Division of Neuromuscular Diseases, Washington University School of Medicine; Chief of Neurology, St Louis ConnectCare, Consulting Staff, Barnes Jewish Hospital
Glenn Lopate, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Aamir Hashmat, MD, and Zaineb Daud, MD, to the development and writing of this article.

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