Dott. M.M. CIAMMAICHELLA

Dirigente Medico

UOC Medicina Interna I° per l'Urgenza

(Direttore: Dott. G. Cerqua)

A.C.O. S. Giovanni – Addolorata, Roma

 

 

 

POLYMIOSITIS

 

 

 

KEY-WORDS: Polymiositis

 

 

INTRODUCTION
CLINICAL
WORKUP
TREATMENT
MEDICATION
FOLLOW-UP
MISCELLANEOUS
BIBLIOGRAPHY

 


INTRODUCTION

 

Background: Polymyositis (PM) is an inflammatory muscle disease of unknown etiology. PM, dermatomyositis (DM) and inclusion body myositis are the major members of a group of syndromes called the idiopathic inflammatory myopathies.

Polymyositis usually presents as symmetric pain and weakness of the proximal limb and neck flexor muscles. Less commonly, the distal musculature or muscles of glutition are involved. Symptoms develop over several weeks to months.

Similarly, dermatomyositis has an insidious onset and involves proximal muscles. However, this disease also includes the presence of a characteristic rash.

There are no strictly defined diagnostic criteria for PM-DM; however, Bohan and Peter have proposed those which are most widely cited. These include the typical rash of dermatomyositis, a history and physical examination which reveal symmetric, proximal muscular weakness, elevated serum muscle enzymes, electromyographic evidence of myopathic abnormalities and characteristic muscle biopsy findings.

Much of the literature on PM and DM groups them together as one disease. It has become apparent that dermatomyositis is not simply polymyositis with the addition of a rash. Each disease has characteristic clinical differences, histopathologic findings and immune markers.

Pathophysiology: In both diseases there are immune-mediated muscle inflammation and vascular damage. In PM, the immune system is primed to act against previously unrecognized muscle antigens. In DM, there is complement-mediated damage to endomysial vessels and to microvasculature of the dermis.

Frequency:

  • In the U.S.: Overall, the annual incidence is 1:100,000/y.

Mortality/Morbidity:

  • The mortality is 20% over a 5-y period.
  • Patients with advanced age, cardiac or pulmonary involvement or dysphagia have a higher mortality.

Race: PM is most common among blacks. In one study, the incidence of the disease among the Bantu in South Africa, was 10 times that seen in whites.

Sex: PM is most prevalent in women. The female to male ratio is 2:1.

Age:

  • Polymyositis is an adult disease and is rare to non-existent under the age of 20.
  • Dermatomyositis, although primarily an adult disease, is also seen in children, usually between the ages of 5-14 y.

 

 


 CLINICAL

 

 

History:

  • Patients present with symmetric proximal muscle pain and weakness.
  • Muscle pain may be reported at rest or with use.
  • Symptoms develop over weeks to months.
  • Dysphagia (30%) and aspiration may be present if the muscles of glutition are involved.
  • Arthralgias are often reported.
  • Difficulty kneeling, climbing or descending stairs, raising their arms and arising from a sitting or lying position
  • Joint pain
  • Rash over the face, chest and hands

Physical:

  • Muscles tender to palpation
  • Sensory testing and reflexes are normal.
  • Muscle atrophy
  • In dermatomyositis, a characteristic heliotrope rash may precede or accompany muscle weakness.
    • The heliotrope rash is a confluent, purplish-red, edematous periorbital eruption.
    • Other rashes seen with DM include erythematous nail beds and a scaly erythematous papular eruption over the knuckles.
    • Associated Findings:
      • Conduction defects, arrhythmias and myocarditis
      • Interstitial lung disease or aspiration pneumonia

Causes:

  • The etiology is unknown.
  • Muscle inflammation is immune mediated.
  • Various hypotheses exist; some believe a viral trigger causes autoimmune injury.



 

WORKUP

 

 

Lab Studies:

  • Creatine phosphokinase (CPK), aldolase, myoglobin, lactate dehydrogenase (LDH), AST and ALT may be elevated.
  • In practice, usually only the CPK and aldolase are tested. CPK is the most sensitive and specific and is usually 5-50 times above normal.
  • The erythrocyte sedimentation rate (ESR) is usually elevated.
  • Myoglobinuria
  • Positive rheumatoid factor (RF) (over 50% of patients)
  • Positive antinuclear antibody (ANA) (under 50% of patients)
  • Leukocytosis (over 50% of patients)

Imaging Studies:

  • Magnetic Resonance Imaging (MRI):
    • MRI has shown signal abnormalities of muscle due to inflammation, edema or scarring.
    • This may guide muscle biopsy.
    • Many clinicians choose the biopsy site based on the EMG and clinical examination and feel that MRI is not required.

Other Tests:

  • Electromyography (EMG) reveals characteristic myopathic abnormalities.
  • Electrocardiography (ECG) may reveal arrhythmias or conduction disturbances.

Procedures:

  • Inflammatory changes are seen on muscle biopsy (e.g., deltoid or quadriceps femoris). However, the biopsy may occasionally be normal due to patchy involvement.

 

 

 


 TREATMENT

 

 

Emergency Department Care:

  • Generally, this is an insidious disease with gradual progression.
  • Acute treatment involves having an awareness of polymyositis so that appropriate studies, such as CPK, aldolase and ESR, are measured.
  • Complications, such as aspiration pneumonia, may be the presenting illness.

Consultations:

  • A neurologist or rheumatologist is the primary consultant.
  • Consider a dermatologist if the heliotropic rash of dermatomyositis is present.

 

 


MEDICATION

 

 

Therapy is based on immune suppression with steroids. If this is not successful, other immunosuppressive agents are used. Steroids are started at a high dose and tapering begins at 1-3 mo, depending upon the clinical response.

 

Drug Category: Corticosteroids - These agents have anti-inflammatory properties and may cause profound and varied metabolic effects. In addition, these agents modify the body's immune response to diverse stimuli.

Drug Name

Prednisone (Deltasone) - It is useful in the treatment of inflammatory and allergic reactions. By reversing increased capillary permeability and suppressing PMN activity, it may decrease inflammation.

Adult Dose

0.05-2 mg/kg/d PO, divided bid-qid (Taper over 2 wk as symptoms resolve.)

Pediatric Dose

4-5 mg/m2/d or 1-2 mg/kg PO qd (Taper over 2 wk as symptoms resolve.)

Contraindications

Avoid use in patients with documented hypersensitivity to this drug and those with viral, fungal or tubercular skin lesions.

Interactions

Prednisone clearance may decrease when used concurrently with estrogens.
When used with digoxin, it may increase digitalis toxicity secondary to hypokalemia.
Monitor patients for hypokalemia when taking this medication concurrently with diuretics.

Pregnancy

B - Usually safe but benefits must outweigh the risks.

Precautions

Patients receiving glucocorticoids are at risk for multiple complications, including severe infections.
The abrupt discontinuation of glucocorticoids may cause an adrenal crisis. Hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression and infections are possible complications of glucocorticoid use.

 

Drug Category: Immunosuppressants - These agents are useful in the treatment of autoimmune disease.

Drug Name

Azathioprine (Imuran) - It inhibits mitosis and cellular metabolism by antagonizing purine metabolism and inhibiting the synthesis of DNA, RNA, and proteins.
It is a second line agent occasionally used with steroids to allow a lower steroid dose. It is also used if a relapse of the disease occurs during tapering of steroids. Treatment for 6 mo may be required.

Adult Dose

Starting dose, 25-50 mg/kg/d PO with titration upward to 2-3 mg/kg/d

Pediatric Dose

Initial dose: 2-5 mg/kg/d PO or IV
Maintenance dose: 1-2 mg/kg/d

Contraindications

Avoid use in patients with documented hypersensitivity to this drug or related products.

Interactions

Allopurinol increases the toxicity of azathioprine.
Concurrent use with ACE inhibitors may induce severe leukopenia.
Plasma levels of the methotrexate metabolite may be increased when used concurrently.
Azathioprine may decrease the effects of anticoagulants.
Cyclosporine plasma levels may be decreased when used concurrently with azathioprine.
The pharmacologic actions of neuromuscular blockers may be decreased or reversed by azathioprine.

Pregnancy

D - Unsafe in pregnancy

Precautions

The immunosuppression caused by azathioprine increases the risk of neoplasia. Exercise caution in patients with liver disease and renal impairment. Hematologic toxicities are possible with this medication.

 

Drug Name

Methotrexate (Folex) - The mechanism of action of methotrexate in the treatment of inflammatory reactions is unknown. It may affect immune function and usually ameliorates the symptoms of inflammation (e.g., pain, swelling, and stiffness). It is also considered a second line agent when there is no response to prednisone.

Adult Dose

Initially administer 7.5 mg PO and increase by 2.5 mg/wk to a total of 20/mg/wk

Pediatric Dose

5-15 mg/m2/wk PO or IM as a single dose or as 3 divided doses, given 12 h apart

Contraindications

Avoid use in patients with documented hypersensitivity to this drug or related products and those diagnosed with alcoholism or hepatic insufficiency.
Do not administer to patients with documented immunodeficiency syndromes, preexisting blood dyscrasias, such as bone marrow hypoplasia, leukopenia, thrombocytopenia or significant anemia.

Interactions

Oral aminoglycosides may decrease the absorption and blood levels of concurrent oral methotrexate.
Charcoal lowers the plasma levels of PO and IV methotrexate and may be particularly significant with high dose therapies.
Folic acid or its derivatives, contained in some vitamins, may decrease the response to methotrexate.
NSAIDs administered concurrently with methotrexate may cause a fatal interaction.
Indomethacin and phenylbutazone may increase methotrexate plasma levels, possibly by inhibiting renal prostaglandin synthesis or through competitive renal secretion.
Phenytoin serum concentrations may be decreased by methotrexate.
Probenecid, salicylates and sulfonamides, including TMP-SMZ may increase the therapeutic effects of MTX. It may also increase the toxicity of methotrexate.
Procarbazine may increase the nephrotoxicity of methotrexate.
Methotrexate may increase plasma levels of thiopurines.

Pregnancy

D - Unsafe in pregnancy

Precautions

Monitor CBCs monthly and liver and renal function q1-3mo during therapy. Monitoring should be performed frequently during the initial dosing or when changing doses. It should also be monitored when there is a risk of elevated methotrexate levels such as dehydration.
Methotrexate has toxic effects on the hematologic, renal, GI, pulmonary and neurologic systems.
Stop methotrexate immediately if there is a significant drop in blood counts. Aspirin, NSAIDs or low dose steroids may also be administered concomitantly with this medication. However, the possibility of increased toxicity with concomitant use of NSAIDs, including salicylates, has not been tested.

 

Drug Category: Immunoglobulins - These agents are used to neutralize antibodies that may be associated with autoimmune diseases.

Drug Name

Intravenous Immunoglobulin (IVIG) - IVIG has been used as treatment in patients who have refractory. There are conflicting reports about its effectiveness.

Adult Dose

2 g/kg IV slowly given daily for 3-5 d (Repeat at monthly intervals.)

Pediatric Dose

Use the same regimen as in adults.

Contraindications

Avoid use in patients with documented hypersensitivity to this product and those with IgA deficiency and anti-IgE/IgG antibodies.

Interactions

Interferes with the immunization against measles, mumps and rubella virus

Pregnancy

C - Safety for use during pregnancy has not been established.

Precautions

Immunoglobulin infusions may increase serum viscosity and thromboembolic events. It is also associated with the development of aseptic meningitis and renal insufficiency.



 

 

FOLLOW-UP

 

 

Further Outpatient Care:

  • Physical therapy should begin early in the course of illness to maintain mobility and strength.
  • Continuing clinical assessment and muscle enzyme abnormalities guide the duration of treatment.

Complications:

  • Pneumonia
  • Infection
  • Myocardial infarction
  • Carcinoma (especially breast and lung)
  • Severe dysphagia
  • Respiratory impairment
  • Aspiration pneumonitis
  • Steroid myopathy
  • Complications of steroid therapy

Prognosis:

  • Overall, the mortality for polymyositis and dermatomyositis is 20% over 5 y.
  • There is significant morbidity associated with these diseases and significant morbidity as a result of the drugs used in treatment.
  • Some deaths are due to malignancy, which is associated with dermatomyositis.
  • Residual weakness (30%)
  • Persistent active disease (20%)
  • Survival is worse for women and African-Americans.
  • Most patients improve with therapy.
  • Full recovery is expected in 50%.



 

MISCELLANEOUS

 

 

Medical/Legal Pitfalls:

  • Consider an underlying malignancy when diagnosing dermatomyositis.

 

 

 


 BIBLIOGRAPHY

  • Amato AA, Barohn RJ: Idiopathic inflammatory myopathies. Neurol Clin 1997; 15: 616-647.
  • Dalakas MC, Sivakumar K: The immunologic and inflammatory differences between dermatomyositis, polymyositis, and sporadic inclusion body myositis. Curr Opin Neurol 1996; 3: 235-239.
  • Koopman WJ: Polymyositis/dermatomyositis classification Criteria. Arthritis and Allied Conditions 1997; 17-18.
  • Mastaglia FL, Ojeda VJ: Inflammatory myopathies: Part 1. Ann Neurol 1985; 17: 215-227.
  • Olsen NJ, Park JH: Inflammatory myopathies: issues in diagnosis and management. Arthritis Care Res 1997; 3: 200-207.