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Polymyositis/Dermatomyositis

- Symmetric proximal muscle weakness (1) causing difficulty when - Arising from sitting or lying positions - Climbing stairs - Raising arms

- Diagnosis of muscle component (myositis) usually relies on four findings: - Weakness - Creatine kinase (CK) and/or aldolase elevation - Abnormal electromyogram (EMG) - Findings on muscle biopsy

- Microscopic findings: - Muscle fiber degeneration - Phagocytosis of muscle debris - Perifascicular muscle fiber atrophy - Inflammatory cell infiltrates in adult form - Via electron microscopy: inclusion bodies (IBM only) - Sarcoplasmic basophilia

para>Elderly patients with myositis or dermatomyositis are at increased risk of neoplasm.

Pediatric Considerations

Childhood dermatomyositis is likely a separate entity associated with cutaneous vasculitis and muscle calcifications.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Inflammatory process, mediated by T cells and cytokine release, leading to damage to muscle cells (predominantly skeletal muscles)
  • In patients with IBM, degenerative mechanisms may be important.
  • Unknown; potential viral, genetic factors

Genetics

Mild association with human leukocyte antigen (HLA) " DR3, HLA-DRw52

RISK FACTORS

Family history of autoimmune disease (e.g., systemic lupus, myositis) or vasculitis

COMMONLY ASSOCIATED CONDITIONS

  • Malignancy (in 15 " 25%)
  • Progressive systemic sclerosis
  • Vasculitis
  • Systemic lupus erythematosus (SLE)
  • Mixed connective tissue disease

DIAGNOSIS

HISTORY

  • Symmetric proximal muscle weakness (1) causing difficulty whenArising from sitting or lying positionsClimbing stairsRaising arms
  • Joint pain/swelling
  • Dysphagia
  • Dyspnea
  • Rash on face, eyelids, hands, arms

PHYSICAL EXAM

Proximal muscle weakness

  • Shoulder muscles
  • Hip girdle muscles (trouble standing from seated or squatting position, weak hip flexors in supine position)
  • Muscle swelling, stiffness, induration
  • Distal muscle weakness is seen only in patients with IBM.
  • Rash over face (eyelids, nasolabial folds), upper chest, dorsal hands (especially knuckle pads), fingers ( "mechanic 's hands " )
  • Periorbital edema
  • Calcinosis cutis (childhood cases)
  • Mesenteric arterial insufficiency/infarction (childhood cases)
  • Cardiac impairment; arrhythmia, failure

DIFFERENTIAL DIAGNOSIS

  • Vasculitis
  • Progressive systemic sclerosis
  • SLE
  • Rheumatoid arthritis
  • Muscular dystrophy
  • Eaton-Lambert syndrome
  • Sarcoidosis
  • Amyotrophic lateral sclerosis
  • Endocrine disordersThyroid diseaseCushing syndrome
  • Infectious myositis (viral, bacterial, parasitic)
  • Drug-induced myopathies:Cholesterol-lowering agents (statins)ColchicineCorticosteroidsEthanolChloroquineZidovudine
  • Electrolyte disorders (magnesium, calcium, potassium)
  • Heritable metabolic myopathies
  • Sleep-apnea syndrome

DIAGNOSTIC TESTS & INTERPRETATION

  • Diagnosis of muscle component (myositis) usually relies on four findings:WeaknessCreatine kinase (CK) and/or aldolase elevationAbnormal electromyogram (EMG)Findings on muscle biopsy
  • Presence of compatible skin rash of dermatomyositis

Initial Tests (lab, imaging)

  • Increased CK, aldolase
  • Increased serum AST (aspartate aminotransferase)
  • Increased LDH (lactate dehydrogenase)
  • Myoglobinuria
  • Increased ESR
  • Positive rheumatoid factor (<50% of patients)
  • Positive antinuclear antibody (ANA) (>50% of patients)
  • Leukocytosis (<50% of patients)
  • Anemia (<50% of patients)
  • Hyperglobulinemia (<50% of patients)
  • Anti-HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) seen in patient with statin-associated necrotizing autoimmune myositis
  • Myositis-specific antibodies (antisynthetase antibodies) described in a minority of patients:Anti-Jo-1 is the most common but has been found in <20% of patients.Associated with an increased incidence of interstitial lung disease
  • Chest radiograph as part of initial evaluation to assess for associated pulmonary involvement or malignancy

Follow-Up Tests & Special Considerations

  • Changes in muscle enzymes (CK or aldolase) correlate with improvement and worsening.
  • MRI to assess muscle edema and inflammation may be used in some patients to determine best biopsy site or response to therapy.

Diagnostic Procedures/Other

  • EMG: muscle irritability, low-amplitude potentials, polyphasic action potentials, fibrillations
  • Muscle biopsy (deltoid or quadriceps femoris)

Test Interpretation

  • Microscopic findings:Muscle fiber degenerationPhagocytosis of muscle debrisPerifascicular muscle fiber atrophyInflammatory cell infiltrates in adult formVia electron microscopy: inclusion bodies (IBM only)Sarcoplasmic basophilia
  • Muscle fiber increased in size
  • Vasculopathy (childhood polymyositis/dermatomyositis)

TREATMENT

GENERAL MEASURES

General evaluation for malignancy in all adults, particularly with dermatomyositis, at initial evaluation and during follow up

MEDICATION

First Line

  • Prednisone40 to 80 mg/day PO in divided doses (4)[B]Consolidate doses and reduce prednisone slowly when enzyme levels are normal.Probably need to continue 5 to 10 mg/day for maintenance in most patients.
  • For steroid-refractory or steroid-dependent patients: azathioprine 1 mg/kg PO (arthritis dose) once daily or BIDMethotrexate 10 to 25 mg PO weekly, useful in most steroid-resistant patients
  • Rash of dermatomyositis may require topical steroids or oral. hydroxychloroquine.
  • Patients with IBM have very poor response to steroids and other first- and second-line drugs in general.

Second Line

  • Other immunosuppressant drugs (e.g., cyclophosphamide, chlorambucil, cyclosporine, mycophenolate, tacrolimus) can be added to steroids.
  • Combination methotrexate and azathioprine also may be useful in refractory cases.
  • IVIG (5)[B] and rituximab (6)[B] have been reported to be helpful in a small series of patients with refractory disease.
  • Contraindications: Methotrexate is contraindicated with previous liver disease, alcohol use, pregnancy, and underlying renal disease (use with extreme caution in patients with serum creatinine >1.5 mg/dL in general).
  • PrecautionsPrednisone: Adverse effects associated with long-term steroid use include adrenal suppression, sodium and water retention, hypokalemia, osteoporosis, cataracts, and increased susceptibility to infection.Azathioprine: Adverse effects include bone marrow suppression, increased liver function tests, and increased risk of infection.Methotrexate: Adverse effects include stomatitis, bone marrow suppression, pneumonitis, and risk of liver fibrosis and cirrhosis with prolonged use.

ISSUES FOR REFERRAL

  • Diagnostic uncertainty, usually related to elevated muscle enzymes without typical symptoms of findings of muscle weakness
  • Poor response to initial steroid therapy
  • Excessive steroid requirement (unable to taper prednisone to <20 mg/day after 4 to 6 months)

SURGERY/OTHER PROCEDURES

None indicated, other than initial biopsy

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

  • Inability to stand, ambulate
  • Respiratory difficulty
  • Fever or other signs of infection
  • Inpatient evaluation seldom needed

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Patient Monitoring

  • Follow muscle enzymes along with muscle strength and functional capacity.
  • Monitor for steroid-induced complications (e.g., hypokalemia, hypertension, and hyperglycemia).
  • Bone densitometry and consideration of calcium, vitamin D, and bisphosphonate therapy
  • If azathioprine, methotrexate, or other immunosuppressant is used, appropriate laboratory monitoring should be done periodically (e.g., hematology, liver enzymes, and creatinine).
  • Attempt to decrease and/or discontinue steroid dose as patient responds to therapy.
  • Maintain immunosuppression until patient 's muscle strength stabilizes for prolonged period depending on individual patient parameters, risks of medication, risk of relapse; time period undefined (months, years).

DIET

Moderation of caloric and sodium intake to avoid weight gain from corticosteroid therapy.

PATIENT EDUCATION

  • Curtail excess physical activity in early phases when muscles enzymes are markedly elevated.
  • Emphasize range-of-motion exercises.
  • Gradually introduce muscle strengthening when muscle enzymes are normal or improved and stable (7)[B].

PROGNOSIS

  • Residual weakness: 30%
  • Persistent active disease: 20%
  • 5-year survival 65 " 75%, but mortality is 3-fold higher than general population (8,9).
  • Survival is worse for women and African Americans and those with dermatomyositis, IBM, or cancer.
  • Most patients improve with therapy.
  • Patients with IBM respond poorly to most therapies (10).
  • 20 " 50% have full recovery.

COMPLICATIONS

  • Pneumonia
  • Infection
  • Myocardial infarction
  • Carcinoma (especially breast, lung)
  • Severe dysphagia
  • Respiratory impairment due to muscle weakness, interstitial lung disease
  • Aspiration pneumonitis
  • Steroid myopathy
  • Steroid-induced diabetes, hypertension, hypokalemia, osteoporosis

REFERENCES

11 Dalakas MC. Inflammatory muscle diseases. N Engl J Med 2015;372(18):1734 " 1747.22 Mohassel P, Mammen AL. The spectrum of statin myopathy. Curr Opin Rheumatol. 2013;25(6):747 " 752.33 Meyer A, Meyer N, Schaeffer M, et al. Incidence and prevalence of inflammatory myopathies: a systematic review. Rheumatology (Oxford). 2015;54(1):50 " 63.44 Aggarwal R, Oddis CV. Therapeutic approaches in myositis. Curr Rheumatol Rep. 2011;13(3):182 " 191.55 Wang DX, Shu XM, Tian XL, et al. Intravenous immunoglobulin therapy in adult patients with polymyositis/dermatomyositis: a systematic literature review. Clin Rheumatol. 2012;31(5):801 " 806.66 Oddis CV, Reed AM, Aggarwal R, et al. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013;65(2):314 " 324.77 Alemo Munters L, Dastmalchi M, Andgren V, et al. Improvement in health and possible reduction in disease activity using endurance exercise in patients with established polymyositis and dermatomyositis: a multicenter randomized controlled trial with a 1-year open extension followup. Arthritis Care Res. 2013;65(12):1959 " 1968.88 Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep. 2012;14(3):275 " 285.99 Schiopu E, Phillips K, MacDonald PM, et al. Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine. Arthritis Res Ther. 2012;14(1):R22.1010 Machado P, Brady S, Hanna MG. Update in inclusion body myositis. Curr Opin Rheumatol. 2013;25(6):763 " 771.

CODES

ICD10

  • M33.20 Polymyositis, organ involvement unspecified
  • M33.90 Dermatopolymyositis, unspecified, organ involvement unspecified
  • M33.92 Dermatopolymyositis, unspecified with myopathy
  • M33.22 Polymyositis with myopathy

ICD9

  • 710.4 Polymyositis
  • 710.3 Dermatomyositis

SNOMED

  • 31384009 Polymyositis (disorder)
  • 396230008 Dermatomyositis (disorder)
  • 281357005 Idiopathic polymyositis
  • 281358000 idiopathic dermatomyositis (disorder)

CLINICAL PEARLS

  • Corticosteroids alone may be sufficient in patients who have rapid improvement in weakness and muscle enzymes. However, most patients require azathioprine, methotrexate, or other immunosuppressive medications.
  • The risk of associated malignancy is higher in patients >50 years and in those with cutaneous manifestations.
  • Elevated muscle enzymes (e.g., CK and aldolase) are seen frequently as transient phenomena in patients with febrile illness and injuries; may return to normal on repeat.
  • In patients with persistently elevated muscle enzymes and symptoms and findings of muscle weakness, EMG followed by muscle biopsy should be the initial studies considered.
  • Suspect IBM in older patients with very slow onset and progression of symptoms, poor response to steroids and immunosuppressive therapy, and atypical patterns (asymmetric, sometimes distal) of muscle weakness.
  • Suspect autoimmune necrotizing myositis in patients who develop myopathy while taking lipid-lowering drugs (statins) but fail to improve or worsen after withdrawal of statin therapy.