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 when
- Arising from sitting or lying positions
- Climbing stairs
- Raising 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 disorders
- Thyroid disease
- Cushing syndrome
- Infectious myositis (viral, bacterial, parasitic)
- Drug-induced myopathies:
- Cholesterol-lowering agents (statins)
- Colchicine
- Corticosteroids
- Ethanol
- Chloroquine
- Zidovudine
- Electrolyte disorders (magnesium, calcium, potassium)
- Heritable metabolic myopathies
- Sleep-apnea syndrome
DIAGNOSTIC TESTS & INTERPRETATION
- 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
- 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 degeneration
- Phagocytosis of muscle debris
- Perifascicular muscle fiber atrophy
- Inflammatory cell infiltrates in adult form
- Via 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
- Prednisone
- 40 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 BID
- Methotrexate 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).
- Precautions
- Prednisone: 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.