POLYMYOSITIS/DERMATOMYOSITIS

Christopher M. Wise, MD

 BASICS

DESCRIPTION

•  Systemic connective tissue disease characterized by inflammatory and degenerative changes in proximal muscles, sometimes accompanied by characteristic skin rash

–  If skin manifestations (Gottron sign [symmetric, scaly, violaceous, erythematous eruption over the extensor surfaces of the metacarpophalangeal and interphalangeal joints of the fingers]; heliotrope [reddish violaceous eruption on the upper eyelids]) are present, it is designated as dermatomyositis.

–  Different types of myositis include the following (1):

  Idiopathic polymyositis

  Idiopathic dermatomyositis

  Polymyositis/dermatomyositis as an overlap (usually with lupus or systemic sclerosis or as part of mixed connective-tissue disease)

  Myositis associated with malignancy

  Necrotizing autoimmune myositis (often statin-associated) (2)

  HIV-associated myopathy

•  Inclusion-body myositis (IBM), a variant with atypical patterns of weakness and biopsy findings

•  System(s) affected: cardiovascular, musculoskeletal, pulmonary, skin/exocrine

•  Synonym(s): myositis; inflammatory myopathy; antisynthetase syndrome (subset with certain antibodies)

EPIDEMIOLOGY

Incidence

•  Estimated at 1.2 to 19/million population/year (3)

•  Predominant age: 5 to 15 years, 40 to 60 years, peak incidence in mid-40s

•  Predominant sex: female > male (2:1)

Prevalence

2.4 to 33.8 patients/100,000 population (3)

Geriatric Considerations

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

ADMISSION, INPATIENT, AND NURSING CONSIDERATIONS

•  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

  1.  Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372(18):1734–1747.

  2.  Mohassel P, Mammen AL. The spectrum of statin myopathy. Curr Opin Rheumatol. 2013;25(6):747–752.

  3.  Meyer A, Meyer N, Schaeffer M, et al. Incidence and prevalence of inflammatory myopathies: a systematic review. Rheumatology (Oxford). 2015;54(1):50–63.

  4.  Aggarwal R, Oddis CV. Therapeutic approaches in myositis. Curr Rheumatol Rep. 2011;13(3):182–191.

  5.  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.

  6.  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.

  7.  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.

  8.  Marie I. Morbidity and mortality in adult polymyositis and dermatomyositis. Curr Rheumatol Rep. 2012;14(3):275–285.

  9.  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.

10.  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

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.