Polymyositis

Overview

Definition

Polymyositis (PM) is an autoimmune inflammatory myopathy that presents as symmetric proximal muscle weakness. Antisynthetase syndrome is a subtype that shows the presence of antisynthetase antibodies and certain extramuscular manifestations.

Etiology

The exact etiology is unknown.

Possible genetic predisposition:

HLA-A1
HLA-B8
HLA-DR3

Environmental factors:

Infectious:
- HIV
- Human T cell lymphotropic virus type-1 (HTLV-1)
- Hepatitis B and C
- Influenza
- Coxsackie B virus
Drug induced:
- ACE inhibitors
- D-penicillamine
- Hydralazine
- Procainamide
- Phenytoin

Associated medical conditions:

Malignancy
Connective-tissue disorders

Pathophysiology

Unclear triggering event → activation of CD8 T cells and macrophages
Inflammatory cells infiltrate healthy muscle fibers.
Cytotoxic response to unspecified muscle antigens → direct cellular damage to the endomysial layer of skeletal muscles → necrosis of muscle fibers

Clinical Presentation

Symptoms

Muscle weakness:
- Symmetric
- Develops gradually over weeks to months
- Particularly evident when:
  - Climbing stairs
  - Brushing hair
  - Standing up from a seated position
  - Reaching for overhead objects
  - Holding up the head
- Associated myalgias occur in a few patients.
Arthralgias or arthritis:
- Symmetric
- Joints involved:
  - Knees
  - Wrists
  - Hands
- Usually associated with antisynthetase syndrome
Constitutional symptoms:
- Anorexia
- Weight loss
- Fatigue
- Low-grade fever

Physical examination

Reduced muscle strength:
- Affects proximal muscle groups:
  - Deltoid
  - Hip flexors and extensors
  - Neck extensors → dropped head
- Late findings:
  - Muscle trophy
  - Loss of deep-tendon reflexes (due to severely weakened or atrophied muscles)
Sensory examination is normal.
Raynaud’s phenomenon may be present.
There is usually no cutaneous involvement. Exception: “mechanic’s hands”:
- Hyperkeratotic eruptions over the finger pads and lateral aspects of fingers
- Associated with antisynthetase syndrome

“Dropped head” in polymyositis: caused by weakness in the extensor muscles of the neck
Image by Lecturio.
“Mechanic’s hands” associated with antisynthetase antibodies in polymyositis: hyperkeratosis resulting in fissures, roughness, and scaling on the pad of the thumb and the lateral aspect of the index finger
Image: “Patient 3” by Department of Respiratory Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka City, Tokyo 181-8611, Japan. License: CC BY 2.0

Systemic manifestations

Respiratory:
- Interstitial lung disease (5%–30% of cases)
  - Dry cough
  - Dyspnea
  - Bilateral crackles
  - Seen with anti-synthetase syndrome
- Diaphragm and chest-wall muscle weakness
  - Respiratory insufficiency
GI: pharyngeal and esophageal involvement (approximately 30% of patients)
- Dysphagia
- Dysphonia
- Gastroesophageal reflux
Cardiovascular (rare):
- Abnormalities in atrioventricular conduction
- Myocarditis
- Dilated cardiomyopathy

Diagnosis

Diagnostic workup

Initial laboratory tests:
- CBC
  - Leukocytosis
  - Thrombocytosis
- Inflammatory markers
  - ↑ Erythrocyte sedimentation rate (ESR)
  - ↑ CRP
- Muscle enzymes
  - ↑↑ CK
  - ↑ Aldolase
  - ↑ AST and ALT
  - ↑ LDH
- ANA positivity
  - Nonspecific and not diagnostic
  - Seen in ⅓ of patients
Followed up based on myositis-specific antibody testing:
- Anti-signal recognition protein (anti-SRP) antibodies
  - Specific for inflammatory myopathies
  - Associated with severe myositis
- Anti-Jo-1 antibodies
  - Anti-histidyl tRNA synthetase antibody
  - Seen in anti-synthetase syndrome
  - Occurs in 20%–30% of patients
Additional studies if the diagnosis is unclear due to nonspecific or atypical findings:
- Electromyography (EMG):
  - Consists of nerve-conduction studies, including repetitive nerve stimulation and needle examination of muscles
  - Altered in 90% of cases
  - Common findings: ↑ insertional activity, spontaneous fibrillation, short-duration motor unit potential, and complex repetitive discharges
  - Can support the diagnosis, but is not diagnostic
- MRI of skeletal muscles:
  - Indicates muscle inflammation, edema, fibrosis, and calcification
  - Nonspecific, and cannot distinguish between rhabdomyolysis, muscular dystrophy, or metabolic myopathies
- Muscle biopsy:
  - Most accurate test to confirm the diagnosis
  - Findings: endomysial invasion of lymphocytes, areas of necrosis with some regeneration, fibrosis

Histological findings in polymyositis:
Muscle biopsy from a patient with polymyositis showing endomysial inflammatory cells (arrows) and variations in fiber size

Image: “Muscle biopsy” by Neurology, Saint Louis University, Saint Louis, MO, USA. License: CC BY 4.0

Electromyography findings in polymyositis: comparison chart showing the differences in EMG activity for different pathologies

Image by Lecturio.

Evaluation of systemic manifestations

Interstitial lung disease:
- Chest radiography
- Pulmonary function tests
Dysphagia:
- Barium swallow
- Esophageal manometry
Conduction abnormalities: ECG
Myocarditis or cardiomyopathy: echocardiography

Screening for malignancy

Patients diagnosed with PM should be evaluated for possible underlying malignancy.
Workup is based on age and sex of the patient.
Initial workup:
- Mammography
- Pap smear
- Colonoscopy
- CT of thorax, abdomen, and pelvis
Additional studies ordered based on risk factors, symptoms, or abnormal initial workup:
- Cancer antigen 125 (CA 125)
- Transvaginal ultrasound (for women at high risk of ovarian cancer)
- Upper endoscopy (for esophageal cancer)
- MRI
- PET

Management

A multidisciplinary approach including pharmacological and non-pharmacological therapies is used in the management of PM.

Rheumatology consultation
Medical therapy:
- Systemic glucocorticoids (1st line)
  - 50% of patients with PM will not respond to steroids alone.
  - Therapy is usually needed for 9–12 months.
  - Slowly tapered off
  - Levels of muscle enzymes are monitored to determine response to therapy.
- Immunosuppressive therapy:
  - Methotrexate, azathioprine
  - Used in conjunction with glucocorticoid therapy
- IV immunoglobulin (IVIG):
  - Used in patients with severe life-threatening weakness (e.g., severe dysphagia, respiratory insufficiency)
  - Provides more rapid onset of action than steroids
- For recurrent or refractory disease:
  - Rituximab
  - Mycophenolate mofetil
  - Tacrolimus
Physiotherapy to maintain and improve muscular function
Management of dysphagia:
- Speech therapy
- Elevate the head of the bed.
- Diet modifications
- Enteral feeding for patients with severe dysphagia
Prophylaxis (while on long-term corticosteroids):
- Osteoporosis:
  - Calcium and vitamin D supplementation
  - Bisphosphonates for high-risk patients and individuals with osteoporosis
- Pneumocystis jirovecii: trimethoprim-sulfamethoxazole
- Appropriate immunization

Complications and Prognosis

Complications

Malignancy:
- Usually detected within the 1st year of diagnosis
- Incidence lower than in dermatomyositis
- Observed in men > 60 years of age with severe systemic involvement
- Most common: non-Hodgkin’s lymphoma, and bladder, lung, breast, ovarian, stomach, pancreatic, prostate, and colorectal cancer
Respiratory complications:
- Interstitial lung disease → pulmonary hypertension and cor pulmonale
- Aspiration pneumonia due to dysphagia
Cardiovascular involvement (rare):
- Conduction abnormalities → arrhythmia
- Myocarditis or dilated cardiomyopathy → heart failure
- ↑ Risk of myocardial infarction and thromboembolism
Adverse effects of medical therapy:
- Corticosteroid therapy:
  - Osteoporosis and compression fractures
  - Insulin resistance → diabetes mellitus
  - Hypertension
  - Dyslipidemia
  - Weight gain
  - Growth delay in children
  - Steroid-induced myopathy
- Immunosuppression therapy:
  - Opportunistic infections
  - Upper respiratory tract infections and pneumonia
  - Skin infections
  - Bacteremia and sepsis

Prognosis

PM is a chronic illness.
Most patients are highly responsive to medical therapy.
30% of patients may have residual weakness.
Mortality:
- 5-year survival rate > 80%
- Often related to:
  - Malignancy
  - Pulmonary complications
  - Cardiac involvement
  - Aspiration

Differential Diagnosis

Dermatomyositis (DM): an autoimmune inflammatory myopathy resulting from immune-complex deposition in the muscle capillaries. Patients present with symptoms similar to those observed in PM, and also exhibit characteristic cutaneous manifestations (e.g., heliotrope rash, Gottron’s sign). Diagnosis is based on clinical presentation and antibody evaluation, and may be confirmed with biopsy. Management includes systemic glucocorticoids, immunosuppressants, and screening for malignancy.
Inclusion body myositis (IBM): an inflammatory myopathy characterized by slowly progressing muscle weakness. However, the weakness is asymmetrical and involves distal muscles, especially those of the hands. Physical examination reveals significant muscle atrophy. Diagnosis is confirmed based on biopsy, which shows inclusion bodies within the muscle tissue. Inclusion body myositis is refractory to steroids and must be excluded in refractory cases of PM.
Polymyalgia rheumatica: an inflammatory condition that affects adults > 55 years of age. Patients present with pain and stiffnesses of the proximal muscles. There is no muscle weakness or atrophy. Diagnosis is clinical, revealing findings of elevated inflammatory markers. Management is with corticosteroids. Patients should be evaluated for temporal arteritis.
Drug-induced myopathy: Certain drugs (e.g., statins) can cause myopathy and myotoxicity, which can result in muscle weakness and myalgias. The CK levels are also elevated. Patient history and a review of medications can lead to the diagnosis. Management includes withdrawal of the offending medication. Treatment with steroids may be necessary.
Hypothyroidism: a thyroid-hormone deficiency caused by thyroid, hypothalamic, or pituitary disorders. Proximal muscle weakness is a common presenting complaint. Patients usually exhibit multiple other systemic manifestations, including intolerance to cold conditions, neuropsychiatric changes, dry skin, constipation, and bradycardia. Thyroid function tests can aid in the diagnosis. Management is with thyroid hormone replacement.
Cushing’s syndrome: an endocrine disorder characterized by chronic exposure to exogenous or endogenous corticosteroids. Patients with Cushing’s syndrome may display proximal muscle weakness due to atrophy of the gluteal and upper-leg muscles. The characteristic truncal obesity, moon face, and easy bruising may also be present. Diagnosis is based on clinical history and cortisol studies. Management depends on the underlying cause.

References

Sarwar, A., Dydyk A.M., Jatwani S. Polymyositis. (2020). StatPearls Publishing. Retrieved January 19, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK563129/
Greenberg, S.A. (2020). Inflammatory myopathies. In L. Goldman MD & A.I. Schafer MD (Eds.), Goldman-Cecil Medicine (pp. 1745–1750.e2). Retrieved from https://www.clinicalkey.es/#!/content/3-s2.0-B9780323532662002538
Yancey, K.B., Lawley, T.J. (2018). Immunologically mediated skin diseases. In J.L. Jameson, A.S. Fauci, D.L. Kasper, S.L. Hauser, D.L. Longo & J. Loscalzo (Eds.), Harrison’s Principles of Internal Medicine, 20e. New York, NY: McGraw-Hill Education. Retrieved from accessmedicine.mhmedical.com/content.aspx?aid=1156513509
Gelber, A.C., Levine, S.M., & Darrah, E. (2019). In Hammer G.D., McPhee S.J. (Eds.), Inflammatory Rheumatic Diseases. New York, NY: McGraw-Hill Education. accessmedicine.mhmedical.com/content.aspx?aid=1156660913
Ernste, F.C., Reed, A.M. (2013). Idiopathic inflammatory myopathies: Current trends in pathogenesis, clinical features, and up-to-date treatment recommendations. Mayo Clinic Proceedings, 88(1), 83–105. doi: http://dx.doi.org/10.1016/j.mayocp.2012.10.017
Rahman, A., Giles, I. (2017). Rheumatic disease. In P. Kumar Professor & M. Clark Dr. (Eds.), Kumar and Clark’s Clinical Medicine (pp. 645–706). https://www.clinicalkey.es/#!/content/3-s2.0-B9780702066016000184
Dinulos, J. G. H. (2021). In Dinulos J. G. H., MD (Ed.), Connective tissue diseases. doi: http://dx.doi.org/10.1016/B978-0-323-61269-2.00017-4
Seetharaman, M. (2021). Polymyositis. In Diamond, H.S. (Ed.), Medscape. Retrieved January 21, 2021, from https://emedicine.medscape.com/article/335925-overview
Nevares, A.M. (2020). Autoimmune myositis. [Online] MSD Manual Professional Version. Retrieved January 21, 2021, from https://www.merckmanuals.com/professional/musculoskeletal-and-connective-tissue-disorders/autoimmune-rheumatic-disorders/autoimmune-myositis
Miller, M.L, and Amato, A.A. (2020). Overview of the approach to the idiopathic inflammatory myopathies. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 21, 2021, from https://www.uptodate.com/contents/overview-of-and-approach-to-the-idiopathic-inflammatory-myopathies
Miller, M.L. (2019). Initial treatment of dermatomyositis and polymyositis in adults. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 21, 2021, from https://www.uptodate.com/contents/initial-treatment-of-dermatomyositis-and-polymyositis-in-adults
Miller, M.L., Vleugels, R.A., and Amato, A.A. (2020). Clinical manifestations of dermatomyositis and polymyositis in adults. In Ramirez Curtis, M., and Ofori, A.O. (Eds.), UpToDate. Retrieved January 21, 2021, from https://www.uptodate.com/contents/clinical-manifestations-of-dermatomyositis-and-polymyositis-in-adults
Miller, M.L. (2020). Diagnosis and differential diagnosis of dermatomyositis and polymyositis in adults. In Ramirez Curtis, M. (Ed.), UpToDate. Retrieved January 21, 2021, from https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-dermatomyositis-and-polymyositis-in-adults

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