Hospital Medicine

Myositis

Myositis

I. Problem/Condition.

Myositis is characterized by loss of the integrity of skeletal muscles for various reasons. This destruction leads to patients complaining of weakness, fatigue, or pain. There is usually a release of muscle specific enzymes into the bloodstream.

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

Myositis can be divided into inherited and acquired disorders. The inherited disorders are rare and should be considered only if the inpatient workup does not reveal an obvious cause or if the pattern of illness is highly suggestive of an inherited disorder.

Secondary myopathies may be due to causes (acronym "TIE TIP") as shown below:

  • Trauma.

  • Inflammatory/autoimmune conditions (dermatomyositis [DM], polymyositis [PM], and inclusion body myositis).

  • Endocrine/electrolyte derangements (hypo/hyperthyroidism, hypo/hyperparathyroidism, adrenal and pituitary disorders, hypokalemia, hypophosphatemia).

  • Toxins/drugs (statins, fibrates, antipsychotic drugs causing neuroleptic malignant syndrome, verapamil, amiodarone, D-penicillamine, colchicine, α-interferon, cyclosporine, tacrolimus, steroids, HIV-protease inhibitors, zidovudine, cocaine, heroin, amphetamines, PCP, alcohol).

  • Infection with viruses (Influenza A and B viruses, Enteroviruses, HIV, HTLV-1, Hepatitis B and C viruses), fungi (Candida species, Cryptococcus neoformans, Histoplasma capsulatum,Coccidioides species, Aspergillius species, Fusarium species), parasites (Trichinella species, Taenia solium, Toxoplasma gondii, Trypanosoma cruzi, Sarcocystis species, Microsporidiaspecies, Toxocara canis), and bacteria (S. aureus, group A and B streptococcus, Clostridium species, Aeromonas).

  • Paraneoplastic processes which may induce a necrotizing myopathy (in addition to the association of malignancy with dermatomyosoitis and polymyositis).

The inherited disorders include conditions such as:

  • Dysferlinopathies (e.g., Limb-girdle muscular dystrophy type 2b and Miyoshi myopathy).

  • Dystrophinopathies(e.g., late onset Becker muscular dystrophy, fascioscapulohumeral dystrophy, and Duchenne muscular dystrophy, though the latter would not be a diagnostic dilemma as it would almost always present in early childhood).

  • Enzyme deficiencies leading to metabolic derangements (McArdle disease, phosphofructokinase and acid maltase deficiency, mitochondrial myopathy).

B. Describe a diagnostic approach/method to the patient with this problem.

Myositis should first be distinguished from simple myalgia (muscle pain) which can accompany a variety of illnesses. This is usually accomplished by the presence of an elevated creatinine kinase (CK) level.

The presence of myoglobinuria and/or a reduced GFR should be elicited so that prompt management with isotonic intravenous fluids can be started.

A careful assessment for the presence of a rapidly progressive infection should be completed as this may be life or limb threatening.

If the tetrad of fever, altered mental status, extrapyramidal syndrome, and autonomic instability are present in the setting of antipsychotic use, prompt transfer to the ICU should be sought and treatment for neuroleptic malignant syndrome begun.

Finally, a more detailed history and physical examination should be performed with the addition of targeted diagnostic imaging and laboratory investigation.

1. Historical information important in the diagnosis of this problem.

  • Obtain medication history focusing on common culprits: statins, fibrates, antipsychotics.

  • Obtain social history focusing on recreational drug use, specifically cocaine, alcohol, and amphetamines.

  • Obtain past medical/family/surgical history to identify patients with thyroid and parathyroid disease, malignancy, or inherited diseases.

  • Is there local or diffuse involvement?

  • Is there muscle pain?

  • Is there any history of recent overuse injury or trauma?

  • Any changes in the color of the urine?

  • Is there muscle weakness?

  • What is the pattern of weakness (e.g., proximal, distal, small muscle groups, large muscle groups)?

  • Are the cranial nerves involved? (e.g., double vision, difficulty swallowing, recurrent aspiration pneumonia, etc.)

  • Any symptoms suggestive of infection in the affected muscle (e.g., rubor, tumor, calor, dolor)?

  • Any symptoms suggestive of upper respiratory tract infection (e.g., cough, sputum production, dyspnea, etc.)?

  • Any complaints of skin rashes?

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

Feel for crepitus in involved muscle to determine if gas gangrene is present.

The following maneuvers may help determine the pattern and location of muscle involvement:

  • Facial - Inability to smile or whistle.

  • Ocular - Ptosis or disconjugate eye movements.

  • Bulbar - Nasal speech.

  • Neck - Poor head control.

  • Trunk - Difficulty sitting up, protuberant abdomen, scoliosis, lumbar lordosis.

  • Shoulder girdle - Scapular winging.

  • Forearm/hand - Inability to make a fist, finger or wrist drop.

  • Pelvic girdle - Gower's sign (patient that has to use his hands and arms to "walk" up his own body from a squatting position due to lack of hip/thigh muscle strength), waddling gait.

  • Leg/foot - Foot drop, inability to walk on heels or toes.

  • Respiratory - Use of accessory muscles to breathe.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

  • CK level.

  • Potassium, calcium, phosphate, TSH, HIV, PTH, urinalysis.

  • Nerve conduction studies (NCS) and electromyography (EMG) to confirm that muscle is site of disease.

  • Magnetic resonance imaging (MRI) may have limited role in deciding which muscle to biopsy to diagnose polymyositis or to determine extent of underlying infection.

  • Muscle biopsy (avoid severely weak muscles or muscles that were recently punctured during EMG).

  • Molecular genetic studies performed on peripheral blood samples may obviate the need for biopsy when a hereditary myopathy is suspected.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Electromyography (EMG) helps determine the site of disease within the peripheral nervous system. Peripheral causes of weakness can be divided into neuropathic processes, myopathic processes, and diseases affecting the neuromuscular junction.

In neuropathic conditions, the motor axon is injured, leaving muscle fibers of entire motor units without innervation. The muscle fibers become hyperexcitable, leading to spontaneous depolarization and contraction of a single muscle fiber, which is detected on EMG as fibrillations or positive sharp wave potentials.

In myopathic conditions, muscle fibers within the motor units degenerate, leaving a smaller amplitude and shorter duration potential. In the inflammatory myopathies (e.g., PM and DM), EMG findings often mimic those seen in neuropathic conditions including fibrillations, positive sharp wave potentials, and increased insertional irritability.

Muscle biopsy may be required to make a definitive diagnosis. Typical myopathic abnormalities include central nuclei, both small and large hypertrophic round fibers, split fibers, and degenerating and regenerating fibers. Inflammatory myopathies are characterized by the presence of mononuclear inflammatory cells in the endomysial and perimysial connective tissue between fibers, and occasionally around blood vessels. In addition, in dermatomyositis, atrophy of fibers located on the periphery of a muscle fascicle, perifascicular atrophy, is a common finding. Chronic myopathies frequently show evidence of increased connective tissue and fat.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

LDH, AST, ALT, CK isoenzymes (such as CK-MM, CK-MB), myositis associated antibodies (e.g., anti-Jo1), ANA, RF.

III. Management while the Diagnostic Process is Proceeding.

Although their efficacy has never been confirmed in a randomized controlled trial (RCT), corticosteroids are the traditional first-line treatment for dermatomyositis and polymyositis, once other disorders that can mimic immune-mediated myopathy have been excluded. It is usual to start treatment with oral prednisolone at a dose of ~1 mg/kg/day and it is preferable to avoid using higher doses because of the greater risk of steroid side effects.

In patients with more severe weakness, and particularly if there is weakness of the bulbar or respiratory muscles, a quicker response may be achieved by starting treatment with intravenous methylprednisolone (3-5 pulses of 0.5-1.0 g) and then continuing with oral prednisolone.

Early use of steroid sparing agents such as methotrexate, mycophenolate, and azathioprine are recommended for ongoing treatment in consultation with a rheumatologist. IVIG has been used in steroid-resistant cases. Biologic agents such as rituximab have shown promise in treatment resistant dermatomyositis.

A. Management of Clinical Problem Myositis

Discontinue all drugs that could potentially contribute to development of myositis.

For rhabdomyolysis, see section on rhabdomyolysis.

For neuroleptic malignant syndrome, see section on neuroleptic malignant syndrome.

For necrotizing myositis or gas gangrene, obtain emergent surgical consultation for debridement and initiate antibiotics:

  • Penicillin G 4 million units every 4 hours

  • Clindamycin 900 mg every 8 hours

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.

Immunosuppression.

IV. What's the evidence?

Jackson, CE. "A Clinical Approach to Muscle Diseases". Semin Neurol. vol. 28. 2008. pp. 228-240.

Sewry, CA. "Congential Myopathies". Curr Opin Neurol. vol. 21. 2008. pp. 21-569.

Rider, LG, Miller, FW. "Deciphering the clinical presentations, pathogenesis, and treatment of the idiopathic inflammatory myopathies". JAMA. vol. 305. 2011. pp. 183-190.

Crum, NF. "Bacterial, Fungal Parasitic, and Viral Myositis". Clinical Microbiology Reviews. vol. 21. 2008. pp. 473-494.

Cox, S. "Idiopathic inflammatory myopathies: diagnostic criteria, classification and epidemiological features". International Journal of Rheumatic Diseases. vol. 13. 2010. pp. 13-117.

Nirmalananthan, N, Holton, JL, Hanna, MG. "Is it really myositis? A consideration of the differential diagnosis". Opinion in Rheumatology. vol. 16. 2004. pp. 684-691.

Smith, EC, Gharbawy, AE, Ko, DD. "Metabolic Myopathies: Clinical Features and Diagnostic Approach". Dis Clin N Am. vol. 37. 2011. pp. 201-217.

Dalakas, MC. "Toxic and drug-induced myopathies". J Neurol Neurosurg Psychiatry. vol. 80. 2009. pp. 832-838.

Baer, AN. "Paraneoplastic Muscle Disease". Rheum Dis Clin N Am. vol. 37. 2011. pp. 185-200.

Trollor, JN, Chen, Xiaohua, Perminder, S. "Neuroleptic Malignant Syndrome Associated with atypical antipsychotic drugs". CNS Drugs. vol. 23. 2009. pp. 477-492.

Needham, M, Mastaglia, FL. "Immunotherapies for Immune-Mediated Myopathies: A Current Perspective". Neurotherapeutics. 2015. pp. 1-15.

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