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Inflammatory Myopathies

Contributor: Soumya Chatterjee, MD, MS, FRCP

CASE 1

A 68 year old female presents with a several month history of progressive weakness and fatigue.  Previously very active, she now notes difficulty arising from a chair or the toilet, lifting cooking pots off the stove and reaching for items above her head. Her husband has to assist her with dressing. She has difficulty swallowing and chokes easily if she is not careful.

On examination, her vital signs are normal. She has to push herself out of the chair using her hands and requires assistance stepping up on the exam table. New erythema over the face, neck, upper chest and upper back is noted.  Her cardiac, lung and abdominal exams are normal. Strength in her distal extremities is intact. On proximal muscle testing, while she is able to raise her thigh and arms against gravity, she cannot hold them there against even light resistance. She also has difficulty sitting up from a lying position and has to turn to the side to do so.  Reflexes and sensation are intact.

What features of the patient's history and physical examination suggest an inflammatory muscle disease? What work-up would be indicated at this point? 

Progressive and painless weakness of proximal muscle groups suggests inflammatory myopathy.  The work-up should include the following laboratory tests, which are remarkable for an elevated creatine kinase of 3000 U/L (reference range: 30 – 220 U/L); AST is 180 U/L(reference range: 7 - 40 U/L) and ALT is 150 U/L (reference range: 0 – 45 U/L); Anti-nuclear antibody (ANA) and anti-Jo-1 antibody are negative.  There is increased water content in the bilateral thigh muscles as demonstrated in this STIR MRI picture. Electromyogram is consistent with an inflammatory myopathy while nerve conduction velocity testing is normal.

How do you explain the abnormalities above? 

In this case elevations in AST and ALT are likely secondary to muscle damage and do not necessarily reflect liver damage. The abnormality of the thigh muscles on MRI suggests muscle edema, as seen in muscle inflammation, but it is non-specific. This finding helps to confirm there is a muscle abnormality, and may distinguish between focal involvement, such as might be seen with injury or strain, versus diffuse involvement such as with a systemic process like myositis. Even in systemic inflammatory muscle disease, there is a variable degree of involvement within muscle groups so that a blind biopsy may yield a falsely normal report; areas of abnormal MRI signal thus help direct the site for biopsy to give the best yield. MRI changes may also serve as a possible imaging modality for following treatment response.

What percent of myositis cases have a negative ANA?  What percent are anti-Jo-1 (anti-histidyl tRNA synthetase) positive?

It is generally recognized that approximately 90% of all inflammatory myopathy patients will be positive for either a nuclear or a cytoplasmic antibody.  The presence of a positive ANA is therefore much lower once those with cytoplasmic antibodies are excluded.  Therefore, greater than 20% of myositis patients have a negative ANA. The rate of positive anti-Jo-1 antibodies is approximately 20% of all those with an inflammatory myopathy.

What other work-up should be pursued at this point?

  • The classic constellation of clinical findings including the rash and muscle weakness, EMG results and MRI findings makes a diagnosis of dermatomyositis. Opting to pursue incisional muscle biopsy would not be unreasonable if there is any question regarding diagnosis. A diagnosis of new onset myositis in an older adult patient should mandate an evaluation for an underlying malignancy, since myositis, particularly dermatomyositis can present as a paraneoplastic process. The extent of the malignancy screen is debated but should at a minimum include all age-appropriate cancer screening. If the suspicion is strong for the presence of an underlying malignancy, particularly if the patient fails to respond to therapy as expected, a more aggressive evaluation, including CT scan of the chest, abdomen and pelvis, is indicated.
  • In this case, because of the known association of malignancy with the inflammatory myopathies, a cancer work-up is initiated and a pelvic mass is found on a CT scan of the patient's abdomen.  Pathology of the resected mass demonstrates a poorly differentiated tumor, most likely of ovarian origin. At the time of the mass resection, an incisional biopsy of the quadriceps muscle is also performed demonstrating an acute inflammatory cell infiltrate consistent with dermatomyositis. High dose oral prednisone at 1 mg/kg/day are begun for the myositis and she is referred to oncology for treatment of her malignancy.

CASE 2

A 52-year old previously healthy male is admitted to the hospital for a one month history of fever and progressive dyspnea. He has failed two courses of outpatient oral antibiotics for a presumed community-acquired pneumonia. Review of systems is positive for new polyarticular joint pain and muscle aches.

On examination he is febrile to 102º F. He appears ill and uncomfortable. His respiratory rate is 30 and the use of accessory muscles of respiration with speech is noted. Pulse oximetry on room air is 88% and he is placed on supplemental oxygen. On lung exam, fine diffuse bilateral crackles are heard loudest in the bases but extending up to the level of the scapular tip. Cardiac and abdominal examinations are normal.

Bilateral interstitial infiltrates are seen on chest X-ray. CT scan of the chest demonstrates ground glass opacities and diffuse interstitial changes. Laboratory studies are notable for a mild anemia consistent with chronic disease. WBC count is 11,000/cu mm with a normal differential. AST and ALT are elevated at twice the upper limits of normal. CT and ultrasound of the liver are normal. Viral hepatitis and HIV studies are negative. Cultures of blood and sputum are negative, including cultures obtained by bronchoscopy. ANA, rheumatoid factor and anti-CCP antibodies are negative. 

He is initially treated with broad-spectrum IV antibiotics with no improvement. He has continued fever and progressive worsening of his respiratory status. Open-lung biopsy is obtained. Pathology demonstrates non-specific interstitial pneumonitis with no organisms identified.

Because of worsening joint complaints, rheumatology is consulted post-operatively. 

His physical examination is notable for mild synovitis in the MCP and wrist joints, and knees. On skin examination he has roughening along the edges of his fingers consistent with mechanic's hands. He denies Raynaud symptoms but dilated capillaries are found on nailfold capillaroscopy. On muscle strength testing there is subtle weakness proximally. He is able to resist against pressure, but only with difficulty and is not able to stand-up from a squatting position. The strength in distal muscle groups and reflexes are intact.  CK obtained at that time is elevated at 900 U/L (reference range: 30 – 220 U/L).

What disorder can tie the above findings together? 

The constellation of muscle abnormalities (proximal weakness with an elevated CK, AST and ALT), fever, mechanic's hands, inflammatory arthritis, and interstitial lung disease is characteristic of the well-classified anti-synthetase syndrome, a subset of the inflammatory myopathies.

What further work-up is indicated, and which antibody is classically seen?

  • Subsequent EMG and STIR MRI of the thighs are consistent with an inflammatory muscle process. Anti-Jo-1 (anti-histidyl tRNA synthetase antibody) is positive. An incisional muscle biopsy further confirms the diagnosis of dermatomyositis. High dose steroids are instituted, initially with IV pulse due to the progressive lung function deterioration, followed by high-dose oral daily therapy.
  • Because the constellation of clinical findings is so characteristic for an inflammatory myopathy it is debatable whether a muscle biopsy would actually be necessary. Even with active disease, a muscle biopsy may not demonstrate the inflammation since involvement is often patchy within the muscle. Since the antigen for Jo-1 is located in the cell cytoplasm rather than the nucleus, it does not produce nuclear immunofluorescence on ANA testing, and the ANA is not required for diagnosis.

Patient Care

  1. Identify the characteristic clinical manifestations of the muscle disease of both dermatomyositis and polymyositis to be found on a detailed history and physical examination and utilize appropriate evaluation strategies, including laboratory, radiographic, neuromuscular studies, and pathology for diagnosis and management of both the muscle disease and visceral involvement.
  2. Create a differential diagnosis of an elevated creatine kinase, and be able to employ the appropriate studies to differentiate the inflammatory myopathies from other causes.
  3. Recognize the appearance of the rashes and skin manifestations characteristic of dermatomyositis (including heliotrope rash, shawl and V-sign, Gottron's papules, and mechanic's hands).
  4. Identify and recognize the examination findings of nailfold capillary abnormalities.
  5. Identify and recognizecalcinosisand its association with inflammatory muscle disease.
  6. Differentiate inclusion body myositis from the other inflammatory myopathies and understand how the clinical presentation and treatment differ.
  7. Recognize when therapy is needed and be able to initiate appropriate treatment.
  8. Recognize and institute referral for subspecialty care when further diagnostic or therapeutic intervention is indicated.
  9. Explain the risks and benefits of medications commonly used for treatment including corticosteroids and the potential role for other immunosuppressive therapy.
  10. Identify interstitial lung disease as a common manifestation of myositis, including CT findings and mechanic's hands.
  11. Recognize the association of an underlying malignancy and be able to institute appropriate malignancy screening.
  12. Recognize the association of myositis overlap syndromes,including other systemic connective tissue disorders.

Medical Knowledge

  1. Identify the clinical features regarding muscle involvement in the inflammatory myopathies. 
  2. Describe and recognize the common rashes associated with dermatomyositis: heliotrope, Gottron's papules, V-sign/shawl sign and mechanic's hands.
  3. Describe and recognize the systemic features that may be present in patients with an inflammatory myopathy with an emphasis on lung involvement.
  4. Identify the most common autoantibodies associated with myositis and their clinical significance, particularly that of the anti-Jo-1 (anti-histidyl tRNA synthetase) antibody and the anti-synthetase syndrome.
  5. Recognize the association of myositis with malignancy.
  6. Describe the differences between polymyositis and dermatomyositis.
  7. Describe the histological features which distinguish inclusion body myositis from polymyositis,dermatomyositis and steroid myopathy
  8. Recognize the association of myositis and the human immunodeficiency virus.
  9. Generate a differential diagnosis for the presentation of muscle weakness and an elevated creatine kinase.
  10. Recognize the diagnostic modalities available (including EMG,MRI and muscle biopsy) which can be utilized as part of the evaluation of an elevated creatine kinase and/or muscle weakness.
  11. Describe the relationship and potential overlap of myositis with other systemic connective tissue diseases.
  12. Distinguish steroid-induced myopathy from an inflammatory myopathy.
  13. Recognize the different drug-related myopathies (including but not limited to the myopathies that can be seen with HIV therapies, statins, and colchicine) and compare their clinical features with those of the autoimmune, inflammatory myopathies.
  14. Recognize the usefulness of corticosteroids in the treatment of the inflammatory myopathies.
  15. Relate at least three immunosuppressive therapies(other than corticosteroids) that are used in the treatment of the inflammatory myopathies, either as steroid-sparing agents or for recalcitrant disease, and identify their potential toxicities.

Interpersonal and Communication Skills

  1. Explain to the patient and family the need for close monitoring of the patient and details of follow up.
  2. Discuss the potential complications and course of the disease, in a way that incorporates patients' perspectives.
  3. Explain the importance of age appropriate cancer screening in inflammatory myopathies.
  4. Discuss activity restrictions and the role of physical therapy in myositis treatment.
  5. Explain the benefit and potential toxicity of glucocorticoid therapy.
  6. Discuss the options for treatment with immunosuppressive agents and corticosteroids along with the potential benefit, toxicity and monitoring requirements.
  7. Explain the rationale for a malignancy evaluation.
  8. Explain the rationale for pulmonary monitoring.
  9. Summarize the information to be provided to a specialist to whom one might refer a patient with suspected inflammatory muscle disease.

Professionalism

  1. Display integrity and honesty in discussing patient care issues and management.
  2. Insure patient privacy.
  3. Promote patient autonomy in clinical and therapeutic decisions.
  4. Acknowledge and include family and social support as designated by the patient.
  5. Provide adequate time and accessibility to address patient concerns.
  6. Communicate in a timely fashion with other members of the patient's health care team including the primary care physician.
  7. Serve as the patient's advocate.

Practice-Based Learning and Improvement

  1. Utilize web-based resources to supplement and update current knowledge base and to explore patient-specific problems.
  2. Incorporate evaluation and feedback into practice and management.
  3. Utilize errors and complications to improve understanding and future management.
  4. Set learning goals in diagnostic strategies and management.

Systems-Based Practice

  1. Identify barriers to accessing optimal medical care for each individual patient and utilize alternative resources when available to overcome these barriers.
  2. Engage and incorporate the input of all medical providers including other physicians, the nursing staff, and physical and occupational therapists as necessary.
  3. Serve as a source of learning and education for other members of the health care team for the patient.
  4. Utilize the existing health care system to support and establish patient care goals.
  5. Incorporate considerations of cost and risk-to-benefit ratios in clinical evaluations, monitoring and therapeutic decisions, for the individual patient.
  6. Recognize the impact of both the diagnostic and therapeutic interventions on the health care system, both locally and globally.

Key References

  1. Amato AA, Barohn RJ. Evaluation and treatment of inflammatory myopathies. J of Neurol Neurosurg & Psychiatry. 80(10):1060-1068, Oct 2009.
  2. Chatterjee S,Prayson R, Farver C. Anti-synthetase syndrome: Not just an inflammatory myopathy. Cleveland Clinic Journal of Medicine. 80(10):655-666, Oct 2013.
  3. Dalakas M.Toxic and drug-induced myopathies. J of Neurol Neurosurg & Psychiatry. 80(8):832-838, Aug 2009.
  4. Danko K, Ponyi A, Molnar P, Andras C, Constantin T.Paraneoplastic myopathy. Curr Opin Rheum. 21(6):594-598, Nov 2009.

Questions

Answer Key

Key References

Last updated February 2015.

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