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.