Profound Weakness in a Young Woman

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A 33-year-old woman presents with arm and leg weakness of about 2 months’ duration. Her symptoms were initially subtle and relatively mild, but during the past 2 weeks they have progressively worsened. She is now unable to raise herself from a chair, can walk only with small shuffling steps, and cannot lift her hands above her head to brush her hair. In the past several days, she has had difficulty with swallowing solid foods and has had a few episodes of urge incontinence. Her daughter notes that in the past 2 weeks her mother has had increasing redness of the face.

HISTORY

The patient has no significant medical history and takes no medications. She denies alcohol use and has a trivial tobacco use history.

PHYSICAL EXAMINATION

Vital signs are normal. Cheeks and eyelids are erythematous. Pupils are equal, round, and reactive to light, and extraocular movements are intact. Visual acuity is grossly normal and symmetrical. No significant lymphadenopathy is detected. Lungs are clear, and heart rate and rhythm are regular with no murmurs. Bowel sounds are audible, and no abdominal masses are noted. Neurological examination reveals 5/5 grip and finger strength but profound 2/5 weakness of the proximal arms and the hip girdle muscles bilaterally.

LABORATORY EVALUATION

A complete blood cell count is normal. Albumin level is 3.98 g/dL; alanine aminotransferase (ALT) level, 31 U/L; and aspartate aminotransferase (AST) level, 578 U/L. Lactate dehydrogenase (LDH) level is 1831 U/L, and erythrocyte sedimentation rate is 65 mm/h. An MRI study of the brain is normal.

Which of the following is the most likely diagnosis?A. Multiple sclerosis.
B. Dermatomyositis.
C. Guillain-Barr syndrome.
D. Myasthenia gravis.

(answer on next page)

CORRECT ANSWER: B

This patient has dermatomyositis. She has the symmetrical proximal muscle weakness and facial rash that are consistent with this diagnosis, and results of a muscle biopsy are confirmatory.

Clinical features of dermatomyositis. This inflammatory myopathy presents with painless proximal muscle weakness preceded by a facial rash. The appearance of the rash can vary, but it generally manifests as a heliotropic rash on the upper eyelids and face, a papulosquamous eruption on the dorsa of the fingers (the Gottron sign), or an erythematous rash on the anterior chest and upper torso (often referred to as the “shawl” rash). This rash is the only clinical finding that differentiates dermatomyositis from polymyositis. Both diseases can present with varying degrees of proximal muscle weakness and usually develop over weeks to months.

Typical complaints associated with proximal muscle weakness are difficulty in raising oneself from a chair, climbing stairs, or lifting the arms above the head. Complaints consistent with distal muscle and fine motor weakness-such as difficulty in buttoning a sweater or gripping an object-are not typical of this diagnosis. However, in advanced cases of inflammatory myopathies, the oropharyngeal striated muscles and the thoracic muscles may be involved, resulting in difficulty with swallowing and respiratory muscle weakness.

Distinguishing inflammatory myopathies from other causes of muscle weakness. Facial, lid, and extraocular muscle weakness are not typical of dermatomyositis or polymyositis. These complaints should instead raise suspicion of myasthenia gravis (choice D).

Multiple sclerosis (choice A) is a relatively common cause of weakness and neurological symptoms in women this age. However, the symmetrical nature of this patient’s symptoms and the presence of a rash are not typical of multiple sclerosis. Also, the normal MRI scan of the brain is essentially exclusionary.

Guillain-Barr syndrome (choice C) causes weakness of the extremities, but its characteristic onset is distal (eg, in the fingers, toes, and feet) rather than proximal, as was the case in this patient. Moreover, biochemical evidence of muscle inflammation or necrosis is not seen in either Guillain-Barr syndrome or multiple sclerosis.

Laboratory findings. Although laboratory results in dermatomyositis and polymyositis are not always diagnostic, significant enzyme elevations are strongly suggestive in the presence of a consistent history and physical findings. The creatine kinase (CK) level is often elevated 50 to 100 times the normal value. ALT, AST, LDH, and aldolase levels are also typically elevated. A positive antinuclear antibody (ANA) titer is seen in about 70% of patients with dermatomyositis or polymyositis, and anti-Jo-1 antibodies are detected in about 25%.¹ MRI of affected tissue shows abnormal signal in the striated muscle and may help identify a good location for biopsy. A muscle biopsy is often performed to confirm the diagnosis.

Pathogenesis. Dermatomyositis is an autoimmune microangiopathy that affects the skin and muscles. The mechanism of disease involves activation and deposition of complement, which results in lysis of endomysial capillaries, capillary necrosis, perivascular inflammation, muscle ischemia, and the destruction of muscle fibers. Research into the immunopathological process involved in the disease is ongoing, but the up-regulation of various cytokines, chemokines, and intracellular adhesion molecules are thought to play an integral role in both dermatomyositis and polymyositis. Thus, these diseases respond to immunotherapeutic and immunomodulatory agents.

Treatment. Corticosteroids are the mainstay of treatment for the inflammatory myopathies. Because treatment is empirical, dosing varies. Generally, a high dose of corticosteroid (such as 1 g/d of intravenous methylprednisolone or 100 mg/d of oral prednisone) is given for 3 to 5 days; the dosage is then tapered over 3 to 4 weeks. The goals of therapy are to increase muscle strength and treat extramuscular manifestations. If these goals are not met, some patients may require other immunosuppressive agents, such as azathioprine or methotrexate.

Most patients respond to corticosteroid therapy to some degree, especially if it is initiated early in the course of the disease. The prognosis is best when corticosteroid treatment is started as soon as dermatomyositis is diagnosed. However, at least one-third of patients may still have some residual disability.

Associated disorders. Dermatomyositis and polymyositis can have extramuscular manifestations-probably because of their autoimmune nature. Pulmonary manifestations include interstitial lung disease. Aside from the initial rash, dermatological manifestations include subcutaneous calcifications that can cause ulceration and infection. The frequency of cancer is also increased in patients with dermatomyositis. In addition, dermatomyositis can be part of an overlap syndrome with other autoimmune diseases, especially systemic sclerosis and mixed connective-tissue disorder. Generally, an association with cancer or pulmonary fibrosis results in a poorer prognosis.

Outcome of this case. Further testing revealed a CK level of 41,756 U/L and an aldolase level of 132.4 U/L. MRI of the patient’s shoulder girdle showed patchy, diffuse edema in the major muscles consistent with myositis. A muscle biopsy of the left thigh was performed, and pathology examination of the specimen revealed a necrotizing, inflammatory myopathy. Immediately after the biopsy, pulse corticosteroid treatment was initiated (intravenous methylprednisolone, 1 g/d for 3 days), followed by oral prednisone. In the first week of treatment, some improvement was noted. The patient was then transferred for acute rehabilitation of her proximal muscle weakness.

References:

REFERENCE:1. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 2003;362:971-982.

FOR MORE INFORMATION:

•Bohan A, Peter JB. Polymyositis and dermatomyositis (first of two parts). N Engl J Med. 1975;292:344-347.

•Bohan A, Peter JB. Polymyositis and dermatomyositis (second of two parts). N Engl J Med. 1975;292:403-407.

•Polisson RP, Crocker JT, Mueller PR, et al. Case records of the Massachusetts General Hospital. Case 29-2005.
A 68-year-old man with periorbital swelling, rash, and weakness. N Engl J Med. 2005;353:1275-1284.

•Saguil A. Evaluation of the patient with muscle weakness. Am Fam Physician. 2005;71:1327-1336.