THE CASE
A 55-year-old woman developed subacute progression of myalgias and subjective weakness in her proximal extremities after starting a new exercise regimen. The patient had a history of unilateral renal agenesis, type 2 diabetes, and hyperlipidemia, for which she had taken atorvastatin 40 mg/d for several years before discontinuing it 2 years earlier for unknown reasons. She had been evaluated multiple times in the primary care clinic and emergency department over the previous month. Each time, her strength was minimally reduced in the upper extremities on examination, her renal function and electrolytes were normal, and her creatine kinase (CK) level was elevated (16,000-20,000 U/L; normal range, 26-192 U/L). She was managed conservatively with fluids and given return precautions each time.
After her myalgias and weakness increased in severity, she presented to the emergency department with a muscle strength score of 4/5 in both shoulders, triceps, hip flexors, hip extensors, abductors, and adductors. Her laboratory results were significant for the presence of blood without red blood cells on her urine dipstick test and a CK level of 25,070 U/L. She was admitted for further evaluation of progressive myopathy and given aggressive IV fluid hydration to prevent renal injury based on her history of unilateral renal agenesis.
Infectious disease testing, which included a respiratory virus panel, acute hepatitis panel, HIV screening, Lyme antibody testing, cytomegalovirus DNA detection by polymerase chain reaction, Epstein-Barr virus capsid immunoglobulin M, and anti-streptolysin O, were negative. Electrolytes, inflammatory markers, and kidney function were normal. However, high-sensitivity troponin-T levels were elevated, with a peak value of 216.3 ng/L (normal range, 0-19 ng/L). The patient denied having any chest pain, and her electrocardiogram and transthoracic echocardiogram were normal. By hospital Day 4, her myalgias and weakness had improved, CK had stabilized (19,000-21,000 U/L), cardiac enzymes had improved, and urinalysis had normalized. She was discharged with a referral to a rheumatologist.
However, 10 days later—before she could see a rheumatologist—she was readmitted to a community hospital for recurrence of severe myalgias, progressive weakness, positive blood on urine dipstick testing, and a rising CK level (to 24,580 U/L) found during a follow-up appointment with her primary care physician. At this point, Neurology and Rheumatology were consulted and myositis-specific and myositis-associated autoantibody tests were sent out. Magnetic resonance imaging (MRI) of her thighs was performed and showed diffusely increased T2 signal and short tau inversion recovery in multiple proximal muscles (FIGURE).
DIAGNOSIS
Given her symmetrical proximal muscle weakness (which was refractory to IV fluid resuscitation), MRI findings, and the exclusion of infection and metabolic derangements, the patient was given a working diagnosis of myositis and treated with 1-g IV methylprednisolone followed by a 4-month steroid taper, methotrexate 20 mg weekly, and physical therapy. This working diagnosis was later confirmed with the results of her autoantibody tests.
At her 1-month follow-up visit, the patient reported minimal improvement in her strength, new neck weakness, and dysphagia with solids. Testing revealed anti–3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody levels of more than 200 U/L (negative < 20 U/L; positive > 59 U/L), which pointed to a more refined diagnosis of anti-HMGCR immune-mediated necrotizing myositis.
DISCUSSION
Myositis should be in the differential diagnosis for patients with symmetrical proximal muscle weakness. Bohan and Peter devised a 5-part set of criteria to help diagnose myositis, shown in the TABLE.1,2 This simple framework broadens the differential and guides diagnostic testing. Our patient’s presentation was fairly typical for anti-HMGCR myositis, a subset of immune-mediated necrotizing myositis,3 with a pretest probability of 62% per the European League Against Rheumatism/American College of Rheumatology classification criteria.2 Probability of this diagnosis was further increased by the high-titer anti-HMGCR, so biopsy and electromyography (EMG), as noted by Bohan and Peter, were not pursued.
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