Inflammatory muscle disease
This week on BrainWaves, I am joined by Dr. Megha Dhamne, previously a neuromuscular fellow at the Cleveland Clinic. She walks us through the case of a middle aged woman with progressive proximal muscle weakness and was thought to have an inflammatory myopathy. But which one?
The patient in question is a 49 year old right handed Caucasian female with a history of hypertension who was referred to the neuromuscular clinic for evaluation of progressive muscle weakness and myalgias over the past 5-6 months. She had a flu like illness preceding the muscle pain and cramps which were present in her arms and thighs. She also had shoulder pain. This was followed a few days later by difficulty climbing stairs, getting in and out of the car and had to pull herself up from a chair. She had difficulty combing her hair, reaching her back while showering and also could no longer lift her 2 and ½ year old granddaughter with her arms. She could still drive her car with good strength in her feet. She had no problems buttoning – unbuttoning her blouse, opening jars and did not drop objects from her hands. She thinks she has lost her muscle mass over the shoulders and her thighs.
For the sake of making it easier to digest, I’ve emphasized the features of her exam that are suggestive of a proximal pattern of muscle weakness with relative sparing of the distal muscles. It’s a non-focal pattern, non-lateralizing to one side or another which might have suggested a unilateral intracranial process, and there does not seem to be an obvious corticospinal pattern of weakness where the flexors of the arm are weaker than the extensors and the extensors of the legs are weaker than the flexors. Moving down the motor fiber pathway, now that we think it’s less likely to be in the brain or spine, could it be a radiculopathy as the nerves exit the spinal column? Probably not given the widespread distribution of the weakness. Could it be the nerves themselves? Sure, a symmetric progressive polyneuropathy, and something like CIDP or one of its variants, might be possible were the weakness is more distal than proximal. But her weakness is very very proximal. So already I am thinking about disorders which preferentially affect the shoulders and hip flexor muscle groups and the neuromuscular junction, conditions like myasthenia gravis, dermatomyositis, and polymyositis. If her symptoms had not come on so abruptly and progressed so rapidly, I might also be considering one of the heritable or congenital myopathy syndromes like one of the limb-girdle or other muscular dystrophies, proximal myotonic myopathy (aka, myotonic dystrophy type 2), and disorders of lipid metabolism. Alternatively systemic illnesses like uremia, hyper/and hypothyroidism, vitamin D deficiency, adrenal dysfunction, parathyroid disease, scleroderma, and some medications (statins, steroids, colchicine, and alcohol most notably) can also cause proximal weakness, and would be something worth considering. So these need to be ruled in or out.
But something in the history stood out. The antecedent illness. And a rash. When Dr. Dhamne got to the systemic
examination, she noted it was unremarkable except for a purplish colored rash over the knuckles bilaterally and over the extensor aspects of the elbows, knees, anterior aspect of the chest, neck and abdomen, lower back and medial and outer aspect of both thighs. This rash had persisted over the past several months, accompanying the weakness. And while the rash was described as pretty diffuse, some parts sounded consistent with the rash we see in dermatomyositis.
The next step would be to confirm the presence of a myositis. An inflammation of the muscle tissue, which results in breakdown and release of muscle enzymes. So Dr. Dhamne checked a creatine kinase and aldolase, but these were normal. The metabolic panel was also normal. TSH – 3.50, Free T4 – 1.1. Vitamin D3 – 25.7. ANA positive, titer 1:160. ANCA – negative. RF < 20. Anti ENA panel – negative.
I should mention that the CK is only elevated in 70% of cases of dermatomyositis. It’s more important here that the ANA was abnormal, suggesting an autoimmune etiology. So now we need to test for specific antibodies. And even these are not perfect tests, probably because we have not identified all the antibodies associated with inflammatory muscle diseases. Here is a brief list of some of the major antibodies to know as a neurologist:
To make matters interesting, our patient’s antibody panel was negative. So a muscle biopsy was performed, and the slides looked much like the featured image associated with this article. Notably, there was prominent perifascicular
atrophy and inflammatory infiltrate with CD4+ cells and macrophages. These findings are consistent with the diagnosis of dermatomyositis. But the case doesn’t end there. These patients, even when seronegative, should be screened for associated conditions like interstitial lung disease and an underlying malignancy. And current expert recommendations advise a minimum of 5 years of continued surveillance to identify an occult cancer. In the meantime, there are several treatment options–many of which are not unlike those we provide other patients with inflammatory diseases (corticosteroids, IV Ig, azathioprine, methotrexate, etc.). See below:
Our patient was treated with corticosteroids and IV Ig with subjective clinical improvement. But as newer antibodies are becoming identified, and the underlying pathogenesis of inflammatory muscle disease is increasingly understood, we plan to develop more targeted therapies in the coming years. So stay tuned for that.
BrainWaves’ podcasts and online content are for medical education purposes only and should not be used in routine clinic decision making. At no point in this episode are we recommending doctors to biopsy chunks of muscle just because you haven’t figured out why a patient is experiencing weakness.
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- Mammen A. Autoimmune muscle disease. Handbook of clinical neurology. 2016;133:467-84.
- Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, Evans SR and Felson DT. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet. 2001;357:96-100.
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- Gordon PA, Winer JB, Hoogendijk JE and Choy EH. Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis. The Cochrane database of systematic reviews. 2012:CD003643.