A 43-year-old man comes to the office with muscle weakness. His symptoms began 6 weeks ago and are worst in the hips and shoulders. The weakness has had a progressive course so that he is now having difficulty rising from chairs and combing his hair. The patient has had to reduce his regular exercise regimen due to weakness and has requested a modified work schedule for his job as a building maintenance manager. He has no history of spinal injury and no neck pain. Past medical history is insignificant, and the patient takes no medications. Muscle biopsy reveals major histocompatibility complex class I molecule overexpression on the sarcolemma with CD8⁺ lymphocyte infiltration. Which of the following is the most likely cause of this patient's condition?

Question

Quizplus · Accepted Answer

11ec160b_3b68_38ad_9249_4d4ab907d91f_MD0001_00 This patient, a middle-aged man with progressive, symmetric proximal muscle weakness, has typical symptoms of polymyositis. The weakness may be painless or associated with diffuse myalgias. Muscle enzyme levels (eg, creatine kinase) are invariably elevated, and autoantibodies (eg, antinuclear antibodies, anti-Jo-1 antibodies) are present in most cases. Polymyositis is similar to dermatomyositis, although it lacks the typical skin findings; both may occur independently or as a paraneoplastic manifestation of an underlying malignancy. Polymyositis is an inflammatory myopathy triggered by unknown, possibly viral, antigens. It likely represents a cell-mediated immune response against myocytes. Increased expression of major histocompatibility complex class I antigens on the sarcolemma has been demonstrated and likely leads to presentation of autoantigens to CD8⁺ cytotoxic cells that subsequently initiate myocyte destruction. Muscle biopsy in polymyositis reveals inflammation, patchy necrosis, and regeneration and fibrosis of muscle fibers. Infiltration of the endomysium by macrophages and CD8⁺ lymphocytes is typically seen. (Choice A) Joint involvement in systemic sclerosis may cause arthralgias and contractures, but muscle weakness is not seen. (Choices B and C) Myasthenia gravis is caused by anti-acetylcholine receptor autoantibodies and is characterized by episodic weakness that initially affects the ocular/bulbar musculature. The Eaton-Lambert myasthenic syndrome is a paraneoplastic condition causing fatigable weakness in the extremities; it is caused by autoantibodies to presynaptic calcium channels. Light microscopy of muscle biopsy specimens is normal in these conditions. (Choice D) Polyarteritis nodosa is an uncommon systemic vasculitis that presents with intermittent episodes of abdominal pain, peripheral neuropathy, renal insufficiency, and severe hypertension. Biopsy is characterized by transmural inflammation of the arterial wall with fibrinoid necrosis. (Choice E) Polymyalgia rheumatica (PMR) causes myalgias of the shoulder and pelvic girdle muscles, often with systemic symptoms (eg, fever, weight loss). Weakness is not typical, and PMR occurs almost exclusively in patients age >50. Educational objective: Polymyositis causes symmetric proximal muscle weakness. Muscle biopsy reveals inflammation, necrosis, and regeneration of muscle fibers. Over-expression of major histocompatibility complex class I proteins on the sarcolemma leads to infiltration with CD8⁺ T lymphocytes and myocyte damage. __________ References: Mechanisms of disease: signaling pathways and immunobiology of inflammatory myopathies. (http://www.ncbi.nlm.nih.gov/pubmed/16932688)

A 43-Year-Old Man Comes to the Office with Muscle Weakness