Myalgias and myositis: Pathology review

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A 41-year-old woman is evaluated by the outpatient physician for 5-months of generalized fatigue and diffuse soft-tissue pain. The pain is present in the upper extremities, lower extremities, and back. She feels tired every morning despite getting adequate sleep in the evening. Past medical history is notable for hypertension that is currently managed with propranolol. Temperature is 37.2°C (98.9°F), blood pressure is 136/88 mmHg, pulse is 61/min, and respiratory rate is 15/min. Physical examination reveals 5/5 strength and full range-of-motion in the upper and lower extremities. Soft-tissue tenderness is elicited at multiple locations across the patient’s body. Laboratory results are as follows:  

 
Laboratory value  Result
 Hemoglobin  14.8 g/dL 
 Leukocyte  7,800/mm3 
 Erythrocyte sedimentation rate (ESR)   7 mm/h 
 Serum creatinine kinase  27 U/L 
 Antinuclear antibodies  Negative 

Which of the following additional findings would most likely be found in this patient?

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On your rounds, you see two individuals. First is Yu Yan, a 58-year-old female who presents with a 2-week history of fatigue, weight loss, fevers, and bilateral pain with stiffness in the shoulder and hip girdles. These symptoms are worse at night and last for more than an hour. She also mentions that she finds it hard to get out of bed in the morning due to stiffness. On examination, her wrists and finger joints are painful and swollen, but there’s no muscle weakness. Then you see Elizabeth, a 38-year-old female who has a 4-year history of body pain. The pain was initially limited to her neck, but it has gradually spread and she now complains of constant pain all over. She does not sleep well and is chronically fatigued. Examination revealed many tender points throughout her body but no sign of joint swelling or muscle weakness. Blood tests were performed in both. In Yu Yan’s case, there was an increase in inflammatory markers, but creatine kinase levels were normal. In Elizabeth’s, blood tests were completely normal.

Both people have myalgias, or muscle pain. There are many causes but let’s start with myopathies, which are neuromuscular disorders in which the primary symptom is muscle weakness due to muscle cell dysfunction. There are two main inflammatory myopathies, polymyositis and dermatomyositis.

First, polymyositis is an autoimmune disease where there’s inflammatory infiltration in striated muscles that cause muscle damage. Now, the cause is still unknown, but polymyositis is often associated with other autoimmune diseases, including Sjogren syndrome, rheumatoid arthritis, scleroderma, and mixed connective tissue disease. It is thought that there’s an overexpression MHC class I molecules and muscular autoantigens, which end up triggering a primarily cell-mediated immune response that inappropriately activates CD4+ and CD8+ T-cells. This is probably due to molecular mimicry, which is when an immune cell mistakes a protein in the body as being foreign due to their similar structure. Sometimes, humoral immunity can also kick in when B-cells get activated by the autoantigens and make antibodies against them. These include histidyl-tRNA synthetases, also called Jo-1; a helicase protein known as Mi-2; and components of the signal-recognition particle, or SRP for short, which helps with protein trafficking within the cell. The bottom line is that these two immune reactions result in inflammation in and around the muscles that are being attacked, attacks which occur repeatedly over time, and can involve different muscle groups.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Idiopathic Inflammatory Myopathies: A Review of the Classification and Impact of Pathogenesis" Int J Mol Sci (2017)
  4. "Evaluation and management of polymyositis" Indian Journal of Dermatology (2012)
  5. "Clinical presentation and evaluation of dermatomyositis" Indian Journal of Dermatology (2012)
  6. "Fibromyalgia syndrome: etiology, pathogenesis, diagnosis, and treatment" Pain Res Treat (2012)
  7. "Inflammatory Muscle Diseases" New England Journal of Medicine (2015)
  8. "Polymyalgia rheumatica" BMJ (2013)
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