AssessmentsMyalgias and myositis: Pathology review
USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
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:
|Erythrocyte sedimentation rate (ESR)||7 mm/h|
|Serum creatinine kinase||27 U/L|
Which of the following additional findings would most likely be found in this patient?
Content Reviewers:Yifan Xiao, MD
Contributors:Ursula Florjanczyk, MScBMC, Victoria Cumberbatch, Sam Gillespie, BSc, Daniel Afloarei, MD
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.
Symptoms of polymyositis include progressive and bilateral weakness and muscle wasting. Weakness usually develops slowly over weeks to months, and its intensity can vary from mild to near paralysis. Sometimes, the affected muscles can be tender or painful due to inflammation. Now, the disease mostly affects proximal, big muscle groups, like the shoulder or hips and it usually spares distal muscles like those in the hands and feet. As a result, individuals might have difficulties doing things like getting up, lifting their arms, and climbing stairs. In this case, you should know that Gowers sign might be present, which is when people use their arms to help them stand up from a squatting position or when getting up from a chair. Classically, this is a sign of Duchenne muscular dystrophy but it can also be seen in inflammatory myopathies including polymyositis and dermatomyositis. Neck flexors are also commonly affected, resulting in neck pain and weakness. When the muscles of the pharynx or esophagus are involved, it causes dysphagia or difficulty in swallowing. Sometimes, the diaphragm and intercostal muscles can be weakened, which causes difficulty breathing and this is made worse because inflammatory myositis is often accompanied by interstitial lung disease where the parenchyma of the lungs undergo fibrosis and scarring. Sometimes the cardiac muscles are also affected. Although this is usually asymptomatic, it can result in conduction disturbances, myocarditis, or congestive heart failure.
Diagnosis is based on identifying a variety of serum autoantibodies, such as anti-nuclear antibodies and myositis-specific antibodies, like anti-Jo-1, anti-Mi-2, and anti-SRP. Next, remember there’s elevated serum levels of muscle enzymes such as aldolase or creatine kinase, which are released when muscles get damaged. Additionally, electromyography can be used to detect regions of dead muscle cells that cause abnormal electrical signals conduction. Another high-yield diagnostic tool is muscle biopsy, and it can show inflammatory infiltrates, mainly composed of CD8+ T-cells, macrophages, and varying stages of necrosis. Other pathologic findings can include endomysial infiltration by mononuclear cells, endomysium being the thinner portion of the intramuscular connective tissue that surrounds every single