Myalgias and myositis: Pathology review

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Case Study0:00–1:13

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.

Pathology1:13–1:34

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.

Polymyositis1:34–6:29

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 muscle fiber; capillary obliteration; overexpression of MHC class I molecules on the muscle cell sarcolemma; and increased amounts of connective tissue.
Pulmonary function tests can be used when there’s suspicion of respiratory involvement, usually detecting a restrictive pattern if there’s interstitial lung disease.
Treatment of polymyositis typically focuses on suppressing the immune response, usually with corticosteroids. In addition, specialized exercise therapy can help maintain muscle function.Dermatomyositis is another autoimmune disease where the immune system attacks its own muscles, but this time it also affects the skin.

Dermatomyositis6:29–11:16

The exact trigger for dermatomyositis is unknown. However, there are a few suspected genetic and environmental factors associated with the disease, like infection with coxsackievirus or specific tumor antigens, such as those in ovarian, lung, or breast tumors.
In dermatomyositis, it is believed that autoantigens in endothelial cells lining the capillaries in muscle and skin cells, trigger a humoral-immune response.
The resulting autoantibodies attach to the endothelial cells lining the capillaries near the perimysium, and activate the complement cascade, which, in turn, leads to the formation of a membrane attack complex that damages the endothelial cells.
Now, antibodies also bind to small soluble autoantigens, like nuclear or cytoplasmic fragments resulting from cell destruction, and form antigen-antibody complexes.
Small antigen-antibody complexes are not very immunogenic, so they don’t get removed from the bloodstream very quickly. As a result, the complexes persist and they reach the basement membrane of various blood vessel walls, once again activating the complement and causing damage.
Cell-mediated immunity can also be involved, and it’s usually associated with activated CD4+ T-cells, which cause further damage while also infiltrating the surrounding muscle and skin tissue.
Ok, so the bottom line is that inflammation and cellular destruction result in the loss of blood vessels, which causes tissue ischemia and necrosis in the affected muscle and skin tissue.
Symptoms of dermatomyositis are similar to those in polymyositis except there’s also skin manifestations. When there’s muscle damage, there can be bilateral weakness, muscle atrophy, and muscle pain and tenderness that mostly affects proximal, big muscle groups, like the shoulder or hip.
In severe cases, the muscles of the pharynx or esophagus can be affected causing dysphagia and aspiration pneumonia. Now a high yield concept that you need to know for you exams is that unlike polymyositis, the skin is also involved.
One classic finding is a purplish rash on the upper eyelids, called a “heliotrope rash” which is named after a purple flower.
A similar rash can involve the shoulders, upper chest, and back, resembling a “shawl.” Another sign is a malar rash in the shape of a butterfly, on both cheekbones and the nasal bridge.
Another classic finding is Gottron's papules, which are red, often scaly, bumps overlying the knuckles of the fingers. These rashes can be photosensitive, meaning they worsen when exposed to sunlight, and are itchy and painful.
Individuals might also present with irregular, darkened, thickening of the fingers and these make the hands look like they’re covered in grease or oil, so it’s called “Mechanic’s hands.” One last thing to remember is that although dermatomyositis doesn’t cause cancer, it’s associated with an increased risk of of hidden malignancy, like ovarian, lung, and stomach cancer.
So remember to keep an eye out for people with dermatomyositis who also develop non-specific symptoms like fever, night sweats, and weight loss.
The diagnosis of dermatomyositis is similar to that of polymyositis, but it’s based on the combination of skin and muscle findings.
Typically there are non-specific autoantibodies like antinuclear antibodies, or ANA, and myopathy-specific antibodies like anti-Mi-2 and anti-Jo-1.
There can also be increased levels of muscle enzymes, like creatine kinase, and abnormal findings on an electromyograph.
A muscle biopsy might show signs of muscle atrophy and perimysium inflammation with CD4+ T cells. Treatment typically focuses on suppressing the immune response, usually with corticosteroids, such as prednisone.
Antimalarial medications such as hydroxychloroquine and chloroquine, are sometimes effective in the management of skin rashes, along with sun avoidance and wearing protective clothing.Let’s switch to polymyalgia rheumatica, an autoimmune rheumatic disease resulting in severe joint stiffness and pain.

Polymyalgia Rheumatica11:16–15:18

Now, the cause is not well understood, but it seems to be associated with both genetic and environmental factors. For example, those with a certain gene for MHC class II molecules, also called a human leukocyte antigen, or HLA–DR4, are more likely to develop the disease.
This is especially true after an infection with adenovirus or parvovirus B19, most likely due to molecular mimicry. Polymyalgia rheumatica is also strongly associated with giant-cell arteritis.
This is a condition where there’s granulomatous inflammation of the walls of the arteries, especially in the branches of the carotid like the superficial temporal artery, which is why the disease is also called temporal arteritis.
Additionally, it is thought that the resulting autoantigens trigger both a humoral and a cell-mediated immune response. The autoantibodies and the activated T-cells enter the circulation and end up reaching the large joints, where they ultimately lead to joint inflammation.Now, symptom-wise, the disease often affects women over 50 years of age.
Something high-yield to keep in mind is that although it’s called polymyalgia, the muscles themselves are not inflamed or weakened and actually appear normal on biopsy.
However, there might be muscle pain, mostly resulting from damage to the structures surrounding the joints, like the tendons and bursae, which affects nearby nerves in the muscle.
In this case, it is called referred pain. Typically, polymyalgia is characterized by pain and stiffness of the shoulder and hip, which start as one-sided and then progress to both sides within weeks.
Symptoms are more severe in the morning and at night, they last more than 45 minutes, and improve after activity. They can also make it hard to get out of bed or up from a chair as well as lifting the arms above shoulder height.
Sometimes, inflammatory cytokines can travel through the bloodstream and reach other organs and cause additional symptoms.
For example, interleukin-1 and interleukin-6 travel to reach the brain, where they act as pyrogens, inducing fever. Other symptoms can include fatigue, and loss of appetite which can lead to weight loss.
Also, those with associated temporal arteritis can present severe unilateral headache, jaw pain while chewing, vision problems, and even blindness on the affected side due to occlusion of the ophthalmic artery.
The diagnosis of polymyalgia rheumatica can be confirmed by increased inflammatory markers, like a high erythrocyte sedimentation rate, or ESR, and C-reactive protein, or CRP.
Since there is little damage to the muscles, muscle enzymes like creatine kinase, usually remain normal, which distinguishes polymyalgia rheumatica from other inflammatory muscle disorders, like polymyositis.
X-rays of the affected joints can show signs of non-erosive joint disease.Treatment focuses on suppressing the immune response, usually with low doses of corticosteroids like prednisone.
Specific exercises and a healthy diet can also help strengthen the muscles and bones, as well as improve flexibility of affected joints.

Fibromyalgia15:18–18:46

Giant-cell arteritis requires high-dose corticosteroids prior to temporal artery biopsy to prevent blindness.And the last disorder is fibromyalgia; a chronic condition that causes widespread muscle pain and tenderness in various parts of the body, alongside sleep disturbances, chronic fatigue, and mood disorders.
The condition is common in women 20 to 50 years old, and it tends to run in families, which suggest a genetic component, while environmental factors like psychological stress, depression, trauma, child abuse, and infection might also contribute to its development.
Actually, its pathophysiology isn’t well understood, but unlike the other diseases we covered, there doesn’t seem to be any damage to the muscles or joints.
The problem is due to how the brain receives pain signals. Generally speaking, the affected individuals seem to have low levels of serotonin, which is involved in inhibiting pain signals, and elevated levels of substance P, which is involved in propagating pain signals.
Together, these are thought to cause hypersensitivity to pain, which hints that fibromyalgia might be a condition that affects the central nervous symptom, causing what’s known as central sensitization syndrome.
The syndrome might also cause other types of sensitivities affecting everything from how individuals sleep, to how they feel, to how they think.You also need to keep in mind that the symptoms and diagnosis of fibromyalgia go hand in hand, as diagnosis is usually established on a clinical basis.
First, there’s widespread pain in at least four regions of the body. There are also tender points in the body.
These points are symmetrically distributed over the individual’s muscles, joints, and tendons, like the spine of the scapula or the lateral epicondyle of the femur.
Although the number of tender points used to be part of the diagnostic criteria, it is not considered relevant anymore. And because the neurochemical abnormalities that occur in fibromyalgia also regulate mood, sleep, and energy, symptoms related to mood, sleep, and fatigue problems are common in fibromyalgia.
For example, some might have difficulty concentrating and remembering things, sometimes called “fibro fog,” while others might have a poor sleep and might wake up unrefreshed and having a headache.
Typically there are no laboratory abnormalities specifically associated with this condition. Treatment of fibromyalgia requires a holistic approach.
Regular exercise like cardiovascular fitness training which includes fast walking, biking, swimming, or water aerobics can help by reducing pain and fatigue.
Relaxation techniques and good sleep hygiene can also help. If these approaches don’t work, antidepressants like amitriptyline and serotonin-nor-epinephrine reuptake inhibitors can help by elevating serotonin and norepinephrine levels.
Finally, neuropathic pain agents like pregabalin and gabapentin which slow nerve impulses by inhibiting high-voltage-activated calcium channels, can help control pain.
They can also help with sleep problems since one of their side effects is sedation. Ataxia is another side effect that can occur, and it represents a lack of voluntary coordination of muscle movements.

Review18:46–20:22

All right, as a quick recap, polymyositis is an inflammatory disorder of the muscles caused mainly by CD8+ T-cells destroying muscle tissue.
Symptoms of polymyositis include bilateral weakness and muscle wasting affecting proximal muscle groups like the shoulder or hips.
Gowers sign, muscle pain, dysphagia, interstitial lung disease and myocarditis can also be present. Dermatomyositis is an inflammatory disorder of the muscles and the skin, mediated mainly by complement activation and autoantibodies like ANA, anti-Mi-2, and anti-Jo-1 that result in bilateral proximal muscle weakness and photosensitive skin rashes.
People with this disorder are at an increased risk of developing hidden malignancies. Polymyalgia rheumatica is an inflammatory disorder that affects the joints and not the muscles.
The myalgia is due to referred pain. The most commonly affected joints are the shoulds and hips and its associated with temporal arteritis.
Finally, fibromyalgia is a chronic condition that causes widespread muscle pain, excessive tenderness in many areas of the body, sleep, cognitive and mood abnormalities.
The main cause is suspected to be increased sensitivity to pain, so similar to polymyalgia rheumatica, there’s no muscle damage so creatinine kinase will not be elevated.

Summary20:22–21:37

Now, back to our cases. First, Yu Yan presented with symptoms suggestive of polymyalgia rheumatica.
These include a history of fatigue, weight loss, fevers, inflamed joints, and bilateral pain and stiffness in the shoulder and hip girdles.
Symptom duration and complications are also characteristics of polymyalgia: they are worse at night, last for more than an hour, and cause difficulties getting out of bed in the morning.
The lack of muscle weakness makes myositis unlikely. The diagnosis was indirectly confirmed by a blood test, which showed increased inflammatory markers and normal creatine kinase levels.
X-rays of the affected joints are also needed to exclude other causes of joint disease. Elizabeth, on the other hand, came in with a 4-year history of chronic widespread body pain, fatigue, and sleep problems.
Examination revealed many tender points throughout her body but no sign of joint swelling or weakness. Considering her clinical picture, the fact
Myalgias and myositis: Video, Causes, and Symptoms | Osmosis