Inflammatory myopathies: Clinical sciences

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Introduction0:00–0:36

Inflammatory myopathies are a group of autoimmune conditions associated with muscle inflammation and subsequent progressive muscle wasting and weakness.
These conditions occur when immune cells like lymphocytes and macrophages infiltrate skeletal muscle fibers, causing widespread inflammation.
Inflammatory myopathies include five conditions: dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myositis, inclusion body myositis, and polymyositis.
Now, if your patient presents with chief concerns suggesting inflammatory myopathy, your first step is to perform a focused history and physical.

Stable0:36–1:29

Patients usually report symptoms of proximal muscle weakness, commonly affecting the shoulder and pelvic girdle muscles.
So, they might find it difficult to do activities like combing their hair, standing up from a sitting position, or climbing stairs.
To remember this, think hair, chairs, and stairs! They might also report difficulty swallowing or a skin rash.
Additionally, some individuals have a positive personal or family history of autoimmune or inflammatory diseases, like lupus, scleroderma, or Sjogren syndrome.
Finally, the physical examination can reveal symmetric proximal muscle weakness, with or without skin abnormalities like a rash.At this point, you should suspect inflammatory myopathy, so be sure to order serum creatine kinase and electromyography, or EMG.

CK and EMG1:29–2:32

Now, If your patient’s creatine kinase levels are normal and EMG reveals normal findings or evidence of neuropathy, consider an alternative diagnosis, like motor neuron disease, peripheral polyneuropathy, or myasthenia gravis.
On the other hand, if labs reveal elevated creatine kinase, usually ten times the upper limit of normal or more, and the EMG shows a myopathic process, such as fibrillations and early recruitment of muscle fibers, diagnose inflammatory myopathy!Here’s a clinical pearl to keep in mind!
Non-inflammatory conditions, such as electrolyte imbalances, hypothyroidism, Cushing syndrome or adrenal insufficiency, can also result in myopathy, so you should always check serum electrolytes, magnesium, TSH and morning cortisol screen for these conditionsAlright, now once you confirm the presence of an inflammatory myopathy, your next step is to identify the underlying cause of muscle inflammation.

Myositis- Specific antibody panel2:32–3:37

First, order myositis-specific antibodies, such as anti-Mi-2 and anti-Jo-1 antibodies. However, keep in mind that these antibodies can be associated with more than one disease, so you will need to interpret the results along with history and physical exam findings.
Also, don’t forget to obtain a muscle biopsy, which is the gold standard for diagnosis. And here’s another clinical pearl!
Once you confirm the diagnosis of inflammatory myositis, it's important to screen your patient for extramuscular manifestations and various associated malignancies.
This might involve lung imaging and pulmonary function tests to detect interstitial lung disease; electrocardiography and echocardiography to detect cardiac disease; and cancer screening tests, like a mammogram and prostate examination, as well as an endoscopy or a colonoscopy.Now, let’s have a look at various underlying causes of inflammatory myopathies, starting with dermatomyositis.

Dermatomyositis3:37–3:37

Dermatomyositis3:37–6:48

As the name implies, it affects both the skin and the muscles. In this case, a physical exam typically reveals Gottron papules, which are raised red lesions over the knuckles; or Gottron sign, which is a red, flat, scaly rash over extensor surfaces of joints.
Additionally, these patients often develop a Heliotrope rash, which refers to red-to-purple discoloration and edema of the eyelids.
Other findings include a V-sign, or v-shaped redness on the anterior neck and chest, and a shawl sign, which refers to a red discoloration on the back of the neck and shoulders.
You might also notice nail bed telangiectasias and subcutaneous calcium deposits. Now, one physical exam finding that distinguishes dermatomyositis from similar conditions like scleroderma and systemic lupus erythematosus is poikiloderma, which refers to areas of skin affected by skin atrophy, hyper- and hypopigmentation, that are typically seen in chronic disease; and telangiectasias.
Also, in patients with dermatomyositis, the anti-Mi-2 antibodies are typically positive. Finally, the muscle biopsy will reveal inflammation of the perimysium, which is a thin layer of fibrous tissue surrounding a muscle fascicle; as well as degeneration of muscle fibers.
With these findings, diagnose dermatomyositis! Now, here’s a high-yield fact!
Dermatomyositis can have extramuscular manifestations, including interstitial lung disease and esophageal dysphagia; as well as cardiac conditions, like congestive heart failure, myocarditis, and conduction defects.
It can also be associated with breast, ovarian, lung and prostate cancer, as well as non-Hodgkin lymphoma. On the flip side, there’s a variant of dermatomyositis called amyopathic dermatomyositis, which affects the skin but spares muscles!
This type of dermatomyositis is diagnosed with a skin biopsy rather than a muscle biopsy.Once you diagnose dermatomyositis, you can start the initial treatment.
This involves high-dose glucocorticoids, and once symptoms improve, taper them off to a maintenance dose. In some cases, you could add disease-modifying anti-rheumatic drugs, or DMARDs, such as methotrexate or azathioprine.
Consider these medications in individuals with rapidly progressive disease, suboptimal response to glucocorticoid monotherapy, severe extramuscular organ involvement, clinical worsening during glucocorticoid tapering, and glucocorticoid side effects, such as worsening of hyperglycemia in diabetes or iatrogenic Cushing syndrome.
Finally, advise your patient to protect their skin from sun exposure.Now, let’s move on to antisynthetase syndrome! These patients will likely report fever, shortness of breath, and muscle and joint pain.

Antisynthetase Syndrome 6:48–7:59

Additionally, they might have a history of interstitial lung disease. Physical exam reveals inspiratory crackles, swollen joints, and a sign called mechanic’s hands, which is cracking of thickened skin on the tips and sides of the fingers.
You might also observe Raynaud phenomenon, which refers to vasoconstriction of blood vessels, typically in fingers and toes, resulting in discoloration and pain.
Finally, serology could reveal anti-Jo-1 antibodies; while the muscle biopsy typically shows perimysial inflammation and degeneration of muscle fibers.
With these findings, you can diagnose Antisynthetase Syndrome and proceed with treatment. This primarily relies on high-dose glucocorticoids followed by tapering to maintenance doses.
Again, in severe cases, consider combining glucocorticoids, DMARDs, or an immunosuppressant like mycophenolate mofetil.Next up is immune-mediated necrotizing myopathy.
This disease could be associated with a history of taking HMG-CoA reductase inhibitors, better known as statins. These patients might also have a history of scleroderma, and their physical exam might show sclerodactyly, which is a tightening and thickening of the skin of the fingers.

Immune-mediated necrotizing myopathy7:59–9:02

Myositis-specific antibodies are usually positive, but the first line test is anti-signal recognition particle antibodies, or anti-SRP for short.
The patient’s muscle biopsy typically reveals necrotic and regenerating muscle fibers with few or no inflammatory cells.
With these findings, diagnose immune-mediated necrotizing myopathy! The initial treatment consists of glucocorticoids plus a DMARD, like methotrexate.
In refractory cases, add intravenous immunoglobulin or the immunosuppressant rituximab to the regimen. Now let’s move on to inclusion body myositis.

Inclusion Body Myositis9:02–9:59

This is associated with proximal and distal muscle weakness, such as in the forearms and legs. This weakness is often asymmetrical and evident on the physical exam.
Of note, the skin is usually not affected with this myopathy! Myositis-specific antibodies might be positive; whereas muscle biopsy reveals inflammatory cells, rimmed vacuolated muscle fibers, and intracellular amyloid deposits.
If you find this constellation of findings, diagnose inclusion body myositis! Now, unlike other myopathies, the management here primarily relies on preserving functional capacity with physical, occupational, and speech therapy, since inclusion body myositis is not responsive to glucocorticoids or steroid-sparing medications.
Finally, let’s have a look at polymyositis! We saved this for last because it’s a diagnosis of exclusion, since it overlaps with the other inflammatory myopathies.

Polymyositis9:59–10:53

Your patient may report shortness of breath, difficulty swallowing, and joint pain, with no rashes on physical exam. Regarding labs, myositis-specific antibodies are often positive, but none are specific to the disease.
The most distinguishing feature is the muscle biopsy, which shows inflammation of the endomysium, the thin fibrous layer surrounding individual muscle fibers; and degeneration of muscle fibers.
With these findings, diagnose polymyositis! Treatment consists of initial high-dose glucocorticoids, tapering to a maintenance dose once symptoms are controlled, and often in combination with DMARDs, like methotrexate.Alright, as a quick recap… Inflammatory myopathies are autoimmune conditions associated with muscle inflammation and subsequent progressive muscle wasting and weakness.

Review10:53–11:37

Based on clinical presentation, lab results, muscle biopsy findings, and electromyography, you can categorize five inflammatory myopathies.
Dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myositis, and polymyositis are all treated with glucocorticoids and possibly DMARDs, immunosuppressants, and IVIG.
On the other hand, the management of inclusion body myositis primarily relies on physical therapy, occupational therapy, and speech therapy.
Inflammatory myopathies: Clinical Sciences: Video | Osmosis