Dermatomyositis

Definitions & Key takeaways

Dermatomyositis (DM) is a rare autoimmune disease that leads to inflammation and damage of the muscles and skin. It is associated with complement system activation, and autoantibodies like ANA, anti-Mi-2 and, anti-Jo-1 which result in proximal muscle weakness and photosensitive skin rashes. DM presents with muscle weakness, which often becomes worse over time, as well as a distinctive skin rash.

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Introduction0:00–0:25

In dermatomyositis, “-itis” refers to inflammation, “myos-“ to the muscles and “dermato-“ to the skin, so dermatomyositis is an inflammatory disorder which involves both the skin and the muscles.
Dermatomyositis is considered to be an autoimmune disease, meaning that the immune system has gone rogue and started attacking its own muscles and skin.

Physiology0:25–2:15

Okay, normally, the cells of the immune system are always hanging around, ready and excited to spot and fight against anything foreign that could cause harm inside the body.
B- lymphocytes produce antibodies against a specific part of these foreign pathogens, called antigen. The tips of these antibodies strongly binds to this antigen, while the base of the antibody, called the constant region, gets recognized by complement proteins.
These complement proteins are a group of small proteins made by the liver that work together. One complement protein cuts or cleaves the next one, activating it and creating an enzymatic cascade.
This process gets started with C1, the first of the complement proteins, which binds to the Fc, or the constant region of two antibody attached to the pathogen.
C1 then cleaves C2 and C4. Portions of the C2 and C4 binds to the antigen and form an enzymatic complex that cleaves C3 into two portions, C3a and C3b.
C3b joins the enzymatic complex and then the complex is able to cleave C5 into two portions, C5a and C5b portion. C5a and C3a float off into the blood where they attract other cells of the immune system to the affected area.
Meanwhile, C5b, C6, C7, C8 and multiple C9 proteins, come together on the surface of the pathogen to form the membrane attack complex or MAC.
The MAC attacks pathogenic cells, such as bacteria, by creating a channel in the cell membrane. Because cells have more solutes in them than the outside environment, water flows into the cell by the process of osmosis, and that causes the cell to swell up and burst, which is called cell lysis.

Pathology2:15–4:10

In dermatomyositis, immune cells confuse normal muscle and skin proteins with foreign antigens. This process is called molecular mimicry because from the perspective of the immune cells, a host protein is mimicking a foreign or tumor protein.
When normal proteins in our body trigger an immune response, that protein is called an autoantigen. These autoantigens get picked up by B- lymphocytes, which begin producing antibodies against them.
In dermatomyositis, the autoantigens are usually found in various spots, like the endothelial cells lining the capillaries in muscle and skin cells, as well as soluble antigens coming from the nucleus or cytoplasm of destroyed muscle cells and skin cells.
So, in the first case, autoantibodies attach to the endothelial cells lining the capillaries near the perimysium, which is a sheath of connective tissue around bundles of muscle fibers.
Upon binding, these antibodies activate the complement cascade, leading to formation of the membrane attack complex which causes the endothelial cells to lyse.
The complement proteins also attract more inflammatory cells, like macrophages, to the area. In addition, autoantibodies also bind to small soluble antigens, such as nuclear proteins that get released from damaged cells and form antigen-antibody complexes.
Small antigen- antibody complexes are not very immunogenic, meaning that they don’t get removed from the bloodstream very quickly.
As a result, these immune complexes float around in the blood longer and make their way to the basement membrane of various blood vessel walls, once again activating the complement and causing further damage.
All this inflammation and cellular destruction results in the loss of blood vessels, and that leads to tissue ischemia in the affected muscle and skin tissue.

Causes4:10–4:38

The exact trigger for dermatomyositis is unknown, but there are some specific genetic and environmental factors. For example, a person with a certain gene for an immune protein called human leukocyte antigen, or HLA, specifically HLA- DR3 or HLA- DR5, might develop the dermatomyositis after getting exposed to a foreign pathogen like coxsackievirus or specific tumor antigens, such as those in ovarian, lung, or breast tumors.

Symptoms4:38–5:52

Symptoms of dermatomyositis are typically related to the tissue involved. When muscles are involved, there may be bilateral weakness, muscle atrophy and muscle pain and tenderness that mostly affects proximal, big muscle groups, like the shoulder or hip.
That pattern of muscle weakness can cause difficulty getting out of a chair or combing hair. In severe cases, the muscles of the pharynx or esophagus can be affected causing dysphagia, or difficulty in swallowing.
When the skin is involved, there can be a purplish rash on the upper eyelids, called a “heliotrope rash” after a purple flower.
The rash can involve the shoulders, upper chest, and back, resembling a “shawl”. Less commonly, there’s a malar rash, in the shape of butterfly, involving both cheekbones and the nasal bridge.
Another classic finding is Gottron's sign which are flat, red, scaly papules over the back of the fingers, elbows, or knees.
The rashes are photosensitive, meaning that they worsen in sunlight, and are often itchy, painful, and can bleed. The diagnosis of dermatomyositis is based on the combination of skin and muscle findings.

Diagnosis5:52–6:21

Typically there are autoantibodies, like antinuclear antibodies, or ANA, anti-Mi-2 and anti-Jo-1. There are often increased levels of muscle enzymes, such as creatinine kinase, and abnormal findings on an electromyograph or EMG.
A muscle biopsy might show signs of inflammation of the perimysium. Treatment of dermatomyositis typically focuses on suppressing the immune response, usually with corticosteroids, such as prednisone.

Treatment6:21–6:43

Antimalarial medications, especially hydroxychloroquine and chloroquine, are sometimes effective in the management of skin rashes, along with sun avoidance and wearing protective clothing.

Review6:43–7:03

All right, as a quick recap, 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.