Dermatomyositis
Template:Short description Template:Cs1 config Template:Use dmy dates Template:Infobox medical condition (new) Dermatomyositis (DM) is a long-term inflammatory autoimmune disorder which affects the skin and the muscles. Its symptoms are generally a skin rash and worsening muscle weakness over time. These may occur suddenly or develop over months. Other symptoms may include weight loss, fever, lung inflammation, or light sensitivity. Complications may include calcium deposits in muscles or skin.<ref name=":0">Template:Cite journal</ref><ref name=GHR2017/>
Dermatomyositis is an autoimmune disorder featuring both humoral and T-cell autoimmune processes.<ref name=":0" /> Dermatomyositis may develop as a paraneoplastic syndrome associated with several forms of malignancy.<ref>Template:Cite journal</ref> It is known to be associated with several viruses, especially coxsackievirus, but no definitive causal link has been found.<ref name=":0" /> Dermatomyositis is considered a type of inflammatory myopathy.<ref name=GHR2017>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Diagnosis is typically based on some combination of symptoms, blood tests, electromyography, and muscle biopsies.<ref name=NORD2015>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Eighty percent of adults<ref>Template:Cite journal</ref> and sixty percent of children with juvenile dermatomyositis have a myositis-specific antibody (MSA).<ref>Template:Cite journal</ref>
Although no cure for the condition is known, treatments generally improve symptoms.<ref name=GHR2017/> Treatments may include medication, physical therapy, exercise, heat therapy, orthotics, assistive devices, and rest.<ref name=GHR2017/> Medications in the corticosteroids family are typically used with other agents such as methotrexate or azathioprine recommended if steroids are not working well.<ref name=GHR2017/> Intravenous immunoglobulin may also improve outcomes.<ref name=GHR2017/> Most people improve with treatment and in some, the condition resolves completely.<ref name=GHR2017/>
About one in 100,000 people receive a new diagnosis of dermatomyositis each year.<ref name=NORD2015/> The condition usually occurs in those in their 40s and 50s with women being affected more often than men.<ref name=NORD2015/> People of any age, however, may be affected.<ref name=NORD2015/> The condition was first described in the 1800s.<ref>Template:Cite book</ref>
Signs and symptomsEdit
The main symptoms include several kinds of skin rash along with muscle weakness in both upper arms or thighs.<ref name=Cal2006>Template:Cite journal</ref> Although dermatomyositis is closely related to polymyositis and is sometimes assumed to be a complication of that disease, most patients with dermatomyositis develop skin symptoms before any muscle involvement.<ref name=":0" />
SkinEdit
One form the rashes take is called "heliotrope" (a purplish color) or lilac, but may also be red. It can occur around the eyes along with swelling, but also occurs on the upper chest or back what is called the "shawl" (around the neck) or "V-sign" above the breasts and may also occur on the face, upper arms, thighs, or hands.<ref name=":1">Template:Cite journal</ref> Another form the rash takes is called Gottron's sign, which is red or violet, sometimes scaly, slightly raised papules that erupt on any of the finger joints (the metacarpophalangeal joints or the interphalangeal joints).<ref name=":1" /><ref name="Kuhn2016rev" /> Gottron's papules may also be found over other bony prominences including the elbows, knees, or feet. All these rashes are made worse by exposure to sunlight, and are often very itchy, painful, and may bleed.<ref name="Kuhn2016rev" />
If a person exhibits only skin findings characteristic of DM, without weakness or abnormal muscle enzymes, then he or she may be experiencing amyopathic dermatomyositis (ADM), formerly known as "dermatomyositis sine myositis".<ref name="Callender2016rev" />
MusclesEdit
People with DM experience progressively worsening muscle weakness in the proximal muscles (for example, the shoulders and thighs).<ref name=":2">Template:Cite journal</ref> Tasks that use these muscles: standing from sitting, lifting, and climbing stairs, can become increasingly difficult for people with dermatomyositis.<ref name=":2" />
RespiratoryEdit
In some people, the condition affects the diaphragm muscle, the lungs directly (through inflammation), or both. This causes difficulty breathing, and dermatomyositis is considered to be a restrictive lung disease in patients with these symptoms. Respiratory symptoms occur in about 40% of people with dermatomyositis, and in these people, the symptoms may slowly progress and frequently are identified as an eventual cause of death. The main driver of respiratory failure in most of these patients is the damage to the lung interstitia, rather than diaphragm weakness.<ref name=":0" />
CardiacEdit
In dermatomyositis, many patients have mild myocarditis and cardiac conduction system abnormalities which may be detected if the patient undergoes special testing. However, these abnormalities typically have no symptoms or clinical consequences.<ref name=":0" /> In a study of 26 patients with dermatomyositis or polymyositis, only one patient reported chest pain.<ref>Template:Cite journal</ref>
More rarely, these abnormalities can cause greater issues and lead to arrhythmias, heart failure, or damage to heart valves.<ref name=":0" /> For those dermatomyositis patients who do have cardiac symptoms caused by the disease, their clinical course may be much worse than usual.<ref>Template:Cite journal</ref>
OtherEdit
Around 30% of people have swollen, painful joints, but this is generally mild.<ref name="MerckMan2013" />
Later in the course of the disease, patients often experience difficulty swallowing, called dysphagia, which makes it hard to move food from the mouth to the stomach. The muscles of the esophagus may become weak, leading to reduced or irregular movements that prevent proper swallowing. Additionally, individuals might suffer from gastroesophageal reflux disease (GERD), where stomach acid flows back into the esophagus, causing heartburn and irritation.<ref name=":0" />
- Examples of dermatomyositis
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Gottron's papules on finger joints
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Gottron's papules on the elbows of a person with juvenile DM
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Gottron's papules
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Gottron's bumps on a person with juvenile DM
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Gottron's papules in a severe case of juvenile dermatomyositis
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Heliotrope with swelling around the eyes
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Heliotrope
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Facial rash
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Severe rash on the hands, extending up the forearm
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Forearm rash
CausesEdit
Template:See also The pathogenesis of dermatomyositis involves an autoimmune-mediated process characterized by immune complex deposition and complement activation, leading to microangiopathy in both muscle and skin tissues. The specific mechanism of tissue injury is variable, depending on the specific autoantibodies and immune cell types involved.<ref>Template:Cite journal</ref> The microangiopathy has a non-uniform pattern: within a single muscle fiber, some capillaries may be heavily affected while others seem to be unharmed.<ref name=":3" />
In contrast to polymyositis, which pathologically centers on damage to the endomysium of muscle fibers, dermatomyositis damages both the endomysium and the perimysium. This indicates that tissue damage from dermatomyositis is not limited to the capillaries and the tissues immediately surrounding them; it also damages the larger vessels of the muscle fibers and skin tissue, potentially causing wider structural damage.<ref name=":3">Template:Cite journal</ref>
The complement system plays a crucial role in the tissue injury of dermatomyositis, through the formation and deposition of immune complexes. Autoantibodies target muscle and skin antigens, leading to the activation of the classical complement pathway, ultimately forming the membrane attack complex (MAC) on the endothelial cells of microvasculature.<ref name=":0" /> MAC causes direct endothelial cell damage by perforating the cell membrane and ultimately lysing (destroying) the cell due to osmotic effects.<ref>Template:Cite journal</ref> The destruction of vascular endothelium results in increased vascular permeability, furthering the pro-inflammatory immune cell infiltration of the tissue, and also results in tissue ischemia due to the lack of blood flow. Additionally, complement fragments facilitate the recruitment and activation of inflammatory cells like macrophages and T lymphocytes, further driving the inflammatory response and resulting damage to local tissue. However, the specific sequence of complement activation is not completely understood and may depend on the pathological subtype of the disease.<ref name=":0" /><ref>Template:Cite journal</ref>
As many as 40% of cases of dermatomyositis are paraneoplastic manifestations of an underlying cancer.<ref name=":0" /> The most commonly associated cancers are ovarian cancer, breast cancer, and lung cancer overall,<ref name="Di2014">Template:Cite journal</ref> but the most frequent associations can vary depending on patient race or ethnicity.<ref name=":0" />
Inherited genetic factors play at least a partial role in developing the disease, and HLA subtypes HLA-DR3, HLA-DR52, and HLA-DR6 seem to create a disposition to autoimmune dermatomyositis.<ref name="MerckMan2013" />
DiagnosisEdit
The diagnosis of dermatomyositis is based on five criteria, which are also used to differentially diagnose with respect to polymyositis:<ref name=Callender2016rev/>
- Muscle weakness in both thighs or both upper arms
- Using a blood test, finding higher levels of enzymes found in skeletal muscle, including creatine kinase, aldolase, and glutamate oxaloacetate, pyruvate transaminases and lactate dehydrogenase
- Using electromyography (testing of electric signalling in muscles), finding all three of: erratic, repetitive, high-frequency signals; short, low-energy signals between skeletal muscles and motor neurons that have multiple phases; and sharp activity when a needle is inserted into the muscle
- Examining a muscle biopsy under a microscope and finding mononuclear white blood cells between the muscle cells, and finding abnormal muscle cell degeneration and regeneration, dying muscle cells, and muscle cells being consumed by other cells (phagocytosis)
- Rashes typical of dermatomyositis, which include heliotrope rash, Gottron sign, and Gottron papules
The fifth criterion is what differentiates dermatomyositis from polymyositis; the diagnosis is considered definite for dermatomyositis if three of items 1 through 4 are present in addition to 5, probable with any two in addition to 5, and possible if just one is present in addition to 5.<ref name=Callender2016rev/>
Dermatomyositis is associated with autoantibodies, especially antinuclear antibodies (ANA).<ref name=MerckMan2013/> Around 80% of people with DM test positive for ANA and around 30% of people have myositis-specific autoantibodies which include antibodies to aminoacyl-tRNA synthetases (anti-synthetase antibodies), including antibodies against histidine—tRNA ligase (Anti-Jo1); antibodies to signal recognition particle (SRP); and anti-Mi-2 antibodies.<ref name=MerckMan2013/>
Magnetic resonance imaging may be useful to guide muscle biopsy and to investigate involvement of internal organs;<ref>Template:Cite journal</ref> X-ray may be used to investigate joint involvement and calcifications.<ref>Template:Cite journal</ref>
A given case of dermatomyositis may be classified as amyopathic dermatomyositis if only skin is affected and no muscle weakness for longer than 6 months is seen according to one 2016 review,<ref name=Callender2016rev>Template:Cite journal</ref> or two years according to another.<ref name=Kuhn2016rev/>
ClassificationEdit
Dermatomyositis is a form of systemic connective tissue disorder, a class of diseases that often involves autoimmune dysfunction.<ref name=MerckMan2013>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
It has also been classified as an idiopathic inflammatory myopathy, along with polymyositis, necrotizing autoimmune myositis, cancer-associated myositis, and sporadic inclusion body myositis.<ref name=Cardiac2016rev>Template:Cite journal</ref>
A form of this disorder that occurs prior to adulthood is known as juvenile dermatomyositis.<ref name="pmid18586175">Template:Cite journal</ref>
TreatmentEdit
No cure for dermatomyositis is known, but the symptoms can be treated. Options include medication, physical therapy, exercise, heat therapy (including microwave and ultrasound), orthotics and assistive devices, and rest. The standard treatment for dermatomyositis is a corticosteroid drug, given either in pill form or intravenously. Immunosuppressant drugs, such as azathioprine and methotrexate, may reduce inflammation in people who do not respond well to prednisone. Periodic treatment using intravenous immunoglobulin can also improve recovery. Other immunosuppressive agents used to treat the inflammation associated with dermatomyositis include cyclosporine A, cyclophosphamide, and tacrolimus.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Physical therapy is usually recommended to prevent muscle atrophy and to regain muscle strength and range of motion. Many individuals with dermatomyositis may need a topical ointment, such as topical corticosteroids, for their skin disorder. They should wear high-protection sunscreen and protective clothing. Surgery may be required to remove calcium deposits that cause nerve pain and recurrent infections.<ref name=NINDSinfo2015/>
Antimalarial medications, especially hydroxychloroquine and chloroquine, are used to treat the rashes, as is done for similar conditions.<ref name=Kuhn2016rev/>
Rituximab is used when people do not respond to other treatments.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
As of 2016, treatments for amyopathic dermatomyositis in adults did not have a strong evidence base; published treatments included antimalarial medications, steroids, taken or orally or applied to the skin, calcineurin inhibitors applied to the skin, dapsone, intravenous immunoglobulin, methotrexate, azathioprine, and mycophenolate mofetil. None appears to be very effective; among them, intravenous immunoglobulin has had the best outcomes.<ref name=Callender2016rev/>
PrognosisEdit
The cutaneous manifestations of dermatomyositis may or may not improve with therapy in parallel with the improvement of the myositis. In some people, the weakness and rash resolve together. In others, the two are not linked, with one or the other being more challenging to control. Often, cutaneous disease persists after adequate control of the muscle disease.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
The risk of death from the condition is much higher if the heart or lungs are affected.<ref name="Cardiac2016rev" /><ref name="NINDSinfo2015">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Before the advent of modern treatments such as prednisone, intravenous immunoglobulin, plasmapheresis, chemotherapies, and other drugs, the prognosis was poor.<ref name="squid57squid">Page 285 in: Thomson and Cotton Lecture Notes in Pathology, Blackwell Scientific. Third Edition</ref>
EpidemiologyEdit
Incidence of DM peaks at ages 40–50, but the disease can affect people of all ages.<ref>Template:Cite journal</ref><ref name="NORD2015" /> It tends to affect more women than men.<ref name="NORD2015" /> The prevalence of DM ranges from one to 22 per 100,000 people.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
HistoryEdit
The diagnostic criteria were proposed in 1975 and became widely adopted.<ref name=Kuhn2016rev>Template:Cite journal</ref><ref>Template:Cite journal and Template:Cite journal</ref> Amyopathic DM, also called DM sine myositis, was named in 2002.<ref name=Kuhn2016rev/>
People who were affected with dermatomyositisEdit
- Opera singer Maria Callas (1923–1977) allegedly had dermatomyositis from 1975 until her death.<ref>{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref>
- Actor Laurence Olivier (1907–1989) had dermatomyositis from 1974 until his death.<ref>{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref>
- American football running back Ricky Bell (1955–1984), the runner-up for the Heisman Trophy in 1976, and the number-one pick in the NFL draft in 1977, died at the age of 29 from heart failure caused by this disease.<ref>{{#invoke:citation/CS1|citation
|CitationClass=web }}</ref>
- Rob Buckman (1948–2011) a doctor, comedian, and author, and the president of the Humanist Association of Canada.<ref>Template:Cite news</ref>
- Samantha, Indian actress diagnosed in 2022.
- Suhani Bhatnagar (2005–2024), Indian actress.<ref>Template:Cite news</ref>
- Tim Rooney (1947-2006), American actor and son of Mickey Rooney.<ref>Template:Cite news</ref>
ResearchEdit
As of 2016, research was ongoing into causes for DM, as well as biomarkers;<ref>Template:Cite journal</ref> clinical trials were ongoing for use of the following drugs in DM: ajulemic acid (Phase II), adrenocorticotropic hormone gel (Phase IV, open label), IMO-8400, an antagonist of Toll-like receptor 7,8 and 9 (Ph II), abatacept (Phase IV, open label), and sodium thiosulfate (Phase II).<ref name=Kuhn2016rev/>
ReferencesEdit
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External linksEdit
Template:Portal Template:Medical resources Template:Systemic connective tissue disorders Template:Paraneoplastic syndromes