Dermatomyositis

Dermatomyositis
Discrete red areas overlying the knuckles in a person with juvenile dermatomyositis. These are known as Gottron's papules.
Specialty	Rheumatology
Symptoms	Rash, muscle weakness, weight loss, fever[1]
Complications	Calcinosis, dysphagia, interstitial lung disease, heart disease (rarely), joint pain, other autoimmune conditions
Usual onset	40s to 50s[2]
Duration	Long term[1]
Causes	Autoimmune (Type III hypersensitivity)
Risk factors	Other autoimmune conditions, ovarian cancer, breast cancer, lung cancer, other cancers
Diagnostic method	Based on symptoms, blood tests, electromyography, muscle biopsies[2]
Differential diagnosis	Polymyositis, inclusion body myositis, scleroderma[2]
Treatment	Medication, physical therapy, exercise, heat therapy, orthotics, assistive devices, rest[1]
Medication	Corticosteroids, methotrexate, azathioprine[1]
Frequency	~ 1 per 100,000 people per year[2]

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.^[3][1]

Dermatomyositis is an autoimmune disorder featuring both humoral and T-cell autoimmune processes.^[3] Dermatomyositis may develop as a paraneoplastic syndrome associated with several forms of malignancy.^[4] It is known to be associated with several viruses, especially coxsackievirus, but no definitive causal link has been found.^[3] Dermatomyositis is considered a type of inflammatory myopathy.^[1] Diagnosis is typically based on some combination of symptoms, blood tests, electromyography, and muscle biopsies.^[2] Eighty percent of adults^[5] and sixty percent of children with juvenile dermatomyositis have a myositis-specific antibody (MSA).^[6]

Although no cure for the condition is known, treatments generally improve symptoms.^[1] Treatments may include medication, physical therapy, exercise, heat therapy, orthotics, assistive devices, and rest.^[1] Medications in the corticosteroids family are typically used with other agents such as methotrexate or azathioprine recommended if steroids are not working well.^[1] Intravenous immunoglobulin may also improve outcomes.^[1] Most people improve with treatment and in some, the condition resolves completely.^[1]

About one in 100,000 people receive a new diagnosis of dermatomyositis each year.^[2] The condition usually occurs in those in their 40s and 50s with women being affected more often than men.^[2] People of any age, however, may be affected.^[2] The condition was first described in the 1800s.^[7]

The main symptoms include several kinds of skin rash along with muscle weakness in both upper arms or thighs.^[8] 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.^[3]

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.^[9] 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).^[9][10] 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.^[10]

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".^[11]

People with DM experience progressively worsening muscle weakness in the proximal muscles (for example, the shoulders and thighs).^[12] Tasks that use these muscles: standing from sitting, lifting, and climbing stairs, can become increasingly difficult for people with dermatomyositis.^[12]

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.^[3]

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.^[3] In a study of 26 patients with dermatomyositis or polymyositis, only one patient reported chest pain.^[13]

More rarely, these abnormalities can cause greater issues and lead to arrhythmias, heart failure, or damage to heart valves.^[3] For those dermatomyositis patients who do have cardiac symptoms caused by the disease, their clinical course may be much worse than usual.^[14]

Around 30% of people have swollen, painful joints, but this is generally mild.^[15]

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.^[3]

• Examples of dermatomyositis
• 
  Gottron's papules on finger joints
• 
  Gottron's papules on the elbows of a person with juvenile DM
• 
  Gottron's papules
• 
  Gottron's bumps on a person with juvenile DM
• 
  Gottron's papules in a severe case of juvenile dermatomyositis
• 
  Heliotrope with swelling around the eyes
• 
  Heliotrope
• 
  Facial rash
• 
  Severe rash on the hands, extending up the forearm
• 
  Forearm rash

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.^[16] The microangiopathy has a non-uniform pattern: within a single muscle fiber, some capillaries may be heavily affected while others seem to be unharmed.^[17]

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.^[17]

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.^[3] MAC causes direct endothelial cell damage by perforating the cell membrane and ultimately lysing (destroying) the cell due to osmotic effects.^[18] 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.^[3][19]

As many as 40% of cases of dermatomyositis are paraneoplastic manifestations of an underlying cancer.^[3] The most commonly associated cancers are ovarian cancer, breast cancer, and lung cancer overall,^[20] but the most frequent associations can vary depending on patient race or ethnicity.^[3]

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.^[15]

The diagnosis of dermatomyositis is based on five criteria, which are also used to differentially diagnose with respect to polymyositis:^[11]

1. Muscle weakness in both thighs or both upper arms
2. 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
3. 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
4. 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)
5. 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.^[11]

Dermatomyositis is associated with autoantibodies, especially antinuclear antibodies (ANA).^[15] 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.^[15]

Magnetic resonance imaging may be useful to guide muscle biopsy and to investigate involvement of internal organs;^[21] X-ray may be used to investigate joint involvement and calcifications.^[22]

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,^[11] or two years according to another.^[10]

Dermatomyositis is a form of systemic connective tissue disorder, a class of diseases that often involves autoimmune dysfunction.^[15][23]

It has also been classified as an idiopathic inflammatory myopathy, along with polymyositis, necrotizing autoimmune myositis, cancer-associated myositis, and sporadic inclusion body myositis.^[24]

A form of this disorder that occurs prior to adulthood is known as juvenile dermatomyositis.^[25]

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.^[26]

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.^[27]

Antimalarial medications, especially hydroxychloroquine and chloroquine, are used to treat the rashes, as is done for similar conditions.^[10]

Rituximab is used when people do not respond to other treatments.^[28][29]

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.^[11]

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.^[30][31]

The risk of death from the condition is much higher if the heart or lungs are affected.^[24][27]

Before the advent of modern treatments such as prednisone, intravenous immunoglobulin, plasmapheresis, chemotherapies, and other drugs, the prognosis was poor.^[32]

Incidence of DM peaks at ages 40–50, but the disease can affect people of all ages.^[33][2] It tends to affect more women than men.^[2] The prevalence of DM ranges from one to 22 per 100,000 people.^[34][35][36]

The diagnostic criteria were proposed in 1975 and became widely adopted.^[10][37] Amyopathic DM, also called DM sine myositis, was named in 2002.^[10]

• Opera singer Maria Callas (1923–1977) allegedly had dermatomyositis from 1975 until her death.^[38]
• Actor Laurence Olivier (1907–1989) had dermatomyositis from 1974 until his death.^[39]
• 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.^[40]
• Rob Buckman (1948–2011) a doctor, comedian, and author, and the president of the Humanist Association of Canada.^[41]
• Samantha, Indian actress diagnosed in 2022.
• Suhani Bhatnagar (2005–2024), Indian actress.^[42]
• Tim Rooney (1947-2006), American actor and son of Mickey Rooney.^[43]

As of 2016, research was ongoing into causes for DM, as well as biomarkers;^[44] 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).^[10]

 This article incorporates public domain material from NINDS Dermatomyositis Information Page. United States Department of Health and Human Services. Retrieved 12 December 2016.