Dermatomyositis
Autoimmune disease of skin and muscle
From Wikipedia, the free encyclopedia
Dermatomyositis (DM) is a group of sytemic autoimmune inflammatory diseases primarily affecting the skin and skeletal muscles.[3][4] 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. Distinct myositis-specific autoantibodies (MSA) define clinically and pathologically distinct DM subtypes, each associated with characteristic disease manifestations, prognosis, and treatment response.[3][5]
| 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] |
Eighty percent of adults[6] and sixty percent of children with juvenile dermatomyositis have a MSA.[7] These autoantibodies, produced by locally infiltrating plasma cells, can enter various cell types and disrupt the function of their target autoantigens, inducing cellular damage and inflammation that directly drive disease pathogenesis.[8][9][10][11] Dermatomyositis may develop as a paraneoplastic syndrome associated with several malignancies, in which tumors harbor genetic alterations, including somatic mutations, in genes encoding the specific autoantigens targeted by the patient’s corresponding autoantibodies.[12][13][14][15] It is known to be associated with several viruses, especially coxsackievirus, but no definitive causal link has been found.[16] Diagnosis is typically based on some combination of symptoms, blood tests, electromyography, and muscle biopsies.[3]
Current treatment of dermatomyositis relies on immunosuppressive agents such as corticosteroids, methotrexate, mycophenolate mofetil, azathioprine, tacrolimus, and cyclosporine, with intravenous immunoglobulin (IVIG) widely used for refractory or severe disease.[17][18] Rituximab remains an important therapeutic option despite mixed clinical trial results.[19] Emerging targeted therapies, including Janus kinase (JAK) inhibitors[20][21][22][23][24] and agents targeting the type I interferon pathway, such as dazukibart,[25] have demonstrated promising efficacy. Novel approaches such as CD19 chimeric antigen receptor (CAR) T-cell therapy,[26] plasma cell–directed therapies,[27][28] and neonatal Fc receptor (FcRn) inhibitors, such as efgartigimod, are also showing encouraging results,[29] offering the potential for sustained treatment-free disease control in the case of CD19 CAR-T cell therapy. Overall, with timely diagnosis and appropriate treatment, the prognosis of DM is generally favorable.
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.[30]
Signs and symptoms
The main symptoms include several kinds of skin rash along with muscle weakness in both upper arms or thighs.[3]
Skin
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.[31] 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).[31][32] 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.[32]
If a person exhibits only skin findings characteristic of DM, without weakness or abnormal muscle enzymes, may be classified as having amyopathic or clinically amyopathic dermatomyositis (ADM), formerly known as "dermatomyositis sine myositis".[33]
Muscles
People with DM experience progressively worsening muscle weakness in the proximal muscles (for example, the shoulders and thighs).[34] Tasks that use these muscles: standing from sitting, lifting, and climbing stairs, can become increasingly difficult for people with dermatomyositis.[34]
Respiratory
The primary cause of respiratory failure in dermatomyositis is interstitial lung disease, resulting from damage to the lung interstitium.[3] This is particularly prominent in patients with anti–MDA5 autoantibodies, who are at high risk of developing rapidly progressive interstitial lung disease.[16] 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, contributing to increased morbidity and mortality.
Cardiac
In dermatomyositis, patients can develop 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.[16]
More rarely, these abnormalities can cause greater issues and lead to arrhythmias, heart failure, or damage to heart valves.[16] For those dermatomyositis patients who do have cardiac symptoms caused by the disease, their clinical course may be much worse than usual.[35]
Other
Around 30% of people have swollen, painful joints, but this is generally mild.[36]
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.[16]
- 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
Etiopathogenesis
Recent studies suggest that the pathogenesis of DM is driven by the pathogenic internalization of autoantibodies.[37][38][39] Although these antibodies target intracellular proteins, evidence indicates that they can enter different cell types and disrupt the function of their target autoantigens causing inflammation and damage.[38][39] For example, anti-Mi-2 autoantibodies bind PHD-containing proteins,[40][41] including component of the NuRD complex, inducing derepression of multiple genes,[38] and in anti-MDA5 dermatomyositis, autoantibodies activate MDA5 directly inducing the activation of type I interferon pathways.[38]
The type I interferon pathway is especially prominent in DM and has become a major therapeutic target.[42][43] Clinical responses to JAK inhibitors,[44][45][46][47][48] anti-IFNβ therapy,[49] and agents targeting the interferon receptor support the importance of this pathway in disease activity. Conversely, a negative trial of complement inhibition in immune-mediated necrotizing myopathy[50] has challenged earlier models in which complement-mediated muscle injury was considered central to that subtype.[51][52][53]
The characteristic pathological feature is perifascicular muscle involvement, often accompanied by vasculopathy. Plasma cells are found in close proximity to affected areas with high type I interferon expression and have been observed to externalize immunoglobulin heavy- and light-chain RNA into surrounding muscle cells, suggesting that this may be a potential mechanism for immunoglobulin entry into affected cell types shared across different forms of DM.[39]
DM is paraneoplastic in up to 40% of cases, most commonly in association with underlying malignancy in patients with anti–TIF1γ autoantibodies.[16] A majority of patients with paraneoplastic dermatomyositis harbor somatic mutations or other genetic alterations in tumor genes encoding the target autoantigens of their corresponding autoantibodies, suggesting that, in this context, autoantibody production arises secondary to an anti-tumor immune response that fails to achieve effective tumor control.[12][13][14][15]The most commonly associated cancers are ovarian cancer, breast cancer, and lung cancer overall,[54] but the most frequent associations can vary depending on patient race or ethnicity.[16]
Inherited genetic factors confer a predisposition to developing these diseases, and HLA subtypes HLA-DR3, HLA-DR52, and HLA-DR6 seem to create a disposition to DM.[36]
Diagnosis
The diagnosis of dermatomyositis is based on five criteria, which are also used to differentially diagnose with respect to polymyositis:[33]
- 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.[33]
Up to 80% of people with DM will have a positive ANA. A negative ANA does not exclude the diagnosis. [36] 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.[36]
Magnetic resonance imaging may be useful to guide muscle biopsy and to investigate involvement of internal organs;[55] X-ray may be used to investigate joint involvement and calcifications.[56]
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,[33] or two years according to another.[32]
Classification
Dermatomyositis is a form of systemic connective tissue disorder, a class of diseases that often involves autoimmune dysfunction.[36][57]
It has also been classified as an idiopathic inflammatory myopathy, along with polymyositis, necrotizing autoimmune myositis, cancer-associated myositis, and sporadic inclusion body myositis.[58]
A form of this disorder that occurs prior to adulthood is known as juvenile dermatomyositis.[59]
Treatment
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.[60]
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.[61]
Antimalarial medications, especially hydroxychloroquine and chloroquine, are used to treat the rashes, as is done for similar conditions.[32]
Rituximab is used when people do not respond to other treatments.[62][63]
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.[33]
Prognosis
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.[64][65]
The risk of death from the condition is much higher if the heart or lungs are affected.[58][61]
Before the advent of modern treatments such as prednisone, intravenous immunoglobulin, plasmapheresis, chemotherapies, and other drugs, the prognosis was poor.[66]
Epidemiology
History
People who were affected with dermatomyositis
- Opera singer Maria Callas (1923–1977) allegedly had dermatomyositis from 1975 until her death.[72]
- Actor Laurence Olivier (1907–1989) had dermatomyositis from 1974 until his death.[73]
- 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.[74]
- Rob Buckman (1948–2011) a doctor, comedian, and author, and the president of the Humanist Association of Canada.[75]
- Samantha, Indian actress diagnosed in 2022.
- Suhani Bhatnagar (2005–2024), Indian actress.[76]
- Tim Rooney (1947–2006), American actor and son of Mickey Rooney.[77]
Research
As of 2016, research was ongoing into causes for DM, as well as biomarkers;[78] 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).[32]
