| disease | Dermatomyositis |
| alias | Heterochromic Dermatomyositis, DM |
Dermatomyositis (DM), also known as poikilodermatomyositis, is one of the autoimmune connective tissue diseases. It primarily affects the striated muscles, presenting as non-suppurative inflammatory lesions dominated by lymphocyte infiltration, which may or may not be accompanied by various skin lesions and can also involve various visceral damages. Polymyositis (PM) refers to this group of disorders without skin involvement.
bubble_chart Etiology
The exact cause of the disease is not yet fully understood. It may be related to viral infection, abnormal immune recognition of self, and vascular pathology, with possible interconnections among these factors. For example, a slow viral infection of striated muscle fibers could alter their antigenicity, leading the immune system to mistakenly identify them as "foreign," thereby triggering vasculitis and the onset of the disease.
(1) Immunological Research Given the elevated serum immunoglobulins in patients and muscle biopsy specimens showing deposits of IgG, IgM, and C3 as well as the complement membrane attack complex C56-C9 in microvessels, the degree of deposition appears to correlate with disease activity. Arahata and Engel demonstrated a significant increase in B cells in the inflammatory sexually transmitted disease foci of DM, suggesting enhanced local humoral effects. However, some researchers argue that these antibody deposits are a consequence rather than a cause of muscle injury. Others have found that peripheral blood stranguria lymphocytes in patients exhibit higher transformation rates and macrophage migration inhibition compared to controls when exposed to striated muscle antigens, with these effects positively correlating with disease activity and decreasing with glucocorticoid treatment. In vitro tissue culture studies show that peripheral blood stranguria lymphocytes from patients exhibit cytotoxic effects on myoblasts, possibly due to the release of lymphotoxins or direct adhesion and invasion of muscle fibers.
Some researchers note that this disease shares many clinical and immunological abnormalities with SLE and scleroderma. For instance, some cases show positive LE cells, antinuclear antibodies, and wind-dampness-like factors. Fluorescent antibody techniques reveal immunoglobulin deposits in the epidermal basement membrane and vascular walls, and serum tests detect anti-polymyositis antigen-1 (anti-PM-1) and anti-myosin antibodies, supporting the autoimmune disease hypothesis. In patients with concurrent malignancies, tumor resection can alleviate symptoms. Intradermal tests using tumor extracts from patients yield positive results, as do passive transfer tests. Antibodies against tumors are found in patient sera, suggesting that these malignancies act as self-antigens, triggering antibody production. Tumor tissues may also share cross-antigenicity with normal muscle fibers, tendon sheaths, blood vessels, and connective tissues, leading to cross-reactive antigen-antibody reactions and tissue damage, further supporting the autoimmune hypothesis.(2) Infectious Hypothesis Recent electron microscopy studies of patient muscles and skin lesions have revealed virus-like particles resembling paramyxoviruses or orthomyxoviruses in muscle cell nuclei, vascular endothelial cells, perivascular histiocytes, and fibroblast cytoplasm and nuclear membranes. A report identified Coxsackie A9 virus in the affected muscles of an 11-year-old girl, supporting the infectious hypothesis. However, animal experiments have so far failed to induce muscle inflammation by injecting patient muscle tissue or plasma, and no antiviral antibodies have been detected in patient blood.
(3) Vascular Pathology Hypothesis Vascular pathology, particularly in childhood DM, has been described. Any diffuse vascular pathology can cause ischemia in striated muscles, leading to single-fiber necrosis and muscle infarction. In DM/PM, especially in children, evidence of capillary endothelial injury, thrombosis, immune complex deposition in muscle vasculature, thickened capillary basement membranes, and reduced capillaries—particularly in the perifascicular regions—have been observed.
bubble_chart Clinical Manifestations
It can occur at any age, with a slight predominance in females. Some cases present with prodromal symptoms such as irregular fever, Raynaud's phenomenon, arthralgia, headache, fatigue, and lack of strength. The onset is mostly gradual, while a minority of cases present acutely or subacutely. Muscles and skin are the two main symptom groups of this disease. Skin lesions often precede muscle involvement by weeks to years, while in a few cases, myopathy appears first, followed by skin lesions. Some patients experience simultaneous onset of muscle and skin symptoms.
(1) Muscle Symptoms: Typically, striated muscles are affected, though smooth muscles and myocardium may also be involved. Muscles in any part of the body can be affected, but the limb muscles are usually the first to be involved, with proximal muscles more commonly affected than distal ones. The shoulder girdle and pelvic girdle muscles are often the earliest to be affected, followed by the upper arm and thigh muscles, and then other muscle groups. The lesions are usually symmetrical, though in rare cases, they may be limited to a single limb muscle group, a single muscle, or occur sequentially in multiple muscles. Patients typically experience lack of strength initially, followed by muscle pain, tenderness, and movement pain. As muscle strength declines, various motor dysfunctions and specific postures may appear. Symptoms vary depending on the extent, severity, and location of muscle involvement. Common manifestations include difficulty raising arms, moving the head, or standing up after squatting, as well as an unsteady gait. In severe cases, rapid muscle weakness may lead to specific postures such as a drooping head or forward-sloping shoulders. In extreme cases, the patient may become completely immobile, unable to even turn over. When the pharyngeal, upper esophageal, or palatal muscles are affected, hoarseness and dysphagia may occur. Involvement of the diaphragm and intercostal muscles can lead to shortness of breath and respiratory distress. Myocardial involvement may result in heart failure, and ocular muscle involvement can cause diplopia. Affected muscles may feel normal or slightly tender, and fibrosis may lead to hardening or firmness, potentially causing joint contractures and functional impairment. There are also reports of myasthenia gravis-like syndromes, characterized by painless muscle weakness that worsens with activity. The skin over the affected muscles may thicken or become edematous.
In cases of chronic sexually transmitted diseases, multiple keratotic small papules, spotted pigmentation, fine capillary dilation, grade I skin atrophy, and depigmentation may occasionally appear, known as the vascular atrophic poikilodermatous nature of disease dermatomyositis. Occasionally, on the basis of poikilodermatous eruptions, the rash may appear fiery red or even brownish-red, with extensive lesions, particularly prominent on the head and face, resembling a flushed appearance after intoxication. This is accompanied by numerous deep brown or grayish-brown pinpoint-sized pigmented spots, along with visible clusters of tortuous, tree branch-like dilated capillaries, referred to as malignant erythema, which often indicates the presence of an accompanying malignant tumor.
In addition, there may be subcutaneous nodules, calcium deposits discharged through the skin forming fistula disease tubes. Sometimes, in atypical cases, only purplish-red patches appear on the eyelids, one or both sides or the root of the nose, or diffuse erythema, pityriasis-like scaling, alopecia areata, or urticaria, polymorphic erythema-like patches, livedo reticularis, Raynaud's phenomenon, etc., may occur on the scalp. Some cases are sensitive to sunlight.
In recent years, literature reports that about 8% of cases present only with skin rashes, and no muscle lesions are observed even after long-term follow-up, which is referred to as dermatomyositis of the cutaneous type.
In pediatric patients, in addition to the above descriptions, the characteristics include a history of upper respiratory infections before onset, absence of Raynaud's phenomenon and scleroderma-like changes, and diffuse or localized calcium deposition in the skin, muscles, and fascial membranes, which is more common than in adults. Vascular lesions, ulcers, and bleeding in the gastrointestinal tract are also present, differing from adults.
Furthermore, patients may experience irregular fever, which can be the initial symptom of the disease or occur during its progression, often presenting as irregular low-grade fever. In acute sexually transmitted disease cases, the fever may be higher, with about 40% of cases experiencing fever. Arthralgia may occur, with deformities and restricted movement in the elbow, knee, shoulder, and finger joints, mostly secondary to fibrosis and contractures of adjacent muscle lesions. X-rays in some cases show disappearance of joint spaces and destruction of the bone cortex, with about 20% having joint lesions. Superficial lymph nodes generally show no significant enlargement, though a few may present with string-like enlargement in the neck. Cases with cardiac involvement may exhibit abnormal heart function, tachycardia or bradycardia, cardiomegaly, myocardial damage, atrial fibrillation, and heart failure. There may also be pleuritis, interstitial pneumonia, and about one-third of cases show grade I to moderate hepatomegaly with a firm texture. Gastrointestinal involvement may reveal poor esophageal motility, slow passage, esophageal dilation, and pear-shaped barium retention on barium meal examination. Ocular muscle involvement may cause diplopia, and the retinal membrane may sometimes show exudates or hemorrhage, or retinal choroiditis, or subarachnoid hemorrhage.
Additionally, this disease may overlap with SLE, scleroderma, and other conditions.
bubble_chart Auxiliary Examination
The blood picture usually shows no significant changes, sometimes presenting with grade I anemia and leukocytosis. Approximately one-third of cases exhibit eosinophilia, and the erythrocyte sedimentation rate is moderately increased. Total serum protein remains unchanged or decreases, with a reduced albumin-globulin ratio, decreased albumin, and increased α2 and γ globulins.
(1) Immunological Testing Two types of autoantibodies can be detected in the serum of DM/PM patients.
1. Antibodies Directly Against Muscles and Their Components Wada et al. used highly purified myosin in radioimmunoassays and found that 90% of PM patients tested positive for myosin antibodies, while no such antibodies were detected in other connective tissue disease patients. Nishikai et al. reported that myoglobin antibodies were present in 71% of myositis patients, less than 15% in other connective tissue disease patients, and none in healthy individuals.
2. Antinuclear Antibodies and Cytoplasmic Antibodies LE cells are positive in about 10% of cases, and antinuclear antibodies are positive in approximately 1/5 to 1/3 of cases, primarily with a fine speckled nuclear pattern.
⑴ Anti-Jo-1 Antibody: The antigen is histidyl-tRNA synthetase, a cytoplasmic antibody. It is positive in 30–40% of PM cases, <5% in DM cases, and rare in juvenile DM. It may also appear in overlap syndromes, particularly those associated with Sjögren’s syndrome, and is closely linked to interstitial lung disease.
⑵ Anti-Mi-2 Antibody: The Mi-2 antigen is a nuclear protein, positive in about 8% of cases, and occasionally seen in juvenile DM or DM associated with malignancy.
⑶ Anti-PM-1/PM-Scl Antibody: The antigen is a nucleolar protein, with a positivity rate of 8–12%. It may also occur in cases overlapping with scleroderma.
⑷ Anti-PL-7 Antibody: This is an anti-threonyl-tRNA synthetase antibody, found in 3–4% of myositis patients.
⑸ Anti-PL-12 Antibody: This is an anti-alanyl-tRNA synthetase antibody, with a positivity rate of 3%. Both anti-PL-7 and anti-PL-12 antibodies are rare in non-myositis patients and belong to the same subclass of myositis as the anti-Jo-1 antibody-related disorders.
⑹ Other Cytoplasmic Antibodies Found in Myositis Patients: ① Fer antibody; ② Mas antibody (both are rare); ③ Ro/SS-A and La/SS-B antibodies, typically positive in 7–8% of myositis patients, often seen in cases overlapping with other connective tissue diseases; ④ Anti-U1SmRNP antibody, positive in 10–15% of DM/PM patients.
3. Other Immunological Tests About one-third of patients show grade I to moderate reduction in C4, while C3 is occasionally decreased. Some reports indicate hereditary C2 deficiency in DM. Some cases exhibit elevated CIC.
Direct immunofluorescence of affected muscle capillaries, particularly in juvenile cases, reveals deposits of IgG, IgM, and complement. However, focal deposits of Ig and C are observed at the dermo-epidermal junction in skin lesions, without continuous deposition, distinguishing it from SLE.
(2) Increased urinary creatine excretion Under normal circumstances, the synthesis process of creatine first involves arginine transferring its amidino group to glycine to form guanidinoacetic acid. Next, guanidinoacetic acid accepts a methyl group from methionine to become creatine, which is synthesized in the liver. Most of it is taken up by muscles and exists in the form of phosphocreatine containing high-energy phosphate bonds. The high-energy phosphate bond can be transferred to adenosine diphosphate (ADP) under the catalysis of creatine kinase to form adenosine triphosphate (ATP). When ATP synthesis increases, part of the phosphate can be stored in phosphocreatine through a reverse reaction. Creatine is metabolized in muscles, dehydrated to form creatinine, and then excreted in urine. Physiological creatinuria may occur during growth periods, before and after menstruation in women, and in the elderly, but the total 24-hour excretion does not exceed 4 mg per kilogram of body weight. In this disease, due to muscle pathology, the uptake of creatine decreases, and the amount of creatine involved in muscle metabolism also decreases. Consequently, the formation of creatinine is reduced, leading to elevated blood creatine levels and decreased creatinine levels. As a result, a large amount of creatine is excreted in urine while creatinine excretion decreases. In patients with dermatomyositis, the 24-hour urinary creatine excretion can even reach as high as 2 g.
(3) Serum sarcoplasmic enzyme determination: Serum creatine phosphokinase (CPK), aldolase, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase levels are elevated, especially CPK. The increase in serum enzymes often parallels the progression and regression of muscle lesions in this disease, reflecting disease activity. Generally, levels decrease 3–4 weeks before muscle strength improves and increase 5–6 weeks before clinical relapse, serving as a predictor of disease deterioration. When a patient's CPK value is elevated, the CKMM1: CKMM <30% and CKMM1: >1 indicate severe PM. Untreated active myositis patients typically show abnormalities, but this enzyme is not specific to muscles. The liver contains a significant amount of aldolase, which can also increase in liver disease. Carbonic anhydrase III is an isoenzyme unique to skeletal muscle and may increase during skeletal muscle injury.
(4) Electromyographic changes: These show myogenic atrophy, commonly including loss of vitality, fibrillation, and denervation phenomena in affected muscles, presenting as irregular, involuntary discharge waveforms. Not all muscle fibers are equally affected, with many normal fibers scattered among them. With mild exertion, short-duration polyphasic motor units appear, while maximal exertion shows low-voltage interference with increased polyphasic waves.
(5) Histological changes
1. Muscle changes: Muscles are extensively or partially affected. In the initial stage, muscle fibers show swelling, loss of striations, hyalinization of sarcoplasm, increased nuclear membrane cells, separation, and fragmentation. In progressive disease, muscle fibers may undergo hyaline, granular, or vacuolar degeneration, sometimes even necrosis, or complete replacement of muscle structure by connective tissue. Calcification may be observed, along with interstitial inflammatory changes, vascular dilation, intimal thickening, luminal narrowing, or even thrombosis. Perivascular infiltration by lymphocytes, plasma cells, and histiocytes occurs, primarily in striated muscles, though some cases may involve smooth or cardiac muscles with similar lesions.
Some scholars consider the most characteristic pathological change in DM to be perifascicular atrophy, where muscle fiber atrophy and injury are concentrated around muscle bundles. Cross-sections often show significantly reduced fiber diameters at the edges of the bundles. Some attribute this to DM lesions being largely confined to the epimysium, with fibrous thickening causing atrophy of fibers surrounding the bundle edges. Others suggest perifascicular atrophy results from chronic ischemia due to vascular injury interrupting blood supply to peripheral muscle bundles.
2. Skin changes: In the initial edematous erythema stage, epidermal keratinization, atrophy of the spinous layer, loss of rete ridges, liquefaction degeneration of basal cells, and full-thickness dermal mucinous edema are observed. Vascular dilation is accompanied by predominantly perivascular lymphocyte infiltration, with some histiocytes and pigment incontinence. In progressive disease, collagen fibers swell, homogenize, and sclerose, vessel walls thicken, subcutaneous fat undergoes mucoid degeneration, calcification occurs, and the epidermis further atrophies, along with skin appendages.
(6) Others: Myoglobin is present in skeletal and cardiac muscles. Normally, only small amounts are found in blood and urine. Severe muscle injury releases large amounts of myoglobin, making serum myoglobin a marker for disease activity. Visible hemoglobin-like pigment in urine increases with worsening conditions and decreases during remission. Some reports note increased urinary 3-methylhistidine excretion as a marker of muscle injury, though it lacks specificity.
Based on the patient's symmetrical proximal muscle weakness, pain, and tenderness, along with characteristic skin lesions such as periorbital purplish-red edematous patches, Gottron's sign, and rigid dilated capillary erythema at the nail fold, the diagnosis is generally straightforward. Combined with elevated serum muscle enzymes (CPK, LDH, AST, ALT, and aldolase), increased 24-hour urinary creatine excretion, and, when necessary, electromyographic changes and muscle biopsy, the disease can be confirmed.
bubble_chart Treatment Measures
In cases without tumor complications, corticosteroid therapy is effective. The usual adult dose is equivalent to prednisone 60–100 mg/d, approximately 1 mg/(kg·d). For severe cases or if the initial dose is ineffective, it can be increased to 1.5 mg/(kg·d). The dose for children is typically higher than that for adults, at 1.5 mg/(kg·d). For mild symptoms, a smaller dose may be used. Clinical symptoms, urinary creatine excretion, and serum myoplasmic enzyme levels serve as reference indicators for adjusting corticosteroid doses. Generally, muscle strength recovery lags behind improvements in myoplasmic enzymes and urinary creatine excretion by several weeks. In recent years, high-dose methylprednisolone pulse therapy (intravenous infusion of 1 g for 3 consecutive days, followed by prednisone 600 mg/d) has been used for severe cases. Approximately one-third of cases show poor response to corticosteroid therapy. Immunosuppressants, particularly methotrexate administered intravenously in combination with corticosteroids, have shown some efficacy in improving muscle strength. Cyclophosphamide and azathioprine may also be used. Other adjunctive treatments include nonsteroidal anti-inflammatory drugs, anabolic steroids such as nandrolone phenylpropionate, antimalarial drugs (e.g., chloroquine), and vitamin E. For severe cases, intravenous supplementation with compound amino acid injections, adenosine triphosphate (ATP), coenzyme A, and energy mixtures may be administered. Recently, cyclosporine and plasma dialysis have also shown some effectiveness. Additionally, physical therapy is recommended: passive exercises to prevent contractures during the acute phase of severe inflammation, performed twice daily, with active exercises discouraged; during the convalescence stage, slow active exercises are encouraged. Other therapies such as tuina, hydrotherapy, and diathermy may be employed as appropriate to prevent muscle atrophy and contractures. Rehabilitation training is provided for patients with functional loss.
In adults, particularly those aged 40–50 or older, a thorough examination for concurrent tumors is essential. If a tumor is detected, definitive treatment should be administered, which may improve or alleviate dermatomyositis symptoms. If no tumor is found initially, regular follow-up every 3–6 months is necessary.
For pediatric dermatomyositis patients, all suspected foci of infection should be eliminated, and antibiotic therapy combined with corticosteroids can yield favorable results.
The disease course is mostly chronic and progressive in the majority of cases, trending toward gradual recovery over 2–3 years, with only a minority resulting in death. Therefore, among the few cases presenting acutely with marked {|###|}lack of strength{|###|}, the prognosis is often poor, with death frequently due to concurrent infections. Another small subset of cases exhibits recurrent episodes, alternating between exacerbation and remission, ultimately achieving relief.
The incidence of concurrent tumors varies from 9% to 52%, generally occurring after the age of 40. The older the age of onset, the higher the likelihood of associated tumors. Reports indicate that among male patients over 50 years old, the incidence can be as high as 71%. Schuerman reviewed 344 cases in the literature, finding 12% with concomitant malignancies, while William reported 15% and Gallen 24%. The incidence of malignancies in dermatomyositis patients far exceeds that in polymyositis patients. Some suggest this may be related to the use of immunosuppressants in dermatomyositis patients. Among the 135 cases reported by the authors, 12 (8.89%) had concurrent tumors, with dermatomyositis typically preceding tumor development. The most common tumor sites, in order, are the stomach, ovary, {|###|}uterus{|###|}, gallbladder, nasopharynx, lung, esophagus, and others.
This disease needs to be differentiated from the following conditions:
(1) Systemic lupus erythematosus (SLE) The skin lesions are distinguished by edematous butterfly-shaped erythema on the malar region, dark erythema on the extensor surfaces of the finger (toe) joints, periorbital edematous purplish erythema, purplish erythema on the extensor surfaces of the interphalangeal and metacarpophalangeal (metatarsophalangeal) joints, and stiff capillary dilation erythema at the nail fold. In SLE, multi-system involvement primarily affects the kidneys, whereas dermatomyositis mainly involves the proximal limb muscles, with hoarseness and dysphagia also being common. Additionally, serum myoplasmic enzyme levels and urinary creatine excretion are significantly elevated in dermatomyositis patients. If necessary, electromyography and muscle biopsy can aid in differentiation.
(2) Systemic scleroderma Late-stage (third-stage) dermatomyositis lesions, such as skin sclerosis, subcutaneous calcification, and histologically observed connective tissue swelling, sclerosis, and adjacent skin atrophy, may resemble systemic scleroderma. However, in the initial stage (first stage) of systemic scleroderma, Raynaud's phenomenon and swelling of the face and extremities followed by sclerosis and atrophy are characteristic. In terms of muscle involvement, dermatomyositis shows significant changes in the initial stage (first stage), presenting as substantial myositis, whereas in systemic scleroderma, muscle lesions typically appear in the advanced stage and are interstitial myositis, which can help differentiate the two.
(3) Polymyalgia rheumatica This condition usually occurs in individuals over 40 years old, with diffuse pain more commonly affecting the proximal upper limbs than the lower limbs, accompanied by generalized weakness. Patients cannot pinpoint whether the pain originates from muscles or joints. There is no muscle weakness, though grade I atrophy may occur due to disuse. Serum CPK levels are normal, and electromyography shows either normal results or grade I pathological changes.
(4) Eosinophilic myositis This condition is characterized by subacute onset of myalgia and proximal muscle weakness. Serum myoplasmic enzymes may be elevated, electromyography reveals myopathic changes, and muscle biopsy shows myositis with eosinophilic inflammatory infiltration, sometimes presenting as focal changes. It is considered a subtype within the spectrum of hypereosinophilic syndrome.
