Polymyositis and dermatomyositis PM/DM are autoimmune inflammatory myopathies, a group of connective tissue diseases with chronic, nonsuppurative inflammatory lesions of the transverse muscle or with characteristic skin changes. The main clinical manifestations are symmetrical muscle weakness of the extremities, increased serum myokinase levels in laboratory tests, especially a marked increase in creatine kinase, myogenic damage in electromyography, and histopathology suggesting varying degrees of muscle inflammation and necrosis.
[Epidemiology]
Polymyositis and dermatomyositis are global diseases, with incidence rates varying, generally thought to be between 0.5 and 8 per 100,000. Polymyositis and dermatomyositis can occur at any age and are approximately twice as common in women as in men.
[Etiology]
The etiology of this disease is still unknown, and it is currently thought to be a group of autoimmune diseases induced by immune-mediated, infectious and non-infectious environmental factors in certain genetically susceptible individuals.
(i) Genetic factors: HLA-BDR3, DR6, and DRW52 were found to occur more frequently in patients with polymyositis than in the control population, so the susceptibility of patients may be HLA-based, and myositis lesions occur in susceptible individuals under the influence of certain factors.
(ii) Infectious factors: polymyositis/dermatomyositis may be a chronic inflammatory process resulting from an autoimmune response induced after certain viral infections. The viruses involved include influenza virus, coxsackievirus, poliovirus, and retrovirus. In addition, certain bacterial and parasitic infections are also associated with the development of myositis.
(iii) Immunological factors: Most patients with polymyositis/dermatomyositis have detectable autoantibodies in the serum, including anti-nuclear, anti-Jo-1, anti-RNP and anti-PM-Scl antibodies. In addition, immunoglobulin and complement deposits are seen in the muscle and skin vessel walls of patients with polymyositis/dermatomyositis, suggesting that immune factors are involved in the development of polymyositis/dermatomyositis.
[Pathogenesis]
Polymyositis/dermatomyositis is caused by a combination of genetic and environmental factors that lead to changes in the antigenic nature of the transverse muscle tissue or abnormalities in the body’s own immune function, resulting in muscle tissue damage. Both cellular and humoral immune abnormalities play a role in this disease.
(a) Abnormal cellular immunity: Inflammatory cell infiltrates, mostly lymphocytes and macrophages, are seen in muscle biopsies of patients with polymyositis/dermatomyositis. A large number of T-lymphocytes and macrophages are seen in the myocytes and subendothelium of polymyositis; a large number of B-lymphocytes infiltrate around the subcutaneous vessels in patients with dermatomyositis. The above indicates that cellular immunity plays an important role in this disease.
(b) Abnormal humoral immunity: multiple autoantibodies are present in the serum of patients with polymyositis/dermatomyositis, and immunoglobulins are elevated in the serum of patients, and immunoglobulin deposits are seen in the endomysium and myofascicular membrane. These phenomena suggest that humoral immunity also plays an important role in this disease.
[Pathology]
The basic pathological changes of polymyositis/dermatomyositis are T- and B-lymphocyte infiltration, myofibrillar heterogeneity, focal distribution of myofibrillar degeneration and/or necrosis, myocyte regeneration, fibrosis, and muscle atrophy. The cutaneous lesions are predominantly perivascular inflammation with inflammatory cell infiltration in both the skin and subcutaneous tissue. Early pathological changes in classic myositis are swelling of myofibers, loss of transverse lines, hyalinization of the sarcoplasm, increased nucleation of myofibrillar cells, and infiltration of inflammatory cells (lymphocytes, macrophages, plasma cells). In the late stage of the disease, the muscle fibers are separated and broken, and then they become glassy, granular or vacuolated, necrotic, or the muscle structure disappears completely and is replaced by fibrous tissue. The most striking pathological feature of the muscle in patients with dermatomyositis is the infiltration of inflammatory cells such as lymphocytes around the blood vessels between the muscle bundles and the damage and atrophy of the muscle fibers concentrated around the muscle bundles, which are significantly smaller in diameter at the edge of the muscle bundles as seen in cross-sections.
[Clinical manifestations]
The disease has an insidious onset and mostly develops slowly, with systemic manifestations of moderate or low-grade fever, malaise, lethargy, and weight loss.
(a) Myositis: myopathy is one of the important clinical manifestations of the disease, and typical patients show symmetrical muscle weakness with gradual increase in the proximal muscles of the upper and lower extremities. Myasthenia gravis mostly starts from the pelvic girdle and lower limb muscle groups, such as difficulty in going upstairs, difficulty in standing after squatting, slow gait, and swaying instability. When the upper extremities are involved, there is a decrease in grip strength, difficulty in raising the arms and difficulty in combing the hair. If the cervical muscles are involved, the patient’s head cannot be lifted off the pillow when lying down, and in severe cases, the patient cannot turn over, and the head cannot be held upright when sitting or standing. If the pharyngeal and esophageal muscles are involved, the patient may have hoarseness, slurred pronunciation and difficulty in swallowing. The measurement of muscle strength can help to determine the degree and extent of muscle damage, and can be used as an important clinical indicator to observe the disease development and treatment effect. Muscle strength is generally classified into 6 levels. level 0: complete paralysis; level 1: muscle contraction can be present but cannot produce mobile movements; level 2: limb can move in the plane but cannot be lifted over gravity; level 3: limb can be lifted off the plane but cannot resist resistance; level 4: limb can resist resistance but muscle strength is weak; level 5: normal muscle strength.
(ii) Skin lesions: Skin lesions may appear before or after muscle lesions or simultaneously with muscle lesions, and skin lesions are often the first symptom in patients with dermatomyositis. The rash includes: 1. Gottron’s sign: a purple-red maculopapular rash appearing on the extensor side of the metacarpophalangeal joint, proximal phalangeal joint and elbow joint, flattened on the top surface, partially scaly, and after a long time, skin atrophy and hypopigmentation may occur. 2. The skin may be locally atrophic with capillary dilation, hyperpigmentation or hypopigmentation. 4. Mechanic’s hand: The skin on the lateral and palmar surfaces of the patient’s hands appears keratinized, cracked and desquamated, resembling hands that have been operated with oil for a long time. 5. Calcification: A few patients may have subcutaneous calcified spots or calcified plaques on the shoulders, elbows, thighs, knees and spine. The skin on the surface of the calcification may appear as ulcers and sinus tracts.6. Other: Patients with dermatomyositis may also develop nail degeneration, fingertip ulcers and Raynaud’s phenomenon.
（Some patients with polymyositis/dermatomyositis may develop arthralgia or arthritis, with proximal interphalangeal joints, metacarpophalangeal joints and wrist joints being the most commonly involved, with occasional joint deformities, but no destruction of bone and joint on X-ray.
(iv) Pulmonary changes: Pulmonary lesions in patients with polymyositis/dermatomyositis are mainly manifested as interstitial lung lesions, aspiration pneumonia and pleurisy. Patients may present with cough, sputum and dyspnea.
(v) Cardiovascular system changes: Some patients may present with palpitations, precordial discomfort and dyspnea. ST-T changes, arrhythmias, mitral valve prolapse and pericardial effusion can be seen on electrocardiogram and echocardiogram.
(vi) Digestive changes: Patients with polymyositis/dermatomyositis may have dysphagia and esophageal reflux due to involvement of esophageal and pharyngeal muscles, and a few patients may develop peptic ulcers.
(vii) Renal changes: The disease rarely involves the kidneys, and focal proliferative glomerulonephritis may occur in some patients, but most have normal renal function.
(H) Other: 10-30% of patients have malignant tumors, such as gastric cancer, lung cancer and breast cancer. In addition, myositis can be significantly relieved after removal of the tumor.
[Laboratory tests and auxiliary examinations]
(I) Laboratory tests
1
Serum muscle enzymes: serum muscle enzyme profile is the most commonly used test for this disease, which is simple and reliable, including creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), etc. The level of muscle enzyme activity is related to the severity of the disease, and can be used as a basis for diagnosing the disease and judging the efficacy of treatment. Creatine kinase is the most sensitive of the above-mentioned enzymes.
2
Autoantibodies: About 20-30% of patients with this disease are positive for antinuclear antibodies, of which the spotted type is the most common. In recent years, a group of antibodies specific for myositis have been identified, including 1) anti-Aminoyl tRNA synthetase antibodies (anti-Jo-1, EJ, PL-12, PL-7 antibodies): among them, anti-Jo-1 antibodies are specific for myositis, with a positivity rate of about 20-50%. These antibodies highlight interstitial lung fibrosis and are often accompanied by symptoms such as polyarthritis, Raynaud’s phenomenon and mechanic’s hand, called anti-synthetase syndrome or anti-Jo-1 syndrome. 2) Anti-SRP (signal-recognition
(2) Anti-SRP (signal-recognition particle) antibodies: SRP is a ribonucleoprotein complex. Anti-SRP antibodies are the same as anti-synthetase antibodies, but the antigens are different. Patients with positive anti-SRP antibodies are more common in males and are characterized clinically by an acute onset, heavy myositis, heavy myocardial damage, poor response to glucocorticoids, and a poor prognosis. Although this antibody is more specific for polymyositis, the rate of positivity is low (4%). 3) Anti-Mi-2 antibody: It is a specific antibody for dermatomyositis, with a positivity rate of about 21%. 95% of those positive for this antibody can see a rash, but interstitial lung lesions are rare and the prognosis is better.
(b) Electromyography: It is one of the diagnostic tools for this disease. 90% of polymyositis/dermatomyositis show myogenic injury changes in electromyography, which are characterized by 1) low amplitude, short-range polyphasic waves; 2) enhanced insertional (electrode) provocation, manifested as positive sharp waves, spontaneous fibrillation waves; 3) spontaneous, disorganized, high-frequency discharges.
(c) Skin and muscle biopsy: about 2/3 of patients showed pathological changes typical of myositis, and the other 1/3 showed atypical changes or even normal muscle biopsy. The basic pathological changes of polymyositis/dermatomyositis are inflammatory cell infiltration, muscle fiber degeneration and/or necrosis, myocyte regeneration, fibrosis, and muscle atrophy. The cutaneous lesions are mainly perivascular inflammation with inflammatory cell infiltration in both the skin and subcutaneous tissue. In addition, the muscle changes are often focally distributed, and the uneven thickness of the muscle fibers is another pathological feature of the disease.
[Diagnosis]
Polymyositis/dermatomyositis is still diagnosed using the diagnostic criteria proposed by Bohan and Peter in 1975. They are as follows.
1, Symmetrical, progressive proximal muscle weakness.
2. muscle biopsy shows necrotic, regenerative, and inflammatory changes in the muscle, which may be accompanied by atrophy of the muscle fascia.
3. Elevated serum muscle enzyme profile.
4. EMG shows the following myogenic damage: 1) low amplitude, short time frame, polyphasic waves of motor unit potentials; 2) increased fibrillation, positive sharp waves and insertional activity; 3) spontaneous high frequency discharges.
5, skin changes: including Gottron’s sign, to the positive purple erythema, exposed areas of the rash.
Anyone with 1 to 4 can be diagnosed with polymyositis, and 3 of 1-4 with rash can be diagnosed with dermatomyositis.
[Differential diagnosis]
Typical patients with polymyositis/dermatomyositis have evidence of symmetric proximal muscle weakness, elevated muscle enzymes, electromyography suggestive of myogenic damage, and muscle biopsy, so the diagnosis is not difficult, but those with atypical symptoms need to be differentiated from other diseases.
Diseases that need to be differentiated from polymyositis/dermatomyositis.
(i) Rheumatic polymyalgia.
Rheumatic polymyalgia mostly occurs in elderly people over 50 years old, mainly manifesting as pain in the proximal muscle groups such as scapular girdle and pelvic girdle or trunk area, which may be accompanied by morning stiffness and joint pain. Laboratory tests may show rapid blood sedimentation and elevated C-reactive protein. Unlike polymyositis/dermatomyositis, the patient’s muscle enzyme profile and electromyography are normal, and muscle biopsy shows normal muscle fibers.
(ii) Systemic lupus erythematosus.
SLE mostly occurs in young women, with fever, rash, arthritis and impaired renal function as the main manifestations. Laboratory tests may show a variety of autoantibodies, especially anti-Sm antibodies and anti-dsDNA antibodies are important for diagnosis. The rash of SLE is mostly symmetrical butterfly erythema on the face, which is obviously different from the rash of dermatomyositis. In addition, the muscle enzyme spectrum, electromyography and muscle biopsy of SLE patients are mostly without significant abnormalities.
(iii) Myasthenia gravis.
Myasthenia gravis is a chronic disease caused by impaired transmission of neuromuscular junction, mainly manifested by extremely easy fatigue of the involved skeletal muscles, aggravated by activity, partially recovered after rest, and effective with anticholinesterase drug treatment. The disease is most commonly associated with extraocular muscle involvement, manifested by ptosis, diplopia and strabismus. Serological examination shows increased anti-acetylcholine receptor antibodies, while myoenzymatic spectrum, electromyography and muscle biopsy have no significant abnormalities.
(iv) Other: hypokalemia, hypomagnesemia, hyperthyroidism, certain bacterial and viral infections, and toxic reactions to certain drugs may also cause myositis-like symptoms.
[Treatment]
(a) General treatment: Patients should rest in bed during the active period of the disease, and appropriate activities can be performed during the recovery period, but excessive fatigue should be avoided.
(ii) Drug therapy.
1 Glucocorticoid: Glucocorticoid is the drug of choice for the treatment of polymyositis/dermatomyositis, and prednisone is the most widely used. The starting dose of prednisone is 1~1.5mg/kg/day, which can be gradually reduced according to the improvement of the disease and the improvement of the muscle enzyme profile. prednisone should be reduced slowly, and generally the amount of reduction should not be more than 10mg per month. in addition, the treatment time should be long, often more than 1 year. Immunosuppressants should be added in patients with severe disease or those who do not respond well to glucocorticoid therapy.
2 Immunosuppressants: Immunosuppressant therapy can be considered in the following cases: (1) poor response to glucocorticoid therapy; (2) contraindications to hormones; (3) glucocorticoid therapy is effective, but serious adverse reactions occur or relapse after drug reduction. The combination of immunosuppressants and glucocorticosteroids can provide rapid relief of clinical symptoms, reduce the dosage of hormones and reduce complications. Commonly used immunosuppressive agents include methotrexate, cyclophosphamide and azathioprine.
3 Other treatments: Some patients have been treated with antimalarial drugs, cyclosporine A, immunoglobulin intravenous shock, plasma exchange, etc., all of which have achieved certain efficacy.
[Prognosis]
With the correct application of glucocorticoids and immunosuppressants, the prognosis of polymyositis/dermatomyositis has been significantly improved, with a 5-year survival rate of more than 80%. The most common causes of death in this disease are cardiopulmonary involvement and secondary infections.