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 levels of serum muscle enzymes in laboratory tests, especially creatine kinase, myogenic damage in electromyography, and histopathology suggesting varying degrees of muscle inflammation and necrosis.
I. Epidemiology
Polymyositis and dermatomyositis are global diseases, and the incidence varies among reports, but is generally considered to be between 0.5 and 8/100,000. Polymyositis and dermatomyositis can occur at any age and are about twice as common in women as in men.
II. Etiology
The etiology of this disease is still unknown, and is currently believed to be a group of autoimmune diseases induced by immune-mediated, infectious and non-infectious environmental factors in certain genetically susceptible individuals: 1.
1, genetic factors: It was found that HLA-BDR3, DR6, DRW52 are more frequent in patients with polymyositis than in the control population, so the susceptibility of patients may be HLA-based, and susceptible individuals develop myositis lesions under the action of certain factors.
2. Infection factors: polymyositis/dermatomyositis may be a chronic inflammatory process resulting from an autoimmune response induced by certain viral infections. The viruses in question include influenza virus, coxsackievirus, poliovirus and retrovirus. In addition, certain bacterial and parasitic infections are also associated with the development of myositis.
3, immune factors: most patients with polymyositis / dermatomyositis can be detected in the serum autoantibodies, including anti-nuclear antibodies, anti-Jo-1 antibodies, anti-RNP antibodies 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.
III. 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 abnormalities of cellular and humoral immunity play a role in the disease:.
1. Abnormal cellular immunity: Inflammatory cell infiltrates, mostly lymphocytes and macrophages, are seen in muscle biopsy tissues 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.
2. 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.
IV. 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 myasthenia. 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 lymphocytes and other inflammatory cells 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-section.
V. Clinical manifestations
The disease starts insidiously, mostly develops slowly, and the systemic manifestations include moderate or low fever, malaise, lethargy and weight loss.
1, myositis: myopathy is one of the important clinical manifestations of the disease, and typical patients show symmetrical muscle weakness of the proximal muscles of the upper and lower extremities that gradually worsen.
2. Skin lesions: Skin lesions may appear before or after, or simultaneously with, muscle lesions, and skin lesions are often the first symptom in patients with dermatomyositis. Skin rashes include.
(1) Gottron’s sign: It presents as a purplish-red maculopapular rash on the extensor side of the metacarpophalangeal and proximal phalangeal joints and elbow joints, with a flattened top surface and some scaling, and may develop skin atrophy and hypopigmentation over time.
(2) Purple erythema toward the sun: a dark purple-red edematous rash appearing on the upper eyelids and around the orbits bilaterally, which is a characteristic rash of dermatomyositis.
(3) Cutaneous heterochromatosis: a diffuse dark purple maculopapular rash appearing on exposed areas such as the back of the shoulder, anterior neck, and V-zone of the anterior chest. The skin may show local atrophy 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, and ulcers and sinus tracts may appear on the skin of the calcified surface.
(6) Other: Patients with dermatomyositis may also develop nail degeneration, finger ulcers and Raynaud’s phenomenon, etc.
(3) Arthropathy: Some patients with polymyositis/dermatomyositis may develop arthralgia or arthritis, with proximal interphalangeal joints, metacarpophalangeal joints and wrist joints being most commonly involved.
4. Pulmonary changes: Pulmonary lesions in patients with polymyositis/dermatomyositis are mainly manifested as interstitial lung lesions, aspiration pneumonia and pleurisy. Patients may develop cough, coughing sputum and dyspnea.
5. 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 ECG and echocardiogram.
6. Digestive system 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.
7, renal changes: the disease rarely involves the kidneys, individual may appear focal proliferative glomerulonephritis, but most of the kidney function is normal.
8, other: 10-30% of patients with malignant tumors, the common ones are stomach cancer, lung cancer and breast cancer. In addition, myositis can be significantly relieved after removal of the tumor.
VI. Laboratory tests and auxiliary examinations.
1.Laboratory tests.
(1) serum muscle enzymes: serum muscle enzyme profile is the most commonly used test for this disease, simple and reliable, including creatine kinase (CK), lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), etc., the high or low 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. 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, 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-recognitionparticle) antibodies: SRP is a ribonucleoprotein complex, anti-SRP antibodies and anti-synthetase of aminyl tRNA Anti-SRP antibodies are the same as anti-cytoplasmic protein autoantibodies, but the antigens are different. Patients with positive anti-SRP antibodies are more common in males and are characterized by an acute onset, heavy myositis, severe myocardial damage, poor response to glucocorticoids, and 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.
2, electromyography.
It is one of the diagnostic tools of the disease. 90% of polymyositis/dermatomyositis show changes of myogenic injury in EMG
About 2/3 of patients show pathological changes typical of myositis, and the other 1/3 show atypical changes on muscle biopsy, or even normal. The basic pathological changes in polymyositis/dermatomyositis are inflammatory cell infiltration, myofiber degeneration and/or necrosis, myocyte regeneration, fibrosis, and myasthenia. 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 muscle fibers is another pathological feature of the disease.
VII. Diagnosis
The diagnostic criteria proposed by Bohan and Peter in 1975 are still used for polymyositis/dermatomyositis. 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.Serum muscle enzyme profile is elevated.
4.Electromyography shows the following myogenic damage
5.Skin changes: including Gottron’s sign, purplish erythema to the positive, rash in exposed areas, etc.
The diagnosis of polymyositis can be confirmed for all those with 1 to 4.
VIII. Differential diagnosis
A typical patient with polymyositis/dermatomyositis has 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.
1. 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.
2. Systemic lupus erythematosus.
SLE mostly occurs in young women, with fever, rash, arthritis and impaired renal function as the main manifestations. Laboratory tests can 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 obvious abnormalities.
3. myasthenia gravis.
Myasthenia gravis is a chronic disease caused by transmission disorder of neuromuscular junction, mainly manifested by the 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 muscle enzyme profile, electromyography and muscle biopsy have no significant abnormalities.
4, other: hypokalemia, hypomagnesemia, hyperthyroidism, certain bacterial and viral infections, certain drug toxic reactions, etc. can also cause myositis-like symptoms.
IX. Treatment
1.General treatment: Patients should rest in bed during the active period of the disease, and appropriate activities can be carried out during the recovery period, but should avoid excessive fatigue.
2.Medication
X. 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.