mixed connective tissue disease
Introduction
Introduction to mixed connective tissue disease Mixed connective tissue disease (MCTD) is a type of overlap syndrome found in recent years, which has similar performance to other collagen diseases such as systemic lupus erythematosus, dermatomyositis and systemic sclerosis, but with three Any one of them is not completely consistent and cannot be attributed to any symptom of collagen disease. Therefore, it is called mixed connective tissue disease. This disease has little clinical manifestation of kidney damage, but it has high titer in immunological serum. Anti-RNP antibodies, and hormone therapy is effective. basic knowledge The proportion of the disease: the female incidence rate is about 0.5%, and the male incidence rate is about 0.001%. Susceptible people: no specific population Mode of infection: non-infectious Complications: chronic lymphocytic thyroiditis
Cause
The cause of mixed connective tissue disease
(1) Causes of the disease
The etiology of this disease is still inconclusive. In view of the combination of systemic lupus erythematosus, dermatomyositis and systemic sclerosis, it is an independent disease or a different subtype of the same disease. Controversy, but generally speaking, it is recognized by autoimmune theory that it may be based on the disorder of genetic immune regulation, and the autoantibodies appear on the components of damage, degradation and mutation of the own tissue, thereby causing immunopathological processes. :1 This disease and autoimmune diseases in systemic lupus erythematosus, dermatomyositis and systemic sclerosis have a lot of common performance, 2 measured sensitive and specific high titer anti-RNP antibody, Ig deposition at the basement membrane of the epidermis, Immunofluorescence has a spot-type antinuclear antibody similar to systemic lupus erythematosus. 3 anti-nuclear antibodies are almost all positive, and other serum antibodies such as rheumatoid factor and anti-nuclear factor are also partially positive. 4 is representative of autoimmune disease. In patients with renal disease of systemic lupus erythematosus, some patients can detect anti-RNP antibodies.
(two) pathogenesis
The main mechanism of the pathogenesis of this disease is as follows:
1. Genetic family analysis showed that all patients with human leukocyte antigen-B8 (HLA-B8) were prone to mixed collagen disease, and their inhibitory T lymphocytes (T8 cells) were inferior. Some people think that B8 may be an immune response. In the control of the disorder, the inhibitory T lymphocytes are related to the control of immune response genes. When the T lymphocyte function is low, the immune response genes are out of control, resulting in immune disorders in vivo (humoral immunity and cellular immune disorders), when inhibitory T When lymphocyte function is low, it can cause humoral immunity, cellular immunity is low, and T8 cells can also inhibit autoimmune reactivity. Once its function is deficient, it can produce autoantigen antibody reaction, form immune complex, and form antigen excess. Soluble immune complexes, in turn, can reach other organs of the body along with blood circulation, where they precipitate and cause tissue damage.
2. Virus infection
The mechanism by which viral infection causes autoimmune dysfunction may have the following three aspects:
(1) The cytotoxic effect of virus-infected T cells is enhanced, resulting in destruction of tissue cells.
(2) The T cell function of the virus infection is inhibited, resulting in enhanced B cell production of antibodies.
(3) host endogenous infection or endogenous viral products, through the homologization of the virus to the HLA-B8 positive host, the virus can be planted on the surface of white blood cells, thus the emergence of anti-viral and anti-viral infection cell reactions, these The reaction includes cellular immune response and humoral immune response. The virus can change the tissue components to produce autoantigenicity, stimulate the B cells to produce corresponding antibodies, react with antigens and antibodies, form immune complexes, cause tissue damage, and the cells infected by the virus are Under the action of cytotoxicity, the fragments are released, which can cause the body to undergo self-sensitization, thus producing anti-cell component antibodies. In addition, the virus stimulates lymphocytes to produce neutralizing factors and promote autoimmunity.
3. Anti-lymphocyte antibodies
It has been found that patients with mixed connective tissue disease have an anti-lymphatic antibody (anti-lymphocyte antibody) in the serum. This antibody is essentially IgM and has a destructive effect on surrounding T and B cells. Its activity and peripheral blood leukocytes and lymphocytes count. In inverse proportion, its activity increased during the active period of the disease, and decreased during the remission period. The positive rate of skin, nerve and esophageal symptoms was high, but it was not related to kidney changes and joint symptoms.
4. Pathology
(1) skin microscopic examination showed hyperkeratosis of the epidermis, epithelial atrophy; edema and hyperplasia of collagen fibers in the dermis; degeneration and necrosis of subcutaneous adipose tissue; thickening of the small vessel wall of the subcutaneous tissue, hyperplasia of the intima, swelling, with varying degrees of Inflammatory infiltration, perivascular fibrous tissue hyperplasia, hyaline degeneration.
(2) Muscle microscopy has degeneration, striated muscle transverse stripes are unclear, the pathological features of this disease are both systemic lupus erythematosus, dermatomyositis and systemic sclerosis, and there are differences, such as different degrees of muscle The inflammatory changes are different from systemic sclerosis; the blood vessels are generally inflammatory, no fibrin-like degeneration, and different from systemic lupus erythematosus.
5. Chinese medicine etiology and pathogenesis
(1) Cause: The cause of this disease is not only internal or external.
Internal factors are less responsible for the lack of congenital endowment, yin and yang, qi and blood deficiency or imbalance, causing visceral dysfunction in the long-term, often caused by exogenous evils, or by the acquired diet, such as eating spicy and sweet, and getting wet, raw Heat, oysters; or gluttony cold, hurt spleen yang; or by excessive fatigue, dystrophy after illness; or internal injury, damage to organs, air, etc., can lead to imbalance in the body environment and become the disease The basics.
1 Innate deficiency: Insufficient congenital talent, yin and yang disorders, partial kidney yin deficiency, it is yin deficiency internal heat, external evils take advantage of the virtual, "evil people in the yin is sputum", sputum first in the yin, yin Virtual basis, blood deficiency has fire, long-term yin and blood loss, yin and yang, qi and yin deficiency, when the external sense is induced, the depth of the disease is yin and yang.
2 Kidney yang dysfunction: spleen kidney yang dysfunction, yin and cold condensate, re-sensation of external evils, the course of disease is prolonged for a long time, the evils of phlegm and collaterals can be internalized in the organs, causing visceral dysfunction, Yuanyang deficiency Insufficient true yin, qi and blood deficiency, multiple parts of the body and organs damage, and even life-threatening.
The external cause is mostly caused by external sensation, or the skin is retained, the joint is blocked, or the internal organs are invaded.
Six kinky feelings: the body is not enough blood, the outside is not solid, the ignorance is not dense, the evil of the wind and cold is taken by the virtual attack, condensed in the skin, blocked in the meridian, causing the loss of the battalion, qi and blood stasis, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , Wind, cold, heat, wet, dry, fire, external damage to the skin, internal energy damage and blood stasis.
(2) Pathogenesis:
1 Physique and onset: This disease occurs mostly in women, females are feminine bodies, spleen yin and yang deficiency, external evils into the cold, can damage the spleen and kidney, water is not wet, so visible limb swelling; Yang deficiency blood supply can not be promoted, one can block the joint muscle and bone pain in the choroid, the second can stay in the skin, sputum, ecchymosis; spleen yang deficiency, Zhongzhou lost, can have limb muscle pain, fatigue, female Another characteristic of the disease is emotional factors, sorrowful anger, dark consumption of yin and blood, and heat for a long time, so there may be symptoms of yin deficiency and heat generation, such as long-term fever, dry mouth and nose, skin Spotted rashes, etc.
In addition, congenital endowment and acquired adjustment are important factors influencing the constitution. Sometimes it can cause the conversion of yin and yang in the body, and increase the complexity of disease manifestation.
2 invading the viscera, the change of the disease is often manifested as kidney yin and yang imbalance, with the development of the disease, can affect the various organs and produce a variety of pathological products, injury to the spleen and stomach can be seen bloating, poor appetite, constipation; injured lung Chest tightness, suffocation, difficulty in breathing can occur; those who are involved with the heart can be seen with convulsions, and even those with chest pain; those with liver can be seen with flank pain, phlegm and phlegm; the kidney damage is worse, urinary dysfunction, edema, etc. Smooth bloating, abdominal pain, cough, and asthma; gasification is unfavorable, when the fluid stops, it is phlegm, and in the veins, it can be phlegm.
3 blood stasis: due to illness, long-term qi and blood run poorly, and blood stasis is phlegm, wet coagulation is phlegm, phlegm and blood stasis Even dirty, blocked upper focus, heart and lung injury, asthma, chest tightness, chest pain, palpitations; resistance to the middle focus, spleen and stomach damage, transport and dereliction of duty, poor appetite, lack of blood, blood deficiency, heat, blood, blood not Excessive bleeding outside the veins, blood stasis, purple spot, rash or seeing hematuria; hindering the lower focus, liver and kidney damage, loss of essence, backache edema, ascites anemia; upper sputum is partial rickets, phlegm and blood stasis Joint pain can be seen in the joints, subcutaneous nodules can be seen under the skin, dysphagia can be seen in the pharynx, and symptoms can be seen in the chest flank, phlegm and stasis or endogenous, cohesive skin tendon, blood Kneeling, lost in support, the hand edema is a dachshund-like swelling, the skin of the fingertips is hard; the blood vessels are blocked, the yang is not up to the end, so the skin of the extremities is white or cyanosis; the muscles and joints of the meridian tendon joints are blocked. Soreness and weakness.
Prevention
Mixed connective tissue disease prevention
Primary prevention
(1) The cause of MCTD is related to the autoimmune dysfunction. Therefore, it is necessary to strengthen physical exercise, have a reasonable life law, and maintain a happy mood to improve the body's immune function.
(2) Strengthen nutrition and supplement vitamins.
(3) Pay attention to keep warm and avoid being affected by the cold.
2. Secondary prevention
(1) Early diagnosis: MCTD has no early diagnostic criteria, mainly relying on comprehensive diagnosis. Any clinically encountered polyarthritis or joint pain, Raynaud's phenomenon, muscle pain without fixed parts, inconspicuous finger swelling, varying degrees of anemia And the increase in erythrocyte sedimentation rate, the unexplained decline in lung function or the simultaneous atypical clinical features of systemic lupus erythematosus, polymyositis, systemic sclerosis or both, that is, the possibility of the disease should be considered. Anti-nuclear antibody (ANA) and anti-ribonucleoprotein antibody (RNP) tests are helpful for early diagnosis of MCTD.
(2) Early treatment: Because the disease has multiple systems, the characteristics of multiple organ damage, clinical manifestations, and the degree of lesions vary greatly, so the treatment plan must be based on the specific circumstances of each patient, emphasizing individualized treatment.
1 arthritis, rash, serositis, myositis, anemia, leukopenia, mild renal damage can be treated with small and medium doses of glucocorticoids.
2 Mild arthritis can be controlled by non-steroidal anti-inflammatory drugs such as ibuprofen or naproxen. For those with erosive arthritis without kidney involvement, it is advisable to apply gold preparation or penicillamine early.
3 skin damage can be treated with antimalarials and chloroquine.
4 Reynolds phenomenon using calcium antagonists such as nifedipine, diltiazem can reduce symptoms and reduce seizures.
5 patients with severe myositis, need to use a larger dose of glucocorticoids and need to maintain a longer time.
6MCTD's severe renal disease is an indication of the use of high-dose glucocorticoids, if necessary with an immunosuppressive agent such as cyclophosphamide.
7 TCM syndrome differentiation and treatment.
3. Three levels of prevention
(1) Adhere to regular treatment and avoid and reduce the side effects of hormones, immunosuppressive agents, and non-steroidal drugs.
(2) Adhere to functional exercise and enhance autoimmune function.
(3) Life should be regular, moderate work and rest, and appropriate rest when symptoms are significant.
(4) Pay attention to the warmth of the extremities, avoid pregnancy, overwork and severe mental stimulation.
Complication
Mixed connective tissue disease complications Complications Chronic lymphocytic thyroiditis
About one-third of patients have fever, and 6% to 7% of patients are associated with Sjogren's syndrome and chronic lymphatic thyroiditis, occasionally with generalized lymphadenopathy.
Symptom
Symptoms of mixed connective tissue disease Common symptoms Articular deformity Abdominal distension Abdominal pain Dull pain Breathing difficulty Powerless myalgia Pigment abnormality Leukopenia nodules
Typical clinical manifestations are Raynaud's phenomenon, polyarthritis or multiple joint pain, diffuse swelling of the hands and fingers or conical thinning of the fingers or appearance of the sausage, low esophageal motility and multiple myalgia, lung lesions The onset of this disease is very varied. Most of them have the Raynaud phenomenon as the earliest manifestation, but there are also muscle pain and tenderness accompanied by muscle weakness. Some patients have fever and polyarthritis as early complaints. The patients were characterized by erythematous skin lesions, fever, myocarditis, arrhythmia, and generalized lymphadenopathy (Figures 1, 2).
Systemic lupus erythematosus, dermatomyositis and systemic sclerosis, the performance of the three can exist at the same time, can also appear in separate months or years, with multiple organ involvement.
Joint performance
93% to 96% of patients have joint pain, and 2/3 of them have obvious arthritis. Most patients do not have joint deformity. Only a few patients have typical rheumatoid arthritis changes, and subcutaneous nodules appear.
2. Skin performance
Renault phenomenon is the most common, accounting for 84% to 87%, and often the initial or precursor symptoms of the disease, swollen fingers, accompanied by local skin tightening, thickening accounted for 47% to 88%, systemic lupus erythematosus Erythema, telangiectasia, finger atrophic erythematous spots, dermatomyositis-like orbital erythema, scattered non-scarring focal alopecia, and pigment abnormalities (hypopigmentation or increase).
3. Muscle performance
Muscle pain is most common in the lower back, scapula, and proximal extremities. Most patients have subjective pain and tenderness, but the degree of performance is different, often accompanied by muscle weakness. Some patients show subjective myalgia without tenderness. Sometimes muscle pain does not occur clinically, but muscle biopsy shows inflammatory myopathy changes, while serum muscle enzymes increase.
4. Digestive system performance
About 2/3 of the patients have low esophageal motor function, which is characterized by obstruction or dull pain behind the sternum when swallowing dry food, more obvious in the lying position, accompanied by esophagitis in the later stage, and different degrees of pain when swallowing food. Can have intestinal motility, low abdominal pain, abdominal distension and constipation alternately, some patients may have mild to moderate liver, splenomegaly.
5. Respiratory system performance
Lighter without respiratory symptoms, severe breathing difficulties after exercise, pulmonary hypertension, pleurisy, etc., physical examination can be heard and wet voice and dry voice.
6. Circulatory system performance
Cardiac involvement is rare, and most manifestations include pericarditis, myocarditis, whole heart disease, or valvular heart disease.
7. Urinary system performance
The literature reports that kidney involvement is rare (0% to 10%), although some lesions are mild, but some patients can die of progressive renal failure, some are persistent or intermittent proteinuria, mirror Lower hematuria, granule cast, red blood cell cast, such as renal biopsy, diffuse membranous glomerulonephritis, focal nephritis or only vascular stromal cell proliferation, microscopic examination for hypertensive vascular changes, Glomerular cell hyperplasia and localized basement membrane thickening, accompanied by significant intimal hyperplasia and luminal occlusion.
8. Urinary system performance
About 10% of patients have neurological symptoms, usually trigeminal neuralgia, sometimes transient mental disorders, multiple peripheral neuralgia, cerebral infarction, aseptic meningitis, and convulsions.
Examine
Examination of mixed connective tissue disease
1. Blood routine and blood sedimentation
White blood cells are generally normal or decreased. If infected, white blood cells can be elevated, red blood cells can be mildly or moderately decreased, and platelets can also reduce blood sedimentation when the disease is active.
2. Urine routine
Some patients have a small amount of proteinuria, red blood cells, and sometimes tube type.
3. Biochemical inspection
Serum muscle enzymes (alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, aldolase, lactate dehydrogenase) are elevated in muscle involvement, and gamma globulin is elevated in 3/4 patient protein electrophoresis.
4. Immunological examination
Fluorescent antinuclear antibody titer increased, and it was spotted, serum complement level was normal, anti-dsDNA antibody was 12% positive, E-rosette test and phytohemagglutinin (PHA) test were mostly low, blood coagulation test The extractable nuclear antigen (ENA) antibody has a high titer (1:1000 to 1:1 million), while the systemic lupus erythematosus has a low titer (1:10 to 1:1000), extractable nuclear antigen ( ENA) antibody and anti-ribonucleoprotein (RNP) antibody titers are elevated, which is of great significance for the clinical diagnosis of this disease. Immunofluorescence deposition and speckle epithelial nucleus staining can be seen in skin fluoroscopy, and a few patients have rheumatoid factor and lupus cells. The Coomb test was positive.
5. ECG examination
Most of them are sinus tachycardia. Individual patients have myocardial inflammatory changes or ventricular premature contractions, atrial fibrillation, migratory rhythm, and coronary insufficiency.
6. Electromyography
Two-thirds of patients showed varying degrees of inflammatory myopathy.
7. X-ray inspection
(1) Chest radiography: Both lungs have interstitial changes in the lungs, which are more common in the two lung fields. The thickened lung texture is interwoven into a fine mesh, and 30% of patients may have irregularly flaky shadows, sometimes There is a small amount of pleural effusion, and the heart appears as pericardial effusion or myocarditis in the early or active stage of the disease. The heart shadow is generally enlarged, and the pulsation disappears or weakens.
(2) barium meal examination: the main change of esophagus is weakened or even disappeared, the lumen relaxes and expands, the expectorant passes slowly, the residence time is long, and the middle and lower segments are obvious. The small intestine shows intestinal dilatation, mucosal folds become thick, disorder and peristalsis decrease. Slow, expectorant scattered, similar to intestinal malabsorption syndrome.
8. Pulmonary function test
Two-thirds of patients showed a decrease in gas diffusion function, and about half of patients had restrictive ventilatory dysfunction.
9. Other
When a goiter is found, a thyroid biopsy is performed. If the pathological section of the biopsy shows a decrease in the acinar glia, the acinus is replaced by tissue cells and giant cell granuloma. There are different degrees of lymphoid cells between the acinus. Plasma cell infiltration and fibrosis are reliable evidence of chronic lymphocytic thyroiditis.
Diagnosis
Diagnosis and diagnosis of mixed connective tissue disease
Diagnostic criteria
There is no clear and unified diagnostic criteria for this disease, mainly based on comprehensive judgment. Any clinical encounter with polyarthritis or joint pain, Raynaud's phenomenon, no fixed part of muscle pain, unexplained finger swelling, varying degrees of anemia and erythrocyte sedimentation rate Increase, or the patient has atypical clinical features of systemic lupus erythematosus, dermatomyositis, systemic sclerosis or both, that is, the possibility of the disease should be considered, ANA should be performed, where the titer is greater than 1:160, and spotted, the anti-RNP antibody titer increased, you can confirm the diagnosis.
In 1987, Sharp proposed the following diagnostic criteria for the disease:
Main standard
(1) Myositis (severe).
(2) The lungs involve 1CO diffusion function <70%;
2 pulmonary hypertension;
3 Lung biopsy showed proliferative vascular injury.
(3) Renault phenomenon or esophageal peristalsis function is reduced.
(4) Swelling of the hand or hardening of the fingers.
(5) Anti-ENA antibody titer 1:10000, anti-UIRNP antibody positive, anti-Sm antibody negative.
2. Secondary criteria
(1) Hair loss.
(2) Leukopenia is less than 4 x 109 / L.
(3) anemia hemoglobin female
(4) pleurisy.
(5) Pericarditis.
(6) Trigeminal neuropathy.
(7) Arthritis.
(8) erythema on the cheek.
(9) Thrombocytopenia <100×109/L.
(10) Myositis (mild).
(11) There is a history of swelling in the back of the hand.
3. Confirmed diagnosis
(1) 4 major clinical criteria.
(2) Serological anti-RNP antibody positive, titer > 1: 4000, except anti-Sm antibody positive.
4. Possible diagnosis
(1) Clinical:
13 main criteria.
22 major criteria (1, 2 or 3) and 2 secondary criteria.
(2) Serological anti-RNP antibody positive, titer > 1:1000.
5. Suspicious diagnosis
(1) Clinical:
13 main criteria.
22 main criteria.
31 major standards or 3 secondary standards.
(2) Serological anti-RNP antibody positive, titer 1:100.
Differential diagnosis
The disease is similar to systemic lupus erythematosus, dermatomyositis, systemic sclerosis, so it should be noted that the identification of the above diseases can rely on clinical features and immunological specific examination, if necessary, combined with histological pathological changes, generally It is not difficult to identify, it is quite difficult to identify the overlap syndrome associated with systemic lupus erythematosus by clinical symptoms. The list of overlapping syndromes associated with systemic lupus erythematosus is identified as follows (Table 1):
The disease must also be differentiated from adult Still disease and vasculitis disease. The latter two can extract nuclear antigen (ENA) antibodies and are negative for RNP antibodies.
