Systemic lupus erythematosus in pregnancy
Introduction
Introduction to pregnancy with systemic lupus erythematosus Systemic lupus erythematosus (SLE) is a common autoimmune disease, and the cause is still not well understood, but most studies suggest that the pathogenesis of SLE is the result of the interaction between genetic factors and environmental factors, due to the presence of more serum in SLE patients. Autoantibodies (especially antinuclear antibodies) can reach the organs of the body along with the blood circulation, and the lesions can affect a variety of organs and tissues. Before the 1950s, suffering from SLE was equivalent to terminal illness. It was often considered impossible to get married. Even if you were married, you could not give birth, because fertility can seriously worsen SLE disease and even endanger life. With the improvement of SLE diagnosis and treatment technology, the survival rate of patients has been significantly improved, and the quality of life has also been greatly improved. SLE is no longer an incurable disease. SLE patients can not only get married, but also have children. Because the incidence of SLE is closely related to sex hormones, SLE patients can make SLE disease worse after pregnancy, and are prone to miscarriage, fetal death, pregnancy-induced hypertension, and fetal growth retardation (IUGR). ) Obstetric complications, so the fertility problem of SLE patients is still a restricted area for medical staff and patients. basic knowledge The proportion of illness: 0.002% Susceptible population: pregnant women Mode of infection: non-infectious Complications: fetal growth restriction, fetal death, premature delivery
Cause
Pregnancy with systemic lupus erythematosus
(1) Causes of the disease
The exact etiology and pathogenesis of SLE has not yet been elucidated. As a typical autoimmune disease (AID), like all AIDs, its pathogenesis is multifactorial, including heredity, endocrine, various infections, environment and The immune function of the body caused by dysfunction of the reticuloendothelial system and other factors, in which genetics and hormones play a more important role.
1. Genetic quality: In addition to family aggregation (sister, mother and daughter with SLE), there are racial differences, which are related to certain genes. In the investigation of SLE patients in northern China, HLA-DR2 and HLA-DR2 were found. The HLA-DR9 frequency is high.
2. Hormone effects: The experiment confirmed that the hypothalamic-pituitary-adrenal axis regulates the release of cytokines, thereby affecting the inflammatory response. The cytokines synthesized by cells in the body act on the pituitary and increase the secretion and release of pro-inflammatory hormones such as PRL. Experiments have shown that PRL can activate T lymphocytes and transform immature B cells into plasma cells that secrete immunoglobulin, resulting in an increase in blood immunoglobulins.
3. Immune dysfunction: Interleukin (IL) also plays an important role in the pathogenesis of SLE. It has been found that the levels of IL-3 and IL-6 secreted by peripheral monocytes in SLE patients in China are significantly higher than those in normal people. The level of IL-2 is lower than that of normal people, and the increase of serum IL-8 is related to the activity of SLE. The remission or deterioration of the disease during pregnancy is caused by hormone secretion from the placenta and fetal inhibitory T-cell (Ts). The effect of active factor engraftment.
4. Physical factors: Ultraviolet radiation in sunlight is a cause, which can induce damage or exacerbate the original lesions. Therefore, it has been suggested that ultraviolet rays act on epidermal cells to convert DNA in the nucleus into thymine dimer. The latter has strong antigenicity and stimulates the body to produce DNA antibodies.
5. Infection: Some people think that the pathogenesis of SLE is related to certain viral or bacterial infections. In recent years, B cells in SLE patients have been found to be abnormally active, which is presumed to be caused by EB virus infection.
In short, with the deepening of molecular immunology and molecular biology research, the days of elucidating the multifactorial pathogenesis of SLE will come.
(two) pathogenesis
1. SLE is a typical immune complex disease. A variety of autoantibodies are found in the serum of patients, which bind to the corresponding antigens to form immune complexes. These immune complexes are deposited in organs and blood vessels, causing damage to multiple organs. The clinical manifestations of various types of lupus disease are different. Among them, acute necrotizing arteriitis and arteritis are the main lesions of this disease. In almost all patients, the blood vessels in the affected organs of the whole body have DNA and resistance. The allergic reaction formed by the deposition of immune complexes such as DNA, the active lesions are mainly cellulose-like necrosis, the vascular wall fibrosis is more obvious in the chronic phase, the vascular lumen is narrow, the organ is not supplied with blood, lymphocytes infiltrate around the blood vessels, edema and Increased matrix, SLE patients have a variety of autoantibodies, mainly antinuclear antibodies, which can attack the denatured or damaged nuclei, so that the nuclear chromatin is lost, evenly swollen, extruding cell bodies, forming lupus bodies, when complement When present, promote neutrophils, macrophages phagocytose lupus bodies, form lupus cells, lupus cells are characteristic lesions of SLE, except for SLE patients In addition to antinuclear antibodies, anti-nucleotide antibodies, anti-riboprotein antibodies, anti-erythrocyte antibodies, anti-leukocyte antibodies, anti-platelet antibodies, etc., tissue damage of SLE is mainly caused by DNA and anti-DNA complexes. Glomerular lesions, followed by specific red blood cells, white blood cells, platelet damage, causing lupus nephritis, hemolytic anemia, leukopenia, thrombocytopenic purpura, lupus nephritis is an immune complex deposited in the kidney, active lupus nephritis patients, due to Complement C3, C4, C50 high catabolism, decreased anabolism, increased extravascular distribution of complement, decreased levels of C3, C4, C50 in serum, glomerular and tubular lesions, leading to proteinuria, decreased renal function, severe kidney Functional failure.
Possible pathological factors of neurogenic lupus are:
(1) Cerebrovascular inflammatory lesions.
(2) Immunopathological effects of anti-brain cell antibodies.
(3) Blood-brain barrier dysfunction.
The main changes in the brain are small vasculitis, fibrosis, vascular wall necrosis and proliferative hypertrophy, limited microembolism in the formation of brain parenchyma, and corresponding softening of the brain tissue, so patients with brain SLE have neurological, psychiatric symptoms, and anti- Phospholipid antibody and vascular endothelial cell membrane phospholipids inhibit the release of arachidonic acid, decrease prostaglandin production, vasoconstriction, increase platelet aggregation, clinical manifestations of high blood pressure or thrombosis, antiphospholipid antibodies can directly affect the injury Vascular endothelial cells, inhibit the release of plasminogen activator, promote thrombosis, and cause local embolism of the brain. Clinically, patients with brain-type SLE may also have seizures or hemiplegia, and may also have psychiatric symptoms.
Peripheral vascular embolization, resulting in limb necrosis or Raynaud's phenomenon, internal iliac artery, uterine artery and spiral artery damage, resulting in placenta, villus ischemia, poor blood flow in the villus interstitial, resulting in fetal oxygen and nutrient supply disorders, Therefore, SLE pregnant women are prone to repeated abortion, fetal growth restriction, fetal death, perinatal hypoxia.
2. The effect of pregnancy on systemic lupus erythematosus SLE has different severity of disease, different effects, mild kidney damage before pregnancy, normal renal function, and the disease persists without immunosuppressive treatment. The renal function of most patients remains. Good, but 10% of kidney function is impaired, postpartum recovery, another 10% of kidney function is impaired, and can not fully recover after delivery (Fine 1981). Mor-Josef (1984) suggested that nearly 80% of patients had no major changes during pregnancy. However, the remaining patients have different degrees of increased disease; this situation is more common in patients with active disease who have not yet fully controlled or patients whose condition has been controlled, but who automatically reduce or stop taking corticosteroids after pregnancy, in addition to aggravating kidney burden and In addition to aggravating kidney damage, it can also stimulate erythema, fever, joint pain and other fatal damage to the mother. Some patients have reported postpartum deterioration, pulmonary embolism, pulmonary hemorrhage, pulmonary hypertension, cardiac vascular embolism, etc. The use of corticosteroids, immune function is affected, postpartum can easily cause infection.
However, if the patient is pregnant during the quiescent period, even if there is kidney disease, the pregnancy can develop smoothly, the pregnancy outcome is good, 60% can reach full term, get healthy newborn, Burkett (1985) based on 156 patients, 242 pregnancy progress The situation and outcomes were raised: if the condition was relieved for more than 6 months, the renal function was good (serum creatinine concentration 133 mol/L, creatinine clearance rate 60 ml/min, or urine protein amount 3 g / 24 h), and the pregnancy progress and outcome were good.
According to the investigation and analysis in China: According to the different conditions, pregnancy and postpartum can aggravate the condition of SLE, the deterioration rate is 17% to 55%, 44 cases are pregnant during the remission or control period of the disease, and 16 cases (32.6%) are worse during pregnancy. 5 cases in the early and middle stages, 11 cases after 28 weeks of gestation, therefore, the SLE is relieved for more than half a year or during the control period (symptom control or maintenance of prednisone only 5 to 10 mg / d) to allow pregnancy; active period and obvious heart Renal dysfunction (including endocarditis, myocarditis, heart failure, nephrotic syndrome, advanced glomerulonephritis, etc.) should terminate the pregnancy, during pregnancy must be closely monitored for the mother and baby, timely treatment of comorbidities, planned to proceed Interventional premature delivery can safely pass through pregnancy.
3. The effect of systemic lupus erythematosus on pregnancy SLE maternal prevalence rate is high, the incidence of pregnancy-induced hypertension can reach 18% to 25%, especially those with renal SLE, sometimes difficult to identify with severe pre-eclampsia, according to reports Its incidence is closely related to the condition of SLE. The active type of 21 cases complicated with pregnancy-induced hypertension is as high as 52.4%, while none of the stable type 33 cases occur. For example, SLE involves the central nervous system. In severe cases, convulsions can occur, and eclampsia The convulsions are similar; thrombocytopenia is accompanied by (or no) hemolysis, which is more confusing.
SLE has damage to all organs of the system, which can directly damage the placenta, leading to 30% of placental dysfunction (47.6%, 18% of SLE active and stable placental insufficiency, respectively), renal SLE with hypertension The incidence of placental dysfunction caused by vasospasm in pregnant women has increased significantly. It has been confirmed that SLE antibody can damage the placenta and cause placental dysplasia. This immune damage causes small vessel wall ischemia, hypoxia and fibrinoid necrosis and acute Atherosclerosis, resulting in placental dysplasia, reduced villus area, affected by substance exchange function, and reduced nutrient intake in the fetus, is an important cause of abortion in SLE pregnant women, fetal death, and fetal growth retardation (IUGR). The fetus is prone to intrauterine distress.
SLE autoantibodies can also directly harm the fetus through the placenta. According to Zhang Jianping (1995), the spontaneous abortion rate is 20.6% (related to direct antibody attack on the embryo), premature birth 20.8%, fetal growth restriction (FGR) 25%, fetal 5.5% in the death palace and 6.9% in the newborn.
SLE pregnant women in the blood against the Segway syndrome A, B antigen antibodies, and possibly other antibodies, is IgG, can penetrate the placenta into the carcass, causing neonatal SLE, due to diffuse myocarditis caused by fibrosis, such as Occurring between the atrioventricular node and the His bundle, congenital atrioventricular block (heartblock) can occur, causing the onset of Adam-Stokes (abrupted heart block, loss of consciousness or with convulsions) or heart failure, Therefore, pacemakers need to be installed, heart block can also occur in the fetus, pregnant women are still normal, but SLE symptoms or other connective tissue diseases will definitely occur in the future. MeCune (1987) reported 24 children with congenital lupus erythematosus. There were 12 cases with heart block, 10 cases with skin lesions, 2 cases with both; 3 cases died in the neonatal period, 5 cases in 11 cases required a pacemaker, the incidence of offspring and pregnant women during pregnancy There is no obvious relationship between the severity of the illness.
Prevention
Pregnancy with systemic lupus erythematosus prevention
Early diagnosis is a prerequisite for early treatment. For patients with mild fever, fatigue, pleurisy, rash and other mild cases, oral lupus Kangtai granules, artesunate tablets and non-steroidal anti-inflammatory drugs such as indomethacin, fenbide and other adjuvant treatments; in addition to the application of lupus Kangtai and Qing In addition to artesunate, glucocorticoids and other immunosuppressive agents are also used, and Chinese medicine is used for dialectical treatment.
Regular regular follow-up, comprehensive examination every 1-2 months, according to changes in the condition, adjust the dosage. Hormones can be gradually reduced or stopped when the condition is relieved. Practice has proved that Chinese medicine plays an important role in promoting and maintaining the relief of the disease, reducing the side effects of hormones, regulating the body's immune function, and preventing infection.
Because of the many factors inducing systemic lupus erythematosus, the disease is often in an unstable state, and the recurrence (activity) and remission are the clinical features. Therefore, in the practice of treatment, doctors should prevent recurrence, guide patients to cooperate with treatment, and make self-protection as an important goal.
Complication
Pregnancy with systemic lupus erythematosus complications Complications, fetal growth restriction, intrauterine premature delivery
SLE patients have obstetric complications accounting for 30%, including repeated abortion, embryonic cessation, fetal growth restriction, fetal death, premature delivery, perinatal hypoxia, early pregnancy hypertensive disease.
Symptom
Pregnancy with systemic lupus erythematosus symptoms Common symptoms Joint pain pleural effusion fatigue convulsion chest pain nephrotic syndrome renal failure edema nodules morning stiffness
Most patients with SLE have a slow onset. The main complaints and symptoms vary with the organ system involved. According to Hahn (1998), the clinical symptoms and incidence are as follows: 95% of patients have systemic symptoms including fever, fatigue , fatigue, weight loss and general discomfort, about 95% of SLE patients have musculoskeletal symptoms, including severe joint pain, manifested as symmetrical arthritis, half of the joint morning stiffness, muscle pain, fatigue, severe muscle atrophy, 85% SLE The patient has changes in the blood system, including anemia, hemolysis, leukopenia, thrombocytopenia, lupus anticoagulants in the serum, and skin damage in about 80% of SLE patients. The prominent features are facial butterfly erythema, distributed in the nose and double Buccal, a small number of erythema is also seen in other parts, erythema is slightly edematous, aggravated after sun exposure, small nodules and Raynaud's phenomenon at the extremities, poor skin elasticity, hair loss, oral ulcers, 60% of SLE patients have spirit, nerve Symptoms, about 50% of patients have nephritis and mental, neurological symptoms, performance is extremely inconsistent, lighter only psychological barriers, such as difficult to get along with family or colleagues, meaning Obstacles; severe cases of epilepsy, hemiplegia or subarachnoid hemorrhage, 60% of patients have heart, lung changes, when there is myocarditis, clinical manifestations of chest tightness, palpitations, shortness of breath, can not be supine, heart enlargement, and even heart Depletion, SLE lesions involving the serosa, clinical manifestations of pericarditis, pleurisy, pleural effusion, dyspnea, chest pain, pulmonary fibrosis, also known as lupus lung, chest X-ray film visible patchy infiltration shadow, 60% of patients There are nephritis manifestations, proteinuria, tubular urine, advanced progression to nephrotic syndrome and to renal failure, clinical manifestations of elevated blood pressure, edema, laboratory tests found proteinuria, cells and cast in urine, plasma protein reduction, A /G inverted, elevated cholesterol, 45% of patients have gastrointestinal manifestations, such as loss of appetite, nausea, vomiting, abdominal pain, diarrhea, 15% of patients with vascular embolism: 10% of venous thrombosis, 5% of arterial embolism, clinical symptoms are limb pain When a vascular embolism occurs, the dorsal artery of the foot may disappear.
Examine
Pregnancy with systemic lupus erythematosus
1. Detection of autoantibodies does not have organ-specific autoantibodies and organ-specific autoantibodies.
(1) No organ-specific autoantibodies: subdivided into anti-nuclear antibodies and anti-cytoplasmic antibodies.
(2) Organ-specific autoantibodies, which have the following three antibodies:
1 anti-blood cell antibody.
2 anti-lymphocyte antibodies.
3 other: anti-thyroid globulin, transverse diaphragm antibody, anti-neural tissue component antibody.
2. Anti-phospholipid antibody detection refers to a group of antibodies with anti-phospholipid components, which are present in infectious diseases, malignant tumors, and even in patients without any clinical manifestations. They have various names according to their detection methods and clinical manifestations. Anticardiolipin antibodies, LAC, and the like in SLE patients are anticardiolipin antibodies.
(1) anti-ardiolipin antibodies (ACL): it can occur in a variety of connective tissue diseases, the SLE positive rate is up to 42.4%, ACL antibodies are IgG, IgA, IgM, of which IgG type is the most see.
(2) Lupus anticoagant (LAC): Con-hey has a detection rate of 6% to 10%, which is named after it can prolong the coagulation process of phospholipids in vitro.
3. Other tests ESR can be accelerated in normal pregnancy, but generally does not exceed 40mm/h. When pregnancy is combined with SLE, the erythrocyte sedimentation rate is accelerated, suggesting SLE activity. Some people think that erythrocyte sedimentation rate exceeds 100mm/h, indicating that the disease is serious, which is related to the worsening of postpartum condition. .
4. Immunopathological examination
(1) Renal puncture or tissue examination: The pathological diagnosis provided by this method is valuable for many lupus nephritis and estimated prognosis, including at least light microscopy, fluoroscopy, electron microscopy if necessary, and identification of lymphocytes by immunohistochemistry. Subtype and composition of sediments.
(2) Skin lupus belt test: The patient's skin was examined by direct immunofluorescence technique, and a localized immunoglobulin precipitation band appeared at the junction of the epidermis and the dermis, which was yellow-green, and was immunoglobulin (mainly IgG) and complement. The conjugate of the epidermal dermal junction, the positive rate of SLE patients is 50% to 70%. If the material is taken from the lesion site, all kinds of skin are positive, so the normal skin should be taken from the exposed site to improve the specificity of the test. In the treatment, the immunofluorescence banding disappears with the relief of the disease, so it can be used as one of the indicators for the diagnosis of curative effect.
5. X-ray examination of thoracic X-ray examination with interstitial pneumonia as the main changes, the two lungs have small inflammatory shadows and discoid atelectasis, pleural effusion, etc., as well as the general heart enlargement caused by myocarditis Pericardial effusion.
Diagnosis
Diagnosis and diagnosis of pregnancy complicated with systemic lupus erythematosus
diagnosis
1. According to the diagnostic criteria revised and formulated at the Second Academic Conference of Rheumatology of the Chinese Medical Association in 1985
(1) Buccal rash or discoid erythema.
(2) Photoallergy.
(3) Painless ulcers in the mouth or nasopharynx, hair loss.
(4) Arthritis.
(5) serositis, pleurisy, pericarditis.
(6) Renal lesions: proteinuria, red blood cells and/or casts appear in the urine.
(7) Abnormal nervous system: convulsions, mental disorders.
(8) Abnormal blood system: hemolytic anemia or leukopenia or thrombocytopenia.
(9) Immunological abnormalities: lupus cell positive or antinuclear antibodies (ANA, a general term for various nuclear component antibodies) are positive; ANA titers are increased.
(10) Anti-Sm antibody positive: Sm antibody is a kind of anti-nuclear antibody, a marker antibody of SLE, and an anti-nuclear antibody specific for SLE.
There are 4 positives (including 1 immunological index) which can be diagnosed as SLE; less than 4, but still suspected of SLE, should be further examined, such as lupus test positive, and / or renal biopsy showed immune complex Physical kidney changes can also be diagnosed.
2. During pregnancy and puerperium, blood routine and liver and kidney function tests should be repeated to judge the pathological activity.
(1) ESR test is widely used in clinical practice, but even if the erythrocyte sedimentation rate is accelerated, it will not help the diagnosis during pregnancy.
(2) When hemolysis occurs, the Coomb test is positive, anemia, reticulocyte increase and non-binding hyperbilirubinemia, and thrombocytopenia and leukopenia.
(3) If the serum transaminase activity is increased, suggesting that the liver is involved, and the serum bilirubin concentration is increased, in combination with bilirubin, azathioprine treatment can reduce liver function abnormalities.
(4) Sustained proteinuria is increasing, and there are other nephrotic syndrome manifestations or abnormal serum creatinine concentrations, suggesting that the condition is exacerbated.
3. According to the SLE condition, the disease activity is divided into four phases from the beginning of pregnancy:
(1) Remission period: The patient has stopped taking corticosteroids for more than 1 year, and there is no clinical manifestation of SIE.
(2) Control period: refers to the clinical activity of no SLE in the case of applying a small amount of hormones.
(3) Active period: refers to patients with fever, rash, mouth ulcers, arthritis or organ damage, etc., of which several clinical manifestations of SLE activities.
(4) The first onset of pregnancy: refers to the initial clinical symptoms of SLE during pregnancy, the signs.
Differential diagnosis
Hypertensive disorder of pregnancy
Patients with renal SLE and hypertensive disorder complicating pregnancy may have edema, hypertension, proteinuria, brain type SLE can occur epilepsy, and the clinical manifestations of eclampsia episodes of severe hypertensive disorder are difficult to distinguish, due to two Different treatment methods are especially important for identification. It can be distinguished by laboratory tests:
(1) SLE patients with positive immunological indicators (such as ANA, etc.), negative immune index in patients with hypertensive disorder complicating pregnancy.
(2) Serum complements such as C3, C4, and C50 are elevated in hypertensive disorders during pregnancy, and complement is decreased during SLE activity.
(3) termination of pregnancy, hypertensive disorder of pregnancy is relieved immediately, SLE can not be alleviated.
It is necessary to identify the hypertensive disorder of pregnancy and the exacerbation of SLE, because the fundamental measure of hypertensive disorder in pregnancy is to terminate the pregnancy. If the condition of SLE is aggravated, the treatment method is different. It is necessary to increase the dose of prednisone or use other immunosuppression. Agent.
Anemia
The most common during pregnancy is iron deficiency anemia, nutritional anemia, supplementation with iron, folic acid, adjustment of diet, most can be corrected, anemia in SLE patients may be immune-induced hemolytic anemia, patients with normal pigmentation, normal cell anemia, And often accompanied by thrombocytopenia, SLE immune antibody index was positive, anti-human globulin test was positive; nutritional anemia immune antibody index was negative, anti-human globulin test was negative.
3. Primary thrombocytopenic purpura
About 25% of patients with SLE have thrombocytopenia at the time of onset, are mistaken for primary thrombocytopenic purpura, differentiated by bone marrow aspiration, and do not reduce megakaryocytes in SLE patients; primary thrombocytopenic purpura megakaryocytes decrease, antinuclear antibodies And other immunological tests, such as positive immunological indicators support SLE, such as negative can rule out SLE.
4. Lymph node enlargement
5% of patients with SLE have onset of lymphadenopathy, lymph nodes up to 2 to 4 cm in diameter, and with hypothermia, lymph node biopsy, excluding lymph node tuberculosis and Hodgkin's disease.
