Pediatric lupus nephritis
Introduction
Introduction to pediatric lupus nephritis Lupus nephritis, also known as systemic lupus erythematosus (SLEN), is a systemic lupus erythematosus with clinical manifestations and renal dysfunction of kidney disease, or glomerulonephritis lesions found only during renal biopsy. Systemic lupus erythematosus is a well-recognized autoimmune disease, and most of its lesions involve several systems or organs. Children with LN lesions are often severe, refractory cases are more, some patients with SLE are mainly extra-renal symptoms, and kidney damage is light; another patient is mainly characterized by kidney damage, and the extra-renal symptoms are not obvious, the latter is easily misdiagnosed as the original Primary glomerular disease. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: retinitis, nephrotic syndrome, renal failure
Cause
Causes of pediatric lupus nephritis
Genetic factors (25%):
Genetic epidemiological data found that SLE has a family aggregation tendency, the coincidence rate of identical twin SLE is 25% to 70%, which is significantly higher than that of fraternal twins (2% to 9%). The incidence of close relatives is also high in patients with this disease. 12% of children with SLE have reported similar diseases in their close relatives. The incidence of other autoimmune diseases is also higher than the total incidence of the population. However, a large number of genetic studies have confirmed that SLE is polygenic, located in the sixth pair. Multiple loci in the chromosome are associated with pathogenesis, especially hereditary complement gene defects (deficiencies in early complement components such as C1r, C1s, C2 and C4), human leukocyte antigen (HLA) genes (HLA-B8, BWl5, DR2, DR3), T cell surface antigen receptor (TCR) gene, immunoglobulin gene and other classical immune response gene polymorphisms are also related to SLE, including Japanese, Chinese HLA-DR2 site frequency increased, Western European bloodline white The frequency of HLA-DR2 and/or DR3 sites increased. The incidence of SLE in Han Chinese in southern China was related to DRBl*0301 and DQBl*0608. Black Americans were related to DRB1*1503, DQAl*0102 and DQBJ*0602, but other population studies did not find HLA-II gene and SLE have This correlation, further study found.
Certain HLA-II locus polymorphisms are associated with autoantibodies in SLE patients, especially polymorphic sequences shared by different HLA-DQ alleles may result in the production of certain autoantibodies, such as high levels of dsDNA. Of antibody patients, 96% have HLA-A-DQBl*0201 (linked to HL, A-DR3 and DR7), DQBl*0602 (linked to DR2 and DRw6) or DQBl*0302 (linked to HLA-DR4 haplotype) Alleles, others have found that anti-cardiolipin antibody-positive SLE patients are closely related to HLA-DQBl*0301 (DQW7), *0302 (DQW8), *0303 (DQW9), *0602 (DQW6) alleles, It is speculated that the SLE disease gene is located in the MHC region and is in linkage disequilibrium with HI, A-I, and class II genes. Under normal conditions, complement components play a key role in the fixation and effective clearance of immune complexes. When genetic defects are lacking, it will lead to the deposition of immune complexes in the kidneys, but the data show that complement defects are rare in SLE, and the kidney defects in patients with complement deficiency are often not serious. The clinical manifestations are not typical, involving more boys. , so it does not represent the pathogenesis of most SLE, but also indicates the SLE Gene transfer is certainly a variety of complex features.
Environmental and infectious factors (25%):
(1) Ultraviolet light: Ultraviolet light is considered to be one of the causes of triggering SLE. It has been found that ultraviolet light (mainly UV 290-320 nm) can induce skin keratinocytes to produce interleukin-1 (IL-1), IL-3, IL. -6 and tumor necrosis factor (TNF); ultraviolet light can also attenuate macrophage clearance of antigen and inhibit T cell activation; about one-third of SLE patients develop symptoms after photoallergic or ultraviolet radiation, data indicate that ultraviolet light can make cells The internal DNA is converted into a thymine dimer, which enhances its antigenicity and induces anti-DNA antibodies.
(2) drugs or chemicals: Some drugs can cause photosensitivity in patients with SLE, such as sulfa drugs, tetracycline; some drugs can induce the production of autoantibodies such as procainamide, hydralazine and so on. Some spices, dyes, hair dyes, pyrotechnics, and fungi can also induce SLE. Some people think that the antigenic degeneration of this drug or chemical substance combined with nuclear protein is also an important cause of the body's own immune damage.
(3) Infection: Infection-induced SLE has also been studied. In recent years, it has been found that human immunodeficiency virus (HIV) infection can cause SLE; infection with herpes simplex virus can cause elevated serum Sm antigen concentration; SLE patients often have more serum. Increased antibody titers (such as rubella, Epstein-Barr virus, flu, measles, etc.), especially C-type RNA viruses.
Endocrine factors (25%):
Most of the patients with SLE are female, and the estrogen level is increased in both men and women, and the androgen level is lowered. It is speculated that high levels of estrogen can directly act on B cells to activate them, resulting in the proliferation of activated B cells secreting autoantibodies. The discovery of estrogen in animals can exacerbate their condition, and androgens can alleviate the condition.
Self-organized antigen variation (10%):
Various factors such as ultraviolet radiation, drugs, chemicals, pathogen infections may destroy their own tissues, expose the hidden antigens of tissues or change the structure of normal tissue antigens, and stimulate the body's own immune damage.
Prevention
Pediatric lupus nephritis prevention
1. Early diagnosis, timely and correct treatment, long-term regular follow-up, according to changes in the condition, adjust the dosage.
2. Avoid predisposing factors
(1) Sun exposure, ultraviolet radiation.
(2) Cold stimulation can cause the disease to recur, avoid cold stimulation, to prevent cold.
(3) Some drugs are obviously related to the onset, such as penicillin, sulfonamides, phenylbutazone, hydralazine (hydralazine), procainamide, chlorpromazine, phenytoin, isoniazid, oral contraception Drugs, etc., can make patients with lupus erythematosus in remission period into active period and laboratory changes.
(4) Systemic lupus erythematosus and pregnancy have adverse effects, such as fetal abnormalities, miscarriage, premature delivery or stillbirth. Conversely, pregnancy can exacerbate or relapse in the last 3 months of pregnancy and months after delivery.
3. Grasp the early signs of recurrence: If the original symptoms, joint pain, fever, fatigue, etc. reappear, should be diagnosed early, carry out necessary examinations, and take timely measures if there are activities, early drug treatment and Chinese medicine treatment.
4. Food should be light and easy to digest. It is not advisable to overeat greasy and thick food. Reasonable use of foods such as fish, meat, eggs and fresh fruits is beneficial to the treatment and rehabilitation of this disease. During the stable period, participate in physical activities to enhance physical fitness.
5. Psychotherapy: Maintaining good mood is very important for the outcome of the disease. Maintaining a good emotional state and maintaining a relatively stable immune function is an important guarantee for avoiding recurrence and early recovery.
Complication
Pediatric lupus nephritis complications Complications retinitis nephrotic syndrome renal failure
Renal failure, hypertension, epilepsy, hemiplegia, cerebrovascular accident, multiple peripheral neuritis, retinitis, pleurisy, pneumonia, pulmonary hemorrhage, perforation of intestinal necrosis, pericarditis, myocarditis, etc. Mainly complicated by acute and chronic nephritis syndrome, nephrotic syndrome, renal tubular syndrome, and may be combined with larger renal vascular thromboembolism, renal capillary thrombotic microvascular disease, causing renal dysfunction, especially renal failure.
Symptom
Pediatric lupus nephritis symptoms common symptoms fatigue loss of appetite kidney damage dyspnea proteinuria hematuria hypothermia lymphadenopathy thrombocytopenia mucosal damage
1. Systemic manifestations: a variety of, more than 80% have fever, multiple types of heat, high fever, low fever, intermittent or persistent fever, have varying degrees of loss of appetite, fatigue and weight loss.
2. Skin mucosal symptoms: 70% to 80% of children with lupus have skin mucosal damage. Typical butterfly erythema is only found in 50% of cases. The rash is located on the cheeks and bridge of the nose. It is bright red with clear edges and mild edematous erythema. Capillary vasodilation and scaly can be seen. When the inflammation is heavy, blisters can be seen, and the ecdysis is generally scar-free after regression, and there is no pigmentation.
3. Other skin mucosal symptoms: Children with discoid erythema are less than adults, showing bleeding rash, macule, reticular leukoplakia, urticaria, purpura, mouth ulcers, nasal mucosal ulcers, increased skin lesions or new appearance after sun exposure The rash, about 10% to 20% of the sick children have no rash performance.
4. Musculoskeletal symptoms: about 70% to 90% of the sick children have joints, muscle symptoms, such as arthritis, joint pain, about 1/3 of children with muscle pain, arthritis can be either migratory or Persistence, joint damage and deformity are rare.
5. Cardiovascular symptoms: visible pericarditis, myocarditis, whole heart inflammation and various small vasculitis, Raynaud's phenomenon is rare in pediatrics, in recent years has begun to pay attention to cases of coronary arteritis and myocardial infarction in sick children.
6. serositis: 30% of children with multiple serositis, such as aseptic pleurisy, peritonitis, acute lupus pneumonia and pulmonary hemorrhage, the above lesions can be expressed as acute fever, dyspnea, cough, chest pain, pleural effusion Abdominal pain, diarrhea, nausea, vomiting, ascites, if intestinal necrosis, perforation, need surgical treatment; severe pulmonary hemorrhage can die quickly.
7. Hematological symptoms: There are many degrees of anemia, 50% of children with peripheral blood leukopenia decreased, 15% to 30% of children with thrombocytopenia, a small number of children with thrombocytopenia as the first symptom.
8. Neurological symptoms: Lupus encephalitis is a serious complication of SLE, the relative incidence is about 30% (20% to 50%), 5% of children with neurological symptoms as the first symptom, manifested as diffuse brain dysfunction (consciousness, disorientation, intelligence, memory loss, mental abnormalities, etc.) or localized brain dysfunction, such as epilepsy, cerebrovascular accident, hemiplegia, aphasia, peripheral neuropathy is rare, manifested as multiple peripheral neuritis.
9. Other symptoms: liver enlargement (75%), abnormal liver function, splenomegaly (25%), superficial lymphadenopathy (about 50%), scleritis, iritis, retinitis, etc. Eye symptoms.
10. Renal symptoms: Lupus nephritis is very common in SLE and is a key factor threatening the quality of long-term life. The clinical manifestations of lupus nephritis mainly include the following forms:
(1) Light type: asymptomatic proteinuria or (and) hematuria, about 30% to 50% of children with LN exhibit this type, no edema, no hypertension, only mild to moderate proteinuria (usually <2.5g/ d) and/or hematuria.
(2) Chronic nephritis type: insidious onset, slowly progressing nephritic syndrome, varying degrees of renal insufficiency, hypertension.
(3) acute nephritis or acute nephritis syndrome: 35% to 50% of patients have high blood pressure, varying degrees of proteinuria, more red blood cell casts in the urine sediment, renal insufficiency or failure, acute nephritis onset similar to the chain Acute nephritis after cocci infection, the onset of acute nephritis is similar to other acute nephritis, which is characterized by acute progression of oliguric acute renal failure, but these two onsets are rare in LN.
(4) Nephrotic syndrome: This type accounts for about 40% of the total number of LN, and can be clinically manifested as simple nephrotic syndrome or nephrotic syndrome with obvious nephritic syndrome.
(5) renal tubular damage type: renal tubular acidosis with renal calcification, stones, urinary magnesium loss, about 44% of patients with LN have different degrees of renal tubular dysfunction, clinical types can also be changed, when hematuria, proteinuria, kidney When the function is diminished and the hypertension is aggravated, the clinical type or pathological type is changed, and the prognosis is poor.
Examine
Examination of pediatric lupus nephritis
1. Urine check:
Proteinuria, hematuria and cells, protein tube types are common.
2. Blood test:
Most of them have different degrees of anemia, some people have leukopenia, thrombocytopenia, more than 90% of patients have a marked increase in erythrocyte sedimentation rate, blood albumin is reduced, globulin is elevated, and globulin is elevated, but if there is severe proteinuria, globulin The absolute value is also reduced.
3. Immunological examination:
(1) Antinuclear antibodies (ANAAs): If immunofluorescence analysis of ANA is peripherally the most significant for the diagnosis of SLE, suggesting that dsDNA antibody is positive, the antibody is highly specific for SLE and is associated with disease activity.
(2) Anti-double-stranded DNA (dsDNA) antibody: direct detection of dsDNA antibody positive rate of 50% to 80%, but specificity is greater than 90%, and often suggests kidney damage, occasionally in Sjogren's syndrome, rheumatoid arthritis And active hepatitis.
(3) Anti-Sm antibody: About 25% to 40% of patients are positive for anti-Sm antibodies, but their specificity is up to 99%.
(4) Other autoantibodies: anti-single-stranded DNA (ssDNA) antibody, high positive rate, low specificity, 26% to 45% of patients with anti-ribonucleoprotein (RNP) antibody positive, but the specificity is not high, anti-dry comprehensive Significant (SS) A, B antibody sensitivity, poor specificity, anti-neutrophil cytoplasmic antibody (ANCA) positive in necrotizing vasculitis, anti-cardiolipin antibody positive cases are common recurrent, multiple sexual activity, vein Embolization, thrombocytopenia and miscarriage.
(5) Complement: C1q, C3, C4, and CH50 are often reduced during the SLE activity period.
(6) Circulating immune complex is positive.
4. Lupus erythematosus cell (LEC):
The positive rate of LEC in SLE patients can reach 60% to 85%, but it can also be seen in other connective tissue diseases.
5. Lupus belt test:
Based on normal skin exposed to sunlight, direct immunofluorescence was used to detect the junction between the epidermis and the dermis. A fluorescent band of IgG and C3 deposition was observed. 80% of patients with active SLE were positive, and other autoimmune diseases were also positive.
6. Renal puncture examination: The diagnosis rate of systemic lupus erythematosus is 100%. Even if there is no clinical abnormality in the kidney, abnormal biopsy will be found in the kidney.
7. Others: Live tissue examination such as liver, lung, gastrointestinal, peripheral nerve, muscle, synovial membrane, etc. are helpful for the differential diagnosis of systemic lupus erythematosus. X-ray, B-ultrasound, electrocardiogram and other tests are routinely performed.
8. Electrocardiogram: When there is myocardial disease, pulmonary hypertension, pericarditis or electrolyte imbalance, the electrocardiogram has abnormal changes.
9. Radiographic inspection:
(1) X-ray: can detect pericarditis, pleurisy, pneumonia, lung infection, pulmonary hemorrhage, arthritis in patients with systemic lupus erythematosus.
(2) CT scan and magnetic resonance examination: have diagnostic or differential diagnostic value for the nervous system, heart, lung, mediastinum, abdomen, pelvic cavity, and spinal joint disease.
10. Ultrasound examination: Ultrasound has guiding significance for serositis, myocarditis, liver, spleen, lymphadenopathy, gallbladder, pancreas, kidney, urinary tract, uterus and prostate lesions in patients with systemic lupus erythematosus, and can also be used for vasculitis. Check.
Diagnosis
Diagnosis and diagnosis of lupus nephritis in children
diagnosis
Most of the diagnostic criteria of this disease refer to the diagnostic conditions proposed by the American College of Rheumatology in 1982. Four or more of the 11 criteria can be used to diagnose the disease. The domestic adult multi-center trial has a specificity of 96.4% and a sensitivity of 93.1. %, the main missed diagnosis is early, mild, atypical cases. The criteria proposed by the Chinese Rheumatology Association in 1987 increased the low-complement C3, skin lupus test and renal biopsy characteristics, and its diagnostic specificity was 93.6%, and the sensitivity was improved. It is 97.5%, and patients with onset of primary nephrotic syndrome can be found early.
Diagnostic criteria for systemic lupus erythematosus (Amendment of the American College of Rheumatology, 1982):
1. Buccal erythema: a fixed erythema that spreads over the ankle or is higher than the skin, often does not involve the nasolabial fold.
2. Discoid erythema: The erythema of the uplift is covered with horny scales and hair follicle embolization, and the old lesions may have atrophic scars of the skin.
3. Light sensitivity: Sun exposure causes skin irritation.
4. Oral ulcers: painless ulcers in the mouth or nasopharynx.
5. Arthritis: Non-erosive arthritis involving 2 or more peripheral joints characterized by swelling, pain or exudation of the joints.
6. Serositis:
1 pleurisy: chest pain, pleural friction or pleural effusion;
2 pericarditis: abnormal ECG, pericardial friction or pericardial effusion.
7. Kidney disease:
1 proteinuria > 0.5g / d or >.
2 cell tube type: can be red blood cells, hemoglobin, granular tube type or mixed tube type.
8. Nervous system abnormalities:
1 convulsions: non-drug or metabolic disorders, such as uremia, ketoacidosis or electrolyte imbalance.
2 mental illness: non-drug or metabolic disorders, such as uremia, ketoacidosis or electrolyte imbalance.
9. Hematological abnormalities:
1 hemolytic anemia with increased reticulocytes.
2 leukopenia <4 × 109 / L, at least 2 times.
3 lymphocytes decreased <1500/l, at least 2 times.
4 thrombocytopenia <100 × 109 / L (except drug effects).
10. Immunological abnormalities:
1LE cells are positive.
2 anti-dsDNA antibody positive.
3 anti-Sm antibody positive.
4 syphilis serum test false positive immunofluorescence anti-nuclear antibody titer abnormality or equivalent to other test titer abnormalities of this method, rule out drug-induced "lupus syndrome".
11. Anti-nuclear antibodies:
The immunofluorescence antinuclear antibody titer is abnormal or equivalent to other test titers of the method, and the drug-induced "lupus syndrome" is excluded.
Differential diagnosis
Differential diagnosis and attention to other rheumatic diseases, such as juvenile rheumatoid arthritis systemic type, polyarticular type, dermatomyositis, scleroderma, mixed connective tissue disease, multiple vasculitis, etc. Nephropathy, heart disease, hemolytic anemia, thrombocytopenic purpura, histiocytosis, chronic active hepatitis and neurological diseases are confused, pay attention to identification.
