drug-induced lupus
Introduction
Introduction to drug-induced lupus Drug-induced lupus refers to lupus-like disease caused by taking certain drugs. The pathogenesis is still unclear. Studies have shown that T cell research shows that T cell DNA methylation plays a key role in regulating gene expression and cell differentiation. Invasion of the skin, muscles, skeletal system, chest and abdomen, pericardium, kidney, a large number of pericardial effusion can cause pericardial tamponade. basic knowledge The proportion of illness: 0.0025% Susceptible people: no special people Mode of infection: non-infectious Complications: edema, pericarditis, myocarditis, arteriosclerosis, pulmonary edema
Cause
Cause of drug-induced lupus
(1) Causes of the disease
Drugs are the main cause of this disease. So far, more than 70 drugs have been found to cause lupus-like diseases, or aggravate existing lupus. Among the more related drugs are chlorpromazine, hydralazine, isoniazid, and A. Kitoba, penicillamine, procainamide and quinidine, with the advent of new drugs including cytokines and their inhibitors, the number of drugs that cause lupus-like diseases may increase.
(two) pathogenesis
The pathogenesis of drug-induced lupus is unknown, and its appearance is related to various factors such as the drugs used, genetic quality and immune abnormalities.
1. Acetylation phenotype: The difference in human response to drugs is determined by genetics. According to the different metabolism of hydralazine, procainamide and isoniazid, the population can be divided into fast acetylation and slow acetylation. Two phenotypes, the slow acetylated genotype is homozygous for the acetyltransposase recessive gene, slow acetylation accounts for 50% to 60% of Caucasians, and 5% to 20% of yellows. Although hydralazine, procainamide-induced drug-induced lupus can be seen in both phenotypes, but slow acetylation occurs in ANA and drug-induced lupus, and the cumulative dose of drug required is lower, so most Patients with drug-induced lupus are slow acetylers.
2. DNA-hypomethylation: Studies have shown that T cell DNA methylation plays a key role in regulating gene expression and cell differentiation, usually methylation of DNA regulatory sequences is accompanied by gene suppression, and hypomethylation With gene expression, procainamide or hydralazine can inhibit the methylation of T cell DNA, and human CD4+ T cells activated in vitro can become self-reactive after treatment with procainamide or hydroxybenzamine. The cell, 5-azacytidine, is a potent DNA methylation inhibitor that has the same effect on T cells. Self-reactive T cells can kill autophages, secrete IL-4 and IL-6 promotes the differentiation of B cells into antibody-secreting cells, suggesting that drug-modified T cells play an important role in inducing drug-induced lupus.
3. Complement: The classical complement pathway plays an important role in the clearance of immunoconjugates. The metabolites of hydralazine, penicillamine, isoniazid and procainamide can inhibit the covalent binding of C4 and C2, thereby inhibiting Activation of C3 leads to an immune complex clearance disorder, and an increase in circulating immune complexes in patients with drug-induced lupus has been reported.
4. Drug-DNA interaction: The interaction of hydralazine with the DNA-histone complex makes histones difficult to be digested by proteases and thus maintains their antigenicity. Consistent with this hypothesis: the core of histones It is the object recognized by the drug lupus autoantibodies.
5. Others: Recent data indicate that when the activated neutrophil myeloperoxidase converts the drug or its metabolite into an activated product, the product can directly pass the cytotoxic effect or cause an immune disorder, making the drug The tissue of lupus is damaged.
Prevention
Drug-induced lupus prevention
It is the key to control the use of drugs that induce the disease in a timely manner. Prevention of drug poisoning is not appropriate for newborns and babies. Patients with anemia, heart, lung, kidney, and liver disease are contraindicated for repeated use of this drug for a long time.
1. Take care of children and prevent accidental consumption of poisons and drugs.
2. Adolescents can develop self-injury poisoning and pay attention to the physical and mental health problems of adolescents.
3. Strengthen publicity and popularize related anti-drug knowledge such as plant medicines.
Complication
Drug-induced lupus complications Complications edema pericarditis myocarditis arteriosclerosis pulmonary edema
1, kidney complications
Some patients with lupus can cause kidney complications, edema, and edema in the patient, affecting the patient's body.
2, cardiac complications
Lupus erythematosus disease can also cause some problems in the patient's heart, which can easily lead to cardiac complications such as pericarditis, myocarditis, arteriosclerosis and other diseases.
3, pulmonary complications
When the condition is more serious, it will lead to acute pulmonary edema and other diseases.
Symptom
Symptoms of drug-induced lupus Common symptoms Spotted fever, fever, proteinuria, hematuria, constrictive pericarditis, pleural effusion, pericardial effusion
1. General symptoms: Half of the patients may have fever and weight loss. There is no special heat type in fever. It can be as high as 41 °C, and the weight loss is different, but it can be very serious.
2. Skin: Discoid lupus, butterfly erythema and other non-specific rashes and maculopapular rash can occur, but not as common in systemic lupus erythematosus, oral ulcers, Raynaud's phenomenon and severe hair loss are also rare in systemic lupus erythematosus.
3. Musculoskeletal system: very common, can affect 80% of patients, drug-induced lupus arthritis is similar to systemic lupus erythematosus, usually non-deformed, involving multiple joints, symmetric distribution, uncommon arthritis The small joints of the hand are most susceptible, followed by the wrist, elbow, shoulder, knee, and ankle joints. The joint exudation is not common. The synovial fluid is usually non-inflammatory (white blood cells <2×109/L). Even LE cells can be found. Myalgia is seen in 50% of drug-induced lupus, which can be very serious. Myalgia is often diffuse, affecting the proximal and distal muscle groups. Patients who take procainamide for a long time may have muscle weakness and no drug-induced lupus. Other performance.
4. pleurisy: common in pleurisy and pleural effusion, LE and ANA can be measured in pleural effusion, have diagnostic value, pulmonary infiltration and pulmonary parenchymal lesions in procainamide-induced drug lupus than in hydralazine and More common in systemic lupus erythematosus.
5. Pericarditis: Pericardial involvement is more common in procainamide-induced lupus than in hydralazine-induced lupus, usually milder, but constrictive pericarditis, massive pericardial exudation, and pericardial tamponade have also been reported. In some cases, LE cells can be detected in pericardial effusions.
6. Kidney: Kidney involvement is not common, but mild hematuria or proteinuria is not uncommon. In rare cases, there may be obvious impaired renal function. The pathological findings of renal biopsy are indistinguishable from systemic lupus, focal type, membrane Types and proliferative glomerulonephritis with or without crescent formation can be seen, complement and immune complex deposition can also be seen.
Examine
Drug-induced lupus examination
Abnormal blood is rare in systemic lupus erythematosus, with mild anemia, leukopenia, occasionally thrombocytopenia, promethazine, methyldopa and chlorpromazine-induced lupus may have Coombs test positive, but obvious Hemolysis is rare.
Homogeneous ANA positive is the most common serum abnormality, anti-Sm antibody, anti-DsDNA antibody is rare in systemic lupus erythematosus.
ANA in drug-induced lupus is mainly targeted at histones, but anti-histone antibodies are not specific for drug-induced lupus. 50% to 80% of systemic lupus erythematosus has anti-histone antibodies, rheumatoid arthritis, and Felty syndrome. Anti-histone antibodies can also be detected in juvenile rheumatoid arthritis and undifferentiated connective tissue disease.
Anti-histone antibodies in systemic lupus erythematosus can target all histones, H2A-H2B or H3-H4 complexes, mainly targeting H1 and H2b, different drug-induced lupus, and specificity of anti-histone antibodies, Plu The anti-histone protein in cainamide-induced lupus is mainly IgG, and the anti-histone antibody of asymptomatic patients taking procainamide for I(M2A-H2B)-DNA complex and chromatin is IgM, DNA H2A-H2B dimer, unlike procainamide-induced lupus, hydralazine-induced lupus anti-histone antibodies target a wider range of epitopes, often targeting DNA-free histones, including H3 And H4, as well as H3-H4, H2A-H2B and H1, (HZA-H2B)-DNA antibodies can be assayed in penicillamine, quinidine, and sulfasalazine-induced lupus.
Diagnosis
Diagnosis and identification of drug-induced lupus
diagnosis
At present, there is no specific diagnostic criteria. For example, if the patient has no systemic lupus erythematosus in the past, the clinical and serum manifestations of lupus appear during the course of taking a certain drug. The clinical symptoms are quickly relieved after the drug is stopped, and the serum abnormality is slowly improved. For drug-induced lupus.
Differential diagnosis
Drug lupus is similar to systemic lupus erythematosus, but it is very different, mainly in:
1 drug-induced lupus does not necessarily meet the diagnostic criteria for lupus in ACR;
2 drug-induced lupus patients have other diseases, for the medical treatment of this disease, are taking certain drugs, such as patients with rheumatoid arthritis taking penicillamine, patients with hypertension taking hydralazine or methyldopa;
3 The age of patients with drug-induced lupus is older than that of patients with systemic lupus erythematosus;
4 There is no female predominance in patients with drug-induced lupus;
5 drug-induced lupus symptoms are mild, with systemic symptoms, arthritis, pleurisy, pericarditis, similar to senile systemic lupus erythematosus, these symptoms are reversible, gradually disappear after stopping the drug;
6 drug-induced lupus and systemic lupus can be ANA, LE cells positive, but anti-DNA antibodies, anti-Sm antibodies are rare in drug-induced lupus.
In patients with other rheumatism, the symptoms of drug-induced lupus can be mistaken for the aggravation of the primary disease, thereby strengthening the treatment of the primary disease, making the disease more serious, so the disease should be considered in the differential diagnosis.
