Glucocorticoids (hereinafter referred to as hormones) are widely used in China, but there are phenomena of improper clinical use. Improper use includes both overuse, i.e., using hormones when they should not be used, and underuse, i.e., not using hormones when they should be used, or using small doses of hormones when large doses should be used. Both overuse and underuse can cause damage to a patient’s health.
Since there are differences in the use of hormones in the treatment of SLE by different doctors, it is necessary to standardize the application of hormones in SLE and try to formulate simple, standardized and reasonable principles of hormone application according to different conditions so as to benefit more patients.
I. Basic principles of hormone therapy for SLE
The basic principles of hormone therapy for SLE include
For induction of remission and long-term maintenance therapy, the starting dose should be adequate, followed by slow reduction and long-term maintenance.
Assessing the severity and activity of SLE and developing an individualized treatment plan.
Assessing the presence of relative contraindications to hormone use and, in patients with relative contraindications, rigorously assessing the need for hormone use according to the needs of the condition.
To recommend the use of prednisolone or methylprednisolone in patients with hepatic impairment.
Observation of efficacy and assessment of organ function during treatment.
Monitor possible complications during hormone use and adjust the treatment plan in a timely manner.
II. Hormone usage and dosage
The usage of hormone includes systemic application (intravenous injection and oral administration) and local application (local skin application, joint cavity injection, intraocular injection, etc.). According to the needs of the disease, hormones can be taken in the morning, given every other day or given in daily doses. Hormones can be divided into 4 dose ranges.
Low dose: Prednisone ≤ 7.5 mg/d (methylprednisolone ≤ 6 mg/d).
Medium dose: prednisone 7.5-30mg/d (methylprednisolone 6-24mg/d)
High dose: prednisone 30-100mg/d (methylprednisolone >24-80mg/d)
Super high dose (shock therapy): methylprednisolone 500-1000mg/d intravenously for 3-5 d. The higher the dose of hormone, the more effective it is, but also the greater the side effects. Hormone is like a double-edged sword, how to minimize the side effects of hormone while pursuing the efficacy is one of the most important concerns of clinicians.
Application of hormones in the treatment of systemic lupus erythematosus
1. Definition of the severity of SLE and lupus crisis
Mild SLE: SLE is clearly diagnosed and important target organs (including kidney, blood system, respiratory system, cardiovascular system, digestive system and central nervous system) are not involved.
Moderate and heavy SLE: It means that there is involvement of important organs and affects their functions.
Renal involvement: glomerulonephritis, acute glomerulonephritis, nephrotic syndrome.
Hematologic involvement: hemolytic anemia, granulocytopenia, thrombocytopenia, thrombotic thrombocytopenic purpura
neurological involvement: convulsions, impaired consciousness, coma, stroke, transverse myelitis, mononeuritis or polyneuritis, psychiatric symptoms, demyelinating syndrome
digestive system involvement: intestinal obstruction, mesenteric vasculitis, acute pancreatitis
respiratory system involvement: alveolar hemorrhage, pulmonary hypertension, pneumonia, interstitial fibrosis of the lungs
cardiovascular system involvement: pericardial tamponade, myocarditis, etc.
Others: cutaneous vasculitis, severe skin damage, myositis, etc.
Definition of lupus crisis: life-threatening acute and severe SLE is called lupus crisis, and the main clinical manifestations include
Acute glomerulonephritis.
Severe central nervous system damage.
Severe hemolytic anemia.
Severe thrombocytopenic purpura.
Severe granulocyte deficiency.
Severe cardiac damage.
Severe lupus pneumonia or alveolar hemorrhage.
Severe lupus hepatitis.
Severe vasculitis, etc.
2.Treatment of mild SLE
For the treatment of mild SLE, hormone is not the first choice of treatment drug.
Firstly, non-steroidal anti-inflammatory drugs and antimalarials are applied, and hormones can be considered after the treatment is ineffective.
Short-term local application of hormones can be used for the treatment of skin mucosal lesions, but the use of strong hormonal topical drugs for the face should be avoided as much as possible, and even if used, it should not exceed 1 week.
3. Treatment of moderately active SLE
The treatment of moderately active SLE is generally divided into 2 stages, namely induction of remission and maintenance therapy. Hormone combined with immunosuppressive therapy is recommended.
Induction remission therapy: The hormone dosage is usually prednisone, which is taken at dawn, or in divided doses if acute symptoms such as persistent high fever need to be controlled. Immunosuppressive drugs are usually added at the same time.
Maintenance therapy: After 4-8 weeks of induction remission therapy, the hormone is slowly reduced by 10% of the original dose every 2 weeks.
Maintenance therapy dose: Prednisone, if allowed
In the process of drug reduction, if the disease is unstable, the original dose can be maintained temporarily or the dose can be increased or combined with immunosuppressive therapy as appropriate.
4.Treatment of heavy SLE
Treatment of severe SLE especially emphasizes individualized program and requires the combination of other immunosuppressive drugs.
SLE treatment is also divided into 2 phases, namely induction of remission and maintenance therapy.
Immunosuppressive agents such as cyclophosphamide, azathioprine, methotrexate, mycophenolate, cyclosporine, and tacrolimus are available. Cyclophosphamide is one of the first-line drugs for the treatment of severe SLE, especially for patients with severe lupus nephritis and vasculitis.
5. Treatment of lupus crisis
In lupus crisis, high-dose methylprednisolone shock therapy is usually required to help patients overcome the crisis.
After the disease is controlled, the hormone should be gradually reduced until the minimum dose for disease control is reached, so as to avoid serious adverse reactions caused by the long-term use of large amounts of hormones.
In severe neuropsychiatric lupus, including transverse myelitis, intrathecal dexamethasone 10 mg/methotrexate 10 mg can be administered once a week for 3-5 times, if central infection is excluded.
Methylprednisolone shock therapy can only resolve the symptoms in the acute phase, and subsequent treatment must continue with hormone application and in conjunction with other immunosuppressive agents. The side effects of hormone should be closely observed before, during and after high-dose hormone shock therapy, including the occurrence of complications such as infection, gastrointestinal bleeding, diabetes mellitus and femoral head necrosis.
6. Treatment of patients during pregnancy and lactation
Contraindications to pregnancy in patients with SLE.
Severe relapse of SLE within the past 6 months, such as active lupus nephritis.
Severe pre-eclampsia or HELLP syndrome despite treatment.
severe pulmonary hypertension
Severe restrictive lung disease
Chronic renal failure.
Hormone application in patients before and during pregnancy.
Pregnancy is not affected when there is no significant organ damage before pregnancy, the disease is stable for 1 year or more, cytotoxic immunosuppressants are discontinued for 6 months, and hormones are maintained with prednisone ≤10 mg/d only.
Hormones should be used with caution during pregnancy and the lowest effective dose should be applied, preferably prednisone <20mg/d.
In the event of active disease, severe life-threatening conditions require immediate termination of pregnancy.
If pregnancy can continue after evaluation of the condition, increase the hormone dose as appropriate. Prednisone, prednisolone, and methylprednisolone are recommended, and dexamethasone and betamethasone are not recommended.
The use of hormones during the third trimester of pregnancy may increase the risk of fetal cleft lip and palate; therefore, the use of medium to high doses of hormones during the third trimester of pregnancy is not recommended.
Patients who have been treated with hormones for a long time should be treated with stress doses at the time of delivery.
Intravenous methylprednisolone shock therapy may be considered in case of disease recurrence.
In late pregnancy, dexamethasone may be used to promote fetal lung maturation.
During lactation, prednisone is relatively safe at 20-30 mg/d. It is recommended to take hormones for more than 4 h before lactation. Calcium and vitamin D supplementation until the end of the lactation period.
Management of congenital heart block in fetal lupus syndrome: The most common cardiac manifestation of fetal lupus syndrome is congenital heart block, which has a high morbidity and mortality rate. Trans-placental administration of fluorinated hormones (dexamethasone and betamethasone) improves the survival of fetuses with congenital heart block, but these drugs also carry a higher risk of intrauterine growth retardation and preterm delivery.
Prevention of morbid pregnancy due to antiphospholipid antibodies: Antiphospholipid antibodies are present in about 1/4-1/2 of SLE patients, and the main problem facing pregnancies in SLE patients exposed to antiphospholipid antibodies is the increased risk of morbid pregnancy. Anticoagulation therapy is the primary means of prevention, and the combination of hormones and aspirin may reduce the risk of morbid pregnancy, but the occurrence of maternal complications should be considered.
7. Adverse effects of hormones
Hormone therapy for SLE has a long course and care should be taken to protect the hypothalamic-pituitary-adrenal axis. It is recommended to avoid the use of long-acting and super-long-acting hormones such as dexamethasone, which have a large impact on the hypothalamic-pituitary-adrenal axis.
Long-term or high-dose or irregular use of hormones can induce and aggravate infections, lead to osteoporosis and aseptic necrosis of the femoral head, peptic ulcers, neuropsychiatric disorders, hypertension, diabetes mellitus, hyperlipidemia, sodium retention, hypokalemia, glaucoma, Cushing’s syndrome and a series of other adverse reactions, and in severe cases even lead to death of patients.
The adverse effects of hormone application are related to its dose and duration of treatment, and need to be regularly observed and evaluated to ensure the efficacy and safety, and to improve the survival rate and prognosis of SLE treatment.