Rational application of glucocorticoids in the treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-system damage and the presence of multiple autoantibodies in the serum. It is one of the common rheumatic diseases in children. SLE in children is more severe than in adults and is more likely to affect important organs, especially the kidneys, heart, and nervous system [1,2]. Systemic symptoms are also more common than in adults, such as fever (60%-100%), fatigue, weight loss, hair loss, and systemic inflammatory changes, such as lymphadenopathy (30%-40%) and hepatosplenomegaly.

Glucocorticoids (GC) have a wide range of anti-inflammatory and immunosuppressive effects. They are currently the basic drugs for the treatment of childhood SLE. They are widely used in the treatment of childhood SLE and generally require a long period of application. Long-term use of GC can lead to a series of adverse reactions in the body, including repeated infections, hypertension, diabetes, osteoporosis, glaucoma or cataracts, especially affecting the growth and development of children, and seriously reducing the quality of life of children. Therefore, it is particularly important to use GC rationally, attach importance to GS medication education, improve children's medication compliance, and give full play to its therapeutic effect.

1. Glucocorticoids commonly used in the treatment of systemic lupus erythematosus

Commonly used GCs in clinical practice can be divided into short-acting, medium-acting and long-acting. Since the treatment course of GCs for children with SLE is relatively long, long-acting GCs that have a greater impact on the hypothalamus-pituitary-adrenal axis should be avoided. Commonly used glucocorticoids in clinical practice include methylprednisolone and prednisone.

2. Principles of glucocorticoid treatment of systemic lupus erythematosus

1. Mildly active SLE: Nonsteroidal anti-inflammatory drugs and antimalarial drugs are preferred. Low-dose GC can be used if necessary [3,4]. Low-dose GC usually has fewer adverse reactions, but long-term use may be detrimental to the height growth of children. Since SLE in children often affects multiple systems and is more severe than that in adults, most children with SLE still require GC treatment [5].

2. Moderately active SLE: Oral administration of adequate GC (prednisone 1.5-2.0 mg/(kg·d), maximum dose 60 mg/d) is required, combined with immunosuppressive therapy such as cyclophosphamide, azathioprine, methotrexate, leflunomide, etc.

3. Severely active SLE and lupus crisis: divided into two stages: induction remission and maintenance treatment. In the induction remission stage, sufficient GS combined with immunosuppressants should be used for treatment. Severely active SLE, especially children with lupus crisis, require high-dose intravenous methylprednisolone pulse treatment. The commonly used dose is 15-30 mg/(kg·d), and the maximum dose is 500-1000 mg/d, which is used for 3 consecutive days. At the same time, cyclophosphamide (CTX) pulse treatment is combined. In the maintenance treatment stage, the dose of GS should be gradually reduced according to the condition, and finally maintained with a small dose.

4. When special organs are affected: (1) Lupus nephritis: In principle, GS combined with immunosuppressants are given for treatment. Renal puncture biopsy is performed to clarify the pathological type according to the severity of clinical manifestations. Different treatment plans are used according to different pathological types; (2) Lupus of the nervous system: It is one of the manifestations of severe lupus and lupus crisis. Methylprednisolone combined with CTX double shock treatment is often required for induction of remission to quickly control the disease.

3. Precautions for the use of glucocorticoids

During the long-term treatment of systemic lupus erythematosus, special attention should be paid to preventing Cushing's syndrome, infection, osteoporosis, aseptic necrosis of the femoral head, steroid diabetes, hypertension, hormone-induced glaucoma and cataracts, and growth retardation. For the prevention and treatment of osteoporosis, it is recommended to supplement vitamin D 600-800 U/d and calcium 1000-1200 mg/d during GC treatment. Long-term GC users should monitor bone density regularly (every 6-12 months). For those with severe bone density loss and a history of brittle fractures, it is recommended to add bisphosphonates to counteract bone resorption. During high-dose methylprednisolone shock treatment, various infections, especially tuberculosis and fungi, should be fully excluded. At the same time, close observation should be made for complications such as hypertension, stress gastric ulcer bleeding, increased blood sugar, and eye damage. While using GC, efforts should be made to minimize adverse reactions.

4. Pay attention to the medication education of glucocorticoids

When using GS for the first time, parents should be informed to ensure that their children get enough rest, especially those who are taking immunosuppressants at the same time. They should take personal protection to avoid infection during medication. Take GS as prescribed by the doctor. Do not change the dosage or stop the medication without authorization. Go to the outpatient clinic for regular follow-up visits and adjust the dosage according to changes in the condition. Some children may experience excitement of the nervous system, such as excitement, insomnia, and irritability when using GS for the first time. These are adverse reactions of hormones and are usually tolerable. They can continue to be used. As the efficacy of use increases and the dosage decreases, the above symptoms will gradually decrease to disappear. Some children may experience eye pain and headache. If the symptoms do not improve or continue to worsen, be alert to the possibility of drug-induced glaucoma and go to the hospital for treatment in time.

References:

[1] Zhan Zhongping, Liang Liuqin, Chen Dongying, et al. Comparative study of systemic lupus erythematosus in children and adults[J]. Journal of Southern Medical University, 2008, 28(011):1990-1992.

[2] Tucker LB, Menon S, Schaller JG, et al. ADULT- AND CHILDHOOD-ONSET SYSTEMIC LUPUS ERYTHEMATOSUS: A COMPARISON OF ONSET, CLINICAL FEATURES, SEROLOGY, AND OUTCOME[J]. British Journal of Rheumatology, 1995(9):866.

[3] Expert Group of the Chinese Systemic Lupus Erythematosus Research Collaborative Group. Expert consensus on the rational use of glucocorticoids in patients with systemic lupus erythematosus [J]. Chinese Journal of Internal Medicine, 2014, 53(6): 502.504. DOI: 10.3760/cma.j.issn.0578-1426. 2014.06.023.

[4] Kuhn A, Bonsmann G, Anders HJ, et a1. The diagnosis and treatment of systemic lupus erythematosus[J]． Dtseh Arztebl Int. 2015.1 12(25):423-432． DOI: 10．3238／arztebl． 2015.0423．

[5] Chinese Medical Association Pediatrics Branch Children's Drug Use Committee, Chinese Medical Association Pediatrics Branch Immunology Group, Chinese Journal of Pediatrics Editorial Board. Expert consensus on the use of glucocorticoids in pediatric rheumatic diseases (Part 1) [J]. Chinese Journal of Pediatrics, 2018(3):166-173.

Meng Yan, Hebei Provincial Children's Hospital