Drug therapy: 

1. Analgesics (pain relievers) 

2. Nonsteroidal anti-inflammatory drugs (NSAIDs) 

3. Steroids 

4. Antimalarial drugs 

5. Immunomodulators/immunosuppressants 

6. Biologics 

7. Other related treatments, such as intravenous immunoglobulin 

8. Adjunctive therapy, such as controlling high cholesterol and osteoporosis 
    

Non-drug therapy:

​

1. Rehabilitation therapy (physical therapy and occupational therapy) 

Principles and Side Effects of Drug Therapy

(1). Analgesics: 

Used for joint or related tissue pain: 

• Paracetamol (acetaminophen) 

• Tramadol 

Used for neuropathic pain or fibromyalgia: 

• Anticonvulsants (e.g., gabapentin, pregabalin) 

• Antidepressants (e.g., tricyclic antidepressants, duloxetine) 
   

(2) Nonsteroidal anti-inflammatory drugs (NSAIDs): 

Includes traditional NSAIDs and COX-2 inhibitors, which can relieve pain and control inflammation (e.g., arthritis, synovitis). 

• Traditional NSAIDs: ibuprofen, naproxen, indomethacin, diclofenac, piroxicam 

• COX-2 inhibitors: celecoxib, etoricoxib 

• COX-2 inhibitors can reduce gastrointestinal ulcers and discomfort, but caution is still needed regarding blood pressure, kidney function, edema, and cardiac function. 
   

(3) Steroids: 

Steroid medications can be classified as long-acting or short-acting, and can be taken orally, injected, or topically applied. Different doses are used based on the patient's condition. 

• High dose: 500mg or 1,000mg intravenous injection 

• High dose: 1mg/kg per day 

• Medium dose: 0.5mg/kg per day 

• Low or physiological dose: 10mg or below 
   

In most cases, the side effects of steroids are proportional to the dose used. Therefore, once the acute condition is under control, the dose should be gradually reduced to minimize side effects. Additionally, some traditional Chinese medicines have anti-inflammatory effects through the hypothalamic-pituitary-adrenal axis. Research has shown that licorice, a Chinese herb, also has glucocorticoid and mineralocorticoid effects. 
 

When using steroid medications, attention should be paid to electrolyte loss, osteoporosis, blood sugar, lipid levels, and blood pressure control. Moreover, individuals who frequently use steroids may experience delayed wound healing and should be cautious about the risk of infection. It is worth noting that using high-dose steroids for a short period (one to two months) may lead to osteonecrosis. 

(4). Antimalarial drug

This type of medication is commonly known as "golden chicken extract" and is used to treat lupus erythematosus. It has a history of over a hundred years. In mainland China, it is known as "Fenle." In the past, most hospitals used the antimalarial drug Chloroquine (250mg per pill), but now they have switched to Hydroxychloroquine (200mg per pill). Although this medication is more expensive, it has fewer side effects. 

Hydroxychloroquine has milder side effects such as gastrointestinal discomfort, dizziness, headache, and slight drowsiness, while severe side effects are rare. Some patients may experience skin pigmentation changes, and about 10% of patients may develop a rash with increased sensitivity. 

Data shows that compared to the traditional Chloroquine, Hydroxychloroquine significantly reduces the chances of heart, muscle, and retinal changes. Studies have shown that even with long-term use of Hydroxychloroquine for five to seven years, there is only a 0.3% chance of developing retinal changes. The risk is even lower if the dosage is controlled at a certain level, such as 6.5mg/kg/day based on ideal body weight. Regular retinal examinations can help detect any visual impairment early and preserve vision. 

(5). Immune Modulating/Suppressing Drugs 

Immune modulating drugs are mainly used in the following situations: 

• When important organs such as the kidneys, nervous system, heart, and lungs are under attack. 

• When constitutional symptoms or joint and skin manifestations are not controlled even after using antimalarial drugs or low-dose steroids. 

• As an alternative to or in conjunction with steroids to reduce their dosage (steroid-sparing drugs). 
   

 i) Mycophenolate Mofetil (MMF) 

Originally used as an anti-rejection medication, MMF has been widely used in the treatment of lupus erythematosus in recent years, especially in lupus nephritis. The usual dosage is 1g twice daily, which can be gradually reduced to 500mg twice daily after improvement of the condition. 

In the treatment of active Class IV nephritis, MMF has similar efficacy to intravenous cyclophosphamide but with fewer side effects such as hair loss or menstrual changes. During the remission or maintenance phase, MMF is more effective than azathioprine in reducing relapses. 

Common side effects include gastrointestinal discomfort such as abdominal pain, slight nausea, and diarrhea. Patients can discuss with their doctors to adjust the dosage to improve their condition. Additionally, about 10% of patients may experience more severe infections, so monitoring of white blood cell count, liver function, and kidney function is necessary during the medication period. 

ii) Azathioprine (AZA) 

Azathioprine, also known as AZA, is primarily used as a steroid-sparing drug or as a maintenance treatment following cyclophosphamide. Its mechanism of action involves suppressing the immune system by interfering with the production of purines in the body. The commonly prescribed dosage is 2mg/kg per day. 

The main side effects of Azathioprine include gastrointestinal discomfort, with about 12% of patients experiencing nausea or vomiting. Approximately one-fourth of patients may experience leukopenia (low white blood cell count) or elevated liver enzymes, which increases the risk of infections. Studies have shown that patients with low or deficient levels of the enzyme TPMT may experience further leukopenia and bone marrow suppression. Therefore, it is recommended to assess TPMT activity through blood tests based on individual patient circumstances. It is worth mentioning that the concomitant use of uric acid-lowering medications (such as Allopurinol or Febuxostat) significantly increases the risk of bone marrow suppression. 

iii) Cyclophosphamide (CTX) 

Cyclophosphamide, also known as CTX, is a potent immunosuppressant. Some studies have shown similarities between its pharmacological effects and the Chinese herb Tripterygium wilfordii (also known as "Leigongteng" or "Thunder God Vine"). Cyclophosphamide primarily affects the production of deoxyribonucleic acid (DNA) and inhibits cell division. It is mainly used for severe complications such as encephalitis, severe nephritis, pulmonary hemorrhage, and myelitis. 

The administration of cyclophosphamide can be oral (approximately 1-2mg/kg per day) or intravenous (500mg every two weeks for a total of 6 doses; 500-1,000mg/m2 body surface area once a month for 6 doses). When administered intravenously, the drug's accumulation in the body is lower, resulting in fewer side effects. 

Common side effects of cyclophosphamide include gastrointestinal discomfort (such as indigestion or nausea), hemorrhagic cystitis, leukopenia, hair loss, abnormal menstruation, amenorrhea, and susceptibility to infections. In the long term, it may slightly increase the risk of bladder cancer. 

iv) Cyclosporine A (CYCA) and Tacrolimus 

In the past, drugs like Cyclosporine A and Tacrolimus were used to reduce rejection, mainly by reducing T-cell-related activation. Tacrolimus is a newer and more expensive medication. The common dosages are as follows: 

• Cyclosporine A: 2.5mg-4mg/kg per day 

• Tacrolimus: 0.1mg-0.2mg/kg per day 
   

These drugs are more commonly used in Type V (membranous) nephritis cases. Side effects include hypertension, tremors, gastrointestinal discomfort, renal dysfunction, elevated triglyceride levels, and susceptibility to infections. When using Tacrolimus, it is necessary to monitor and control blood glucose levels, while Cyclosporine A may cause increased hair growth. 

v) Methotrexate (MTX) 

Methotrexate, also known as MTX, is an important medication for treating rheumatoid arthritis. It primarily targets folic acid and subsequently affects DNA production. When patients with systemic lupus erythematosus experience active arthritis, it is an alternative option to hydroxychloroquine. The commonly prescribed dosage is 0.3mg/kg per week, taken once a week. 

Side effects of methotrexate include oral ulcers, gastrointestinal discomfort, and, in some cases, leukopenia and elevated liver enzymes. Patients can take folate supplementation one to two days after taking MTX to reduce these side effects. 

Due to a deeper understanding of systemic lupus erythematosus (SLE) in recent years, targeted biologics have been developed for its treatment. As SLE patients have particularly active B cells, drug research has focused on this aspect. 

(6). Biologics
 

1. Belimumab: Belimumab is a biologic approved by the U.S. Food and Drug Administration (FDA) for the treatment of SLE since 2011. It works by inhibiting the binding of B-lymphocyte stimulator (BLyS) to B cells, thereby reducing B cell activity. The recommended dosage is 10mg/kg administered intravenously every two weeks for the first three doses, followed by once every four weeks.  
   
   Also have 200mg subcutaneous pen also ready. Patient can do weekly injections with autoinjector.  
   
   Benlysta also not only indicated for SLE but also Lupus Nephritis .
   
   Common side effects include injection reactions (approximately 17%), allergies (13%), feeling of being suffocated (15%), and diarrhea (12%). 
    

2. Rituximab: Rituximab has not yet received formal approval but has been mentioned in some case reports and clinical applications. Two randomized comparative studies have not shown significant differences between Rituximab and conventional drugs. Rituximab primarily targets the CD20 antigen on B cells to achieve B cell depletion. The usual regimen is two intravenous infusions of 1,000mg each, two weeks apart. 
   
   Side effects include injection reactions (approximately 10%-30%), headache, fever, chills, and gastrointestinal discomfort. 

​

​

​

Reference: 

Hong Kong Rheumatism Foundation: Dance with Lupus: Care and Treatment of Systemic Lupus Erythematosus. Joint Publishing (H.K.) Co., Ltd., 2017.