What triggers systemic lupus erythematosus (SLE)?

Triggers of Systemic Lupus Erythematosus (SLE)

Systemic lupus erythematosus (SLE) is triggered by a complex interplay of genetic susceptibility and environmental factors, with the most significant environmental triggers being ultraviolet light exposure, infections, medications, smoking, and living near agricultural areas with chemical exposures.

Genetic and Environmental Interaction

SLE develops when environmental triggers interact with genetic predisposition, leading to immune system dysregulation. This interaction involves:

• Genetic susceptibility as the foundation
• Environmental factors that initiate or exacerbate the disease
• Epigenetic changes that alter gene expression without changing DNA sequence

Major Environmental Triggers

1. Ultraviolet (UV) Light Exposure

• Strong evidence links UV radiation to both disease onset and flares 1, 2
• Mechanism: UV light damages DNA and induces apoptosis, releasing nuclear antigens that trigger autoimmune responses
• Prevention: Photo-protection is recommended for all SLE patients 3

2. Infections

• Various infections can trigger SLE onset or flares 1
• Cytomegalovirus (CMV) antigenaemia has been reported in 18-44% of patients, particularly those treated with pulse methylprednisolone and cyclophosphamide 3
• Tuberculosis incidence is higher in SLE patients than the general population 3

3. Medications

• Certain drugs can induce lupus-like syndromes or exacerbate existing SLE 2
• Common culprits include:
  • TNF-α inhibitors
  • Procainamide
  • Hydralazine
  • Minocycline
  • Some biologics

4. Smoking

• Both active and passive smoking significantly increase SLE risk 4
• Passive smoking showed an odds ratio of 24.116 (95% CI 1.763-329.799) in a case-control study 4
• Smoking may reduce the effectiveness of antimalarials, which are cornerstone treatments 3

5. Chemical Exposures

• Living near agricultural areas with pesticide exposure increases risk (OR 58.556,95% CI 1.897-1807.759) 4
• Heavy metals like lead (blood levels ≥0.075 mg/L) show significant association (OR 18.981,95% CI 1.228-293.364) 4

6. Hormonal Factors

• Explains female predominance (9:1 female to male ratio)
• Estrogens may contribute to disease development and flares 5, 6
• Pregnancy can trigger disease onset or flares in susceptible individuals

Protective Factors

• Regular physical activity appears protective (p=0.006) 4
• Maintaining adequate vitamin D levels may be beneficial, especially since many SLE patients avoid sun exposure 3

Prevention and Management Strategies

The EULAR and GLADEL-PANLAR guidelines recommend:

1. Photo-protection for all SLE patients 3
2. Vaccination against common infections, with special considerations:
   • Inactivated vaccines are generally safe and recommended
   • Live vaccines should be avoided in patients on immunosuppressive therapy 3
   • Pneumococcal vaccination is recommended due to high risk of infection 3
3. Smoking cessation should be strongly encouraged 3
4. Medication review to identify and discontinue potential triggering drugs
5. Regular monitoring for disease activity every 6-12 months in stable patients 3

Treatment Approach

When SLE is triggered, treatment should follow these principles:

1. All patients should receive antimalarials (hydroxychloroquine 5 mg/kg/day) unless contraindicated 3, 7
2. Glucocorticoids should be prescribed at the lowest possible dose and for the shortest time 7
3. Early initiation of immunomodulatory agents to achieve remission or low disease activity 7
4. Treatment should be tailored based on organ involvement and disease severity 7

Conclusion

Understanding SLE triggers is crucial for both prevention and management. While genetic predisposition creates susceptibility, environmental factors often determine disease onset and flares. Identifying and mitigating these triggers, particularly UV exposure, infections, and smoking, should be part of comprehensive SLE management.