Can Viral Illness Trigger SLE?
Yes, viral and bacterial infections can serve as environmental triggers for the development or exacerbation of SLE in genetically predisposed individuals, though the relationship is complex and bidirectional. 1
Evidence for Infection as a Trigger
The mechanism by which infections may precipitate SLE involves molecular mimicry, where specific microbial agents share structural similarities with self-antigens, potentially inducing autoimmune responses in susceptible individuals. 1, 2
Epstein-Barr virus (EBV) has the strongest evidence as a viral trigger for SLE, with research demonstrating that EBV infection may play a major role not only in molecular mimicry but also in causing aberrations of B cells and apoptosis, leading to a state of perpetual heightened immune response in SLE patients. 1
The Paradox: SLE Patients Are More Susceptible to Infections
While infections may trigger SLE, patients with established SLE are paradoxically at higher risk of developing infections due to:
- Inherent genetic and immunologic defects (complement deficiencies, mannose-binding lectin polymorphisms, elevated Fcγ III and GM-CSF levels, osteopontin polymorphism) 1, 2
- The disease itself, characterized by aberrant immune responses and complement dysregulation 3
- Broad-spectrum immunosuppressive therapy used to treat severe disease manifestations 1, 2
Infections account for 25-50% of overall mortality in SLE patients, with more than 20% of hospitalizations due to infections. 3, 4
Clinical Implications and Diagnostic Challenges
Distinguishing Infection from Lupus Flare
A critical clinical caveat is differentiating between a lupus flare and an acute infection, as both can present with fever and systemic symptoms. 1, 2
Elevated C-reactive protein (CRP) and adhesion molecules may aid in diagnosing infection rather than lupus flare, as CRP is typically not elevated in active lupus alone. 1, 2
The Vaccine Controversy
The relationship between infections and SLE creates a therapeutic dilemma regarding vaccination:
- Influenza infection itself is more likely than influenza immunization to trigger Guillain-Barré syndrome and other autoimmune phenomena. 3
- Vaccines can trigger development of autoantibodies (ANA, anti-dsDNA) in SLE patients and healthy individuals without causing clinically significant illness. 3
- In lupus patients who developed high titers of anti-dsDNA antibodies following immunization, titers returned to baseline by 12 weeks, suggesting immunization is usually innocuous. 3
Risk Factors for Infection-Triggered Disease Activity
Patients at highest risk for infection-related complications or disease exacerbation include those with:
- Severe disease flares and active renal disease 2
- Treatment with moderate or high doses of corticosteroids (>7.5-10 mg/day prednisone) 2, 5
- Immunosuppressive agents, particularly high-dose methylprednisolone or cyclophosphamide 2, 5
- Genetic susceptibility factors (complement deficiencies, mannose-binding lectin polymorphisms) 1, 2
Practical Management Approach
Prior to initiating immunosuppression, screen for chronic infections including tuberculosis, hepatitis B, hepatitis C, and HIV to prevent reactivation or exacerbation. 3, 2
Hydroxychloroquine has a well-known protective role against infection in addition to other beneficial properties and is recommended for all SLE patients where no contraindication exists. 5, 6
Vaccination is recommended despite theoretical concerns, as the benefits of preventing serious infections outweigh the minimal risk of triggering autoimmune phenomena. 3