Immune dysregulation in systemic lupus erythematosus (SLE) results in the autoimmune manifestations of SLE, but also leads to an impaired immune response to pathogens and vulnerability to infections in SLE patients. These patients exhibit a complex immune dysfunction, characterized by both impaired cellular and humoral immunity alongside defects in innate immunity. This occurs even in the absence of immunosuppressive therapy, highlighting the intrinsic nature of the immune dysregulation. Consequently, infection-related complications remain a significant cause of morbidity and mortality in SLE.¹

The respiratory tract, urinary tract, skin and soft tissue are among the most common sites of infection in SLE patients, frequently caused by an increased susceptibility to common pathogens such as Streptococcus pneumonia, Escherichia coli and Staphylococcus aureus. However, these patients are also at an increased risk of Herpes zoster, Mycobacterium tuberculosis and even opportunistic pathogens such as Pneumocystis jirovecii and Cryptococcus neoformans or Cytomegalovirus disease.²

The risk of these infections in SLE patients is also greatly impacted using immunosuppressive medication.³ Depending on the mechanism of immune suppression, susceptibility to infections with different pathogens will increase. Prolonged use of corticosteroids, for instance, is associated with mycobacterial disease and risk of Pneumocystis jirovecii pneumonia. Anti-CD20 therapy (rituximab), however, increases the risk of hepatitis B reactivation, viral infections and common pathogens causing respiratory infections.⁴

Knowledge of which pathogens to expect, in the often severely immunocompromised SLE patient, is essential in guiding diagnostics in case of acute inflammatory disease, especially because it can be difficult to distinguish between an infection and SLE flare. Moreover, it must guide infection prevention strategies. Recent data show a hopeful reduction in the proportion of mortality contributed to infectious diseases in an Italian cohort of SLE patients, indicating an overall better management of the infectious disease risk in the SLE patient.⁵

References

1. Chan SCW, Lau CS. Systemic lupus erythematosus and immunodeficiency. Rheumatol Immunol Res. 2021;2(3):131–38. doi: 10.2478/rir-2021-0019.

2. Barber MRW, Clarke AE. Systemic lupus erythematosus and risk of infection. Expert Rev Clin Immunol. 2020;16(5):527–38. doi: 10.1080/1744666x.2020.1763793.

3. Pego-Reigosa JM, Nicholson L, Pooley N, et al. The risk of infections in adult patients with systemic lupus erythematosus: Systematic review and meta-analysis. Rheumatology (Oxford). 2021;60(1):60–72. doi: 10.1093/rheumatology/keaa478.

4. Anvari S, Tsoi K. Hepatitis B virus reactivation with immunosuppression: A hidden threat? J Clin Med. 2024;13(2) doi: 10.3390/jcm13020393.

5. Zen M, Salmaso L, Barbiellini Amidei C, et al. Mortality and causes of death in systemic lupus erythematosus over the last decade: Data from a large population-based study. Eur J Intern Med. 2023;112:45–51. doi: 10.1016/j.ejim.2023.02.004.

Learning Objectives At the end of this presentation participants will be able to:

• Explain how immune dysregulation in SLE leads to both autoimmune manifestations and increased susceptibility to infections

• Identify common infection sites and typical pathogens in patients with SLE, even in the absence of immunosuppressive therapy

• Describe how different immunosuppressive medications used in SLE treatment can further increase susceptibility to specific pathogens

• Discuss the challenges in diagnosing infections in SLE patients and the importance of considering both infection prevention and early diagnosis