Infections as triggers and complications of systemic lupus erythematosus

doi:10.1016/j.autrev.2008.07.019

Autoimmunity Reviews

Volume 8, Issue 1, October 2008, Pages 24-28

https://doi.org/10.1016/j.autrev.2008.07.019 Get rights and content

Abstract

A growing body of experimental and clinical evidence supports the pivotal role of infections in the induction or exacerbation of systemic lupus erythematosus (SLE). Infections can be responsible for aberrant immune response leading to a loss of tolerance towards native proteins. Molecular mimicry, especially between Sm or Ro autoantigens and EBV Nuclear Antigen-1 response, as well as the over-expression of type 1 INF genes are among the major contributors to SLE development.

On the other hand infections are very common in SLE patients, where they are responsible for 30–50% of morbidity and mortality.

Several factors, either genetic, including complement deficiencies or mannose-binding lectin deficiency or acquired such as severe disease manifestations or immunosuppressant use, predispose SLE patients to infections. All types of infections, including bacterial, viral and opportunistic infections, have been reported and the most frequently involved sites of infections are the same as those observed in the general population, including respiratory, skin, and urinary tract infections.

Some preventive measures could be adopted in order to reduce the rate of infections in SLE patients: i.e. screening for Mycobacterium tuberculosis and for some chronic viral infections before immunosuppressive treatment; adequate prophylaxes or drug adjustments when indicated, and pneumococcal and influenza vaccinations in patients with stable disease.

Section snippets

Infections as SLE trigger

A growing body of experimental and clinical data supports the pivotal role of infections in the induction and/or exacerbation of SLE [4].

It is believed that SLE occurs when an environmental trigger acts on a genetically predisposed individual, leading to a loss of tolerance towards native proteins [4]. Viruses such as Cytomegalovirus (CMV), Epstein–Barr (EBV) and Parvovirus B19 are frequently involved as environmental triggers in SLE autoimmunity [4].

“Molecular mimicry/cross reactivity” is an

Infections as SLE complication

Infections are very common in SLE patients where they are responsible for 30–50% of morbidity and mortality [4], [11], [12].

Recent epidemiological evidence has clearly shown that short- and medium-term survival rate of patients affected with SLE has greatly improved in the last decades, but unfortunately long-term prognosis still remains very poor [13]. This means that the current treatment for SLE is more effective than that used in the past, but in the long-term, complications of the disease

How to reduce infection rate in SLE

With the aim of lowering infection rate in SLE, some preventive strategies should be used early in the disease course [38], [39].

First of all, we should try to optimize treatment using corticosteroids and immunosuppressants at the lowest effective dosage and to adapt the treatment to the single patient according to the disease severity and to the patient’s general condition [39].

Before using immunosuppressants and/or a high dosage of corticosteroids, a systematic screening for M. tuberculosis

Take-home messages

•
There is a clear evidence that pathogens, especially viruses, can trigger SLE.
•
Infection is a major source of morbidity and mortality in SLE.
•
The most common cause of infections is pyogenic bacteria; however, the frequency of opportunistic infections is increasing due to aggressive immunosuppressive therapy.
•
Some preventive strategies could be adopted in order to reduce the rate of major infections in SLE.

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Se incluyeron 40 casos (34 mujeres) con 35,5 años en promedio. La principal causa de fiebre fue la coexistencia de infección y actividad (17/40; 43%), seguida de fiebre solo por actividad (14/40; 35%). La infección más frecuente fue neumonía (10/40; 25%) y la actividad más común fue renal (21/40; 53%). Para diagnosticar «fiebre por infección con o sin actividad», comparado con «fiebre solo por actividad», la PCR tuvo un ABC: 0,86 (IC 95%: 0,75-0,97) con 5,4 mg/dl como mejor punto de corte (S: 76,9%; E: 85,7%; VPP: 90,9; VPN: 66,6%). Para diagnosticar «fiebre solo por actividad», comparado con «fiebre por infección c/s actividad», la razón VSG/PCR tuvo ABC: 0,83 (IC 95%: 0,68-0,98), con 21,42 como mejor corte (S: 78,6%; E: 84,6%; VPP: 73,3%; VPN: 88,0%).
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In patients with systemic lupus erythematosus (SLE) and fever, the causes are infection and/or activity. We assessed the diagnostic accuracy of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) to discern these causes.
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We included 40 cases (34 women) with an average age of 35.5 years. The main cause of fever was the coexistence of infection and activity (17/40; 43%), followed by fever only due to activity (14/40; 35%). The most frequent infection was pneumonia (10/40; 25%) and the most common activity was renal (21/40; 53%). To diagnose”fever due to infection with-or-without activity”, compared to “fever only due to activity”, CRP had an AUC: .86 (95% CI: .75-.97) with 5.4 mg/dl as the best cut-off value (Se: 76.9%; Sp: 85.7%; PPV: 90.9; NPV: 66.6%). To diagnose “fever due to activity only”, compared to “fever due to infection with or without activity”, the ESR/CRP ratio had an AUC: .83 (95% CI: .68-.98) with 21.42 as the best cut-off value (Se: 78.6%; Sp: 84.6%; PPV: 73.3%; NPV: 88.0%).
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To develop recommendations for the prevention of infection in adult patients with systemic autoimmune rheumatic diseases (SARD).
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Infections as triggers and complications of systemic lupus erythematosus

Abstract

Section snippets

Infections as SLE trigger

Infections as SLE complication

How to reduce infection rate in SLE

Take-home messages

Autoimmun Rev

Infect Dis Clin N Am

Autoimmun Rev

Semin Arthritis Rheum

Mayo Clin Proc

Autoimmun Rev

Clearance of dying cells and autoimmunity

Autoimmunity

Autoantigen, innate immunity, and T cells cooperate to break B cell tolerance during bacterial infection

J Clin Invest

Infections and SLE

Autoimmunity

Epstein–Barr virus and molecular mimicry in systemic lupus erythematosus

Autoimmunity

Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry

Nat Med

Role of Epstein–Barr Virus in systemic lupus erythematosus

Curr Opin Rheumatol

Interferon and granulopoiesis signatures in systemic lupus erythematosus blood

J Exp Med

Toll-like receptors in systemic autoimmune disease

Nature Rev Immunol

Lupus around the world: systemic lupus erythematosus and infections: a retrospective study in Saudis

Lupus

DNA methylation: its contribution to systemic lupus erythematosus

Clin Exp Med

Long-term prognosis and causes of death in systemic lupus erythematosus

Am J Med

Mortality in systemic lupus erythematosus

Arthritis Rheum

Environment and systemic lupus erythematosus: an overview

Autoimmunity

Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus

Hum Mol Genet