What is Systemic Lupus Erythematosus (SLE)?

From the Guidelines

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease characterized by immune complex deposition and vasculopathy, affecting multiple organs and tissues, with a complex interplay of genetic susceptibility and environmental factors, and is more common among women, with an estimated prevalence of 20 to 150 cases per 100,000 population 1.

Definition and Pathogenesis

SLE is a prototypic chronic multi-organ autoimmune disease, with clinical heterogeneity, and can affect any organ and tissue of the human body, including joints, skin, kidneys, heart, lungs, and brain. The pathogenesis of SLE is not fully understood, but it is believed to result from a complex interplay between genetic susceptibility and environmental factors, with dysregulation of type-1 interferon being a common denominator 1.

Clinical Features and Diagnosis

The clinical features of SLE vary widely between individuals, but common symptoms include fatigue, joint pain, rash, and fever. Diagnosis is based on a combination of clinical and laboratory findings, including the presence of antinuclear antibodies and other specific autoantibodies.

Treatment and Management

Treatment of SLE depends on symptom severity and affected organs, and may include medications such as hydroxychloroquine, corticosteroids, and immunosuppressants, as well as biologic medications like belimumab, with the goal of achieving remission or low disease activity and preventing flares 1.

• Key treatment principles include:

• Using hydroxychloroquine as the cornerstone medication for mild symptoms
• Adding corticosteroids and immunosuppressants for moderate to severe disease
• Considering biologic medications like belimumab for persistent symptoms
• Monitoring for flares and adjusting treatment accordingly

Recent Updates and Recommendations

Recent studies have provided new evidence for the management of SLE, including the use of anifrolumab and belimumab in extrarenal disease, and combination treatments with belimumab or voclosporin in lupus nephritis, with the goal of achieving remission or low disease activity and preventing adverse outcomes 1. The most recent and highest quality study, published in 2024, recommends a treatment approach that prioritizes remission and low disease activity, with a focus on combination treatments and biologic medications, and emphasizes the importance of monitoring and adjusting treatment to prevent flares and adverse outcomes 1.

From the Research

Definition and Characteristics of Systemic Lupus Erythematosus (SLE)

• Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by inflammation and immune-mediated injury to multiple organ systems, including the mucocutaneous, musculoskeletal, hematologic, and kidney systems 2.
• SLE can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations 3.
• The disease is associated with immune-mediated damage to multiple organs and increased mortality 2.

Pathogenesis of SLE

• B-cells abnormalities leading to autoantibody production play a central role in Systemic Lupus Erythematosus (SLE) pathogenesis 3.
• The targets of biological therapies are directed toward the B cell depletion, interference in the co-stimulation signals and the blockade of cytokines 3.

Diagnosis and Treatment of SLE

• Although there are no uniformly accepted diagnostic criteria for SLE, the 2019 European Alliance of Associations for Rheumatology (formerly the European League Against Rheumatism)/American College of Rheumatology classification criteria developed for scientific study are an estimated 96.1% sensitive and 93.4% specific for SLE 2.
• The primary goal of treatment is to achieve disease remission or quiescence, defined by minimal symptoms, low levels of autoimmune inflammatory markers, and minimal systemic glucocorticoid requirement while the patient is treated with maintenance doses of immunomodulatory or immunosuppressive medications 2.
• Hydroxychloroquine is standard of care for SLE and has been associated with a significant reduction in mortality 2, 4.
• Treatments in addition to hydroxychloroquine are individualized, with immunosuppressive agents, such as azathioprine, mycophenolate mofetil, and cyclophosphamide, typically used for treating moderate to severe disease 2, 4.

Treatment Options for Refractory SLE

• In cases of treatment failure or intolerance, mycophenolate mofetil or even azathioprine may be considered as an alternative treatment 5.
• As a last resort, after having weighed up the individual benefit-risk ratio, leflunomide, belimumab, rituximab or abatacept may be considered, on a case-by-case basis, and anti-TNF antibodies may be considered in exceptional cases 5.
• Biologic agents targeting specific pathways (i.e. T-B lymphocyte interaction, cytokines and complement) have been also proposed as new tools for SLE treatment 3.