What is the definition of early Systemic Lupus Erythematosus (SLE)?

From the Guidelines

Early Systemic Lupus Erythematosus (SLE) is defined as the initial phase of this chronic autoimmune disease when symptoms are beginning to manifest but may not yet meet the full diagnostic criteria for established SLE, characterized by the presence of autoantibodies and some clinical manifestations that suggest lupus. The definition of early SLE is crucial for prompt intervention and prevention of disease progression. According to the latest evidence, early SLE is characterized by the presence of autoantibodies, particularly antinuclear antibodies (ANA), along with some clinical manifestations that suggest lupus, such as unexplained fever, fatigue, joint pain, mild rashes, or photosensitivity 1. During this early stage, patients may experience intermittent symptoms that come and go, making diagnosis challenging. Laboratory findings might show some abnormalities like low complement levels, elevated inflammatory markers, or the presence of specific autoantibodies like anti-dsDNA or anti-Smith antibodies, though not always at levels seen in established disease.

Some key points to consider in the definition of early SLE include:

• The presence of autoantibodies, particularly ANA
• Clinical manifestations that suggest lupus, such as unexplained fever, fatigue, joint pain, mild rashes, or photosensitivity
• Intermittent symptoms that come and go, making diagnosis challenging
• Laboratory findings that show some abnormalities, but not always at levels seen in established disease The EULAR/ACR 2019 criteria provide a simple, direct, and precise classification method that can be easily implemented and even integrated in computer applications 1. However, the multifactorial nature of SLE potentially generates a very large number of different phenotypes for which there is no evidence of a common aetiology or a pathogenic association.

In terms of management, the 2019 update of the EULAR recommendations for the management of SLE provides guidance on the use of medications such as hydroxychloroquine, glucocorticoids, and immunosuppressive agents 1. The use of hydroxychloroquine is recommended for all patients with SLE, unless contraindicated, at a dose not exceeding 5 mg/kg/real BW. The pathophysiology of SLE involves dysregulation of the immune system where the body produces antibodies against its own tissues, leading to inflammation and potential damage across multiple organ systems if left untreated. Prevention of disease flares is an additional milestone of SLE treatment, and consistently reported risk factors for a higher disease flare rate include younger age at disease onset, no use of antimalarials, persistent generalised disease activity and serological activity (anti-dsDNA, low complement) 1.

From the Research

Definition of Early Systemic Lupus Erythematosus (SLE)

• Early SLE refers to the initial stages of the disease, where symptoms and clinical manifestations first appear 2, 3.
• The definition of early SLE is not strictly defined in terms of a specific time frame, but rather by the presence of early symptoms and signs of the disease, such as constitutional, mucocutaneous, and musculoskeletal symptoms 3.
• These early symptoms can include fatigue, lupus-specific rash, mouth ulcers, alopecia, joint pain, and myalgia, and can occur before the diagnosis of SLE is made 3.

Characteristics of Early SLE

• Early SLE is often characterized by a higher prevalence of positive family history for autoimmune diseases, systemic symptoms at presentation, internal organs involvement, and shorter time between symptoms onset and diagnosis 4.
• Autoantibodies, such as antinuclear antibody (ANA), anti-double-stranded DNA (anti-dsDNA), and anti-Smith (anti-Sm), can appear before clinical manifestations in SLE patients, and their presence can be used to predict the development of the disease 2, 5.
• Early diagnosis and treatment of SLE can increase the remission rate and improve patient prognosis, highlighting the importance of identifying new biomarkers and therapeutic options for early SLE treatment 2.

Diagnostic Approach to Early SLE

• The diagnostic approach to early SLE involves a systematic evaluation of clinical manifestations and autoantibody profiles, using the latest classification criteria 3.
• A combination of clinical and laboratory findings, including the presence of autoantibodies and immune complex deposition, is used to diagnose SLE 3.
• Early referral and diagnosis of SLE are crucial to improve treatment outcomes and reduce the burden of disease 3.