What is Systemic Lupus Erythematosus (SLE): A Detailed Overview

What is Systemic Lupus Erythematosus (SLE): A Detailed Overview

Lupus is a chronic inflammatory autoimmune disorder in which the body’s immune system mistakenly attacks its own healthy cells and tissues. This results in abnormal immune function and the production of autoantibodies, leading to tissue damage.1

There are four main types of lupus:

 

  1. Systemic Lupus Erythematosus (SLE):
  • Most common type of lupus, often simply referred to as “lupus.”
  • Distinguished from other types by its multi-organ involvement.1
  • If it develops in childhood, it is known as childhood-onset Systemic Lupus Erythematosus (cSLE), which accounts for approximately 10–20% of SLE cases.
  • Most cases appear in adulthood between the ages of 15 and 44.2

 

  1. Neonatal and Pediatric Lupus Erythematosus (NLE):
  • A rare condition affecting infants born to mothers with lupus.
  • Caused by the transplacental passage of maternal autoantibodies.
  • Only 1% of infants with maternal autoantibodies develop NLE.
  • Primarily affects the heart, liver, and skin.1

 

  1. Cutaneous Lupus Erythematosus (CLE):
  • It affects only the skin, causing rashes and lesions.
  • Three main subtypes of Cutaneous Lupus Erythematosus (CLE):
      • Discoid Lupus Erythematosus (DLE) – Chronic scarring and photosensitive dermatosis, which may progress to or coexist with SLE.1
      • Subacute Cutaneous Lupus Erythematosus (SCLE) – Characterized by lesions that appear on sun-exposed areas.
      • Acute Cutaneous Lupus Erythematosus (ACLE) – Often presents with a classic “butterfly rash” on the face.2

 

  1. Drug-Induced Lupus Erythematosus (DILE):
  • Triggered by certain medications.2
  • Affects multiple organs, but symptoms usually resolve once the medication is discontinued.1
 

Since, SLE is the most common and complex form of lupus, this article provides a detailed overview of Systemic Lupus Erythematosus (SLE).

 

Systemic Lupus Erythematosus (SLE): A Closer Look

 

SLE is a chronic autoimmune disorder which causes inflammation and immune mediated injury in multiple organ systems including Cardiovascular, Hematologic, Gastrointestinal, Integumentary (skin and related structures), Musculoskeletal, Neuropsychiatric, Pulmonary, Renal, Reproductive systems.(3,4) Without appropriate treatment, SLE can lead to severe flare-ups and organ damage. While the condition affects both men and women, it is more prevalent in women of childbearing age (20–40 years). This is likely due to the influence of estrogen, which modulates lymphocyte activation.5 Therefore, women with SLE face an increased risk of fetal growth restriction, spontaneous abortion (miscarriage), stillbirth and Pre-eclampsia (high blood pressure during pregnancy).3

The prevalence of SLE varies across different ethnic and geographic populations. Studies suggest that individuals of African, Latin American, and Asian descent have higher rates of SLE compared to Caucasians. The estimated global prevalence is between 20 to 150 cases per 100,000 people.6 Lupus remains a complex and multifaceted disease requiring comprehensive medical management to improve patient outcomes and quality of life.

 

Causes of Systemic Lupus Erythematosus (SLE)

 

The exact cause of SLE remains unknown. However, multiple factors including genetic, hormonal, immunological and environmental influences contribute to its development.

  1. Genetic Factors:

Individuals with a family history of lupus or other autoimmune diseases have a higher likelihood of developing SLE. This increased susceptibility is due to inherited genetic variants passed from parents.7 Scientists have identified around 50 gene variants associated with SLE. A combination of these genetic factors—such as HLA-DRB1, DR3, DQA2, CR2, and FCGR2A/B, as well as TREX1 mutations and complement deficiencies (C1q, C2, and C4) contribute to disease manifestation.5 For instance:

  • C1q deficiency impairs the removal of apoptotic cellular debris, increasing the risk of SLE.
  • C4 deficiency affects the elimination of self-reactive B cells, leading to excessive immune responses and lupus development.1
 
  1. Hormonal Factors:

Hormones regulate various physiological processes and their role in SLE has been widely studied. The higher prevalence of lupus in women suggests a link between estrogen and immune system activity. Estrogen has been observed to stimulate T cells, B cells, macrophages, and cytokines, which are key players in immune function.1 Additionally, SLE symptoms often worsen before menstruation and during pregnancy, further implicating estrogen’s influence.7 However, no direct causative relationship between estrogen and lupus has been confirmed.

 
  1. Environmental Factors:

For individuals genetically or hormonally predisposed to lupus, exposure to environmental triggers can significantly increase the risk of developing the disease. Common environmental triggers include:

  • Ultraviolet (UV) radiation: UV exposure, including UVA and UVB rays, stimulates keratinocytes, leading to B cell activation and autoantibody production.
  • Infections: The Epstein-Barr Virus (EBV) has been linked to lupus onset, particularly in children.
  • Silica dust: Common in agricultural and industrial workers, prolonged exposure increases SLE risk.
  • Medications: Certain drugs including sulfa antibiotics, tetracyclines, procainamide, and hydralazine, can induce lupus-like symptoms.
  • Stress: Both physical and emotional stress can exacerbate lupus symptoms.
  • Other factors: Poor sleep, excessive exertion, unhealthy habits, injuries, surgeries, and childbirth may act as lupus triggers.7
 
  1. Epigenetic Modifications:

Epigenetics involves changes in gene expression without altering DNA sequences. Environmental factors influence these modifications, which have been linked to lupus development. Key epigenetic alterations associated with SLE include:

  • DNA hypomethylation
  • Histone modifications
  • Overexpression of MicroRNA Mir215

Understanding and recognizing potential triggers that worsen lupus symptoms can help individuals to take preventive measures. By identifying these factors, patients can adopt strategies to reduce flare-ups and improve overall health.  

 

 

Effects of Triggering Factors in Individuals Predisposed to Lupus

 

Systemic Lupus Erythematosus (SLE) has a complex pathogenesis. When an individual predisposed to lupus is exposed to triggering factors, the immune system produces excessive antibodies that bind with specific autoantigens to form immune complexes. These immune complexes get deposited in various organs, leading to multi-organ damage.8

Mechanism of Autoimmune Response in SLE: A key factor in SLE is defective clearance of apoptotic cells. Under normal conditions, apoptotic cells (cells undergoing programmed death) are efficiently cleared by phagocytic cells such as macrophages and dendritic cells. However, in individuals with SLE, this process is impaired due to genetic mutations in C1q, DNASE1, and TREX1, leading to the persistence of apoptotic cell debris. This debris presents antigens on the cell surface, turning them into antigen-presenting cells (APCs).

  • T-cell activation: T lymphocytes recognize these antigens and bind to the major histocompatibility complex (MHC) on APCs, triggering T-cell activation, cytokine release, inflammation, and hyperactivation of B cells.
  • B-cell response: Activated B cells produce autoantibodies, particularly Immunoglobulin G (IgG), targeting self-antigens and contributing to organ damage.
  • T-cell and B-cell interaction: Specific T and B cells interact to further amplify the production of harmful autoantibodies, worsening the autoimmune response.1

 

 

Common Symptoms of SLE

 

Individuals with SLE may experience a wide range of symptoms, including:

  • Extreme fatigue
  • Malaise (general discomfort and unease)
  • Fevers
  • Joint pain or swelling (Arthralgia)
  • Swelling in hands, feet or around the eyes
  • Headaches
  • Photosensitivity (sensitivity to sunlight or fluorescent light)
  • Chest pain while breathing deeply
  • Malar rash (a red or purplish butterfly-shaped rash across the cheeks and nose)
  • Hair loss
  • Mouth or nasal ulcers
  • Raynaud’s disease (fingers and toes turning white or blue in response to cold or stress) (9,10)
  • Loss of appetite

If you experience these symptoms, it is advisable to consult a healthcare professional for an accurate diagnosis and appropriate treatment. 

 

Understanding SLE: Debunking Misconceptions

 

SLE is an autoimmune disorder and is not contagious. A common misconception is that lupus is a communicable disease that can spread through physical contact, air, bodily fluids, or genetics. However, this is not true. Since lupus is not caused by bacteria, viruses, or fungi, it cannot be transmitted from person to person. While the exact cause of lupus remains unknown, research suggests that a combination of genetic and environmental factors plays a significant role in its development. Early diagnosis and appropriate medical intervention are crucial in preventing complications and improving quality of life. With ongoing advancements in medical research, there is hope for better treatment options and improved outcomes for those living with lupus.  

 

References

 

  1. William Maidhof, Olga Hilas. Lupus: An Overview of the Disease and Management Options. Pharmacy and Therapeutics (P&T). 2012 Apr;37(4):240-246, 249.
  2. National Resource Centre on Lupus. The four different types of lupus. Lupus Foundation of America. Updated August 8, 2022.Acessed on February 17, 2025. Available from: The Four Different Types of Lupus | Lupus Foundation of America
  3. Lam, N. V., Brown, J. A. & Sharma, R. American Family Physician.2023;107 (4), 383-395.
  4. Siegel, C. H. & Sammaritano, L. R. Systemic Lupus Erythematosus. JAMA.2024;331 (17), 1480-1491.
  5. Kumar Ravi, Kumar Abhay et al. A cross-sectional study of clinical and laboratory characteristics of systemic lupus erythematosus in tribal region of Jharkhand at RIMS, Ranchi. Journal of Family Medicine and Primary Care. 2022;11(12): p7836-7841.
  6. Roaa A. Aljohani, Ghada A. Aljanobi, Khaled Alderaan and Mohammed A. Omair. Exploring the quality of life and comorbidity impact among patients with systemic lupus erythematosus in Saudi Arabia. Saudi Medical Journal. October 2024;45(10):1071-1079. DOI: https://doi.org/10.15537/smj.2024.45.10.20240432
  7. National Resource Centre on Lupus. What causes lupus. Lupus Foundation of America. Updated April 30, 2024. Accessed on February 18, 2025. Available from: https://www.lupus.org/resources/what-causes-lupus
  8. Liuliu Quan, Jiawen Dai, Yuan Luo, Lin Wang, Yue Liu, Jiaqi Meng, Fan Yang,Xin You. The 100 top-cited studies in systemic lupus erythematosus: A bibliometric analysis. Human Vaccines & Immunotherapeutics. 2024; 20(1). https://doi.org/10.1080/21645515.2024.2387461
  9. Cojocaru M, Cojocaru IM, Silosi I, Vrabie CD. Manifestations of systemic lupus erythematosus. Maedica (Bucur). 2011 Oct;6(4):330-6.
  10. National Resource Centre on Lupus. Lupus symptoms. Lupus Foundation of America. Updated July 25, 2023. Accessed on February 18, 2025. Available from: Lupus Symptoms | Lupus Foundation of America

 

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