SLE

Autoimmune diseases occur when the body produces autoantibodies against its own cells or organs causing damage. About 80% of people diagnosed with an autoimmune disease are women1. Systemic Lupus Erythematosus (SLE) is an autoimmune disease that shows a strong sex bias. In fact, women are 9 times more likely to be diagnosed with SLE2.

What is SLE?

SLE is an autoimmune disease where the immune system attacks its own tissues, leading to further inflammation, organ, and tissue damage. SLE is a relatively uncommon disease with its global incidence being highly variable across the world. In Europe, the incidence of SLE is 6.5–85 patients in every 100,000 people3. African-Caribbean and Hispanic individuals have an increased risk of SLE2.

Symptoms of SLE are highly variable and are transient in nature. The term “lupus” is Latin for “wolf’s bite” and was used in the Middle Ages to describe the characteristic facial butterfly-shaped erosive rash. The three most common symptoms include tiredness, rash, and joint pain or swelling. Other less common symptoms include fever, hair loss, depression, mouth ulcers, and anxiety2.

SLE is thought to be caused by a combination of genetic and environmental components. The biggest risk factor is being female. Individuals who have a sibling diagnosed with SLE are 30 times more likely to develop SLE, suggesting a strong genetic link. Numerous immune gene polymorphisms have been shown to occur in SLE, particularly in the toll-like receptor pathways. Environmental components include ultraviolet light, particularly sunlight, and infectious viruses. The Epstein-Barr virus is one such virus that is implicated in causing SLE2.

SLE is commonly diagnosed in women aged 15–45 years old. However, due to the heterogeneity of the disease, getting a correct diagnosis is often a long (~6-year) and tricky process4. SLE mimics other illnesses such as rheumatoid arthritis, rosacea, and fibromyalgia5. To further complicate matters, 1 out of 4 women diagnosed with SLE will also have a diagnosis of at least one other autoimmune disease6. There is no one definitive diagnostic test for SLE. Diagnosis involves imaging tests, serological tests for antinuclear antibodies, full blood counts, urine tests and biopsies5.

Political Interest in SLE

NHS England released a clinical commissioning policy for rituximab for the treatment of refractory SLE in adults and post-pubescent children.7 The use of rituximab was not licensed prior to the policy update in 2020, with rituximab selectively targeting B cells, hence, reducing the inflammatory response.7 Although this is promising, there is a clear need for greater government support for women with SLE.

Current Treatments

SLE is amongst the top 20 leading causes of death in young women8. Despite this, there is currently no cure for SLE. Instead, the aim of treatment is to induce remission, where the disease is under control and the symptoms are minimised or absent9. It is recommended that all patients are treated with the antimalarial drug hydroxychloroquine as this reduces inflammation which drives organ damage. Hydroxychloroquine also helps to control lipid and glucose levels, reducing the risk of cardiovascular disease. During a flare-up, glucocorticoids are administered to help reduce inflammation. If disease activity cannot be controlled with the prior treatments, then immunosuppressants such as methotrexate may be given. If certain autoantibodies are present, the biologic belimumab may be used10.

Current treatments fail to adequately reduce the chronic pain associated with SLE. In fact, 65% of patients in one survey said they found chronic pain the most unbearable aspect of SLE6. Immunosuppressant therapy fails to stop flares, symptomatic disease, in up to 50% of patients3.

SLE significantly impacts several areas of life including education, career, and emotional and sexual well‑being3. About 55% of patients with complications from SLE will face a complete or partial loss of income because of the inability to work full time6. There is an urgent need for new therapies to help reduce the burden of SLE on all aspects of a woman’s life.

What Might the Future Hold?

As mentioned earlier, SLE presents with vague symptoms and is relatively uncommon, leading to misdiagnoses or delays in diagnosis. The earlier treatment begins, the more effective it is likely to be. Awareness of SLE remains low which further hinders diagnosis. The UK annual SLE awareness month in October is helping to raise much-needed awareness and funds for research. General practitioners need additional training to recognise and treat SLE effectively11. GlaxoSmithKline and Exagen are collaborating to create both accurate diagnostic and monitoring tools for SLE to reduce time to diagnosis down from 6 years. Their diagnostic tool will measure cell‑bound complement activation products to hopefully provide a definitive diagnosis of SLE4.

Not only is there an urgent need to raise awareness of SLE, but there is also a need to promote SLE research. Research is essential for understanding the biological processes that lead to disease and to discover better treatments.

What are Potential New Treatments for SLE?

BEAT-Lupus is the UK’s first clinical trial to use a combination of biological treatments. The results from this Phase II clinical trial are promising with treatment with belimumab after rituximab reducing the levels of the autoantibody that drives disease and reduced numbers of severe flare-ups12. Another promising area of research is investigating whether mesenchymal stem cells can be used in the treatment of SLE to dampen the inflammatory response. Early-stage clinical trials suggest that mesenchymal stem cells can be used safely to induce long-term remission and can help to reduce multiorgan injuries in patients with SLE13. Larger scale Phase II clinical studies are underway in the US14.

Clearly, SLE predominantly affects women more than men, and although important research is underway to advance the development of treatments, further work is required to promote awareness, reduce the disease burden, and improve the quality of life of women living with SLE.

To learn more about SLE please look at the links below:

  1. https://www.lupusuk.org.uk/
  2. https://www.lupus.org/
  3. https://www.nhsinform.scot/illnesses-and-conditions/immune-system/lupus

References

  1. Angum, F., Khan, T., Kaler, J., Siddiqui, L. & Hussain, A. The Prevalence of Autoimmune Disorders in Women: A Narrative Review. Cureus 12, e8094.
  2. Bertsias, G., Cervera, R. & Boumpas, D. T. Chapter 20: Systemic Lupus Erythematosus: Pathogenesis and Clinical Features. in EULAR Textbook on Rheumatic Diseases 476–505 (EULAR, 2012).
  3. Cornet, A., Andersen, J., Myllys, K., Edwards, A. & Arnaud, L. Living with systemic lupus erythematosus in 2020: a European patient survey. Lupus Sci. Med. 8, e000469 (2021).
  4. Exagen Inc. Exagen announces collaboration with GSK to drive greater awareness about challenges facing lupus diagnostics and management. Exagen Inc. https://exagen.com/exagen-announces-collaboration-with-gsk-to-drive-greater-awareness-about-challenges-facing-lupus-diagnostics-and-management/ (2018).
  5. Systemic Lupus Erythematosus. Lupus treatment; information. https://patient.info/doctor/systemic-lupus-erythematosus-pro.
  6. Lupus facts and statistics | Lupus Foundation of America. https://www.lupus.org/resources/lupus-facts-and-statistics.
  7. NHS England. Clinical Commissioning Policy: Rituximab for refractory Systemic Lupus Erythematosus (SLE) in adults and post-pubescent children [200402P]. 2020. Available at: https://www.england.nhs.uk/wp-content/uploads/2020/07/Rituximab-for-refractory-Systemic-Lupus-Erythematosus-in-adults-and-post-pubescent-children-2.pdf.
  8. Yen, E. Y. & Singh, R. R. Lupus – An Unrecognized Leading Cause of Death in Young Women: Population-based Study Using Nationwide Death Certificates, 2000–2015. Arthritis Rheumatol. Hoboken NJ 70, 1251–1255 (2018).
  9. Fanouriakis, A. et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Rheum. Dis. 78, 736–745 (2019).
  10. Kuhn, A. et al. The Diagnosis and Treatment of Systemic Lupus Erythematosus. Ärztebl. Int. 112, 423–432 (2015).
  11. Why does lupus get misdiagnosed so much? Lupus Trust UK https://www.lupus.org.uk/lupus-trust-uk-news/2021/6/7/why-does-lupus-get-misdiagnosed-so-much.
  12. Versus Arthritis. BEAT-Lupus clinical trial shows promise of new treatment for lupus. Versus Arthritis https://www.versusarthritis.org/news/2021/june/beat-lupus-clinical-trial-shows-promise-of-new-treatment-for-lupus/ (2021).
  13. Cheng, R.-J. et al. Mesenchymal Stem Cells: Allogeneic MSC May Be Immunosuppressive but Autologous MSC Are Dysfunctional in Lupus Patients. Cell Dev. Biol. 7, 285 (2019).
  14. Stem Cell Research | Lupus Foundation of America. https://www.lupus.org/our-work/stem-cell-research.
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