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This site is intended for US Healthcare Professionals only.

SLE
Systemic Lupus
Erythematosus

SLE
Systemic Lupus
Erythematosus

Introduction

Systemic lupus erythematosus (SLE) is a chronic disease that causes inflammation in connective tissues and can impact a variety of body systems resulting in renal, dermatological, cardiovascular, respiratory, digestive, and nervous system clinical presentations. The exact prevalence is difficult to determine because many of the signs and symptoms of SLE resemble those of other disorders. Diagnosis may be delayed for years, and the condition may never be diagnosed in some affected individuals.1

Overview

Pathogenesis

SLE is triggered by the abnormal activation of innate immunity.2 T cell and antigen stimulation leads to hyperactive B cells, which increases production of autoantibodies. As a result, and in conjunction with the inappropriate disposal of apoptotic cellular material, immune complexes form and are deposited throughout the body; these then induce inflammatory reactions and organ damage.3

Epidemiology

SLE can affect people young and old, but women are affected far more than men (estimates range from 4-12 women for every 1 man). And women between 15 to 44 years—childbearing age—are at the highest risk of developing SLE. In the United States, minority racial and ethnic groups (eg, Blacks/African Americans, Hispanics/Latinos, Asians, and American Indians/Alaska Natives) are affected more than Whites/Caucasians. While most people with SLE do not have a direct family member with the disease, people with an immediate family member with SLE have only a slightly higher risk for the disease.5

Signs & Symptoms

Signs and symptoms of SLE may include:

  • Joint pain and swelling
  • Arthritis
  • Fatigue
  • Skin rashes
  • Fever
  • Malaise
  • Hair loss
  • Weight loss
  • Oral ulcers
  • Photosensitivity
  • Chest pain when taking a deep breath

Clinical manifestations will vary between patients, as will the frequency and intensity of flares. All SLE patients will experience joint pain and swelling, and roughly half of SLE patients will experience a butterfly-shaped rash over their cheeks and nose. Additional signs and symptoms will also vary between patients depending on which body systems become affected.4

Disease & Clinical Trial Tools

Given the complex multi system nature of lupus, measuring disease activity accurately remains a challenging and demanding task. For instance, lupus is known for its variability both between patients and also in the same patient over time. In addition, clinicians still struggle to define what disease activity means and how it should be measured. Still, several tools have been developed over the years to attempt to create a standardized assessment of disease activity and outcome domains in clinical research. Many assessment tools have been able to detect clinical improvement and have proven reliability, validity, and sensitivity to changes seen in observational studies; some of these tools have also been used in randomized controlled trials. Here are a few of the most common.6

Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)7 and Safety of Estrogens in Lupus National Assessment (SELENA)8

The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Safety of Estrogens in Lupus National Assessment (SELENA) are pertinent to clinical trial tools.

SLEDAI is a standard scale for evaluating disease activity. The SELENA study modified the original SLEDAI to also encompass ongoing disease activity in rash, mucosal ulcers, and alopecia descriptors. The SLEDAI-2000 (SLEDAI-2K) further added persistent disease activity in proteinuria, and has been proven effective in predicting mortality and disease activity.

Download SLEDAI and SELENA

Systemic Lupus International Collaborating Clinics (SLICC)9

Pertinent to clinical trial tools, the Systemic Lupus International Collaborating Clinics (SLICC) criteria for SLE classification identifies 17 criteria, both clinical and immunological.

SLE classification requires:

  • Fulfilment of 4 or more criteria, with at least 1 clinical and 1 immunological
  • Or
  • Biopsy-confirmed lupus nephritis and ANA or anti-dsDNA antibodies

Download SLICC

British Isles Lupus Assessment Group (BILAG)10

The British Isles Lupus Assessment Group (BILAG) index assesses disease activity in SLE based on the physician’s “intention to treat.” Pertinent to clinical trial tools, the computerized index scores each of eight organ-based systems with a separate letter score and has proven sensitivity and specificity.

Download BILAG

Composite Responder Indexes—Systemic Lupus Responder Index (SRI) and BILAG-Based Combined Lupus Assessment (BICLA)11

Composite responder indexes combine individual organ and system assessments. The first composite index to be used in randomized controlled lupus trials, the Systemic Lupus Responder Index (SRI) combines the BILAG, SELENA-SLEDAI, and physician global assessment of disease activity (PGA) indexes. Another composite index, the BILAG-based Combined Lupus Assessment (BICLA) includes criteria from the BILAG-2004, SLEDAI-2000, and PGA indexes.

Both pertinent to clinical trial tools, the two indexes are different in that SRI response requires full improvement in some organs while BICLA response requires partial improvement in all organs.12

Download BICLA

Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)13

Pertinent to clinical trial tools, the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) quantifies the activity and damage caused by CLE.

Presenting a more complete clinical picture, the CLASI comprises two scores:

  • The activity score (CLASI-A) evaluates erythema, scale/hyperkeratosis mucous membrane involvement, acute hair loss, and non-scarring alopecia.
  • The damage score (CLASI-D) evaluates dyspigmentation and scarring (including scarring alopecia).

Download CLASI

References

  1. NIH GHR SLE. https://ghr.nlm.nih.gov/condition/systemic-lupus-erythematosus#statistics. Accessed July 5, 2020.
  2. Contin-Bordes C, Lazaro E, Pellegrin JL, et al. Systemic lupus erythematosus: from pathophysiology to treatment. Rev Med Interne. 2009;30(12 Suppl):H9-13.
  3. Maidhof W, Hilas O. Lupus: an overview of the disease and management options. Pharm Ther. 2012;37(4):240-249.
  4. Systemic Lupus Erythematosus. U.S. National Library of Medicine. https://medlineplus.gov/ency/article/000435.htm. Published March 23, 2020. Accessed April 9, 2020.
  5. Centers for Disease Control and Prevention. https://www.cdc.gov/lupus/facts/detailed.html#risk. Accessed June 18, 2020.
  6. Mikdashi J, Nived O. Measuring disease activity in adults with systemic lupus erythematosus: the challenges of administrative burden and responsiveness to patient concerns in clinical research. Arthritis Res Ther. 2015;17:183.
  7. Gladman DD, Ibanez D, Urowitz MB. Systemic Lupus Erythematosus Disease Activity Index 2000. J Rheumatol. 2002;29(2):288-291.
  8. Petri M, Kim MY, Kalunian KC, et al. Combined oral contraceptives in women with systemic lupus erythematosus: Appendix. N Engl J Med. 2005;353(24):2550-2558.
  9. Petri M, Orbai A-M, Alarcon GS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus.
    Arthritis Rheum. 2012;64(8):2677-2686.
  10. Hay EM, Bacon PA, Gordon C, et al. The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus. Q J Med. 1993;86:447-458.
  11. Murphy C-L, et al. From BILAG to BILAG-based combined lupus assessment–30 years on. Rheumatology. 2016;55:1357-1363.
  12. Thanou A, Chakravarty E, James JA, Merrill JT. Which outcome measures in SLE clinical trials best reflect medical judgment? Lupus Sci Med. 2014;1:e000005.
  13. Albrecht J, Taylor L, Berlin JA, et al. The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus.
    J Invest Dermatol. 2005;125(5):889-894.