Systemic lupus erythematosus (SLE)

Systemic lupus erythematosus is the classic prototype of a chronic, multisystem, inflammatory connective tissue disorder of autoimmune origin (1).

• often follows a relapsing and remitting pattern (1)
• the disease is characterised by the presence of a wide spectrum of autoantibodies (1)
  • 98% of SLE patients have antinuclear antibodies (ANA) but are non-specific
  • anti-double-stranded DNA (dsDNA) seen in around 70% of cases is highly specific for SLE
  • other autoantibodies present in SLE patients include - anti-Smith, anti-ribosomal P and anti-proliferating cell nuclear antigen (PCNA) (3)
• it is non-organ specific and characterised by vasculitis
• due to its broad clinical presentation the disease may vary from rash and arthritis through anaemia and thrombocytopenia to serositis, nephritis, seizures, and psychosis (1)
  
  
• SLE, as a chronic inflammatory disorder, is thought to be driven by autoantibodies that target multiple organ systems including joints, skin, and kidneys
  • SLE is characterized by pathogenic autoantibodies that target specific tissues, however many additional cell types (for example B cells, T cells) and cytokines (for example type I interferon (IFN-I)-a) are involved in the inflammatory response (2)
  • dysregulation of both adaptive and innate immunity plays a role in the pathogenesis of SLE
    • adaptive immunity and SLE
      • B cells play a central role in the pathogenesis of SLE, mainly by producing autoantibodies but also by producing cytokines and by presenting antigens to T cells
      • SLE can occur secondary to defective proteins that regulate T cells in the dysfunctional clearance of immune cells
        • thus part of the pathology of SLE may be due to loss of the immune tolerance and the persistence of attractive B- and T-cell populations
    • innate immunity and SLE
      • dysregulation of the innate immune system also contributes to SLE
      • immune complexes of autoantibodies with endogenous RNA and DNA can be taken up by plasmacytoid dendritic cells
        • leads to activation of toll-like receptor (TLR)7 and TLR9, respectively, and generates IFN-I
          • IFN-I can lead to further augmentation of adaptive immunity by enhancing the antigen-presenting function of monocytes and dendritic cells and activating B cells
            

Clinical variants of lupus erythematosus

Some of the clinical variants of lupus erythematous include the following (3):

• systemic lupus erythematosus (SLE)
• cutaneous lupus erythematosus (CLE) (including subacute cutaneous lupus erythematosus (SCLE) and discoid lupus erythematosus (DLE))
• child-onset lupus erythematosus
• neonatal lupus erythematosus
• drug-induced lupus erythematosus (DILE)

Management principles (1,4):

• mild disease characterized as constitutional symptoms, mild rash or arthritis, and thrombocytopenia with a platelet count no less than 50,000/mm3
  • is recommended to be treated with the addition of glucocorticoids
• moderate disease activity, characterized as rheumatoid-like arthritis, more severe skin disease or cutaneous vasculitis affecting <18% of body surface area, serositis, or thrombocytopenia with a platelet count no less than 20,000/mm3
  • is recommended to be treated with the addition of immunosuppressive agents to antimalarials and glucocorticoids (options include methotrexate, azathioprine, mycophenolate, or calcineurin inhibitors, with the addition of belimumab in refractory cases)
• severe disease activity, categorized as major organ threatening disease such as kidney and central nervous system disease
  • is recommended to be treated with the addition of mycophenolate, cyclophosphamide, or rituximab

References:

1. Gordon C, Amissah-Arthur MB, Gayed M, et al. The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults. Rheumatology (Oxford). 2017 Oct 6.
2. Dema B, Charles M. Advances in mechanisms of systemic lupus erythematosus. Discov Med. 2014 May;17(95):247-55
3. Yazdany J, Dall'Era M. Definition and Classification of Lupus and Lupus Related Disorders. Chapter 2. In: Wallace D, Hahn BH, editors(s). Dubois' Lupus Erythematosus. Ninth edition. Elsevier Inc, 2019:15-22.
4. Morand E F, Fernandez-Ruiz R, Blazer A, Niewold T B. Advances in the management of systemic lupus erythematosus BMJ 2023; 383 :e073980 doi:10.1136/bmj-2022-073980