26th January 2024

Background

There are four major types of lupus: systemic lupus erythematosus, lupus of the skin, drug-induced lupus erythematosus and neonatal lupus erythematosus. 

Systemic lupus erythematosus (SLE) is the most common and is a chronic autoimmune disease that can affect multiple organs, including the skin, joints and kidneys. 

Lupus of the skin can be subdivided into three main categories, each with their own distinctive lesions. These are 1) acute cutaneous lupus, 2) chronic cutaneous lupus erythematosus or discoid lupus erythematosus (DLE) and 3) subacute cutaneous lupus erythematosus. 

Drug-induced lupus has a similar presentation to SLE and is caused by drugs such as hydralazine, procainamide, isoniazid and minocycline. 

Neonatal lupus erythematosus is a rare condition that affects babies of women who have autoantibodies (Anti-Ro and Anti-La), which act on the neonates’ heart conduction system, leading to heat block. 

Epidemiology 

SLE is the most common form of Lupus – affecting approximately 70% of all patients diagnosed. There is a higher prevalence in females with the age of onset at diagnosis, most often between 15 and 45 years. 

The prevalence of SLE is higher among Asian, African American, African Caribbean and Hispanic individuals compared to Caucasians.

Pathophysiology 

The exact aetiology of SLE is unknown as it is thought to be multifactorial. 

Genetic factors:

Generally, no single polymorphism is associated with a high risk for developing SLE. However, the combination of susceptibility genes and the absence of protective genes confer enough genetic susceptibility to cause disease development. 

The following genetic factors are associated with SLE:

• The most common genetic predisposition is at the MHC locus – Class I HLA (HLA – A, B, C) and Class 11 HLA molecules (HLA – DR, DQ, DP) 
• Loci of particular interest – Anti-La, Anti-Sm, Anti- dsDNA, Anti- Ro (associated with neonatal heart block) 
• Deficiencies of complement components – C1q, C4A, B, C2, TREX1 
• Gene Polymorphisms in DNA repair genes – ATG5, DNASE1

Hormonal and Immunological Factors 

• An increase in CD4+ and CD8 + T cells due to excess or unopposed oestrogen release may lead to autoantibodies which eventually lead to the clinical findings of SLE. This may account for the higher prevalence in women.
• Elevated levels of circulating IFN-alpha correlate with active disease. The presence of genetic predisposing factors leads to increased expression of IFN-alpha-inducible RNA transcripts by mononuclear cells, which in turn causes these elevated levels. 
• Dysregulation of apoptosis among different cell types – T lymphocytes and the Fas/Fas ligand pathway causes an abnormal programmed cell death and an aberrant lymphoid population, contributing to autoimmune activity. 
• In lupus nephritis, there is deposition of immune complexes in the mesangium and activation of complement in the glomerular basement membrane, causing inflammation, which eventually leads to necrosis and scarring. There are also elevated circulating levels of TNF-alpha, which correlate with active disease.