Pathogenesis

Genetic + environmental factors → inflammatory cascade of cytokine, chemokine and inflammatory cell response → activation of keratinocytes, endothelial cells and dendritic cells → production of type I interferon → recruitment and activation of CD4+ and CD8+ cytotoxic T cells → cytotoxic keratinocyte damage with a lichenoid tissue reaction and vacuolar interface change

  1. Increased risk for Subacute CLE:
    • HLA-B8-DR3 (including tumor necrosis factor 2) – MHC-II
    • C2 and C4 deficiencies
  2. Increased risk of SLE, Subacute CLE & DLE:
    • TYK2 (innate immunity)
    • IRF5 (innate immunity)
    • CTLA4 – Cytotoxic T lymphocyte antigen 4 (B and T cell function)
  3. Familial chilblain lupus:
    • TREX1

Subacute CLE and neonatal lupus

  • Anti-Ro
  • Anti-Ro60 – cell survival following ultraviolet radiation – targets misfolded non-coding RNAs for degradation
  • Anti-Ro52 – proinflammatory – targets interferon regulatory factor 3 and 8 for degradation + immune complex formation
  • Anti-La
  • ANA (may be present in CLE patients in absence of SLE, but is not diagnostic of LE)

Environmental/other factors

  • UVB > UVA acts as trigger and / or exacerbated CLE
    by keratinocyte apoptosis, nuclear antigen exposure and inflammation
  • Cigarette smoking (more extensive and recalcitrant disease, decreases response to antimalarials)
  • Viruses
  • Drugs

Hydralazine, procainamide, isoniazid, quinidine, methyldopa, phenytoin, chlorpromazine, minocycline, TNF-α inhibitors)

Antifungals, antihypertensives (thiazides, CCB, ACEI), TNF-α inhibitor, PPIs, anti-epileptics, taxanes, thrombocyte inhibitors, naproxen