Clinical Immunology: Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE)

• SLE is the most common connective tissue disease.
• Around 90% of affected individuals are women.
• The peak age at onset is between 20 and 30 years.
• SLE usually presents with non-specific symptoms including fever, skin rash, arthralgia, oral ulcers, weight loss, hair loss, and Raynaud's phenomenon.

Diagnostic Criteria for SLE

• Malar rash: fixed erythema, flat or raised, sparing the nasolabial folds.
• Discoid rash: erythematous raised patches with adherent keratotic scarring.
• Photosensitivity: rash due to unusual reaction to sunlight.
• Oral ulcers: oral or nasopharyngeal ulceration, which may be painless.
• Arthritis: non-erosive, involving two or more peripheral joints.
• Serositis: pleuritis (pleuritic pain or rub, or pleural effusion) or pericarditis (rub, effusion).
• Renal disorder: persistent proteinuria > 0.5 g/day or cellular casts.
• Neurological disorder: seizures or psychosis.
• Haematological disorder: haemolytic anaemia or leucopenia, or lymphopenia, or thrombocytopenia.
• Immunological disorder: anti-DNA or anti-Smith or antiphospholipid antibodies.
• Antinuclear antibody (ANA) disorder: abnormal titre of ANA by immunofluorescence.

Management of SLE

• Mild to moderate SLE:
  • Avoid exposure to sunlight and use sunblock.
  • Use NSAIDs, hydroxychloroquine, and steroids.
  • Consider Azathioprine, Methotrexate, and control of CV risk factors.
• Life-threatening lupus:
  • Methylprednisolone IV.
  • Cyclophosphamide IV.
  • Mycophenolate mofetil (MMF).
  • Rituximab.
  • Biologics: Belimumab.

Antiphospholipid Syndrome (APS)

• Clinical syndrome presented mainly by recurrent miscarriages and recurrent arterial and venous thrombosis.
• Characterized by the presence of anticardiolipin antibodies and lupus anticoagulants, which target protein C or β2-glycoprotein, leading to thrombosis.
• May occur alone (primary APS) or in association with other autoimmune diseases like SLE, SSc, and RA.

Clinical Features of APS

• Thromboembolic events: venous thromboembolism, arterial thromboembolism.
• Adverse pregnancy outcome: recurrent first trimester abortion (≥ 3), unexplained fetal death after 10 weeks' gestation, and severe early pre-eclampsia.
• Livedo reticularis, skin necrosis, and catastrophic APS (acute vascular occlusion in 3 different organs within a short time, less than one week).

Diagnostic Criteria of APS

• Arterial or venous thromboembolic events.
• Adverse pregnancy outcome (repeated abortions, premature labor, intrauterine fetal death).
• Livedo reticularis.
• Positive antiphospholipid antibodies (lupus anticoagulants, anticardiolipin antibodies, anti-beta2 glycoprotein) at least 3 months apart.

Treatment of APS

• Primary prophylaxis against thrombotic events:

  • Aspirin.
  • Statins.
  • Hydroxychloroquine.
  • Vitamin K antagonists (Warfarin).

• Secondary prophylaxis against thrombotic events:

  • Vitamin K antagonists (Warfarin).
  • The desired INR target: ≥ 2.
  • Direct oral anticoagulants (DOAC): ±.

• Treatment of APS during pregnancy aims to improve the pregnancy outcome:

  • Aspirin + Heparin.
  • Aspirin + Low Molecular Weight Heparin (LMWH).