Makindo Medical Notes

Related Subjects: | Systemic Lupus Erythematosus (SLE) | Drug-Induced Lupus Erythematosus | Discoid Lupus Erythematosus (DLE) | Neonatal Lupus Erythematosus | Rheumatology Autoantibodies

SLE is a multisystem disease primarily affecting females. The most serious complication occurs in those who develop lupus nephritis, which requires prompt diagnosis and management.

About

• Autoimmune rheumatic disease
• Common chronic multisystem connective tissue disorder
• More common in Afro-Caribbean and Asian populations
• Certain drugs can cause lupus-like syndromes (see Drug-Induced Lupus)

Aetiology

• Primarily affects young females (age 20-40) with a female to male ratio of 9:1
• Associated with HLA-B8, DR2, DR3, and A1
• Linked to complement gene deficiencies (C1q, C2, C4)
• Genetic factors: 25% concordance in identical twins
• Presence of autoantibodies targeting intracellular and nuclear components
• Hormonal factors: more common in females, also seen in Klinefelter's syndrome
• Triggers include certain drugs (e.g., hydralazine, isoniazid, procainamide, penicillamine) and UV light exposure

Pathology

• Immune complex deposition leads to tissue damage
• Potential defect in the apoptosis gene, leading to abnormal cell death
• Fibrinoid necrosis in vessel walls
• Haematoxylin bodies, often phagocytosed by neutrophils, form LE cells
• Characteristic "onion-skin" lesions in splenic arteries
• Elevated levels of IL-10 and alpha-interferon

American College of Rheumatology Criteria (4/11 criteria required for diagnosis)

• Malar rash – spares nasolabial folds
• Discoid rash – scaling, follicular plugging
• Photosensitivity
• Oral or nasal ulcers
• Non-erosive arthritis – tenderness, swelling, effusion
• Serositis – pleuritis or pericarditis
• Renal disorder – proteinuria >3+ or >0.5 g/24 hrs
• CNS involvement – seizures or psychosis
• Haematological – thrombocytopenia, haemolytic anaemia, leucopenia, or lymphopenia
• Immunological – positive anti-dsDNA, anti-Sm antibodies, or anticardiolipin
• Raised antinuclear antibody (ANA) – found in 95% of cases

Clinical Features

• Systemic: Fatigue, malaise, weight loss, depression, fever, raised ESR
• Dermatology:
  • Butterfly (malar) rash over cheeks and nose
  • Photosensitive skin rashes
  • Urticaria and purpura
  • Discoid lupus – scarring alopecia, follicular plugging, hyperkeratosis
  • Livedo reticularis
• Neurological:
  • Antiphospholipid syndrome and strokes
  • Acute psychosis, focal epilepsy
  • Migraines, cerebellar ataxia, aseptic meningitis
  • Cranial nerve palsies, polyneuropathy
• Renal: Lupus nephritis
  • Glomerulonephritis, nephrotic or nephritic syndrome
  • Interstitial nephritis, rapidly progressive glomerulonephritis
  • End-stage renal failure requiring dialysis or transplantation
• Haematological: Normochromic, normocytic anaemia, low platelets, leucopenia, or thrombocytopenia
• Cardiac/Vascular:
  • Pericarditis, myocarditis
  • Libman-Sacks endocarditis (non-bacterial thrombotic endocarditis)
  • Secondary Raynaud's syndrome, vasculitis
  • Premature atherosclerosis, arterial and venous thrombosis (APS)
• Pulmonary:
  • Pleurisy and pleural effusions
  • Restrictive lung disease ("shrinking lung syndrome")
  • Pulmonary vasculitis, pneumonitis, secondary pulmonary hypertension
• Joints: Symmetrical arthritis, arthralgia, morning stiffness, Jaccoud’s arthropathy (deforming, non-erosive polyarthritis)
• Gastrointestinal: Oral ulcers, mesenteric vasculitis
• Pregnancy: Increased risk of neonatal lupus and heart block if SSA/SSB positive

Lupus Rash

Investigations

• FBC:
  • Anaemia of chronic disease or haemolytic anaemia
  • Iron deficiency anaemia (from NSAIDs)
  • Low or high WCC and platelet counts
• Renal:
  • Raised creatinine in AKI or CKD
  • Proteinuria; renal biopsy in severe cases of lupus nephritis
• Inflammatory Markers:
  • ESR is usually raised
  • CRP is normal unless infection or other cause present
• Autoantibodies:
  • ANA positive in 99% (absence makes SLE unlikely)
  • Anti-dsDNA (more specific, present in 50%)
  • Rheumatoid factor (present in 25%)
  • Antiphospholipid antibodies (check in cases of fetal loss or thrombotic events)
  • Anti-Smith and Anti-Ro (SSA)
• Complement Levels: Low C3 and C4 during active disease
• APTT: Elevated in antiphospholipid syndrome (APS)
• Echo: Evaluate for Libman-Sacks endocarditis
• Lymph Nodes: Lymphadenopathy with follicular hyperplasia and necrosis in interfollicular zones

Renal Disease Classification

• I: Minimal mesangial lupus nephritis
• II: Mesangial proliferative lupus nephritis
• III: Focal lupus nephritis
• IV: Diffuse lupus nephritis
• V: Membranous lupus nephritis
• VI: Advanced sclerosing lupus nephritis

Management

• Basics: Simple analgesics and NSAIDs for mild symptoms. Avoid UV light in photosensitive cases; use low-dose steroid creams for skin issues
• Mild Disease: Chloroquine or hydroxychloroquine for skin and joint involvement
• Moderate/Severe Disease: Steroids (e.g., Prednisolone 30 mg/day) followed by gradual dose reduction. Consider steroid-sparing agents (e.g., azathioprine, mycophenolate mofetil)
• Immunosuppressive Agents: Methotrexate, leflunomide
• Biologics: Rituximab (anti-CD20) for refractory cases
• Serositis: Treat with NSAIDs or oral steroids
• Antiphospholipid Syndrome (APS): Use warfarin to prevent thrombosis
• Pregnancy: High-risk pregnancies require close monitoring. Hydroxychloroquine, azathioprine, and steroids may be used. Anticoagulant therapy may be necessary for APS cases.

References

• Systemic Lupus Erythematosus (SLE)
• SLE and Pregnancy