Systemic Lupus Erythematodes, Rheumatoid Arthritis

1. Systemic Lupus Erythematosus (SLE)

A multisystem autoimmune disease that can affect any organ — mostly skin, kidney, serosal membranes, joints, heart. Relapsing–remitting; characterized by a wide range of autoantibodies, especially ANA. Female:male = 9:1, onset 20–40 years.

Autoantibodies

• ANA — against nuclear antigens (DNA, histones); ~95% sensitive (not specific). Detected by immunofluorescence.
• Anti-dsDNA and anti-Sm — highly specific; anti-dsDNA tracks renal disease activity.
• Antibodies vs blood cells (RBC, platelets, lymphocytes) and antiphospholipid → thrombosis + thrombocytopenia.

Pathogenesis

• Genetic — familial/HLA association; complement deficiency (classical pathway) → defective IC clearance.
• Environmental — UV (DNA damage → apoptosis → nuclear antigen release), smoking, sex hormones, drugs (procainamide → DNA demethylation).
• Immunological — type I interferon (IFN-α), TLR activation of self-reactive B cells, failure of B-cell tolerance.

Pathomechanism & morphology

• Type III — DNA/anti-DNA immune complexes (LE/hematoxylin bodies).
• Type II — antibodies vs blood cells → cytopenias; vs clotting factors → clotting disorders.
• Lesions reflect IC deposition: acute necrotizing vasculitis (fibrinoid → fibrous), butterfly (malar) rash (photosensitive), non-deforming arthritis, Libman–Sacks endocarditis (mitral), serositis, CNS microinfarcts.
• Lupus nephritis = most important feature — 6 classes (I normal → II mesangial → III focal → IV diffuse, most serious/common, “wire-loop” → V membranous, nephrotic → VI sclerosing, ESRD).
• Clinical: young woman with malar rash, fever, arthritis, pleuritic pain, photosensitivity; death from renal failure, infection, CNS involvement.

2. Rheumatoid Arthritis (RA)

A systemic chronic inflammatory disease mainly affecting joints → non-suppurative proliferative synovitis → destruction of articular cartilage and bone → disabling arthritis. Female:male = 5:1, peak 40–50 years.

Pathogenesis

• Genetically predisposed host (HLA-DR4) + infection (EBV, mycobacteria)/smoking trigger.
• CD4⁺ T-cell cytokine-mediated inflammation:
  • Macrophages → degradative enzymes, IL-1/IFN-γ → synovial/fibroblast proliferation → cartilage destruction.
  • B cells → rheumatoid factor (IgM against Fc of IgG) and anti-CCP (more specific) → immune complexes deposit in joints.
  • RANK ligand (TNF-driven) → ↑ osteoclast activity → bone erosion.

Morphology & clinical

• Symmetric small-joint arthritis (hands, feet, wrists); chronic synovitis with hyperplasia, perivascular CD4/plasma cell infiltrate, angiogenesis, osteoclast erosion.
• Pannus (proliferating synovium/granulation tissue) → erodes cartilage/bone → ankylosis. Progression: synovitis → pannus → ankylosis.
• Rheumatoid nodules (extensor forearm; central fibrinoid necrosis), necrotizing vasculitis, interstitial lung fibrosis, anemia of chronic disease.
• Clinical: morning stiffness, symmetric joint pain → ulnar deviation/claw deformity; Raynaud; complications include cervical (atlantoaxial) instability.

	SLE	RA
Antibodies	ANA, anti-dsDNA, anti-Sm	RF, anti-CCP
Joints	Non-deforming arthritis	Erosive, deforming (pannus)
Key organ	Kidney (lupus nephritis)	Joints; lung fibrosis
Heart	Libman–Sacks endocarditis	Pericarditis, nodules

💡 High-yield: SLE — ANA (sensitive), anti-dsDNA/anti-Sm (specific), type III IC → lupus nephritis (class IV most serious), malar rash, Libman–Sacks endocarditis, 9:1 female. RA — RF + anti-CCP, HLA-DR4, symmetric small-joint synovitis → pannus → ankylosis, rheumatoid nodules, morning stiffness.