Systemic lupus erythematosus

Question 1

Criteria for Dx of SLE

Answer 1

• 4 or more of the following (serially or simultaneously)
• Malar rash or discoid rash
• Photosensitivity
• Oral ulcers or non-erosive arthritis
• Serositis
• Renal d/o
• Hematologic, neurologic, or immunologic d/o
• Positive ANA

Question 2

Antinuclear Abs

Answer 2

• Target many nuclear antigens like dsDNA, histones, ribonucleoprotein
• Can be identified using immunofluorescence
• Topoisomerase and centromere targeting is systemic sclerosis
• ANAs characteristic of SLE: anti-dsDNA, anti-smith (spliceosome)
• ANAs are not cytotoxic, and most (but not all) cannot penetrate the cell membrane
• Thus most ANAs are not deleterious (do not cause injury)
• But infants w/ mothers that have SLE can develop neonatal lupus syndrome (mother’s ANA can cross the placenta)

Question 3

Organ-specific autoAbs

Answer 3

• Bind to surface Ag epitopes (anti-coagulant Abs make thrombosis more likely)
• Then activate complement and cause lysis of target cell
• Cause premature removal of cell via macrophages/monocytes
• Cause inactivation (apoptosis?)

Question 4

Pathogenicity of autoAbs

Answer 4

• ANA, anti-cytoplasmic Ags (1st mechanism): immune complexes form from Ab binding, there is complex deposition in tissue
• The complexes lead to complement activation and inflammation, both of which lead to tissue damage
• Anti-RBC, anti-WBC, anti-platelet (2nd mechanism): surface antigens accessible, leading to complement activation
• This leads to lysis, removal of cells from circulation and impaired function

Question 5

Induction of autoimmunity

Answer 5

• Genetic, environmental, and hormonal factors contribute
• These factors lead to impairment of immune regulation, abnormal T cell levels/Treg/cytokines
• Leads to autoreactive B cells
• Finally decreased clearance and apoptosis
• This last step leads to formation of Abs against self-Ags

Question 6

Pathologic changes in SLE

Answer 6

• Inflammatory changes
• Blood vessel abnormalities
• Immune complex deposits

Question 7

Rashes seen in SLE

Answer 7

• Butterfly (malar) rash: symmetrical rash on cheeks, nose, chin, forehead
• Under fluorescent microscopy, there is a bright band at the epidermis/dermal junction
• This is seen at the junction in many rash diseases, but this can be seen at a site that is not covered by a rash in SLE (very specific)
• Can also see diffuse alopecia and photosensitivity

Question 8

Skin lesions in SLE

Answer 8

• Mucosal ulcers (both lips and palate)
• Cutaneous vasculitis open lesions (usually on fingers)
• Purpuric skin lesions due to cutaneous vasculitis (can be anywhere
• Digital gangrene also causes by cutaneous vasculitis
• Chronic discoid LE: white spots on arms, face, can also cause scarring alopecia

Question 9

Inflammatory arthritis in SLE

Answer 9

• Fusiform (spindle shaped) swelling of the PIP joints
• The inflammation is symmetric and bilateral
• Usually involves MTP/MCP/PIP joints, also elbows and knees
• The joint inflammation is NOT erosive like it is in RA

Question 10

Hematologic abnormalities 1

Answer 10

• Anemia: anemia of chronic disease, Fe deficiency, autoimmune hemolytic anemia (+ combs: hemolysis)
• Leukopenia: lymphopenia associated w/ disease activity
• Thrombocytopenia: autoimmune destruction of platelets
• Arterial thrombosis can lead to distal gangrene (no inflammation histologically)

Question 11

Hematologic abnormalities 2

Answer 11

• Circulating anticoagulants (increases risk of thrombosis in veins and arteries): antiphospholipid Ab syndrome (Abs bind to coagulation proteins that normally bind to phospolipis to be activated, but instead the self-Ab activates them)
• Antiphospholipid syndrome results in pregnancy complication (spontaneous abortions, premature delivery)

Question 12

Respiratory abnormalities in SLE

Answer 12

• Pleurisy w/ or w/o effusion
• Parenchyma: interstitial lung fibrosis, acute lupus pneumonitis, alveolar hemorrhage, functional loss
• Histologically see: thickened alveoli, fibrosis, inflammation

Question 13

Cardiac involvement in SLE

Answer 13

• Pericarditis w/ or w/o effusion, pericardial tamponade
• Myocarditis
• Endocarditis
• Vasculitis, accelerated atherosclerosis

Question 14

Neuropsych changes in SLE

Answer 14

• Can be CNS or peripheral, ranges from 15-75% of pts

- Variable presentations

Question 15

SLE glomerulonephritis 1

Answer 15

• Inflammation and destruction of renal glomeruli
• Due to immune complex deposition and complement activation
• Also T cell mediated injury
• Majority of SLE pts develop it, 10-30% progress to end stage renal disease (ESRD)
• Renal damage is most important predictor of mortality for SLE pts (prognosis much worse for those w/ lupus nephritis)

Question 16

SLE glomerulonephritis 2

Answer 16

• Renal damage can lead to HTN, proteinuria, total renal failure
• Histologically there is obvious invasion of immune cells, congested, increase in cellularity
• The immune complexes that damage the glomeruli either react to the DNA Ags that are caught in the glomeruli (immune complexes formed in situ), or the immune complexes are circulating and get caught in the glomeruli

Question 17

Neonatal lupus syndrome

Answer 17

• Rare, starts w/ transient photosensitive skin rash, develops after birth
• Congenital heart block (fibrosis of AV node)
• Transient cytopenias
• Liver abnormalities

Question 18

Clinical course of SLE

Answer 18

• Majority of pts have chronic irregular course (periods w/ activity and periods w/o)
• May go into remission
• Rarely there is acute rapid fulminant (severe onset)

Question 19

Survival rates in SLE

Answer 19

->90% have 10 yrs survival (not shared by all racial ethnicities)