Systemic Lupus Erythematosus

Question 1

SLE basic

Answer 1

AI disease causing inflammation of lots of things

Question 2

Pathogenesis of SLE

Answer 2

Most mediated by AB formation

Normal apoptotic cells release nuclear antigens that remain unrecognized by immune system

In SLE, an abnormal response recognizes these

Enhanced IFN, others secretion, but reduced secretion of IL2 and TGFB

Lack of these means can’t form Tregs

Sustained formation of autoAbs and can’t clear them

These them deposit and activate complement leading to local inflam response

Question 3

Environmental factors

Answer 3

Clearest is estrogen

Women higher risk and more if on birth control

Estradiol binds receptors on lymphocytes, increasing activation and prolonging immune response

UV light can precipitate flare due to apoptosis of skin cells or DNA alteration

EBV infections that mimic seuqneces on human splicesosomes

Exposure to tobacco smoking or silica dust

Question 4

Genetics and SLE

Answer 4

25-50% with monozygotic

C1q and C2 def have clearest association

Complement def likely diminishes clearance of immune complees and reduces clearance of apoptoci cels

Question 5

Epidemiology and SLE

Answer 5

90% female

More in African-american

May be some geographic

Question 6

Most common organ sx at presentation

Answer 6

Hematologic, malar rash, oral ulcers, either arthtis or arthralgias

Question 7

Cutanoues sx

Answer 7

Photosensitivty
Butterfly rash
Oral ulcers
Discoid skin lesions

Question 8

Renal sx

Answer 8

Nephritis - glomerular inflammation with hematuria or proteinuria

Nephrotic syndrome - hypoalbuminemia, edema, and proteinuria

End stage renal dx

Question 9

Neuro and MSK sx

Answer 9

Cog
Headaches
Psychosis
Seisures

Arthralgias - migratory and symmetric joint pain
Polyarthritis - non-erosive inflammation of hands, wrist, and kness

Question 10

Hematologic and cardiopulm sc

Answer 10

Anemia of chronic dz
Leukopenia
thrombocyto
Hemolytic

Pleuri/pericarditis
Myocarditis and endocarditis

Question 11

Dx of SLE (ABs)

Answer 11

Find at least one autoantibody

ANAs is essential

Anti-dsDNA is more specific…also Anti-sm…may be positive during flares but neg when controlled

20% have antiphospholipid antibodies

Question 12

Inflam markers and dx of SLE

Answer 12

Increase ESR but not CRP

Low C3, C4, or CH50 because immune complexes bind complement

Question 13

Other dx of SLE

Answer 13

May biopsy skin or kidney and show Ig at dermal-epidermal junction

Kidney biopsy can help clssify stage of kindey dz

Deposits have a full horse pattern positive for IgG, IgA, IgM, and C3

glomerular endothelial cells also have tubuloreticular inclusions composed of ribonucleoprotein

Question 14

Non pharm managment

Answer 14

Exercise, stop smoking, sunscreen

NSAIDs can be used

Question 15

Hydroxychloroquine and chloroquine MOA and SE

Answer 15

Block stimulation of BCRs through inhibiton of TLRs

NV, skin rash, headache, corneal deposits and retinopathy

Question 16

Azathioprine MOA and SE

Answer 16

Prodrug converted to 6-MP by RBCs…puring analog that interferes with DNA synthesis and suppressing CMI

Bone marrow suprpression, liver toxicity, N/V

Question 17

Methorexate MOA and SE

Answer 17

FOlate antimetabolite interfering with DNA synthesi and producing anti-inflam effect

Liver, bone marrow, dyspepsia, N/V

Question 18

Mycophenolate mofetil MOA and SE

Answer 18

Inhibitor of purine syunthesi in lymphocytes, leading to decreased B and T cell proliferation

BM, N and diarhea

Question 19

Riuximab MOA and SE

Answer 19

Loss of CD20 proetin expression in pre-B-cells rresulting in B cell depletion

PML, Hep B reactivation

Question 20

Cyclophosphamide MOA and SE

Answer 20

Alkylating agent, binds and crosslinks DNA leading to altered cell function and reducted in B and T cells

BM, hemorrhagic cystitis, secondary cancer

Question 21

Mild and severe flares

Answer 21

Mild - add GC like prednisone

Severe- high dose GC and cyclophosphamide

Question 22

Prognosis of SLE

Answer 22

Most common get flares with remission

Some get organ failure

Some have almost none

CNS, renal, and infection are most liilely causes of death

Question 23

Drug-induced lupus

Answer 23

Procainamide, dispyramide, propafenon, hydralazine, minocycline, isoniazid, IFN and TNF lpha inhibitors

Prevent with SLE like syndrome

Test ANA and anti-histone

anti-histone more specific for drug-induced

Discontinue

Question 24

Neonatal LE

Answer 24

Placental transfer of maternal autoantibodies to the fetyus

Anti-Ro (SSA0 or anti-La (SSB)

Facial skin rash in first month

UV light exposure

May habve hematolgoci or congenital heart block

Self-limiting unless congenital heart block