SLE

Question 1

Autoantibody in neuro lupus

Answer 1

Ribosomal P Abs

Question 2

Most specific antibody in SLE

Answer 2

Anti smith -most specific (renal and CNS disease)
Others -anti ds DNA, SSA,SSB
U1RNP- MCTD, myositis, Raynauds

Question 3

Risk factors for poor outcome in pregnancy

Answer 3

Active disease in last 6-12 months
Serological activity (ds-dna,complements)
Lupus nephritis
Anti SSA,SSB
aPL serology
Organ damage

Question 4

Autoantibody associated with congenital heart block in neonate

Answer 4

Anti- SSA/anti Ro (1-3% risk)

Risk in subsequent pregnancy -13-17%

Question 5

Role of HCQ in SLE

Answer 5

Decreases flares, progression to renal and CNS lupus
Decreases end organ damage,doubles response to MMF
Protects against CHB in SSA positive mothers

Question 6

Monoclonal antibody in refractory SLE

Answer 6

Belimumab
MOA- blocks the B lymphocyte stimulator (BLyS), a soluble protein that binds to B cells. This molecule is overexpressed in people with lupus

Question 7

Highest risk of thrombosis in SLE

Answer 7

Triple positive- B2 microglobulin, anti Cardiolipin, lupus anticoagulant
Of these highest risk - lupus anticoagulant (look for prolonged APTT)

Question 8

Anticoagulation in APLS

Answer 8

Asymptomatic /primary prevention -No RX/low dose aspirin
Secondary prevention - Warfarin INR 2-3, indefinitely
Pregnancy
Prior thrombosis -therapeutic LMWH+Aspirin
Prior pregnancy loss -low dose daily LMWH+aspirin

Question 9

Lupus nephritis features

Answer 9

30-50% of SLE
Worse prognosis in Asians, African -American and Hispanic
Glomerular hematuria, proteinuria/NS, AKI
Renal biopsy gold standard

Question 10

Histopathological features in lupus nephritis

Answer 10

Subendothelial immune deposits(wire loops), hypercellularity
Leukocyte infiltration
Fibrinoid necrosis, hyaline thrombi
Deposits -IgG, IgA,Ig M, C1q, C3

Question 11

Poor prognostic features in proliferative lupus nephritis

Answer 11

High Cr at presentation
Failure to achieve remission
High chronicity index on Bx
Ethnicity -African -American, Hispanic

Question 12

Cyclophosphamide vs MMF in induction Rx for lupus nephritis

Answer 12

Cyclophosphamide preferred with severe disease

as higher risk of relapse and ESRF with MMF

Question 13

Cause of deaths in SLE

Answer 13

Early deaths -active disease, infection

Late - coronary atherosclerosis, SLE, treatment complications

Question 14

Genetic mutations predisposing to SLE

Answer 14

Deficiencies of complement componenets C1q,C4A,B,C2
TREX1 gene mutations -encodes 3’repair endonuclease1
required to degrade DNA
MHC -hla-dr2,dr3,drb10301/1501
INF related pathway genes -IRF5,IRAK-1,TLR7,STAT4
T/B cell signalling/survival pathway, Immune complex clearance

Question 15

MOA of drug induced lupus

Answer 15

DNA hypomethylation -procainamide, hydralazine

Question 16

Epigenetic changes in SLE

Answer 16

Hypomethylation of DNA including IFN related genes
Aberrant expression of certain miRNAs in peripheral blood
Hypo or hyperacetylation of histones in pro-inflammatory genes (TNF alpha, IL-6)

Question 17

Immunopathogenesis of LSE

Answer 17

Loss of self tolerance to auto antigens
Increased apoptotic material serving as auto ags due to decreased phagocytosis and increased cellular apoptosis
Autoag form IC with autoab and trigger inflammatory cascade

Question 18

Enviornmental factors in SLE

Answer 18

UV light -> inf cytokine release from keratinocytes ->T cell DNA hypomethylation
Infection -EBV
Smoking
Pollutants -silica

Question 19

Drugs causing lupus

Answer 19

Procainamide, Hydralazine,diltiazem, INH, Methyldopa,chlorpromazine, INF-alpha
Serious manifestations rare (renal,CNS)
Anti histone ab -associated with certain drugs (procainamide, hydralazine, INH)
Resolves with withdrawal of drug
TNF inhibitors -cause autoabs, clinical lupus rare

Question 20

Hormonal abnormalities in lupus

Answer 20

Decreased DHEA, androgen, hyper prolactinemia

Question 21

Arthritis features in SLE

Answer 21

Arthralgias more than arthritis
Symm, polyarticular, migratory
Site- knee, wrist, finger joints
Morning stiffness less prominent
Non deforming, non erosive
Rhupus -RA/SE overlap, antiCCP associated with erosive disease
Avascular necrosis can occur in hip/kneeupto 40%

Question 22

Cardiovascular manifestation in SLE

Answer 22

Pericarditis is the MCC cardiac SLE manifestation
Myocardial -arryth, conduction abnorm
Valvular - Mitral>aortic, regur>stenosis
Libman Sacks endocarditis -rare
CAD - Increased risk, occurs at earlier age

Question 23

Pulmonary manifestations in SLE

Answer 23

PLeurisy
Parenchymal -rare
Pulmonary HTN , shrinking lung syndrome -rare

Question 24

GI manifestations

Answer 24

Deranged LFT
Auto immune hepatitis, acute pancreatitis
Intestinal pseudo obstruction

Question 25

Hematological manifestations

Answer 25

Anemia, AIHA, leucopenia, Thrombocytopenia(ITP can occur before SLE onset), TTP Evans syndrome -AIHA+ITP LNE Splenomegaly

Question 26

Neuropsychiatric manifestation

Answer 26

Aseptic meningitis, CVD,Seizure,Myelitis | Peripheral -GBS, autonomic neuropathy, MG, plexopathy

Question 27

Renal lupus

Answer 27

``` Class I-Minimal mesangial Class II -Mesangial proliferative Class III- Focal (<50% of glomeruli) (hematuria, pnuria,low GFR, +/-nephrotic syndrome) Class IV- Diffuse(nephrotic syndrome) Class V- Membranous (nephrotic syndrome) Class VI-Advanced sclerosing ```

Question 28

Auto ab in SLE

Answer 28

Mostly ANA positive | Dense fine speckled ANA pattern -less probablity of AI disesea

Question 29

Disease activity markers

Answer 29

ESR>CRP Increased anti-ds DNA ab Low C3,C4

Question 30

Management of disease

Answer 30

Minor disease -HCQ, NSAIDS, steroids Major -Steroids, Aza, Mtx, leflu,Cycloph,Cyclosp,Tac,MMF Rituximab for refractory disease

Question 31

Indications for renal biopsy in SLE

Answer 31

--Increased Serum Cr without alt cause --Confirmed pnuria>1gm/24hrs --Combinations of pnuria>0.5g/24hrs and hematuria>5RBC OR proteinuria>0.5gm/24hrs plus cellular casts

Question 32

Poor prognosis indicators in renal lupus

Answer 32

Disease severity( higher Cr at presentation,pnuria) Class, activity,chronicity scores Interstitial fibrosis and crescents Delay in diagnosis/treatment HTN, Low hematocrit, black race Socioeconomic class Differential gene expression on Bx -BAFF/APRIL,NFKB,IL-6 Improvement in pnuria to<0.7-0.8g/day at 12months predicts better long term outcome

Question 33

Treatment of lupus nephritis

Answer 33

``` Class I,II,VI -No immunosuppression Class III, IV(+/- V) - immunosuppression Induction(Pulse steroids+ MMF/Cycloph), maintainance(MMF/ Aza) , serological monitoring ACEI if pnuria>0.5g/day Target BP< 130/80 Statins if LDL >2.6mmol/L PLEX for thrombotic microangiopathy ```

Question 34

Targeted therapy in SLE

Answer 34

RITUXIMAB BELIMUMAB Human mAb- binds to soluble BAFF/BLyS preventing binding to its receptor on B cells S/E -depression, suicide Efficacy in musculoskl,mucocut, hematological domains and QOL Anti-IFN receptor Ab -Anifrolumab

Question 35

Pregnancy in SLE

Answer 35

Plan pregancy when SLE quiscent for 6 months(esp lupus nephritis) Flares can occur any trimester, post partum. Risk factors -active disease 6months prior to conception, h\o lupus nephritis, discontinuation of HCQ

Question 36

Contraindications to pregnancy in lupus

Answer 36

``` Severe pulm HTN (Sys PAP>50mmHg) Severe restrictive lung disease Advanced renal insufficiency Advanced HF Previous severe pre eclampsia /HELLP despite Rx CVA within 6 months Severe disease flare within 6 months ```

Question 37

Differentiating features bet pre-eclampsia and lupus nephritis

Answer 37

Hematuria/Active urinary sediment -> LN Complement levels ->Low in LN, N/H in PE Anti-ds DNA levels - > Increased in LN, N in PE PE - Elevated liver enzymes, high uric acid

Question 38

Antiphospholipid Ab ab and pregnancy

Answer 38

Asymptomatic pt - consider low dose aspirin (LD ASA) Prior obst morbidity - LD ASA+ Prophylactic LMWH Prior thrombosis -therapeutic LMWH until 6/12 post partum