lupus

Question 1

SLE: Loss of tolerance to ______ leads to immune system mediated damage to self

Answer 1

self

Question 2

SLE is rarer than RA?

Answer 2

yep At most one hundredth of RA

Female predominance (7-15:1)
In children and older lupus populations this ratio is not as high.

Question 3

Increased frequency in close relatives
30-50% concordance in monozygotic twins
Ethnic and racial susceptibilities may support genetic influence
HLA-DR2 and –DR3: weak associations
STAT4 (a transcription factor) gene variant allele on chromosome 2 confers increased risk of rheumatoid arthritis and SLE

Answer 3

genetic factors of SLE

Question 4

SLE central defect

Answer 4

apoptosis

Increased frequency in close relatives
30-50% concordance in monozygotic twins
Ethnic and racial susceptibilities may support genetic influence
HLA-DR2 and –DR3: weak associations
STAT4 (a transcription factor) gene variant allele on chromosome 2 confers increased risk of rheumatoid arthritis and SLE

Question 5

_____________ activation and its activation of the innate immune response may play a central role in perpetuating the autoreactive immune response

Answer 5

Toll-like receptor

Question 6

A strong ___________ is a hallmark of the cytokine profile in SLE. Mimics what might be seen in a chronic viral infection

Answer 6

interferon-1 induced gene transcript signature (with IFN-α the dominant mediator)

Question 7

SLE _________ serum complement levels are a marker for disease activity (particularly C3 and C4)

Answer 7

decreased

Activates complement cascade so abundantly that one sees complement depleted/consumed faster than it can be made

Question 8

SLE marker for disease activity

Answer 8

Anti-dsDNA

Question 9

most specific ab but no correlation with disease activity

Answer 9

anti-Sm(ith)

Question 10

Anti SSA (Ro), -SSB (La)

Answer 10

seen in both SLE and sjorgen

Question 11

Tregs cells are diminished in number and activity

Answer 11

yea

Question 12

Anti-RNP –

Answer 12

seen in SLE and “mixed connective tissue disease”

Question 13

Antiphospholipid antibodies (APLA)

Answer 13

when pathogenic - thrombosis, fetal loss

Anticardiolipin, lupus anticoagulant, false + VDRL all represent APLA

Question 14

Immune complexes in SLE

Answer 14

deposition in vessels and tissues initiates inflammation leading to damage

Question 15

Constitutional symptoms – nonspecific but can be profound (which do we see?)
Fatigue
Weight loss
Fever, sweats, chills
Lymphadenopathy

Answer 15

all of these can be seen in SLE

Question 16

Inflamation of muscles with release of muscle enzymes. Only rarely progresses to actual weakness thus usually a laboratory finding (elevation of creatine phosphokinase)

Answer 16

Myositis –

Question 17

cutaneous manifestations

Answer 17

1. malar rash- in 50% brought on by photosensitive, transient or chronic and similar appearing rashes seen in pregnancy
2. photosensitivity- 50%
3. discoid annular scaly plaques; scarring , head and neck arms
4. subacute cutaneous lupus- small erythematous papules that coalesce into patterns; nonscarring
5. bullous lupus rashes
6. alopecia
7. vascular- raynaud’s, telangiectasia

Question 18

. Deposits of multiple immune elements such as complement components and immunoglobulins (eg: IgM, IgG, etc)) may be found at the dermal-epidermal juncture

Answer 18

Positive lupus band test in SLE skin

Question 19

Probably the most morbid manifestation of SLE. This used to be a major cause of mortality in the pre-steroid era.

Answer 19

lupus nephritis

Nearly all patients have EM and immunofluorescent renal abnormalities; 50% have clinically apparent disease.
Usually but not always occurs in the first years of the disease.

Question 20

what happens in lupus nephritis?

Answer 20

immune complexes and complement deposit in glomeruli in capillary wall, subepithelium, subendothelium, and mesangium invoking inflammation and cellular proliferative and fibrotic (scarring) response

Question 21

Urinary findings in lupus nephritis:

• what type of cells do we see?
• • is there protein in the urine?
• Casts?

Answer 21

Hematuria (RBC) > pyuria (WBC)
Proteinuria
Casts – RBC casts most ominous

Question 22

class II GN

Answer 22

mesangial proliferative GN

Question 23

Class III GN

Answer 23

focal proliferative GN

Question 24

Class IV GN

Answer 24

diffuse proliferative GN

Question 25

For guiding treatment in SLE GN:

Class I and II (mesangial)

Class III and IV (proliferative GN)

Class V (membranous) -

In longstanding cases biopsy helps show the degree of permanent damage that will not be treatment responsive

Answer 25

Class I and II (mesangial) – may treat gingerly or not at all and watch closely for any transition to more aggressive histology

Class III and IV (proliferative GN) warrant steroids and other immunosuppressive therapy

Class V (membranous) - different treatment algorithm

Question 26

worst Class GN prognosis

Answer 26

Class IV

Question 27

an alkylating agent that works by slowing or stopping cell growth; greatest impact on most activated cells
Also used as chemotherapeutic agent in some cancer treatments

Answer 27

cyclophosphamide (cytoxan)

Question 28

an inhibitor of inosine-5’-monophosphate dehydrogenase. It depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation
Major use in preventing transplant rejection

Answer 28

mycopenolate (cellcept)

Question 29

_____________ significantly reduced the risk of renal failure at 9+ years compared to oral corticosteroids alone

Answer 29

Cyclophosphamide

Question 30

____________ has become the treatment of choice for proliferative lupus nephritis due to its favorable toxicity profile

Answer 30

Mycophenolate

Question 31

pulmonary manifestations in SLE (3)

Answer 31

1. pleurisy
2. interstitial inflammation- pneumonitis
3. vascular disease- PHTN

Question 32

Cardiac manifestations in SLE (4)

Answer 32

1. CAD
2. pericardial involvment
3. myocardial involvement
4. endocardial involvement- libman-sacks verrucous

Question 33

libman-sacks

Answer 33

verrucous endocarditis- immune complex deposition at valve edge

Question 34

neuropsychiatric lupus (2)

Answer 34

1. diffuse cerebral dysfunction

2. focal cerebral dysfunction- hypercoag. leading to stroke

Question 35

what is the target site in the glomerulus that leads to the highest risk of kidney failure?

Answer 35

glomerular endothelial cells

Question 36

management of SLE (3)

Answer 36

1. antimalarials such as hydroxychloroquine
2. corticosteroids for flares
3. biologic therapies that target b-cell suppression

Question 37

An ANA of 1:80 or greater is necessary in order for a patient to fulfill criteria

Answer 37

yep