Systemic lupus erythematosus

Question 1

What is SLE

Answer 1

Systemic autoimmune disease

Chronic relapsing and remitting

Question 2

What is the genetic association

Answer 2

Unknown aetiology –multi-factorial genetic

(HLA-DR3)

Question 3

What systems are are invoved in the pathology

Answer 3

Mutli-system:
CNS            
Heart 
Kidney        
Blood 
Heart           
Skin and Joints
Foetus         
Lungs

Question 4

Who are most likely to get lupus

Answer 4

Most likely Female (10:1 ratio)
Probably young when started (age of onset15-47)
Increased risk in Afro-Caribbean/Asian

Question 5

Outline the pathogenesis

Answer 5

Innate susceptibility (HLA type/immunoregulatory genes/ complement/hormones)
+
Environmental stimuli

Leads to

Autoimmune proliferation and
autoantibody production

Question 6

T/F- anti-nuclear antibodies is diagnostic of lupus

Answer 6

F….. up to 5% of population have this

Question 7

Outline the stages leading to SLE

Answer 7

A. Loss of self-tolerance

B. Production of auto-antibody

C. Desposition of immune complexes

D. Immune complex inflammation

E. Tissue fibrosis and damage

Question 8

What happens in loss of self tolerance

Answer 8

Failure to clear apoptotic cells, exposing nuclear antigens to immune system

APCs such as DCs take up nuclear antigens, they are recognised internally by TLRs

APC may present the self-antigen to autoreactive cell

Question 9

What happens in production of autoantibody

Answer 9

Pathomnemonic

Autoreactive T cells provide help to B cells, producing large quantities of autoantibody

The antibodies form immune complexes

Question 10

What happens with deposition of immune complexes

Answer 10

Circulating ICs not cleared and become deposited in tissues like kidney or skin

Question 11

What happens in immune complex associated inflammation

Answer 11

IC deposited in tissues not cleared, and elicit inflammation with complement activation (classical pathway) and activation of macrophaes and neutrophils via surface Fc receptors which bind IgG

Question 12

What happens in fibrosis and damage

Answer 12

Production of pro-inflammatory and pro-fibrotic cytokines. Leads to irreversible tissue damage

Question 13

Clinical features of SLE:

Presentation

Answer 13

Malaise, fatigue, fever, wt loss

Lymphadenopathy

Question 14

Clinical features of SLE:

Specific features of SLE

Answer 14

• Butterfly rash (=malar rash), alopecia
• Arthralgia
• Raynaud’s phenomenon

Question 15

Clinical features of SLE:

Answer 15

• Inflammation kidney, CNS, heart, lung
• Accelerated atherosclerosis
• Vasculitis

Question 16

SLE criteria

Answer 16

Use the ACR criteria

S-Serositis
O-oral ulcers
A-arthritis
P-Photosensitivity

B-Blood (all low)
Renal-proteinuria
Immunological- ANA, anti-dsDNA
N-neurological-seizures/psychosis

M-Malar rash
D- discoid rash

Question 17

Differential diagnosis with SLE

Answer 17

ANA positive due to infection/malignancy

Other autoimmune CTD

Cutaneous SLE- without systemic involvement

Drug induced Lupus-

Question 18

Drugs inducing lupus

Answer 18

procanamide, hydrazine, quinidine, isonizaide

Question 19

How is SLE diagnosed

Answer 19

ANA antibodies

Other

Haem

Renal

Question 20

What diseases associated with thedollowing antinuclear body patterns

Homogenous
Speckled
Nucleolar
Fine speckled

Answer 20

Homogenous: Abs to DNA …. SLE

Speckled- Abs to Ro, La, Sm, RNP… SLE/overlap

Nucleolar- Abs to topoisomerase….. scleroderma

Fine speckled- Abs to Centromere… CREST (limited custanous scleroderma

Question 21

Other than ANAs what other antibodies might you check

Answer 21

Anti-dsDNA and Sm more specific for SLE but less sensitive

Anti-Ro and/or Lo- common in subacute cutaneous LE. Neonatal lupus syndrome and Sjorens

Question 22

Outline ‘other tests’ for SLE

Answer 22

• Increased complement consumption
• Anti-cardiolipin antibodies
• Lupus anticoagulant
• ß1 glycoprotein

Question 23

Haematology lab tests in SLE

Answer 23

• Lymphopaenia, normochromic anaemia

* Leukopaenia, AIHA, thrombocytopaenia

Question 24

Renal lab tests in SLE

Answer 24

Proteinuria, haematuria

Active urinary sediment

Question 25

How is severeity of SLE assessed

Answer 25

1. Identify pattern of organ involvement 2. Monitor function of affected organs * Renal * Lungs/CVS - * Skin, haematology, eyes 3. Identify pattern of autoantibodies expressed * Anti-dsDNA, anti-Sm - renal disease * Anti-cardiolipin antibodies

Question 26

What are the signs of disease activity in SLE

Answer 26

* Wt loss, fatigue, malaise, hair loss * Alopecia * Rash

Question 27

What are the lab diagnoses of disease activity in SLE

Answer 27

* ESR * Increased complement consumption * Increased anti-dsDNA * Other Abs e.g ANA and CRP poor indicators

Question 28

What is mild, moderate and severe SLE

Answer 28

MILD: -joint +/- skin involvement MODERATE: - inflammation of other organs - pleuritis, pericarditis, mild nephritis SEVERE: -sever inflammation in vital organs: sever nephritis, CNS disease, pulmonary disease, cardiac involvemnet, thombcytopenia

Question 29

Treatment of mild SLE

Answer 29

Paracetemol +/- NSAID (monitor renla function) Hydroxychloroquine (in arthropathy, cutaneous manifestations and mild diseases activity) Topical corticosteroids

Question 30

Treatment of severe SLE

Answer 30

Oral steroids or IV methylprednisolone + Immunosupressants- severe organ disease - Cyclophosphamide - Mycofenalate Mofitil (MMF) - Rituximab (anti-CD20 monoclonal anti-body) for Lupus Nephritis Maintenance treatment with low dose oral steroids (<5mg/day) and immunosuppressants (methotrexate, azathioprine or MMF)

Question 31

Why do lupus patients need sun bock

Answer 31

lupus is very photosensitive

Question 32

What if lupus patuets get pregnant

Answer 32

Anti-RO antibodies in pregnancy- need to be monitored due to risk of congenital HB

Question 33

When is hydroxychloroquine used?

Answer 33

Hydroxychloroquine commonly used for skin and joint disease

Question 34

Prognosis and survival of lupus

Answer 34

15 year survival : no nephritis 85% | nephritis 60%

Question 35

When is prognosis worse in lupus

Answer 35

Prognosis also worse if black, male, | low socio-economic status

Question 36

What is going to be causig mortality in SLE

Answer 36

Early mortality: Active lupus - Renal failure - CNS disease - Infection ``` Late mortality: Myocardial infarction (due to accelerated atherosclerosis) ```

Question 37

Overal treatment strategies for SLE

Answer 37

Symptomatic Immune-modulating Immunosuppressive

Question 38

What do the clinical features of SLE depends on

Answer 38

Organ affected