Systemic Lupus Erythematosus

Question 1

What diseases come under the category of ‘connective tissue disease’?

Answer 1

SLE

Systemic sclerosis

Dermatomyositis/polymyositis

Sjogren’s syndrome

Mixed connective tissue disease

Question 2

Which gender does SLE more commonly affect?

Answer 2

Females 9:1

Question 3

Describe the presentation of SLE including some specific features.

Answer 3

Malaise, fatigue, weight loss, fever
lymphadenopathy

Specific features:
Butterfly rash

Alopecia

Arthralgia

Long history of Raynaud’s phenomenon

Question 4

Describe the characteristics of the rash seen in SLE.

Answer 4

It tends to go across the nose

It may look a bit like acne

It is not painful or itchy

Some rashes become depigmented when the inflammation spreads to the dermis (depigmentation and scarring is irreversible)

Question 5

Describe the pathogenesis of SLE.

Answer 5

SLE patients have a defect in apoptosis

Apoptotic cells are not cleared properly so they persist and expose their nuclear antigens and autoantibodies are generated against these nuclear antigens

The defect in apoptosis is combined with B/T cell hyperactivity

The overactive B cells are exposed to the nuclear antigens and the plasma cells begin to produce autoantibodies that circulate and form immune complexes

The immune complexes deposit in tissues and activate complement leading to inflammation

Chronic inflammation cuases tissue fibrosis and damage

Question 6

What is the first investigation performed in the diagnosis of SLE?

Answer 6

Check for anti-nuclear antibodies (this is not specific for SLE though)

Question 7

The pattern with which the antinuclear antibodies bind to the nuclear antigens is important in reaching a diagnosis. List some different patterns, the antigens and disease they are associated with.

Answer 7

Homogenous – DNA - SLE

Speckled – antibodies to Ro, La, Sm and RNP - SLE overlap syndromes

Nucleolar – topoisomerase – scleroderma

Fine speckled - Centromere – limited cutaneous scleroderma aka CREST

Question 8

What conditions are associated with the presence of anti-Ro and anti-La antibodies?

Answer 8

Neonatal lupus syndrome

Subacute cutaneous lupus erythematosus

Question 9

What are some other tests that can be done for SLE?

Answer 9

Measuring complement levels

Anti-cardiolipin antibodies

Lupus anticoagulant

Beta 1 glycoprotein

Question 10

Describe the haematological features of SLE.

Answer 10

SLE is generally associated with low blood counts

Thrombocytopenia

Lymphopenia

Normocytic anaemia

Autoimmune haemolytic anaemia

Question 11

What renal changes might occur in SLE?

Answer 11

Proteinuria

Haematuria

Active urinary sediment

Question 12

List some clinical features that could help pre-empt severe attacks in SLE.

Answer 12

Malaise,

weight loss,

alopecia,

rash

Question 13

List some laboratory markers that could help pre-empt severe attacks in SLE.

Answer 13

Raised ESR

Raised anti-dsDNA antibodies

Reduced complement levels

Question 14

Describe the differences between mild, moderate and severe disease in SLE.

Answer 14

Mild – skin and joint involvement

Moderate – inflammation of other organs (e.g. pleuritis, pericarditis)

Severe – severe inflammation of vital organs

Question 15

Describe the treatment of mild disease.

Answer 15

Paracetamol and NSAIDs - monitor renal function

Hydroxychloroquine (good for arthropathy and cutaneous manifestations)

Topical corticosteroids

Question 16

Describe the treatment of moderate disease.

Answer 16

ORAL GLUCORTICOIDS

Start with a HIGH dose and titre downwards

Question 17

Describe the treatment of severe disease.

Answer 17

Immunosupressants:
Mycofenalate

Rituximab

Cyclophosphamide – one used if there is severe organ involvement
Problem – infertility

Question 18

Name and explain the mechanism of action of two new treatments for severe disease.

Answer 18

Mycophenolate mofetil
 Reversible inhibitor of inosine monophosphate dehydrogenase
 This is the rate limiting step in de novo purine synthesis
 Lymphocytes rely heavily on de novopurine synthesis

Rituximab
 Anti-CD20 antibody
 Causes depletion of B cells
 Useful in lupus nephritis

Question 19

SLE has and early peak and a late peak in mortality. What are the usual causes of the two peaks?

Answer 19

Early – renal failure, CNS disease, infection

Late – MI and stroke

Question 20

What can usually be seen on the blood film of a patient with SLE?

Answer 20

Schistocytes (evidence of microangiopathic haemolytic anaemia)

Teardrop cells

Spherocytes

Few leukocytes

Few platelets

Question 21

Describe the appearance of a renal biopsy in a patient with SLE

Answer 21

Hypercellular

Mesangial proliferation

Crescent development

Question 22

What is the aetiology of SLE?

Answer 22

Unknown - linked to HLA-RD3 and the environment (UV, drugs, microbal response)

Question 23

What are the SLE - ACR criteria?

Answer 23

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