Rheumatoid Arthritis and SLE Tutorial

Question 1

What are the key connective tissue disorders?

Answer 1

Systemic Lupus Erythematosus (SLE)

Sjorgen’s syndrome

Autoimmune inflammatory muscle disease

• Polymyositis
• Dermatomyositis

Systemic sclerosis (scleroderma)

• Diffuse cutaneous
• Limited cutaneous

Overlap syndromes

Question 2

What is RA?

Answer 2

Chronic joint inflammation that can result in joint damage

Primarily = synovitis = inflammation in the synovium

Associated with autoantibodies =

• Rheumatoid factor (RF)
• Anti-cyclic citrullinated peptide (CCP) antibodies

Question 3

What is the main disease in seronegative inflammatory arthritis? How is it characterised?

Answer 3

Ankylosing spondylitis

Chronic spinal inflammation that can result in spinal fusion and deformity

Site of inflammation includes the enthesis (connective tissue between tendon or ligament and bone) = enthesitis

No autoantibodies (‘seronegative’)

Question 4

What are some other seronegative spondyloarthropathies?

Answer 4

Ankylosing spondylitis
Reactive Arthritis (Reiters syndrome)
Arthritis associated with psoriasis (psoriatic arthritis)
Arthritis associated with gastrointestinal inflammation (enteropathic synovitis)

Question 5

What is SLE?

Answer 5

Systemic lupus erythematosus

Autoimmune disease = chronic tissue inflammation in the presence of antibodies directed against self antigens
These form antigen-antibody complexes AKA immune complexes that are responsible for glomerulonephritis, vasculitis, and a variety of other SLE manifestations

Multisystem disorder = can affect everywhere but particularly joints, skin and kidneys

Associated with autoantibodies =

• Antinuclear antibodies (ANA)
• Anti-double stranded DNA antibodies (anti-dsDNA)
• Anti-phospholipid antibodies

Question 6

What are the broad similarities in connective tissue disorders?

Answer 6

More often arthralgia rather than an arthritis
i.e. pain in joints and tenderness, but no redness, swelling, heat
If there is arthritis, this is typically non-erosive

Serum antibodies are characteristic for different connective tissue disorders

Raynaud’s phenomenon is common in these conditions

Question 7

What is the purpose of serum autoantibodies?

Answer 7

Aids diagnosis
Correlated with disease activity
May be directly pathogenic

Question 8

What is Raynaud’s phenomenon?

Answer 8

Ischaemic changes affecting the fingers =

Intermittent vasospasm of digits on exposure to cold

Typical colour changes – white to blue to red

• Vasospasm leads to blanching of digit
• Cyanosis as static venous blood deoxygenates
• Reactive hyperaemia

Raynaud’s phenomenon is most commonly an isolated and benign condition (‘Primary Raynaud’s phenomenon’)

Question 9

What demographic is SLE diagnosed in?

Answer 9

Females aged between 15 – 45 years

Question 10

What are the clinical manifestations of SLE?

Answer 10

Malar rash – erythema that spares the nasolabial fold
Photosensitive rash
Mouth ulcers
Hair loss
Raynaud’s phenomenon
Arthralgia and sometimes arthritis
Serositis (pericarditis, pleuritis, less commonly peritonitis)
Renal disease – glomerulonephritis (‘lupus nephritis’)
Cerebral disease – ‘cerebral lupus’ e.g. psychosis

Question 11

What is the pathogensis of SLE?

Answer 11

Currently incompletely understood

Apoptosis leads to translocation of nuclear antigens to membrane surface –> Impaired clearance of apoptotic cells results in enhanced presentation of nuclear antigens to immune cells –> B cell autoimmunity –> Tissue damage by antibody effector mechanisms e.g. complement activation and Fc receptor engagement

Question 12

What are the key autoantibodies in rheumatology and which rhumatological disease are they most relevant in?

Answer 12

RA = rheumatoid factor (RF) and anti cyclic citrullinated peptide(CCP) antibody

SLE = antinuclear antibodies (ANA), anti-double stranded DNA antibodies (anti-dsDNA), anti-phospholipid antibodies

OA = none

Reactive arthritis = none

Gout = none

Ankylosing Spondylitis = none

Systemic vasculitis = antinuclear cytoplasmic antibodies (ANCA)

Question 13

What investigations are conducted in SLE?

Answer 13

Screen for organ system involvement by investigating:

Inflammation:
- High ESR but C-reactive protein is typically normal unless infection or serositis/arthritis

Haematology:
- Haemolytic anaemia, Lymphopenia, Thrombocytopenia

Renal:

• Very important to measure urine protein (most commonly urine protein:creatinine ratio [uPCR])
• Look at albumin

Immunological

• Antinuclear antibodies
• Anti-double-stranded DNA antibodies - highly specific, correlate with disease activity
• Complement consumption – e.g. low C4 and C3

Clotting – antiphospholipid antibodies
- Lupus anticoagulant and anti-cardiolipin antibodies

Question 14

Why might all the investigation results from SLE not be caused by SLE?

Answer 14

If the patient is currently being / has been treated

Some changes in investigations may reflect adverse reactions to medications e.g. abnormal liver function (‘transaminitis’) or fall in neutrophil count (neutropenia)

Question 15

Why does C3 and C4 decrease as SLE progresses?

Answer 15

Due to activation of the classical pathway leading to inflammation

Immune complexes found in SLE activate the complement pathway - this is part of our innate immunity and causes inflammation

So the immune complexes activate the complement system via the classical pathway, which includes C4 and C3

So the more immune complexes produced in SLE, the more activation of the classical complement pathway = C3 and C4 are used up

Therefore, C3 and C4 being to fall as SLE progresses

Question 16

So in an SLE (lupus) patient, what will their levels of immune complexes and C3/C4 be?

Answer 16

High levels of immune complexes

Low levels of C3 and C4

Question 17

Case 1 - 22F
Increasing lethargy
Arthralgia
Shortness of breath
Chest pain on inspiration
Skin photosensitivity 
Ankle swelling 

HPC = fingers changing colour over the last 3 years

Examination = dull lung bases, quiet heart sounds, peripheral oedema

Bloods = high ESR, normal / low CRP, low lymphocytes, high albumin

What other questions would you ask?

Answer 17

Any mouth ulcers?

Any hair loss?

Any rashes?

Any fevers?

Does your skin photosensitive rash spare your nasolabial folds?

Have you noticed any muscle weakness?

Any PMH of DVT? / Any PMH of miscarriages?

Any FH of autoimmune disorders?

Question 18

What clinical signs would you look for on examination?

Answer 18

Signs of mouth ulcers?

Pleural rub - pain on inspiration = pleuritis

Dull lung sounds = fluid, so maybe pleural effusion

Quiet heart sounds = pericardial effusion?

Peripheral oedema = nephrotic syndrome / kidney involvement

Question 19

What tests would you do?

Answer 19

Urine dipstick test - proteinuria

Look for positive ANA and anti-dsDNA

High ESR and normal / low CRP

Kidney biopsy if there is kidney involvement - as management is dependent on biopsy findings

Increased complement deposition in the nephrons = low C3 and C4

Question 20

What are the differential diagnoses?

Answer 20

SLE = most likely - photosensitive rash, high ESR low CRP, lymphopenia, involvement of lungs

Scleroderma = possible but less likely due to lung involvement

Question 21

What is the management plan for the most likely diagnosis?

Answer 21

Acute management
Steroids and hydroxychloroquine = to suppress the immune system

Long term =
Immunosuppresive agents
If suggestive of clotting - anticoagulants / antithrombotic therapy