Rheumatoid Arthritis and SLE

Question 1

What are key connective tissue disorders?

Answer 1

Systemic Lupus Erythematosus (SLE)
Sjögren’s syndrome
Autoimmune inflammatory muscle disease - Polymyositis, Dermatomyositis
Systemic sclerosis (scleroderma) - Diffuse cutaneous, Limited cutaneous
Overlap syndromes

SASOS

Question 2

Describe the key pathology of rheumatoid arthritis

Answer 2

Synovitis where site of chronic inflammation is the synovium. Has associated autoantibodies such as rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) antibodies. Chronic joint inflammation results in joint damage.

Question 3

List seronegative spondylarthropathies

Answer 3

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

Question 4

Describe ankylosing spondylitis

Answer 4

Chronic spinal inflammation that can result in spinal fusion and deformity
Site of inflammation includes the enthesis (enthesitis) - the site of insertion of a tendon, ligament, fascia, or articular capsule into bone
No autoantibodies (‘seronegative’)

Question 5

What is SLE and the main associated autoantigens

Answer 5

Chronic tissue inflammation in the presence of antibodies directed against self antigens
Multi-site inflammation but particularly the joints, skin and kidney

Associated with autoantibodies:
Antinuclear antibodies
Anti-double stranded DNA antibodies
Anti-phospholipid antibodies

Question 6

What are characteristics of connective tissue disorders?

Answer 6

Arthralgia and arthritis is typically non-erosive
Serum autoantibodies are characteristic:
May aid diagnosis
Correlate with disease activity
May be directly pathogenic

Question 7

What are features of Raynaud’s phenomenon?

Answer 7

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

Question 8

Who is a typical SLE patient and what are clinical manifestations?

Answer 8

Prototypic autoimmune disease typically diagnosed in female aged between 15 – 45 years.
Malar rash – erythema that spares the nasolabial fold - often the only sign of SLE
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 9

Describe proposed pathogenesis of SLE

Answer 9

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

Question 10

Elaborate on anti-phospholipid antibodies

Answer 10

Also termed anti-cardiolipin antibodies and associated with risk of arterial and venous thrombosis in SLE; may also occur in absence of SLE in what is termed the ‘primary anti-phospholipid antibody syndrome’

Question 11

What antibody is associated with systemic vasculitis?

Answer 11

Antinuclear cytoplasmic antibodies (ANCA)

Question 12

What are key investigation findings for SLE?

Answer 12

Inflammation: high ESR but C-reactive protein is typically normal unless infection or serositis/arthritis
Haematological signs: Haemolytic anaemia, Lymphopenia, Thrombocytopenia
Renal: earliest/best clinical sign is proteinuria measured with urine dipstick, check urine protein:creatinine ratio [uPCR], 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 13

Describe disease activity of lupus

Answer 13

Unwell lupus patient has LOW complement C3 and C4 levels and HIGH levels of anti-ds-DNA antibodies. Known as serologically active lupus.

Question 14

Describe effect of lupus on blood components

Answer 14

Immune thrombocytopenic purpura caused by lupus. Haemolytic anaemia with bone marrow trying to respond with reticulocytosis.

Question 15

What are 4 points about lupus management?

Answer 15

Hydroxychloroquine is recommended in all patients with lupus
Maintenance treatment glucocorticoids should be minimised and, when possible, withdrawn.
Appropriate initiation of immunomodulatory agents (methotrexate, azathioprine, mycophenolate) can expedite the tapering/discontinuation of glucocorticoids.
In persistently active or severe disease we use cyclophosphamide and B cell targeted therapies (rituximab and belimumab).