Rheumatoid arthritis and SLE

Question 1

what are the key connective tissue disorders?

Answer 1

• SLE
• Sjogren’s syndrome
• Autoimmune inflammatory muscle disease
  
  • Polymyositis
  • Dermaotmyositis
• Systemic sclerosis (scleroderma)
  
  • Diffuse cutaneous
  • Limited cutaneous
• Overlap syndromes

Question 2

what is rheumatoid arthritis features?

Answer 2

• Chronic joint inflammation that can result in joint damage
• Site of inflammation is the synovium (synovitis)
• Associated with autoantibodies:
  
  • Rheumatoid factor
  • Anti-cyclic citrullinated peptide (CCP) antibodies

Question 3

what is ankylosing spondylitis?

Answer 3

• Chronic spinal inflammation that can result in spinal fusion and deformity
• Site of inflammation includes the enthesis
• No autoantibodies (‘seronegative’)

Question 4

what are the seronegative spondyoarthropathies?

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

• 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 (increased risk clotting-thrombosis)
• Formation of immune complexes
• Prototypic autoimmune disease typically diagnosed in females aged 15-45 years

Question 6

what are the clinical manifestations of SLE?

Answer 6

• 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 7

what is the pathogenesis of SLE?

Answer 7

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 8

what are the investigations of SLE?

Answer 8

• 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 9

what is the complement consumption in SLE?

Answer 9

immune complexes can activate the complement system – innate immunity à inflammation

• high immune complexes = increased consumption of C4 and C3
• Unwell patient has Low complement C3 and C4 and high anti-dsDNA antibodies
• Normal C3 = 0.7-1.7

Question 10

what is the managment SLE?

Answer 10

• Treatment in SLE aims at remission or low disease activity and prevention of flares
  
  • 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)
• Patients with SLE should be assessed for their antiphospholipid antibody status
  
  • If raised = higher risk thrombosis= anticoagulant treatment
• Patients with SLE should be assessed for their infectious and cardiovascular diseases risk profile
• Pregnancy planning- many drugs contraindicated in pregnancy

Question 11

what is Sjogren’s syndrome?

Answer 11

• Autoimmune exocrinopathy
  
  • lymphocytic infiltration of especially exocrine glands and sometimes of other organs (extra-glandular involvement)
• Exocrine gland pathology results in
  
  • Dry eyes (xerophthalmia)
  • Dry mouth (xerostomia)
  • Parotid gland enlargement
• Commonest extra-glandular manifestations are non-erosive arthritis and Raynaud’s phenomenon
• Termed ‘secondary’ Sjögren’s syndrome if occurs in context of another connective tissue disorder e.g. SLE

Question 12

what is inflammatory muscle disease?

Answer 12

• Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash
• Skin changes in dermatomyositis:
  
  • Lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds
  • Red or purple flat or raised lesions on knuckles (Gottron’s papules)
  • Subcutaneous calcinosis
  • Mechanic’s hands (fissuring and cracking of skin over finger pads)
• Elevated CPK, abnormal electromyography, abnormal muscle biopsy (polymyositis = CD8 T cells; dermatomyositis = CD4 T cells in addition to B cells)
• Associated with malignancy (10-15%) and pulmonary fibrosis

Question 13

what is systemic sclerosis (scleroderma)?

Answer 13

• Thickened skin with Raynaud’s phenomenon
  
  • Dermal fibrosis, cutaneous calcinosis and telangiectasia
• Skin changes may be limited or diffuse
  
  • Diffuse systemic sclerosis
    
    • Fibrotic skin proximal to elbows or knees (excluding face and neck)
    • Anti-topoisomerase-1 (anti-Scl-70) antibodies
    • Pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
    • Short history of Raynaud’s pheno menon
  • Limited systemic sclerosis
    
    • Fibrotic skin hands, forearms, feet, neck and face
    • Anti-centromere antibodies
    • Pulmonary hypertension
    • Long history of Raynaud’s phenomenon
• Can cause digital infarcts

Question 14

what is overlap syndrome?

Answer 14

• When features of more than 1 connective tissue disorder are present e.g. SLE and inflammatory muscle disease we can use the term overlap syndrome
• When incomplete features of a connective tissue disease are present we can use the term undifferentiated connective tissue disease
• In one instance a group of patients with features of seen in SLE, scleroderma, rheumatoid arthritis, and polymyositis were identified by the presence of an autoantibody:
• Anti-U1-RNP antibody*
• ….this condition was termed Mixed Connective Tissue Disease (‘MCTD’)

Question 15

what are the auto-antibodies seen in:

diffuse systemic sclerosis

limited systemic sclerosis

dermato/ polymyositis

sjogren’s syndrome

mixed connective tissue disease

Answer 15

Question 16

what can serum antibodies be used for?

Answer 16

• May aid diagnosis
• Correlate with disease activity
• May be directly pathogenic

Question 17

what is Raynaud’s phenomenon?

Answer 17

• 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 isolated and benign condition

Question 18

what are the key autoantibodies in:

1. rheumatoid arthritis
2. systemic lupus erythematosus
3. osteoarthritis
4. reactive arthritis
5. gout
6. ankylosing spondylitis
7. systemic vasculitis

Answer 18