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BRS Year 2 > Rheumatoid Arthritis and SLE Tutorial > Flashcards

Rheumatoid Arthritis and SLE Tutorial Flashcards

Connective Tissue Disorders

1
Q

What are the key connective tissue disorders?

A

Systemic Lupus Erythematosus (SLE)

Sjorgen’s syndrome

Autoimmune inflammatory muscle disease

  • Polymyositis
  • Dermatomyositis

Systemic sclerosis (scleroderma)

  • Diffuse cutaneous
  • Limited cutaneous

Overlap syndromes

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2
Q

What is RA?

A

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
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3
Q

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

A

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’)

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4
Q

What are some other seronegative spondyloarthropathies?

A

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

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5
Q

What is SLE?

A

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
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6
Q

What are the broad similarities in connective tissue disorders?

A

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

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7
Q

What is the purpose of serum autoantibodies?

A

Aids diagnosis
Correlated with disease activity
May be directly pathogenic

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8
Q

What is Raynaud’s phenomenon?

A

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’)

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9
Q

What demographic is SLE diagnosed in?

A

Females aged between 15 – 45 years

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10
Q

What are the clinical manifestations of SLE?

A

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

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11
Q

What is the pathogensis of SLE?

A

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

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12
Q

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

A

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)

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13
Q

What investigations are conducted in SLE?

A

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

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14
Q

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

A

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)

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15
Q

Why does C3 and C4 decrease as SLE progresses?

A

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

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16
Q

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

A

High levels of immune complexes

Low levels of C3 and C4

17
Q 
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?

A

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?

18
Q

What clinical signs would you look for on examination?

A

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

19
Q

What tests would you do?

A

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

20
Q

What are the differential diagnoses?

A

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

Scleroderma = possible but less likely due to lung involvement

21
Q

What is the management plan for the most likely diagnosis?

A

Hydroxychloroquine
Maintenance steroids should be withdrawn
Immunomodulatory agents: methotrexate, azathioprine, mycophenolate- can speed up tapering of of glucocorticoids
In persistently active or severe disease: cyclophosphamide and B cell depletion (rituximab, belimumab)

Asses for antiphospholipid antibody
Assess for infection and CVD risk
Pregnancy planning- some treatments (e.g. cyclophosphamide) need to be stopped

22
Q

What are anticardiolipin antibodies associated with?Where else might anticardiolipin antibodies be present?

A

Associated with risk of venous and arterial thrombosis

May be present without SLE in primary antiphospholipid antibody syndrome

23
Q

What are types of anti-nuclear antibodies?

A 
If ANA is positive we screen for what type. These include:
Anti-Ro
Anti-La
Anti-centromere
Anti-sm
Anti dsDNA
Anti-SCl 70

Cytoplasmic antibodies:
Anti-tRNA antibodies
Anti-ribosomal P antibodies

24
Q

What are different patterns of ANAs that we see in SLE?

A

Homogenous
Speckled
Nucleolar
Fine speckled

25
Q

What is the significance of the different antibodies we see in SLE?

A

ANA: seen in all SLE cases, not specific for SLE

Anti- dsDNA: Specific for SLE. Serum conc. correlated with disease activity

Anti-phospholipid antibody: associated with venous and arterial thrombosis

Anti-SM antibody: Specific for SLE. Serum level does NOT correlate with disease activity

Anti-Ro and Anti-La antibody: antigen is ribonucleoprotein. Secondary Sjogren’s syndrome. Neonatal lupus syndrome

Anti-ribosomal P antibody: Cerebral lupus

26
Q

What would be indicative of active glomerulonephritis in SLE?

A

Large rise in Protein:creatinine ratio

27
Q

What is Sjogren’s syndrome?

A

Autoimmune exocrinopathy: lymphocytic infiltration, esp. of exocrine glands and sometimes other organs

Symptoms:
Dry eyes (xerophthalmia
Dry mouth (xerostomia) - can lead to problems in dental hygiene
Parotid gland enlargement

Extraglandular manifestations:
Non-erosive arthritis, raynaud’s phenomenon

Secondary sjogren’s syndrome: occurs in context if another connective tissue disorder e.g. SLE

28
Q

What test can we do for Sjogren’s syndrome?

A

Salivary gland biopsy- will should lymphocytic infiltration, mainy helper T cells and some B cells

Schirmer’s test: asses tear production. Filter paper placed under lower eyelid and wetness measured after 5 mins. Abnormal is <5mm

29
Q

What is inflammatory muscle disease?

A

Proximal muscle weakness due to autoimmune-mediated inflammation either with (dermatomyositis) or without (polymyositis) a rash

Associated with malignancy (10-15%) and pulmonary fibrosis

30
Q

What are symptoms of inflammatory muscle disease?

A

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)

31
Q

What are symptoms of systemic sclerosis?

A

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 phenomenon

Limited systemic sclerosis*
• Fibrotic skin hands, forearms, feet, neck and face
• Anti-centromere antibodies
• Pulmonary hypertension
• Long history of Raynaud’s phenomenon

*CREST: Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasia (spider veins)

32
Q

What is overlap syndrome?

A

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’)

33
Q

What are key autoantibodies for different connective tissue disorders?

A

Diffuse systemic sclerosis
• Anti-Scl-70 antibody
• also termed antibodies to topoisomerase-1

Limited systemic sclerosis
• Anti-centromere antibodies

Dermato-/Polymyositis
• Anti-tRNA transferase antibodies
• E.g. histidyl transferase (also termed anti-Jo-1 antibodies)

Sjögren’s syndrome
No unique antibodies but typically see
• Antinuclear antibodies - Anti-Ro and anti-La antibodies
• Rheumatoid factor

Mixed connective tissue disease
• Anti-U1-RNP antibodies

BRS Year 2 (110 decks)

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