Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Year 2 - BRS > 8.6 - Lupus and related autoimmune connective tissue diseases > Flashcards

8.6 - Lupus and related autoimmune connective tissue diseases Flashcards

1
Q

What are the autoimmune connective tissue disorders? (4)

A
  • systemic lupus erythematosus (SLE)
  • autoimmune inflammatory muscle disease (myositis)
  • systemic sclerosis (scleroderma)
  • Sjogren’s syndrome
  • (NB overlap syndromes can occur, especially in children)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Why is the term ‘connective tissue disorder’ not entirely accurate?

A

Often involvement of other organs - ‘multisystem autoimmune rheumatic diseases’ might be better

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the main site of inflammation in rheumatoid arthritis?

A

Synovium

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What autoantibodies is rheumatoid arthritis associated with? (2)

A
  • rheumatoid factor (RF)
  • anti-cyclic citrullinated peptide (CCP) antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What can ankylosing spondylitis result in?

A

Chronic spinal inflammation that can result in spinal fusion and deformity (increased thoracic kyphosis and loss of normal lumbar lordosis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the site of inflammation in ankylosing spondylitis?

A

Enthesis (bamboo spine - enthesitis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Are there autoantibodies associated with ankylosing spondylitis?

A

No autoantibodies - seronegative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Does SLE have innate or adaptive immune system involvement?

A

Autoimmune disease involving disturbance of both innate and adaptive immune systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What autoantibody is associated with SLE?

A

Antibodies to nuclear components (ANA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the mechanism of chronic tissue inflammation in SLE?

A

Autoantibodies –> antibody-antigen (immune complexes) and other mechanisms –> circulate in blood and deposit in tissue–> chronic tissue inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Where does inflammation affect the most in SLE?

A

Multi-site inflammation but particularly the joints, skin and kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How are arthralgia and arthritis different between RA and autoimmune connective tissue disorders (e.g. SLE)?

A
  • arthralgia (joint pain) and arthritis (joint inflammation) are present in both but in SLE they are typically non-erosive (unlike in RA)
  • this is because there is no underlying synovitis in SLE but there is in RA
  • no obvious bedside inflammation of joints in SLE but there is in RA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How are serum antibodies important in diagnosing autoimmune connective tissue disorders (e.g. SLE)? (3)

A
  • useful diagnostically - may aid diagnosis
  • some correlate with disease activity
  • may be directly pathogenic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Describe Raynaud’s phenomenon and the triphasic colour change seen in autoimmune connective tissue disorders (e.g. SLE).

A
  • Raynaud’s phenomenon is common in these conditions
  • intermittent vasospasm of digits
  • usually triggered by cold exposure
  • typically triphasic colour changes:
    • WHITE - vasospasm leads to blanching of digit
    • BLUE - cyanosis as static venous blood deoxygenates
    • RED - reactive hyperaemia (painful)
  • severe Raynaud’s –> tissue ischaemia, ulcers and necrosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What usually triggers Raynaud’s phenomenon?

A

Cold exposure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What can severe Raynaud’s phenomenon lead to?

A

Tissue ischaemia, ulcers and necrosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe the epidemiology of SLE.

A
  • typical onset between 15-45 years
  • F:M ~9:1
  • prevalence and severity varies by ancestry: African > Asian > White European
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are the clinical manifestations of SLE like and how can this affect diagnosis?

A
  • clinical manifestations are highly variable, which causes diagnostic difficulties
  • disease may range from mild to life-threatening
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What deformity may be seen in the digits of someone with SLE?

A

Swan neck deformity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What are some clinical features of SLE? (6 subtypes)

A
  • skin and mucosa:
    • malar rash - erythema that spares the nasolabial fold
    • photosensitive rash
    • mouth ulcers
    • hair loss
  • vascular: Raynaud’s phenomenon
  • MSK: arthralgia and sometimes arthritis (non-erosive)
  • internal organs:
    • serositis (pericarditis - pain on leaning forward, pleuritis - pain on breathing in, less commonly peritonitis)
    • renal disease - glomerulonephritis (lupus nephritis)
    • cerebral disease - ‘cerebral lupus’ e.g. psychosis
    • myocarditis
  • haematological:
    • autoimmune thrombocytopenia
    • haemolytic anaemia
    • lymphopenia
  • other:
    • lymphadenopathy
    • fever in absence of infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the main autoantibodies associated with SLE? (3)

A
  • antinuclear antibodies (ANA)
  • anti-double stranded DNA (anti-dsDNA)
  • anti-phospholipid antibodies
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How can antinuclear antibodies (ANA) be used in diagnosis of SLE?

A
  • a hallmark feature of SLE is the presence of ANA
  • found in all SLE patients
  • negative ANA effectively rules out SLE
  • however, ANA is not specific for SLE - may be seen in other autoimmune diseases, infection or even healthy people
  • if ANA +ve, the laboratory will report strength
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

The laboratory does further specific autoAb tests to see what ANA are reacting to - what can these autoAb be? (7 - bold indicates may be positive in SLE)

A
  • anti-ds-DNA antibodies
  • anti-Ro
  • anti-La
  • anti-centromere
  • anti-Smith (Sm)
  • anti-RNP
  • anti-Scl-70
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are antiphospholipid (APL) antibodies?

A

As well as ANA, some SLE patients have antibodies directed to phospholipids on cell surfaces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are antiphospholipid (APL) antibodies associated with increased risk of? (2)

A
  • thrombosis - arterial (e.g. stroke), venous (e.g. DVT)
  • pregnancy loss (miscarriage)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What is anti-phospholipid antibody syndrome?

A
  • persistent presence of APL + a clinical event
  • can also occur in the absence of SLE (‘primary anti-phospholipid antibody syndrome’ i.e. ANA will be negative)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Describe the significance of antinuclear antibodies (ANA).

A
  • seen in all SLE cases
  • not specific for SLE
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Describe the significance of anti-double stranded DNA antibodies (anti-dsDNA).

A
  • specific for SLE
  • serum level of antibody correlates with disease activity
29
Q

Describe the significance of anti-phospholipid antibodies.

A
  • 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’
30
Q

Describe the significance of anti-Sm antibodies.

A
  • antigen is a ribonucleoprotein
  • specific for SLE
  • serum level of antibody does NOT correlate with disease activity
31
Q

Describe the significance of anti-Ro and anti-La antibodies. (Not tested)

A
  • antigen = ribonucleoprotein
  • secondary Sjogren’s syndrome
  • neonatal lupus syndrome (transient rash in neonate, permanent heart block)
32
Q

What are the key autoantibodies associated with rheumatoid arthritis? (2)

A
  • rheumatoid factor
  • anti-cyclic citrullinated peptide antibody (AKA antibodies to citrullinated peptide antigens - ACPA)
33
Q

What are the key autoantibodies associated with SLE? (7)

A
  • antinuclear antibodies (ANA)
  • anti-double stranded DNA antibodies (anti-dsDNA)
  • anti-phospholipid antibodies (APL)
  • anti-Smith
  • anti-Ro
  • anti-La
  • anti-RNP
34
Q

What are the key autoantibodies associated with osteoarthritis?

A

None

35
Q

What are the key autoantibodies associated with reactive arthritis?

A

None

36
Q

What are the key autoantibodies associated with gout?

A

None

37
Q

What are the key autoantibodies associated with ankylosing spondylitis?

A

None

38
Q

What are the key autoantibodies associated with systemic vasculitis? (Not tested)

A

Anti-neutrophil cytoplasmic antibodies (ANCA)

39
Q

What is the immunopathogenesis of SLE? (3)

A
  • overactivity of type 1 interferon pathway (innate immunity, normally IRT viral infection)
  • complement pathway abnormalities (innate immunity)
  • autoreactive B and T cells (adaptive immunity)
40
Q

How is the immune system generating a response to nuclear antigens in SLE (should be hidden inside the cell) - the ‘waste disposal hypothesis’?

A
  • 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
41
Q

What types of investigation do we do for SLE? (5)

A
  • inflammation: high ESR but normal CRP (unless infection or serositis/arthritis)
  • haematology: haemolytic anaemia, lymphopenia, thrombocytopenia
  • renal:
    • very important to measure urine protein (urinalysis + quantify with urine protein:creatinine ratio - uPCR)
    • creatinine (part of U&Es, measure renal function)
    • look at albumin (can be low due to proteinuria)
    • kidney biopsy if persistent proteinuria
  • immunological: ANA, anti-dsDNA, complement consumption (low C3 and C4), anti-phospholipid antibodies
  • in treated patients SOME changes may reflect adverse reactions to medication e.g. abnormal LFTs (transaminitis) or neutropenia
42
Q

What adverse effects can occur from SLE medication? (2)

A
  • abnormal LFTs - transaminitis
  • neutropenia
43
Q

How do we measure disease activity in SLE? (2)

A

Combination of:

  • clinical symptoms and signs
  • investigations e.g. measuring complement levels (C3&C4) and anti-dsDNA antibodies
44
Q

What does an unwell patient with SLE typically have? (2)

A
  • low complement C3 and C4 levels
  • high anti-dsDNA antibodies
45
Q

What is the aim of SLE treatment?

A

Remission or low disease activity and prevention of flares

46
Q

What do we need to balance when considering SLE treatment?

A

Balance between controlling disease vs avoiding iatrogenic harm (especially steroids)

47
Q

What are some side effects of steroids for treating SLE? (3)

A
  • infection
  • osteoporosis
  • avascular necrosis - often affects hips, higher incidence in lupus especially in presence of APL antibodies
48
Q

What can speed up the tapering/discontinuation of glucocorticoids for SLE?

A

Appropriate initiation of immunomodulatory agents

e.g. methotrexate, mycophenolate, azathioprine

49
Q

What does specific choice of treatment for SLE depend on?

A

Disease severity and organ manifestations

50
Q

What drug do we recommend to all patients with lupus?

A

Hydroxychloroquine

51
Q

What drug type do we use for acute flares of lupus?

A

Steroids for acute flare but aim to withdraw as soon as safe to do so (appropriate initiation of immunomodulatory agents e.g. mycophenolate, methotrexate, azathioprine to speed up withdrawal)

52
Q

What do we use to manage mild lupus?

A

Hydroxychloroquine alone may be sufficient

53
Q

What do we use to manage more serious lupus?

A

Immunomodulatory agents (mycophenolate, methotrexate, azathioprine)

54
Q

What do we use to manage renal disease in lupus?

A

Mycophenolate +/- rituximab

55
Q

What do we use to manage persistently active lupus?

A
  • B cell targeted therapies:
  • rituximab = anti-CD20 monoclonal antibody, depletes B cells
  • belimumab = anti-BAFF antibody (BAFF = B cell survival factor/cytokine)
56
Q

What do we use to manage severe/life-threatening disease (e.g. myocarditis) in lupus?

A

IV steroids + IV cyclophosphamide (+/- rituximab)

57
Q

What do we use to manage patients with SLE and antiphospholipid antibody syndrome (i.e. episode of clot + APL positive)?

A

Anticoagulation e.g. warfarin

58
Q

What is an emerging therapy for SLE?

A

Anifrolumab (interferon receptor blockade)

59
Q

What is the link between SLE and pregnancy?

A
  • SLE typically affects women during reproductive years
  • consider both risk of disease and drugs to both mother and foetus
  • best outcomes with pre-pregnancy planning and getting SLE into remission first

e.g. APL antibodies can increase miscarriage risk

60
Q

What are some specific considerations you need to take into account when looking at SLE and pregnancy? (4)

A
  • antiphospholipid antibodies associated with miscarriage (can reduce risk with aspirin or heparin)
  • pregnancy increases haemodynamic demands - will worsen renal dysfunction
  • Ro antibodies (SLE) can cause foetal heart block
  • drug considerations:
    • MMF, cyclophosphamide, methotrexate and warfarin are teratogenic
    • hydroxychloroquine, azathioprine and LMWH are safe
61
Q

What are the two types of autoimmune inflammatory muscle disease (myositis)?

A
  • polymyositis
  • dermatomyositis
62
Q

What are the two types of systemic sclerosis (scleroderma)?

A
  • diffuse cutaneous
  • limited cutaneous
63
Q

Describe Sjogren’s syndrome (NOT TESTED)

A
  • autoimmune exocrinopathy - lymphocytic infiltration of exocrine glands
  • exocrine gland pathology results in dry eyes (xerophthalmia), dry mouth (xerostomia) and parotid gland enlargement
  • sometimes extra-glandular manifestations: non-erosive arthritis, Raynaud’s phenomenon, pleural effusion, autoimmune hepatitis
  • autoantibodies: Ro+, La+, RF often +, CCP -
  • termed ‘secondary Sjogren’s syndrome’ if occurs in context of another CTD e.g. SLE
64
Q

Describe inflammatory muscle disease. (NOT TESTED)

A
  • autoimmune-mediated inflammation of muscle
  • causes proximal muscle weakness and sometimes pain
  • dermatomyositis = muscle and skin inflammation
  • polymyositis = muscle only, no rash
  • investigations:
    • bloods: elevated CK
    • electromyography
    • muscle biopsy (polymyositis = CD8 T cell infiltrate; dermatomyositis = CD4 T cell in addition to B cells)
  • NB associated with malignancy (10-15%) and pulmonary fibrosis
65
Q

What are the skin changes in dermatomyositis? (2)

A
  • lilac-coloured (heliotrope) rash on eyelids, malar region and naso-labial folds
  • red/purple flat or raised lesions on knuckles (Gottron’s papules)
66
Q

What is systemic sclerosis? (NOT TESTED)

A

Thickened skin with Raynaud’s phenomenon:

  • dermal fibrosis
  • cutaneous calcinosis
  • telangiectasia
67
Q

What are the features of limited systemic sclerosis? (4)

A
  • fibrotic skin limited to hands, forearms, feet, neck and face
  • anti-centromere antibodies
  • pulmonary hypertension
  • long history of Raynaud’s phenomenon
68
Q

What are the features of diffuse systemic sclerosis? (4)

A
  • fibrotic skin proximal to elbows or knees (excluding face and neck)
  • anti-Scl-70 antibodies
  • pulmonary fibrosis, renal (thrombotic microangiopathy) involvement
  • short history of Raynaud’s phenomenon
69
Q

What is CREST syndrome? (Type of limited systemic sclerosis)

A
  • Calcinosis
  • Raynaud’s phenomenon
  • Esophageal dysmotility
  • Sclerodactyly
  • Telangiectasia

Year 2 - BRS (84 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions