Rheumatology Flashcards

1
Q

Causes of inherited CTD

A

Marfan’s syndrome
Ehlers-Danlos syndrome
Osteogenesis imperfecta
Alport’s syndrome

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2
Q

Causes of autoimmune CTD

A

SLE
RA
Sjogren’s
PM/DM
MCTD
Scleroderma
Overlap/UCTD

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3
Q

HLA region which strongest links with development of autoimmune CTD

A

HLADRB1

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4
Q

HLA class II sits on what chromosome

A

Chromosome 6

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5
Q

HLA class I sits on what chromosome

A

Chromosome 15

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6
Q

HLA class II presents to which cell

A

CD4 T cells

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7
Q

HLA class I presents to which cell

A

CD8 T cells

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8
Q

Function of HLA class II

A

Recognition of self
Presentation foreign peptides to CD4 cells

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9
Q

Role of HLA in SLE

A

Both HLA-DR and HLA-DQ loci implicated in SLE, particularly HLA-DRB1

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10
Q

Ethnic differences in HLE loci for SLE

A

Higher risk of SLE in African American and Hispanic for HLA DRB11503 and HLADRB108

Protective risk of SLE in Caucasian for HLA DRB1*0301

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11
Q

Effect of race on clinical manifestations of SLE

A

Non Caucasian ethnicities significantly higher frequency of lupus nephritis, neuropsychiatric SLE, severe haematologic manifestations and APLS

Asian ethnicities increased prevalence and severity, increased renal disease and increased auto-antibodies

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12
Q

SLE in Australian Indigenous population

A

Prevalence 2-4x of Caucasians
High disease activity and higher incidence of LN
Tend to have higher morbidity and mortality

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13
Q

Predisposing genes in SLE

A

HLA genes
STAT 4

Others include IRF5, IRAK1, TNFAIP3, SRP1, TLR7

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14
Q

Environmental factors that contribute to SLE

A

Oestrogen - can stimulate type 1 IGN pathway (whilst progesterone inhibits it), higher risk of autoimmunity
UV light - higher rate of formation of auto-antibodies
Microbiome
Infection - EBV, CMV, COVID

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15
Q

Major pathways of signalling B and T cells in SLE

A

Overexpression of IFN (biggest one)
Overexpression of neutrophils
Overexpression of plasmablasts

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16
Q

Role of type I interferon in SLE

A

Type I IFN is produced in response to a viral infection - acts as an alarm signal
- produced by most cells, but particular APCs
- induced by viral nucleic acid
Recruiter of T cells, B cells and neutrophils

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17
Q

Cytokines involved in SLE

A

TNF –> neutrophil recruitment, monocyte activation, sustains type I IFN expression
IL-6 –> B cell proliferation
IL-17 –> recruitment of inflammatory cells
IL-10 –> B cell proliferation, loss of tolerance
BAFF –> B cell survival (CD19, CD20), T cell activation
IFN Type 1

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18
Q

Role of Type 1 IFN in SLE

A

Reduction of Treg cells - loss of tolerance
Increase NETs - IL-17, inflammation
Increase BAFF - B cell proliferation, loss of tolerance

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19
Q

In SLE, type I IFN is initially produced in response to

A

Production of host nucleic acids

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20
Q

Dermatological and MSK manifestations of SLE

A

Malar rash
Photosensitive rash
Discoid rash
Subacute cutaneous lupus erythematosus
Periungal erythema/capillary dilatation –> pathogenic Raynaud’s
Alopecia
Mucosal ulcers - PAINLESS
Charcot’s arthropathy - reversible, non erosive arthritis

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21
Q

Classes of lupus nephritis

A

Class I - mesangial immune deposits without hypercellularity
Class II - mesangial immune deposits with hypercellulary
Class III - focal proliferative (<50% of glomeruli)
Class IV - diffuse proliferative (>50% of glomeruli)
Class V - membranous
Class VI - advanced sclerosing lesions

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22
Q

Indications for treatment of lupus nephritis

A

Class III-V indicated for treatment (proliferative/membranous)

Class I-II - treatment not required
Class IV - treatment refractory

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23
Q

Clinical manifestations of CNS lupus

A

Seizures
Headaches
Stroke syndromes
Transverse myelitis
Coma
Dementia
Ataxia
Rigidity, tremor
Chorea
Aseptic meningitis
Psychiatric disorders
SAH
Hemiballismus
Cranial neuropathy
Peripheral neuropathy
Mononeuritis multiplex
MS-like disorder
GBS

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24
Q

MRI findings on CNS lupus

A

T2 white matter lesions
- sensitive but not specific
- does not correlate to disease activity

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25
Q

Antibodies/serology in SLE

A

ANA - all patients
anti-dsDNA
anti-Sm - higher risk of patients
anti-Ro/La - higher risk of neonatal heart block
Complement

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26
Q

Marker of disease activity in SLE

A

Complement level - though not for all patients

Not dsDNA

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27
Q

Findings of serologically active SLE

A

High dsDNA and/or low complement levels

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28
Q

Diagnosis of APLS

A

Presence of at least 1 of 3 antibodies (on multiple occasions)
- Beta 2 glycoprotein, anticardiolipin, lupus anticoagulant
Thrombotic event

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29
Q

Target for SLE management

A

Aim for remission
If not possible, aim for low disease activity state

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30
Q

Treatment for SLE

A

Treat the lesion not diagnosis

Hydroxychloroquine - standard of care

Anti-malarials
- skin and joint disease

Steroids
- Low dose for skin, joint or musculocutaneous disease
- Medium dose for serosal, moderate haem disease
- High dose for renal, significant haem disease

MTX
- skin and joint disease

Azathioprine
- for everything

Mycophenolate mofetil
- Class III-IV GN
- Or if azathioprine intolerant

Cyclophosphamide
- severe proliferative GN and if other management fails

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31
Q

Toxicity of hydroxycholoquine

A

Ocular toxicity
- requires annual review after 5 years of therapy

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32
Q

Management of lupus nephritis

A

Induction therapy
- IV glucocorticoids (e.g., methylprednisolone)
PLUS other immunosuppressants (e.g., mycophenolate or cyclophosphamide)

Maintenance of remission
- Oral prednisone
PLUS mycophenolate OR azathioprine
- Refractory or relapsing disease: Rituximab may be considered.

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33
Q

Indication for biologic therapy in SLE

A

Persistently active disease, frequent flares despite adequate treatment

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34
Q

Biologic therapy used in SLE

A

Rituximab - CD20 antibody –> effective if high dsDNA, low complement
Belimumab - anti-BAFF –> add on therapy for lupus nephritis
Voclosporin - calcineurin inhibitor –> add on therapy for lupus nephritis, not PBS supported yet
Other therapies not PBS supported yet - Anifrolumab (anti-TFN1) and eculizumab

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35
Q

Preventative management in SLE

A

Annual CVS risk factor screening
Immunisations
Bone health
BP in lupus nephritis
Cancer screening
Reproductive health

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36
Q

B cell therapy works best in which group of SLE patients

A

Serologically active patients

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37
Q

Clinical features of Sjogren’s

A

Sicca symptoms (all patients)

Dental disease
Non-erosive arthritis
Lymphocytic infiltration into skin and organs - renal, respiratory, mucocutaneous, MSK, risk of NHL

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38
Q

Indication for lymphoma annual screening

A

If more than 2 risk factors, do annual screening

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39
Q

Management for Sjogren’s disease

A

Sicca symptoms
- education, artificial tears, secretagogues, treatments for complications
Systemic manifestations
- HCQ, MTX, leflunomide, mycophenolate
- +/- glucocorticoids

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40
Q

Scleroderma definition

A

Slow initial inflammation leading to fibrosis of connective tissues

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41
Q

Division of scleroderma disease and relevance to mortality

A

Limited - below elbow and knee, face involvement, truncal sparing
Diffuse - everywhere else

Diffuse disease related to higher mortality

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42
Q

CREST symptoms

A

Calcinosis
Raynaud’s
Oesophageal dysmotility
Sclerodactyly
Telangiectasia

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43
Q

Hand clues for scleroderma

A

Early - oedematous “puffy fingers”
Induration phase - some damage present
Late - sclerodactyly, lots of damage present

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44
Q

Findings of Raynaud’s

A

Primary
- not associated with tissue damage - no signs present
- no underlying disease

Secondary
- Due to underlying disorder
- Structural microvascular abnormalities present

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45
Q

Pulmonary involvement in scleroderma

A

Limited skin disease - higher chance of primary PAH

Diffuse skin disease - higher risk of ILD and secondary PAH

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46
Q

Autoantibodies present in scleroderma

A

Scl-70
- associated with diffuse skin disease
- higher risk of ILD

Centromere staining pattern
- associated with limited skin disease
- higher risk of primary PAH

RNA polymerase III
- rapidly progressing skin disease
- high risk of renal crisis

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47
Q

Indications for systemic immunosuppressive therapy in SLE patients

A
  • Severe and progressive diffuse skin involvement
  • ILD
  • Myocarditis
  • Severe inflammatory myopathy and/or arthritis
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48
Q

Features of myopathies

A

Weakness
Painless
Arthritis
Raynauds
ILD

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49
Q

Classical skin features of DM

A

Heliotrope rash
Shawl/V sign
Gottron’s papules

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50
Q

Treatment principle of myopathies

A

Glucocorticoids + steroid sparing agent +/- IVIg

If rapidly progressing variant, use cyclophosphamide or MMF + steroid + IVIg

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51
Q

Anti-synthetase syndrome clinical features

A

Myositis
ILD
Arthropathy
Fever
Raynaud’s
Mechanic’s hands

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52
Q

Positive autoantibody in anti-synthetase

A

Anti-Jo1

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53
Q

Features of amyopathic dermatomyositis

A

Classic DM skin findings + more cutaneous features i.e. ulceration
Risk of rapidly progressive ILD particularly in MDA-5 disease

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54
Q

Positive antibodies with dermatomyositis and its associations

A

Anti Mi2 –> classical DM
Anti SAE –> severe cutaneous disease
Anti MDA5 –> poor outcomes, hypo-amyopathic
Anti TIF-1y/a –> associated with cancers, requires yearly cancer screening
Anti NXP2 –> also associated with cancers, diffuse calcinosis

55
Q

Features of sine scleroderma

A

No detectable skin involvement however has other features (i.e. Raynaud’s, digital ulcers, PAH) and positive antibodies specific for systemic sclerosis

56
Q

Groups of inflammatory myopathies

A

Group 1 - sporadic IBM
Group 2 - polymyositis
Group 3 - Dermatomyositis
Group 4 - Non-specific myositis
Group 5 - immune mediated necrotising myopathy

57
Q

Features of IBM

A

Insidious, asymmetrical onset affecting upper extremities
Quadriceps weakness
Finger flexor weakness
Dysphagia

58
Q

Features of non-IBM

A

Acute-subacute
Proximal muscle weakness

59
Q

Features of immune mediated necrotising myopathy

A

Resembles polymyositis
Muscle necrosis

Biopsy - paucity of inflammatory infiltrate compared to PM

60
Q

Autoantibodies associated with IMNM

A

Anti SRP –> aggressive, severe muscle weakness with lung involvement. Refractory to immunomodulators. Often require rituximab

Anti HMG-CoA reductase –> generally resistant to treatment, purely myopathic phenotype without skin or lung involvement

61
Q

Myositis associated antibodies

A

Anti SSA/Ro 60
Anti Ro 52/TRIM21
Anti SSB/La
Anti-PM-Scl75
Anti-PM-Scl100
Anti-ku
Anti-U1RNP

62
Q

Classification of spondyloarthropathies

A

Axial spondyloarthritis i.e. non-radiographic axial SpA, ankylosing spondylitis
Reactive arthritis
Psoriatic arthritis
Arthritis associated with IBD

63
Q

Clinical features of spondyloarthritis

A

IBD
Arthritis - oligoarticular, lower limb
Sacroiliitis
Enthesitis
Dactylitis
Uveitis
Psoriasis
HLAB27 positive
FHx
IBD
Recent infection

64
Q

Definition of inflammatory back pain

A

Chronic > 3 months
Onset before age of 40
Insidious onset
Improvement with exercise
No improvement with rest
Nocturnal pain improving on waking i.e. responds to NSAIDs

65
Q

Features of ankylosing spondylitis

A

Radiographic features of sacroiliitis
Inflammatory arthritis of axial skeleton
Extra-axial and extra-articular involvement
Progressive stiffening and fusion of spine
Strong association with HLAB27

66
Q

Pathogenesis of new bone formation in AS/SpA

A

Enthesis is primary source of pathology
- insertion of tendons/ligaments onto bone
- annulus fibrosis in spine
- ?mechanical stress

New bone formation
- in sacro-iliac joints, vertebra
- leads to ankylosis
- occurs at site of enthesitis/inflammation

67
Q

Clinical features of AS

A

Axial features
- Inflammatory back pain
- Alternating and poorly localised buttock pain
- Restriction in spinal movement

Extra-axial involvement
- Hip arthritis
- Peripheral arthritis/synovitis
- Enthesitis especially at Achilles, plantar fascia, chest wall, pelvic brim
- Acute anterior uveitis
- IBD
- Osteopenia
- Cauda equina
- Increase CVD risk, AR, conduction disturbance
- Chest wall restriction
- Apical fibrosis
- Secondary amyloidosis

68
Q

Investigations in AS

A

HLAB27
Inflammatory markers
Imaging of sacro-iliac joints, cervical and thoraco-lumbar spine

69
Q

Imaging changes in sacro-iliitis

A

Early - erosions, sclerosis at joint margins
Later - pseudo-widening
Last - joint space narrowing progressing to ankylosis

70
Q

Radiographic grading of sacroiliitis

A

Grade 0 - normal
Grade 1- suspicious changes
Grade 2 - minimal abnormality, small areas of erosion/sclerosis, normal joint width
Grade 3- unequivocal abnormality, erosion, sclerosis, joint widening, narrowing or partial ankylosis
Grade 4 - severe abnormality, total ankylosis

71
Q

Features of sacro-iliitis on MRI

A
  • Bone marrow oedema (active inflammation)
  • Erosions detected earlier
  • Synovitis, enthesitis
  • Features of spinal involvement
72
Q

Risk factors for more rapid and increased radiographic progression in AS

A

Rapid
- Men who are HLAB27 positive
- Patients with more damage at baseline
- Patients with higher inflammatory markers
- Higher disease activity states

Increased
- Pts with long standing, advanced AS
- early axial SpA (radiographic and non-radiographic)

73
Q

First line treatment for AS

A

Physiotherapy
NSAIDs
Can consider sulfasalazine or MTX for peripheral arthritis (though not effective for axial disease)

74
Q

Indications and examples of biologic treatment for AS

A

Indicated for those with inadequate response to NSAIDs and physiotherapy

TNF inhibitors i.e. Infliximab, adalimumab, etanercept
IL-17A inhibitors - secukinumab
Certolizumab
Upadacitinib

75
Q

Pathogenesis of psoriatic arthritis

A

Genetic risk factors - first degree relative
Tissue specific factors
Obesity
Psoriasis

76
Q

Clinical features of psoriatic arthritis

A

Distinct patterns of joint involvement
- Asymmetric oligoarthritis/monoarthritis
- Polyarthritis - symmetric
- Spondyloarthritis - axial, AS-like
- DIP joint with nail disease
- Arthritis mutilans

Dactylitis (40-50%)
Enthesitis (30-50%)
Skin disease
Nail changes - pitting, onycholysis, nail plate crumbling

77
Q

Comorbidities of PsA

A

Increased CVD
Higher prevalence of metabolic syndrome
Obesity

78
Q

Investigation findings in PsA

A

Elevated inflammatory markers
RF and CCP NEGATIVE
Imaging
- Erosion with new bone formation - “Pencil in cup”
- Ankylosis

79
Q

Treatment options for psoriatic arthritis

A

NSAIDs + CSI for symptomatic treatment
csDMARDs
Anti-TNF
Anti-IL17A
Anti-p40 subunit IL12/23
Anti-IL23
JAK inhibitors

80
Q

Treatment considerations for psoriatic arthritis

A

MSK manifestations
- peripheral arthritis
- axial involvement
- enthesitis
- dactylitis
Psoriasis manifestations
- skin and/or nails
Co-morbditis
- IBD, uveitis
- metbolic syndrome

81
Q

Nomenclature of vasculitis

A

Immune complex small vessel vasculitis
- Cryoglobulinemic vasculitis
- IgA vasculitis (Henoch-Schnolein)
- Hypocomplementemic urticarial vasculitis

Medium vessel vasculitis
- Polyarteritis nodosa
- Kawasaki disease

Large vessel vasculitis
- Takayasu arteritis
- Giant cell arteritis

ANCA-associated small vessel vasculitis
- Microscopic polyangiitis
- Granulomatosis with polyangiitis
- Eosinophilic granulomatous with polyangiitis

82
Q

Pathogenesis of GCA

A

Unclear aetiology - associated with genetic factors and possible triggering event

Two key cytokine influences
- IL-6 –> inflammatory response
- IFN-y –> produced by Th1 cells (under IL-12 and IL-18), local vascular effect

83
Q

Clinical features of GCA

A

Constitutional symtoms
- fever, malaise, anorexia, weight loss
Cranial symptoms
- new heaadache (could be temporal, occipital or frontal)
- jaw/tongue claudication
- scalp tenderness
Associated with PMR
- inflammatory shoulder and pelvic girdle symptoms
Ocular symptoms
- temporary vision loss (amaurosis fugax, monocular)
- permanent vision loss
- diplopia
Extra-cranial/large vessel disease
- Aortic and branches involvement
- Cough

84
Q

Causes of ocular complications in GCA

A

AION
Central retinal artery occlusion
Intracerebral (posterior circulation)

85
Q

Investigation findings of GCA

A

Inflammatory markers
Temporal artery biopsy
- gold standard test though this is flawed (may have skip lesions)
- intimal hyperplasia, inflammatory cell infiltrate, disruption of internal elastic lamina, giant cells
Temporal artery US
Imaging of large vessel/extra cranial disease
PET/MRI scans

86
Q

Management of GCA

A

Steroid management
- GCA without visual Sx: Pred 40-60mg daily
- GCA with visual Sx: IV methylpred for 3 days then pred

Tocilizumab

87
Q

Definition of GPA

A

Necrotising granulomatous inflammation, usually involving upper and lower respiratory tract, small to medium vessels or necrotising GN

Positive PR3-ANCA (65-75%)
Positive MPO-ANCA (20-30%)
ANCA ~5%

88
Q

Definition of MPA

A

Necrotising vasculitis with few or no immune deposits, predominantly affecting small vessels
Necrotising arterties and necrotising GN may be present

Positive MPO-ANCA (55-65%)
Positive PR3 ANCA (20-30%)
ANCA 5-10%

89
Q

Definition of eosinophilic GPA

A

Eosinophil-rich and necrotising granulomatous inflammation often involving respiratory tract, associated with asthma and eosinophilia

90
Q

Similarities of GPA and MPA

A

Small-medium sized necrotising vasculitis
Predilection for renal involvement - pauci-immune necrotising GN
Pulmonary involvement - cough, haemoptysis
Constitutional symptoms
Cutaneous involvement

91
Q

GPA specific clinical features

A

ENT manifestations - crusting, sinusitis, hearing loss, saddle nose
Subglottic/airway stenosis, nodules/cavities
Peripheral nerve involvement in 15% of patients
Retro-orbital pseudotumour, other granulomatous masses

cANCA-PR3 predominant

92
Q

MPA specific features

A

Rhinosinusitis, sensori-neural hearing loss
ILD
Peripheral involvement in 70% of pts - MMN, peripheral neuropathy

pANCA-MPO predominant

93
Q

Management of GPA/MPA

A

High dose GC + rituximab
High dose GC + cyclosphosphamide

94
Q

Clinical features of EGPA

A

Prodromal phase
- Severe allergic asthma attacks (chief concern)
- Allergic rhinitis/sinusitis

Eosinophilic phase
- Lung disease
- Pericarditis
- Gastrointestinal involvement: bleeding, ischemia, perforation

Vasculitic phase
- Skin nodules, palpable purpura
- Mononeuritis multiplex (loss of motor and sensory function with wrist or foot drop), symmetric or asymmetric polyneuropathy
- Pauci-immune glomerulonephritis

95
Q

Treatment of EGPA

A

Nonsevere disease
Oral glucocorticoids: e.g., prednisone
PLUS a glucocorticoid-sparing agent: e.g., mepolizumab (preferred), methotrexate, OR mycophenolate mofetil

Severe disease
High-dose glucocorticoids: e.g., methylprednisolone pulses OR prednisone
PLUS a glucocorticoid-sparing agent: e.g., rituximab (preferred) OR cyclophosphamide

96
Q

Clinical features of takayasu arteritis

A

Constitutional Sx
Carotidynia
Arterial stenosis/occlusion –> claudication, absent pulses
Discordant BP, bruits
Aortic dissection, aortic root dilatation with aortic valve regurgitation

97
Q

Clinical features of polyarteritis nodosa

A

Constitutional symptoms
Skin changes - purpura, panniculitis, livedo, necrotising vasculitis in dermis
Renal - infarctions/ischaemia leading to impairment, HTN
Neurological - MMN, neuropathy
GI - mesenteric angina, wt loss, bowel perforation
Myalgias

98
Q

Diagnosis of PAN

A

ANCA negative
Aneurysms on angiography/CTA/MRA
Biopsy of involved tissue

99
Q

Clinical features of IgA vasculitis

A

Preceded by infection especially URTI

Purpura
Arthralgia/arthritis
GI Sx - abdo pain, nausea, GI haemorrhage
Renal - haematuria +/- proteinuria, progression to ESKD

100
Q

Diagnosis of IgA vasculitis

A

Usually made on biopsy
Leukocyclastic vasculitis with IgA deposition present

101
Q

Causes of cryoglobulinaemic vasculitis

A

Hepatitis C (most common)
Hepatitis B
CTD e.g. SLE
Primary Sjogren’s

102
Q

Clinical features of cryoglobulinaemic vasculitis

A

Classic triad - purpura, weakness, arthralgia
Constitutional Sx
Peripheral neuropathy
Renal disease - GN

103
Q

Diagnosis and management of cryoglobulinaemic vasculitis

A

Presence of cryoglobulinaemia
RF positive
Low complement

Screen for underlying causes - HCV/HBV/HIV, ANA/ENA/dsDNA, SPEP

Assess disease extent - CK, MSU, FBC, LFTs etc.

Treatment of underlying disease
Severe disease with GC + RTx

104
Q

Characteristics of hypocomplementaemic urticarial vasculitis

A

Clinical urticaria with cutaneous leucocytoclastic vasculitis on biopsy

Low complement levels

Urticaria
Arthralgia
Major organ involvement

105
Q

Triggers of RA

A

Smoking
Silica
Gingivitis
Gut microbiota

106
Q

Risk factors for RA

A

HLA DRB gene (-01, -04)
STAT4
PADI
PTPN22
Smoking
Periodontitis
Gut dysbiosis
Anti-CCP

107
Q

Cells involved in pathogenesis of RA

A

TNF
IL-1
IL-6
JAK signalling
Citrullination
T reg (protective factor)
OPG (protective factor)

108
Q

What cell is most predominant in RA synovial fluid

A

Neutrophils

109
Q

What is involved in joint lining inflammation in RA?

A

Synovitis
Bone erosion
Pannus
Cartilage degradation

110
Q

Pathogenesis of RA

A

TNF, IL-1, IL-6 –> PG, COX –> Swelling/pain

IL-2, IGN –> RANKL –> bone damage

IL-12, IL-15, IL-18, IL-17 –> MMP, aggrecanase –> cartilage loss

111
Q

Main T cells involved in RA

A

Th1
Th17
T reg cells

112
Q

Role of Treg cells in RA

A

Produced by thymus
Suppress activation and expansion of naive T cells and its differentiation to effector T cells i.e. T helper cells

113
Q

X-ray findings in RA

A

Destruction of peri-articular bone (osteopenia)
Erosions

114
Q

Pathogenesis of bone erosion in RA

A

Mediated by osteoclasts
Inflammation promotes osteoclast activity (driven by cytokines TNF, IL-1, IL-6) causing erosions

115
Q

Protective factors of bone erosions in RA

A

Osteoprotegrin (OPG) protects bone by blocking osteoclast development

116
Q

Clinical features of RA

A

Small joint involvement
Symmetrical
AM stiffness lasting one hour
Can be either monoarthritis or polyarthritis
Heberden’s nodes
Osteophytes
Juxta-articular sclerosis
DIP joints spared

117
Q

Investigation findings in RA

A

RhF or anti-CCP –> one third of RA pts are seronegative
Imaging findings - nodules, erosions

118
Q

Pathologies with DIP sparing

A

RA
SLE

119
Q

Pathologies with DIP involvement

A

Psoriasis
Gout
OA

120
Q

Rheumatoid factor characteristics

A

Autoantibody (usually IgM) directed against Fc portion of IgG

121
Q

Rheumatoid factor has high titre in which conditions

A

RA (70-90%)
Sjogren’s (75-95%)
Cryoglobulinemia (40-100%)

122
Q

Anti-CCP in RA

A

Highly specific for RA (90% specificity)
Highly predictive of RA in asymptomatic and early undifferentiated arthritis
Reasonable sensitivity
Marker of erosive disease but not useful in assessing current RA activity

123
Q

Predictors of severity in RA

A

Presence of erosions
Anti-CCP
RF

124
Q

Indicators of RA activity

A

CRP
ESR
Swollen joint count

125
Q

What should MTX not be combined with in RA?

A

Leflunomide - increases risk of ILD, pancytopenia etc.

126
Q

Biologic therapy in RA

A

TNF blockade
IL-1 blockade
IL-6 blockade
Costim blockade
B cell depletion
JAK kinase blockade

127
Q

Agents available for TNF blockade

A

Infliximab - Chimeric IgG1 monoclonal Ab
Etanercept - Rh TNF recombinant
Adalimumab - human monoclonal Ab

128
Q

Precautions for TNF blockade

A

TB
Congestive heart failure
Demyelinating disease
Lymphoma
Lupus-like syndrome or serology ANA/dsDNA
Cancer in last 5 years
Infections - do not initiate whilst active infection present

129
Q

MOA of B cell therapies

A

Anti CD20 - B cell depleting
Anti CD22 - B cell modulating
Anti CD 40/CTLA1Ig - blocking co-stimulation
BlySL/BAFFL - Blocks B cell activation/differentiation

130
Q

MOA of rituximab

A

Chimeric monoclonal Ab to CD20

131
Q

MOA of tofacitinib

A

JAK1/3 inhibitor –> blocks multiple cytokines

132
Q

MOA of baracitinib

A

JAK 1/2 inhibitor
Increased risk of infection and VTE

133
Q

Current therapy in RA

A

Non-biologic DMARDs
- MTX
- Leflunomide
- SSP
- HCQ

Biologic DMARDs
- Anti TNF - Etanercept, infliximab, adalimumab, golimumab, certilizumab
- Rituximab - anti CD20
- Abatacept - CTLA4-Ig
- Tocilizumab - IL-6 inhibitor
- Tofacitinib - JAK1/3 inhibitor
- Baricitinib - JAK1/2
- Upatacitinib - JAK inhibitor

134
Q

Relationship between RA and CVD

A

RA is an independent risk factor for CAD
Atherogenesis/RA inflammatory pathology overlap
CRP directly associated with risk

CVS risk management and inflammation crucial