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Rheumatology Flashcards

1
Q

Catastrophic Antiphospholipid Syndrome

A

Rare, life threatening form of APS
Characterised by micro and macrovascular thrombosis of multiple organs that develop either simultaneously or in short succession

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2
Q

Mechanism of Obstetric Antiphospholipid Syndrome

A

Direct trophoblast inhibition

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3
Q

Overarching rule for Antiphospholipid Syndrome testing

A

Persistent positivity required

(positive result on two tests done at least 3 months apart)

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4
Q

When are the different antiphospholipid syndrome antibodies significant?

A

Cardiolipin >40
Anti-Beta2 Glycoprotein >40 or >99th percentile
Lupus Anticoagulant: positive

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5
Q

Risk stratification for Antiphospholipid Syndrome

A

High: Positive Lupus Anticoagulant, any Cardiolipin or Beta2-Glycoproteinresult

Moderate: Negative Lupus Anticoagulant, moderate to high Beta2 glycoprotein and/or Cardiolipin

Low: Negative Lupus Anticoagulant, low titre Cardiolipin and/or Beta2 glycoprotein

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6
Q

Who needs primary thromboprophylaxis in Antiphospholipid Syndrome?

A

High risk aPL profile, low risk aPL profile but have SLE, history of obstetric antiphospholipid syndrome

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7
Q

Management of Thrombosis in Antiphospholipid Syndrome

A

Warfarin indicated, DOAC inferior. Target INR 2.5-3.5, increasing to 3-4 if recurrent on therapy.

Lifelong if unprovoked, recurrent or high risk aPL profile, otherwise as per usual guidelines

Recurrence: lifelong, increase INR target, add Aspirin, consider change to LMWH

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8
Q

Management of Antiphospholipid Syndrome during pregnancy

A

High risk aPL but no history of thrombosis or pregnancy complications: Aspirin monotherapy

History of obstetric APS but no thrombosis (≥3 recurrent spontaneous miscarriages prior to 10 weeks, history of foetal loss)
- Aspirin + prophylactic dose heparin during pregnancy

History of thrombosis: therapeutic dose heparin, which needs to be continued for 6 months post partum

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9
Q

Diagnosis of Sjogren’s

A

Schirmer test <5mm wetting in 5 minutes = dryness
ANA, Ro/La (SSa/SSb)

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10
Q

Primary Lymphoma type associated with Sjogren Syndrome

A

Mucosal Associated Lymphoid Tissue Lymphoma

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11
Q

Clinical features of SJogren’s associated with higher lymphoma risk

A

Lymphadenopathy
Recurrent parotid swelling
Monoclonal gammopathy
Depressed C4
Decreased RF (if elevated at baseline)

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12
Q

What population needs additional testing prior to starting Allopurinol, and what testing is this?

A

Four South East Asian patients, need to check HLAB58*01

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13
Q

HLA associated with Behcet’s?

A

HLA B51

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14
Q

Etanercept

A

TNF Inhibitor

Shouldn’t be used for IBD → increases risk of bowel perforation

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15
Q

Infliximab

A

TNF Inhibitor

First line biologic for IBD, good for fistulas, perianal disease

Risk of anti-drug antibodies

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16
Q

Adalimumab

A

TNF Inhibitor

Risk of anti drug antibodies

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17
Q

Certolizumab

A

TNF Inhibitor

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18
Q

Golimumab

A

TNF Inhibitor

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19
Q

Anakinra

A

IL-1 Inhibitor

Less effective for inflammatory arthritis, so not used much. Can be used for gout, TRAPS, Familial Mediterranean Fever

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20
Q

Tocilizumab

A

IL-6 Inhibitor

In GCA: Reduces flares by 40%, faster steroid wean.
Drops CRP drastically as IL-6 drives acute phase reactant production
GIACTA Trial key

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21
Q

Secukinumab

A

IL-17 Inhibitor

Used for Psoriasis, PsA, AS, Axial Spondyloarthritis

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22
Q

Ixekizumab

A

IL-17 Inhibitor

Only really used for PsA/Psoriasis

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23
Q

Ustekinumab

A

IL-12/23 Inhibitor

Good for joints, less so skin

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24
Q

Guselkumab

A

IL-23 Inhibitor

Good for joints, less so skin

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25
Abatacept
T cell costimulation blockade. Blocks CD28 from binding to CD80/86 → reduced Treg suppression and limitation of T effector cell activity In a sense is a CTLA-4 analogue. SO downregulated T cell activity overall. Similar efficacy to TNF Inhibitors in RA
26
Rituximab
Anti CD20 → depletes B cells, blocks formation of new antibodies Can cause hypogammaglobulinaemia
27
Belimumab
Inhibits B cell activation Can be used in Lupus
28
Tofacitinib
JAK Inhibitor: Reduced DNA transcription in lymphocytes High risk of cardiovascular disease, stroke, VTE, cancer in older patients and smokers
29
Upadacitinib
JAK Inhibitor: Reduced DNA transcription in lymphocytes High risk of cardiovascular disease, stroke, VTE, cancer in older patients and smokers
30
Baricitinib
JAK Inhibitor: Reduced DNA transcription in lymphocytes High risk of cardiovascular disease, stroke, VTE, cancer in older patients and smokers
31
Lofgren Syndrome
Pathognomic presentation of sarcoid Fever plus triad of: - Migratory polyarthritis - Erythema nodosum - Bilateral hilar lymphadenopathy 70-80% experience spontaneous remission, and biopsy is not required to confirm diagnosis
32
Biopsy in Sarcoid
Gold standard for diagnosis. Skin lesions a good option as easily accessible Noncaseating granulomas containing - Giant cells - Asteroid bodies - Schaumann bodies
33
Indications for Immunosuppression in Sarcoidosis
- Symptomatic, progressive disease - Persistent pulmonary infiltrates - Progressive decline in lung function
34
Sarcoidosis staging
1. Bilateral Hilar Lymphadenopathy, no pulmonary infiltrates 2. Pulmonary infiltrates, No Bilateral Hilar lymphadenopathy 3. Both bilateral hilar lymphadenopathy and pulmonary infiltrates 4. Substantial pulmonary fibrosis
35
Sarcoidosis Pathology
Granulomas produced following macrophage activation → Th1 cell activation → IFN-gamma release → epithelioid cell and multinucleated giant cell formation Epithelioid cells produce ACE and recruit fibroblasts leading to fibrosis Alveolar macrophages increase calcitriol leading to hyperphosphataemia, hypercalcaemia, renal failure. Driven by 1-alpha hydroxylase
36
Mitochondrial Myopathy
Maternal inheritance External ophthalmoplegia, Ptosis, exertional muscle weakness. However also subtypes such as MELAS (encephalopathy, myopathy, lactic acidosis, stroke like episodes) Lactic acidosis, CK normal Muscle Biopsy shows: Ragged red fibres but no inflammatory cells or necrosis
37
Risk Factors for RA
Smoking is key risk factor. 25% of all RA and 35% of seropositive RA attributable to smoking Obesity, silica, shared epitope all increase risk Moderate alcohol intake reduces risk slightly
38
Key HLA for Rheumatoid Arthritis
HLA-DRB1 Concept of shared epitope Around 60% heritable PTPN22 SNP is other key gene
39
Most specific test for Rheumatoid Arthritis
Anti-CCP
40
DAS-28
Key tool for monitoring RA <2.6 = remission >5.1 = active
41
Poor prognostic factors for Rheumatoid Arthritis
Low socioeconomic/education Female Advanced age at onset Increased DAS28 Presence or high tires of RF and/or ACPA (i.e. seropositive does worse) Presence of erosions Smoking Delayed diagnosis/treatment
42
How much do TNF Inhibitors increase infection risk?
~5%
43
Key extra-articular manifestations and complications of RA
- Scleritis - Sicca - Atherosclerosis - Pulmonary: ILD, pleural effusion - Renal amyloid (a-a)
44
MPO-ANCA
Microscopic Polyangitis ANCA present >90% Necrotising GN +/- pulmonary capillaritis
45
PR3-ANCA
Granulomatosis with polyangitis ANCA present >80% Respiratory involvement core feature Can have a pauci-immune GN
46
EGPA
Eosinophil rich granulomatous inflammation of respiratory tract Often also have Atopy 40% ANCA positive, more common if have GN as well as lung involvement. MPO typical
47
Most common presenting feature (or at least first clinical feature) of GPA/EGPA?
ENT involvement
48
ILD patterns in ANCA
pANCA (MPO, MPA): UIP cANCA (PR3, GPA): NSIP
49
What infection is commonly ANCA positive?
Infective Endocarditis (c-ANCA) Cystic Fibrosis, esp. Pseudomonas aeruginosa
50
What drugs can induce ANCA?
Hydralazine Carbimazole/Propylthiouracil Minocycline Penicillamine
51
What is Avacopan, and when might it be used?
C5a receptor inhibitor Used for ANCA vasculitis Reduces cumulative corticosteroid exposure
52
Mepolizumab
IL-5 Inhibitor Can be used in non-severe/refractory EGPA
53
What is the biggest risk factor for GCA/PMR?
Age Essentially does not occur in those <50
54
When should Aspirin be used in GCA?
Critical/flow limiting cerebral artery disease. However some bosses will use in all
55
Which antibody is associated with Scleroderma Renal Crisis?
RNA polymerase III Abrupt onset moderate to severe hypertension Urine sediment often normal, or mild proteinuria Progressive renal failure Steroids can precipitate, also very hard to wean them if it occurs.
56
Which Rheumatologic condition is associated with GAVE?
Scleroderma
57
U1-RNP
Mixed Connective Tissue Disease
58
Nucleolar ANA
Diffuse SSC
59
Centromere ANA pattern
Limited SSc
60
Anti Scl-70
Diffuse SSc
61
PMSCL 100/75
Myositis/Scleroderma overlap
62
First line treatment for SSc related inflammatory arthritis
MTX Second line: Glucocorticoids
63
Treatment for SSc related skin disease
MTX first line for mild disease, MMF if not responding MMF first line if severe 3rd line IV cyclophosphamide
64
Treatment for SSc related ILD
MMF first line for induction and maintenance IV CYC 2nd line for induction, RTX 3rd line AZA 2nd line for maintenance, CYC 3rd line
65
Treatment for SSc related PAH
Mild: - 1st: PDE5i (sildenafil, tadalafil) - 2nd: add ERA (Bosentan, Ambrisentan) - 3rd line: Prostanoid Moderate: - Start with prostanoid - 2nd line ERA + PDE5i - 3rd line: ERA + prostanoid
66
Treatment for SSc related Myocarditis
1st line MMF or high dose steroids In conjunction with normal CCF treatment 2nd line: IV CYC or RTX
67
Poor Prognostic Factors in SSC
- Increasing age - Sclerdoderma renal crisis - PAH - Pulmonary Fibrosis - Rapid onset/progression - Associated malignancy
68
Poor prognostic factors and SLE
- Age: onset >50, or <30 with organ involvement - Haemolytic anaemia - Male - Renal lupus within 1 year of presentation - Neuropsychatric lupus
69
What gene mutation is associated with SLE pathogenesis
PTP-N22
70
Immunopathogenesis of SLE
Increased apoptosis → excess antigen → CRP and C1q overwhelmed Formation of neutrophil extracellular trans (NETs) → NETosis Immune complexes important in nephritis
71
Stages/Classes of Lupus Nephritis
I. Minimal change (Excellent prognosis) II. Mesangial LN (Excellent prognosis) III. Focal proliferative (Variable prognosis) IV. Diffuse proliferative (Variable prognosis)
72
Anti sm antibodies
Renal and Neurological Lupus
73
Drug Induced Lupus Causes
6-12% of lupus is drug induced High Risk (5-20%) - Procainamide) - Hydralazine Low Risk: Anti TNF, PPI, Statins, Chemo, ACEi, Propylthiouracil, Minicycline, Methyldopa, D-penicillamine
74
Antibodies in Drug Induced Lupus
100% ANA positive Anti-histone antibodies classic dsDNA, esp in TNFi ANCA (MPO): Hydralazine, minocycline, PTU

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