Rheumatology Flashcards
Catastrophic Antiphospholipid Syndrome
Rare, life threatening form of APS
Characterised by micro and macrovascular thrombosis of multiple organs that develop either simultaneously or in short succession
Mechanism of Obstetric Antiphospholipid Syndrome
Direct trophoblast inhibition
Overarching rule for Antiphospholipid Syndrome testing
Persistent positivity required
(positive result on two tests done at least 3 months apart)
When are the different antiphospholipid syndrome antibodies significant?
Cardiolipin >40
Anti-Beta2 Glycoprotein >40 or >99th percentile
Lupus Anticoagulant: positive
Risk stratification for Antiphospholipid Syndrome
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
Who needs primary thromboprophylaxis in Antiphospholipid Syndrome?
High risk aPL profile, low risk aPL profile but have SLE, history of obstetric antiphospholipid syndrome
Management of Thrombosis in Antiphospholipid Syndrome
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
Management of Antiphospholipid Syndrome during pregnancy
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
Diagnosis of Sjogren’s
Schirmer test <5mm wetting in 5 minutes = dryness
ANA, Ro/La (SSa/SSb)
Primary Lymphoma type associated with Sjogren Syndrome
Mucosal Associated Lymphoid Tissue Lymphoma
Clinical features of SJogren’s associated with higher lymphoma risk
Lymphadenopathy
Recurrent parotid swelling
Monoclonal gammopathy
Depressed C4
Decreased RF (if elevated at baseline)
What population needs additional testing prior to starting Allopurinol, and what testing is this?
Four South East Asian patients, need to check HLAB58*01
HLA associated with Behcet’s?
HLA B51
Etanercept
TNF Inhibitor
Shouldn’t be used for IBD → increases risk of bowel perforation
Infliximab
TNF Inhibitor
First line biologic for IBD, good for fistulas, perianal disease
Risk of anti-drug antibodies
Adalimumab
TNF Inhibitor
Risk of anti drug antibodies
Certolizumab
TNF Inhibitor
Golimumab
TNF Inhibitor
Anakinra
IL-1 Inhibitor
Less effective for inflammatory arthritis, so not used much. Can be used for gout, TRAPS, Familial Mediterranean Fever
Tocilizumab
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
Secukinumab
IL-17 Inhibitor
Used for Psoriasis, PsA, AS, Axial Spondyloarthritis
Ixekizumab
IL-17 Inhibitor
Only really used for PsA/Psoriasis
Ustekinumab
IL-12/23 Inhibitor
Good for joints, less so skin
Guselkumab
IL-23 Inhibitor
Good for joints, less so skin
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
Rituximab
Anti CD20 → depletes B cells, blocks formation of new antibodies
Can cause hypogammaglobulinaemia
Belimumab
Inhibits B cell activation
Can be used in Lupus
Tofacitinib
JAK Inhibitor: Reduced DNA transcription in lymphocytes
High risk of cardiovascular disease, stroke, VTE, cancer in older patients and smokers
Upadacitinib
JAK Inhibitor: Reduced DNA transcription in lymphocytes
High risk of cardiovascular disease, stroke, VTE, cancer in older patients and smokers
Baricitinib
JAK Inhibitor: Reduced DNA transcription in lymphocytes
High risk of cardiovascular disease, stroke, VTE, cancer in older patients and smokers
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
Biopsy in Sarcoid
Gold standard for diagnosis. Skin lesions a good option as easily accessible
Noncaseating granulomas containing
- Giant cells
- Asteroid bodies
- Schaumann bodies
Indications for Immunosuppression in Sarcoidosis
- Symptomatic, progressive disease
- Persistent pulmonary infiltrates
- Progressive decline in lung function
Sarcoidosis staging
- Bilateral Hilar Lymphadenopathy, no pulmonary infiltrates
- Pulmonary infiltrates, No Bilateral Hilar lymphadenopathy
- Both bilateral hilar lymphadenopathy and pulmonary infiltrates
- Substantial pulmonary fibrosis
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
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
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
Key HLA for Rheumatoid Arthritis
HLA-DRB1
Concept of shared epitope
Around 60% heritable
PTPN22 SNP is other key gene
Most specific test for Rheumatoid Arthritis
Anti-CCP
DAS-28
Key tool for monitoring RA
<2.6 = remission
>5.1 = active
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
How much do TNF Inhibitors increase infection risk?
~5%
Key extra-articular manifestations and complications of RA
- Scleritis
- Sicca
- Atherosclerosis
- Pulmonary: ILD, pleural effusion
- Renal amyloid (a-a)
MPO-ANCA
Microscopic Polyangitis
ANCA present >90%
Necrotising GN +/- pulmonary capillaritis
PR3-ANCA
Granulomatosis with polyangitis
ANCA present >80%
Respiratory involvement core feature
Can have a pauci-immune GN
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
Most common presenting feature (or at least first clinical feature) of GPA/EGPA?
ENT involvement
ILD patterns in ANCA
pANCA (MPO, MPA): UIP
cANCA (PR3, GPA): NSIP
What infection is commonly ANCA positive?
Infective Endocarditis (c-ANCA)
Cystic Fibrosis, esp. Pseudomonas aeruginosa
What drugs can induce ANCA?
Hydralazine
Carbimazole/Propylthiouracil
Minocycline
Penicillamine
What is Avacopan, and when might it be used?
C5a receptor inhibitor
Used for ANCA vasculitis
Reduces cumulative corticosteroid exposure
Mepolizumab
IL-5 Inhibitor
Can be used in non-severe/refractory EGPA
What is the biggest risk factor for GCA/PMR?
Age
Essentially does not occur in those <50
When should Aspirin be used in GCA?
Critical/flow limiting cerebral artery disease. However some bosses will use in all
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.
Which Rheumatologic condition is associated with GAVE?
Scleroderma
U1-RNP
Mixed Connective Tissue Disease
Nucleolar ANA
Diffuse SSC
Centromere ANA pattern
Limited SSc
Anti Scl-70
Diffuse SSc
PMSCL 100/75
Myositis/Scleroderma overlap
First line treatment for SSc related inflammatory arthritis
MTX
Second line: Glucocorticoids
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
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
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
Treatment for SSc related Myocarditis
1st line MMF or high dose steroids
In conjunction with normal CCF treatment
2nd line: IV CYC or RTX
Poor Prognostic Factors in SSC
- Increasing age
- Sclerdoderma renal crisis
- PAH
- Pulmonary Fibrosis
- Rapid onset/progression
- Associated malignancy
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
What gene mutation is associated with SLE pathogenesis
PTP-N22
Immunopathogenesis of SLE
Increased apoptosis → excess antigen → CRP and C1q overwhelmed
Formation of neutrophil extracellular trans (NETs) → NETosis
Immune complexes important in nephritis
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)
Anti sm antibodies
Renal and Neurological Lupus
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
Antibodies in Drug Induced Lupus
100% ANA positive
Anti-histone antibodies classic
dsDNA, esp in TNFi
ANCA (MPO): Hydralazine, minocycline, PTU
