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Dunedin- Rheumatology Flashcards

1
Q

What is the larger contributor for a risk of rheumatoid arthritis ?

A

(1) Smoking (2) genetics

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2
Q

What HLA is associated with RA?

A

HLA-DRB1
MHC Class 2, Chromosome 6

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3
Q

Describe some genes associated with RA

A

PTPN22 SNP- together with HLA-DRB1 gives 50% genetic risk

IL2RA (chromosome 10p15)
PTPN2 (Chromosome 18p11)
Chromosome 12q24 region

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4
Q

Describe Mucosal origins hypothesis

A
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5
Q

Describe Anti-CCP

A

As sensitive as, and more specific than, IgM RF in early and fully established RA

Marker of erosive disease

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6
Q

What other things can cause rheumatoid factor to be high?

A

Chronic viral hepatitis
infection

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7
Q

When diagnosing RA, what is the time frame?

A

> 6 weeks

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8
Q

Co-morbidities and RA treatment

A

*dose reduction MTX when eFFR <60mls/min

*Contraindication MTX, LEF liver disease or transaminitis

*Contraindication: Chronic infection

  • Consideration: recent malignancy

*Manage actively: Hep B or Hep C

*Various specific CI- VTE and JAKI, CHF, and MS with TNFI

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9
Q

What is the first line treatment for RA?

A

Methotrexate with oral prednisone with weaning. if still active ADD cDMARDS, if still active ADD bDMARDS or tsDMARDS

(1) DMARDS (methotrexate, salazopyrine, hydoxychloroquine, leflunomide)

(2) Biologics (TNFalpha inhibitors, B-cell inhibition, Anti-IL-6 co stimulatory receptor blocker)

(3)targeted synthetic tsDMARDS (Janus kinase inhibitors)

glucocorticoids, NSAIDS

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10
Q

Any “cept” eg etanercept

A
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11
Q

What age group is at risk with JAK inhibitors?

A

> 65 years

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12
Q

Can immune checkpoint inhibitors be used in RA?

A

Yes

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13
Q

What is Peresolimab?

A

Peresolimab is a humanized IgG1 monoclonal antibody designed to stimulate the endogenous programmed cell death protein 1 (PD-1) inhibitory pathway.

can be used in mod-severe RA disease

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14
Q

Methotrexate and the lungs?

A

Methotrexate causes Acute PNEUMONITIS NOT ILD

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15
Q

What is the pathophysiology of scleroderma?

A

*Initial microvascular/endothelial damage

*Initial microvascular/endothelial damage, Followed by an autoimmune response with inflammation

*Finally characterized by diffuse fibrosis

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16
Q

What is the scleroderma spectrum

A

Limited cutaneous AKA CREST

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17
Q

Describe limited cutaneous systemic sclerosis vs diffuse cutaneous systemic sclerosis

A

Limited cutaneous: CREST
- calcinosis, Raynaud’s, oesophageal dysmotility, sclerydactyl, telangiectasia + PULMONARY ARTERY HTN

Diffuse cutaneous systemic sclerosis:
- extensive skin involvement: proximal limbs and trunk.
Renal disease
pulmonary interstitial fibrosis

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18
Q

What is the most common cause of death in diffuse cutaneous systemic sclerosis?

A

Pulmonary fibrosis

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19
Q

Discuss renal crisis in Diffuse sclerosis

A

*Precipitated by steroids
*Anti RNA Polymerase III
*abrupt onset of mod-severe hypertension
*urine sediment normal or reveals only mild proteinuria with few cells or casts
* progressive renal failure

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20
Q

Describe cardiac involvement in systemic sclerosis

A

*Ischaemia including in response to cold exposure
*contraction band fibrosis
*right ventricular changes with pulmonary HTN

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21
Q

Describe GI involvement in systemic sclerosis

A

*GAVE (watermelon stomach) with chronic blood loss
*oesophageal dysmotility and reflux
*‘shrinking stomach’ with early satiety
*small bowel dysmotility with bacterial overgrowth
*malabsorption
*volvulus
*Faecal incontinence
*cachexia

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22
Q

Describe auto-antibodies in scleroderma

A

Diffuse: Scl-70 (anti-topoisomerase), RNA polyermase III, U3-RNP

Limited: centromere, Th/To, U11/U12 RNP

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23
Q

Which antibody is associated with mixed connective tissue disease?

A

U1-RNP

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24
Q

What antibody is associated with Myositis/Scleroderma

A

PMScl 100/75

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25
What is the relevance of absent antibodies in scleroderma?
increased association with malignancy
26
Describe nail fold capillaroscopy
27
What is the Rodnan skin score?
used in scleroderma, treatment is based on it
28
Treating scleroderma
Scleroderma renal crisis: ACEI Scleroderma inflammatory arthritis: Methotrexate Skin involvement: Methotrexate, MMF, IV cyclophosphamide, HSCT Lung disease or cardiac disease: MMF Pulmonary arterial HTN: PDE5i, ERA (bosentan, ambrisentan) raynauds or digital ulcers: CCB GI: high dose PPI, promotability agents, oesophageal dilation
29
Digitial ulcers and scleroderma
strong association with pulmonary HTN
30
Describe spectrum of vasculitis
31
Out of the ANCA vasculitis, which ones produce granulmonas?
GPA (wegeners) eosinophilic granulomatous w polyangitis (EGPA)
32
Differentiate between PR3-ANCA and MPO- ANCA
GPA: PR3-ANCA (sometimes MPA too) MPA: MPO- ANCA
33
What lung disease is pANCA associated with vs cANCA?
pANCA- UIP cANCA- NSIP
34
Urinary eosinophilia
interstitial nephritis NOT vasculitis
35
Erythema nodosum
36
Livido reticularis
37
Pyoderma gangrenosum
38
Describe ANCA patterns in other disease
IBD can have ANCA autoimmune hepatitis infective endocarditis (c-ANCA) Cystic fibrosis (pseudomonas aeruginosa)
39
What drugs cause Drug-Induced ANCA?
Hydralazine Carbimazole/propylthiouracil minocycline penicillamine
40
Treating vasculitis:
Severe: IV Methylpred, cyclophosphamide, rituximab Non-organ threatening: Pred + methotrexate, Aza, MMF Maintenance of remission: Ritux, MMF, Methotrexate, Aza, leflunamide some evidence of mepoluzimab (IL-5), Plasma exchange, avacopan (C5a receptor inhibitor)
41
How to determine severity of EGPA vasculitis?
(1) Age>65 (2) Renal impairment at presentation (3) cardiac insufficiency (4) Gastrointestinal involvement (5) absence of ENT disease
42
What is the gold standard for GCA?
Temporal artery biopsy >10mm sample highly specific reasonably useful within 2 weeks of starting steroids
43
What is the biggest risk factor for GCA?
Age
44
What is the temporal artery US sign in GCA?
*Halo sign *compression test : thickened arterial wall remains visible on compression *stenosis *occlusion
45
What is the management of GPA?
if vision threatened --> IV methylpred or oral pred methotrexate, leflunamide, tociluzimab Large vessel involvement: antiplatelet therapy in patients with critical/flow-limiting cerebral artery disease
46
What is Anti-DFS70?
dense fine speckled a type of ANA usually a NEGATIVE associated with autoimmune rheumatic disease
47
What are poor prognostic factors for SLE?
1) Age extremes. onset >50 years or <30 years 2) Haemolytic anaemia 3) Male 4) renal lupus within 1 year of presentation 5) neuropsychiatric lupus
48
What are risk factors for SLE?
*Infection: CMV parvovirus, EBV * Smoking *Drugs- esp TNFis * Sun exposure * T and B cell receptor signalling PTP-N22 gene
49
Describe some things involved in immunopathogenesis of SLE
apoptosis --> high cell turnover --> nucleic materials released from dying cells --> CRP and C1q assist removal of nucleic waste --> APC can take up the nucleic acids and present to T and B cells often in the kidney --> Neutrophil extracellular trans (NETOSIS) --> immune complex formation
50
What are the main types of lupus?
1) Discoid lupus 2) Subacute cutaneous lupus 3) Systemic lupus with low risk of serious harm 4) Systemic lupus with risk of serious harm
51
Describe the urine in systemic lupus with low risk of serious harm
no urinary casts, RBCs or proteinuria
52
What type of arthritis does lupus cause?
non-erosive small joint poly arthritis correctable deformity (Jaccoud's arthropathy) tenosynovitis
53
Describe symptoms of lupus with risk of serious harm
*Vasculitic rash *neurology: seizures, psychosis, mononeuritis multiplex, peripheral or cranial neuropathy, organic brain syndrome, acute confusion *lupus headache *Endocarditis= liebmann-sachs, pericardial effusion *renal involvement: nephritis, heavy proteinuria, reduced GFR *pregnancy associated complications: pre-eclampsia, HELLP syndrome, neonatal heart block *haemolytic anaemia
54
describe lupus vasculitis
55
Generally lupus spares the lung. true or false?
TRUE- however can get shrinking lung syndrome
56
Describe lupus nephritis
Class 1- minimal mesangial Class 2- mesangial proliferative Class 3- Focal Class 4- Diffuse
57
Describe cerebral lupus
really bad headache. poor prognostic sign! anxiety, depression seizures Focal neurological signs investigate with PET scan and do formal cognitive testing
58
What is the most common feature of lupus?
(1) Arthritis (2) Rash (3) serositis (4) photosensitivity
59
Relevant of Anti Ds-DNA in SLE
very specific 97% titres correlate with disease activity elevation correlates with lupus nephritis can be seen in drug induced lupus
60
ENA and their associations
Anti-Ro (60): SCLE, Sjogren's syndrome Anti-La: Sjögren's syndrome and SLE Anti- Sm: renal and neurological lupus (lupus with RSH) AntiU1 RNP: MCTD, SLE Anti Ro 60 is different to 52. Ro60 is specifically subcutaneous
61
What drugs are likely to cause drug induced lupus?
high risk: procainamide, hydralazine Low risk: PPI, anti-TNF, statins, chemotherapeutic drugs, ACEi, PTU, minocycline, methyldopa, D-penicillamine tetracyclines
62
Autoantibodies in drug induced lupus
Anti-histone DsDNA in TNFi ANCA (MPO)- hydralazine, minocycline and propylthiouracil
63
What is the management of SLE?
flare: pred, NSAID, immunosuppressant (cytoxan, azathioprine, methotrexate,) treating major organ involvement: cyclophosphamide, mycophenolate, calcineurin inhibitors rituximab, obinutuzumab (both in renal lupus), belimumab , anifrolumab JAKi, sexukinumab, ustekinumab, lenalidomide for severe cutaneous disease, targeted dendritic cell monoclonal ab: litifilimab
64
What do you expect blood test in SLE?
Reduced CH50 Low C4 (risk factor, can be genetically determined) C3- alternate pathway High ESR, CRP can be normal FBC: lymphopenia, neutropenia, thrombocytopaenia Haemolytic Urine; protein, granular cast, RBCs, WBCs
65
Conventional DMARDS are only for peripheral SpA. True or false?
True Also ustekinumab also only peripheral
66
What is the diagnostic criteria of Spondylarthritis?
note sacroilitis can be on MRI or X-RI
67
Treatment for Uveitis?
topical steroids
68
Pathogenesis of axial spondylarthritis
69
Infection associated arthritis
70
What bacteria is associated with erythema nodosum?
campylobacter
71
What does Keratoderma Blennorrhagicum look like in reactive arthritis?
72
DISH vs Ankylosing spondylitis
73
What test is best to look for active inflammatory lesions in Ankylosing spondylarthritis?
MRI- T2 for bone oedema T1- for sclerosis, erosions and fatty lesions however some can have positive MRI findings and be healthy
74
What is gold standard for detecting structural changes (erosions) in ankylosing spondylarthritis?
CT scan
75
Treatment of spondylarthritis?
76
Regarding spondylarthritis, if Uveitis or IBD what drugs to use?
TNF inhibitors but NOT etanercept
77
Regarding spondylarthritis, if psoriasis what drugs to use?
IL-17 eg secukinumab, ixekizumab can use IL-12/23 --> not good for axial disease
78
First line for axial spondylarthritis?
Should use NSAID. trial 2 different ones! if still not working then biologic
79
Describe myositis specific antibody subset
Anti-NXP-2 young onset dermatitis or disease associated with malignancy in adults
80
What lung problem is associated with Anti-synthetase syndrome?
Pulmonary interstitial fibrosis: BOOP (bronchiolitis obliterates organising pneumonia) AKA Cryptogenic organising pneumonia (COP)
81
Antibodies associated with dermatomyositis
Anti-Mi2 TIF-1y MDA-5 Mj
82
Sights of dermatomyositis?
heliotrope rash gottrons papules mechanisms hands shawl rash peau d'orange
83
How to treat immune mediated inflammatory myopathies?
IV methylprednisone then oral prednisone methotrexate (1st choice) maybe Aza, MMF, calcineurin inhibitors
84
Antibodies in anti-phospholipid syndrome
anticardiolipin lupus anticoagulant B2GP1 Anti-domain 1 B2GP1 anticomplex phosphatidylserine-prothrombin- anti-PS/PT
84
Primary thromboprophylaxis of anti phospholipid syndrome
Low dose aspirin for: *triple positive antibodies asymptomatic patients with no hx of VTE *women with pure obstetric APS and positive antibodies *Patients with SLE and one or more ACL ab beneficial in reducing risk of arterial embolism borderline effect in reducing VTE as effective as low intensity warfarin Hydroxychloroquine: in SLE LMWH: triple positive or high risk (postpartum, post surgical, immobilisation)
85
Secondary thromboprophylaxis in anti-phospholipid syndrome
- if provoked can do 6 months of anticoagulation then aspirin - otherwise warfarin - CANNOT USE RIVAROXOBAN can possibly do warfarin + aspirin if arterial thrombosis
86
What is Catastrophic APS syndrome (CAPS) and how to treat it?
Clinically: * overwhelming widespread thrombosis: renal, cardiac, cutaneous, cerebral, pulmonary and gastrointestinal thrombi *multiple organ failure occurring within 1 week of presentation * adult respiratory distress syndrome *aPL antibodies Pathophysiology * acute endothelial injury, cytokine storm, systemic inflammation, and a microangiopathic thromboses Management: 1) full dose anticoagulation (start with IV heparin) 2) high dose glucocorticoids (methylpred) 3) Plasma exchange If infection too --> add IVIG if SLE too --> cyclophosphamide If MAHA too --> add rituximab possible role for eculizumab
87
Ehlers danlos syndrome associated with lens dislocation. True or false
false marfans is associated with lens dislocation
88
Describe discoid lupus
80% of lesions above the neck scarring depigmentation alopecia mucosal lesions can progress to SLE (5-25%)
89
Describe subacute cutaneous lupus (SCLE)
Photo-sensitive, non-scarring rash pleurisy oral ulceration arthritis/arthalgia tenosynovitis
90
Describe the patterns of ANA
homogenous- SLE - Anti-dsDNA and anti-histone Speckled- SS, MCTD - anti-Ro/La, anti-Sm, anti-RNP Nucleolar- scleroderma (diffuse cutaneous) Cytoplasmic- myositis

Aisha (45 decks)

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