Rheumatology Flashcards
(126 cards)
1
Q
Abatacept
A
2
Q
Alkylating Agents
A
3
Q
Anti-CCP or ACPA
A
4
Q
Auto-antibodies of scleroderma (systemic sclerosis)
- Which (1) related to limited disease
- Which (2) related to diffuse disease
- Which (1) decreases the risk of severe lung disease
- Which (1) increases the risk of ILD
- Which (1) is associated with renal disease, skin involvement and malignancy
A
5
Q
Autoantibodies in SLE
A
6
Q
Autoantibodies in SLE
Most Sensitive
Most Specific
Implication of Dense Fine Speckled ANA
A
7
Q
Azathioprine
Cyclosporin
Leflunomide
Methotrexate
A
8
Q
Azathioprine and TMPT
Drugs not to combine with AZA
A
9
Q
Behcet’s disease
- HLA association
- Describe disease course and Rx
A
HLA-B51!
10
Q
Belimumab - drug profile
A
11
Q
Best treatment for palindromic Rheumatism
A
Palindromic rheumatism (PR) is a syndrome characterised by recurrent, self-resolving inflammatory attacks in and around the joints, consists of arthritis or periarticular soft tissue inflammation. Course is often acute onset, with sudden and rapidly developing attacks or flares. There is pain, redness, swelling, and disability of one or multiple joints. The interval between recurrent palindromic attacks and the length of an attack is extremely variable from few hours to days. Attacks may become more frequent with time but there is no joint damage after attacks. It is thought to be an autoimmune disease, possibly an abortive form of rheumatoid arthritis.
Hydroxychloroquine
12
Q
Causes of Visual Loss in GCA
- ?most common
- and which vessel is involved
A
13
Q
Comparison of the various forms of Spondyloarthritis
A
14
Q
Contraindications to anti-TNFa therapy (5)
A
Malignancy within the past 5 years
15
Q
Contraindications to pregnancy in SLE (7)
A
16
Q
Cytokine Modulators in RA
- abatacept
- anakinra
- baricitinib
- rituximab
- tocilizumab
- tofacitinib
A
17
Q
Definition of Inflammatory Back Pain:
A
18
Q
Diagnosis of Sjogren’s Syndrome
A
19
Q
Diagnosis of Sjogren’s Syndrome
A
20
Q
Diagnostic Criteria for SLE
A
Definitions
- Discoid rash - red rash raisedm disk-shaped patches
- serositis - inflamamtion of linign around the lungs
- Kidney disoder - persistent proteinuria or celular casts in the urine
- Neurologic disorder - seizures or psychosis
- Blood disorder - anaemia, leukopenia, lymphopenia or thrombocytopenia
21
Q
Difference between limited and generalised GPA (Wegner’s)
A
The absence/presence of renal involvement
22
Q
DMARDs and pregnancy
A
csDMARDs during pregnancy
- Minimal foetal and maternal risk
- hydroxychlorquinine, sulfalazine and azathioprine
- May be used selectively
- corticosteroids, ored does nto cross the placenta, try to limit to 10mg per day - risk of gestational diabetes, small for gestational age babies, preterm delivery
- NSAIDs, safest during 2nd trimester, avoid during 3rd trimester due to risk of premature closure of ductus arteriosus
- Moderate to high risk of foetal harm
- Methotrexate
- Leflunomide
23
Q
Epidemiology and Causes of Polyarteritis Nodosa
A
24
Q
Epidemiology and Pathogenesis of Takayasu arteritis
A
25
Epidemiology and Presentation of Ank. Spond
Most common spondylitis - 1% of the population
* males \> females 3:1
* main determinant = frequency of HLA B27 in population approx 5%
26
Epidemiology of Scleroderma (Systemic Sclerosis)
27
Features Favouring MCTD over SLE other primary autoimmunes
28
Felty's syndrome HLA association
HLA DRW4
29
General Management of SLE (5)
30
Hydroxychloroquine
- which SLE patient's should be prescribed
- Benefits (7)
- Main concerning SE and RF for this
31
Hypersensitivity Vasculitis
32
Impact on SLE on:
Fertility
Pregnancy
Flares
33
Implications of anti-Ro and anti-La antibodies in SLE and pregnancy
34
Implications of anti-Ro and anti-La antibodies in SLE and pregnancy
35
Implications of APLS antibiodies in SLE and pregnancy
36
Implications of Primary Sjogren's Syndrome
37
Indications for Renal Bx in SLE
38
Indicators of Poor Prognosis in RA (6)
39
**Induction and Maintence** Therapies for lupus nephritis
**Class III, IV +/- V**
40
Interpretation of Synovial Fluid
41
Is plasma exchange of benefit in ANCA associated pauci-immune glomerulonephritis? What do the trials show for management of ANCA associated vasculitis according to disease severity?
**Yes MEPEX trial**
* better renal recovery but no change in mortality
* should be used in those with severe renal involvement (Cr \>500)
42
Key driver of pathology in CPP arthropathy
**NLRP3 -\> activates IL-1**
43
Limited vs Diffuse Systemic Sclerosis
44
Management of Fibromyalgia
Education is key!
**Medications:**
* TCAs
* Gabapentinoids
* SNRIs
* Tramadol
* Low-dose naltrexone
* Propranolol
**Management – interventions best AVOIDED**
* **Opioids**
* **Paracetamol**
* **NSAIDs**
* **_Glucocorticoids_**
* Benzodiazepines
* Most CAM therapies
* Cannabinoids?
45
Management of Raynaud's Disease
46
Measures of Disease Activity in SLE (5)
47
Most common cardiovascular manifestation of SLE
Pericarditis
48
Most common cause of drug induced ANCA+ vasculitis
**Hydralazine**
49
Most sensitive autoantibody for drug induced lupus
Anti Histone
50
Most significant complication of SLE in pregnancy
CHB for baby! :(
51
Mucocutaneous Lupus
- Types
- which are photosensitive
- which needs to be treated aggressively?
52
Other autoantibodies of RA (3)
53
Other features of Psoriatic Arthritis
54
Polyarteritis Nodosa
- Is it ANCA positive or negative?
- Common or rare
- Most common secondary cause
- Presentation + most common organ
- Treatment
55
Polyarteritis Nodosa Presentation
56
Poor prognostic markers in RA
57
Predictors of Severe Lung Disease in Scleroderma (5)
58
Preferred immunosuppressive agent for Rx of ILD and skin disease in scleroderma
Skin
* Mycophenlate is likely the treatment of choice for severe skin disease. May spontaneously remit
59
Presentation of **Acute Calcium Pyrophosphate crystal pathologies**
Clinical presentation
Acute CPP crystal arthritis:
* **Typically monoarthritis**; **_knee_** most common; wrist, shoulder, ankle, elbow.
* Acute inflammatory arthritis.
* Self-limited: 1-3 weeks duration.
**Chronic CPP crystal inflammatory arthritis:**
* Can mimic seronegative rheumatoid arthritis, polymyalgia rheumatica.
**Osteoarthritis with CPPD:**
* Causes OA in joints not typically involved (MCP joints, wrists, elbows).
Synovial fluid analysis:
* **Synovial fluid leukocytosis, \>90% neutrophils**
* **Rhomboid or rod-shaped crystals**.
* Compensated polarised light microscopy: minority (20%) show weak positive birefringence
* Harder to identify than MSU crystals.
Plain radiographs:
* **Involvement at sites uncommon for primary osteoarthritis (MCP joints, wrists, elbows, shoulders).**
60
Proportion of patient's with psoriasis who have PsA
30%
61
Psoriatic Arthritis
- Most common pattern
- HLA association
- Other skin manifestations
- Rx
- Important association
62
Psoriatic Arthritis
- Onset of skin vs joint
- Patterns (5)
63
Psoriatic Arthritis - treatment
* **NSAIDs** –Symptom relief
* **csDMARDs**– Methotrexate, Sulfasalazine, Leflunomide
* Surprisingly **little data; efficacy of MTX** controversial –20mg weekly effective
* **Anti-TNF** –Adalimumab, Certolizumab pegol, Etanercept, Golimumab, Infliximab
* **Anti-IL17** –Secukinumab, Ixekizumab
* **Anti-p40 subunit IL12/23** –Ustekinumab; anti-p19 subunit IL-23 -guselkumab
64
RA and pregnancy
65
RA and surgery
- which drug to consider increasing
- which drug to consider withholding
66
Radiographic hallmarks of RA (6)
67
Radiological findings of joint disease
68
Recommended treatment for induction and maintence for Wegner's (GPA)
**Oral cyclophosphamide** for **induction for 3 months**
Then **PO azathioprine or MTx for maintenance**
**Azathioprine \> mycophenolate**
69
Rheumatoid Arthritis
- Important pro-inflammatory cytokines (2)
- HLA association (1)
- Describe the hand involvement
- What % have extra-articular disease?
- What % are seronegative?
- Which drug is the backbone of therapy?
- Which is the best biologic DMARD
70
Risk Factors and Pathogenesis of SLE
71
Risk Factors for Calcium Pyrophosphate Arthritis
72
Risk Factors for Rapid Progression in Ank. Spond
73
Risk Factors for Renal Crisis in Scleroderma (5)
74
Scleroderma Renal Crisis
- presentation
- treatment
ACEi, ACEi, ACEi! CAPTOPRIL
* Untreated, can progress to end stage renal disease over 1-2 months
* **_Mainstay of treatment is effective and prompt blood pressure control_**
* **_improves/stabilizes renal function in up to 70% and improves 1 year survival up to 80%_**
75
Secukinumab
76
Should Rituximab be used in ANCA vasculitis
**_No._**
Increased risk of relapse at 18 months
77
Spondylosis vs DISH (Diffuse Idiopathic Skeletal Hyperostosis) vs Ank Spond
78
Structure of RhF
-2 associations
**IgM** antibodies directed **against IgG**
79
Summary of IBD associated Spondyloarthritis
* Estimates vary - approx 10-20% of IBD patients
* More common in those with:
* other extra-intetsinal features
* complications of bowel disease
* large bowel invovlement (for Crohn's)
* Two subtypes
* axial - asymptomatic sacro-ilitis in up to 20%
* peripheral
* peripheral arthritis
* usually acute, oligoarticular and lower limb
* deformities/erosions rare
* can be self-limiting, related to flares of IBD
* Rarel, progressive independent of IBD activity
* Can see other features of SpA eg. ethesitis
* Axial disease
* Same clinical presentation as AS
Treatment
* NSAIDs - use with caution
* DMARDs - sulfalazine, joints and bowel
* Not effective in axial disease
* Controlling bowel disease often helps
* surgery in Crohns not usually helpful
* Anti-TNF for joints and bowel
* Axial disease treat as per AS
80
Summary of Reactive Arthritis
- timing
- infections
- Rx
- natural Hx
81
Systemic Complications of Primary Sjogren's Syndrome
82
TNFalpha antagonists
83
Treatment of GCA
84
Treatment of Lupus Nephritis
- Name each of the 6 classes
- Name which require immunosuppression
- what are the 4 adjunctive therapies?
TREATMENT
- Induction = glucocorticoids + cyclo OR MMF
Maintenance = MMF or AZA
85
Treatment of Polyarteritis Nodosa (PAN)
86
Treatment of Takayasu arteritis
87
Ustekinumab
88
Vaccines and bDMARDs or tsDMARDs
89
What are the classic causes of drug induced lupus (SLE)?
* *Procainamide** and **hydralazine** the classics
- genetic differences resulting in slower acetylation increase risk
Minocycline and TNF blockers more common now
90
What are the relative **5yr mortality rates for the small and medium vessel vasculitides?**
* Microscopic polyangiitis (MPA) 28%
* Polyarteritis nodosa (PAN) 25%
* Eosinophilic Granulomatosis with Polyangiitis (EGPA)(Churg Strauss) 14%
* Granulomatosis with Polyangiitis (GPA)(Wegener's) 13%
* Higher risk of relapse with **anti-PR3 or cardiovascular involvement**
* Lower risk of relapse with renal involvement
91
What characterises **Granulomatosis with Polyangiitis (GPA)(Wegener's)**?
**ANCA +ve vasculitis**
* **90% cANCA (PR3) +**ve in generalised, 60% in limited
**Presentation**
* **ENT involvement in 95%:** sinusitis, **epistaxis, saddle-nose deformity**, subglottic stenosis, otitis media, sensorineural hearing loss
* **pulmonary:** haemorrhage, stridor, dyspnoea, wheezing, cavitating nodules
* **renal:** glomerulonephritis picture (segmental necrotising pauci immune)
* skin
* **opthalmologic in 50%** (can get retroorbital granulomata), episcleritis
**Management**
* l**imited (ENT only): prednisolone** + azathioprine or methotrexate
* **severe:** prednisolone + cyclophosphamide or rituximab (equivalent)
92
What disease when it occur's with Wegner's causes worsened Wegner's Phenotype
Alpha1 antitrypsin deficiency - especially Z genotype
93
What is polyarteritis nodosa (PAN)?
**_Systemic necrotising medium vessel vasculitis_**
* - note frequently get **overlap with microscopic polyangiitis** (and then can get the GN/lung haemorrhage, etc)
Associated with **Hep B in 1/3: higher mortality (34% vs 19%)**
Also associated with **hep C, HIV, hairy cell leukaemia**
**Presentation**
* organ ischaemia with infarction (bowel, kidney)
* **_don't get_** glomerulonephritis or lung haemorrhage
* **coronary arteries, neuropathy**
* orchitis, retinitis
**Investigations**
* **biopsy:** focal, segmental pan-mural necrotising inflammation of medium-sized arteries with predeliction for bifurcations and branch points of muscular arteries
* **angiogram:** stenoses, aneurysms, thrombosis
* **ANCA -ve** (unless in overlap with MPA)
**Management**
* high dose prednisolone + cyclophosphamide -\> pred + azathiorpine maintenance
* 80% 5yr survival
* antivirals if hep B +ve
94
What is Takayasu arteritis?
**Chronic inflammatory granulomatous large vessel vasculitis**
* cause unclear
* more common in Asians and South Americans
**Affects aorta and its branches**
* - Subclavian, carotid, vertebral, brachiocephalic, pulmonary arteries
**Diagnostic criteria (3+/6 sens 90.5%, spec 97.8%)**
* - young woman \<40yrs
* - limb claudication
* - decreased brachial artery pulse
* - differential limb SBP \>10mmHg
* - subclavian artery or aortic bruit
* - abnormal angiogram
**_Angiogram the gold standard_**
* - beading, stenosis, aneurysm
PET can be useful for diagnosis
* - doesn't predict relapse or progression
**Use CTA -\> MRA for monitoring**
* - to avoid having to regularly irradiate them
**Management**
* **1st line high dose steroids +- steroid sparing**
* - tociluzimab (IL-6 inhibitor) works
* - rituximab works
* - anti TNFa work
95
Which **connective tissue** has the highest mortality
SCLERODERMA
96
What characterises **eosinophilic granulomatosis with polyangitis (EGPA)?**
**Asthma**
* - later in life without a history of atopy
**Sinus abnormalities**
**Peripheral eosinophilia**
* - \>10% one of the defining features
* - Present at Dx in \<=80%, rapidly responds to therapy
**Neuropathy in \>75%**
* - mononeuritis multiplex
* - cerebral haemorrhage or infarction important causes of death
**Pulmonary infiltrates**
* - PFTs often obstructive
**Rash in 50%**
* - purpura, nodules, urticarial rashes, livido
**GI**
* - ischaemic bowel, pancreatitis, cholecystitis portend poor prognosis
**Cardiac**
* - Involvement portends poor prognosis
* - Pericarditis, MI, ECG changes
**Renal in 25%**
* - proteinuria, GN, CRF/CKD, infarct
**ANCAs in 50%**
97
What is the treatment for eosinophilic granulomatosis with polyangitis?
**_Steroids the mainstay_**
* - 50% of untreated die by 3 months
* - Treated have 6yr survival 70%
* - \>90% achieve clinical remission, ~25% relapse
**_Cytotoxic agents may be used_ in presence of poor predictors**
* - Cardiac, renal, GI
* - Cyclophosphamide: doesn't increase survival but associated with reduced relapses and better response to treatment
* - Others MTx, azathioprine, IVIg, interferon a
98
With what is **reactive arthritis** most commonly associated?
After **1% of nongonococcal urethritis** and **2% of enteric infections**
* - Y enterocolitica, shigella, to a lesser extent c jejuni and salmonella; may occur after c difficile
* - Only a minority have the classic findings: **urethritis, conjunctivitis, uveitis, oral ulcers, rash**
Most commonly in **young men** and linked to **HLA-B27 locus**
Most recover within **6 months**
* *Predictors of longer course**
- male
- post-chlamydial
- extra articular features
- HLA-B27 +ve
99
What are the various **lung manifestations** and their frequencies in the connective tissue diseases **(CTD)?** WHy is it important to separate them from IPF?
Note it's **uncommon** to see **ILD in SLE**
Important to differentiate **_due to prognostic factors_**
100
What does an elevated AMA indicate?
Associated with _**primary biliary cirrhosis (cholangitis), and multiple others
- 95% of those with PBC have AMA ab**_
9 antigens have been identified, M1-M9
Can also be seen in **Sjogren's, systemic sclerosis, pulmonary TB, leprosy**
101
What are the toxicities associated with cyclophosphamide?
**Bone marrow**
* cytopoenias: granulocytes then platelets then RBC
* Nadir at 7-14 days, recovery by 21 days
**Infection**
* Bacterial, opportunistic, viral
* PCP prophylaxis indicated
**Gonadal toxicity**
* Cumulative dose independent risk factor for toxicity
* Should sperm/egg bank in those wanting fertility
* Women: infertility and premature menopause
* Men: decrease sperm count and irreversible azoospermia
* Teratogenic
**Malignancy**
* **All haematological malignancies**: lymphoma, MDS, leukaemia, myeloproliferative
* Risk increases with cumulative dose
* Skin and other cancers too
**Bladder toxicity**
* Haemorrhagic cystitis and bladder cancer. Due to toxic metabolite acrolein
* Cumulative dose related. Marked increase in risk of **bladder cancer after haemorrhagic cystitis**
* Can give **MESNA t**hat neutralises the toxic metabolites to reduce haemorrhagic cystitis
* Monitor urinalysis monthly on treatment and yearly off
**SIADH**
102
What is the classic renal manifestation of **Sjogren's syndrome**? How are they treated?
* **Tubulointerstitial nephritis** with predominant lymphocytic infiltrate
* Can also be associated with **type 1 (distal) RTA, diabetes insipidus, moderate ARF (AKI)**
* **Treatment**
* **Glucocorticoids +- maintenance azathioprine/MMF** to prevent relapse
103
What type of **renal manifestation** is associated with **IgG4 disease?**
* **Form of AIN**
* Dense **inflammatory infiltrate containing IgG4-**expressing plasma cells
* Also associated with
* autoimmune pancreatitis
* sclerosing cholangitis
* retroperitoneal fibrosis
* chronic sclerosing sailadenitis
104
What is scleroderma **(systemic sclerosis) renal crisis?** What's the prognosis?
**Malignant hypertension,** **rapid decline in renal function**, nephrotic proteinuria, haematuria, encephalopathy, pulmonary oedema, hypertensive retinopathy
* occurs in **5-10% of those with systemic sclerosis**
* usually within the **first 4yrs**
* **highest risk in diffuse cutaneous or rapidly progressive**, or recently commenced high dose steroid
* linked to **speckled ANA, anti-RNA polymerase**, and **absence of anti-centromere**
**Pathology**
* arcuate artery intimal and medial proliferation with luminal narrowing
* 'onion skinning'
**Prognosis _(untreated mortality ~100%)_**
* 40-60% never recover renal function
* **captopril (only ACEi with data)** improves outcomes but mortality at 5yrs still 30-40%
* If renal function not back by 24 months it's probably not coming back
105
Which patients with antiphospholipid syndrome have the highest risk of thrombosis?
**Venous more common than arterial thrombosis**
* - 20-30% with APLS get **low limb DVT** (the most common location)
* - most common **arterial is cerebrovasular**
**Lupus anticoagulant (LA) highest**
* - OR ~10 for **first VTE,** ~6 for recurrence, ~10 for arterial
**Anticardiolipin**
* - **NOT a risk for first VTE** (OR 0.7), OR 1-6 for recurrence
* **- IS** a risk for **arterial thrombosis**
**Beta 2 glycoprotein**
* - **OR 2.4 for first VTE**, no data for recurrence or arterial
* - and it's the anti domain 1 IgG antibody that carries the real risk
* *_LA or triple positivity the big predictors of recurrent thrombosis_**
- recurrence rate 5-12% per year
106
What **proportion of those with SLE have renal involvement** (lupus nephritis)? How does it present? Classes? Treatment?
* *~50% at diagnosis,** ~60% at some point during disease
- Most severe in African-American females
Markedly **increased mortality in those with lupus nephritis compared to base population**
**Pathophysiology**
* - Circulating immune complex deposition with complement activation and damage, leukocyte infiltration and cytokine release, activation of procoagulant factors
* - In situe complex formation from bidning of nuclear antigens
* - Antiphospholipid antibodies triggering thrombotic microangiopathy
**Clinical**
* - **Proteinuria** most common
* - **Hypertension, haematuria, renal failure, active sediment can all be present**
* **- dsDNA** correlates best with **renal disease**
* - **hypocomplementaemia is common** (70-90%)in acute lupus nephritis and can herald a flare
**Classification**
* Class I/II = limited to mesangium = excellent prognosis
* Class III/IV = proliferative = poor prognosis = treatment
* - S = segmental, G = global, A = active, C = chronic
* Class V = membranous and can be mixed with III/IV, in which case requires treatment
* Class VI = Advanced Sclerosing = \>=90% of glomeruli globally sclerosed
NIH biopsy scores (helps to decide re: immunosuppression)
**Treatment (ONLY stage III/IV +/- V)**
* **Induction** with pred/**methylprednisolone + MMF** or **cyclo** for 2-6 months
* **Maintenance** with **MMF or azathioprine (MMF \> aza for maint)**
Microthrombosis due to antiphospholipid antibodies is a poor prognostic factor
- Even with anticoagulation
Transplant
- ~20% reach ESRF requiring dialysis or transplant. Disease usually becomes quiescent, thought due to uraemia immunosuppression
- Survival comparable to those transplanted for other reasons
107
Which **subtype of ANCA** is more associated with **granulomatosis with polyangiitis (Wegener's)?** What abou**t microscopic polyangiitis**?
cANCA -\> PR3-ANCA for Wegener's
pANCA -\> MPO-ANCA for MP
108
What is cryoglobulinaemia? What are the types? Who gets them? How do they present?
**Cryoglobulins**
* **- Ig and complement** components that **precipitate** upon refrigeration of serum
* - Precipitation **reverses on warming**
* **- low C4 in 70-90%**
**Cryoglobulinaemia**
* - systemic inflammatory syndrome generally with small-medium vessel vasculitis due to CG-containing immune complexes
* - types 2 and 3 referred to as mixed cryoglobulinaemia
* - in 2 and 3 IgM acts as rheumatoid factor that combines with Fc of usually IgG
**Type I (isolated monoclonal Igs)**
* - **10-15%**
* **- Hyperviscocity** secondary to high levels of **monoclonal CG** in lymphoproliferative disorders
* - Present with signs of **hyperviscocity** and/or thrombosis
* - Raynaud's, digital ischaemia, livedo reticularis, purpura
* - **Neurological symptoms** or **peripheral neuropathy**
* - Predominantly affects the skin, kidney, and bone marrow
**Type 2 (immunocomplexes of monoclonal IgM; usually with polyclonal IgG)**
* - 50-60%
* - Strongly associated with HCV
**Type 3 (immunocomplexes of polyclonal IgM; usually with polyclonal IgG)**
* - 25-30%
* - Strongly associated with HCV and CTDs
**Types 2 & 3**
* - Skin, peripheral nervous system, and kidney
* - Arthralgias (\>70%), fatigue, malaise common
* - Raynaud's (~50%)
* - Sensory changes/weakness due to peripheral neuropathy
* - Palpable purpura in 90-95%
* - Meltzer's triad: Purpura, arthralgias, and weakness seen in 25-30%
* - Causes 2% of biopsy proven GN -\> membranoproliferative GN
**Treatment**
* Underlying disease in secondary:
* hep C associated antivirals + rituximab superior to antivirals alone. Rituximab superior to standard immunosuppression
* ritux + pred superior to alkylating + pred in non-infectious secondary
* PEx for severe or life threatening complications
109
What are the two types of ANCA test?
Indirect immunoflourescence = more sensitive
* *Enzyme Linked Immunosorbent Assay (ELISA) = more specific**
- Identifies the antibody
- C-ANCA by proteinase 3 (PR3)
- P-ANCA by myeloperoxidase (MPO)
110
What **proportion are ANCA positive** and what is the subtype in:
* GPA, MPA, EGPA, Pauci-immune renal limited vasculitis, anti-GBM, drug induced ANCA-associated vasculitis
111
What are the conditions other than vasculitis which can be associated with ANCA positivity?
* **• Autoimmune liver**
* o 90% of PSC
* o 70% of chronic, active autoimmune hepatitis
* **• Rheumatoid arthritis**
* o Seen in 20%
* **• Pulmonary**
* o Seen in 90% of cystic fibrosis --\> Correlated with worse disease
* o See in 5% of ILD
* **• Gastrointestinal**
* ANCA associated with UC
* pANCA +ve, ASCA –ve = 57% sens 97% spec
* ASCA associated with Crohn’s
* pANCA –ve, ASCA +ve = 50% sens 97% spec
112
Does a rise in **ANCA titres predict disease flare in vasculitis**? Does **conversion from positivity to negativity** carry any meaning?
Rise in titres **not predictive of a flare**
Conversion to negativity **associated with, but not proof of, remission**
113
What is anti-CCP? What is rheumatoid factor (RF)? Do they predict anything? Are they specific or sensitive?
**Anti-CCP = IgG** antibodies against proteins containing citrulline
* Most **specific antibody for RA** (also predicts development of RA)
* Sens 65%, spec 95%
* mean onset *prior to clinical disease 4.8yrs*
* **Positivity predicts erosive disease and progressive joint damage**
* May be seen in **SLE, Sjogren's, Psoriatic Arthritis (PsA), tuberculosis**
**RF = IgM autoantibody against Fc portion of IgG, forming immune complexes**
* *- Less specific than anti-CCP*
* - Sens 60%, spec 88%; found in 15% of baseline population
* - Can act as a type 2 or 3 cryoglobulin
* **- Positivity associated with more severe joint disease and extra-articular manifestations**
* - Seen commonly in: Sjogren's, hep B/C, viral infection, PBC
**Other RA associations**
* Age
* CTD
* Sjogren’s 70%
* SLE 30%
* PM 10%
* Type 2 or 3 cryoglobulinaemia, as mentioned above
* PBC
* Chronic infections
* Lymphoma/leukaemia
114
What proportion of those with **rheumatoid arthritis (RA) are ANA positive**?
30-40%
115
What two factors are associated with the large majority of atraumatic cases of avascular necrosis?
How do they present?
**Glucocorticoids and ETOH abuse associated with \>80% of atraumatic cases**
* Risk goes up with dose in both
* Low risk in \<15-20mg/day of prednisolone
**~50% with sickle cell develop osteonecrosis by 35yrs**
**Presentation**
* Most late in the course
* Most commonly anterolateral femoral head but can affect anywhere
* Pain is most common: weightbearing/movement in most. Rest pain in 2/3, night pain in 1/3
116
What are the imaging findings in avascular necrosis?
**Xray**
* normal for months after process begins
* crescent sign is pathognomonic, representing subchondral collapse
* later stages show loss of sphericity and collapse
* *Radionucleotide has very poor sensitivity**
* *- doughnut sign =** increased turnover at the junction of dead and reactive bone
* *MRI is ~100% sensitive**
- surgery based on MRI alone can result in **overtreatment**
117
What are giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)? Go through their epidemiology and pathophysiology
**GCA = medium/large vessel vasculitis predominantly affecting the thoracic aorta and its branches**
* - most common vasculitis in those \>50yrs
* - very rare for it to involve intracranial vessels
**PMR =** inflammatory disorder characterised by **stiff/aching neck/shoulder/pelvic girdle**
* - most common inflammatory rheumatic disease in the elderly
**Epidemiology**
* Both affect \>50yr old F:M 3:1
* PMR 3-10x more common than GCA
* 20% with PMR have GCA features
* 50% with GCA have musculoskeletal PMR features
* Both associated with **HLA-DRB1\*04** in Northern Europeans
**Pathophysiology of GCA**
* hypothesised due to **dendritic activation by toll like receptors** (TLRs), resulting in chemokines recruiting **CD4s and macrophages**
* **TLRs are expressed variably** and so would account for the **'skip lesions'**
* **_transmural inflammation_** with **TH1 and TH17** specifically are greatly increased in GCA affected tissues
**Histology of GCA**
* - Muscular arteries with well developed elastic laminae and vasa vasorum
* - Classic feature **disruption of internal elastic lamina and intimal thickening, stays even with steroid treatment**
* **- 50% have giant cells** at **intima/media** junction
* - mainly **CD4 and macrophage infiltration**
* - VZV antigen present in GCA +ve much more frequently than controls (Neurology 2015)
Pathophysiology of **PMR is poorly understood**
* Histology shows synovial infiltration by macrophages and T-cells
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What are the clinical and investigation findings in giant cell arteritis (GCA)?
**Headache is temporal and resistant to analgesia**
Visual loss usually due to **anterior ischaemic optic neuritis** with a **chalky white disc.** May be posterior ischaemic optic neuritis which doesn't have white disc
**Jaw claudication quite specific**
**CVA risk factors**
* - age, IHD risk factors, lack of systemic manifestations, moderate inflammatory markers
* - any other iscahemic complication greatly increases risk
Clinical large vessel involvement t**ypically after 3-4yrs**
* - TAA 9%, AAA in 6.5%
* *Investigations**
- ESR \>40 in 90%
* *- IL-6 and BAFF correlate with ESR/CRP**
- CRP a superior marker of disease activity
- Temporal artery biopsy the gold standard, **_negative in 10-20%_**
- Significantly lower yield as duration on steroids increases: 78% +ve in \<2 weeks; 65% +ve in 2-4weeks; 40% +ve in \>4weeks
* *- U/S may show the halo sign: hypoechoic rim around the lumen**
* *- PET shows severity and extent** but doesn't look at the wall or lumen
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What are the **clinical and investigation findings in polymyalgia rheumatica (PMR)?** What do you need to differentiate it from?
**_Morning stiffness and aching are the hallmark_**
* - 100% in shoulders
* - 50-70% in neck/pelvis
* - bilateral, worse at night, worse with movement
**40% have consitutional symptoms**
* *25%** have peripheral arthritis
- asymmetric, non-erosive, self-limited, steroid responsive
* *12% develop remitting seronegative symmetrical synovitis with pitting oedema**
- distinct entitity that responds much more quickly to steroids than PMR and can be seen in many other conditions
**Investigations**
* - ESR \>40 in 90%
* - 1/3 have subclinical large vessel arteritis on PET
* - 4% with PMR and no GCA features have positive temporal artery biopsy
* - MRI and U/S are 90% specific and sensitive when looking for: bilateral subacromial, subdeltoid, trochanteric, or cervical bursitis
* - peri rather than intraarticular inflammation
**Can be hard to differentiate late onset rheumatoid arthritis or spondyloarthritis from PMR**
* +ve RF/CCP point to RA
* Erosions = RA
* Rapid and dramatic response to steroids point to PMR
* Anterior uveitis, HLA-B27, sacroiliitis point to spondyloarthritis
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What are the diagnostic critera for giant cell arteritis (GCA) and polymyalgia rheumatica (PMR)?
How are they treated?
**GCA (differentiation from other vasculitis rather than diagnostic tool): \>=3 of the below is sens 93.5%, spec 91.2%**
* \>50yrs onset
* New headache
* Temporal artery abnormality clinically
* ESR \>=50
* Abnormal artery biopsy
**GCA**
* **- 40-60mg prednisolone daily,** prevents **ischaemic events which are usually irreversible.** Pulse methylpred or higher dose oral if visual symptoms
* **- Aim to wean to 10-15mg by 3 months** and then discontinue by 6-24 months
* **- Aspirin** recommended based on retro data
* - MTX decreases relapse rate but not adverse events despite sparing steroid
* - Azathioprine can be used
* - TNFi doesn't work
* - Tocilizumab works very well but not data yet on whether it alters ischaemic events
**PMR**
* **- 15-20mg prednisolone daily** with slow wean over months
* - exquisitely rapid response
* - 50-70% improvement expected in 3-5 days, if not then question diagnosis
**Look out for steroid complications**
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Which subtype of giant cell arteritis (GCA) is associated with increased mortality?
GCA with thoracic aneurysm
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Go through the different picture on joint aspirations of various aetiologies.
What is the specificity and sensitivity of gram stain in septic arthritis?
**Gram stain**
* - Non-gonococcal sens 50-70%, spec high
* - Gonococcal sens \<10%, spec high
**Characteristics associated with septic effusion. Higher the WBC count more specific for a septic joint**
* - WBC \>25,000: sens 77%, spec 73%
* - WBC \>50,000: sens 62%, spec 92%
* - WBC \>100,000: sens 22%, spec 99%
* - PMN proportion \>=0.9: sens 73%, spec 79%
* - LDH \>250U/L: sens 100%, spec 51%
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With what are **anti-Ro/SS-A and anti-La/SS-B associated?**
* *Primarily found in Sjogren's**
- Both in 30-60%
- Ro only in 50-70% Sjogren's
- La rarely alone: seen in SLE or Sjogren's
**Ro only seen in 30% of SLE**
* **Ro** can cross the placenta and cause **neonatal lupus**
**Others**
* Coeliac, polymyositis (PM), autoimmune liver disease
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What is psoriatic arthritis (PsA)? What is its epidemiology, pathology and pathogenesis?
* *Inflammatory musculoskeletal disease with autoimmune and autoinflammatory features**
- usually in individuals with psoriasis
**Epidemiology**
* **~3% of white people have psoriasis**
* ~15% of those with psoriasis have psoriatic arthritis
* duration and severity of psoriasis increase development of PsA
* psoriasis directly associated with HLA-cw\*0602
* **HLA-B27 associated with psoriatic spondylitis**
* first degree relatives have higher risk of psoriasis, PsA, and other spondyloarthritides
* **30% with psoriasis have an affected first degree relative**
* 35-72% concordance in monozygotic twins for psoriasis, 10-30% for PsA
**Pathogenesis**
* Diffuse infiltration with T and B-cells, macrophages, NK cells
* Plasmacytoid dendritic cells play a key role in psoriasis, some evidence they participate in PsA
* **IL-17/23 are important, from TH17 T-cells**
* marked increase in osteoclastic precursors and upregulation of RANKL in synovium is consistent with extensive bone remodelling
**Pathology**
* **inflamed synovium like RA,** but with **less hyperplasia/cellularity and more tortuous vascular pattern**
* shows **_prominent enthesitis,_** unlike RA
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What are the clinical features of psoriatic arthritis (PsA)? The five general patterns?
* *In 60-70% psoriasis precedes joints**
- 15-20% appear within a year
- 15-20% arthritis before psoriasis
Typically occurs in **4th-5th decade**
**90% with PsA have nail changes,** 40% of psoriasis do
* - pitting, horizontal ridging, onycholysis, yellowing, dystrophic hyperkeratosis
**Hallmarks**
* **- dactylitis in \>30%**
* - **enthesitis** present in most but not always appreciable
* - finger shortening due to osteolysis is characteristic of PsA
* - back and neck pain/stiffness common
**_Patterns_**
* Oligoarthritis
* - ~30% have asymmetric oligoarthritis
* - usually a knee or other large joint with a few small joints
* Polyarthritis
* - 40% have symmetric polyarthritis
* - may be indistinguishable from RA in the joints involves
* - often has characteristic features to help differentiate
* Axial
* - isolated in 5%
* - may be indistinguishable from idiopathic ankylosing spondylitis (AS)
* - PsA more neck and less thoracolumbar involvement
* - AS doesn't get nail changes
* Isolated DIPJ arthropathy with nail disease
* - in 5%
* Arthritis mutilans in a small percentage
* - telescoping with gross destruction
* Extraarticular
* - ocular in 7-33%: conjunctivitis or uveitis
* - uveitis in PsA more often bilateral, chronic, and/or posterior
* - aortic insufficiency in \<4%, usually with longstanding disease
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