Rheumatology Flashcards
1
Q
What is the role of long term antibiotic therapy in reactive arthritis?
A
RCT 2010 - long term combination of doxycycline 100mg PO BD and rifampicin 300mg PO BD for 6 months in post chlamydial reactive arthritis was found to be useful.
2
Q
When should you treat scleroderma lung disease?
A
US scleroderma lung study showed that FVC <70% or HRCT extent >20% were more likely to respond to cyclophosphamide.
3
Q
How do you treat scleroderma skin disease?
A
Nothing really works.. most rheumatologists will start with methotrexate 15-25mg/week
d-Penicillamine can also be tried.
High dose steroids are not helpful and may increase risk of renal crisis.
4
Q
5 factors which predict severe disease in ankylosing spondylitis
A
- Juvenile onset
- Poor NSAID response
- Peripheral involvement - dactylitis, oligoarthritis
- Poor social support
- Smoking
5
Q
What is the role of hydroxychloroquine in SLE?
A
It is the backbone therapy. Everyone should be on it.
Effective for skin and joint disease, and reduces flare in chronic therapy.
6
Q
What is the significance of fatty deposition on MRI scan of spine in AS?
A
Presence of fatty deposition on MRI spine carries the highest risk of future syndesmophyte formation, even if inflammation is suppressed with TNF alpha inhibitors. (RR upto 3.3)
7
Q
What is the disease association of Anti-SRP?
A
Almost always seen in PM, not DM and it is mostly refractory to treatment.
SeRious Polymyiositis
8
Q
6 Causes of acute anterior uveitis
A
- Idiopathic
- Diseases associated with HLA-B27 (eg, ankylosing spondylitis, reactive arthritis, inflammatory bowel disease, psoriasis) may manifest as unilateral acute anterior uveitis; they have a high tendency to recur at some later time in the same eye or contralateral eye; 50% of HLA-B27–positive patients with acute anterior uveitis will develop an associated seronegative spondyloarthropathy; 25% of patients with HLA-B27–associated systemic illness will develop acute anterior uveitis
- Behçet’s disease
- Sarcoidosis
- Trauma
- Infections (herpes zoster, herpes simplex, CMV, syphilis, postoperative or metastatic endophthalmitis)
9
Q
Serum urate level aim for chronic tophaceous gout and for patients with no tophi?
A
Saturation point for urate is 0.42
In chronic tophaceous gout, aim is <0.30
For gout without tophi = <0.36
10
Q
What is the role of MRI in myositis?
A
To guide biopsy.
Not used for diagnosis/screening.
11
Q
Treatment of ILD in scleroderma
A
IV cyclophosphamide with prednisolone 20mg alternate days and azathioprine orally is current in fashion. However recent 2016 suggests that MMF is better tolerated and may be as effective.
12
Q
Autoantibody associations:
Anti-Ro
Anti-La
Anti-Sm
Anti-U1RNP
A
Ro: neonatal lupus, lymphopenia, photosensitivity, Sjogrens
La: Sjogrens, neonatal lupus
Sm: renal and CNS disease
U1RNP: myositis, raynauds
13
Q
5 most common microbia causes of reactive arthritis
A
- Chlamydia - 4% develop reactive arthritis
- Salmonella
- Yersinia/Shigella
- Campylobacter
- Clostridium
14
Q
Drugs which interacts with tocilizumab (IL-6 inhibitor)
A
CYP3A4 meds such as atorvastatin, CCBs, warfarin, cyclosporine.
Decreased IL-6 activity resulted in increased CYP3A4 activity and hence decreased exposures of CYP3A4 substrates
15
Q
Extraarticular features of RA (6 systems)
A
- Eyes - sicca syndrome, scleritis
- Skin - rheumatoid nodules (only in RF+)
- Vasculitis - ischaemic ulcers, digital gangrenes
- Neurologic - C spine cord compression, mononeuritis multiplex
- Lung - pleural effusions, nodules, ILD (basal predominance)
- Lymphoma - 2-3x increased risk
16
Q
How do you diagnose PAN?
A
Need to demonstrate skip lesions of varying chronological ages not corresponding to a single vascular supply.
Demonstrate focal, segmental pan-mural necrotising inflammation of medium sized arteries with predilection for bifurcations and branch points of muscular arteries.
Affects skin, kidneys, GIT and testes (causing orchitis and testicular artery ischaemia)
17
Q
Anti-Ku and Anti-PM-Scl
A
Seen in overlap myositis/systemic sclerosis
18
Q
What is the natural history of reactive arthritis?
A
70% - resolves in 6-12 months
25% - chronic relapse and remitting course
5% - destructive arthritis
Can consider DMARDs such as methotrexate and sulfasalazine in protracted course.
Short course of prednisone can also be considered.
19
Q
Management of lupus nephritis:
- Induction
- Maintenance
- Other adjunctive measure
A
Induction: Prednisone with MMF or IV/oral CYC.
IV CYC + IV methylpred for severe nephritis.
Maintenance: Pred + AZA/MMF (CYC not recommended for maintenance therapy)
Adjunctive measures:
- HCQ as a backbone therapy
- ACEI f proteinuria >0.5g/day
- Target BP <130/80
- Statins if LDL >2.6mmol?l
20
Q
Mechanism of action of Tofacitinib?
Efficacy?
SE?
A
Novel oral JAK 1/3 inhibitor.
Similar efficacy to adalimumab in MTX resistant RA.
Side effects - raised LFTs, increased LDL and HDL, neutropenia. (similar to tocilizumab)
21
Q
Disease association with anti-Mi2?
A
Seen in PM/DM.
Shawl rash.
Treatment responsive.
22
Q
Palindromic rheumatism - presentation, natural history and treatment
A
Intermittent episodes of arthritis and periarthritis, sudden onset, peaks within hours lasting 24-48 hours. Can involve single or multiple joints. Affects upto 1 in 8 RA patients.
Patients presenting with PR initially - 2/3 eventually progress to RA especially if seropositive to RF/ACPA.
Remaining 1/3 - 50% will undergo remission, 50% will have ongoing palindromic rheumatism.
First line treatment is with hydroxychloroquine - decreases progression to RA. If seropositive, usually started on methotrexate.
23
Q
What is an important differential diagnosis of sacroilitis on XR?
A
Osteitis Condensans Ilii OCI
Occurs in multiparous women, bilateral SI involvement
Triangular area of dense sclerosis on iliac side but does not involve the SIJ itself.
CT is useful in differentiating it from sacroilitis.
Carries a benign prognosis and resolves spontaneously.
24
Q
Investigation and management of familial Mediterranean fever syndrome
A
Clinical diagnosis - genetic testing can be helpful but its absence or presence does not exclude nor establish the diagnosis. Given high genetic frequency with low penetrance amongst some ethnic backgrounds (Ashkenazi Jews, Armenians), clinical correlation is required.
Look for proteinuria - if present, need to suspect renal amyloidosis.
Colchicine is important first line treatment
If failed on colchicine - anakinra (IL-1 inhibitor), etanercept (decoy TNF alpha receptor)
25
What features distinguishes raynauds phenomenon seen in Systemic Sclerosis from Primary Raynauds?
Primary Raynauds - occurs bilaterally.
In Systemic sclerosis - asymmetric involvement, associated with ulcers, digital pitting, calcinosis, and abnormal capillary nailfold loops
26
What is the role of baseline HRCT in scleroderma?
Extent of disease on baseline HRCT is a useful prognostic marker and helps to identify patients who may need more aggressive therapy.
Significant survival difference is present between limited lung <20% vs extensive lung >20% and also FVC >70% vs FVC <70%.
There is only little change in extent of disease on serial HRCT therefore little value in serial HRCT once diagnosis of ILD is made. Serial PFTs are more useful.
27
Non-pharmacological and pharmacological management of fibromyalgia
Non pharmacological:
1. Graded aerobic exercise
2. CBT
3. Massages, acupuncture etc..
4. Address social issues
Pharmacological:
1. Analgesics - paracetamol, tramadol, NSAIDs
2. TCAs - reduce pain, fatigue and improve sleep
3. Dual 5HT/NA reuptake inhibitor such as duloxetine - improves pain, fatigue and function
4. Pregabalin/gabapentin - improves pain, sleep, fatigue and general well being
28
Frequency of ANA Positivity in following conditions:
* Mixed connective tissue disease:
* Drug-induced lupus erythematosus:
* Systemic lupus erythematosus:
* Sjögren syndrome:
* Scleroderma:
* Polymyositis-dermatomyositis:
* Rheumatoid arthritis:
* Normal:
* Mixed connective tissue disease: 100%
* Drug-induced lupus erythematosus: 100%
* Systemic lupus erythematosus: 95%-100%
* Sjögren syndrome: 80%
* Scleroderma: 60%-95%
* Polymyositis-dermatomyositis: 49%-74%
* Rheumatoid arthritis: 40%-60%
* Normal: Less than 4%
29
What malignancy is associated with Sjogrens syndrome?
Lymphoma - 44x higher than incidence in an age matched healthy population.
Most common type is NHL. Others include follicular, lymphoplasmacytoid and DLBCL, MALT.
30
XR changes associated with OA
1. Subchondral cyst
| 2. Bony sclerosis
31
Compare ACPA to RF.
Similar sensitivity (80%) but greater specificity (95%)
Better predictor of erosive disease.
Not associated with extraarticular features unlike RF
Detectable PRIOR to onset of clinical disease (mean of 4.8 years)
32
Association with HLA-DRB1?
Associated with seropositive RA positive for RF/ACPA
33
Role of colour doppler USS of cranial arteries
Does not replace biopsy, but can be useful in:
1. Guide for biopsy site
2. Unable to biopsy
3. Past negative biopsy with flares
Looking for hypoehoic wall thickening caused by oedema (sn/sp 75%)
34
What is the overall sensitivity of temporal artery biopsy in GCA?
It is about 40%
This is due to skip lesions and the fact that GCA is a disease of entire cranial artery system, not just temporal arteries.
At least 3 cm of temporal artery is required to be diagnostic. Positive for at least 1week.
35
Poor prognostic markers in scleroderma
Younger age
African descent
Rapid progression of skin symptoms
Greater extent of skin involvement
Anemia
Elevated erythrocyte sedimentation rate (ESR)
Pulmonary, renal, and cardiac involvement
36
Bowel involvements in scleroderma
1. Small bowel dysmotility leading to bacterial overgrowth, causing malabsorption and diarrhoea. Cyclical antibiotics can be helpful.
2. Constipation due to large bowel dysmotility, faecal incontinence. Treat with biofeedback training.
3. Oesophageal reflux in 90%. PPIs can decrease incidence of oesophageal stricture.
4. Telangiectasia in stomach and other GIT can cause iron deficiency anaemia.
37
Association between DM/PM with malignancy
Incidence is about 15% with DM, 9% with PM. Can pre-date the diagnosis of myositis or occurs within 2 years following the diagnosis. All types of malignancies are seen.
Minimum investigations - FOB, mammography, pelvic USS in women, CT C/A/P
38
Clinical features of familial mediterranean fever
Hereditary autoinflammatory disease
Recurrent and short durations of fever lasting 1-3 days
Serositis - peritonitis, pleuritis, arthritis, myalgia etc
Chronic inflammation leads to secondary amyloidosis (serum amyloid A protein)
Treatment with colchicine which prevents development of amyloidosis and is good for treating fevers, peritonitis and pleuritis.
39
Anti-SRP
Antibody against polypeptide complex transporting proteins to ER. Specific for necrotising autoimmune myositis.
40
Risk factors for development of PHTN in scleroderma
1. Disease duration - around 12-14 years
2. DLCO <50%
3. Diffuse scleroderma may have higher incidence - evidences are conflicting
Suspect PHTN when DLCO <50% with minimal fibrosis in HRCT. High mortality if not treated (untreated 2 year survival is <50%)
41
Onset of psoriasis in relation to psoriatic arthritis?
70% - before
15% - concurrent
15% - after onset of arthritis
42
4 Differential diagnosis of dactylitis
1. Psoriartic arthritis
2. Reactive arthritis
3. Gout
4. Sarcoidosis
Infrequently seen in AS
43
A must thing to remember in use of Tocilizumab?
It is a potent IL-6 inhibitor therefore CRP will be normal even in severe infection.
44
Mechanism of action of leflunomide
Indication?
SE?
Inhibits dihydro-orotate dehydrogenase which is a key enzyme in de novo pyrimidine synthesis. Pyrimidine is required for T cell proliferation and activation.
Most comonly used if MTX is not tolerated or not responding adequately to MTX.
Notable SE: LFT derangements, diarrhoea, peripheral neuropathy, ILD
45
5 poor prognostic markers in RA
1. Radiographic erosions at baseline (strongest marker)
2. RF/ACPA titre
3. Smoking
4. Chronic systemic inflammation
5. HLA DRB1*04 homozygosity
46
Name the predictors for radiographic progression in non-radiographic axSpA in:
1. SIJ (3 factors)
2. Spine (4 factors)
SIJ
1. Baseline radiographic sacroilitis
2. Baseline inflammatory changes on MRI
3. Elevated CRP (elevated <50%)
Spine
1. Baseline syndesmophytes
2. Elevated CRP
3. Smoking
4. Male sex
47
What is the advantage of Secukinumab (IL17 inhibitor) over TNF alpha inhibitor?
Requires fewer injections
| Absent of TB/MS flare risk
48
Action of Tocilizumab?
IL-6 inhibitor. Used in RA, systemic juvenile idiopathic arthritis.
49
What is the role of Rituximab in ANCA associated vasculitis?
Rituximab induction AND maintenance is superior to Cyclophosphamide and azathioprine.
However funding is the issue...
Rituximab can be used if intolerant of cyclophosphamide for induction therapy.
It is NOT funded for maintenance therapy.
50
What is the risk of using systemic steroids in psoriasis?
Although systemic steroids may lead to rapid clearing of psoriasis, these agents should not be used in the event that if they are abruptly discontinued, a limited plaque psoriasis may blossom into potentially life-threatening generalized pustular or erythrodermic psoriasis.
51
What are the 4 predictors of longer course in reactive arthritis?
HLA B27
Male
Post chlamydial infection
Extraarticular features
52
Treatment of pulmonary fibrosis in scleroderma?
Use IV/PO cyclophosphamide
53
Environmental toxins associated with scleroderma
1. Vinyl chloride
2. Toxic oil
3. Silica miners
54
Describe the action and indication of Belimumab.
Anti-BAFF (BLys) monoclonal antibody.
Used in SLE (effects are modest)
BLys transgenic mouse gets Sjogrens and lupus features.
Inhibition of BLys leads to limited B cell survival and activation.
55
What are the predictors of severe lung disease in scleroderma?
1. Black men
2. Early decline in lung function.
Scl-70 and extent of skin diseases are associated with increased risk of lung disease, but are not predictors of severity of lung disease itself.
56
Felty's syndrome
Hallmark features are - persistent neutropenia, thrombocytopenia, splenomegaly and RA.
BMB will show normal myelopoiesis with maturation arrest.
Increased risk of lymphoproliferative disorder.
Management is with aggressive immunosuppression with GCSF/GM-CSF support
57
4 risk factors for renal disease in scleroderma
1. Recent onset diffuse disease
2. Truncal skin involvement
3. High dose steroids >15 mg/day
4. RNA polymerase Ab positive
58
what are the features of psoriatic spondyloarthritis?
Occurs in 20% of patients with PsA
Syndesmophytes are less common, however when they do occur they are asymmetrical and appear bulkier
C spine involvement in 75%
59
Limited scleroderma
Long history of Raynauds before development of limited scleroderma. Max skin involvement are hands +/- forearms. Mild slowly progressive skin involvement. Lung disease in 30%, PTHN in 10%, GIT involvement is common but cardiac/renal involvement is rare.
60
Arterial involvements in GCA
1. Aorta and its major branches in 25%
- Aortic dissection and rupture as a late complication
2. Coronary arteries
3. Can also cause limb claudications and ischaemia
61
RA drugs which are considered safe in pregnancy
Prednisone (but not dexamethasone as it crosses placenta)
NSAIDS - as long as it is discontinued 6-8 weeks prior to pregnancy (causes premature closure of ductus arteriosus, and may increase miscarriage)
HCQ, sulfasalazine, azathioprine are safe.
TNF alpha inhibitors are low risk in pregnancy - should be stopped 30-32 weeks to prevent increased passage of these drugs across the placenta.
Contraindicated - MTX, LEF, cyclophosphamide.
62
Antibodies positive in scleroderma and their clinical implications:
```
ANA
Topisomerase I (anti-scl-70)
Anti-centromere antibody
Anti-RNA polymerase I and III
Anti-ThRNP
Anti-PM-Scl
```
Antinuclear antibodies are present in about 90%-95% of affected patients, usually with a speckled or centromere pattern. A nucleolar pattern, although less common, is more specific for systemic sclerosis.
Topoisomerase I antibodies (also known as Scl-70) are present in approximately 30% of patients with diffuse disease (absent in limited disease). Patients harboring Scl-70 antibodies are at higher risk of developing pulmonary parenchymal involvement, in contrast to patients harboring anti-centromere antibodies.
Anticentromere antibodies are present in about 45%-50% of patients with limited disease. They are rare in patients with diffuse disease.
Anti-RNA polymerase I and III antibodies are present in 15%-20% of patients with diffuse disease and correlate with rapid cutaneous involvement and high frequency of renal crisis.
Anti-ThRNP is present mostly in limited disease and is associated with more extensive visceral disease.
Anti-PM-Scl is present in patients with overlap connective tissue disease or with mixed connective tissue disease (MCTD) and is associated with myositis and renal involvement.
63
What is the role of azathioprine in SLE?
Good for nearly everything.
Safe in pregnancy.
Used in lupus nephritis other than class 4
Steroid sparing.
64
Side effects of sulfasalazine
1. Headache
2. Rash
3. GI upset
4. Idiosyncratic reactions (skin reactions, hepatitis, pneumonitis, agranulocytosis, aplsatic anaemia, haemolytic anaemia)
65
How would you treat class III/IV GN in SLE?
Trials have shown following:
Lower dose IV cyclophosphamide followed by azathioprine maintenance is as effective as long term high dose cyclophosphamide.
MMF is equivalent/superior to IV cyclophosphamide and it is less toxic therefore MMF is FIRST LINE.
MMF is also superior to azathioprine in terms of maintenance.
However IV cyclophosphamide is preferred if severe class 4 disease with significant renal impairment or anuria.
Rituximab has NOT been shown to be effective in trials, but they mainly recruited mild-mod severity diseaes.
In conclusion:
1. Use MMF for induction AND maintenance.
2. If severe disease, use IV cyclophosphamide then transition to MMF.
3. If contraindication to MMF, use IV cyclophosphamide then azathioprine
4. If all else fails, try rituximab.
66
Histopathological features of GCA
1. Panarteritis with CD4+ T cell, histiocytes and plasma cells infiltration
2. Giant cell granulomas
3. Disruption of internal elastic lamina
4. Patchy and skip lesions
5. Thrombosis/stenosis the vessel with inflammatory wall thickening
67
Diffuse scleroderma
Recent onset Raynaud's phenomenon and rapid progression of skin disease. 10% renal crisis in first 4 years especially in truncal skin disease.
Lung disease in 30%. GIT/cardiac involvement are common.
Skin involvement does improve over time!
68
Is OCP safe in SLE?
Yes. NEJM trials have shown no increase in disease flares as long as disease is stable.
Avoid OCP in active disease.
IUDs and Depot progesterone are fine in all lupus scenarios.
However if APLS present, avoid oestrogen containing OCP even if anticoagulated. Progestogen only pill is OK.
69
Positive on indirect immunofluorescence for P ANCA, but negative on ELISA. What does this mean?
Antibodies to other azurophilic granules can cause this pattern - BPI, cathepsin G and lactoferrin.
70
Describe methotrexate-induced nodulosis in RA
Development of multiple rheumatoid nodules after introduction of DMARD such as methotrexate. Roughly 10% will develop accelerated nodulosis.
Nodules on histology are characterized by circumscribed lesions with an outer fibrous shell, inner area of central necrosis and palisade of macrophages and fibroblasts between the two.
DRB1*0401 allele predisposes to the condition.
71
XR changes associated with RA
1. Soft tissue swelling
2. Periarticular osteoporosis
3. Marginal osteoporosis
72
What is the association between vitamin D and SLE?
Vitamin D deficiency is common in SLE.
Also vitamin D deficiency is associated with increased disease activity in SLE.
Given high use of prednisone in SLE, screen and treat for vitamin deficiency, and replace vit D especially if using prednisone.
73
How does scleroderma renal crisis present?
Treatment?
1. Malignant hypertension
2. MAHA
3. Mild proteinuria
Treat with ACEI. Bring BP down gently.
74
Pathogenesis of fibromyalgia
Amplification of pain processing with alteration of higher processing due to reduced central 5HT/NA levels which increases sensitivity of nociceptive stimulis.
This is the reason why TCAs, dual 5HT/NA reuptake inhibitors are used.
75
Action of Anakinra?
recombinant form of human IL-1 receptor antagonist, which neutralizes IL-1. Used in treatment of RA.
76
5 Non-RA causes of increased rheumatoid factor
1. Age
2. Chronic infection (eg Hep C)
3. Malignancy
4. CTD eg SLE, sjogrens syndrome
5. Cryoglobulinaemia
77
Why is there an age cut off of <40 for classification of inflammatory back pain in AS?
Studies have shown that majority of the patients with AS would have developed symptoms before age of 40.
78
What is the average age of CAD in SLE?
Peak prevalence in age group 45-55.
| Therefore managing vascular risk factors are important.
79
What do you use for ILD in Systemic Sclerosis?
First line therapy is now MMF and prednisone for 24 months - associated with less SE and less deaths compared to cyclophosphamide.
80
What are the secondary causes of PAN?
Hepatitis B - most common
Others: GAS, Hep C, HTLV-1, CMV, EBV, Parvovirus B19.
81
3 paradoxical effects associated with TNF alpha inhibtiors
1. New onset psoriasis - secondary to cutaneous INF alpha overexpression leading to more efficient triggering ofs kin lesions by trauma or infection
2. Increased frequency of flares of uveitis especially for etanercept
3. Variable incidence of IBD flare: lowest for infliximab
82
Antinuclear antibodies in scleroderma and their disease associations:
```
centromere pattern
Scl-70
RNA polymerase I and III
U1-RNP
Th/To
PM-Scl
```
centromere pattern - decreased risk of severe lung disease
Scl-70 - predictive of ILD
RNA polymerase I and III - associated with renal disease and severe skin involvement
U1-RNP - overlap features
Th/To - poor outcomes in LcSSc
PM-Scl - myositis overlap
83
Clinical features of PMR
Mainly musculoskeletal symptoms including pain/stiffness of shoulder region and neck, shoulder and pelvic girdles and proximal muscles. Usually bilateral and symmetric. Muscle atrophy occurs due to disuse from pain.
Also tenosynovitis and synovitis of proximal joints, but can also get mild inflammatory synovitis and effusions of knees and wrists.
Peripheral joint involvements are not usual! Should think about a PMR mimic eg RA or inflammatory OA.
84
Behcet's disease
Triad of aphthous ulcers, genital ulcers and uveitis.
Multisystemic disease that includes involvement of the mucocutaneous, ocular, cardiovascular, renal, gastrointestinal, pulmonary, urologic, and central nervous systems, as well as the joints, blood vessels, and lungs
Diagnosis is clinical - no lab test exists.
85
What is the classical triad for disseminated gonococcal infection?
1. Polyarthralgia
2. Dermatitis
3. Tenosynovitis (inflammation of tendon) - usually florid
Look for purulent vesicles
Most cases occur within 1 week of onset of menses
86
What are the 2 most specific arthritic features of psoriatic arthritis?
1. DIPJ involvement
| 2. Arthritis mutilans
87
What is the role of ERAP1 in pathogenesis of ankylosing spondylitis?
ErAP1 is involved in trimming of peptides to the optimal length for MHC class 1 presentation. It also cleaves cell surface receptors for the proinflammatory cytokines IL1, 6 and TNF alpha thereby downregulating their signalling.
Abnormalitiesin ERAP1 or 2 may reslut in export of abnormal MHC peptide copmlex to the cell surface causing autoimmunity.
88
How does apremilast work in PsA?
PDE4 enzyme inhibitors, modulating pro-inflammatory mediators at the mRNA expression.
Used in psoriatic arthritis.
Has advantages in oral regimen, no monitoring required, no infection/LFT/malignancy risk, effective in dactylitis and enthesitis.
Disadvantageous in that it only has modest effect compared to TNFi, not effective for spinal disease.
89
Definition of clinical remission of lupus nephritis
What predicts the likelihood of clinical relapse?
Plasma creatinine <124 umol/L, protein excretion <330mg/day, inactive sediments.
Clinical remission at 6 months is important for prognosis - 10 year renal survival is 94% in those who achieve remission vs 31% in those who do not.
Rising dsDNA - 75% likelihood of clinical relapse.
90
What is Lofgren syndrome?
Management?
Acute sarcoidosis characterized by:
1. Bilateral hilar lymphadenopathy
2. Erythema nodosum
3. Fevers
4. Polyarthralgia
Manage with NSAIDs
91
What is the risk of using prednisone >15mg in systemic sclerosis?
Risk of scleroderma renal crisis increased
92
Is HRT safe in SLE?
Yes. It does increase minor flare but no significant increase in major flares.
93
When do you consider bDMARDs in RA?
Consider bDMARDs after 6 months of 2 or more traditional DMARDs.
94
Anti-Jo1
AKA, anti-tRNA antibodies. Seen in antisynthetase syndrome characterized by ILD, fevers, arthritis, myositis and raynauds phenomena with mechanics hands. Poor prognosis with 70% 5 year survival (mainly due to lung disease)
95
Inclusion body myositis
Occurs in older males. Insidious onset of muscle weakness typically involving asymmetric distal areas. Only has a mild elevation in CK. EMG will show neuropathic and myopathic features. Biopsy is needed to confirm - shows endomysial inflammation, rimmed vacuoles, intracellular amyloid deposits or tubulofilaments.
96
Anti-Ro/SSA and Anti-La/SSB
A positive anti-Ro result is indicated by a speckled appearance under immunofluorescence with ultraviolet light.
Anti-Ro levels may be elevated in the following conditions: [1]
Sjögren syndrome: 60%-70% of cases
Systemic lupus erythematosus (SLE): 25% of cases
Both anti-Ro/SSA and anti-La/SSB are usually absent in secondary Sjögren syndrome
When anti-Ro/SSA levels are elevated in SLE, it is often in antinuclear antibody (ANA)–negative lupus
97
4 major criteria in 2010 RA diagnostic criteria
1. Joint involvement
2. Serology to RF/ACPA
3. Acute phase reactant
4. Duration of symptoms - <6 weeks or >6 weeks
98
Pathogenesis of familial Mediterranean fever syndrome?
Nonsense or missense mutations in the MEFV (Mediterranean fever) gene resulting in mutation in pyrin which is involved in inflammasome assemblage
Uninhibited pyrin activity results in uncontrolled production of interleukin-1 (IL-1), leading to episodes of inflammation (with accompanying fever) in the peritoneum, pleura, and joints; persistent subclinical inflammation is also common
Chronic inflammation also predisposes to amyloidisis
99
What is the role of tocilizumab (anti-IL6 inhibitor) in giant cell arteritis?
Extraordinarily effective!
Tocilizumab + prednisone was much better compared to placebo and prednisone alone. Significantly reduced relapse rates.
100
Describe the association between osteoporosis and AS
At least 50% have osteopenia, mainly in thoracic spine.
Vertebral fracture risk is increased 6-8 folds but not fracture of limb bones.
Contributing factors include decreased mobility, inflammation, spinal rigidity, kyphosis.
101
Describe pulmonary manifestations in RA.
Risk factors?
Pleural involvement is most frequent, but can also involve airway disease, nodules and parenchymal infiltration with NSIP or UIP pattern.
Male gender, high RF/anti-CCP
102
How do you treat renal crisis in scleroderma?
Captopril. ACEI class effect. Start at 6.25mg and 6 hourly doubling until controlled.
103
Rheumatoid factor - associations in RA
1. More severe joint involvement and radiographic progression
2. Extraarticular features
3. Increased likelihood of response to B cell depletion (rituximab)
4. Titre may decrease with effective treatment, esp bDMARDs.
104
Haematological manifestations of lupus
1. Anaemia
2. Coombs positive AIHA
3. Cytopenias - thrombocytopenia, leucopenia, lymphopenia
4. TTP/ITP
5. Splenomegaly in 10-45%
6. Lymphadenopathy in 40%
105
2 other differential diagnosis of anterior uveitis
1. Behcet's disease
| 2. Sarcoidosis
106
Describe an important differential diagnosis to consider with spine XR showing syndesmophytes.
DISH (diffuse idiopathic skeletal hyperostosis)
Involves ossification of the anterior longitudinal ligaments. Prevalence of 8-10%
Associated with male patients >50 age
20% have Type 2 DM
NOT HLA B27 associated
Simple treatment with analgesics, NSAIDs.
107
What are the mandatory features on ACR-EULAR 2012 classification criteria for PMR?
1. Age >50
2. Aching of both shoulders
3. Abnormal CRP and/or ESR.
108
What is an important side effect of hydroxychloroquine?
How would you monitor it?
```
Ocular toxicity (maculopathy)
Risk factor is cumulative dose >6.5mg/kg/day usually after 5 years of therapy.
Patients should have regular retinal/macular screening within 12 months of initiation, then 5 years thereafer
```
109
5 associations between Anti-Ro Ab for SLE and Sjogrens syndrome?
1. Neonatal lupus
2. Congenital heart block
3. Photosensitivity in lupus
4. Cutaneous lupus
5. ILD
110
Why are PMR/GCA so sensitive to steroids?
Pathogenesis involves IL-17 axis and Th17 cells which are involved in acute phase response.
111
What is the ethnic distribution of SLE?
Increased prevalence amongst African Americans, Hispanics and Asians.
Asians have severe disease with increased renal disease and increased autoantibodies.
112
Management of DM/PM?
Evidence free zone.
Usually start off with prednisone 1-2mg/kg/day then taper after 1-2 months. Steroid sparing therapy includes azathioprine, MTX, cyclophosphamide, MMF in resistant diseases.
113
XR changes of gout
Punched out appearance with sclerotic margins and overhanging edges.
Juxta-articular osteoporosis absent.
Joint spaces well preserved until very late in the disease process.
114
Options in treatment of acute gout
1. NSAIDS
2. Colchicine
3. Systemic corticosteroids
4. Intraarticular corticosteroids
5. Canakinumab (IL-1b) or IL-1 inhibitors
115
Drugs which can increase colchicine toxicity
1. Amiodarone
2. Cyclosporine
3. Digoxin
4. Anti-fungal agents
5. Diltiazem/verapamil
6. Statins
116
Mechanism of action of colchicine
Microtubule inhibitor. Affects neutrophil function.
Side effects include diarrhoea and vomiting in the short term
long term - neuromyopathy especially in renal impairment (lower limb muscle weakness, ascending paraesthesia, absent reflexes)
117
Uricosuric agents in urate lowering therapy
Probenecid, benzbromarone.
Requires normal renal function, alkalinize urine, good urine volume. Contraindicated if history of renal calculi..
Probenecid - effect is blocked by aspirin!
118
Significance of HLA-B*5801
Risk of SJS with carbamazepine and allopurinol
119
Mechanism of action of allopurinol and febuxostat
Blocks action of xanthine oxidase, which is involved in conversion of hypoxanthine to xanthine, and xanthine to uric acid.
Febuxostat is a non-purine analogue inhibitor of xanthine oxidase. It is metabolized by the liver, therefore no dose reduction required in renal impairment.
120
When to consider urate lowering therapy in gout?
Hyperuricaemia AND:
1. Gouty arthritis
2. Tophi
3. Erosions on XR
4. More than 2 attacks a year
5. urate nephropathy or renal insufficiency or urate calculi
121
Pathogenesis of gout
Either due to increased production (10%) or reduced excretion (90%) in which causes can be genetic or acquired.
122
What sources contribute to the human purine pool?
| How is urate excreted?
Diet 30%, endogenous purine synthesis 70%.
Obesity increases endogenous purine synthesis.
3 forms of excretion
1. Renal excretion (70%)
2. GI excretion
3. Tissue deposition, when other methods are saturated
123
Name 6 clinically important risk factors for gout
1. Older males
2. Hyperuricemia - risk increases with increasing level
3. Obesity - decreases excretion of urate
4. Hypertension - as above
5. Hyperlipidaemia - as above
6. CKD
124
4 factors which stimulate crystals formation
1. Sudden increase/decrease in urate concentration
2. Decreasing temperature (cold reduces solubility)
3. Decreased pH of plasma
4. Osteoarthritis - enhances crystal formation
125
How can gout present in the elderly?
Atypical presentations are more common, with greater polyarticular involvement, women affected more than men, increased pattern of small joint involvement, early tophi formation often noted with first attack.
126
Mechanism of action of colchicine
Side effects?
Microtubule inhibitor - affects neutrophil function.
Useful in acute situation.
SE: diarrhoea, vomiting, neuromyopathy especially in renal failure (presents with muscle weakness of lower limbs, ascending paraesthesia, absent reflexes, EMG/ACS will show mild axonopathy)
127
Management of tophaceous gout
1. Symptom control - first line with colchicine/NSAIDs or second line with prednisone upto 6 months until target urate is reached
2. Lower urate level to target (ONLY AFER ASYMPTOMATIC for 2-4 weeks)
- Uricosuric agents - probenecid
- Xanthine oxidase inhibitor - allopurinol
- Non-purine analogue inhibitor of xanthine oxidase - febuxostat
128
What blocks the effect of probenecid?
Aspirin.
129
Advantage of febuxostat
Hepatic metabolism, therefore no dose reduction required if renal impairment.
130
When should you consider urate lowering therapy?
Hyperuricaemia with following:
1. Acute gouty arthritis
2. Tophis
3. Urate calculi
4. Urate nephropathy OR renal insufficiency
5. Erosions on Xray
131
3 medications associated with increased urate clearance
Fenofibrate - uricosuric
| Losartan and amlodipine - increase urate clearance
132
How does basic calcium phosphate hydroxyapatite arthropathy present?
What is Milwaukee shoulder?
Most often presents with tendinitis, bursitis, periarthritis involving shoulder, rotator cuff, hips, knees, elbows, wrists and ankles.
Spontaneous or associated with mild trauma only.
Milwaukee shoulder - large joint destructive arthropathy involving BCP crystals. In elderly female patients with shoulder pain, initially unilateral but progresses to involve both shoulders. Night pain and use related. Blood effusions on aspirate.
133
Management of GCA
Pulse IV methylprednisolone if visual symptoms, or PO prednisone if no visual symptoms (1mg/kg/OD)
Slow taper once symptoms are controlled - gradual reduction once 10mg/day, reduce by 1mg per month.
Rapid reduction can lead to relapse.
Usually on steroids for 2 years.
May need steroid sparing therapy eg MTX.
Other things to consider:
1. CXR and inflammatory markers every 2 years
2. Bone protection
3. PJP prophylaxis
134
Management of ankylosing spondylitis
1. NSAID and physiotherapy - prevents radiographic progression and good for axial disease
2. Sulfasalazine for peripheral arthritis
3. TNF alpha inhibitors are good for everything except prevent xray progression - axial disease, peripheral arthritis, enthesitis, extraarticular features.
Enthesitis only responds to TNF alpha inhibitors.
135
Management of psoriatic arthritis
1. NSAIDS and physiotherapy are useful for axial manifestations, otherwise NSAIDs provide symptom relief
2. Injected steroids - useful for peripheral arthritis anad may be for dactylitis/enthesitis
3. DMARDS - including MTX, leflunomide, sulfasalazine, for peripheral arthritis
4. TNF alpha inhibitor - good for pretty much for everything
New and emerging treatments - ustekinumab, apremilast, secukinumab
136
SLICC criteria for SLE
Divided into clinical criteria and immunologic criteria
Needs to meet 4 or more criteria, with at least 1 clinical and 1 immunlological.
OR, biopsy proven lupus nephritis with positive ANA or Anti-dsDNA.
Malar rash
Discoid rash
Serositis
Oral/nasal ulcers - PAINLESS
Arthritis/arthralgia, Alopecia (often occurs post flare)
Photosensitivity
Blood - leukopenia, lymphopenia, thrombocytopenia
Renal - proteinuria 0.5g/24hrs or RBC casts
ANA
Immunologic - dsDNA, anti-sm, APLS, low complements, positive DAT
Neurological - seizures, mononeuritis, myelitis, cranial neuropathy etc
137
Efficacy of hydroxychloroquine in SLE
Good for pretty much everything -
1. Reduces flares
2. Reduces organ damage
3. Reduces lipids
4. Reduces thrombosis
5. Triples response to MMF in lupus nephritis
6. Improves survival
138
Anti-Ro associations from greatest to least
1. Subacute cutaneous lupus - 74%
2. Sjogrens - 59%
3. SLE 32%
4. RA 15%
5. Systemic sclerosis 21%
6. Neonatal lupus - only <5% of mothers
139
In what condition does anti-ribosomal P protein antibodies occur?
Specific to SLE.
140
Which genetic factor confers the highest risk for SLE?
Homozygous deficiency of C1q
| Genetic factor that confers the highest hazard ratio (5 to 25) - deficiency of the complement components of C1q
141
Raynauds phenomenon and eventual progression to scleroderma
About 13% of patients initially diagnosed as primary Raynaud's are subsequently diagnosed later as having secondary Raynaud's (associated with connective tissue disorder). An abnormal nailfold capillary pattern was the best predictor of an eventual disease transition. A positive ANA screening test raises the possibility of an underlying autoimmune disease, particularly SLE or Scleroderma (remember that ANA is not specific, especially at low titres). The presence of anticentromere or anti-topoisomerase (Scl-70) antibodies predict the presence of Scleroderma.
142
What is the difference between 1982 SLE criteria and SLICC criteria?
New SLICC criteria is more sensitive (97% vs 83%)
| Old criteria was more specific (96% vs 84% SLICC )
143
Risk factors for scleroderma renal disease
1. Recent onset diffuse disease
2. Truncal skin involvement
3. High dose steroids >15mg/day
4. Scl70 negative
5. RNA polymerase 1 and 3 positive
144
How does abatacept work in RA?
Abatacept is a fusion protein composed of the Fc region of the immunoglobulin IgG1 fused to the extracellular domain of CTLA-4.
In order for a T cell to be activated and produce an immune response, an antigen presenting cell must present two signals to the T cell. One of those signals is the major histocompatibility complex (MHC), combined with the antigen, and the other signal is the CD80 or CD86 molecule (also known as B7-1 and B7-2).
Abatacept binds to the CD80 and CD86 molecule, and prevents the second signal from activating the T cell.
145
5 major side effects of TNF alpha inhibitors
1. Reactivation of TB
2. Infection
3. Demyelinating disease
4. Cardiac failure
5. Autoimmunity - positive ANA in 11%, SLE in 2-5%
146
How effective is tocilizumab monotherapy in RA?
Effective as TNFi and MTX combination.
