Rheumatology Flashcards
What are the typical ages of patients affected with giant cell arteritis?
Primarily affects people aged >50
Peaks at around age 80
Which arteries are typically affected by GCA? Name 5 arteries/groups of arteries.
External carotid branches (e.g. temporal and occipital arteries)
Ophthalmic
Vertebral
Distal subclavian and axillary arteries
Thoracic aorta
What is the pathogenesis of GCA?
Antigenic stimulation via danger pattern recognition on vessel-specific Toll-like receptors on vascular dendritic cells in artery adventitia
CD83+ activated vascular dendritic cells produce T cell-attracting chemokines (CCL19 and CCL21) drawing T cells into the media
Peripheral blood monocytes differentiate into macrophages in vessel wall and produce IL-6 and IL-1B, as well as IFy, CXCL9, 10 and 11, PDGF, FGF and VEGF
IL-6 induces T cells to differentiate into Th17 cells
Vasc smooth muscle cells express NOTCH ligands, which interact with NOTCH receptors on T cells and amplify inflammatory response, switching to synthetic myofibroblasts that proliferate in intima, narrowing vessel lumen
What are the 4 different clinical patterns of GCA?
Isolated cranial GCA (headache, jaw claudication, scalp tenderness) - most cases
Symptomatic LVV (claudication, pulseless limb) with or without cranial signs
Isolated fever or inflammatory response
Isolated PMR with vasculitis on imaging
Do GCA patients with LVV require higher or lower doses of steroids?
Higher
Typically tend to be younger, less likely to present with headaches, lower risk of visual loss
However, higher risk of relapse
Which arteries are typically occluded in GCA that result in visual loss?
Posterior ciliary arteries, resulting in anterior ischaemic optic neuropathy
What are the diagnostic criteria for GCA as per the American College of Rheumatology?
3 of 5 present:
Age at disease onset >50 years
New headache - localised
Temporal artery abnormality
Elevated ESR by >50
Abnormal artery biopsy
What 3 acute phase reactants would you measure in GCA, and what are the estimated optimal cut-off levels?
ESR - 50
CRP - 20
Platelets - 300
CRP + platelets = good diagnostic utility for GCA
What is the most significant long term risk of GCA?
Aortic aneurysm
As well as steroids, what medications should be considered for treatment of GCA? Name 7.
Aspirin - positive role in cerebrovascular disease
Methotrexate
Cyclophosphamide
Azathioprine
Leflunomide
Tocilizumab (anti IL-6)
Ustekinumab
TNFa not recommended for GCA
What are the mandatory (3) and additional criteria for diagnosing polymyalgia rheumatica (6)?
Mandatory
- age > 50
- aching in both shoulders
- abnormal CRP/ESR, or both
Additional (> 4 points w/o USS, > 5 with USS)
- morning stiffness lasting >45 mins (2 points)
- hip pain or reduced range of motion (1 point)
- negative RF/CCP (2 points)
- absence of peripheral synovitis (1 point)
- USS findings - one shoulder with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis, or at least one hip with synovitis or trochanteric bursitis (1 point)
- subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis in both shoulders (1 point)
What are the cut-offs for PMR activity score (PMR-AS)?
PMR-AS < 7 is low disease activity
PMR-AS > 10 defines a flare and suggests adjustment in glucocorticoid dosage
PMR-AS > 17 is high disease activity
How is PMR treated?
Prednisolone 15 mg/day for 4 weeks, then reduced by 2.5 mg every 2 weeks to 10 mg and subsequent reduction by 1 mg per month
Also can give methotrexate to use less GC, particularly to reduced osteoporotic fracture risk
Etanercept has a modest benefit in GC naive PMR patients
Name 5 extra-articular features associated with axial sponyloarthritis.
Anterior uveitis - common
IBD
Psoriasis
Apical fibrosis
Aortic regurgitation
What are the typical XR changes you can expect to see in the spine with AS? Name 3.
Squaring
Syndesmophytes (will progress to bridging syndesmophytes)
Romanus lesion (shiny corners)
When can patients with axial spondyloarthritis commence biologics?
After failing 12 weeks of NSAID and exercise therapy with on-going active disease
Name 6 biologics that can be used in the treatment of axial spondyloarthritis.
Adalimumab
Certolizuma pegol
Etanercept
Golimumab (funded by PBS)
Infliximab
Secukinumab is effective for AS (IL-17A inhibitor)
What are the PBS funding criteria for golimumab on non-radiographic axial spondyloarthropathy?
nr-axSpA as defined by ASAS criteria
Elevated inflammatory markers
Sacroiliitis with inflammation or oedema on non-contrast MRI
Bone marrow oedema on STIR and T1 images (non-contrast)
Failed NSAIDs and exercise for 3 months
BASDAI 4 or more
What are the classification criteria for axial spondyloarthritis?
Patients must have at least 3 months of back pain with age of onset < 45
Sacroiliitis on imaging plus at least 1 SpA feature OR HLA-B27 positive plus at least 2 other SpA features:
- inflammatory back pain
- arthritis
- enthesitis
- uveitis
- dactylitis
- psoriasis
- Crohn’s/colitis
- good response to NSAIDs
- family history for SpA
- HLA-B27
- elevated CRP
What are the classification criteria for peripheral spondyloarthritis?
Arthritis, enthesitis or dactylitis PLUS
1 or more SpA features
- uveitis
- psoriasis
- Crohn’s/colitis
- preceding infection
- HLA-B27
- sacroiliitis on imaging
OR at least 2 other SpA features
- arthritis
- enthesitis
- dactylitis
- inflammatory back pain ever
- family history for SpA
What is the definition of a positive MRI sacroiliac joint?
Subchondral bone marrow oedema
Acute (bilateral) sacroiliitis
STIR sequencing
How is psoriatic arthritis diagnosed?
Presence of established inflammatory articular disease (peripheral arthritis, enthesitis or axial) plus three points from:
- present skin psoriasis (2 points)
- past of family Hx of psoriasis (1 point)
- dactylitis (1 point)
- nail changes - pitting, onycholysis (1 point)
- RF negative (1 point)
- juxta-articular new bone formation on XR (1 point)
What correlates better to psoriatic arthritis, skin or nail disease?
Nail disease
Name 2 co-morbidities associated with psoriatic arthritis.
Cardiovascular disease
Metabolic syndrome
Obesity additionally is associated with worse outcomes
What treatments can be given for psoriatic arthritis? 6 categories
NSAIDs - symptom relief
CsDMARDs - methotrexate, sulfasalazine, leflunomide (but little data for these)
Anti-TNF - adalimumab, certolizumab pegol, etanercept, golimumab, infliximab
Anti-IL17 - secukinumab, ixekizumab
Anti-p40 subunit IL12/23 - ustekinumab
Anti-p19 subunit IL23 - guselkumab
Also apremilast, a phosphodiesterase 4 inhibitor, but this is not PBS listed
Name 5 organisms that can cause reactive arthritis.
Chlamydia
Shigella
Salmonella
Campylobacter
Yersinia
Name 8 extra-articular manifestations of reactive arthritis.
Keratoderma blennorrhagica
Circinate balanitis
Mouth ulcers
Conjunctivitis
Uveitis
Aseptic urethritis
Cervicitis
Prostatitis
What are the treatment options for reactive arthritis? 5 options.
If chlamydia - treat, contact tracing
NSAIDs
Intra-articular glucocorticoids (systemic if unwell)
DMARDs - sulfasalazine for chronic disease, or methotrexate
Name 3 features of IBD that might predispose patients towards having spondyloarthritis.
Having other extra-intestinal features
Complications of bowel disease
Large bowel involvement (for Crohn’s)
What is the most likely cause of death in systemic sclerosis?
Pulmonary arterial hypertension
What pattern of interstitial lung disease is most likely to be seen in systemic sclerosis?
Non-specific interstitial pneumonitis
Name 2 high risk phenotypes in systemic sclerosis for the development of ILD.
Early dc-SSc and anti-Scl70
Early dc-SSc and elevated CRP
How is SSc-ILD graded via HRCT?
<20% = limited disease
> 20% = extensive disease
Indeterminate percentage + FVC 70% or above = limited disease
Indeterminate percentage + FVC <70% = extensive disease
How often should patients with early diffuse SSc with ILD be monitored?
Use spirometry and DLCO
Every 3-4 months for 3-5 years after disease onset, then yearly
No advantage in serial HRCT scans if PFTs are stable
What are the options for treatment of SSc-ILD?
Mycophenolate 3g/day or if intolerant, mycophenolic acid
Oral or IV cyclophosphamide for 6-12 months followed by MMF or azathioprine for severe or progressive disease unresponsive to MMF
Consider nintedanib
Which antibodies would you expect to see in scleroderma renal crisis?
Anti-RNA polymerase III
Which drug can precipitate scleroderma renal crisis?
Cyclosporin A
Name 4 classes of drugs that can be used in SSc-PAH for treatment.
PDE-5 inhibitors (sildenafil, tadalafil)
Endothelin receptor antagonists (ambrisentan, bosentan, macitentan)
Prostacyclin analogues (iloprost, treprostinil, IV epoprostenol for class III or IV disease)
Riociguat
No role for CCB monotherapy
What is the treatment of scleroderma renal crises?
Mainstay of treatment is ACEi
Benefit of combining this with bosentan or plasma exchange
If CNS involvement (encephalopathy) - add nitroprusside
Name 6 non-pharmacological therapies for treating Raynaud’s phenomenon.
Treat underlying cause e.g. cryoglobulinaemia
Keep hands warm/hand warmers
Name pharmacological therapies for Raynaud’s phenomenon (3 stages).
First line -
Which SSc patients benefit from autologous HSCT?
Non-smokers non-responsive to standard treatment along with either:
- dcSSc within the first 4-5 years with mild-to-moderate organ involvement
- lcSSc with progressive visceral involvement
Name 2 complications from SSc affecting the small bowel
Pseudo-obstruction
Bacterial overgrowth
Name 1 complication from SSc affecting the liver.
Primary biliary cirrhosis
Name 2 complications from SSc affecting the large bowel.
Wide-mouth diverticulae
Faecal incontinence
Name 3 diseases that can result following TREX1 gene mutations.
SLE
Aicardi-Goutiere’s syndrome - early onset encephalopathy
RVCL - retinal vasculopathy with cerebral leukodystrophy
Name 4 complement deficiencies that can predispose patients to SLE.
C1q
C2
C4A
C4B
90% risk of SLE in homozygotes for C1q deficiency
Name 3 drugs that can cause drug-induced lupus where you are more likely to see anti-histone antibodies.
Procainamide
Hydralazine
Isoniazid
Name 3 features of Jaccoud’s arthropathy.
Ulnar deviation
Swan-neck deformity
Tenosynovitis
What is the most common manifestation of cardiac disease in SLE?
Pericarditis
What are the two most specific auto-antibodies seen in SLE, and what manifestations are they associated with?
Anti-Smith - renal and CNS disease
Anti-dsDNA - disease activity, nephritis, TNFi induced disease
Name 4 triggers for SLE.
UV light/phototherapy
Sulphonamides
Stress
Oestrogen-containing preparations
What is belimumab, and what is it used in?
Used in SLE
mAb against BAFF/BLyS (B-cell activating factor/B lymphocyte stimulator)
Name 7 contra-indications to pregnancy in SLE.
Severe restrictive lung disease (FVC > 1L)
Severe pulmonary hypertension (sPAP >50)
Advanced renal insufficiency (>2.8 Cr mg/L)
Advanced heart failure
Previous severe pre-eclampsia or HELLP
Stroke within last 6 months
Severe disease flare within 6 months
