Flashcards in Rheumatology 2 - Spondyloarthridides Deck (61):
What are shared features of SpA?
1. Inflamm back pain
2. Peripheral arthritis
5. Extra-articular - ant uveitis, psoriasiform rash, enteric lesions
6. Imaging changes of SIJ and spine
7. Shared genetic background - HLA-B27
What are criteria for IBP?
Age onsef =4/5 required for Dx
What are features of peripheral arthritis in SpA?
Oligoarticular - inflammation of
What are features of enthesitis?
inflammation at sites where ligaments, tendons and joint capsules attach to bone
Typically at sites subjected to greater physical stresses
also affects the axial skeleton including hip and shoulder girdles
What are clinical features of dactylitis?
diffuse fusiform swelling of toe or finger (sausage digit)
flexor tendon sheath inflammation
psoriatic arthritis, reactive arthritis
uncommon in AS
DDx = gout, sarcoidosis
What are extra-articular features of SpA?
Anterior uveitis (iritis)
Skin - psoriasis/psoriasiform lesion
- keratoderma blenorrhagicum
- circinate balanitis
Enteric mucosal lesions
What are other causes of anterior uveitis (other than SpA)?
What is the grading system for SI joint changes?
0 - normal
1 - suspicious
2 - early sacroilitis - minor sclerosis, limited erosion, joint narrowing
3 - definite sacroilitis - severe sclerosis, clear cut erosions, joint space widening, some ankylosis
4 - advanced sclerosis - ankylosis, fusion
look at lower 1/3 of the joint, monitor with imaging every 24 months
What is the clinical criteria for AS?
Mod new york criteria:
1. clinical criteria
- low back pain and stiffness for >3 months which is improved by exercise, not by rest
2. limitations in motion of the lumbar spine in both saggital and frontal planes
3. limitation in chest expansion relative to normal values
2. radiological criterion - sacroilitis grade >=2 bilaterally or grade 3-4 unilaterally
Need 1 clinical and 1 radiological criterion to make Dx
What are features of Osteitis Condensans Ilii (OCI)?
triangular area of dense sclerosis on iliac side, adjacent to lower 1/2 SIJ
Does not involve SIJ!
CT useful in differentiating between OCI and SIJ
What are abnormalities noted on MRI in SIJ disease?
1. inflammatory change on stir images (bone oedema, osteitis)
2. structural change - T1 weighted images - visualise cartilage and subchondral bone, erosion, sclerosis and ankylosis, also look for post inflammatory fatty change
What is the relative Sn of MRI vs XR and CT wrt sacroilitis?
XR and CT are both more sensitive to structural Abn than MRI
What predictors have the strongest LR for AS at 8 years?
SIJ osteitis grade 3 with B27 +ve = LR 8.0
What are features of diffuse idiopathic skeletal hyperostosis?
Ossification of anterior longitudinal ligament
Associated in males, older than 50y, 20% DB, NOT HLA-B27.
Treat with NSAIDs, simple analgesics
What is the concordance between twins and AS?
MZ twins 63%, DZ twins, 12.5%
What are features of HLA-B27?
Class Ia MHC molecule, 8% caucasians
1/3 patients with chronic back pain are HLA-B27 +ve, expected to have Ax-Spa
Less than 5% of HLA-B27 patients develop SpA (20% if 1st deg relative with AS)
What is HLA-B27 most strongly associated with?
Ankylosing spondylitis 85-90%
Reactive arthritis 70%
Psoriatic SpA 60-70%
IBD-associated SpA 50-60%
Acute anterior uveitis 50%
Peripheral psoriatic arthritis 25%
What genes have been assocaited with AS on GWAS?
Region within the IL-1 gene complex
What are functions of ERAP1?
trimming peptides for optimal length for MHC Class I presentation
cleaves cell surface receptors for the proinflammatory cytokines IL-1, IL-6, and TNF, downregulating signalling
What are ASAS classification criteria for Axial spondyloarthritis?
Pt with >=3 months of back pain at age =1 SpA feature OR HLA-B27 plus >=2 SpA features.
What are SpA features?
Inflammatory back pain
good response to NSAID
Family Hx for SpA
What are features of inflammatory markers in AS?
What are predictors of severe disease in AS?
poor response to NSAIDs
poor social supports
hip arthritis ******
What is the relationship between OP and AS?
50% have t-score
What are cardiopulmonary complications of AS?
upper lobe fibrosis
aortic regurgitation, conduction disturbances
- mainly subclinical, seen in long-standing disease, eficacy of AS treatments unknown
What are measurements of spinal mobility?
Modified schrober's - =5cm
>=10cm lateral spinal flexion is normal
What medications are best in peripheral disease?
Sulfasalazine, local corticosteroids, TNF blockers and NSAIDs
What medications are best in axial disease?
primarily NSAIDs and TNF blockers
What is the role of NSAIDs in radiographic progression in AS?
continuous NSAID use has been shown to slow radiographic spinal disease progression vs. intermittent NSAIDs
elevated CRP increases the improvement of disease progression in continuous NSAID treated patients
What are features of TNF inhibitors in AS?
Major improvements in Disease activity, spinal mobility, functional ability, QoL
Long term effectiveness demonstrated
Recurrence within 3-12 weeks of easing TNFi
Some have 40% drug free remission at 40 weeks
All very effective at producing ASAS40 responses
Does Anti-TNFa therapy have utility in non-radiographic Axial SpA?
Yes! significantly improves ASAS20, ASAS40 and ASAS partial remission scores vs placebo
What effect does Anti-TNFa therapy have on radiographic progression in AS?
yes - 50% reduction in odds of progression
delay of >10years to treatment means increased likelihood of progression
What does DKK1 do in AS?
Normally inhibits bone formation, however reduced DKK! function leads to less inhibition of syndesmophyte production
What is the role of IL-17A inhibition?
Secukinumab (anti l-17A) has shown efficacy in AS, in both TNFi naive and inadequate responders.
Effective for enthesitis, dactylitis with fewer injections.
Absence of TB/MS risk, and no immunogenecity.
What is the epidemiology of AS?
may have normal spinal mobility/spinal radiographs in early AS
What is the epidemiology of Psoriatic arthritis?
20-30% of patients with psoriatic skin disease
PsA pts more likely to have severe psoriatic nail lesions, scalp psoriasis, intergluteal psoriasis
70% have psoriasis pre arthritis, 15% after arthrtis, 15% concurrently
What are clinical patterns of PsA?
distal arthritis (DIPJ involvement, most specific)
asymmetric oligoarthritis (less than 5 small and or large joints in asymmetric distribution)
symmetric polyarthritis - similar to RA
athritis mutilans (deforming/destructive arthritis, most specific)
spondyloarthritis - including sacroilitis and spondylitis
What are associated clinical features in PsA?
dactylitis (occur in up to 50%), assoc with radiographic damage
Psoriasis - arthritis precedes PsO in 13-17%
Inflammatory eye disease - uveitis
What are CASPAR criteria for PsA?
evidence of psoriasis
psoriatic nail dystrophy
negative RF test
radiologic evidence of juxta-articular new bone formation
What is the prognosis in PsA?
progressive erosive disease occurs in 68% of patients.
risk factors for progressive joint damage:
- increased number inflamed joints
- raised ESR
- DMARD failure
- presence of joint damage (clin or rad)
What are key radiographic changes in PsA?
destruction - large, eccentric erosions, osteolysis, widened joint space, tuft resorption
bony proliferation - periostitis of shaft of metacarpal/tarsal
- proliferation adjacent to joints
- pencil in cup deformity
What are features of psoriatic spondyloarthropathy?
asymmetrical, unilateral sacroilitis, seen in 20% of patients with psoriatic arthritis
syndesmophytes less common, usually symmetrical
- more frequently paramarginal, and may not be in consecutive vertebrae
- bulkier, tear drop or comma shaped
Cervical spine involvement in 70-75%
What is the rationale of management of psoriatic arthritis?
Start NSAID+/- local glucocorticoid if no adverse factors
If adverse factors and no predom axial disease or severe enthesitis, commence methotrexate (or leflunomide/sulfasalazine if C/I MTX)
Phase III = TNF +/- DMARD or 2nd synthetic (Leflunomide, sulfasalazine, MTX or cycA)
Phase IV - change to second TNF blocking agent +/- DMARD
What do TNFi achieve in PsA?
slow radiographic changes in psoriatic SpA and in peripheral psoriatic arthritis
What is the role of ustekinumab in SpA?
MoAb to shared p40 subunit of Il-12/23
Blocks TH1/TH2 pathways, effective in spinal disease, dactyltits, enthesitis
slows radiographic progression with minimal infection risk
slower onset of action, less effective than TNFi for peripheral disease
What is the role of IL-17A inhibitors in SpA?
highly effective in spinal disease, PASI response very high - rapid onset of action, effective for enthesitis, dactylitis, slows radiographic progression
(secukinumab, ixekizumab, brodalumab)
What is a small molecule therapy in SpA?
Apremilast - small molecule inhibtor of PDE4
modulates production of inflammatory mediators at level of mRNA expression
PDE4 normally degrades cAMP, second messenger in Eosinophils, neutrophils, macrophages, t-cells and monocytes
75% as effective as TNFis, not effective for spinal disease, no radiographic data
What are features of reactive arthritis?
joint inflammation triggered by extra-art bact infection
cannot culture from synovial fluid
urogenical infection (chalmydia) most common
presentations are often florid
most common inflammatory arthritis in young men
What are bacteria implicated in reactive arthritis?
chlamydia 4% dev arthritis
What is the current mechanism for reactive arthritis?
local mucosal infection of urogenital tract or gut
viable organisms or bacterial fragments reach joint via circulation
chlamydia disseminated into joint by infected monocytes
bacterial antigens have been found in joint and circulation
What is the W/U of reactive arthritis?
joint aspiration to exclude septic or crystalline arthritis
chlamydia PCR on 1st void urine
consider stool cultures
if clear Hx of urethritis or diarrhoea, lab confirmation desirable but not essential
What is the natural history of reactive arthritis?
resolves within 6-12 months (70%)
chronic relapsing, remitting course (25%)
destructive arthritis in 5%
What are predictors of a longer course in reactive arthritis?
What is the management of reactive arthritis?
Rest, NSAIDs, IA corticosteroid
Consider short oral CS
DMARDs - MTX and sulfasalazine
Treat patient and partners for urethritis/cervicitis
What is the role of long term antibiotics in reactive arthritis?
long term antibiotics useful in chronic reactive arthritis (longer than 6 months) - e.g. doxycycline 100mg BD and rifampicin 300mg daily
What are features of disseminated gonococcal infection?
Due to N gonorrhoea
can occur in absence of urethral symptoms
deficiency of terminal components of complement cascade 10%
Classic triad: polyarthralgia, dermatitis, tensynovitis
(look for purulent vesicles, most cases occur within 1 week of menses) - positive blood cultures
Septic arthritis - less common
Ix - culture cervix, urethra, rectum, pharynx, synovial fluid
What are predisposing features disseminated gonococcal infection?
pregnancy or immediate post partum state
congenital or acquired complement deficiencies
IV ceftriaxone very effective
What are features of arthritis associated with IBD?
- up to 20% of patients with IBD
- non-deforming, self limited
- may parallel bowel activity, esp in UC
- arthritis may antedate IBD in 10%
What are features of axial disease in IBD associated arthritis?
In up to 50% w HLA-B27 +ve patients w IBD
Activity and severity independent of bowel activity
What is the treatment of IBD associated arthritis?
adequate control of bowel disease
total proctocolectomy results in remission of peripheral artthritis in UC only!
NSAIDs may increase risk of IBD flare
Sulfasalazine = DMARD therapy
Infliximab and adalimumab for peripheral and axial joint disease
Etanercept not effective in inflammatory bowel disease