Seronegative arthritidities Flashcards
Define ankylosing spondylitis
Inflammatory disorder that predominantly affects the axial skeleton
Epidemiology of ankylosing spondylitis (AS) including genetics?
Typical age of onset 20-30y
M:F ratio 2-3:1
Major susceptibility gene is HLA B27, overall contribution to development of AS is 23%
concordance in identical twins is 75% and only 13% in non-identical twins suggesting a polygenic mode of inheritance
Pathological features of sacroiliitis
Synovitis and pannus formation causes eroded joint margins, then replaced with subchondral granulation tissues which becomes ossified causing obliteration of the joint
Pathology of AS in axial skeleton
Inflammatory granulation tissue at junction of vertebra and disc
Erosions occur which are then replaced by bone causing syndesmophytes
Syndesmophytes grow to bridge adjacent vertebra which along with calcification of the longitudinal ligament causes bamboo spine
What are spondyloarthritidies?
Group of overlapping disorders that share clinical features.
Include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, undifferentiated arthritis
What is enthesitis?
Inflammation at insertion of tendon/ ligament
Erosion and ossification causing bony spurs
5 criteria for inflammatory back pain
Age less than 40 Insidious onset, chronic > 3 months Improves with exercise No improvement at rest Pain at night (usually responds to NSAIDs)
What is schobers test?
Mark lumbosacral joint and 10cm above this
Get patient to bend forward maximally and measure between two marks again
Abnormal if difference between two marks less than 14cm ( ie change of less than 4cm from erect distance)
How many patients with anklyosing spondylitis get peripheral arthritis?
25-35%, common in shoulders and hips
What forms the stooped posture in AS?
Flexion deformity of neck Accentuated thoracic kyphosis Loss of normal lumbar lordosis Flexion deformity of hips Buttock atrophy
Extra articular manifestations of AS
Acute anterior uveitis - 70% of patients with AAU have SpA Inflammation of colon/ileum Aortic regurgitation Conduction disturbances Restrictive lung pattern due to kyphosis and reduced chest wall expansion Upper lobe pulmonary fibrosis Retro peritoneal fibrosis Psoriasis Prostatitis Amyloidosis
Lab findings in AS?
HLA B27 positive Elevated CRP/ESR in 50-70% Raised ALP and IgA Normochromic normocytic anaemia Typically negative ANA, RF, CCP
Key points for treatment of AS
Exercise programme and physio VERY IMPORTANT
NSAIDS first line
- continuous treatment slows radiological progression
Anti TNF alpha therapy in those that don’t respond to NSAIDs
- ? whether this improves radiological progression
- makes patients feel much better and cessation leads to rapid relapse
Peripheral arthritis:
- sulfasalazine
- intra-articular steroid injections
(MTX has no benefit)
Complications of AS
Osteopenia
Fractures with potential spinal cord injury - fused spine acts like a long bone when fractured
Cauda equina
Atlantoaxial subluxation
What is the relationship between psoriasis and psoriatic arthritis
5-30% of people with psoriasis have psoriatic arthritis
70% of patients with psoriatic arthritis have preceding psoriasis
30% have a FH of psoriasis
Infections associated with reactive arthritis
Shigella Salmonella Yersinia * Campylobacter C. Diff Chlaymydia *
- higher likelihood of chronicity
What is the time frame between the infection and development of reactive arthritis
Infection 1-4 weeks before
Usually urogenital or enteric
Features of reactive arthritis
Arthritis- acute onset, aymmetric, involving lower extremities Enthesitis Low back pain Dactylitus Conjunctivitis, anterior uveitis Ulcers Keratoderma blenorrhagica Fatigue, weight loss, fever AR, conduction defects, CNS lesions, pleuropulmonary infiltrates
What % of pts with reactive arthritis are HLAB27 positive and what effect does this have on disease progression?
50%
HLA B27 associated with persistence of symptoms and poorer outcome
What is an important differential for reactive arthritis
Disseminated gonococcal disease
- can get oligoarthritis and pustules
Treatment of reactive arthritis
High dose NSAIDs are primary treatment
DMARDS may be trialled in persistent disease
no evidence that antibiotics are helpful in treating enteropathic SpA (obviously treat STI)
Prognosis of reactive arthritis
Typically persists for 3-5 months, can last up to 1 year
Chronic joint symptoms persist in 15% and recurrences can occur
HLAB27 positive have a worse outcome
Shigellosis also has worse prognosis
5 patterns of psoriatic arthritis
DIP arthritis (15%) Asymmetric oligoarthritis (30%) Symmetrical polyarthritis (40%) Axial involvement (5%) Arthritis mutilans
Other features of psoriatic arthritis other then arthritis
Psoriasis Tenosynovitis Enthesitis Dactylitis (50%) Nail changes (pitting, ridges, oncolysis etc) Osteolysis with shortening of digits Ankylosis of PIP joints Morning stiffness Conjunctivitis/uveitis Aortic insuffiency
CAPAR criteria for diagnosis of psoriatic arthritis
Must have inflammatory articular disease (joint, spine or enthesitis) and
3 points:
Current psoriasis, family history or personal history
Psoriatic nail lesions
Negative RF
Dactylitis
Juxtaarticular new bone formation on XRay
Radiographic features of psoriatic arthritis
Pencil in cup deformity Marginal erosions with adjacent new bone formation Osteolysis of terminal phalanges Small joint ankylosis Periostosis at sites of enthesitis
Treatment of psoriatic arthritis
Mild - NSAIDs
Moderate - consider DMARDs (MTX, leflunomide) however have not been shown to improve radiological progression
Severe - TNFa inhibitors (etanercept, adalilumumab, infliximab, goluzimab, certolizumab)
- effective for skin and joint disease
Can use ustekinumab (IL-12/23 humanised mAb)in patients with no response to 2 TNFa inhibitors
- note that hepatotoxicity is more common with MTX and anti-TNF agents in psoriatic arthritis
What are the features of spondyloarthritis?
- Inflammatory back pain
- Arthritis –oligo‐ articular, lower limb
- Sacro‐iliitis
- Enthesitis
- Dactylitis
- Uveitis
- Psoriasis
- HLA B27 positivity
- Family history
- Inflammatory Bowel Disease
- Recent infection – genitourinary or gastro‐intestinal
What are the diagnostic criteria for AS?
At least one clinical and one radiological feature:
Clinical
– Inflammatory Low Back Pain and Stiffness >3/12
– Restriction in Lumbar Forward or Lateral Flexion
– Restriction in Chest Wall Expansion
Radiology
– Bilateral Grade 2 sacro‐iliitis on x‐ray
– Unilateral Grade 3‐4 sacro‐iliitis on x‐ray
(reasonably late signs so often use MRI to detect earlier changes - ‘non-radiographic AS’ or ‘axial spondyloarthritis’)
What are the examination findings in AS?
Characteristic posture
All segments of spine have reduced movement
Chest expansion reduced (costo‐vertebral joints)
L spine: Schooner’s test
T spine: thoracic kyphosis: tragus to wall test
tender sacroiliac joints
peripheral arthritis (hips): intermalleolar distance, fixed flexion deformity
enthesitis
AR - wide pulse pressure, murmur
What % of patients with AS have HLAB27?
92%
- commonest association between HLA subtype and human disease
- also present in 8% of the normal European population
- Haida indians have 50% HLA B27 positivity
What are the radiological features of AS?
sacroiliitis: sclerosis on both sides of the joint
- grades I - IV
lumbar and thoracic spine
- syndesmophytes (run vertically)
- vertebral squaring
- Romanus lesions (shiny lesions at the corners of vertebral bodies)
What is a radiological Ddx for AS?
DISH
- diffuse idiopathic skeletal hyperostosis
- large beaked osteophytes , unilateral, involving 3 adjacent vertebral levels
- never associated with sacroiliitis
- associated with DM
What is non-radiographic axial SpA?
symptoms and clinical features of AS but no x-ray changes (may have MRI STIR changes)
- x-ray changes required for diagnosis of AS
- radiographic progression to AS is 12% per year
- not all progress to AS
What are the clinical patterns of psoriatic arthritis?
DIP arthritis
Nail changes - correlate better with PsA than skin disease
- onycholysis, subungual hyperkeratosis, pitting
Dactylics
Enthesitis
x-ray changes
spodyloarthritis (10% only)
What biological treatments are there for psoriatic arthritis?
Sekukinumab (anti-IL17)
Ustekinumab (anti IL 12/23)
What drugs may worsen psoriatic arthritis?
Steroids - may worsen skin psoriasis and erythroderma
Hydroxychloroquine may worsen skin psoriasis
What is HLAB27?
an MHC class 1 gene found on chromosome 6 Involved in the CD8 receptor binding and peptide presentation
individuals with HLAB27 have a 20 fold increase in developing SpA
What are the main genetic associations with the spondyloarthritides?
HLA B27
ERAP-1
IL-23R
ARTS-1
What are the 7 types of Spondyloarthritides and their prevalence of B27 positivity?
- Ankylosing spondylitis - 92%
- Non-radiographic axial spondyloarthritis
- Undifferentiated peripheral spondyloarthritis - 27%
- Psoriatic arthritis ~50%
- axial and spondylitic forms - 60-70%
- peripheral asymmetric arthritis form - 24% - Reactive arthritis - 80%
- Enteropathic arthritis associated with Crohn’s disease or UC - 30%
- SAPHO syndrome - 13%
What is SAPHO syndrome?
Synovitis Acneiform lesions Pustulosis Hyperostosis Osteitis
a variant form of psoriatic arthritis
weak association with HLAB27
What is the ASAS classification criteria for axial SpA?
Sacroilitis on imaging + 1+ SpA feature
OR
HLAB27 + 2+ SpA features
What are the environmental factors involved in the development of SpA?
intestinal microflora
Colitis
- high rates of subclinical colitis in AS and AS in IBD
- gastroenteritis initiating reactive arthritis
Smoking
- increased risk and severity
What are the important immunological mechanisms behind SpA?
TNF alpha likely to play a major role in inflammation
- SpA’s respond dramatically to TNF alpha blockers
Th17 cells
- important in autoimmune pathology
- primed in the gut in response to intestinal microflora
IL17 and IL23 levels are elevated
- IL17 likely to play a key role in chronic inflammation
What is the pathogenesis behind AS?
Enthesitis is likely to be the initial site of disease
inflammatory infiltrate in the enthuses spreading to subchondral bone
CD8+ lymphocytes and macrophages predominate with release of inflammatory cytokines
- TNF alpha and IL-1
erosions develop with remodelling causing bony spurs
- syndesmophytes form
What is the common pattern of arthritis with enteropathic SpA?
asymmetrical, lower limb oligoarthritis
- activity of arthritis closely related to severity of IBD
What are the genetic links between SpA and IBD?
HLAB27
IL-23R gene
not NOD2 (Crohn’s)
What are the treatment options for enteropathic SpA?
Sulphasalazine can be effective for joint and bowel disease
Anti-TNF therapies improve both joint and bowel disease
Total colectomy in UC leads to resolution of joint disease
