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Rheumatology > Seronegative arthritidities > Flashcards

Seronegative arthritidities Flashcards

1
Q

Define ankylosing spondylitis

A

Inflammatory disorder that predominantly affects the axial skeleton

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2
Q

Epidemiology of ankylosing spondylitis (AS) including genetics?

A

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

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3
Q

Pathological features of sacroiliitis

A

Synovitis and pannus formation causes eroded joint margins, then replaced with subchondral granulation tissues which becomes ossified causing obliteration of the joint

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4
Q

Pathology of AS in axial skeleton

A

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

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5
Q

What are spondyloarthritidies?

A

Group of overlapping disorders that share clinical features.
Include ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, undifferentiated arthritis

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6
Q

What is enthesitis?

A

Inflammation at insertion of tendon/ ligament

Erosion and ossification causing bony spurs

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7
Q

5 criteria for inflammatory back pain

A 
Age less than 40
Insidious onset, chronic > 3 months
Improves with exercise
No improvement at rest 
Pain at night
(usually responds to NSAIDs)
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8
Q

What is schobers test?

A

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)

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9
Q

How many patients with anklyosing spondylitis get peripheral arthritis?

A

25-35%, common in shoulders and hips

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10
Q

What forms the stooped posture in AS?

A 
Flexion deformity of neck
Accentuated thoracic kyphosis
Loss of normal lumbar lordosis
Flexion deformity of hips
Buttock atrophy
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11
Q

Extra articular manifestations of AS

A 
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
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12
Q

Lab findings in AS?

A 
HLA B27 positive
Elevated CRP/ESR  in 50-70%
Raised ALP and IgA
Normochromic normocytic anaemia
Typically negative ANA, RF, CCP
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13
Q

Key points for treatment of AS

A

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)

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14
Q

Complications of AS

A

Osteopenia
Fractures with potential spinal cord injury - fused spine acts like a long bone when fractured
Cauda equina
Atlantoaxial subluxation

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15
Q

What is the relationship between psoriasis and psoriatic arthritis

A

5-30% of people with psoriasis have psoriatic arthritis
70% of patients with psoriatic arthritis have preceding psoriasis
30% have a FH of psoriasis

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16
Q

Infections associated with reactive arthritis

A 
Shigella
Salmonella
Yersinia *
Campylobacter 
C. Diff
Chlaymydia *
  • higher likelihood of chronicity
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17
Q

What is the time frame between the infection and development of reactive arthritis

A

Infection 1-4 weeks before

Usually urogenital or enteric

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18
Q

Features of reactive arthritis

A 
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
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19
Q

What % of pts with reactive arthritis are HLAB27 positive and what effect does this have on disease progression?

A

50%

HLA B27 associated with persistence of symptoms and poorer outcome

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20
Q

What is an important differential for reactive arthritis

A

Disseminated gonococcal disease

- can get oligoarthritis and pustules

21
Q

Treatment of reactive arthritis

A

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)

22
Q

Prognosis of reactive arthritis

A

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

23
Q

5 patterns of psoriatic arthritis

A 
DIP arthritis (15%)
Asymmetric oligoarthritis (30%)
Symmetrical polyarthritis (40%)
Axial involvement (5%)
Arthritis mutilans
24
Q

Other features of psoriatic arthritis other then arthritis

A 
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
25
Q

CAPAR criteria for diagnosis of psoriatic arthritis

A

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

26
Q

Radiographic features of psoriatic arthritis

A 
Pencil in cup deformity
Marginal erosions with adjacent new bone formation
Osteolysis of terminal phalanges
Small joint ankylosis
Periostosis at sites of enthesitis
27
Q

Treatment of psoriatic arthritis

A

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
28
Q

What are the features of spondyloarthritis?

A
  • 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
29
Q

What are the diagnostic criteria for AS?

A

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’)

30
Q

What are the examination findings in AS?

A

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

31
Q

What % of patients with AS have HLAB27?

A

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
32
Q

What are the radiological features of AS?

A

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)

33
Q

What is a radiological Ddx for AS?

A

DISH

  • diffuse idiopathic skeletal hyperostosis
  • large beaked osteophytes , unilateral, involving 3 adjacent vertebral levels
  • never associated with sacroiliitis
  • associated with DM
34
Q

What is non-radiographic axial SpA?

A

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
35
Q

What are the clinical patterns of psoriatic arthritis?

A

DIP arthritis
Nail changes - correlate better with PsA than skin disease
- onycholysis, subungual hyperkeratosis, pitting
Dactylics
Enthesitis
x-ray changes
spodyloarthritis (10% only)

36
Q

What biological treatments are there for psoriatic arthritis?

A

Sekukinumab (anti-IL17)

Ustekinumab (anti IL 12/23)

37
Q

What drugs may worsen psoriatic arthritis?

A

Steroids - may worsen skin psoriasis and erythroderma

Hydroxychloroquine may worsen skin psoriasis

38
Q

What is HLAB27?

A 
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

39
Q

What are the main genetic associations with the spondyloarthritides?

A

HLA B27
ERAP-1
IL-23R
ARTS-1

40
Q

What are the 7 types of Spondyloarthritides and their prevalence of B27 positivity?

A
  1. Ankylosing spondylitis - 92%
  2. Non-radiographic axial spondyloarthritis
  3. Undifferentiated peripheral spondyloarthritis - 27%
  4. Psoriatic arthritis ~50%
    - axial and spondylitic forms - 60-70%
    - peripheral asymmetric arthritis form - 24%
  5. Reactive arthritis - 80%
  6. Enteropathic arthritis associated with Crohn’s disease or UC - 30%
  7. SAPHO syndrome - 13%
41
Q

What is SAPHO syndrome?

A 
Synovitis
Acneiform lesions
Pustulosis
Hyperostosis
Osteitis

a variant form of psoriatic arthritis
weak association with HLAB27

42
Q

What is the ASAS classification criteria for axial SpA?

A

Sacroilitis on imaging + 1+ SpA feature

OR

HLAB27 + 2+ SpA features

43
Q

What are the environmental factors involved in the development of SpA?

A

intestinal microflora
Colitis
- high rates of subclinical colitis in AS and AS in IBD
- gastroenteritis initiating reactive arthritis
Smoking
- increased risk and severity

44
Q

What are the important immunological mechanisms behind SpA?

A

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

45
Q

What is the pathogenesis behind AS?

A

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

46
Q

What is the common pattern of arthritis with enteropathic SpA?

A

asymmetrical, lower limb oligoarthritis

- activity of arthritis closely related to severity of IBD

47
Q

What are the genetic links between SpA and IBD?

A

HLAB27
IL-23R gene

not NOD2 (Crohn’s)

48
Q

What are the treatment options for enteropathic SpA?

A

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

Rheumatology (11 decks)

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