Axial and peripheral spondiloarthritis Flashcards
What are spondyloarthritides?
They are genetically associated with what HLA Class I markers?
The strong association with HLA Class I suggests that there might be a _______ triggering an abnormal immune response in a genetically susceptible individual.
The spondyloarthritides are a group of diseases characterized by axial arthritis (spine, sacroiliac joints), peripheral arthritis, uveitis (inflammation of the iris or ciliary body of the eye), _enthesitis**_(inflammation of the ligamentous-osseous junctions), *mucocutaneous lesions (ocular, oral, or skin rash), dactyllitis (intense diffuse swelling of a finger/toe; “sausage” digits), and genetic associa- tion with the HLA class I marker HLA-B27**.
1- Axial spondyloarthritis [axSpA, including its most advanced form, ankylosing spondylitis (AS)], 2- reactive arthritis, 3- psoriatic arthritis, 4- the inflammatory bowel disease associated arthritis (arthritis associated with Crohn’s disease and ulcerative colitis), and the undifferentiated spondyloarthropathies belong to this group of diseases.
The exact pathogenesis of the disease entities is uncertain. However, there is a strong association with the HLA-B27 antigen suggesting the clinical disease results from an unknown _***infectious organism_ triggering an abnormal immune response in a genetically susceptible individual.
Axial spondyloarthritis (precedes ankylosing spondylitis)
Clinical features:
What is the usual age of occurrence?
Ankylosing spondylitis
Clinical features:
What pain is a typical presentation in patients?
It gets better with?
Does not get better with?
There is a global loss of ______ motion.
Axial spondyloarthritis (including ankylosing spondylitis)
Clinical features:
Unlike rheumatoid arthritis, axSpA frequently affects __________which are areas of cartilaginous union with bone.
Laboratory and radiografts:
What two factors are elevated?
By definition plain radiographs show______.
Complete spinal fusion is known as______ and is developed in 10% of patients.
CRP(mote common) and ESR are elevated.
Sacroilitis
Bamboo spine
Reactive arthritis
History of infectious ______ or _______ precedes onset of arthritis by 2-4 weeks.
Reactive Arthritis
On physical examination sinovitis is seen in the ______ of the body.
What is enthesopathy?
What is Reiter’s syndrome composed of?
Reactive Arthritis Laboratory findings:
Erosive changes of feet, but _____ is usually spaired.
Psoriatic arthritis
Does skin disease correlate with RA?
Psoriatic Arthritis
Peripheral arthritis seen mostly on _____.
Unilateral _____ is seen.
Epidemiology
Pathology
What cytokines are present in the joints?
Is synnovial pannus seen?
Ankylosing Spondylitis
The risk of developing AS solemly due to HLA-B27 is ________.
40%
Ankylosing Spondylitis
HLA-B27 theories
Reactive Arthritis
Which bateria reaches the joint and is still alive but is a latent state?
Is HLA-B27 enough to cause Reactive arthritis?
Th1 or Th2 cytokine release prevails?
Treatment
Key points
C. Therapy is based on our understanding of the pathogenesis:
Sulfasalazine is used to decrease bowel inflammation in AS and inflammatory
bowel disease which leads to improvement in peripheral arthritis.
Antibiotics are used in reactive arthritis due to Chlamydia to eradicate persisting
latent organisms causing ongoing inflammation.
Anti-TNF biologic agents are widely used because excess amounts of TNF-α has
been demonstrated in the joints and entheses, and drive the inflammation. Anti- IL-17 therapies are also effective.
Lecture notes
Lecture notes
Unfolded protein hypothesis:
HLA-B27 has a propensity to misfold in the endoplasmic reticulum causing an unfolded protein stress response. This results in the release of inflammatory cytokines such as IL-23* which can activate proinflammatory Th 17 cells. Notably, endoplasmic reticulum aminopeptidase 1 (ERAP-1) is involved in the trimming of peptides for loading MHC molecules (ie HLA-B27) into the endoplasmic reticulum.
Abnormal loading may contribute to misfolding of HLA-B27 resulting in an unfolded protein stress response and IL-23 production. ERAP-1 and IL-23 polymorphisms both contribute to the genetic risk of developing AS.
