Spondyloarthropathies - HLA B27

Question 1

Spondyloarthritis is associated with what gene?

Answer 1

HLA B27

Question 2

Spondyloarthritis

Answer 2

Inflammatory diseases that involve both the joints and the entheses (the sites where the ligaments and tendons attach to the bones). The most common of these diseases is ankylosing spondylitis or axial spondyloarthritis.

Question 3

What are the different types of spondyloarthritis?

Answer 3

Ankylosing spondyloarthritis

Reactive arthritis

Psoriatic arthritis

Question 4

Reactive arthritis:

Answer 4

Reactive arthritis is joint pain and swelling triggered by an infection in another part of your body, most often your intestines, genitals or urinary tract.

Question 5

Reactive arthritis usually affects where?

Answer 5

Reactive arthritis usually targets your knees and the joints of your ankles and feet. Inflammation also can affect your eyes, skin and urethra.

Question 6

Summary of Axial spondyloarthritis:

Question 7

What is the difference between Ankylosing vs Axial spondyloarthritis?

Answer 7

Ankylosing shows damage to the sacro-illiac joint on x-ray.

Axial present normally on x-ray.

Question 8

What is thought to be the aetiology (cause) of spondyloarthropathies?

Answer 8

Strong link to HLA B27 gene

Amino acid sequence between the antigenbinding region of HLA-B*2705 and nitrogenase from Klebsiella supports molecular mimicry.

• thought to be triggered by Klebsiella infections.

Question 9

What is meant by auto-inflammatory?

Answer 9

Auto-inflammatory diseases are characterized by episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells.

Question 10

How is HLA B27 thought to cause inflammation?

Answer 10

– misfolding of HLA-B27 gene appears to trigger the unfolded protein response (UPR) in macrophages.

– Leads to inflammation and the production of inflammatory cytokines.

Question 11

Pathology of Axial Spondyloarthritis:

Answer 11

Characterized by inflammation in and around the joint.

• The enthesis, the site of ligamentous attachment to bone, is thought to be the primary site of pathology.
• Enthesitis is associated with prominent edema of the adjacent bone marrow and is often characterized by erosive lesions that eventually undergo ossification.
• Sacroiliitis is usually one of the earliest manifestations.

Note: may result in new bone formation and bony ankylosis.

Question 12

What is meant by ankylosis?

Answer 12

Stiffness of a joint due to inflammation in the joint or in the tissues around the joint.

Question 13

Summary of the pathological process of axial spondyloarthritis:

Answer 13

Question 14

Syndesmophytes

Answer 14

A syndesmophyte is a bony growth originating inside a ligament, commonly seen in the ligaments of the spine, specifically the ligaments in the intervertebral joints leading to fusion of vertebrae.

Question 15

Image of ankylosing spondylitis progression:

Answer 15

Question 16

Romanous lesion

Answer 16

An area of inflammation of the bone which leads to the production of syndesmophytes.

Question 17

Clinical features of axSPA:

Answer 17

Chronic lower back pain - intermittent flares and periods of remission.

Fever and weight loss

Morning stiffness

Fatigue

Good response to NSAID’s

Question 18

What helps distinguish inflammatory back pain from mechanical back pain?

Answer 18

• Chronic back pain that develops when young.
• Morning stiffness that lasts 30 minutes.
• Improvement of back pain with exercise but not at rest.
• Nocturnal back pain
• Alternating buttock pain
• Presents with sacro-illiac pain that moves proximally.
• Response to NSAID’s

Question 19

axSPA articular manifestations:

Answer 19

33% of patients present with peripheral enthesitis and peripheral arthritis as well.

Question 20

What test is used to measure restricted spinal movement?

Answer 20

Schober’s test

Question 21

Peripheral enthesitis

Answer 21

Question 22

Diagnosis axSPA

Answer 22

Difficult in the early stages of disease - average of symptoms 5-10years prior to diagnosis.

Based on history.

HLA B27

Imaging:

– X-ray sacroiliac joints

– MRI sacroiliac joints and spine

Question 23

Ankylosing spondylitits requires inflammation in which joint for diagnosis?

Answer 23

Sacroilliac joint

Question 24

Diagnostic pyramid for Axial spondyloarthritis:

Answer 24

Question 25

How are is axSPA and ankylosing spondylitis managed?

Answer 25

Main Treatment = Exercise

Physiotherapy

TNF blockers - reduce inflammation, however does not reduce bony ankylosis.

NSAID’s at lowest effective dose - note these patients may be on NSAID’s for a long time.

IL-17 inhibitors - prevent inflammation.

Question 26

What are the extra-articular manifestation of spondlyoarthropathies?

Answer 26

• Anterior uveitis - often develops before diagnosis
• Psoriasis
• Inflammatory bowel disease - Crohn’s.
• Respiratory restriction:

– Apical fibrosis

– Chest wall restriction

• Cardiac invovement:

– Aortic valve and ischaemic heart disease

• Osteoporosis

Question 27

Anterior uveitis

Answer 27

Anterior uveitis is an inflammation of the middle layer of the eye. This layer includes the iris (colored part of the eye) and the adjacent tissue, known as the ciliary body. If untreated, it can cause permanent damage and loss of vision from the development of glaucoma, cataract or retinal edema.

• painful and lightsensitive

Question 28

Anterior uveitis is very closely linked with

Answer 28

Anterior uveitis is very closely linked with ankylosing spondylitis.

Question 29

Which valve is sometimes affected in ankylosing spondylitis?

Answer 29

Aortic valve

Question 30

Why may restrictive lung disease be a manifestation of ankylosing spondylitis?

Answer 30

Mainly due to the effect of AS on the ribcage:

Costovertebral and costosternal involvement causing limited chest expansion.

Pulmonary fibrosis.

Question 31

Amyloidosis

Answer 31

Amyloidosis is when an abnormal protein called amyloid builds up in your tissues and organs. When it does, it affects their shape and how they work. Amyloidosis is a serious health problem that can lead to life-threatening organ failure.

Question 32

How does AS affect bone health?

Answer 32

Osteopenia and Osteoporosis may occur in patients with longstanding spondylitis.

Greatly increased risk of spinal fracture.

Question 33

Summary of Axial SpA:

Answer 33

Question 34

Psoriatic arthritis

Answer 34

Psoriatic arthritis is a form of arthritis that affects some people who have psoriasis, a condition that features red patches of skin topped with silvery scales.

Most people develop psoriasis first and are later diagnosed with psoriatic arthritis, but the joint problems can sometimes begin before skin patches appear.

Question 35

Summary of Psoriatic arthritis:

Answer 35

Question 36

Summary of enteropathic arthritis:

Answer 36

Question 37

Which bacteria commonly trigger reactive arthritis?

Answer 37

Genitals - Chlamydia trachomatis

Bowel - Campylobacter, Salmonella, Shigella and Yersinia.

Question 38

What other symptoms can reactive arthritis be linked with?

Answer 38

Recent infection

Inflammation of the eyes in the form of conjunctivitis or uveitis.

Urethritis in men or cervicitis in women.

Mouth ulcers

Psoriasis