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Flashcards in BL-SPONDYLO Deck (43):
1

The primary and unique pathologic site in spondyloarthropathies is the

Enthesis

2

Enthesis

The enthesis is the connective tissue between tendon or ligament and bone

3

Spondyloarthropathy genetic association:

HLA-B27

4

bacterial subtypes can induce reactive arthritis. These include all of the following

Chlamydia
Salmonella
Yersinia
Shigella

5

clinical manifestations of spondyloarthropathies

Anterior uveitis
Dactylitis
Keratoderma blennorrhagicum
Sacroiliitis

6

Laboratory studies characteristic of seronegative spondyloarthropathies are

Negative rheumatoid factor (RF) and negative anti-nuclear antibodies (ANA)

7

Seronegative spondyloarthropathies share the clinical features of (7)

Sacroiliitis and spondylitis.

Enthesitis which is the hallmark of the disease.

Peripheral arthritis tends to involve large joints in an asymmetric distribution.

Mucocutaneous lesions and ophthalmologic disease are characteristic and common.

GU and GI is common.

Association with HLA-B27

- rheumatoid factor and antinuclear antibodies.

8

pathogenesis of the seronegative spondyloarthropathies is unknown, may be due to

The HLA-B27 transgenic rat has provided valuable insight into the pathophysiology of the axial arthropathies.

An environmental trigger is probably necessary for the diseases to develop.

HLA-B27 is important in the pathogenesis.

T cells are critical to the pathogenesis.

Cytokine response may be abnormal allowing for persistence of bacterial
products in the joint

9

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.

Tetracycline is used in reactive arthritis due to Chlamydia to eradicate persisting latent organisms causing ongoing inflammation.

Anti-TNF biologic agents are used for severe and resistant cases because excess amounts of TNF-α has been demonstrated in the joints and entheses, and drive the inflammation. Anti-IL-17 therapies may hold promise.

10

Sacroiliitis and spondylitis.

Enthesitis which is the hallmark of the disease.

Peripheral arthritis tends to involve large joints in an asymmetric distribution.

Mucocutaneous lesions and ophthalmologic disease are characteristic and common.

GU and GI is common.

Association with HLA-B27

- rheumatoid factor and antinuclear antibodies.

Seronegative spondyloarthropathies shared features

11

The HLA-B27 transgenic rat has provided valuable insight into the pathophysiology of the axial arthropathies.

An environmental trigger is probably necessary for the diseases to develop.

HLA-B27 is important in the pathogenesis.

T cells are critical to the pathogenesis.

Cytokine response may be abnormal allowing for persistence of bacterial
products in the joint

pathogenesis of the seronegative spondyloarthropathies is unknown

Possible correlates

12

______is used to decrease bowel inflammation in AS and inflammatory bowel disease which leads to improvement in peripheral arthritis.

Sulfasalazine

13

Tetracycline is used in reactive arthritis due to _____ to eradicate persisting latent organisms causing ongoing inflammation.

Chlamydia

14

Anti-TNF biologic agents are used for severe and resistant cases because excess amounts of ______has been demonstrated in the joints and entheses, and drive the inflammation. Anti-IL-17 therapies may hold promise.

TNF-α

15

Can you diagnosis gout with uric acid?

No, not this alone at least

16

Does AS have stiffness in the prolonged morning?

Yes!

Movement helps

17

Lumbosacral spine - both sacroiliac joint spaces are completely obliterated. There is also obliteration of the posterior elements in the distal lumbar area and bridging or "bambooing of the spine". Chest x-ray - "squaring-off of the mid-portion of the thoracic vertebrae but no significant syndesmophyte formation.

Diagnosis?

Ankylosing spondylitis

18

is mechanical back pain episodic?

yes (comes and goes)

it also usually does not have morning stiffness

19

HLA-B27 is ______necessary nor sufficient to cause a reactive arthritis. Clearly, the majority of HLA-B27 positive individuals never develop disease whereas HLA-B27 negative individuals can develop disease.

neither

20

HLA-B27 theories

Arthritogenic peptide hypothesis
Molecular mimicry
Free heavy chain hypothesis
Unfolded protein hypothesis

21

The arthritogenic response might involve specific microbial peptides that bind to HLA-B27 and then are presented in a unique manner to CD8+ (cytotoxic) T cells resulting in disease.

Arthritogenic peptide hypothesis

HLA-B27 theories

22

The induction of autoreactivity to self-antigens might develop as a result of “molecular mimicry” between sequences or epitopes on the infecting organism or antigen and a portion of the HLA-B27 molecule or other self-peptides.

Molecular mimicry:

HLA-B27 theories

23

Joints in AS vs RA?

AS: axial joints
RA: peripheral small joints

24

HLA-B27 heavy chains can form stable homodimers with no associated β-2 microglobulin on the cell surface. These ho-modimers can trigger direct activation of natural killer (NK) cells though recognition via killer cell immunoglobulin-like re-ceptors (KIR).

Free heavy chain hypothesis

HLA-B27 theories

25

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 deveoping AS.

Unfolded protein hypothesis

HLA-B27 theories

26

____% of people have AS

0.1%

27

1.0% of ____ people develop AS

HLA-B27

1/1000 people with this gene get the disease

28

10% of HLA-B27 people with____develop AS

FDR with AS

29

10% of ____ people are HLA-B27

white folks

30

____% of AS pts are HLA-B27

90%

31

would you test HLA-B27 to determine AS?

No, because so many people have the gene w/o disease

1/1000 people with this gene get the disease

32

spondyloarthropathy diseases

AS- bilateral
psoriasis
colitis- bilateral
reactive arthritis
undifferentiated

33

Gut-arthritis connection

Bacterial antigens from the gut could drain through the veno-lymphatic plexus (Batson’s plexus) into the area of the sacroiliac joints and spine.

These antigens could disseminate or be transported by monocytes to joints which lack a vascular basement membrane or to entheses.

34

unilateral spondyloarthropathy diseases

psoriasis
reactive arthritis
undifferentiated

35

Bacterial antigens that reach joints/entheses are taken up by antigen presenting cells through _______. Antigen presenting cells with these bacterial fragments can stimulate the adaptive immune system leading to inflammation.

(Gut-arthritis connection)

Toll-like receptors

36

Ankylosing spondylitis
Demographics

Affects males > females (7:3 ratio)

Onset occurs between 16 and 40 years old, rarely younger or older

Caucasians affected more than other racial groups.

37

two broad theroies for HLAB27

1- CD8 T cells
(mimicary, Arthritogenic peptide hypothesis)

2- Autoinflamitory
(unfolded, heavy chain)

38

IL-23*

interleukin-23 receptor

IL-23 which can activate proinflammatory Th 17 cells.

(Unfolded protein hypothesis)

39

ERAP-1*

endoplasmic reticulum aminopeptidase 1

involved in the trimming of peptides for loading MHC mole-cules (ie HLA-B27) into the endoplasmic reticulum. Abnormal loading may contribute to misfolding

40

Ankylosing spondylitis Rx:

NSAIDs
helps inhibit bone deformities

anti-tnf drugs help with inflammation

41

"Rat bite" erosion on x-ray is likely

Gout

42

Dactylitis

not in RA
is in AS

inflammation of an entire digit (a finger or toe), and can be painful.

43

in AS inflammation factors _____ causing deformity

ARE NOT

in RA, they are