8 - Spondyloarthropathies - Treatment Flashcards Preview

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Flashcards in 8 - Spondyloarthropathies - Treatment Deck (43):
1

Reactive arthritis (reiter's syndrome)

Inflammatory arthritis preceded by infection with enteric pathogens:

Salmonella
Yersinia
Shigella
Campylobacter
The Oculogenital pathogens (Chlamydia trachomatis)

Things that classify it as a spondyloarthritis spectrum condition:
HLA-B*27 association
Pattern of joint involvement
Absence of autoantibodies

2

Post-Chalmydia-Induced ReA

Viable organisms can be detected in the joints

3

Post-Enteric ReA

Viable organisms can NOT be detected in the joints

4

ReA - 2 clinically different forms

Triad of explosive, severe arthritis, conjunctivitis and urethritis along with enthesitis and keratodermic skin and nail lesions

OR

More common, somewhat milder and more self-limited post infectious arthritis without evidence of skin or eye involvement or urethritis

Typically self limited course (~70%) resolving over one or two months.
~30% have a chronic or recurrent course

5

ReA Features

Arthritis is severe and often develops over a few hours
Accompanied by malaise, fatigue, fever
One or both knees or other lower extremity joints
Joint fluid leukocytes > 20,000 (mostly PMNs, with activated macrophages)

6

ReA ddx

Gonococcal or other septic arthritis, especially to be considered if monoarticular
Enthesitis may be prominent (Lover's heel post-chlamydia)
Dactylitis and sacroiliitis may be present, erosions may develop.

7

ReA - Urethritis

Culture negative
Appears at the time of arthritis
Dysuria
Frequency
Urgency
Urethral discharge

Cervicitis & Cystitis in females

Conjunctivitis with marked erythema, pain and tearing

Less common:
Diarrhea
Abdominal pain
Findings of IBD on endoscopy

Uncommon:
Cardiac involvement
Kidney involvement
Severe eye involvement

8

ReA - Specific Infections (Enteric)

Develops 7 - 30 days after enteric infection with certain Gram negative rods:

Salmonella typhimurium
Salmonella paratyphi
Salmonella heidelbergii
Shigella flexneri 2a and 2b, but not Shigella sonnei
Yersinia enterocolitica
Campylobacter jejuni
Campylobacter fetus

They invade intestinal and other cells, likely resulting in the expression of arthritogenic peptides in class I MHC molecules, at the time of ReA, they're usually culture negative

9

ReA - Specific Infections (Venereal)

Develops 7 - 30 days after venereal infection with:

Chlamydia trachomatis
Chlamydia psittaci

10

Reactive Arthritis in the setting of AIDS

Keratodermia Blenorrhagicum:
Pustular psoriasis-like lesions of palms and soles

Psoriasis-like Lesions:
T Cell infiltration
Keratinocytes HLA-DR+ with delayed differentiation
Parakeratosis
Sterile microabscesses

The psoriatic arthritis gets worse as you move further distally

11

What does ReA in the setting of AIDS suggest?

Residual CD8 T cells are central to the disease pathogenesis.

12

Common to all cases of ReA

7 - 30 day delay in development (perhaps clonal expansion of memory/effector CD8s?)
IL-17 is a major cytokine in the joint fluids and Th17 T cells are likely the effector population.

13

HLA-B*27 Epi

70% of northern european caucasions, alaskan inuit and northern asians (frequency more like 25 - 40%) who develop reactive arthritis

0% in central africa, where ReA in the setting of advanced HIV is a major health problem

14

Major non-B*27 allele associated with susceptibility in northern european caucasoids

HLA-B*07
HLA-B*51 associated with susceptibility in some populations

15

B*27 penetrance

Up to 50% of HLA-B*27 individuals develop ReA during major epidemics of dysentery by arthritogenic organisms

16

ReA - Therapy

NSAIDs are sufficient if the ReA features rapidly resolve
Steroids not effective
Sometimes use RA drugs like Methotrexate, sulfasalazine, TNF inhibitors if persistent inflammation
Antibiotic therapy usually not indicated for enteric form unless there is evidence of microbial persistence

Use tetracycline for chlamydia

17

Psoriasis

Skin disease with retardation in keratinocyte differentiation
Induced by cytokines released from activated T cells

Onset - 15 - 30 years
Prevalence ~3% - Common

10 - 20% progress to PsA within 20 years

18

Psoriatic Arthritis

Combination of spondyloarthritis and psoriasis

~15% had no prior psoriasis

19

Psoriatic Arthritis - Diagnostic Characteristics

Psoriasis present or documented
Arthritis with synovitis
Enthesitis
Ankylosed joints (eg hallux rigidus)
Juxta-articular new bone formation
Sacroiliitis and/or spondyloarthritis
DIP joint arthritis
Onychodystrophy, pitting
Dactylitis

20

Psoriatic Arthritis - Exclusions

Fibromyalgia, RF positive rheumatoid arthritis
Intercurrent arthritis, eg Lyme disease
Repetitive motion-induced musculoskeletal syndromes

21

Psoriatic Arthritis - Epi

Most common spondyloarthritis
Prevalence 0.6 - 0.7%
M = F
Early onset (

22

Psoriatic Arthritis - Presentation

Obvious, subtle or no psoriasis
Sometimes only isolated nail disease
Onset typically insidious with stiffness
Sometimes acute mimicking gout
Can be acute following joint injury
Severity remarkably variable (silent ankylosis to crippling osteolysis)

23

Psoriatic Arthritis - Subtypes

Axial involvement and/or peripheral manifestations
Asymmetric joint involvement, predominantly of the lower limbs
Often presents as monoarthritis or oligoarthritis resembling ASp

Symmetrical peripheral arthritis resembling RA

24

Distinctive features of PsA

DIP joint arthritis
Involvement of all joints in one ray
Arthritis mutilans

25

PsA - DIP & nail disease

DIP extensor tendon enthesis forms integral supporting structuer for nail bed

Extensor tendon enthesitis invovles nail bed and other acral structures resulting in onychodystrophy

26

DIP Arthritis - ddx

Heberden's nodes
Chronic tophaceous gout

27

PsA - Nail Involvement

Nail matrix:
Pitting
Onychodystrophy, crumbling
Transverse ridging (beau's lines)
subungual hyperkeratosis
Leukonychia
Onycholysis
Ectatic capillaries

Acral dystrophy:
Nail matrix abnormalities
Acrokeratosis
Often seen in digit involved with DIP arthritis

28

PsA - Dactylitis

Sausage Digit
Widespread inflammatory edema

Due to:
DIP & PIP arthritis of same ray
Enthesitis
Tenosynovitis (Flexor > extensor)
Periostitis
Onychodystrophy

29

PsA - Enthesitis

Subtle and easy to overlook
Nonspecific foot pain
Tennis elbow in the non-dominant hand
Isolated posterior tibial tendinitis

Distribution differentiates from post-traumatic or occupational tendon injury

Occasionally widespread and symmetric

30

Psoriatic Arthritis - Peripheral Joint Patterns

Asymmetric oligoarthritis of small and medium-sized joints

DIP arthritis joints, also involves nails

Symmetric polyarthritis

Arthritis mutilans

31

PsA - Asymmetric oliogarthritis of small and medium sized joints

Classic, with time more joints accumulate

32

PsA - DIP arthritis joints, also involves nails

Classic and unique to psoriatic arthritis
Only ~5 - 10%
Associated paronychia and swelling of the digital tuft may make appreciation of the arthritis difficult

DDX heberden's nodes

33

PsA - Symmetric polyarthritis

Common pattern at onset, but is least specific for PsA
Hands
Wrists
Ankles
Feet

34

PsA - Arthritis mutilans

Osteolytic dissolution of joint with redundant overlying skin and telescoping digits (opera glass hand)
Classic but uncommon
Males and early-onset disease

35

PsA - Radiographic progression of DIP pathology

Joint space narrows
Condylar erosions
Reactive subperiosteal new bone
Pencil in cup

36

PsA - Synovial pathology

Active synovitis tissue biopsy:
CD4 - Primarily polyclonal unexpanded T Cells
CD8 - Mainly clonally expanded T Cells

37

Spondyloarthritis Disorders - Main Perpetrator

CD8 T Cell

Activated CD8 T Cells injure target cell and release cytokines (IFN-γ), reprogramming gene expression of nearby cells

CD8 T cells are CD28-negative, memory/effector cells that receive "signal 2" from NK receptor engagement by stress-induced ligands

Macrophages are activated by the IFN-γ and release cytokines (TNF-α)

Fibroblasts usually have fibrogenic and osteoblastic program activated resulting in heterotropic bone formation

38

Psoriatic Arthritis - Genetics

~40% Simplex, no family history
~60% Multiplex, strongly positive family history, often first degree relatives affected by psoriasis

39

Principal Psoriasis Susceptibility HLA allele

Cw*06:02 - Arthritis is 40 years beyond psoriasis
B*08 - Arthritis happens simultaneously with psoriasis, MOST SEVERE JOINT DISEASE
B*27 - Arthritis happen simultaneously with psoriasis, more severe joint involvementrequires more TNF therapy than Cw*06

40

PsA - C*06:02

Early onset severe psoriasis
Late onset, low penetrance mild musculoskeletal disease

41

PsA - B*27

Early onset MSK disease more synchronous with skin disease
Symmetrical spinal involvement
Entheseal-based disease
Dactylitis
Arthritis Mutilans

42

PsA - B*08

Asymmetrical spinal involvement
Joint fusion/deformity
Dactylitis

43

PsA - Treatment options

Symptomatic measures:
PT
Analgesics
NSAIDs
Local corticosteroid injection can be sufficient SOMETIMES

Broad Spectrum Immune Modulators:
Methotrexate mild- moderate benefit for joint disease, optimal for patient with extensive skin disease
TNF inhibitors especially in patients with predominant spinal disease or with major erosive, entheseal or dactylitic involvement, benefit of combining with methotrexate is controversial