8 - Spondyloarthropathies - Treatment Flashcards

1
Q

Reactive arthritis (reiter’s syndrome)

A

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

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2
Q

Post-Chalmydia-Induced ReA

A

Viable organisms can be detected in the joints

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3
Q

Post-Enteric ReA

A

Viable organisms can NOT be detected in the joints

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4
Q

ReA - 2 clinically different forms

A

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

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5
Q

ReA Features

A

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)

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6
Q

ReA ddx

A

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.

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7
Q

ReA - Urethritis

A
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

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8
Q

ReA - Specific Infections (Enteric)

A

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

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9
Q

ReA - Specific Infections (Venereal)

A

Develops 7 - 30 days after venereal infection with:

Chlamydia trachomatis
Chlamydia psittaci

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10
Q

Reactive Arthritis in the setting of AIDS

A

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

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11
Q

What does ReA in the setting of AIDS suggest?

A

Residual CD8 T cells are central to the disease pathogenesis.

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12
Q

Common to all cases of ReA

A

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.

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13
Q

HLA-B*27 Epi

A

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

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14
Q

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

A

HLA-B*07

HLA-B*51 associated with susceptibility in some populations

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15
Q

B*27 penetrance

A

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

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16
Q

ReA - Therapy

A

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

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17
Q

Psoriasis

A

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

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18
Q

Psoriatic Arthritis

A

Combination of spondyloarthritis and psoriasis

~15% had no prior psoriasis

19
Q

Psoriatic Arthritis - Diagnostic Characteristics

A
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
Q

Psoriatic Arthritis - Exclusions

A

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

21
Q

Psoriatic Arthritis - Epi

A

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

22
Q

Psoriatic Arthritis - Presentation

A
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
Q

Psoriatic Arthritis - Subtypes

A

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
Q

Distinctive features of PsA

A

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