8 - Spondyloarthropathies - Treatment Flashcards
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
Post-Chalmydia-Induced ReA
Viable organisms can be detected in the joints
Post-Enteric ReA
Viable organisms can NOT be detected in the joints
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
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)
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.
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
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
ReA - Specific Infections (Venereal)
Develops 7 - 30 days after venereal infection with:
Chlamydia trachomatis
Chlamydia psittaci
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
What does ReA in the setting of AIDS suggest?
Residual CD8 T cells are central to the disease pathogenesis.
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.
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
Major non-B*27 allele associated with susceptibility in northern european caucasoids
HLA-B*07
HLA-B*51 associated with susceptibility in some populations
B*27 penetrance
Up to 50% of HLA-B*27 individuals develop ReA during major epidemics of dysentery by arthritogenic organisms
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
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
Psoriatic Arthritis
Combination of spondyloarthritis and psoriasis
~15% had no prior psoriasis
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
Psoriatic Arthritis - Exclusions
Fibromyalgia, RF positive rheumatoid arthritis
Intercurrent arthritis, eg Lyme disease
Repetitive motion-induced musculoskeletal syndromes
Psoriatic Arthritis - Epi
Most common spondyloarthritis
Prevalence 0.6 - 0.7%
M = F
Early onset (
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)
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
Distinctive features of PsA
DIP joint arthritis
Involvement of all joints in one ray
Arthritis mutilans
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
DIP Arthritis - ddx
Heberden’s nodes
Chronic tophaceous gout
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
PsA - Dactylitis
Sausage Digit
Widespread inflammatory edema
Due to: DIP & PIP arthritis of same ray Enthesitis Tenosynovitis (Flexor > extensor) Periostitis Onychodystrophy
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
Psoriatic Arthritis - Peripheral Joint Patterns
Asymmetric oligoarthritis of small and medium-sized joints
DIP arthritis joints, also involves nails
Symmetric polyarthritis
Arthritis mutilans
PsA - Asymmetric oliogarthritis of small and medium sized joints
Classic, with time more joints accumulate
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
PsA - Symmetric polyarthritis
Common pattern at onset, but is least specific for PsA Hands Wrists Ankles Feet
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
PsA - Radiographic progression of DIP pathology
Joint space narrows
Condylar erosions
Reactive subperiosteal new bone
Pencil in cup
PsA - Synovial pathology
Active synovitis tissue biopsy:
CD4 - Primarily polyclonal unexpanded T Cells
CD8 - Mainly clonally expanded T Cells
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
Psoriatic Arthritis - Genetics
~40% Simplex, no family history
~60% Multiplex, strongly positive family history, often first degree relatives affected by psoriasis
Principal Psoriasis Susceptibility HLA allele
Cw06:02 - Arthritis is 40 years beyond psoriasis
B08 - Arthritis happens simultaneously with psoriasis, MOST SEVERE JOINT DISEASE
B27 - Arthritis happen simultaneously with psoriasis, more severe joint involvementrequires more TNF therapy than Cw06
PsA - C*06:02
Early onset severe psoriasis
Late onset, low penetrance mild musculoskeletal disease
PsA - B*27
Early onset MSK disease more synchronous with skin disease Symmetrical spinal involvement Entheseal-based disease Dactylitis Arthritis Mutilans
PsA - B*08
Asymmetrical spinal involvement
Joint fusion/deformity
Dactylitis
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
