spondyloarthropathy presentation 2
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SeronegativeSpondyloarthropathies
Dr. osama sayed
daifallh
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Back to basics
Axial skeleton Skull
Vertebral column Vertebrae
Sacrum
Coccyx
Ribs
Sternum
Appendicular skeleton Girdles
Extremities
The skeleton
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Back to basics
Diarthrosis (moveable) Majority of articulations
Contiguous bones are covered by cartilage, connectedby ligaments, and have an interposing synovial sac
Synarthrosis (immoveable) Contiguous bones are in direct contact without
cartilage, syovium, or ligaments
Amphiarthrosis(sort of moveable)
Characteristics of both diarthrosis and synarthrosis Contiguous surfaces are either:
Connected by fibrocartiganeous disks (vertebral joint)
Covered by fibrocartilage andpartialsynovium, and attachedby external ligaments (sacroiliac joint)
Articulations
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Back to basics
Enthesis is the site of bony attachment of
Tendon
Ligament
Cartilage
Joint capsule
Fascia
Enthesis
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spondyloarthropathies
Ankylosing spondylitis (the prototype)
Psoriatic arthritis
Reactive arthritis Formerly called Reiters syndrome)
Enteropathic arthritis
Undifferentiated spondyloarthropathy
Comprise these conditions
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y are ese seases c ass etogether?
HLA-B27 association
Enthesitis (both juxtarticular and extrarticular)
Axial skeleton arthritis (generally secondary to
juxtarticular enthesitis) Spondylitis (inflammation of vertebral bodies)
Sacroiliitis (inflammation of sacroiliac joint)
Peripheral arthritis (generally a synovitis)
Asymmetric (cf rheumatoid arthritis)
Extrarticular manifestations (besides enthesitis)
Seronegativity Rheumatoid factor and ANA negative
Well, because they share these characteristics
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y are ese seases c ass etogether?
Ankylosing spondylitis: 95%
Ethnically matched controls: 8%
Reactive arthritis: 70%
Enteropathic arthritis: 50%
Psoriatic arthritis: 35%
HLA-B27 association
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y are ese seases c ass etogether?
Inflammation of an enthesis It is the Principal pathogenetic mechanism in
spondyloarthropathy
Pathogenesis
CD8 T cells infiltrate entheses Activated macrophages release cytokines (egTNF)
Fibroblasts synthesize new collagen(cf rhematoid arthritis!!)
New bone formation results
Clinical Axial skeleton arthritis (see later)
Enthesopathy at other sites
Calcaneal spurs at plantar fascia insertion
Spurs at Achilles tendon insertion
Manifests as extrarticular or juxtarticular bony tenderness
Enthesitis
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y are ese seases c ass etogether?
Arises from enthesitis
Includesspondylitis andsacroiliitis
Spondylitis
CD8 T cells invade the junction of the annulus fibrosis and thevertebral body (an enthesis)
Annulus fibrosis is replaced by bone (syndesmophytosis)
Vertebral bodies assume a square shape, and ultimately a
bamboo spine
Sacroiliitis CD8 T cells invades the subchondral area at the junction of the
bones and the cartilage (an enthesis)
Cartilage on iliac side is replaced by bone, obliterating the jont
space and hardening the joint
Axial skeleton arthritis
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Ankylosing spondylitis
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AS: Characteristic Pathologic Features
Sieper J. Arthritis Res Ther 2009;11:208Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035
Chronic inflammation in:
Axial structures (sacroiliac joint, spine, anterior chest
wall, shoulder and hip)
Possibly large peripheral joints, mainly at the lower limbs
(oligoarthritis)
Entheses (enthesitis)
Bone formation particularly in the axial joints
Inflammation
Disease activity
Structural damage
Syndesmophytes formation
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AS: Signs and Symptoms
Axial manifestations:
Chronic low back pain
With or without buttock pain
Inflammatory characteristics:
Occurs at night (second part)
Sleep disturbance
Morning stiffness
Limited lumbar motion
Onset before age of 40 years
Inflammatory back
pain (IBP) = Characteristic
symptom
MRI sacro-iliac joint
Inflammation
Disease activity
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Ankylosing spondylitis
Inflammatory back pain requires 4 of these 5
criteria (serves as a screening tool for AS)
Young onset (40 years)
Morning stiffness (30 minutes)
Chronic (3 months)
Activity improves the pain (rest does not) and rapide
response to NSAIDS within 24 hrs
Insidious (not acute)
(mnemonic is YMCA-I)
Diffuse lumbar or gluteal, not focal or radicular
Cf focal pain of disk herniation
Inflammatory back pain
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Most striking feature of AS =New bone formation in the
spine with:
Spinal syndesmophytes
Ankylosis
Both can be seen onconventional radiographyBamboo spine and
bilateral sacroiliitis
X-ray showing
syndesmophytes
Even in patients with longer-
standing disease, syndesmophytes
are present in 50% patients and a
smaller percentage will develop
ankylosis
Sieper J. Arthritis Res Ther 2009;11:208
AS: Structural Damage
Structural damage
Syndesmophytes formation
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Peripheral manifestations
Enthesitis Peripheral arthritis Dactylitis
AS: Signs and
Symptoms
50% patients with
enthesitis1
1Cruyssen BV et al. Ann Rheum Dis 2007;66:1072-10772Sidiropoulos PI et al. Rheumatology 2008;47:355-361
Up to 58% patients
ever had arthritis1
Much smaller number
of patients2
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Why are Dactylitis and Enthesitis Important?
The first abnormality to appear in swollen
joints associated withspondyloarthropathies is an enthesitis2
Likelihood of erosions is higher
for digits with dactylitis thanthose without1
1Brockbank. Ann Rheum Dis 2005;62:188-90;2McGonagle et al. The Lancet 1998;352.
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Ankylosing spondylitis
Restriction of lumbar movement Shobers testmark the patients back at the level of the posterior
iliac spine. Place one finger 5 cm below this mark and a 2ndfinger
10 cm above this mark. Patient is instructed to touch his toes. If
the distance between finegrs increases < 5 cm, lumbar flexion is
limited.
Anterior uveitis (iritis or iridocyclitis) (25%)
Acute eye pain
Increased lacrimation
Photophobia Blurred vision
Aortitis with fibrosis
Aortic insufficiency
Third degree heart block (5%)
Other clinical (besides back pain)
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AS: Extra-articular Manifestations
(EAM)EAM Prevalence in ASPatients (%)Anterior uveitis 30-50
IBD 5-10
Subclinical inflammation of the gut 25-49
Cardiac abnormalitiesConduction disturbances
Aortic insufficiency
1-33
1-10
Psoriasis 10-20
Renal abnormalities 10-35
Lung abnormalities
Airways disease
Interstitial abnormalities
Emphysema
40-88
82
47-65
9-35
Bone abnormalities
Osteoporosis
Osteopenia
11-18
39-59
Elewaut D & Matucci MC. Rheumatology 2009;48:1029-1035
Terminal ileitis
Anterior uveitis
Cardiac
abnormalities
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AS: Extra-skeletal Signs and
SymptomsOther common symptoms seen during the early stages of diseaseinclude: Anorexia
Malaise
Low grade fever
Weight loss
Fatigue
1Missaoui B. et al. Ann Readapt Med Phys 2006;49:305-8, 389-391
Linden VD et al. Chapter 10. In: Firestein, Budd, Harris, McInnes, Ruddy and Sergent, eds. KelleysTextbook of Rheumatology: Spondyloarthropathies. 8thed. Saunders Elsevier;2009:p.1176
Fatigue is a frequent complaint
of patients with AS1
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Laboratory tests
ESR
CRP
CBC
HLA-B27
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Radiographic and imaging
Sacroiliitis
Whiskering at enthesis (calcaneous,
ischial tuberosities, femoral trochanters)
Squaring of vertebrae
Syndesmophytes
Spinal osteoporosis Hip, shoulder
A k l i d liti
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Ankylosing spondylitis
Radiographic evaluation
Sacroiliacjoints
Grade 0 Normal
Grade 1 Suspicious changes
Grade 2 Minimal abnormalitysmall localized areas with
erosion or sclerosis without alterations in joint width
Grade 3 Unequivocal abnormalitymoderate or advancedsacroiliitis with 1 of the following: erosions,
sclerosis, widening, narrowing, or partial ankylosis
Grade 4 Severe abnormalitytotal ankylosis
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Marginal erosions and new bone formation
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Sacroiliitis
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Ossification of SI joint space
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Bamboo spine
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Enthesopathy of heels
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A k l i d liti
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Ankylosing spondylitis
Low back pain 3 months improved by exercise and notrelieved by rest
Limitation of lumbar spine in sagittal and frontal planes
Chest expansion reduction relative to normal values
corrected for age and sex (costovertebral ankylosis,25%)
Radiographic criteria of sacroiliitis
Bilateral grade 2-4 OR
Unilateral grade 3-4
Ankylosing spondylitis is defined by the presence of either
radiographic criterion PLUS any clinical criterion
Modified New York Diagnostic Criteria
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ASAS Classification Criteria for
Axial SpAIn patients with back pain 3 months and age at onset
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Psoriatic arthritis
Inflammatory polyarthritis associated with
psoriasis
May occur prior to the onset of skin
disease
Usually seronegative
M=F
Prevalence rate 0.1%
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Psoriatic arthritis is an enthesitis
DIP joint disease
Spinal inflammation Dactylitis-sausage finger
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Psoriatic ArthritisClinical Variants
Inflammatory DIP disease
Asymmetic oligoarthritis with large and
small joints
Symmetric polyarthritis
Arthritis mutilans
Spondyloarthropathy
Spondylitis and sacroiliitis
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Psoriatic ArthritisOther Features
Nail pitting
Skin disease
Pitting edema
Inflammatory eye disease
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Radiological features of PsA
Lack of juxta-articular osteopenia
Pencil-in cup change
Ankylosis Periostal reaction
Asymmetric sacroiliitis
Coarse syndesmophytes
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Erosive psoriatic arthritis
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Psoriatic ArthritisTreatment
NSAIDs
Little role for systemic steroids, but IA
steroids can be very helpful
Methotrexate
TNF inhibitors
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Management of PsA
NSAIDs
Methotrexate
Sulphasalazine
Leflunomide
Azathioprine
Cyclosporine
Anti TNFtherapies
Intra articular injections of corticosteroids
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Methotrexate
Efficacy in PsA 1stdemonstrated in 1964.
Placebo controlled study of 21 patients
with active skin disease and peripheral
arthritisobservation 3 months.
Improvement in skin and joint involvement.
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Sulfasalazine
5 controlled studies
221 patients treated with 2 g/day over 36
week course. Improvement in tender and
swollen joints.
Its actions appears to be confined to
peripheral arthritis with no benefit in axial
disease
Rare reports of cutaneous improvement.
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Leflunomide (ARAVA)
A selective pyrimidine synthesis inhibitor
that targets activated T cells lacking a
salvage pathway.
Randomised double blind, placebo
controlled study in 188 patients with active
PsA and active rash.
After 6 months 59% met primary efficacy.Compared with 30% of placebo.
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Other options ?
Gold
Cyclosporine A
Azathioprine and 6-mercaptopurine
Antimalarial agents
Colchicine
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InfliximabEtanercept
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Mouse
(Binding site for TNF)
Human (IgG1)
Fc region of
human IgG1
Extracellular domain of
human p75 TNF receptor
CH3 CH2
SS
SS
S
S
S
S
S
S
SSS
S
p
Adalimumab
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Et t i P A
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Stratification (N -205 PsA, active dis.)
- Etanercept 25 mg twice weekly (n=101)
as either Etanercept (n=59) or
Etanercept+MTX (n=42)
- Placebo (n=104) or either placebo alone
(n=61) or Placebo +MTX (n=43)
Gottlieb A. Ann Rheum Dis 2002;61(Suppl1)
Etanercept in PsA
A phase III clinical trial
P t f ti t
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0
10
20
30
40
50
60
1 3 6
Etanercept
Placebo
Months
Gottlieb A. Ann Rheum Dis 2002;61(Suppl1
Percentage of patients
achieving ACR 20
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P valueEtanercept
n= 101
Placebo
n=104
Measure
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55
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Adalimumab (Humira)
Fully human anti-TNF monoclonal
antibody, SC, 40 mg e.o.w
315 patients with PsA
At week 12, ACR 20 in 58% of the
adalimumab-treated patients vs 14% of
the placebo-treated patients .
59% achieved a 75% PASI improvement
response at 24 weeks
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T cell activators blocking
Alefacept (Amevive)
Fully human fusion protein binds CD2 on
memory T cells and blocks interaction with
LFA-3 on the antigen presenting cells.
Efalizumab (Raptiva)
Humanised antibody to the CD11 subunitof LFA1
PsA Treatment Guidelines
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PsA Treatment Guidelines
Establish Diagnosis of Psoriatic Arthritis
Reassess Response to
Therapy and Toxicity
EducationPhysiotherapyAnalgesia
NSAID (continous)
Biologics(anti-TNF)
+/- Corticosteroid inj
Axial DiseasePeripheral
Arthritis
Skin &
Nail
Disease
Dactylitis Enthesitis
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PsA Treatment Guidelines
Mild PsASevere and moderate PsA
(oliygo-polyarthritis?).
Poor prognosis
PsA
Respond NSAIDs and/or
IA steroids
Early DMARD
(MTX,SZP, LEF)
Adequate therapeutic
trial of 2 DMARD
Anti TNF
Respond
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Reactive arthritis
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Reactive arthritis
In 1916, Hans Reiterreported Reiters syndrome:a triad of nongonococcal urethritis, conjunctivitis,
and arthritis that occurred in a young German
officer following an episode of bloody dysentery
Subseqently, more cases were reported following
enteric infections OR venereally acquired
genitourinary infections.
In 1967, the term reactive arthritiswas applied tosimilar cases following Yersiniagastroenteritis
The two terms should be considered synonomous
The term reactive arthritisis increasingly preferred
Interesting historical backdrop
Reactive arthritis
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Reactive arthritis
Clinical syndrome triggered by specific etiologic
agents in a genetically susceptible host
Follows 1-4 weeks after a
Urogenital infection (affects principally men) Usually C. trachomatis
Enteric infection (affects both genddrs equally)
Salmonella
Shigella
Campylobacter
Yersinia
Pathogenesis
Reactive arthritis
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Reactive arthritis
Peripheral arthritis Asymmetric additive oligoarthritis (usually)
Synovitis
Warm
Edematous
Tender
Pain with active or passive movement
Usually lower extremity joints (knee, ankle, subtalar)
Conjunctivitis
Clinical
Reactive arthritis
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Reactive arthritis
Nongonococcal urethritis Occurs in postenteric or postvenereal disease
When it occurs in postvenereal disease, C. trachomatisisoften the etiology
When present, is usally the first symptom In men
Mild dysuria
Mucopurulent urethral discharge
May present as prostatitis or epididymitis
In women Dysuria
Purulent vaginitis or cervicitis with vaginal discharge
Asymptomatic urethritis often features sterile pyuria
Clinical
Reactive arthritis
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Reactive arthritis
Keratoderma blenorrhagica A papulosquamous skin rash
Comprises vesicles that become hyperkeratotic,forming crusts before disappearing Palms/soles
Penis (causing circinate balanitis
Oral ulcers (ususally shallow and painless)
Inflammatory back pain (50% of patients)
Enthesitis (40%) Dactylitis (40%)
Anterior uveitis (20% of patients)
Clinical (continued)
Reactive arthritis
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Reactive arthritisKeratoderma blenorrhagica
Reactive arthritis
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Synovial fluid analysis Pleocytosis (5 000 to 50 000 WBC/mcL) with
polymorphonuclear cell predominance
Protein levels
Glucose normal Cf reduced glucose level in true septic arthritis
Gram stain and culture are sterile
Urethral or cervical smears in patients with
clinical urethritis C. trachomatis
N. gonorrhoeae
Evaluation
Enteropathic Arthritis
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Enteropathic Arthritis
Affects 10-20% of patients with inflammatory
bowel disease (IBD)
Peripheral arthritis affects 10-20% of IBD
patients Generally affects knees, ankles, and feet
Always indicates active IBD
Radiographic axial arthritis affects 10% of IBDpatients
Frequently asymptomatic
Independent of bowel inflammation
Clinical
y are ese seases c ass etogether?
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together?
Physical therapy and exercise Nonsteroidal antiinflammatory agents
Indamethacin
Disease modifying anti-rheumatic drugs(DMARDs) Methotrexate: inhibits recruitment of CD4 and CD8 T
cells
Tumor necrosis factor antagonists Infliximab: a monoclonal antibody that binds to TNF and
inhibits binding of TNF to its receptor
Etanercept: similar emchanism to infliximab
Treatment
Key Actions Attributed to TNFa
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75
Key Actions Attributed to TNFa
InfliximabEtanercept
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Mouse
(Binding site for TNF)
Human (IgG1)
Fc region of
human IgG1
Extracellular domain of
human p75 TNF receptor
CH3 CH2
SS
SS
S
S
S
S
S
S
SSS
S
Adalimumab
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S ff
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Side effects
Good tolerability
The most frequent was injection site reactionin37%
Infection in 35% and headache 17 %
Post marketing : severe infections including TB
and fatalities, demyelinative disorders,lymphoma, rare cases of pancytopenia includingaplastic anemia,vasculitis, drug induced lupus
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79
REMICADE(infliximab)
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( )
Safety
Hypersensitivity reactionsSepsis, pneumocystosis, histoplasmosis,and listeriosis have been reported
Rare cases of lymphoma, demyelinatingdiseases and drug induced lupus
Increased incidence of TB
top related