Reactive and Undifferentiated Spondyloarthropathies…are they the

Ankylosing Spondylitis
Ewa Olech, MD
University of Nevada School of Medicine
Division of Rheumatology
Objectives
Review epidemiology and genetic risks of
SpA
 Examine pathophysiology and the
underlying disease process
 Review clinical features, manifestations
and comorbidities of SpA
 Discuss treatment options and
management strategies

The Spectrum of Spondyloarthritis
Characteristics of the
Spondyloarthritis








Sacroiliac & spinal joint involvement
Peripheral arthritis
Enthesopathy
Common spectrum of extra-articular features
(especially mucocutaneous, ocular)
Negative rheumatoid factor
Familial clustering
Association with HLA-B27
Potential infectious trigger
HLA-B27 and the Seronegative
Spondyloarthritides
Disorder
Ankylosing spondylitis
Reactive arthritis
Psoriatic arthritis
Psoriatic spondylitis
Enteropathic arthritis
Enteropathic Spondylitis
Juvenile Spondyloarthropathy
Undifferentiated Spondyloarthropathy
Acute Anterior Uveitis
HLA-B27
frequency (%)
95%
70%
25%
60%
7%
70%
70%
70%
50%
Most Common Seronegative
Spondyloarthropathies
1.
2.
3.
4.
Ankylosing Spondylitis (AS)
Reactive Arthritis (ReA)
Enteropathic Arthritis (associated with IBD)
Psoriatic Arthritis (PsA)
Pattern of Peripheral Synovitis
in the Spondyloarthropathies
Condition
Pattern of Involvement
Ankylosing
Spondylitis
• Asymmetric large-joint oligoarthritis, primarily lower
extremities
Reactive
Arthritis
• Asymmetric large-joint oligoarthritis, primarily lower
extremities
Enteropathic • Asymmetric large-joint oligoarthritis, primarily lower
Arthritis
extremities
Psoriatic
Arthritis
• Oligoarticular disease: Asymmetric large-joint
oligoarthritis, primarily lower extremities
• Polyarticular disease: Symmetric polyarthritis
involving large and small joints resembling RA
• DIP joint disease: Associated with nail involvement
• Arthritis mutilans: Severely destructive arthritis
involving the hands with shortening of the digits
Epidemiology of AS




The incidence of AS underestimated1
 Between 350,000 - 1 million Americans2,3
 0.1% to 0.9% of the population worldwide4,5
Age of onset typically between 15 - 35 years1,2,3
2-3 times more frequent in men than in women6
The mean delay in the diagnosis: 5-11 years
1The
Spondylitis Association of America. Available at: www.spondylitis.org. Accessed December 2,2004.
2Davis J. Semin Arthritis Rheum. 2004;34:668–677.
3Newman PA, et al. Rheum Dis Clin Am. 2003;29(3):561–571.
4Lawrence RC, et al. Arthritis Rheum. 1998;41(5):778–99.
5Sieper J, et al. Ann Rheum Dis. 2002;61(suppl 3);iii8–18.
6Khan MA. Ann Intern Med. 2002;136:896–907.
Enthesitis is the Hallmark of AS

Enthesitis may affect:
 Capsules and intracapsular ligaments of large synovial
(diarthrodial) joints and apophyseal joints
 Ligamentous structures of cartilaginous joints




intervertebral discs
manubriosternal joints
symphysis pubis
Ligamentous attachments






spinous processes of the vertebrae
illiac crests
trochanters
patellae
calcanei
clavicle
B. Spondyloarthropathies: AS-pathology. In: Hochberg M, et al., eds. Rheumatology 3rd ed.
Edinburgh, Scotland: Mosby;2003:1205. Available at: www.rheumtext.com. Accessed December 6,2004.
Vernon-Roberts
Enthesitis in
Spondyloarthritis
Enthesitis (Heel)
MRI of Achilles Tendinitis
Diffuse bone
marrow edema of
the calcaneous
 Swelling of the
Achilles Tendon
 Fluid collection in
retrocalcaneous
bursa

Inflammatory Enthesitis


Subchondral
bone
inflammation
and
resorption
Periosteal
new bone
formation
McGonagle D. Arthritis Rheum. 1999. 42:1080-1086.
Enthesitis

Enthesitis of the
Spine


Occurs at capsular
and ligamentous
attachments
Involvement of bony
attachment of Anterior
Longitudinal Ligament
Ankylosing spondylitis: thoracic and lumbar
vertebrae "squaring," osteopenia, and ossification
Ankylosing
spondylitis:
lumbar vertebrae,
bamboo spine
Cervical Spine
Normal
Sacroiliitis
Ankylosing spondylitis: advanced sacroiliitis
Ankylosing spondylitis:
advanced sacroiliitis
(radiograph)
AS: Sacroiliitis by MRI
Thick
Arrows:
Subchondral
marrow
inflammation
shown by
increased
MRI signal
Thin Arrow:
Joint cavity
Maksymowych WP. Can Fam Physician. 2004;50:257–262. Available at:
http://www.cfpc.ca/cfp/2004/Feb/vol50-feb-cme-3.asp. Accessed November 3,2004.

Inflammatory versus Mechanical
Low Back pain
Inflammatory pain
Mechanical pain
Age at onset
<40 yr
Any age (usually later)
Type of onset
Insidious
Acute
Symptom duration
>3 mo
<4 wk
Morning stiffness
>30 min
<30 min
Nocturnal pain
Common
Absent
Effect of exercise
Improvement
Exacerbation
Sacroiliac joint
tenderness
Frequent
Absent
Back mobility
Loss in all planes
Abnormal flexion
Chest expansion
Often decreased
Normal
Neurologic deficits
Unusual
Possible
Clinical Features
•
•
Chronic inflammatory low back pain and stiffness1
– Buttock pain
– Symptoms worsen after prolonged periods of
inactivity ('gel phenomenon')
– Symptoms improved with exercise / hot shower
– Some patients may wake-up at night to exercise or
move about for a few minutes before returning to bed
Peripheral joint involvement2
– Synovitis
– Dactylitis
– Enthesitis
1Khan
MA In: Hochberg M, et al., eds. Rheumatology 3rd ed. Edinburgh, Scotland: Mosby;2003:1161–1170.
2Keat A. In: Klippel JH, ed. Primer On The Rheumatic Diseases.
Clinical Features
•
Limitation of spinal mobility and chest expansion
•
Characteristic radiographic findings late in disease
•
Constitutional symptoms may occur in early stages
•
–
anorexia
–
malaise
–
weight loss
–
low-grade fever
–
fatigue
Extraarticular manifestations
Khan
MA. Spondyloarthropathies: clinical features of AS. In: Hochberg M, et al., eds. Rheumatology 3rd ed..
Extraarticular Manifestations of AS
Eyes
Lungs
(Acute Anterior Uveitis)
(Restrictive Lung Disease,
Apical Fibrocystic Disease)
Heart
Kidneys
(Aortic Insufficiency, Heart Block)
(Amyloidosis)
Gut
Skin
(Inflammatory Bowel Disease,
Microscopic Inflammatory Lesion)
(Psoriasis & Nail Changes)
Osteoporosis
Dactylitis
Khan
MA. Ann Intern Med. 2002;136:896–907.
Acute Anterior Uveitis
Most common extraarticular complication
(approximately 1/3 of patients with AS)
 Unilateral, asynchronous with arthritis
flares
 Pain, redness, lacrimation, photophobia,
blurred vision
 Untreated can lead to vision loss

Anterior Uveitis

Pt with AS, red,
sore, gritty eyes,
blurred vision
should get an
urgent
ophthalmologic
examination
Patient Case
26 yrs old Caucasian male
 C/o inflammatory back pain since 20 y/o
 Recently bilateral heel pain
 Constitutional sx: fatigue, low grade fever,
weight loss
 Labs:

HLA B27 – positive
 Elevated CRP

Sacroiliitis –
bilateral grade 3 changes
AS: Modified New York Criteria
1.
Low back pain >3 months
•
•
Improved with exercise
Definite AS equals:
at least 1 criteria
Not relieved by rest
2.
Limited lumbar motion
3.
Reduced chest expansion
4.
Bilateral grade ≥2 sacroiliitis
on x-ray
5.
PLUS
Either 4 or 5
Unilateral grade 3 to 4 on
sacroiliitis on x-ray
van
der Linden S, et al. Arthritis Rheum. 1984;27:361–368.
Ankylosing
spondylitis:
postural
changes
Ankylosing
spondylitis:
ankylosis,
lumbar spine
Schoeber’s
Wall to Occiput
Chest Expansion
Progression of Deformities
TREATMENT OF ANKYLOSING
SPONDYLITIS
Treatment
Exercise
 NSAIDS
 Traditional DMARDs – peripheral arthritis
 Biologics
 Surgery

42
Structures of TNF Inhibitors
Etanercept
(Enbrel®)1
Adalimumab (Humira®),
Golimumab (Simponi®)
Infliximab
(Remicade®)2
Fab′
Receptor
IgG1
Fc
IgG1
Fc
Recombinant
receptor/Fc fusion
protein
Recombinant
human/mouse
chimeric IgG1
Fcfree
Recombinant
human IgG1
Certolizumab pegol
(CIMZIA®)5
1 Fab′
PEG
Recombinant
humanized PEGylated
IgG1 Fab’ fragment
Monoclonal
antibody
42
Approved anti-TNF agents for
Ankylosing Spondylitis
Therapeutic
Agent
Trade
Name
Mechanism of Usual Maintenance
Action
Dose
Route
Infliximab
Remicade
TNF-α
inhibitor
5–10 mg q 4 - 8 wks
IV
Etanercept
Enbrel
TNF-α
inhibitor
50 mg weekly
SQ
Adalimumab
Humira
TNF-α
inhibitor
40 mg q 2 wks
SQ
Golimumab
Simponi
TNF-α
inhibitor
50 mg q 4 wks
SQ
Certolizumab
Pegol
Cimzia
TNF-α
inhibitor
200 mg q 2 wks or
400 mg q 4 wks
SQ
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