Low Back Pain and the
Seronegative
Spondyloarthropathies
Scott R. Burg, D.O.
Orthopaedic and Rheumatologic Institute
Cleveland Clinic
Spondyloarthropathies (SPA)
• A group of common inflammatory
rheumatic disorders characterized by:
- Axial and/or peripheral arthritis, enthesitis,
dactylitis
- Potential extra-articular changes such as
uveitis and skin rash
Common Genetic Predisposition
• HLA-B27 gene
• Association varies widely among
various SPAs and ethnic groups
• Environmental factors seem to
be triggering the diseases in
genetically predisposed
Radiographic Hallmark
• Sacroilitis
SPA
• Characterized by:
-
Sacroilitis
Inflammatory back pain
Peripheral arthropathy
Absence of rheumatoid factor/CCP and
subcutaneous nodules
- Enthesitis
- Extra spinal involvement (eye, heart, lung and skin)
- HLA-B27
• At least 6 other genes associated with ankylosing
spondylitis identified to date
Inflammatory Low Back Pain
• Assumed to be characterized by
inflammation of SIJ and lumbar spine
• Young age of onset
• Continuous pain > 3 months
• Morning stiffness
• Pain improving on activity
Inflammatorty Back Pain
• Unilateral or bilateral
• Alternates from side to side
• Responds well to NSAIDs
Sacroilitis and Inflammatory Low
Back Pain
Prevalence 50%
F.D. Hart Quarterly Journal of
Medicine, 1949
A frequent feature of the pain and stiffness was the
aggravation caused by immobility. Waking in the
morning stiff and in pain, the patient gradually
became more supple during the day, feeling at his
best from the afternoon until bedtime. One patient
noted that by frequent exercise, his condition was
kept in check, but confinement to bed for any cause
made him worse. Another woke himself up (every 2
hours) throughout the night to exercise his spine as
otherwise, he suffered unduly in the morning.
IBP in USA
• Present in 6%
• General back pain 20%
• Performs well as case ascertainment
tool for those who seek care
• SPA in 1%, what constitutes the gap?
IBP Concept
• Distinguishing feature in all criteria sets
developed to identify AS and SPA
• Criteria sets share several key clinical
features
• Diverge on genetic indicators and
radiographic parameters
Value of IBP Concept in Primary
Care Setting
• Defines a group at risk for SPA or AS
• Defense of further diagnostic testing
i.e. imaging or genetic tests
• Negative tests in IBP any justification
for NSAID’s or biologics to treat
symptoms or prevent SPA or AS
Spondyloarthropathies (SPA)
• Ankylosing spondylitis (AS)
• Reactive arthritis (REA)
• Psoriatic arthritis (PSA)
• SPA associated with inflammatory
bowel disease (IBD)
• Undifferentiated SPA (USPA)
• Juvenile onset spondyloarthritis
Ankylosing Spondylitis (AS)
• Most common and most typical
• 0.2-1.2% of Caucasian population.
Variability based on regional, genetic
and environmental factors
• Lower male to female ratio (2-3.1)
based on recent epidemiologic studies
• Higher in HLA-B27 populations
Diagnosis of AS Delayed
• As long as 8 years
• Longer delays in females
Diagnostic and Classification
Criteria
• European spondyloarthropathy study
group (ESSG)
• Assessment in Spondyloarthritis
International Society (ASAS) proposed
new set of diagnostic criteria enabling
identification of SPA before structural
changes occur in the spine
MRI
• Changes now included in new
classification criteria of early axial SPA
• Major tool diagnostically
AS Symptoms
• Early adulthood
• Dull pain buttock / lower lumbar area
• Morning stiffness relived on exertion worsened on
inactivity
• Enthesitis
• Inflammation at bone insertion sites of ligaments or
tendons
• Pain of enthesopathy varies and depends on affected
location
• Frank arthritis 25-35% involving large joints in
asymmetrical fashion
• Neck pain with increased ROM later manifestation
Dactylitis (Sausage Digit)
• PSA
• REA
• Joint and tenosynovial inflammation
Other Clinical Features of AS
• Acute anterior uveitis – 30% often
antedates spondylitis
• AI, CHF, aortitis, angina, pericarditis,
conduction deficits
• Dyspnea, cough, hemoptysis =
pulmonary fibrosis
Reactive Arthritis (REA)
• Arthritis 2-4 weeks after urogenital or enteric
infection often in presence of HLA B27 antigen
• Risk 50% higher in HLA-B27 positive
• HLA B-27 positive associated with severity and
chronicity
• Enthesitis
- 70% of patients
- Heel spur and pain
- Achilles tendonitis
• Knee synovitis with large effusions
• Dactylitis typical
Extra-articular Features
• Urethritis
• Cervicitis
• Vulvovaginitis and salpingitis
• Prostatitis
• Oral ulcers, e. nodosum, conjunctivitis
• Cardiac involvement
Enteropathic Associated Arthritis
(IBD)
• 10% of patients may antedate IBD
• Asymmetric, large joints, lower limb
• Occasional symmetrical, small
joint polyarthritis
Spondyloarthritis and Sacroilitis
• Independent course compared to bowel
disease
• Milder than AS
• HLA-B27 positivity
- Weaker than AS
- 25-60% of patients positive
Undifferentiated
Spondyloarthropathy (USPA)
• Patients without criteria for
well-defined SPA
• Fewer extra-articular changes
• Sacroilitis / spondylitis absent, or
very mild after years of active disease
• Good prognosis
Juvenile Spondyloarthropathy
• Asymmetric
• Lower extremity peripheral
• Boys aged 7-16 years
• Enthesitis and dactylitis prominent
• Systemic manifestations frequent in
juvenile than adult form
Psoriatic Arthritis (PSA)
• Develops in 5-40% of psoriasis patients
• Incidence 7.2 per 100,000/year
• Existing psoriasis patients prevalence
rises from .2% of 7-40%
Arthritis in PSA
• Asymmetric in small and large joints
• Patterns include:
- Mutilans
- Peripheral oligoarthritis / polyarthritis
- Spondylitis
- DIP arthritis (fingers and toes >50%)
Back Pain in PSA
• Cervical spine disease common (>50%)
• Progresses in severity in parallel with
disease of peripheral joints
• Sacroilitis – 20% of patients
• Spondylitis – 5% of patients
PSA
• Nails (83%) or skin precede or
follow joint involvement
• Scalp, behind ears, umbilicus
or gluteal folds
• Fatigue, iritis, uveitis
Biomarkers to Assess PSA
• CRP
• Matrix metalloproteinase-3
• Circulating osteoclast precursors
• HLA-B27 represents axial disease
sacroilitis and spondylitis
Conventional Radiography
• Important outcome domain in clinical
trials of (ASAS)
• Recognition of early bone changes
beneficial in patients early therapy
response to disease progression
• Inexpensive, easy to generate
• Widely available and inexpensive;
rapid and easily studied in randomized
and blinded environments
Imaging Role in Sacroilitis
• MRI and CT – high sensitivity and better
detection of early sacroilitis but cost
prohibits use in routine diagnosis
• Plain radiograph initial diagnostic tool
but large inter and intraobserver
variations documented
Battistone, et. al.
• Oblique views not justifiable
• High specificity (97.8%) low
sensitivity (54.4%)
Radiographic Hallmarks in SPA
• Erosions – earliest – iliac side
• Periostitis
• Bone proliferation at enthesis
• Normal bone mineralization
Progression of Erosive Disease
• Widening of joint
• Reparative bone laid down
behind erosions
• Total fusion of SIJ (ankylosis)
Radiographs
• Poor sensitivity to soft tissue and
bony changes in early SI disease
• Bony changes not evident until
advanced stage of disease
• Reliability unsatisfactory and leads
to therapy delays
Sacroiliac Joint Involvement in (SPA)
• Most common early clinical finding
• First manifestations of disease
Criteria for Classification of SPA
•
•
•
•
ESSG
Amor Criteria
Modified New York Criteria
Criteria sets all fall short as these all
depend on presence of radiological
sacroilitis (often appears late in
disease course)
• Long delay exists between initial
symptoms and establishing a diagnosis
Conventional Radiography
• Assess structural spine changes
• Document more chronic lesions
• Not sensitive to change over 2 years
Computed Tomography
•
•
Superior to radiography
Better definition of bone detail
•
Soft tissue overlap, air, intestinal loops, feces absent
•
Specific contrast windows
•
Observer variation reduced
•
Diagnostic CT performed supine with semicoronal slice and
preferable to axial CT
•
Overall view of cartilaginous joint facets and ligamentous part
of SIJ
•
Superior to MRI in detection of chronic bony changes in the
ligamentous portion of the joint
•
Considerable radiation exposure
CT Findings
• Comparable to chronic changes of MRI
• Better for evaluating joint space
alteration
• Better demonstrating ossification of
enthesopathies not always seen on MRI
• Cannot demonstrate present disease
activity
Use of MRI in SPA
• Key tool for assessment of
inflammation structural damage in AS
MRI
• Imaging method for earlier diagnosis
of sacroilitis
• Identifies both inflammation and
structural changes
• Radiographs only structural changes
MRI Compared to CT and
Conventional X-RAY
• Detects active inflammatory change
• Visualizes soft tissue
• Chronic changes
• Early diagnosis of sacroilitis well
before CT or radiography
• Monitoring disease activity
MRI Disadvantages
• Long examination times
• High cost
• Skilled staff
• Contraindications – i.e. pacemakers
TNF Agents
• Dramatic change in therapeutic
strategies in AS
• Improvement of clinical disease activity
correlates with reduction of acute
skeletal change documented by post
Gadolinium and Stir MRI exams
Blum (1996) and Hanly (1994)
• Prospective study
• MRI 100% specific in clinical sacroilitis
• IBP – 67% specific in early recognition
of sacroilitis
MRI in AS
• Erosion of cartilaginous joint facets
• Concomitant edema and enhancement
of joint and subchondral bone
• Changes on iliac side of joint
• Sacral involvement more frequent in AS
MRI in AS Early Diagnosis
• Sacral involvement
• Fatty marrow degeneration
• Joint space widening
• Pronounced subchondral sclerosis
• Only technique to detect actively
inflamed lesions of SIJ and spine
• Gold standard for efficacy of TNF
therapy in future
Ultrasonography
• Highly sensitive, non-invasive imaging
technique for soft tissue involvement
in SPA
• Entheses initial site of joint
inflammation in SPA
• Enthesopathy often under-estimated
• Higher sensitivity than MRI for early
signs of enthesitis
US in SIJ Involvement in SPA
• Fast
• Inexpensive
• Complements physical exam
identifying origin of IBP
U.S.
• Only visualize superficial part of SIJ
• Cannot visualize cartilaginous portion
• Less sensitive detecting erosions
• Possible to diagnose active sacroilitis
based on increased joint
vascularization of posterior joint
Bone Scintigraphy
• Limited diagnostic value for diagnosis
of established AS or early diagnosis of
probable/suspected sacroilitis
• Sensitivity not higher than 50-55%
• Specificity about 80%
• Radiation exposure lower than CT but
higher than plain radiography
PSA Radiographic Changes
• Entheseal bone formation
• Periostitis
• Entheseal erosions
• Diffuse bone based pathology
Ultrasound in PSA
• 25% more lesions found than on
clinical exam alone
• Achilles abnormalities in 59.2% of
PSA patients
PSA and Sacroilitis
•
•
•
•
25% in two series
78% in a third series
Unilateral
Axial and peripheral disease cause frequent
and severe lesion
• Cartilaginous and ligamentous joint
involvement
• Bony ankylosis less frequent than AS
• Bone eburnation of sacral and iliac surface
more marked in PSA than AS
Reactive Arthritis (REA) and
Sacroilitis
• 50% of patients symmetrical
• Minor changes in distal portion
(synovial)
• Entheses in ligamentous part
Enteropathic ENSPA
• Protzer, et. Al.
• SPA in 10.7% of all CD and 14.4%
of all UC patients
• 26.8% prior to GI symptoms
• 14.4% simultaneous
ENSPA and Sacroilitis
• Often bilateral
• Radiographically similar to AS
• More dominant involvement of
ligamentous portion of joint than
other forms
ENSPA and Imaging
• CT entheseal and ligamentous
- Frequent
• MRI inflammation at entheses
Undifferentiated
Spondyloarthropathy (UPSA)
• Clinical and suggestive of SPA but
not fulfilling diagnostic or
classification criteria
• USPA versus AS lack of grade ≥ 2
bilateral or grade 3 unilateral
sacroilitis on x-ray
Take Home Messages
• Radiological study of SIJ in SPA
represents clinical and imaging
challenges
• Integrated use of different imaging
techniques is suggested to avoid
misdiagnosis
• MRI technique of choice for f/u,
given lack of ionizing radiation
Therapy of SPA
• Basic essential therapy NSAID’s and
PT
• Management of AS
- Symptoms
- Signs
- Disease activity (severity)
- Functional status
Sulfasalazine (SZA)
• Control of peripheral joint involvement
• Reduce spinal stiffness
• No effect on enthesitis, spinal mobility
or physical therapy
Methotrexate
• Modest effect on peripheral joints
• Studies at odds on spine
Systemic Corticosteroids Ineffective
Biphosphonates
• Modest effect
- Osteoporosis
- Inflammatory spinal symptoms
TNF Inhibitors
• Effective in suppressing
inflammation with joint destruction
• Reduce pain
• Fail to slow new bone formation
• Administered early, drug free
remission is possible
ASASD Axial SPA Criteria
• Minimum of 2 NSAID’s for 4 week
minimum (previous 3 months)
• TNF blocker use earlier and for
a minimum of 3 months
TNF Inhibitors in AS
• Infliximab
• Etanercept
• Adalimumab
• Goliumumap
Active SI Inflammation Reduced
Infliximab, Etanercept, Adlmimab
• Reduce signs and symptoms even in
advanced or total spinal ankylosis
• AS or PSA in patients therapied with
Infliximab or Etanercept showed
clinically relevant improvement