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Low Back Pain and the Seronegative
Spondyloarthropathies
Low Back Pain and the Seronegative
Spondyloarthropathies
Scott R. Burg, D.O.
Orthopaedic and Rheumatologic Institute
Cleveland Clinic
Spondyloarthropathies (SPA)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 PredispositionCommon 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 HallmarkRadiographic Hallmark
• Sacroilitis
SPASPA
• 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 PainInflammatory 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 PainInflammatorty Back Pain
• Unilateral or bilateral
• Alternates from side to side
• Responds well to NSAIDs
Sacroilitis and Inflammatory Low Back Pain
Sacroilitis and Inflammatory Low Back Pain
Prevalence 50%
F.D. Hart Quarterly Journal of Medicine, 1949
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 USAIBP 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 ConceptIBP 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
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)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)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 DelayedDiagnosis of AS Delayed
• As long as 8 years
• Longer delays in females
Diagnostic and Classification CriteriaDiagnostic 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
• Changes now included in new classification criteria of early axial SPA
• Major tool diagnostically
MRIMRI
AS SymptomsAS 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)Dactylitis (Sausage Digit)
• PSA
• REA
• Joint and tenosynovial inflammation
Other Clinical Features of ASOther 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)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 FeaturesExtra-articular Features
• Urethritis
• Cervicitis
• Vulvovaginitis and salpingitis
• Prostatitis
• Oral ulcers, e. nodosum, conjunctivitis
• Cardiac involvement
Enteropathic Associated Arthritis (IBD)
Enteropathic Associated Arthritis (IBD)
• 10% of patients may antedate IBD
• Asymmetric, large joints, lower limb
• Occasional symmetrical, small joint polyarthritis
Spondyloarthritis and SacroilitisSpondyloarthritis 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)
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 SpondyloarthropathyJuvenile 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)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 PSAArthritis in PSA
• Asymmetric in small and large joints
• Patterns include:
- Mutilans
- Peripheral oligoarthritis / polyarthritis
- Spondylitis
- DIP arthritis (fingers and toes >50%)
Back Pain in PSABack 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
PSAPSA
• Nails (83%) or skin precede or follow joint involvement
• Scalp, behind ears, umbilicus or gluteal folds
• Fatigue, iritis, uveitis
Biomarkers to Assess PSABiomarkers to Assess PSA
• CRP
• Matrix metalloproteinase-3
• Circulating osteoclast precursors
• HLA-B27 represents axial disease sacroilitis and spondylitis
Conventional RadiographyConventional 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 SacroilitisImaging 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.Battistone, et. al.
• Oblique views not justifiable
• High specificity (97.8%) low sensitivity (54.4%)
Radiographic Hallmarks in SPARadiographic Hallmarks in SPA
• Erosions – earliest – iliac side
• Periostitis
• Bone proliferation at enthesis
• Normal bone mineralization
Progression of Erosive DiseaseProgression of Erosive Disease
• Widening of joint
• Reparative bone laid down behind erosions
• Total fusion of SIJ (ankylosis)
RadiographsRadiographs
• 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)Sacroiliac Joint Involvement in (SPA)
• Most common early clinical finding
• First manifestations of disease
Criteria for Classification of SPACriteria 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 RadiographyConventional Radiography
• Assess structural spine changes
• Document more chronic lesions
• Not sensitive to change over 2 years
Computed TomographyComputed 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 FindingsCT 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 SPAUse of MRI in SPA
• Key tool for assessment of inflammation structural damage in AS
MRIMRI
• 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
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 DisadvantagesMRI Disadvantages
• Long examination times
• High cost
• Skilled staff
• Contraindications – i.e. pacemakers
TNF AgentsTNF 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)Blum (1996) and Hanly (1994)
• Prospective study
• MRI 100% specific in clinical sacroilitis
• IBP – 67% specific in early recognition of sacroilitis
MRI in ASMRI 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 DiagnosisMRI 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
UltrasonographyUltrasonography
• 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 SPAUS in SIJ Involvement in SPA
• Fast
• Inexpensive
• Complements physical exam identifying origin of IBP
U.S.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 ScintigraphyBone 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 ChangesPSA Radiographic Changes
• Entheseal bone formation
• Periostitis
• Entheseal erosions
• Diffuse bone based pathology
Ultrasound in PSAUltrasound in PSA
• 25% more lesions found than on clinical exam alone
• Achilles abnormalities in 59.2% of PSA patients
PSA and SacroilitisPSA 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
Reactive Arthritis (REA) and Sacroilitis
• 50% of patients symmetrical
• Minor changes in distal portion (synovial)
• Entheses in ligamentous part
Enteropathic ENSPAEnteropathic 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 SacroilitisENSPA and Sacroilitis
• Often bilateral
• Radiographically similar to AS
• More dominant involvement of ligamentous portion of joint than other forms
ENSPA and ImagingENSPA and Imaging
• CT entheseal and ligamentous
- Frequent
• MRI inflammation at entheses
Undifferentiated Spondyloarthropathy (UPSA)
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 MessagesTake 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 SPATherapy of SPA
• Basic essential therapy NSAID’s and PT
• Management of AS
- Symptoms
- Signs
- Disease activity (severity)
- Functional status
Sulfasalazine (SZA)Sulfasalazine (SZA)
• Control of peripheral joint involvement
• Reduce spinal stiffness
• No effect on enthesitis, spinal mobility or physical therapy
MethotrexateMethotrexate
• Modest effect on peripheral joints
• Studies at odds on spine
Systemic Corticosteroids IneffectiveSystemic Corticosteroids Ineffective
BiphosphonatesBiphosphonates
• Modest effect
- Osteoporosis
- Inflammatory spinal symptoms
TNF InhibitorsTNF 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 CriteriaASASD 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 ASTNF Inhibitors in AS
• Infliximab
• Etanercept
• Adalimumab
• Goliumumap
Active SI Inflammation Reduced Infliximab, Etanercept, Adlmimab
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