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