ankylosing spondylitis early diagnosis & pitfall - university of colorado health and science center

7/27/2019 Ankylosing Spondylitis Early Diagnosis & Pitfall - University of Colorado Health and Science Center

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Ankylosing Spondylitis:Keys to Early Diagnosis &

Common Pitfalls

Jason Kolfenbach, MD

Assistant Professor, Division of Rheumatology

University of Colorado Health Science Center

LEARNING OBJECTIVES:

1. Recognize key clinical & radiographic findingsuseful in differentiation of mechanical andinflammatory back pain due to SpA

2. Understand the value & limitations of HLA-B27

3. Understand recent data demonstrating lack oftreatment efficacy for the process of boneformation in ankylosing spondylitis


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I have no significant disclosures related

to the content of this presentation

Spondyloarthropathies

Family/spectrum of diseases marked by:

Asymmetric oligoarthritis (typically 2-5 joints)

Axial involvement (rare in other forms of IA)

Antibody (RF, CCP) negativity

HLA-B27 association

Common extra-articular features: acute anterior uveitis;enthesopathy

SpA family: Ankylosing spondylitis Reactive arthritis

IBD-associated arthritis Psoriatic arthritis

Undifferentiated spondyloarthritis


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Ankylosing Spondylitis

Clinical features

Treatment

Difficulties in diagnosis

Ankylosing Spondylitis (AS)

Incidence: ~ 10 cases per 100,000 person-years

Prevalence: estimates vary, ~ 0.5%

SpA family: ~ 1.5% (on par with RA)

Gender: 2:1 to 3:1 male to female

Age at onset: peak onset in 20s; > 95% symptomatic

by 45


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Ankylosing Spondylitis (AS)

Disease predilection for fibrocartilage:

SI joints, symphysis pubis Aortic root

Enthesis (Achilles) Anterior uvea

Intervertebral disks, facet joints

SI involvement early; axial skeleton later

Peripheral arthritis may be significant: hipinvolvement can be associated with significantmorbidity


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AS-Clinical features

Extra-articular features:

acute anterior uveitis upper lung fibrosis

renal amyloidosis neurologic involvement

aortic insufficiency cardiac conduction defects

Poor prognostic indicators at baseline:

Hip involvement Poor NSAID responseOligoarthritis Onset < 16 years old

Dactylitis Loss of ROM at L spine

Elevated ESR

AS-diagnosis

Clinical diagnosis determined from historical &exam features, supported by lab work

Classification criteria

-Developed for research purposes

-Historically poor at identifying early disease

-1984 Modified New York Criteria-ASAS Criteria for axial and peripheral SpA (2009, 2010)

Diagnostic algorithms


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Diagnostic dilemmaA softball

A curveball

What do you call this? What do you do for this?

1984 Modified NY Criteria for AS

Clinical Criteria

M Low back pain > 3 months; improved by exercise & notrelieved by rest

M Limitation of lumbar spine in sagittal and frontal planes

M Chest expansion decreased relative to normal values

Radiographic Criteria

M Bilateral sacroiliitis grade 2-4

M Unilateral sacroiliitis grade 3-4

Definite AS if one radiographic and one clinical feature present


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Has time

passed on the

1984 criteria?

Adequately classifypatients with establisheddisease, but utility inearly disease is limited

Time between symptomonset & diagnosis of AS:

~6-10 years (lateappearance on plainfilm)

Diagnosing AS: Key historical features

Inflammatory back pain (Berlin criteria)Developed in patients < 45 & 3mo back pain

AM stiffness > 30min No improvement with rest

Alternating buttock pain Awakening second of night

2/4 criteria: Sn 70%, Sp 81%; 3/4 criteria: Sn 33%, Sp 98%

Positive family history (SpA, uveitis)Sn 32%; Sp 95%

NSAID responseSn 77%; Sp 85%


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Diagnosing AS: Key exam features

Findings can be specific, but not sensitive,

due to the heterogeneity of disease

Enthesitis: Sn 37%, Sp 89%

Peripheral arthritis: Sn 40%, Sp 90%

Dactylitis: Sn 18%, Sp 96%Anterior uveitis: Sn 22%, Sp 97%

Diagnosing AS: Key lab features

CRP/ESR: Sn 50%, Sp 80%

-limited utility as a sole diagnostic test

HLA-B27: Sn 90%, Sp 90%

-covered ahead


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Diagnosing AS: Key imaging features

X-ray sacroilitis

-X-ray evidence + IBP = AS per 1984 criteria

-Problem: can take years for changes to develop

-Longitudinal study of patients with symptoms of

axial SpA without definitive radiographic findings

60% developed definite AS at 10yrs

Mean time to radiographic change was 9 years

Diagnosing AS: Key imaging features

MRI

-Sn 90%, Sp 90%

-Sn & Sp values differ based on the definition of apositive MRI

-Single area of bone marrow edema in 25% of controls

Standardized definition proposed (ASAS): 2 separate

lesions or 1 lesion that spans two consecutive slices-The ASAS definition does not include erosions;

inclusion of this feature may increase sensitivity inearly IBP populations


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Can we predict who

will developradiographic disease?

MRI & HLA-B27 provide the

highest LR ratio for AS

May be useful tools in

predicting disease

persistence & developmentofestablished disease

(defined by NY criteria)

Diagnosing AS


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2009 ASAS criteria for axial SpA

To be applied to patients with 3mo back pain and symptom

onset while age < 45

Axial SpA if:

Sacroilitis on X-ray or MRI + 1 SpA feature

HLA-B27 positive + 2 SpA features

SpA features:IBP Arthritis Enthesitis Uveitis

Dactylitis Psoriasis IBD HLA-B27+

CRP NSAID response Family history of SpA

Diagnosing AS: Take home message

Symptoms of AS far predate radiographic change; MRImay identify pre-radiographic disease

No factor in isolation can diagnose AS

Combination of factors post-test probability of disease

-Chronic back pain + IBP symptoms = PTP 14%-Chronic back pain + IBP + uveitis = 54%

-Chronic back pain + IBP + uveitis + NSAID response = 85%

MRI and HLA-B27 provide the highest LR for AS


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HLA B27: Utility & limitations


Prevalence varies by ethnicity (per distribution ofHLA-B27)

Caucasian Americans:

8% HLA-B27+

~90% with ASpossess HLA-B27

African Americans:

2% HLA-B27+; therefore AS less common

Only 50% with AS are HLA-B27+

African blacks & Japanese:

HLA-B27 (and AS) nearly absent


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Caucasian populations (8% of population):

If used as a screening test for the population: 2-5%of B27+ people will develop AS

If used as a screening test in 1st degree relatives ofAS probands: 10-20% will develop AS

Chronic LBP + HLA-B27: ~ 30% probability of AS

IBP + HLA-B27: ~ 59% probability of AS

IBP + HLA-B27 + severe MRI sacroilitis: 80%probability of AS

Early treatment: Better outcomes?


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Clinical efficacyNSAIDs effective in symptom relief versus placebo

Clinical efficacy proved for infliximab, etanercept, &adalimumab1,2,3

TNF inhibitors decrease spinal inflammation on MRI4

1) Braun et. al. Lancet. 2002;359:1187-1193

2) Davis JC et. al. A&R. 2003;48:3230-3236

3) Van der Heijde. A&R. 2006;54:21362146

4) Braun et. al. A&R. 2006;54:1646-1652

Does the RA paradigm apply to AS?

The Old Guard

Initiation of DMARD at Dx

Goal directed therapy with remission

aim

Prevention of erosive disease and

long-term disability

The New RegimeUnfortunately, no anti-TNF agent has been shown to haltradiographic progression at two years in AS5,6,7,8

5) Baraliakos. Ann Rheum Dis. 2005;64:1462-1466

6) Van der Heijde. A&R. 2008;58:1324-1331

7) Van der Heijde. A&R. 2008; 58:3063-3070

8) Van der Heijde. Arthriits Res Ther. 2009;11:R127


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Why dont anti-TNF

agents halt radiographic

progression?RA

Tight correlation between disease activity & erosion

TNF RANKL activation osteoclast activation & bone resorption

TNF DKK-1 inhibit WNT pathway (blunt osteoblast path)

AS

No association between disease activity and radiographic progression 9

TNF involved in erosive disease, but reactive bone formation occurs tooDKK-1 levels, while high in RA, are actually low in AS10

TGF/BMP may play a role in bone formation as well9

9) Schett. Ann Rheum Dis. 2007;66:709-711

10) Diarra. Nature Medicine. 2007;13:156-163

What does this mean for patients?

The literature in this area is limited by:

-An average disease duration of 10-15yrs in most studies

-Control arm is a loose term

TNF inhibitors result in excellent clinical response for most patients

These agents can resolve vertebral inflammation, but the recoveredsites still have high rates of syndesmophyte formation

If the initial inflammatory insult is found to trigger bone formation,early intervention could result in disease modification Current evidence has not demonstrated this, however, and further research is

needed


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ankylosing spondylitis early diagnosis & pitfall - university of colorado health and science center

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