seronegative spondyloarthropathie s internal medicine/pediatrics noon conference series june 1, 2006

Seronegative Seronegative SpondyloarthropatSpondyloarthropat

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Internal Medicine/PediatricsInternal Medicine/PediatricsNoon conference seriesNoon conference series

June 1, 2006June 1, 2006

Back to basicsBack to basics

Axial skeletonAxial skeleton SkullSkull Vertebral columnVertebral column

VertebraeVertebrae SacrumSacrum CoccyxCoccyx

RibsRibs SternumSternum

Appendicular skeletonAppendicular skeleton GirdlesGirdles ExtremitiesExtremities

The skeletonThe skeleton


Diarthrosis (moveable)Diarthrosis (moveable) Majority of articulationsMajority of articulations Contiguous bones are covered by cartilage, Contiguous bones are covered by cartilage,

connected by ligaments, and have an interposing connected by ligaments, and have an interposing synovial sacsynovial sac

Synarthrosis (immoveable)Synarthrosis (immoveable) Contiguous bones are in direct contact without Contiguous bones are in direct contact without

cartilage, syovium, or ligamentscartilage, syovium, or ligaments AmphiarthrosisAmphiarthrosis (sort of moveable) (sort of moveable)

Characteristics of both diarthrosis and synarthrosisCharacteristics of both diarthrosis and synarthrosis Contiguous surfaces are either:Contiguous surfaces are either:

ConnectedConnected by fibrocartiganeous disks (vertebral joint) by fibrocartiganeous disks (vertebral joint) CoveredCovered by fibrocartilage and by fibrocartilage and partialpartial synovium, and synovium, and

attached by attached by externalexternal ligaments (sacroiliac joint) ligaments (sacroiliac joint)

ArticulationsArticulations


Enthesis is the site of bony attachment ofEnthesis is the site of bony attachment of TendonTendon LigamentLigament CartilageCartilage Joint capsuleJoint capsule FasciaFascia

EnthesisEnthesis

Seronegative Seronegative spondyloarthropathiesspondyloarthropathies

AAnkylosing spondylitis (the prototype)nkylosing spondylitis (the prototype) PPsoriatic arthritissoriatic arthritis RReactive arthritiseactive arthritis

Formerly called Reiter’s syndrome)Formerly called Reiter’s syndrome) EEnteropathic arthritisnteropathic arthritis UUndifferentiated spondyloarthropathyndifferentiated spondyloarthropathy

Mnemonic is Mnemonic is PURE-A PURE-A (sort of like purée)(sort of like purée)

Comprise these conditions…Comprise these conditions…

Why are these diseases classified Why are these diseases classified together?together?

HHLA-B27 associationLA-B27 association EEnthesitis (both juxtaärticular and nthesitis (both juxtaärticular and

extraärticular)extraärticular) AAxial skeleton arthritis (generally secondary to xial skeleton arthritis (generally secondary to

juxtaärticular enthesitis)juxtaärticular enthesitis) Spondylitis (inflammation of vertebral bodies) Spondylitis (inflammation of vertebral bodies) Sacroiliitis (inflammation of sacroiliac joint)Sacroiliitis (inflammation of sacroiliac joint)

PPeripheral arthritis (generally a synovitis)eripheral arthritis (generally a synovitis) Asymmetric (Asymmetric (cfcf rheumatoid arthritis) rheumatoid arthritis)

EExtraärticular manifestations (besides xtraärticular manifestations (besides enthesitis)enthesitis)

SSeronegativity eronegativity Rheumatoid factor and ANA negativeRheumatoid factor and ANA negative

Well, because they share these characteristics…Well, because they share these characteristics…


Ankylosing spondylitis: 95%Ankylosing spondylitis: 95% Ethnically matched controls: 8%Ethnically matched controls: 8%

Reactive arthritis: 70%Reactive arthritis: 70% Enteropathic arthritis: 50%Enteropathic arthritis: 50% Psoriatic arthritis: 35%Psoriatic arthritis: 35%

HLA-B27 associationHLA-B27 association


Inflammation of an enthesisInflammation of an enthesis Principal pathogenetic mechanism in Principal pathogenetic mechanism in

spondyloarthropathyspondyloarthropathy PathogenesisPathogenesis

CD8 T cells infiltrate enthesesCD8 T cells infiltrate entheses Activated macrophages release cytokines (Activated macrophages release cytokines (egeg TNFTNF)) Fibroblasts synthesize Fibroblasts synthesize new collagennew collagen ( (cfcf rhematoid rhematoid

arthritis!!)arthritis!!) New bone formation resultsNew bone formation results

ClinicalClinical Axial skeleton arthritis (see later)Axial skeleton arthritis (see later) Enthesopathy at other sitesEnthesopathy at other sites

Calcaneal spurs at plantar fascia insertionCalcaneal spurs at plantar fascia insertion Spurs at Achilles tendon insertionSpurs at Achilles tendon insertion Manifests as extraärticular or juxtaärticular bony tendernessManifests as extraärticular or juxtaärticular bony tenderness

EnthesitisEnthesitis


Arises from enthesitisArises from enthesitis IncludesIncludes spondylitis spondylitis andand sacroiliitis sacroiliitis SpondylitisSpondylitis

CD8 T cells invade the junction of the annulus fibrosis CD8 T cells invade the junction of the annulus fibrosis and the vertebral body (an enthesis)and the vertebral body (an enthesis)

Annulus fibrosis is replaced by bone (syndesmophytosis)Annulus fibrosis is replaced by bone (syndesmophytosis) Vertebral bodies assume a square shape, and ultimately Vertebral bodies assume a square shape, and ultimately

a bamboo spinea bamboo spine SacroiliitisSacroiliitis

CD8 T cells invades the subchondral area at the junction CD8 T cells invades the subchondral area at the junction of the bones and the cartilage (an enthesis)of the bones and the cartilage (an enthesis)

Cartilage on iliac side is replaced by bone, obliterating Cartilage on iliac side is replaced by bone, obliterating the jont space and hardening the jointthe jont space and hardening the joint

Axial skeleton arthritisAxial skeleton arthritis

Ankylosing spondylitisAnkylosing spondylitis

Inflammatory back pain requires 4 of these 5 Inflammatory back pain requires 4 of these 5 criteria (serves as a screening tool for AS)criteria (serves as a screening tool for AS) YYoung onset (oung onset ( 40 years) 40 years) MMorning stiffness (orning stiffness ( 30 minutes) 30 minutes) CChronic (hronic ( 3 months) 3 months) AActivity improves the pain (rest does not)ctivity improves the pain (rest does not) IInsidious (not acute)nsidious (not acute)

(mnemonic is YMCA-I)(mnemonic is YMCA-I) Diffuse lumbar or gluteal, not focal or Diffuse lumbar or gluteal, not focal or

radicularradicular CfCf focal pain of disk herniation focal pain of disk herniation

Inflammatory back painInflammatory back pain


Restriction of lumbar movementRestriction of lumbar movement Shober’s testShober’s test – mark the patient’s back at the level of the – mark the patient’s back at the level of the

posterior iliac spine. Place one finger 5 cm below this posterior iliac spine. Place one finger 5 cm below this mark and a 2mark and a 2ndnd finger 10 cm above this mark. Patient is finger 10 cm above this mark. Patient is instructed to touch his toes. If the distance between instructed to touch his toes. If the distance between finegrs increases < 5 cm, lumbar flexion is limited.finegrs increases < 5 cm, lumbar flexion is limited.

Anterior uveitis (iritis or iridocyclitis) (25%)Anterior uveitis (iritis or iridocyclitis) (25%) Acute eye painAcute eye pain Increased lacrimationIncreased lacrimation PhotophobiaPhotophobia Blurred visionBlurred vision

Aortitis with fibrosisAortitis with fibrosis Aortic insufficiencyAortic insufficiency Third degree heart block (5%)Third degree heart block (5%)

Other clinical (besides back pain)Other clinical (besides back pain)


Radiographic evaluationRadiographic evaluationSacroiliacSacroiliac joints joints

Grade 0Grade 0 NormalNormal

Grade 1Grade 1 Suspicious changesSuspicious changes

Grade 2Grade 2 Minimal abnormality – small localized areas Minimal abnormality – small localized areas with erosion or sclerosis without alterations in with erosion or sclerosis without alterations in joint widthjoint width

Grade 3Grade 3 Unequivocal abnormality – moderate or Unequivocal abnormality – moderate or advanced sacroiliitis with advanced sacroiliitis with 1 of the following: 1 of the following: erosions, sclerosis, widening, narrowing, or erosions, sclerosis, widening, narrowing, or partial ankylosispartial ankylosis

Grade 4Grade 4 Severe abnormality – total ankylosisSevere abnormality – total ankylosis

Ossification of SI joint spaceOssification of SI joint space

Bamboo spineBamboo spine


Low back pain Low back pain 3 months improved by exercise and 3 months improved by exercise and not relieved by restnot relieved by rest

Limitation of lumbar spine in sagittal and frontal Limitation of lumbar spine in sagittal and frontal planesplanes

Chest expansion reduction relative to normal values Chest expansion reduction relative to normal values corrected for age and sex (costovertebral ankylosis, corrected for age and sex (costovertebral ankylosis, 25%)25%)

Radiographic criteria of sacroiliitisRadiographic criteria of sacroiliitis Bilateral grade 2-4 ORBilateral grade 2-4 OR Unilateral grade 3-4Unilateral grade 3-4

Ankylosing spondylitis is defined by the presence of Ankylosing spondylitis is defined by the presence of either radiographic criterion PLUS any clinical criterioneither radiographic criterion PLUS any clinical criterion

Modified New York Diagnostic CriteriaModified New York Diagnostic Criteria

Reactive arthritisReactive arthritis

In 1916, Hans In 1916, Hans ReiterReiter reported reported Reiter’s syndromeReiter’s syndrome: a : a triad of nongonococcal urethritis, conjunctivitis, triad of nongonococcal urethritis, conjunctivitis, and arthritis that occurred in a young German and arthritis that occurred in a young German officer following an episode of bloody dysenteryofficer following an episode of bloody dysentery

Subseqently, more cases were reported following Subseqently, more cases were reported following enteric infections OR venereally acquired enteric infections OR venereally acquired genitourinary infections.genitourinary infections.

In 1967, the term In 1967, the term reactive arthritisreactive arthritis was applied to was applied to similar cases following similar cases following YersiniaYersinia gastroenteritis gastroenteritis

The two terms should be considered The two terms should be considered synonomoussynonomous The term The term reactive arthritisreactive arthritis is increasingly preferred is increasingly preferred

Interesting historical backdropInteresting historical backdrop


Clinical syndrome triggered by specific Clinical syndrome triggered by specific etiologic agents in a genetically etiologic agents in a genetically susceptible hostsusceptible host

Follows 1-4 weeks after aFollows 1-4 weeks after a Urogenital infection (affects principally men)Urogenital infection (affects principally men)

Usually C. trachomatisUsually C. trachomatis Enteric infection (affects both genddrs equally)Enteric infection (affects both genddrs equally)

SalmonellaSalmonella ShigellaShigella CampylobacterCampylobacter YersiniaYersinia

PathogenesisPathogenesis


Peripheral arthritisPeripheral arthritis Asymmetric additive oligoarthritis (usually)Asymmetric additive oligoarthritis (usually) SynovitisSynovitis

WarmWarm EdematousEdematous TenderTender Pain with active or passive movementPain with active or passive movement

Usually lower extremity joints (knee, ankle, Usually lower extremity joints (knee, ankle, subtalar)subtalar)

ConjunctivitisConjunctivitis

ClinicalClinical


Nongonococcal urethritisNongonococcal urethritis Occurs in postenteric or postvenereal diseaseOccurs in postenteric or postvenereal disease

When it occurs in postvenereal disease, When it occurs in postvenereal disease, C. C. trachomatistrachomatis is often the etiology is often the etiology

When present, is usally the first symptomWhen present, is usally the first symptom In menIn men

Mild dysuriaMild dysuria Mucopurulent urethral dischargeMucopurulent urethral discharge May present as prostatitis or epididymitisMay present as prostatitis or epididymitis

In womenIn women DysuriaDysuria Purulent vaginitis or cervicitis with vaginal dischargePurulent vaginitis or cervicitis with vaginal discharge

Asymptomatic urethritis often features sterile Asymptomatic urethritis often features sterile pyuriapyuria

ClinicalClinical


Keratoderma blenorrhagicaKeratoderma blenorrhagica A papulosquamous skin rash A papulosquamous skin rash Comprises vesicles that become hyperkeratotic, Comprises vesicles that become hyperkeratotic,

forming crusts before disappearingforming crusts before disappearing Palms/solesPalms/soles Penis (causing circinate balanitisPenis (causing circinate balanitis

Oral ulcers (ususally shallow and painless)Oral ulcers (ususally shallow and painless) Inflammatory back pain (50% of patients)Inflammatory back pain (50% of patients) Enthesitis (40%)Enthesitis (40%) Dactylitis (40%)Dactylitis (40%) Anterior uveitis (20% of patients)Anterior uveitis (20% of patients)

Clinical (continued)Clinical (continued)

Reactive arthritisReactive arthritisKeratoderma blenorrhagicaKeratoderma blenorrhagica


Synovial fluid analysisSynovial fluid analysis Pleocytosis (5 000 to 50 000 WBC/mcL) with Pleocytosis (5 000 to 50 000 WBC/mcL) with

polymorphonuclear cell predominancepolymorphonuclear cell predominance Protein levelsProtein levels Glucose normalGlucose normal

CfCf reduced glucose level in true septic arthritis reduced glucose level in true septic arthritis Gram stain and culture are sterileGram stain and culture are sterile

Urethral or cervical smears in patients with Urethral or cervical smears in patients with clinical urethritis clinical urethritis C. trachomatisC. trachomatis N. gonorrhoeaeN. gonorrhoeae

EvaluationEvaluation

Enteropathic ArthritisEnteropathic Arthritis

Affects 10-20% of patients with Affects 10-20% of patients with inflammatory bowel disease (IBD)inflammatory bowel disease (IBD)

Peripheral arthritis affects 10-20% of IBD Peripheral arthritis affects 10-20% of IBD patientspatients Generally affects knees, ankles, and feetGenerally affects knees, ankles, and feet Always indicates active IBDAlways indicates active IBD

Radiographic axial arthritis affects 10% of Radiographic axial arthritis affects 10% of IBD patientsIBD patients Frequently asymptomaticFrequently asymptomatic Independent of bowel inflammationIndependent of bowel inflammation

ClinicalClinical


Nonsteroidal antiinflammatory agentsNonsteroidal antiinflammatory agents IndamethacinIndamethacin

Disease modifying anti-rheumatic drugsDisease modifying anti-rheumatic drugs (DMARDs)(DMARDs) Methotrexate: inhibits recruitment of CD4 and Methotrexate: inhibits recruitment of CD4 and

CD8 T cellsCD8 T cells Tumor necrosis factor antagonists Tumor necrosis factor antagonists

Infliximab: a monoclonal antibody that binds to Infliximab: a monoclonal antibody that binds to TNF and inhibits binding of TNF to its receptorTNF and inhibits binding of TNF to its receptor

Etanercept: similar emchanism to infliximabEtanercept: similar emchanism to infliximab For axial arthritis, exercises to maintain For axial arthritis, exercises to maintain

posture and flexibilityposture and flexibility

TreatmentTreatment

seronegative spondyloarthropathie s internal medicine/pediatrics noon conference series june 1, 2006

Documents

skeleton slide

synovitis peripheral

ligaments contiguous

extrarticular enthesitis

synarthrosis characteristics

basics enthesis

ana negative rheumatoid

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