seronegative arthritis or spondyloartropaties. introduction spondyloarthritis or seronegative...

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  • Seronegative ArthritisOrSpondyloartropaties

  • IntroductionSpondyloarthritis or Seronegative Spondyloarthritis

    Refers to inflammatory changes involving the spine and the spinal joints.

    Absence of Rheumatoid Factor and ANA

  • Spondyloarthritis

    A group of autoimmune diseases that in common appear mediated by activation of autoreactive CD8 T cells

    Primarily affect joints, skin, eyes and mucous membranes

    Physical stress, inflammation and infection with specific microorganisms trigger the immune response

  • Spondyloarthropathies (SpA)

    Frequent prevalence ~ 0.5%ChronicInflammatoryWith potential disabling outcomesConsist of several disorders

  • SpA consist of several disorders

    Ankylosing spondylitis (ASp)Reiters syndrome (RS) / reactive arthritis (ReA)Psoriatic arthritis (PsA)Undifferentiated spondyloarthritis (USpA)Enteropathic arthritis (ulcerative colitis, regional enteritis)

  • Spondyloarthritis Diseases-features common to all

    1. Clinical:- Affect joints, skin, eyes and mucous membranes in varying proportions with characteristic joint involvement: Spondylitis(inflammation of vertebral discs), sacroiliitis (sacroiliac joints) and enthesitis (tendon insertions). All with granulomatous fibrosis and newbone formation

  • Spondyloarthritis Diseases-features common to allperipheral articular involvement asymmetric mono-oligoarticular

    Common in male

    Sausage digits

  • Spondyloarthritis Diseases-features common to allEnthesopathy Achilles tenosynovitis

    Extra-articular manifestationsOral aphtae, Erythema nodosum, uveitis

    Absence of RF and Rheumatoid nodules

    Absence of Raynouds phenomenon

  • Spondyloarthritis Diseases-features common to all

    2. Genetic: Susceptibility to develop disease is associated with inheritance of certain MHC class I alleles, notably HLA-B27Positive family history

    3. Pathogenesis: Effector/ memoryCD8 T cells are activated and clonally expanded while CD4 T cells or B cells are not involved

  • Spondylitis leads to the development of syndesmophytes and ankylosis

    T cells invade the junctionof annulus fibrosis andvertebral body forminggranulation tissue(activated macrophages, Tcells and fibroblasts)Annulus fibers are eroded,then replaced by fibrocartilagethat ossifies to form asyndesmophyte. Subperiostealnew bone formation ensuesProgressivecartilaginous andperiosteal ossificationforms a bamboo spine,osteoporosis develops

  • SacroiliitisThe subchondral regions of thesynarthrotic SI joints areinvaded by T cells leading tothe formulation of granulationTissue

    The cartilage on the iliac side is eroded first, causing bone plate blurring, joint space widening and reactive sclerosis.Ultimately the resultant fibrous ankylosis is replaced by bone, obliterating the SI joint

  • Enthesitis (enthesopathy)

    Entheses are the specialized fibrocartilagenous region of bone where ligaments, tendons, fascia or joint capsules insert

    Infiltration of entheses by T cells, enthesitis, produces a combination of bone erosions and heterotopic new bone formation. Calcaneal spurs at insertion of plantar fascia and Achilles ligament are classic examples .

  • Inflammatory back pain

    Onset before age 40 Insidious persistent (> 3 mo) dull deep buttock or low back painStiffness/pain upon arising in the morning, or during sleepImprovement with exercise Due to the initial inflammation of enthesitis, spondylitis or sacroiliitis Poorly localized, does not follow nerve root

  • Genetic epidemiology

    HLA-B27 increased, but unevenly, among spondylitis diseases HLA-B27 frequency (%) Ankylosing spondylitis 95Reiters syndrome (reactive arthritis) 70Psoriatic arthritis 20-40Ethnically matched controls 8

    Other class I alleles may also be involved, especially in PsA

  • Spondyloarthropathies ESSG CriteriaPrimary

    Inflammatory Back PainORSynovitisAsymmetricPredominantly in lower extremitiesSecondaryPlus one of following:PsoriasisIBDPositive family historyUrethritis, cervicitis, or acute diarrhea within 1 month of arthritisAlternating buttock painEnthesopathySacroiliitis

  • Ankylosing Spondylitis

  • Ankylosing SpondylitisA progressive autoimmune inflammatory disease characterized by widespread spondylitis and sacroiliitis

    Onset, age 10-35 with dull pain in lumbar or gluteal regions

    Hip, shoulder, knee arthritis in ~30%

    Epidemiology: >95% of those affected are positive for HLA-B27

    Affects 1-3% of HLA-B27 individuals,

    Begins in the Sacroiliac Joints and progresses upwards and can involve the entire spine

  • Ankylosing SpondylitisInflammatory StagesCan be extremely painful (flares)Prolonged morning stiffness (hours)Fatigue (pain & lack of sleep)AnkylosisStiffness increases Significantly reduced ROMAbnormal posture

  • Postural changes Postural changes include loss of lumbar lordosis, buttock atrophyand thoracocervical kyphosis, chest expansion compromised Peripheral joints, notably the hips may develop flexion contracturesor ankylosis. Compensatory knee flexion

  • Other Joints InvolvedInflammatory Arthritis of the hips and shoulders


  • Extra-Articular FeaturesEyes: Acute anterior uveitis (40%)most common extraarticular features of ASAnterior uveitis can precede the onset of AS by several yearsStrongly associated with HLA B27

    Lungs: Rigidity of the chest wall and fibrosis in the upper lungs

    Kidneys: IgA nephropathy (rare)

    Heart: Aortitis (dilation of aortic root), aortic regurgitation

  • Laboratory InvestigationsEvidence of InflammationNormochromic normocytic anemiaElevated ESR/CRPReactive thrombocytosisHLA-B27 found in 90-95% of patients with Ank Spond vs 6-8% of general population

  • Imaging StudiesSacroiliac joints:Standard anteroposterior radiograph of the pelvisFerguson view-15 degree angle to the prone pelvisErosions-pseudowidening of SI JointObliteration of SI jointScintigraphyMRI-visualization of acute sacroiliitisCT-erosions

  • Psoriatic Arthritis

  • Psoriatic arthritisPsoriatic arthritis: an often clinically distinctive complex of enthesitis and arthritis that occurs in the setting of psoriasis

    It may involve the spine or peripheral joints in a variety of patterns,and is initiated or exacerbated by stress or non specific infection

  • ProgressionPolyarticular in 30-50%Like Rheumatoid ArthritisOligoarticular in 40-50%Predominant Spinal Disease in 5%Spinal symptoms usually occur after many years of peripheral arthritisDIP involvement in 5%Arthritis Mutilans in 5%

  • Arthritis mutilansOsteolytic dissolution of joint with redundant overlyingskin and telescoping motion of the digit (opera-glass hand)

  • Sacroiliac InvolvementSacroiliitis in 1/3 of patientsUsually asymmetric (unilateral)May be asymptomaticSpinal InvolvementMay affect any part of the spine in a random fashionDifferent from ankylosing spondylitis

  • Rheumatologic Review of SystemsMucocutaneous InvolvementPsoriatic skin lesionsPsoriatic Nail lesionsEntheseal InvolvementDactylitisOcular Involvement

  • Psoriatic ArthritisNail involvement ~80%Often seen in digitinvolved with DIPArthritis

    Pitting Onycholysis Onychodystrophy Transverse ridging

  • History - PsoriasisPsoriasis present before the onset of joint disease (70%)

    Psoriasis comes with the arthritis (15%)

    Psoriasis comes after the arthritis (15%)

  • Psoriatic Plaque Under the Knee

  • Umbilical Psoriasis

  • DactylitisEntire digit is involved compared to fusiform swelling around a joint

    Dactylitis represents inflammation of the flexor tenosynovium flexor tenosynovitis

  • Progression of DIP arthritisNarrowed joint space & condylar erosionsReactive sub periosteal new bonePencil in cup appearance

  • Management AS and Psoriatic ArthritisGoals of TreatmentImprove painImprove FunctionPrevent Long-term DamageSafely Psoriatic arthritis can lead to a deforming and destructive arthropathy in 20-30%Ankylosing spondylitis can result in significant disability

  • ManagementNSAIDsCan be useful in some cases of mono/oligo arthritisUseful for enthesitisUseful for spinal disease

  • Management: DMARDs

    MedicationPsoriaticAnkylosing SpondylitisHydroxychloroquine (Plaquenil) Rarely with little evidenceNOMethotrexateYESRarely with poor efficacy in spinal diseaseSulfasalazineYESYESLeflunomide (Arava)YESNOGoldYESNOSteroidsYESYES

  • Management: BiologicsBiologics Approved for Psoriatic Arthritis and Ankylosing SpondylitisEtanercept (Enbrel) Infliximab (Remicade)Adalimumab (Humira)Biggest advance in the treatment of spondyloarthropathies in decades!


  • Reactive arthritis has generally beendefined as sterile synovitis developingafter a distant infection.

    Occurs 2-4 weeks after inciting infection

    Most responsible organisms have an affinity for mucous membranes

  • Terms Reactive Arthritis & Reiters Syndrome Synonamous

    1916, Hans ReiterArthritis, Conjunctivitis, Non Gonococcal UrethritisReiter Syndrome ?

  • Classic triad: Arthritis, Urethritis, Conjunktivitis

  • Infectious agentGISGUSOthers Shigella (flexneri)* Salmonell


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