Seronegative Arthritis - PowerPoint Presentation

Seronegative ArthritisOrSpondyloartropaties

IntroductionSpondyloarthritis or Seronegative SpondyloarthritisRefers 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%Chronic Inflammatory With potential disabling outcomes Consist of several disorders

SpA consist of several disordersAnkylosing spondylitis (ASp)Reiter’s syndrome (RS) / reactive arthritis (ReA)Psoriatic arthritis (PsA)Undifferentiated spondyloarthritis (USpA)Enteropathic arthritis (ulcerative colitis, regional enteritis)

Spondyloarthritis Diseases-features common to all1. 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 new bone formation

Spondyloarthritis Diseases-features common to allperipheral articular involvement asymmetric mono- oligoarticular Common in male Sausage digits

Spondyloarthritis Diseases-features common to allEnthesopathy– Achilles tenosynovitisExtra-articular manifestationsOral aphtae, Erythema nodosum, uveitis Absence of RF and Rheumatoid nodules Absence of Raynoud’s phenomenon

Spondylitis leads to the development of syndesmophytes and ankylosis T cells invade the junction of annulus fibrosis and vertebral body forming granulation tissue (activated macrophages, Tcells and fibroblasts) Annulus fibers are eroded, then replaced by fibrocartilage that ossifies to form a syndesmophyte. Subperiosteal new bone formation ensues Progressive cartilaginous and periosteal ossification forms 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 s purs at insertion of plantar fascia and Achilles ligament are classic examples .

Inflammatory back painOnset 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 epidemiologyHLA-B27 increased, but unevenly, among spondylitis diseases HLA-B27 frequency (%) Ankylosing spondylitis 95 Reiter’s syndrome ( reactive arthritis ) 70 Psoriatic arthritis 20-40 Ethnically matched controls 8 Other class I alleles may also be involved, especially in PsA

Spondyloarthropathies ESSG CriteriaPrimaryInflammatory Back PainORSynovitisAsymmetricPredominantly in lower extremitiesSecondary Plus one of following: Psoriasis IBD Positive family history Urethritis, cervicitis, or acute diarrhea within 1 month of arthritisAlternating buttock painEnthesopathySacroiliitis

Ankylosing Spondylitis

Ankylosing SpondylitisA progressive autoimmune inflammatory disease characterized by widespread spondylitis and sacroiliitisOnset, 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 shouldersEnthesitis

Extra-Articular FeaturesEyes: Acute anterior uveitis (40%)Lungs: Rigidity of the chest wall and fibrosis in the upper lungsKidneys: 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

Psoriatic Arthritis

Psoriatic arthritisPsoriatic arthritis: an often clinically distinctive complex of enthesitis and arthritis that occurs in the setting of psoriasisIt 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 jointDactylitis – 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 pain Improve Function Prevent Long-term Damage Safely 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: DMARDsMedication Psoriatic Ankylosing Spondylitis Hydroxychloroquine (Plaquenil ®) Rarely with little evidence NO Methotrexate YES Rarely with poor efficacy in spinal disease Sulfasalazine YES YES Leflunomide (Arava ®) YES NO Gold YES NO Steroids YES YES

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

REACTİVE ARTHRITIS

Reactive arthritisReactive 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 & Reiter’s Syndrome Synonamous1916, Hans ReiterArthritis, Conjunctivitis, Non Gonococcal UrethritisReiter Syndrome ?

Classic triad: Arthritis, Urethritis, Conjunktivitis

Etyology Infectious agent GIS GUS Others Shigella (flexneri)* Salmonella Yersinia Campylobacter Clostridium(difficile) C.pneumoniae Borrelia Neisseria Streptococus Chlamydia (trachomatis)

- symptoms of the triggering infection haveoften been mild and, in about 10% ofcases, the infection has passed unnoticed- Symptoms• malaise,• fatigue• fever• mild arthralgias to severely disabling polyarthritis

Reactive ArthritisConjunctivitisfollows urethritis by several daysSx often mild and transientacute anterior Uveitis possible

Articular manifestations Starts 2-4 weeks after the initial infection Articular symptoms typically appear last additive oligoarticular lower limbs most common

Knee AnkleFoot joints OccasionallyWrist, Elbow, Shoulder, SIE asymetric, oligoarticular Chronic cases Dactilitis Entesopathy. tenosynovitis, plantar facitis, achill tendinitis, bursit

Aşil tendinitSosis parmakSosis parmak Reactive arthritis

Aphtous ulceration

Erithema nodosum

Reactive ArthritisClinical courseNormally limited course running 3-12 months15% with prolonged relapsing arthritis? Relapse?ReinfectionAnkylosing Spondylitis in 10% of cases

Reactive ArthritisLaboratory findingsNormochromic, normocytic anemiaLeukocytosisAcute phase reactants:ESR C-reactive Protein

Reactive ArthritisTreatment:Antibiotics?RestNSAIDsMethotrexate and sulphasalazineIntralesional and intraarticular glucocorticoids Uveitis-glucocorticoids

Enteropathic ArthritisOrSpA associated with inflammatory bowel disease

Enteropathic arthritisArthropathy associated with IBD – (5-20%)Peripheral arthritis Axial involvement – sacroiliitis w /o spondylitis HLA-B27 not implicated here

Enteropathic arthritisAcute, oligoarticular onset Predominantly lower extremities Non-deforming, self-limiting arthritis Association with active bowel symptoms

Enteropathic arthritisPeriarticular featuresEnthesopathyTendonitis Extraarticular features Erytema nodosum Uveitis

Enteropathic arthritis-Therapy NSAID Sulphasalazine Methotrexate Biologic agents – Anti TNF therapy