Seronegative ArthritisOr

Spondyloartropaties

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% Chronic Inflammatory With potential disabling outcomes Consist of several disorders

SpA consist of several disorders

• Ankylosing 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 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 all

peripheral articular involvement– asymmetric mono-oligoarticular

Common in male

Sausage digits

Spondyloarthritis Diseases-features common to all

Enthesopathy– Achilles tenosynovitis

Extra-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 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 ensues

Progressivecartilaginous andperiosteal ossificationforms a “bamboo spine”,osteoporosis develops

Sacroiliitis

The 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 pain• Stiffness/pain upon arising in the morning,

or during sleep• Improvement 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 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 Criteria

Primary

• Inflammatory Back PainOR

• Synovitis• Asymmetric• Predominantly in lower extremities

Secondary• Plus one of following:

• Psoriasis• IBD• Positive family history• Urethritis, cervicitis, or

acute diarrhea within 1 month of arthritis

• Alternating buttock pain

• Enthesopathy• Sacroiliitis

Ankylosing Spondylitis

Ankylosing Spondylitis• A 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 Spondylitis

• Inflammatory Stages– Can be extremely painful (flares)– Prolonged morning stiffness (hours)– Fatigue (pain & lack of sleep)

• Ankylosis– Stiffness increases – Significantly reduced ROM– Abnormal 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

• Enthesitis

Extra-Articular Features• Eyes: Acute anterior uveitis (40%)

• 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 Investigations• Evidence of Inflammation

– Normochromic normocytic anemia– Elevated ESR/CRP– Reactive thrombocytosis

• HLA-B27 found in 90-95% of patients with Ank Spond vs 6-8% of general population

Psoriatic Arthritis

Psoriatic arthritis• Psoriatic 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

Progression• Polyarticular in 30-50%

– Like Rheumatoid Arthritis• Oligoarticular in 40-50%• Predominant Spinal Disease in 5%

– Spinal symptoms usually occur after many years of peripheral arthritis

• DIP 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 Involvement– Sacroiliitis in 1/3 of patients– Usually asymmetric (unilateral)– May be asymptomatic

• Spinal Involvement– May affect any part of the spine in a

random fashion– Different from ankylosing spondylitis

Rheumatologic Review of Systems

• Mucocutaneous Involvement– Psoriatic skin lesions– Psoriatic Nail lesions

• Entheseal Involvement• Dactylitis• Ocular Involvement

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

• Pitting• Onycholysis• Onychodystrophy• Transverse ridging

History - Psoriasis– Psoriasis 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

Dactylitis• Entire 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 Arthritis

• Goals of Treatment– Improve 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

Management• NSAIDs

– Can be useful in some cases of mono/oligo arthritis

– Useful for enthesitis– Useful for spinal disease

Management: DMARDs

Medication Psoriatic Ankylosing Spondylitis

Hydroxychloroquine (Plaquenil®)

Rarely with little evidence NO

MethotrexateYES

Rarely with poor efficacy in spinal

diseaseSulfasalazine YES YES

Leflunomide (Arava®)YES NO

Gold YES NO

Steroids YES YES

Management: Biologics• Biologics Approved for Psoriatic

Arthritis and Ankylosing Spondylitis– Etanercept (Enbrel®) – Infliximab (Remicade®)– Adalimumab (Humira®)

• Biggest advance in the treatment of spondyloarthropathies in decades!

• REACTİVE ARTHRITIS

Reactive arthritis

• 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 & Reiter’s Syndrome Synonamous

• 1916, Hans Reiter– Arthritis, 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 Arthritis

• Conjunctivitis– follows urethritis by several days– Sx often mild and transient– acute 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 • Ankle• Foot joints • Occasionally

– Wrist, Elbow, Shoulder, SIE

asymetric, oligoarticular

• Chronic cases– Dactilitis– Entesopathy. tenosynovitis, plantar facitis,

achill tendinitis, bursit

Sosis parmak

Reactive arthritis

Aphtous ulceration

Erithema nodosum

Reactive Arthritis

• Clinical course– Normally limited course running 3-12 months– 15% with prolonged relapsing arthritis

• ? Relapse• ?Reinfection

– Ankylosing Spondylitis in 10% of cases

Reactive Arthritis

• Laboratory findings– Normochromic, normocytic anemia– Leukocytosis– Acute phase reactants:

• ESR • C-reactive Protein

Reactive Arthritis

• Treatment: Antibiotics? Rest NSAIDs Methotrexate and sulphasalazine Intralesional and intraarticular

glucocorticoids Uveitis-glucocorticoids

Enteropathic ArthritisOr

SpA associated with inflammatory bowel disease

Enteropathic arthritis

Arthropathy associated with IBD – (5-20%) Peripheral arthritis Axial involvement – sacroiliitis w/o

spondylitis HLA-B27 not implicated here

Enteropathic arthritis

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

Enteropathic arthritis

Periarticular features Enthesopathy Tendonitis

Extraarticular features Erytema nodosum Uveitis

Enteropathic arthritis-Therapy

NSAID Sulphasalazine Methotrexate

Biologic agents – Anti TNF therapy