Spondyloarthropathies

Brian E. Daikh, MD7/21/09

Case:

Hx: 20 y.o. male with months of left knee swelling.occasional mouth sores1 episode of bloody diarrhea with ibuprofen4 years of back stiffnessA brother has psoriasis

Exam:Left knee warm with a moderate effusionSpinal flexion limited

Question: What is the DDx and what further information is needed to

determine a diagnosis in this patient?

Spondyloarthropathy: Definitions

• A group of inflammatory arthridites Characterized by:– Synovitis– Enthesitis – inflam. Where tendon connects to bone– Spinal and Peripheral Joint Involvement– Genetic Predisposition– Probable Infectious Cause

• Categories– Ankylosing Spondylitis – Reactive Arthritis– Psoriatic Arthritis– Enteropathic Arthritis – Crohn’s disease, Ulcerative Colitis– Undifferentiated

Spondyloarthropathy: Clinical and Laboratory Features

• Sacroileitis or spondylitis (inflam of ligaments that connect to vert bodies)

• Peripheral arthritis:

– Typically asymmetric and involves the lower limb;

– Upper limb involvement often associated with Psoriatic Arthritis

• Enthesopathy -inflammation at the site of tendinous or ligamentous insertion

• Extra-articular manifestations occur in the minority

• By definition, patients are RF factor negative

• HLA-B27 is present in many individuals, depending on the type of arthritis.

ACR Diagnostic Criteria for Spondyloarthropathy

• Inflammatory Spinal Pain or Joint Synovitis (Asymmetric or predominantly lower limbs)

• AND 1 of the following:

– Positive family history– Psoriasis– IBD– Urethritis or Cervicitis (nongonococcal), or acute diarrhea within

1 month– Buttock pain– Enthesopathy– Sacroileitis

• Sensitivity 78.4% and specificity 89.6%

Differences between RA and Spondyloarthropathy

RA Spondy

Peripheral Arthritis polyarticular pauciarticularSacroileitis xSpondylitis xEnthesitis xSubcutaneous Nudules xRheumatoid Factor xSymmetry x

• Asymmetric peripheral arthritis

• Sausage digits

• Enthesopathy– Achilles tenosynovitis– Plantar fasciitis– Costochondritis

• Acute anterior uveitis/iridocyclitis

• Mucocutaneous lesions

• Nail involvement

• Fatigue, weight loss

• Amyloidosis

• Apical pulmonary fibrosis

• Immunoglobulin A nephropathy

• Cardiac involvement

Spondylarthropathies: nonvertebral manifestations

•Ankylosing spondylitis > 90% (white males)–with uveitis or aortitis ~100%

•Reactive arthritis 50-80%–with sacroiliitis or uveitis 90%

•Juvenile spondylarthropathy 80%•Inflammatory bowel disease–Peripheral Not increased–Axial

•Crohn’s disease 50%•Ulcerative colitis 70%

•Psoriasis –Peripheral Not increased–Axial 50%

HLA-B27 disease associations

HLA-B27

• A member of the MHC Class I gene family• Important in the presentation of processed

antigen to T-cells• Present in 9-11% of the caucasion

population.• A poor screening test; if absent, it is

unlikely the patient has ankylosing spondylitis, but if present, it does not mean the patient has disease.

Pathogenic Role of HLA-B27

• The mechanism is not well defined.

• Arthritogenic Peptide Theory: HLA-B27 may bind unique peptides of self or bacterial origin.

• Molecular Mimicry Theory: Antibodies directed against foreign antigens cross-react with HLA-B27.

• Aberrant Processing Theory: Abnormal folding of protein or expression of heavy chain dimers on the cell surface may lead to abnormal antigen presentation.

Enthesitis

Ankylosing Spondylitis

Ankylosing Spondylitis: Definition and Clinical Features

• A chronic inflammatory arthritis that mainly affects the axial skeleton

• Typical presentation is with low back pain of insidious onset

• Arthritis of the hips and shoulders and enthesopathies are common

• Extra-articular manifestations include: uveitis and rarely aortic valve disease and cauda equina syndrome

Ankylosing Spondylitis - Epidemiology

• Strong HLA-B27 association in all populations

• In Caucasians, AS occurs with a prevalence of 0.5-1.0%

• M:F 5:1

• Incidence and prevalence may be underestimated due to variance in clinical presentation

Characteristics of Back Pain

• Onset– Insidious– Often before age 40

• Duration greater than 3 months• Associated with prominent morning stiffness• Improves with activity

Ankylosing Spondylitis-Initial Management

• History and physical exam– Appropriate history of morning stiffness, measurement of spinal

mobility, examination of peripheral joints, eyes, mouth, skin.

• Laboratory evaluation– CBC, CRP, HLA-B27?

• X-rays– Lumbar spine and sacroiliac joints. C-spine if appropriate

• Other possible modalities-not standard of care at this time.– MRI of the lumbar spine and SI joints if plain x-rays are normal.

AS: Management

• Early diagnosis, patient education, and physical therapy are essential

• Goals of PT are to restore and maintain posture and movement to as near to normal as possible

• Self-management with exercise must be lifelong

• NSAIDS relieve pain and stiffness, but are not disease-modifying

• Sulfasalazine and Methotrexate may be effective (no controlled clinical trials)

• Anti-TNFα agents are very effective in controlled trials. These are the only FDA approved therapies.

Psoriatic Arthritis

Psoriatic Arthritis - Definition

• An inflammatory arthritis associated with psoriasis

• May occasionally be present in the absence of clinically evident psoriasis

Psoriatic Arthritis: Imaging

• Common involvement of wrists, hands, feet, and shoulders.

• In contrast to RA, osteopenia is not observed and DIP joint involvement is common.

• Classic “pencil-in-cup” deformity • May have erosion adjacent to ankylosis or

new bone formation• Periostitis

Psoriatic arthritis-initial evaluation

• History and physical exam– Close attention to the subtle findings of psoriasis, e.g. scalp

involvement, nail pitting. Complete joint exam, including spinal mobility.

• Laboratory evaluation– CBC, chemistries, CRP, RF, anti-CCP antibody (these are to

exclude RA, really)

• Baseline x-rays if appropriate– If the disease is of fairly early onset, baseline x-rays may be

normal.

Psoriatic Arthritis - Treatment

• NSAIDS – mild disease, symptom relief• Intra-articular corticosteroids• DMARDS

– Plaquenil – mild disease– Sulfasalazine – mild disease– MTX – moderate-severe disease– Anti-TNFα agents (These are the only drug

approved by the FDA for the treatment of PsA!) – used in methotrexate nonresponders.

Reactive Arthritis

Reactive Arthritis: Definitions

• Sterile joint inflammation that develops after a previous infection

• The disease is systemic and not limited to the joints

• Triggering infections most commonly originate in the throat, urogenital organs, or GI tract

Epidemiology of Reactive Arthritis

• Most commonly affects young adults

• M = F

• Annual incidence 30-40/100,000

• Worldwide distribution

• Genetic association – HLA-B27

• Frequently associated with infections

Reactive Arthritis: Clinical Features

• Arthritis, enthesitis, tendonitis, tenosynovitis, periostitis, and muscle pain

• Skin and mucous membrane lesions are frequent – oral ulcers and keratoderma blenorrhagicum

• Eye inflammation (uveitis and conjunctivitis)

• Visceral involvement (nephritis and carditis) is rare

• Severity ranges from mild arthralgias to disabling disease

• Spontaneous recovery is common and the prognosis is, in general, good

• Recurrences are not uncommon

• Susceptibility to the disease is strongly linked to HLA-B27 antigen positivity.

Reactive Arthritis: Triggering Infections

• Urogenital Tract– Chlamydia trachomatis– Ureaplasma urealyticum

• Gastrointestinal Tract– Yersinia enterocolitica– Yersinia pseudotuberculosis– Salmonella– Shigella– Campylobacter

• Respiratory Tract– Chlamydia pneumoniae

Reactive arthritis-initial evaluation

• History and physical exam– Appropriate questioning for prodromal illness

• Laboratory evaluation– CBC, chemistries, CRP, urethral or cervical

swabs, stool culture, throat culture.

Reactive arthritis-clinical course

• The clinical course is extremely variable.• The majority of patients have a relatively short, self-

limited course. These patients are often treated successfully with NSAIDs, corticosteroids, and sometimes a short courses of DMARD’s.

• Alternative courses include a waxing and waning course over a period of months or years more chronic, persistent inflammatory arthritis. These patients require treatment with DMARD’s.

Reactive Arthritis: Treatment

• Antibiotics – probably not helpful

• NSAIDS – symptomatic relief

• Sulfasalazine – may be disease modifying, peripheral joints > axial skeleton

• Methotrexate – May be disease modifying

• Anti-TNFα Agents – may be very effective

Conclusions

• The Spondyloarthropathies are a diverse group of inflammatory arthropathies that share the characteristics of arthritis and enthesitis.

• HLA-B27 likely plays a pathogenic role in many of these conditions.

• Extraarticular manifestations are uncommon, but may be severe.

Spondyloarthropathies – Clinical Pearls

• All of these conditions are diagnosed primarily based on clinical features.

• Extra-articular manifestations (skin, eye, GI) may provide important clues.

• X-rays (sacroileitis, spondylitis, erosions) may also provide clues to the Dx.

• Lab tests will not make the Dx

Spondyloarthropathies – Clinical Pearls

• Mild disease (low grade swelling, normal acute phase labs – NSAID, Plaquenil, Sulfasalazine

• Mild-Moderate disease – Sulfasalazine or Methotrexate – except spine – consider TNF blocker.

• Moderate – Severe disease – begin with Methotrexate

• Plaquenil and Sulfasalazine will not affect the skin in Psoriatic Arthritis