Spondyloarthropathies Brian E. Daikh, MD 7/21/09

Case: Hx: 20 y.o. male with months of left knee swelling. occasional mouth sores 1 episode of bloody diarrhea with ibuprofen 4 years of back stiffness A brother has psoriasis Exam: Left knee warm with a moderate effusion Spinal 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 Don’t see these characteristics in Rheumatoid arth.

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. RF (rheumatoid factor)

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% Morning stiffness in pelvic or back that gets better c physical activity

Differences between RA and Spondyloarthropathy RA Spondy Peripheral Arthritis polyarticular pauciarticular Sacroileitis x Spondylitis x Enthesitis x Subcutaneous Nudules x Rheumatoid Factor x Symmetry x Pauciarticular - < 5 joints

Spondylarthropathies: nonvertebral manifestations 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

HLA-B27 disease associations 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% Having gene is a risk factor, but is a poor screening test. There is a genetic risk, but doesn’t mean pt will ever get disease

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 Swollen, erythemetous, tender Source of inflam is where ligament/tendon attaches to bone - recruits osteoblasts - builds bridge across bone and “fuses” bone (ostification of ligaments) - occurs throughout skeleton

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 Spine and eye inflamm

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 Not pain, just stiffness

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. May ankylos (fuse) spine if not taken care of Syndesmophytes – fusion of cervical vertebrae/calcification of ligaments

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

Isolated to spine without peripheral AM – lengths change on fingers/ collapse down due to lack of skeletal integrity

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 Tend to preserve bone density – (Osteopenia) Pencil in cup = PA and nothing else! EXAM pathognomonic

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. Look closely at skin. Serology to exclude RA – may look really similar but these not typically seen in PA

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 May go to skin eye etc

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. Can be all over the place

Reactive Arthritis: Triggering Infections Urogenital Tract Chlamydia trachomatis Ureaplasma urealyticum Gastrointestinal Tract Yersinia enterocolitica Yersinia pseudotuberculosis Salmonella Shigella Campylobacter Respiratory Tract Chlamydia pneumoniae Swollen joints present after active infection. May still find org. by doing cultures.

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. Pt will tell story. Very indicative. Make sure to ask about prodrome of illness. May still identify org. so do cultures. Tx of infection will not tx arthritis

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. 3. Eye inflammation, skin, stomach etc.

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