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Seronegative Arthropathies
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Synonyms: seronegative spondylarthropathy, spondyloarthritis
Heterogeneous group of inflammatory rheumatic diseases with predominant involvement of axial and peripheral joints and enthesitis (inflammation at the site of insertion of tendons and ligaments to bone). Also share other features such as anterior uveitis and bowel lesions similar to those found in Crohn's disease. Symptoms within the specific causes can overlap and may progress from one to another. There is a high incidence of HLA-B27 but negative rheumatoid factor tests. Diseases belonging to the seronegative spondyloarthropathies group include ankylosing spondylitis, Reiter's syndrome, enteropathic arthritis, psoriatic arthritis, Behçet's syndrome and juvenile idiopathic arthritis.
The European Spondylarthropathy Study Group criteria for spondylarthropathy1Inflammatory spinal pain, or synovitis (asymmetric, predominantly in lower extremities) and one or more of the following:
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- Features consistent with the spondylarthropathies, but the patients do not fulfill criteria for any specific spondyloarthropathy.
- May represent either an early phase or incomplete form of specific spondyloarthropathy, or may represent a distinct disease entity.
- Certain features (late average age of onset - 50 years, female to male ratio 3:1, low HLA-B27 positivity) suggest that undifferentiated spondyloarthropathy is distinct from other classic spondyloarthropathies.
- Prevalence appears to be at least high as ankylosing spondylitis and may be as high as 1-2% of the population.2
- Management is usually based on physical therapy, non-steroidal anti-inflammatory drugs and possibly sulphasalazine, but there have been no well-designed clinical trials on the treatment of undifferentiated spondyloarthropathy.
- The prevalence of spondylarthropathies in white populations has been estimated as being about 1.9%.2
- There is a slight preponderance of males in most subsets of spondyloarthropathy.
- HLA-B27 positive individuals have a 20-fold increased risk of developing spondylarthropathy. Geographical variation in the prevalence of spondylarthropathies tends to reflect the proportion of the population who are HLA-B27 positive.3
- Ankylosing spondylitis and undifferentiated spondylarthropathy are the most frequent spondylarthropathy subtypes.
- Individuals with inflammatory back pain who are B27 positive have a 50% likelihood of having sacroiliitis.
Risk Factors
- Family history: increased familial incidence
- HLA-B27 positive
- The mean age at onset is 20 to 40 years. Spondylarthropathies may sometimes be relatively mild and many patients do not seek medical advice.
- Inflammatory back pain: lumbar or dorsal pain at night or stiffness in morning
- Sacroiliitis: buttock pain; pain alternating between the two buttocks is more specific
- Peripheral arthritis: mainly affects the lower limbs and is often but not always asymmetrical
- Enthesitis
- Dactylitis: inflammation involving a whole finger or toe with tendovaginitis and arthritis (sausage digit)
- Non-gonococcal urethritis or cervicitis, or acute diarrhoea one month or less before the onset of arthritis
- Psoriasis, balanitis or inflammatory bowel disease
- Anterior uveitis
- Family history of spondylarthropathy
- Lumbosacral disc herniation with sciatica
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Whipple's disease
- Gout
- Osteoarthritis
- Infection: acute (e.g. staphylococci, streptococci) or chronic (e.g. tuberculosis, brucellosis)
- Malignancies: lymphomas, metastases
Will depend on the clinical presentation and therefore the differential diagnosis
- ESR and CRP: often raised in active disease
- Serum urate, rheumatoid factor, antinuclear antibodies
- Serology testing: in reactive arthritis to look for related bacterial infection
- HLA testing not normally done (high false negative rate)
- X-ray sacroiliac joints
- MRI scan lumbar spine: if consider lumbosacral disc lesion
- X-ray in psoriatic arthritis may show peri-articular osteolysis
- Physical therapy: education, physiotherapy, hydrotherapy and occupational therapy
- Non-steroidal anti-inflammatory drugs
- Disease modifying anti-rheumatic drugs, e.g. sulphasalazine and methotrexate. Indications depend on the specific classification of the spondyloarthropathy.
- TNF alpha blockers: etanercept, infliximab and adalimumab are licensed for progressive psoriatic arthritis4 and severe ankylosing spondylitis5
- NICE recommends the use of etanercept for severe active psoriatic arthritis in adults with at least 3 tender joints and at least 3 swollen joints, and who have not responded adequately to 2 other disease-modifying antirheumatic drugs (used alone or in combination). Infliximab in combination with methotrexate is recommended for those intolerant to etanercept. Etanercept or infliximab should be used under specialist supervision and should be withdrawn if inadequate response after 12 weeks.6
- Surgery: joint replacements
- Extra-articular manifestations are very uncommon but may include:
- Occasional aortitis, mitral valve insufficiency (rare), heart block
- Restrictive lung disease
- Amyloidosis
- The course of spondylarthropathies is highly variable and there may be spontaneous remissions or exacerbations, particularly in the early stages.
- Disease activity generally persists for many decades, rarely entering a long-term remission.
- Poor prognosis is associated with:7
- Hip arthritis
- Limitation of lumbar spine movements
- Dactylitis
- Oligoarthritis
- Young age at onset (less than 16 years)
- Poor efficacy of NSAIDs
- ESR greater than 30
Document References
- Dougados M, van der Linden S, Juhlin R, et al; The European Spondylarthropathy Study Group preliminary criteria for the classification of spondylarthropathy. Arthritis Rheum. 1991 Oct;34(10):1218-27. [abstract]
- Braun J, Bollow M, Remlinger G, et al; Prevalence of spondylarthropathies in HLA-B27 positive and negative blood donors. Arthritis Rheum. 1998 Jan;41(1):58-67. [abstract]
- Olivieri I, van Tubergen A, Salvarani C, et al; Seronegative spondyloarthritides. Best Pract Res Clin Rheumatol. 2002 Dec;16(5):723-39. [abstract]
- Guideline for anti-TNF-alpha in psoriatic arthritis; Kyle S et al. Guideline for anti-TNF-alpha therapy in psoriatic arthritis. Rheumatology (Oxford). 2005 Mar; 44(3):390-7. Epub 2005 Feb 3. Review. No abstract available. Erratum in: Rheumatology (Oxford). 2005 Apr;44(4):569. Rheumatology (Oxford). 2005 May; 44(5):701.
- British Society for Rheumatology; Guideline for PrescribingTNF įlpha Blockers in Adults with Ankylosing Spondylitis. June 2004.
- NICE Technology Appraisal; Psoriatic arthritis - etanercept and infliximab. July 2006.
- Amor B, Santos RS, Nahal R, et al; Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol. 1994 Oct;21(10):1883-7. [abstract]
DocID: 2767
Document Version: 20
DocRef: bgp1165
Last Updated: 3 Oct 2007
Review Date: 2 Oct 2009
The authors and editors of this article are employed to create accurate and up to date content reflecting reliable research evidence, guidance and best clinical practice. They are free from any commercial conflicts of interest. Find out more about updating.
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