3. Seronegative Arthropathies

Seronegative Arthropathies

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Synonyms: seronegative spondylarthropathy, spondyloarthritis

A 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 disease and juvenile idiopathic arthritis.

The European Spondylarthropathy Study Group criteria for spondylarthropathy[1]

Inflammatory spinal pain, or synovitis (asymmetric, predominantly in the lower extremities) and one or more of the following:

  • Family history: first-degree or second-degree relative with ankylosing spondylitis, psoriasis, acute iritis, reactive arthritis or inflammatory bowel disease
  • Past or present psoriasis
  • Past or present ulcerative colitis or Crohn's disease
  • Past or present pain alternating between the two buttocks
  • Past or present spontaneous pain or tenderness on examination of the site of insertion of the Achilles tendon or plantar fascia (enthesitis).
  • Episode of diarrhoea occurring within one month before onset of arthritis
  • Nongonococcal urethritis or cervicitis occurring within one month before onset of arthritis
  • Bilateral grade 2-4 sacroiliitis or unilateral grade 3 or 4 sacroiliitis. Grade 0 is normal, 1 possible, 2 minimal, 3 moderate and 4 completely fused (ankylosed)
  • Features are consistent with the spondyloarthropathies; however, the patients do not fulfil 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 as 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 (NSAIDs) and possibly sulfasalazine, but there have been no well-designed clinical trials on the treatment of undifferentiated spondyloarthropathy.

Save time & improve your PDP on Patient.co.uk

  • Notes Add notes to any clinical page and create a reflective diary
  • Track Automatically track and log every page you have viewed
  • Print Print and export a summary to use in your appraisal
Click to find out more »
  • The prevalence of spondyloarthropathies 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 spondyloarthropathies tends to reflect the proportion of the population who are HLA-B27 positive.[3]
  • Ankylosing spondylitis and undifferentiated spondyloarthropathy are the most frequent spondyloarthropathy 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. Spondyloarthropathies 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 the 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).
  • Nongonococcal 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 spondyloarthropathy.

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.
  • X-ray of the sacroiliac joints.
  • MRI scan of the lumbar spine: if suspecting a lumbosacral disc lesion.
  • X-ray in psoriatic arthritis may show periarticular osteolysis.

HLA testing not normally done (high false-negative rate).

  • Physical therapy: education, physiotherapy, hydrotherapy and occupational therapy.
  • NSAIDs.
  • Disease-modifying anti-rheumatic drugs (DMARDs), eg sulfasalazine and methotrexate. Indications depend on the specific classification of the spondyloarthropathy.
  • Tumour necrosis factor alpha (TNF-alpha) blockers: etanercept, infliximab and adalimumab are licensed for progressive psoriatic arthritis[4] and severe ankylosing spondylitis.[5]
  • The National Institute for Health and Clinical Excellence (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 DMARDs (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 there is inadequate response after 12 weeks.[6]
  • Surgery: joint replacements.
  • The course of spondyloarthropathies 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
Provide feedback

Further reading & references

  1. 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.
  2. 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.
  3. Olivieri I, van Tubergen A, Salvarani C, et al; Seronegative spondyloarthritides. Best Pract Res Clin Rheumatol. 2002 Dec;16(5):723-39.
  4. Guideline for anti-TNF alpha therapy in psoriatic arthritis, British Society for Rheumatology (2005)
  5. Guideline for Prescribing TNF alpha Blockers in Adults with Ankylosing Spondylitis, British Society for Rheumatology (2004)
  6. Etanercept and infliximab for the treatment of psoriatic arthritis, NICE Technology Appraisal (2006)
  7. Amor B, Santos RS, Nahal R, et al; Predictive factors for the longterm outcome of spondyloarthropathies. J Rheumatol. 1994 Oct;21(10):1883-7.
Original Author: Dr Colin Tidy Current Version: Peer Reviewer: Dr Huw Thomas
Last Checked: 20/04/2010 Document ID: 2767  Version: 21 © EMIS

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.