Seronegative arthropathies

Synonyms: seronegative spondylarthropathy, spondyloarthritis

What are seronegative arthropathies?

Seronegative arthropathies are 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).

They 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 group of seronegative spondyloarthropathies include ankylosing spondylitis, reactive arthritis, enteropathic arthritis, psoriatic arthritis, Behçet's disease and juvenile idiopathic arthritis.

The European Spondylarthropathy Study Group criteria for spondylarthropathy¹

How common are seronegative arthropathies? (Epidemiology)²

• Ankylosing spondylitis is the most common, with prevalence in a UK primary care population of around 0.15%. It is higher in populations with a higher background prevalence of HLA-B27 positivity.

• Psoriatic arthritis has been estimated to have a prevalence of 0.25% in the general population and between 6% and 14% of those with psoriasis.³

• Reactive arthritis is rare. The incidence is reported to be between 0.6 to 27 per 100,000. It is more common in adult males in the second and third decades of life. About 1-3% of patients with non-specific urethritis develop an arthritis episode.⁴

• Enteropathic arthritis develops in approximately 5% to 20% of individuals with inflammatory bowel disease and peripheral arthritis occurs in approximately 20% of patients with Crohn's disease and 12% of patients with ulcerative colitis.⁵

Risk factors

• Family history: increased familial incidence.

• HLA-B27, HLA-DR7 and HLA-DQ3 positive. The strongest relationship is between HLA-B27 and AS. In the United States, the prevalence of HLA-B27 is 7% of the general population, but it is present in 90% of those diagnosed with AS.⁶

Presentation

• The mean age at onset is 20-40 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).

• 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 spondyloarthropathy.

Differential diagnosis

• Lumbosacral disc herniation with sciatica.

• Rheumatoid arthritis.

• Systemic lupus erythematosus.

• Whipple's disease.

• Gout.

• Osteoarthritis.

• Infection: acute (eg, staphylococci, streptococci) or chronic (eg, tuberculosis, brucellosis).

• Malignancies: lymphomas, metastases.

Investigations

These 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 is not normally done (high false-negative rate).

Undifferentiated spondylarthropathy

• 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.

• Undifferentiated spondyloarthropathy has a generally low global prevalence of up to 0.7%.⁷

• 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.

Management of seronegative arthropathies⁸⁹¹⁰

Management will depend on the type of seronegative arthropathy and individual patient presentation. See also the separate articles on Ankylosing spondylitis, Reactive arthritis, Enteropathic arthritis, Psoriatic arthritis, Behçet's disease and Juvenile idiopathic arthritis.

• Physical therapy: education, physiotherapy, hydrotherapy and occupational therapy.

• NSAIDs: these are recommended as initial therapy in peripheral and axial arthritides, but their use is controversial in IBD due to associated disease flares.¹¹

• Disease-modifying antirheumatic drugs (DMARDs) - eg, sulfasalazine, methotrexate and the biological DMARDs (adalimumab, certolizumab pegol, etanercept, golimumab and infliximab). Indications depend on the specific classification of the spondyloarthropathy.

• Surgery: joint replacements.

Complications²

Generally, those affected have decreased quality of life, physical function, education and work productivity, and social participation due to pain, stiffness, fatigue, reduced mobility, and sleep problems.

The risk of cardiovascular disease is thought to be increased in people with spondyloarthritis due to the systemic inflammatory nature of the condition, as well as those affected are less able to maintain good cardiovascular fitness.

• Extra-articular manifestations are very uncommon but may include:

  • Occasional aortitis, mitral valve insufficiency (rare), heart block.

  • Restrictive lung disease.

  • Amyloidosis.

Prognosis²

• The course of spondyloarthropathies is very variable and there may be spontaneous remission (particularly in reactive arthritis - symptoms persist for 3–5 months and chronic inflammatory arthritis persists in up to 20% of affected people) or exacerbations, particularly in the early stages.

• Psoriatic arthritis is potentially disabling as 50% of those affected develop irreversible joint damage within 2 years.

• Apart from reactive arthritis, disease activity generally persists for many decades, rarely entering a long-term remission.