Seronegative arthritis

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

Click here: Second Opinion Arthritis Treatment Kit

Therm "seronegative arthritis" refers to a group of conditions causing arthritis of the spine and peripheral joints, often associated with HLA B27, but without a positive rheumatoid factor.

The joint involvement is more limited than in rheumatoid arthritis, and the is distribution different with the lumbo-sacral spine, distal interphalangeal joints tending to be more involved. Enthesopathy (ligament/ tendon to bone junction inflammation) is more common. The disease is usually assymetric.


• Ankylosing Spondylitis - peak incidence 15-35 years
• Reactive Arthritis – 1-2% of patients who suffer acute dysenteric episode or sexually transmitted infection (commonly Chlamydia)


• 6.8% of patients with psoriasis
• Enteropathic arthritis spondylitis (AS) – 1.5% of male population, male:female prevalence 10:1
• 5% of patients with inflammatory bowel disease

All these conditions are more common in patients who are male and those who are HLA B27 positive. Reactive arthritis may be associated with dysentery or sexually transmitted infection. The reason for the association with inflammatory bowel disease or psoriasis to arthritis is not known.


Ankylosing Spondylitis

• Episodic sacroiliac joint inflammation occurs with back pain in the teenage years or early twenties
• Buttock or low back pain is worse in the morning and relieved by exercise
• Retention of lumbar lordosis when the back is flexed is an early sign
• Asymmetrical peripheral joints (usually large) are affected
• Uveitis is strongly suggestive of the diagnosis
• Eventually fixed flexion deformities may develop in the hip

Psoriatic Arthritis

• Patients complain of inflammation involving the distal interphalangeal joints
• Severe arthritis (arthritis mutilans) may occur leading to gross deformity of the fingers (5% of psoriatic arthritis sufferers)
• Patients may develop back and neck pain similar to ankylosing spondylitis during early disease
• Cutaneous psoriatic lesions may be present
• There is interphalangeal joint synovitis and tenosynovitis leading to sausage fingers and toes
• In arthritis mutilans there may be telescoping (shortening) of fingers

Reactive arthritis

• Patients complain of pain and stiffness commonly affecting knee, heel and MTP joints
• They may complain of pain and discharge from the penis or a rash on the feet (keratoderma blennorrhagica)
• Itching and discharge from the eyes (conjunctivitis) is common
• There may be urethritis or balanitis
• Conjunctivitis is common
• Oligoarticular effusions may be noted
• Sausage toe, similar to psoriatic arthritis may be seen

Enteropathic arthritis

• Patients generally have few joints affected
• There may be large joint involvement
• Uveitis is associated with this condition
• Usually affected limbs are asymmetrical and lower limb arthritis is commoner than upper limb

Other conditions to exclude:

• Rheumatoid arthritis – usually a symmetrical small joint polyarthritis, with IgM positive rheumatoid factor in approximately 70% of cases
• Infective monoarthritis – one joint affected, associated with positive bacterial culture from joint fluid and markers of infection in the blood


• ESR and CRP commonly raised in active disease
• Specific bacterial serology testing may be helpful in reactive arthritis to look for related bacterial infection
• HLA B27 will often be positive. However, it may be negative.
• X-ray sacroiliac joints in AS (loss of medial and lateral cortical margin definition, and eventually sclerosis of joint margins). Eventually fusion of sacroiliac joints and calcification of intervertebral ligaments leads to bamboo spine appearance
• X-ray in psoriatic arthritis may show peri-articular osteolysis

Associated Diseases

• Inflammatory bowel disease is associated with enteropathic arthritis
• Salmonella, Shigella or Chlamydia infection may be associated commonly with reactive arthritis
• Psoriasis is associated with psoriatic arthritis although arthritis may pre-date the appearance of skin involvement


Physical therapy has a role, particularly in AS, where effective chest and back exercise may help to prevent chest or spinal deformity

Non-steroidal anti-inflammatory agents (NSAIDS) are the mainstay of pain relief in these conditions.

The time course of reactive arthritis may be shortened by treating the underlying micro-organism.

Disease modifying drugs are also indicated in the management of seronegative arthritis.

Commonly used drugs for psoriatic and enteropathic arthritis include hydroxychloroquine, sulphasalazine, and methotrexate.

Biologic therapy is usually required.

Joint replacement may be indicated for severe disease in large joints such as hip or knee.

Prognosis in AS is getting better. Combining physical therapy and anti-TNF drugs usually results in remission.

Prognosis in reactive arthritis is good, treatment of the underlying causative organism, with NSAIDs for pain relief often achieves remission within a few weeks of diagnosis. Antibiotic therapy is often useful if the disease is caught early.

Enteropathic arthritis often improves when the underlying inflammatory bowel disease is quiescent, but disease modifying drugs may also help to achieve remission.

Psoriatic arthritis may be severe:- "arthritis mutilans" in up to 5% of suffers, these patients may suffer significant deformity and permanent disability. The use of anti-TNF drugs looks very promising.

There are no proven strategies for prevention at present.

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