Seronegative Spondyloarthropathies

Ovid: 5-Minute Orthopaedic Consult

Editors: Frassica, Frank J.; Sponseller, Paul D.; Wilckens, John H.
Title: 5-Minute Orthopaedic Consult, 2nd Edition
> Table of Contents > Seronegative Spondyloarthropathies

Seronegative Spondyloarthropathies
Andrew P. Manista MD
  • Also called “enthesopathies,” these
    inflammatory diseases are associated with a negative rheumatoid factor
    or antinuclear antibody titer that affects the spine and multiple
    peripheral joints.
  • Included in the seronegative
    spondyloarthropathies are AS, reactive arthritis (formerly known as
    Reiter syndrome), psoriatic arthritis, and enteropathic arthritis.
  • Synonym: Reactive arthritis
General Prevention
Although the disease cannot be prevented, careful
treatment and follow-up can prevent contractures and pulmonary and
cardiac complications.
  • Onset is usually before 40 years of age and may occur during adolescence.
  • Males are clinically affected 2–3 times more often than females (1).
  • HLA-B27 gene frequency varies with race (2).
    • Up to 10% of Caucasians
    • 3% of African Americans
    • 0.1% of black Africans
    • Up to 25% of some groups of Native Americans
Risk Factors
  • Male gender
  • HLA-B27 positive (relative risk)
  • Jewish descent (enteropathic arthritis)
>50–90% are HLA-B27 positive (AS, 90%; other
enthesopathies, 50–70%), although, as in AS, only 2% of
HLA-B27-positive persons develop AS (2).
  • Patients have a genetic predisposition with an environmental influence.
  • Many of these patients develop high levels of antibodies directed against Chlamydia, Yersinia, Salmonella, and Campylobacter.
  • Triggering bacteria may share a similar
    antigenic amino acid sequence with a sequence on the B27 molecules,
    rendering these “self” proteins foreign in appearance and therefore
    vulnerable to immunogenic attacks.
Associated Conditions
  • Iritis
  • Aortitis
  • Colitis
  • Arachnoiditis
  • Amyloidosis
  • Pulmonary fibrosis
  • Sarcoidosis
Signs and Symptoms
  • AS: Findings include bilateral sacroiliitis with acute uveitis, insidious onset of back or hip pain, and enthesitis.
  • Reactive arthritis:
    • The classic clinical picture is a young male presenting with the triad of urethritis, conjunctivitis, and arthritis.
    • Other common presenting symptoms include plantar heel pain, oral ulcers, and genital lesions.
  • Psoriatic arthropathies:
    • Affects up to 70% of patients with psoriasis (3).
    • Small joints of the hands (DIP) and feet
      are most commonly involved, with nail pitting, sausage-like digits, and
      “pencil in cup” deformities of these small joints on radiographs.
  • Enteropathic arthritis:
    • Affects up to 20% of patients with Crohn disease or ulcerative colitis (4)
    • Presentation can be similar to that of AS.
    • Asymmetric involvement of large, weightbearing joints (hips and knees) is common.
    • Abdominal manifestations include cramping, abdominal pain, bloody diarrhea (ulcerative colitis), and dehydration.
  • Rheumatoid factor and antinuclear antibody titers
  • HLA-B27 (poor yield because 2% of HLA-B27-positive patients develop seronegative spondyloarthropathies [2])
  • ESR
  • Radiography:
    • Obtain AP pelvis, AP lumbar spine, and lateral lumbar spine radiographs.
    • Additional imaging of symptomatic joints may be indicated.
  • CT or MRI may afford earlier detection of sacroiliitis (5).
  • AS: Findings include symmetric SI joint
    narrowing, squaring of the vertebral bodies, ascending spinal
    syndesmophytes seen with time, and protrusio acetabuli.
  • Reactive arthritis: Findings include SI joint narrowing (can be asymmetric) and variable regions of spinal involvement.
  • Psoriatic arthritis: Findings include
    small joint involvement, commonly the DIP joints of the hands, with a
    “pencil in cup” deformity and autofusion of the joints; bony resorption
    in the hand can be severe.
  • Enteropathic arthritis: Findings are similar to those of AS.
  • Caution should be exercised when evaluating the patient with AS and “minor” trauma.
    • Conventional radiographs may appear normal.
    • MRI scans to evaluate for nondisplaced fractures and epidural hematomas


Pathological Findings
  • Enthesopathy (inflammation at ligament-bone insertion sites)
  • Synovitis
  • Pulmonary fibrosis
  • Colitis
  • Aortitis
Differential Diagnosis
  • AS
  • Reactive arthritis
  • Psoriatic arthritis
  • Enteropathic arthritis
  • Rheumatoid arthritis (seropositive)
  • Infection (Lyme disease)
General Measures
  • Postural training
  • Strengthening and ROM exercises
  • Sleeping on a firm mattress (AS)
  • Avoidance of contact sports (AS)
  • Low impact exercises
  • No dietary restrictions
Special Therapy
Physical Therapy
Physical therapy often is necessary to maintain joint ROM and to prevent contractures.
First Line
  • NSAIDs
  • Disease-modifying agents such as sulfasalazine or methotrexate
  • Eyedrops for uveitis
  • Hip arthritis may be severe, resulting in the need for hip replacement.
  • Cervical, thoracic, and lumbar spinal deformities may occur, necessitating a corrective osteotomy.
  • In general, prognosis is better for pediatric-onset than for adult-onset spondyloarthropathies.
  • In patients with AS, the prognosis is determined by the rate of disease progression.
Cardiac involvement such as aortic insufficiency,
pulmonary fibrosis, gastrointestinal complications such as perforations
or fistulas, and vertebral (cervical) fractures (AS) may occur.
Patient Monitoring
  • Close follow-up with rheumatologists and orthopaedic surgeons is indicated.
  • Depending on the severity of the disease, patients are seen every 3–6 months.
1. van
der Linden SM, Valkenburg HA, de Jongh BM, et al. The risk of
developing ankylosing spondylitis in HLA-B27 positive individuals. A
comparison of relatives of spondylitis patients with the general
population. Arthritis Rheum 1984;27:241–249.
2. Liu
NYN, Weinstein BR. Seronegative spondyloarthropathies. In: Noble J, ed.
Textbook of Primary Care Medicine, 3rd ed. St. Louis: Mosby,
3. Battistone
MJ, Manaster BJ, Reda DJ, et al. The prevalence of sacroiliitis in
psoriatic arthritis: New perspectives from a large, multicenter cohort.
A Department of Veterans Affairs Cooperative Study. Skeletal Radiol 1999;28:196–201.
4. Sands
BE. Crohn’s disease. In: Feldman M, Tschumy WO, Jr, Friedman LS, et
al., eds. Sleisenger & Fordtran’s Gastrointestinal and Liver
Disease, 7th ed. St. Louis: Saunders, 2002: 2005–2038.
5. Resnick
D, Niwayama G. Ankylosing spondylitis. In: Resnick D, ed. Diagnosis of
Bone and Joint Disorders, 3rd ed. Philadelphia: WB Saunders,
Additional Reading
Brinker MR, Miller MD. Basic sciences. In: Miller MD, ed. Review of Orthopaedics, 2nd ed. Philadelphia: WB Saunders, 1996:1–122.
Brown CR, Jr. Medical treatment of arthritis. In: Callaghan JJ, Dennis DA, Paprosky WG, et al., eds. Orthopaedic Knowledge Update: Hip and Knee Reconstruction. Rosemont, IL: American Academy of Orthopaedic Surgeons, 1995:69–78.
Kredich D, Patrone NA. Pediatric spondyloarthropathies. Clin Orthop Relat Res 1990;259:18–22.
Miller-Blair DJ, Tsuchiya N, Yamaguchi A, et al. Immunologic mechanisms in common rheumatologic diseases. Clin Orthop Relat Res 1996;326:43–54.
Reveille JD, Arnett FC, Keat A, et al. Seronegative spondyloarthropathies. In: Klippel JH, ed. Primer on the Rheumatic Diseases, 12th ed. Atlanta: Arthritis Foundation, 2001:239–258.
721.90 AS
Patient Teaching
  • Explain the genetic aspects of the disease.
  • Patients with AS with a sudden onset of neck or back pain must be evaluated for acute fractures.
Q: Does HAL-B27-positive status confer a diagnosis of AS?
No. Although patients with HLA-B27 positive status appear to be at
increased risk of developing reactive arthritis, only 2%of patients
with HLA-B27 status develop AS.
Q: What are some of the systemic involvements, other than the musculoskeletal system, that can be seen in patients with AS?
Iritis, aortitis, colitis, arachnoiditis, amyloidosis, pulmonary fibrosis, sarcoidosis.

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