Ankylosing Spondylitis

Scott Chandler, DO

Kevin deWeber, MD, FAAFP, FACSM, RMSK

BASICS

DESCRIPTION

Ankylosing spondylitis (AS) is a chronic inflammatory, autoimmune arthritis characterized by inflammatory back pain (IBP).
It is the most common and potentially severe subtype of spondyloarthritis (SpA), which includes:
- Reactive (Reiter) arthritis.
- Arthritis/spondylitis with inflammatory bowel disease (IBD).
- Arthritis/spondylitis with psoriasis.
- Unspecified spondylitis.
- AS without confirmed radiographic findings is classified as nonradiographic axial spondyloarthropathy (nr-axSpA) and has similar outcomes and response to treatment.
AS causes inflammation of the sacroiliac (SI) joints, peripheral joints, and entheses (sites where ligaments or tendons attach to bone).
Common sites for enthesopathy include:
- Calcaneus (Achilles and plantar fascia insertions).
- Patella.
- Tibial tubercle.
- Vertebral bodies.
The involvement of vertebral body entheses leads to the characteristic findings of syndesmophytes (vertical bony growths) and eventual fusion, which are responsible for the classic radiographic “bamboo” appearance of the spine in advanced disease.
Synonym(s): axial spondyloarthritis; inflammatory spine disease

EPIDEMIOLOGY

Incidence

Overall incidence: 0.5 to 8.2/100,000/yr
Incidence rate varies directly with prevalence of human leukocyte antigen (HLA)-B27 in given population.
Commonly presents in young adulthood
Predominant age:
- 80% of patients with AS develop symptoms before age 30 yr.
- < 5% of patients with AS present after age 45 yr.
Predominant gender: male > female (˜3:1)

Prevalence

Prevalence of AS is 9 to 30/10,000 depending on HLA-B27 prevalence in the population (1).
Higher in Alaskan Eskimos and some Native American populations owing to higher than average HLA-B27 rate
Lower in African Americans secondary to a lower HLA-B27 rate
Up to 5% of patients evaluated for chronic low back pain are ultimately diagnosed with AS.

ETIOLOGY AND PATHOPHYSIOLOGY

A clear etiologic pathway has not been established.
Speculated that an environmental/infectious trigger in a genetically susceptible individual leads to an inflammatory (T cell and macrophage) immune response that specifically targets SI, peripheral joint, and enthesis inflammation, eventually causing bony proliferation, erosions, sclerosis, and joint destruction.

Genetics

Expression of HLA-B27 antigen is clearly linked to the development of AS, but the exact mechanism is unknown.
Prevalence of HLA-B27 in African Americans is 2-4% and in Caucasians is 8%.

RISK FACTORS

Positive family history of SpA or HLA-B27
90% or more of individuals with AS are HLA-B27 positive, although an individual who is HLA-B27 positive has a 5% chance of having AS.
Reactive arthritis triggered by Chlamydia trachomatis and certain enteric infections (e.g., Shigella, Salmonella, Yersinia, and Campylobacter spp.) predisposes to development of AS.

COMMONLY ASSOCIATED CONDITIONS

Enthesitis—29% (2)
Uveitis/iritis—23%
Psoriasis—10%
Dactylitis—6%
IBD—4%
Rarely, cardiac valve/aortic root involvement

DIAGNOSIS

Diagnosis is primarily based on history of IBP (see “History”) and exam findings with imaging used to confirm diagnosis.
The modified New York criteria have historically been used for research inclusion but have never been validated for clinical use. Their limitation is requirement of radiographic evidence of disease, which may take years to develop; need at least one radiographic criteria and one clinical criteria for definitive diagnosis:
- Radiologic criteria:
  - Bilateral sacroiliitis grades 2 to 4 or
  - Unilateral sacroiliitis grade 3 or 4
- Clinical criteria:
  - Low back pain and stiffness of at least 3 mo duration that improves with exercise but is not relieved by rest
  - Limited lumbar spinal motion in sagittal (sideways) and frontal (forward and backward) planes
  - Chest expansion decreased relative to normal values corrected for age and sex
New criteria to diagnose all causes of IBP, not just AS, have been developed by the Assessment for SpondyloArthritis International Society (ASAS); intended to detect early disease without dependence on radiographic evidence of disease
ASAS-endorsed criteria for IBP (validated clinical rule) (3)[A]:
- Age of onset < 45 yr
- > 3 mo of back pain of insidious onset
- Sacroiliitis on imaging + one SpA feature or positive HLA-B27 + two SpA features
  - SpA features: IBP, arthritis, enthesitis, uveitis, dactylitis, psoriasis, IBD, responds to nonsteroidal anti-inflammatory drugs (NSAIDs), family history of SpA, HLA-B27 positive, elevated C-reactive protein (CRP)
- 82.9% sensitive, 84.4% specific for SpA