Ankylosing Spondylitis: Assessment and Multimodal Treatment

Unlike degenerative spinal diseases, AS is an autoimmune condition that predominantly affects young adults. The mean delay between symptom onset and diagnosis is 7-10 years — one of the longest among rheumatologic diseases, since initial low back pain is frequently attributed to mechanical causes.

Pathophysiology

The Role of HLA-B27

Human leukocyte antigen B27 (HLA-B27) is the genetic factor most strongly associated with AS. This major histocompatibility complex (MHC class I) molecule is involved in presenting antigens to CD8+ T cells. The arthritogenic peptide hypothesis proposes that HLA-B27 presents self or microbial peptides that trigger a cross-reactive autoimmune response against joint tissues.

Another theory suggests that HLA-B27 has a tendency to misfolding in the endoplasmic reticulum, activating the cell stress response (unfolded protein response), which promotes production of pro-inflammatory cytokines such as IL-23 and TNF-alpha.

Inflammation and Ossification

The pathological process in AS follows a unique pattern: inflammation → erosion → new bone formation. The entheses (ligament and tendon insertions on bones) are the primary target of inflammation. In the spine, inflammation of the vertebral corners (spondylitis) is followed by formation of syndesmophytes — bony bridges between the vertebrae that can fuse the spine ("bamboo spine").

Ankylosing spondylitis progression: bilateral sacroiliitis - priority > spondylitis with erosions -> syndesmophytes -> ankylosis (bamboo spine)

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Extra-Articular Manifestations

AS is not limited to the spine. Extra-articular manifestations include acute anterior uveitis (25-30% of patients), inflammatory bowel disease (5-10%), psoriasis (10-15%), cardiac involvement (aortitis, conduction disorders), and apical pulmonary fibrosis (rare). These manifestations share immunological pathways with axial inflammation.

Symptoms

The cardinal symptom is inflammatory low back pain, which is distinguished from mechanical low back pain by specific features: insidious onset, duration greater than 3 months, worsening with rest, improvement with exercise, and prolonged morning stiffness (more than 30 minutes).

Diagnosis

Mechanical vs Inflammatory Low Back Pain

Distinguishing mechanical from inflammatory low back pain is the first and most important step in diagnosing ankylosing spondylitis. Mechanical pain worsens with activity and improves with rest; inflammatory pain worsens with rest and improves with exercise. Other criteria for inflammatory low back pain include: onset before age 40, insidious onset, duration longer than 3 months, morning stiffness longer than 30 minutes, and improvement with NSAIDs within 24 to 48 hours.

A young person with low back pain who wakes in the second half of the night from pain and has to get up and move around before falling back asleep — that is the classic inflammatory pattern. The Berlin Questionnaire and ASAS criteria for inflammatory low back pain help structure this screening. Any young patient with this pattern should be evaluated for spondyloarthritis.

Axial Psoriatic Arthritis: Clinical Overlap

Psoriatic arthritis can have axial involvement in 20 to 40% of cases, with sacroiliitis and spondylitis that radiologically resemble AS. The key clinical differences are: skin or nail psoriasis (present in 80% of psoriatic arthritis cases), more asymmetric sacroiliac distribution, and weaker association with HLA-B27 compared with AS. Dactylitis (sausage finger) is more common in psoriatic arthritis.

The distinction matters because, although anti-TNFs work for both conditions, IL-17 inhibitors are effective in psoriatic arthritis with active skin psoriasis. IL-23 inhibitors (risankizumab, ustekinumab) have shown efficacy in psoriatic arthritis, but trials in axial spondyloarthritis/AS did not confirm significant clinical benefit — they are not used in this indication. The rheumatologist, together with the dermatologist, defines the most appropriate therapeutic strategy.

DISH: The Radiological Mimic

Diffuse idiopathic skeletal hyperostosis (DISH) is a non-inflammatory condition characterized by ossification of the anterior longitudinal ligament and other spinal ligaments, producing a radiological appearance that can be mistaken for advanced AS. It typically affects older men with type 2 diabetes mellitus and obesity, unlike AS which affects young adults. The fundamental distinction is the absence of inflammatory sacroiliitis in DISH — sacroiliac MRI is normal.

On X-ray, DISH osteophytes are "flowing" along the anterior longitudinal ligament ("candle wax" appearance), while AS syndesmophytes are marginal and more symmetric. HLA-B27 is negative in DISH, and inflammatory markers are normal. DISH limits spinal mobility but rarely causes inflammatory symptoms, and does not require biologic treatment.

Treatments

Exercise — Cornerstone of Treatment

Regular exercise is the fundamental cornerstone of AS treatment, recommended by all international guidelines. Exercise programs that combine stretching, strengthening, and aerobic work improve mobility, pain, function, and quality of life. Swimming and hydrotherapy are particularly beneficial for the absence of axial impact.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs are the first-line pharmacological treatment in AS and, unlike in other rheumatic diseases, may have a disease-modifying effect. Studies suggest that continuous NSAID use may slow radiographic progression (syndesmophyte formation) compared with on-demand use. The most commonly used NSAIDs include naproxen, diclofenac, and etoricoxib.

Biological Therapies

TNF-alpha inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab) revolutionized AS treatment. Indicated when NSAIDs are insufficient, they reduce inflammation, improve pain and functionality, and may slow structural progression. ASAS40 response rates (40% improvement) range from 40-50%.

IL-17A inhibitors (secukinumab, ixekizumab) are an effective alternative to anti-TNFs, especially in patients with concomitant psoriasis. JAK inhibitors (tofacitinib, upadacitinib) represent the newest therapeutic class, with the advantage of oral administration.

Acupuncture as a Therapeutic Option

Acupuncture can be considered a complementary therapy in symptomatic management of AS, particularly for pain control and quality-of-life improvement. Preliminary studies suggest benefits in reducing pain and stiffness, although specific evidence for AS is still limited in methodological quality.

Importantly, acupuncture does not replace pharmacological treatment of AS, especially biologics in patients with active disease. Its role is complementary — it can help with residual pain control, sleep improvement, and stress reduction, factors that impact patients' quality of life.

Prognosis and Follow-up

AS prognosis has improved dramatically with the advent of biologics. Most patients on adequate treatment maintain good function and quality of life. Factors associated with worse prognosis include: male sex, early onset, hip involvement, smoking, and persistently elevated CRP.

Myths and Facts

When to Seek Medical Help