Spondyloarthritis: Ankylosing Spondylitis and Psoriatic Arthritis

TL;DR. A family of inflammatory arthritis that behaves differently from rheumatoid arthritis in almost every way. It attacks the spine and the sacroiliac joints, and it inflames entheses, the points where tendons and ligaments anchor into bone, rather than the joint lining. It is more common in men, strongly linked to a single gene variant called HLA-B27, and it comes with inflammation of the eye, the gut, and the skin so often that these are considered part of the disease rather than complications. The most important practical fact is the one that causes the most harm by being unknown: this back pain gets better with exercise and worse with rest, which is the opposite of ordinary back pain, and failing to ask that single question is a large part of why the average diagnostic delay is eight to ten years.

Key takeaways

• Axial spondyloarthritis affects roughly 0.5 to 1 percent of people, comparable to rheumatoid arthritis, and takes an average of 8 to 10 years to diagnose.
• Inflammatory back pain starts before 45, comes on gradually, lasts over three months, produces morning stiffness over 30 minutes, improves with exercise and not with rest, and wakes people in the second half of the night.
• The delay is worse in women, who were long assumed not to get it and who more often have normal X-rays and more widespread symptoms.
• Conventional DMARDs such as methotrexate do not work for spinal disease, which is a fundamental difference from rheumatoid arthritis and a common source of mistreatment.
• Exercise is a first-line treatment, not an adjunct, and it is the only intervention that preserves spinal mobility.
• Acute anterior uveitis occurs in 25 to 40 percent and is a same-day emergency, because untreated it damages vision.

What the family is

In short: Five related conditions sharing a genetic background, a target tissue, and a set of features outside the joints.

Spondyloarthritis (SpA) is an umbrella covering conditions that share features rather than one disease with variants:

The shared features that define the family:

• HLA-B27 association, strongest in axial disease.
• Enthesitis: inflammation where tendons and ligaments insert into bone.
• Dactylitis: a whole finger or toe swelling uniformly, called a "sausage digit".
• Asymmetric arthritis of large joints in the legs, unlike rheumatoid arthritis's symmetrical small joints.
• Extra-articular inflammation: uveitis, psoriasis, and inflammatory bowel disease.
• Absence of rheumatoid factor, which is why these were historically called the "seronegative spondyloarthropathies".

Two ways of dividing it

Modern practice classifies by where the disease predominantly is rather than by old disease names:

• Axial: spine and sacroiliac joints predominant. Subdivided into radiographic axSpA (visible sacroiliac damage on X-ray, which is what "ankylosing spondylitis" traditionally meant) and non-radiographic axSpA (same disease, same symptoms, no X-ray changes yet, and equal symptom burden).
• Peripheral: limb joints, entheses, and digits predominant.

The non-radiographic category exists because X-rays take years to change. Structural damage visible on plain film may take five to ten years to appear, so requiring it for diagnosis guaranteed a decade of delay. MRI detects active inflammation of the sacroiliac joints far earlier, and its adoption is the main reason diagnosis has improved at all.

The history

In short: Skeletons from ancient Egypt, a name from 1893, and one genetic discovery in 1973 that reorganised the whole field.

Fused spines consistent with ankylosing spondylitis appear in ancient Egyptian remains. The condition was described clinically in the late nineteenth century by Vladimir Bekhterev in Russia, Adolph Strümpell in Germany, and Pierre Marie in France, and it is still called Bekhterev's disease in parts of Europe.

1973 is the pivotal year: the association with HLA-B27 was reported independently by two groups, and it was among the first strong HLA-disease associations found. It reframed the disease as immunological and genetic rather than degenerative, and it grouped together conditions that had seemed unrelated.

1990s to 2000s brought the recognition that TNF inhibitors work dramatically in axial disease that had been essentially untreatable beyond physiotherapy and anti-inflammatories. 2010s onward added the IL-17 pathway, and the ASAS classification criteria that formalised non-radiographic disease and made earlier diagnosis possible.

What actually goes wrong

In short: Inflammation at the enthesis, then bone erosion, then paradoxical new bone formation that fuses joints permanently.

The enthesis, not the synovium

This is the key mechanistic difference from rheumatoid arthritis. An enthesis is where a tendon, ligament, or joint capsule anchors into bone, a mechanically stressed transition zone with its own resident immune cells.

In spondyloarthritis, inflammation begins here. The current model:

1. Mechanical stress at entheses activates resident immune cells, which is thought to explain why the disease targets the spine, pelvis, and heel, the most mechanically loaded entheses.
2. IL-23 and IL-17 signalling drives the inflammation. This axis, rather than TNF alone, appears central, which is why IL-17 blockers work.
3. Bone is eroded at the site of inflammation.
4. Then, paradoxically, new bone forms. Unlike rheumatoid arthritis, which only destroys, this disease also builds. Bony bridges called syndesmophytes grow between vertebrae. Over years they can fuse the spine into a rigid column, the bamboo spine of advanced disease.

That paradox has a clinical consequence. Controlling inflammation with biologics does not straightforwardly stop new bone formation, and the relationship between the two processes remains one of the field's genuine unknowns.

HLA-B27

HLA-B27 is present in roughly 80 to 90 percent of people with ankylosing spondylitis of European ancestry, against about 6 to 8 percent of the general population in those countries.

But it is not a diagnostic test. Most HLA-B27-positive people never develop the disease: the lifetime risk in a positive person is only a few percent, rising to around 20 percent if they also have an affected first-degree relative. The gene raises the odds; it does not decide the outcome.

The frequency of HLA-B27 varies dramatically by ancestry, which is why disease prevalence does too: it is very common in some Northern European and Indigenous Arctic populations, common in parts of Asia, and rare in populations of West African descent, where the disease is correspondingly uncommon.

How it causes disease is still unresolved, which is remarkable for an association known for fifty years. Competing explanations include presentation of an as-yet-unidentified peptide, misfolding of the HLA-B27 molecule itself causing cellular stress, and formation of unusual heavy-chain dimers recognised by immune cells.

What it does to the body

In short: Back pain that behaves backwards, plus eyes, skin, gut, and heels.

Inflammatory back pain

The single most useful diagnostic concept in this chapter. Five features distinguish it from the mechanical back pain of Chapter 58:

"Better with exercise, worse with rest" is the question that finds this disease, and it takes five seconds to ask.

Alternating buttock pain is another characteristic feature, reflecting sacroiliac joint inflammation, and is frequently attributed to sciatica.

Elsewhere

The fracture risk in a fused spine deserves emphasis. A rigid spine behaves like a long bone, so a fall that would cause a bruise in anyone else can cause an unstable fracture with spinal cord injury. Any new neck or back pain after even minor trauma in someone with advanced disease needs imaging, not reassurance.

Is it deadly?

In short: Rarely directly, and it raises cardiovascular risk and causes substantial disability, and the biggest cost is the years lost to diagnostic delay.

Axial spondyloarthritis modestly increases mortality, mainly through cardiovascular disease driven by chronic inflammation, plus the fracture risk above. Life expectancy reduction is smaller than in rheumatoid arthritis or lupus.

The dominant burden is disability and lost time. Onset is typically in the twenties, which is precisely when education, career, and family are being established, and the average patient spends close to a decade being told they have a bad back before the diagnosis is made. Work disability rates are substantial, and much of that is preventable with earlier treatment.

Psoriatic arthritis is erosive in a significant proportion and can cause severe joint destruction, including the rare and dramatic arthritis mutilans, in which bone is resorbed and digits shorten and telescope.

Is it contagious?

In short: No, though one member of the family is triggered by infections that are.

Spondyloarthritis is not transmissible.

Reactive arthritis is the interesting exception in the causal chain. It develops one to four weeks after an infection elsewhere, typically:

• Gut: Salmonella, Shigella, Campylobacter, Yersinia (Chapter 34)
• Genital: Chlamydia trachomatis (Chapter 35)

The infection is contagious; the arthritis is not. The joint itself is sterile, and the arthritis is an immune response to the infection rather than infection of the joint. It is more likely in HLA-B27-positive people, usually resolves within months, and becomes chronic in a minority.

The historical name Reiter's syndrome has been abandoned, both because the triad it described (arthritis, urethritis, conjunctivitis) occurs in a minority of cases and because Hans Reiter was convicted at Nuremberg for his role in human experimentation in concentration camps.

Who gets it

In short: Young adults, historically thought to be mostly men, and that assumption is a large part of why women wait longer for diagnosis.

• Prevalence: roughly 0.5 to 1 percent for the family, varying with HLA-B27 frequency.
• Age: onset typically between 20 and 40. Onset after 45 makes the diagnosis unlikely.
• Sex: the male-to-female ratio in radiographic disease is around 2 or 3 to 1; in non-radiographic axSpA it is close to 1 to 1. The traditional teaching that this is a man's disease came from studying the radiographic form, and it has caused sustained diagnostic harm to women.
• Women present differently: more neck and widespread pain, more peripheral joint involvement, higher reported disease activity, less visible radiographic change, and consequently longer delay and more frequent misdiagnosis as fibromyalgia (Chapter 55).
• Family history: a first-degree relative with the disease substantially raises risk.
• Psoriasis: 20 to 30 percent of people with psoriasis develop psoriatic arthritis, usually years after the skin disease. Nail involvement and scalp or intergluteal psoriasis are the strongest predictors, which is why dermatologists screen for joint symptoms.

Treatment, and how it works

In short: Exercise first and permanently, NSAIDs next, then biologics targeting TNF or IL-17, and not methotrexate for spinal disease.

Exercise is a drug here

Physiotherapy and daily exercise are first-line treatment, not lifestyle advice. Structured exercise improves pain, function, and, uniquely, preserves spinal mobility. Supervised group programmes outperform home exercise, and the effect is lost when the exercise stops. Posture work matters, because if a spine is going to fuse, the aim is for it to fuse in a functional position rather than bent forward.

The drugs

Don't be confused: methotrexate is the anchor drug in rheumatoid arthritis and does not work for the spine in spondyloarthritis. This is one of the most consequential differences between two diseases that both cause inflammatory joint pain. Patients with axial disease treated for years with methotrexate on the assumption that inflammatory arthritis means methotrexate lose exactly the time in which biologics would have helped. If your back disease is being treated with methotrexate and not improving, that is a reason to ask about the diagnosis.

Other components

• Smoking cessation, which is associated with worse disease, faster radiographic progression, and poorer treatment response in axSpA specifically.
• Bone protection, because osteoporosis is common and under-treated.
• Uveitis education: every patient should know that a painful red eye means an eye assessment the same day.
• Cardiovascular risk assessment.
• Surgery: hip replacement is common and effective in those with hip involvement; corrective spinal osteotomy is occasionally performed for severe fixed deformity.

Psoriatic arthritis specifically

In short: Five patterns, nail changes as a warning sign, and a treatment choice shaped by whether skin or joints dominate.

Occurs in 20 to 30 percent of people with psoriasis. Usually the skin comes first, by an average of around ten years, though in 10 to 15 percent the arthritis appears first, which makes diagnosis harder.

Five recognised patterns: asymmetric oligoarthritis (few joints); symmetric polyarthritis resembling rheumatoid arthritis; distal interphalangeal predominant (the end finger joints, which rheumatoid arthritis spares); spondylitis; and arthritis mutilans.

Distinctive features that separate it from rheumatoid arthritis:

• Involvement of the end finger joints (DIP), closely associated with nail disease (pitting, ridging, separation from the nail bed, thickening) in the same digit.
• Dactylitis, whole-digit swelling.
• Enthesitis, particularly at the Achilles tendon and plantar fascia.
• Asymmetry.
• Rheumatoid factor and anti-CCP negative.

Treatment follows the domains involved: skin, peripheral joints, axial disease, enthesitis, dactylitis, and nails, and drugs differ in how well they cover each. IL-17 and IL-23 inhibitors are particularly effective for skin; TNF inhibitors cover most domains; methotrexate helps skin and peripheral joints but not axial disease.

What the person can do

In short: Ask the exercise-versus-rest question, exercise daily, treat a red eye as an emergency, and get a diagnosis rather than a label.

• If your back pain improves with exercise and worsens with rest, started before 45, and has lasted over three months, ask specifically about inflammatory back pain and rheumatology referral. This is the single highest-value sentence in the chapter.
• Exercise every day, including spinal mobility and posture work. This is treatment. Stopping loses the benefit.
• A painful red eye with light sensitivity means an eye assessment the same day, not a pharmacy. Untreated uveitis damages vision permanently.
• Do not accept methotrexate as adequate treatment for axial disease.
• Stop smoking, which affects this disease particularly strongly.
• Tell any anaesthetist and any physiotherapist about spinal fusion or restricted neck movement, which affects airway management and manual therapy safety.
• Get any new back or neck pain after a fall imaged if your spine is fused.
• If you have psoriasis, report joint pain, heel pain, or a swollen finger rather than assuming it is unrelated. Early treatment prevents erosion.
• Ask about bone density, since osteoporosis coexists with the new bone formation and is easily missed.

Living with it

In short: A young person's disease with an invisible presentation and a long history of not being believed.

The two defining social features are the delay and the invisibility.

The average person with axial spondyloarthritis spends the better part of a decade being told they have non-specific back pain, are too young for anything serious, or should try to relax. Patient surveys consistently find multiple clinicians seen and multiple wrong diagnoses given, with fibromyalgia and mechanical back pain the commonest. For women the delay is longer.

The disease is also largely invisible: someone in their twenties with severe morning stiffness and crushing fatigue looks entirely well by mid-morning, which affects how employers, families, and benefits systems respond.

Fatigue, sleep disruption from night pain, and depression are all common and under-treated, and they respond partly to controlling the inflammation and partly to being treated in their own right.

What's next

In short: Earlier diagnosis, understanding how HLA-B27 actually causes disease, and whether new bone formation can be stopped.

• Closing the diagnostic delay, through referral rules for young people with chronic back pain and wider use of MRI. This would deliver more benefit than any new drug.
• Understanding HLA-B27, which remains unexplained fifty years after the association was found.
• Preventing structural progression. Whether biologics halt new bone formation, and whether starting earlier changes the trajectory, is unresolved.
• Bimekizumab and dual-cytokine blockade, which inhibits IL-17A and IL-17F together and has shown high response rates across the family.
• Better treatment for enthesitis and for axial psoriatic arthritis, both of which respond less reliably than peripheral joint disease.

Sources and notes

Prevalence estimates and HLA-B27 frequencies by population: Dean et al., Rheumatology, 2014, and Braun and Sieper, The Lancet, 2007. HLA-B27 association: Brewerton et al. and Schlosstein et al., independently in 1973. ASAS classification criteria for axial and peripheral SpA: Rudwaleit et al., Annals of the Rheumatic Diseases, 2009 and 2011. Diagnostic delay of 8 to 10 years and sex differences: multiple national cohort and survey analyses, including Sieper and Poddubnyy, The Lancet, 2017. Inflammatory back pain criteria: Sieper et al., ASAS expert criteria. Subclinical gut inflammation prevalence: Mielants and Van den Bosch series. TNF inhibitors in axSpA: ASSERT, ATLAS, and subsequent trials. IL-17 inhibition: MEASURE and COAST programmes. Failure of IL-23 inhibition in axial disease: Deodhar et al., Arthritis & Rheumatology, 2019. Bimekizumab: BE MOBILE trials. Spinal fracture risk in ankylosing spondylitis: multiple cohort analyses. Psoriatic arthritis incidence among psoriasis patients: Alinaghi et al., meta-analysis, 2019. Reiter eponym: rejected by consensus following historical review.

Open questions. How HLA-B27 causes disease is unresolved. Whether anti-inflammatory treatment prevents new bone formation and spinal fusion is genuinely uncertain. Why IL-23 blockade works in psoriatic skin and peripheral joints but not in the axial skeleton is unexplained and is one of the more interesting puzzles in immunology.

Next: the inflammatory disease of the bowel, which shares much of this biology and behaves very differently. 👉