Medicine chapters
Ankylosing spondylitis and related arthropathies (reactive, psoriatic, enteropathic)
The HLA-B27 linked seronegative spondyloarthritides: ankylosing spondylitis with inflammatory back pain and bamboo spine, reactive arthritis after gut or genital infection, psoriatic arthritis and arthritis with inflammatory bowel disease.
- The spondyloarthritides are seronegative (RF and anti-CCP negative), linked to HLA-B27, and share sacroiliitis, enthesitis, dactylitis, asymmetrical large-joint arthritis and anterior uveitis.
- Ankylosing spondylitis: young man, inflammatory back pain better with exercise, reduced Schober test, sacroiliitis and later bamboo spine; treat with exercise + NSAIDs, then anti-TNF.
- Reactive arthritis follows gut or genital infection (urethritis, conjunctivitis, arthritis); psoriatic arthritis hits DIP joints with nail pitting and pencil-in-cup erosions; enteropathic arthritis tracks IBD.
On this page
Overview
The spondyloarthritides (SpA) are a family of inflammatory arthritides that affect the spine and peripheral joints and share a genetic link with HLA-B27 (an MHC class I antigen). They are called seronegative because rheumatoid factor and anti-CCP are negative.
Members:
- Axial spondyloarthritis, including ankylosing spondylitis (AS).
- Reactive arthritis (after gut or sexually acquired infection).
- Psoriatic arthritis.
- Enteropathic arthritis (with ulcerative colitis or Crohn disease).
Ankylosing spondylitis
Epidemiology and cause
- Young adults: onset late teens to early 30s; male to female about 3:1 (women are diagnosed later and missed more often).
- HLA-B27 is present in over 90% of white patients with AS, compared with about 8% of the general white population.
- Other genes: ERAP-1 and the IL-23/IL-17 axis (basis of IL-17 and IL-12/23 blocking drugs).
- Pathology: enthesitis at ligament attachments erodes bone, then heals with new bone (syndesmophytes), leading to fusion (ankylosis).
Clinical features
Inflammatory back pain (pain in the lower back and buttocks) with these features:
- Age at onset under 45 years.
- Insidious onset.
- Improves with exercise.
- Does not improve with rest.
- Pain at night, better on getting up; morning stiffness.
Four of these five features suggest AS.
The sacroiliac joints are the first joints involved in AS; buttock pain and a stiff lower back in the morning that eases with exercise is the classic story.
Signs and course:
- Earliest joints: sacroiliac joints. Buttock pain may alternate sides.
- Loss of lumbar lordosis and reduced spinal movement in all directions.
- Reduced chest expansion (costovertebral joints fuse); costochondritis gives anterior chest pain.
- Late: fixed thoracic kyphosis ("question mark posture"), stiff neck, hip flexion deformity, and difficulty looking forward.
- Peripheral joints: asymmetric, large joints, especially hips and knees.
Schober test
Mark the skin over the lumbar spine at the level of the dimples of Venus, then 10 cm above and 5 cm below it (15 cm apart). Ask the patient to bend forward. An increase of less than 5 cm means reduced lumbar flexion.
Marks 15 cm apart when standing; on full forward flexion they are 18.5 cm apart.
Increase = 18.5 − 15 = 3.5 cm → under 5 cm → reduced lumbar flexion, consistent with AS
Extra-articular features ("A" list)
- Anterior uveitis: about 30%; the commonest extra-articular feature; can be the first presentation. An ophthalmic emergency.
- Aortic regurgitation (aortitis, up to 1%) and heart block/conduction defects (about 5%).
- Apical lung fibrosis and restricted chest wall.
- Achilles tendinitis and plantar fasciitis (enthesitis).
- Amyloidosis (rare); kidney damage mostly from long-term NSAIDs.
- Axial osteoporosis with risk of spinal fracture, even after minor falls (a fused spine breaks like a long bone and is unstable).
Acute anterior uveitis is the commonest extra-articular feature of all the spondyloarthritides. A red, painful, photophobic eye needs same-day eye review.
The 5 As of AS: Anterior uveitis, Aortic regurgitation, Apical fibrosis, Achilles enthesitis, Amyloidosis.
Investigations
| Test | Finding |
|---|---|
| ESR, CRP | Usually raised |
| RF, anti-CCP | Negative |
| HLA-B27 | Positive in most; supports but does not prove the diagnosis |
| X-ray sacroiliac joints | Blurred margins, erosions (iliac side first, lower joint), then sclerosis and fusion |
| X-ray spine | Squaring of vertebrae, syndesmophytes, late bamboo spine |
| MRI | Shows sacroiliitis (bone marrow oedema) before X-ray changes; best early test |
If the X-ray of the sacroiliac joints is normal but AS is suspected, the next test is MRI of the sacroiliac joints.
Management
- Exercise and physiotherapy daily (posture, spinal mobility, chest expansion, hydrotherapy) are the cornerstone.
- NSAIDs: first-line drug; a long-acting NSAID at night helps morning stiffness.
- Sulfasalazine or methotrexate help peripheral joint disease but not spinal disease.
- Anti-TNF drugs (adalimumab, etanercept, infliximab, golimumab, certolizumab) when NSAIDs fail; they improve spinal and peripheral symptoms.
- IL-17 blockers (secukinumab) and IL-12/23 blocker (ustekinumab) are alternatives.
- Local steroid injections for enthesitis or a single joint; steroid eye drops for uveitis.
- Hip replacement for destroyed hips; spinal osteotomy rarely.
Oral steroids and DMARDs are not effective for the spinal disease of AS. When NSAIDs fail, the next step is a TNF-alpha blocker.
Prognosis
Good with regular exercise and pain control: most patients keep working.
Reactive arthritis
Definition and triggers
A sterile arthritis that follows an infection elsewhere (the joint fluid culture is negative).
| Type | Organisms |
|---|---|
| Post-dysenteric | Salmonella, Shigella, Campylobacter, Yersinia |
| Sexually acquired | Chlamydia trachomatis, Ureaplasma (non-specific urethritis or cervicitis) |
- HLA-B27 raises the risk greatly (30–50 fold in men), but not all patients carry it.
- Mostly young men.
Clinical features
- Arthritis days to weeks after the infection: acute, asymmetrical, lower-limb (knees, ankles, MTP joints).
- Enthesitis (Achilles, plantar fasciitis) and dactylitis.
- Classic triad: urethritis, conjunctivitis, arthritis (formerly "Reiter syndrome"). Conjunctivitis is sterile.
- Acute anterior uveitis in severe or relapsing disease.
- Skin and mucosa: keratoderma blennorrhagica (pustular plaques on soles and palms, like pustular psoriasis), circinate balanitis, painless mouth ulcers, nail dystrophy.
"Can't see, can't pee, can't climb a tree" = conjunctivitis, urethritis, arthritis.
Investigations
- Raised ESR and CRP; RF negative; HLA-B27 often positive.
- Joint aspirate: inflammatory fluid, sterile, no crystals (to exclude septic and crystal arthritis).
- Look for the trigger: urine or genital swabs (NAAT for Chlamydia), stool culture.
Management
- NSAIDs; intra-articular steroid for a big effusion; short oral steroid if severe.
- Treat the infection (e.g. Chlamydia) and screen and treat sexual partners.
- Relapsing or chronic disease: sulfasalazine or methotrexate.
- Prognosis: most recover within about 6 months, but relapses occur.
Psoriatic arthritis
- Arthritis in about 10% of people with psoriasis. It can precede the skin disease (about 15%), so always ask about family history and look at the scalp, navel and nails.
- RF negative.
Patterns
| Pattern | Notes |
|---|---|
| DIP joint arthritis | Most characteristic; with nail pitting and onycholysis |
| Asymmetrical oligoarthritis | Often with dactylitis |
| Symmetrical polyarthritis | Looks like RA but RF negative |
| Spondylitis / sacroiliitis | Often asymmetrical; only about half HLA-B27 positive |
| Arthritis mutilans | About 5%; severe bone loss, telescoping fingers |
- X-ray: central erosions with bone loss producing the "pencil-in-cup" appearance; new bone at entheses.
Management
- NSAIDs; joint injections.
- Methotrexate: treats both skin and joints; sulfasalazine or leflunomide as alternatives.
- Biologics when DMARDs fail: anti-TNF, IL-17 blockers (secukinumab, ixekizumab), ustekinumab; apremilast (PDE4 inhibitor).
- Avoid hydroxychloroquine (can flare psoriasis) and avoid oral steroids (skin rebound on withdrawal).
Psoriatic arthritis can cause a symmetrical polyarthritis that resembles RA. Clues: DIP involvement, nail changes, dactylitis and negative RF.
Enteropathic arthritis
- Seen in up to 10–15% of people who have ulcerative colitis or Crohn disease.
- Two types:
- Peripheral arthritis: asymmetrical, large lower-limb joints; follows bowel activity and settles when colitis is controlled or after colectomy.
- Axial (sacroiliitis/spondylitis): HLA-B27 linked; runs independently of bowel activity.
- Treat the bowel disease. NSAIDs help joints but may worsen colitis. Sulfasalazine helps both bowel and joints; anti-TNF (infliximab, adalimumab) for severe disease.
Comparison
| Feature | AS | Reactive | Psoriatic | Enteropathic |
|---|---|---|---|---|
| Sex | Male | Male | Equal | Equal |
| Trigger/link | HLA-B27 | Gut or genital infection | Psoriasis | IBD |
| Key joints | Sacroiliac, spine | Knees, ankles | DIP, dactylitis | Knees, ankles; spine |
| Skin/mucosa | None | Keratoderma, balanitis | Psoriasis, nail pitting | Erythema nodosum, pyoderma |
| Eye | Anterior uveitis | Conjunctivitis, uveitis | Uveitis | Uveitis, episcleritis |
Expect: inflammatory back pain in a young man, HLA-B27 (over 90% in AS), sacroiliac joints affected first, Schober test, bamboo spine and syndesmophytes, MRI for early sacroiliitis, anterior uveitis as the commonest extra-articular feature, aortic regurgitation, NSAIDs then anti-TNF, reactive arthritis triad after Chlamydia or dysentery, keratoderma blennorrhagica, psoriatic DIP arthritis and pencil-in-cup, methotrexate for skin and joints, and enteropathic arthritis tracking IBD activity.
Quick revision
- Seronegative + HLA-B27 + sacroiliitis + enthesitis + uveitis.
- AS: young man, back pain better with exercise, Schober under 5 cm.
- X-ray: sacroiliac erosions/sclerosis → syndesmophytes → bamboo spine; MRI earliest.
- Extra-articular: anterior uveitis, aortic regurgitation, apical fibrosis.
- AS treatment: exercise + NSAIDs → anti-TNF or IL-17 blocker.
- Reactive: urethritis + conjunctivitis + arthritis; Chlamydia, Salmonella, Shigella, Yersinia, Campylobacter.
- Psoriatic: DIP, nails, dactylitis, pencil-in-cup; methotrexate.
- Enteropathic: peripheral form follows bowel activity.
Written by The House Job from standard references (Kumar and Clark's Clinical Medicine).
FAQ
Why are these conditions called seronegative?
Because rheumatoid factor and anti-CCP antibodies are negative, unlike most cases of rheumatoid arthritis.
Does a positive HLA-B27 test confirm ankylosing spondylitis?
No. It supports the diagnosis, but many healthy people carry HLA-B27; the diagnosis rests on clinical features plus imaging of the sacroiliac joints.
What is the best early imaging test for sacroiliitis?
MRI, which shows inflammation before plain X-rays change.
Is reactive arthritis a joint infection?
No. The joint is sterile; the arthritis is an immune reaction to an infection in the gut or genital tract.
Which drug treats both the skin and joints in psoriatic arthritis?
Methotrexate; biologics such as anti-TNF or IL-17 blockers are used if it fails.