Four seronegative arthritides. One mechanism: enthesitis. One genetic marker: HLA-B27. Zero rheumatoid factor. Learn to split them before clinical medicine test you on the one that fools everyone.
SeronegativeEnthesitisHLA-B27+
Meet the Quartet
All four are seronegative (RF negative), all four share the HLA-B27 link, and all four start at the enthesis (where tendon meets bone). After that, they go four different directions. Tap a card.
Axial IBD-arthritis looks exactly like AS on imaging
From the Attending
The four seronegatives share one mechanism: the immune system attacks the enthesis, the spot where tendon anchors to bone. Enthesitis is the unifying lesion. Everything else, bamboo spine, pencil-in-cup, the reactive triad, bowel coupling, flows from that one starting point. Know the shared platform, then learn the four endings.
Tap each disease to see how tightly it ties to HLA-B27. This is the clinical medicine' favorite data point. The percentages are approximate but the ranking is locked.
HLA-B27 Association Strength
Tap a disease · Watch the bar fill · Read the payoff
Approximate prevalence in disease
Ankylosing Spondylitis
Reactive Arthritis
IBD-Arthritis (axial)
Psoriatic Arthritis
Tap any disease above to reveal its HLA-B27 association and the clinical medicine payoff.
From the Attending
Remember the ranking: AS > ReA > IBD-axial > PsA. The test will give you a HLA-B27 positive patient and ask you to pick the most strongly associated condition. That answer is always AS. The test will also remind you that having HLA-B27 does not mean you will get disease. Most B27 carriers are perfectly healthy. The marker raises risk; it does not guarantee anything.
HLA-B27 positive + sacroiliitis = go straight to AS. Every time.
The Shared Mechanism: Enthesitis
All four diseases attack the same anatomical target: the enthesis. Tap each stage to watch the inflammation cascade unfold.
Enthesitis Cascade
Tap stages in order · Watch the mechanism
The enthesis is where tendon meets bone. In spondyloarthropathies, this junction is the battlefield.
ReA Triad
Can't see (conjunctivitis/uveitis) + can't pee (urethritis) + can't climb a tree (arthritis). All three after a Chlamydia or dysenteric infection.
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AS Pain Pattern
Inflammatory back pain: stiffness worst in the morning, improves with movement. The opposite of mechanical: worse with rest, better with activity.
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Pencil-in-Cup
Psoriatic arthritis erodes the DIP joint until the proximal phalanx looks like a sharpened pencil pushed into a cup. DIP involvement is the key differentiator from RA (which spares DIP).
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IBD Axial vs Peripheral
Peripheral IBD-arthritis tracks the bowel (treat the bowel, treat the joint). Axial IBD-arthritis runs independently and looks just like AS. Two different animals.
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Treatment Rule
NSAIDs are first-line for all four. Refractory cases get anti-TNF agents (etanercept, infliximab). DMARDs (like methotrexate) work for peripheral joints but NOT for axial disease in AS.
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Uveitis Rule
Anterior uveitis (painful red eye) occurs in ALL four spondyloarthropathies, but it is the most classic extra-articular manifestation of AS. Sudden, unilateral, painful, photophobic.
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Which Spondyloarthropathy?
Work through the branches. The clue that matters is often what happened before the arthritis, not the joint exam itself.
Patient has seronegative arthritis with back pain or peripheral joint involvement. What is the clinical context?
Get pelvis X-ray and HLA-B27. Is there sacroiliitis?
Ankylosing Spondylitis. The prototype seronegative axial spondyloarthropathy. First line: NSAIDs. Refractory: anti-TNF. DXA for bone density. Screen for uveitis and aortitis.
Examine the finger closely. Which joints are involved and is the whole digit swollen?
Psoriatic Arthritis. DIP + dactylitis + psoriasis = PsA. Five patterns exist but DIP-predominant with pencil-in-cup is the clinical medicine pattern. NSAIDs first, then methotrexate or anti-TNF.
Classic triad? Can't see, can't pee, can't climb a tree?
Reactive Arthritis. Triggered by Chlamydia (urogenital) or enteric pathogens (Salmonella, Shigella, Campylobacter, Yersinia). Treat the trigger with antibiotics. NSAIDs for joint pain. Most resolve in 3-6 months.
Which joints, and does treatment of bowel disease help the joints?
IBD-Arthritis, Peripheral Type. Tracks bowel activity. Treat the IBD and the joints follow. Sulfasalazine for peripheral joints. NSAIDs may worsen IBD, use cautiously.
IBD-Arthritis, Axial Type. Runs independently of bowel. Clinically indistinguishable from AS on imaging. Anti-TNF agents treat both bowel and axial disease simultaneously.
Clinical Images
clinical medicine test these visuals. Bamboo spine and pencil-in-cup appear more often than any other spondyloarthropathy image. Tap a photo to enlarge.
Ankylosing SpondylitisBamboo spine: syndesmophytes bridging vertebrae on lateral X-ray
Bamboo SpineFull-column fusion: the end-stage of untreated AS
Psoriatic ArthritisHand X-ray: pencil-in-cup erosion at DIP joints
Reactive ArthritisKeratoderma blennorrhagica: pustular skin lesions on feet
Scroll for more images
clinical Walkthrough
26 clinical vignettes. One at a time. Right-click (or long-press) to cross out. Double-click (or double-tap) to highlight. Tap an answer to reveal the chain.
Medically reviewed by Kaitlyn Cocuzzo, MD and Fatima Ali, DO · Last updated July 1, 2026 at 10:03 PM ET
Bone Wizardry is an independent educational resource for visual learning in the medical sciences. It is not affiliated with, endorsed by, or sponsored by any licensing or examination board, contains no real or recalled examination questions, and does not guarantee any educational or examination outcome.
