Group of inflammatory arthritides that are RF-negative, HLA-B27 associated. Includes ankylosing spondylitis, psoriatic arthritis, reactive arthritis, IBD-associated arthritis. Axial inflammation + enthesitis are hallmarks. NSAIDs first-line, then biologics.
Traditional DMARDs (methotrexate, sulfasalazine) do NOT work for axial disease. They only help peripheral joints. For axial SpA, go directly from NSAIDs โ biologics (anti-TNF or anti-IL-17).
Methotrexate for peripheral PsA + skin disease. Apremilast (PDE4 inhibitor) for mild PsA when biologics are not appropriate. Neither works for axial disease.
Clinical Examples
๐ Case 1, Ankylosing Spondylitis
Patient: 24M presenting with 6 months of progressive low back pain and stiffness. Pain is worse in the morning (>1 hour of stiffness), improves with exercise, and wakes him in the second half of the night. No improvement with rest.
Workup:
HLA-B27: Positive
MRI SI joints: Bilateral sacroiliitis with bone marrow edema
CRP: Elevated at 28 mg/L
RF, anti-CCP: Negative (seronegative)
X-ray spine: Early syndesmophytes
Management:
Started on Indomethacin (Indocin) 50 mg TID, partial response after 4 weeks
Escalated to Adalimumab (Humira) 40 mg SC q2 weeks after failing 2 NSAIDs
TB screening (QuantiFERON) negative prior to biologic initiation
Ophthalmology referral for uveitis screening
Key lesson: Young male + inflammatory back pain + bilateral sacroiliitis + HLA-B27+ = classic ankylosing spondylitis. NSAIDs first, then skip DMARDs and go directly to anti-TNF for axial disease.
๐ Case 2, Psoriatic Arthritis
Patient: 45F with known psoriasis ร 10 years, now presenting with painful swollen fingers, โsausage-likeโ left 3rd toe, and pitting of multiple fingernails.
Exam findings:
Dactylitis: Diffuse swelling of left 3rd toe
DIP joint tenderness: Bilateral 2nd and 3rd fingers
Started on Methotrexate (Trexall) 15 mg weekly (peripheral + skin disease)
Folic acid 1 mg daily supplementation
Inadequate response at 3 months โ switched to Secukinumab (Cosentyx) 150 mg SC monthly
Baseline LFTs, CBC, Hep B/C screening before methotrexate
Key lesson: Psoriasis + DIP arthritis + dactylitis + nail changes = psoriatic arthritis. Methotrexate addresses both skin and peripheral joints. IL-17 inhibitors are excellent for both PsA and psoriasis.
๐ Case 3, Reactive Arthritis
Patient: 22M presenting 3 weeks after treated Chlamydia urethritis with acute right knee swelling, bilateral conjunctivitis, and persistent dysuria despite completed doxycycline course.
Naproxen (Aleve) 500 mg BID for joint inflammation
Doxycycline 100 mg BID ร 7 days (re-treat underlying Chlamydia if not fully eradicated)
Ophthalmology referral for conjunctivitis monitoring
HLA-B27: Positive (prognostic, higher risk of chronicity)
Key lesson: Post-GU infection + triad of conjunctivitis/urethritis/arthritis = reactive arthritis. Treat the underlying infection + NSAIDs for arthritis. Most cases self-limited (3โ6 months), but HLA-B27+ patients have higher risk of chronic/recurrent disease.
๐งช Workup
HLA-B27 -positive in 90% of AS, 70% reactive, 50% PsA. Not diagnostic alone (8% of general population is positive).
X-ray pelvis (SI joints) -sacroiliitis (sclerosis, erosions, fusion). May take years to appear.
MRI SI joints -bone marrow edema = early sacroiliitis. Gold standard for early disease.
First-line all SpA. Full-dose, continuous for axial disease.
Indomethacin (Indocin)
25โ50 mg TID
Traditional NSAID for AS. Very effective but GI side effects.
Adalimumab (Humira)
40 mg SC q2 weeks
Anti-TNF. First biologic for axial or peripheral SpA failing NSAIDs.
Secukinumab (Cosentyx)
150 mg SC monthly
Anti-IL-17. Alternative to anti-TNF. Avoid in IBD (can worsen).
Sulfasalazine (Azulfidine)
1โ1.5 g BID
Peripheral joints only. No axial benefit.
๐ On Rounds
Pimp Questions
How do you differentiate inflammatory back pain from mechanical back pain?
Inflammatory: Age of onset < 40, insidious onset, morning stiffness > 30 min, improves with exercise, worse with rest, night pain (second half of night), alternating buttock pain. Mechanical: Any age, often acute onset, worse with activity, better with rest, no morning stiffness. Having 4+ inflammatory features has ~95% specificity for SpA. The key differentiator: inflammatory back pain gets BETTER with movement, mechanical gets WORSE.
Why are traditional DMARDs ineffective for axial SpA?
The pathophysiology of axial SpA involves entheseal inflammation and new bone formation at the spine/SI joints driven primarily by IL-17 and TNF pathways, not the same T-cell/B-cell mediated pathways targeted by traditional DMARDs (methotrexate, sulfasalazine). These drugs act on synovial inflammation (peripheral joints) but cannot penetrate or modulate the entheseal/axial inflammatory process.
What imaging finding differentiates ankylosing spondylitis from mechanical back pain?
Sacroiliitis on MRI is the key differentiator. MRI shows bone marrow edema (bright on STIR/T2 fat-sat sequences) at the sacroiliac joints, representing active inflammation, this is the gold standard for early AS before X-ray changes appear. X-ray findings of sacroiliitis (sclerosis, erosions, joint space narrowing, eventual fusion) may take years to develop. In contrast, mechanical back pain shows no SI joint inflammation on MRI.
Why are IL-17 inhibitors contraindicated in IBD-associated spondyloarthropathy?
IL-17 plays a paradoxical protective role in gut mucosal immunity. While IL-17 drives inflammation in the joints and spine, it is critical for maintaining the intestinal epithelial barrier and defense against gut pathogens. Blocking IL-17 with secukinumab or ixekizumab disrupts this protective function, leading to new-onset or exacerbation of IBD (both Crohnโs and UC).
โก Summary
Shared Features
RF-negative, HLA-B27+, enthesitis, dactylitis, inflammatory back pain, uveitis.
AS
Bamboo spine, sacroiliitis, uveitis, aortic insufficiency. MRI SI joints for early diagnosis.
PsA
DIP joints, nail pitting, dactylitis, pencil-in-cup deformity. Treat with DMARDs โ biologics.
Reactive
"Can't see, pee, climb a tree." Post-GI/GU infection. Chlamydia testing important.
Axial Rx
NSAIDs โ anti-TNF or anti-IL-17 directly. DMARDs DO NOT WORK for axial disease.
Inflammatory Back Pain
Age <40, insidious, AM stiffness >30min, better with exercise, worse with rest.