Musculoskeletal

Spondyloarthritis: ankylosing, psoriatic, reactive, IBD-associated

Clinical Overview and When to Suspect Spondyloarthritis

— Ankylosing spondylitis (AS) / radiographic axial SpA — sacroiliitis on plain film + chronic back pain

— Psoriatic arthritis (PsA) — arthritis + psoriasis (skin or nails); five patterns including DIP-predominant, oligoarticular, polyarticular, spondylitis, arthritis mutilans

— Reactive arthritis (ReA) — sterile arthritis 1–4 weeks after GU (Chlamydia) or GI (Salmonella, Shigella, Yersinia, Campylobacter, C. diff) infection

— IBD-associated (enteropathic) arthritis — peripheral arthritis tracks with bowel activity; axial disease does not

— Young adult (<45) with insidious low back pain ≥3 months, morning stiffness >30 min, improves with exercise, worsens with rest, nocturnal awakening

— Asymmetric large-joint oligoarthritis of lower extremities

— Dactylitis ("sausage digit") or enthesitis (Achilles, plantar fascia)

— Recurrent anterior uveitis, psoriatic plaques, nail pitting, onycholysis

— Recent dysentery or urethritis preceding joint pain

Spondyloarthritis (SpA) is a family of seronegative (RF-negative, anti-CCP–negative) inflammatory arthritides sharing HLA-B27 association, axial and/or peripheral joint involvement, enthesitis, dactylitis, and extra-articular features (uveitis, psoriasis, IBD).

Four overlapping phenotypes:

When to suspect on Step 3:

Board pearl: The classic inflammatory back pain (IBP) criteria — age <40, insidious onset, improvement with exercise, no improvement with rest, pain at night — should prompt SI joint imaging, not another round of NSAIDs and PT referral alone.

Step 3 management: In a primary care visit, IBP features in a young patient warrant HLA-B27, CRP/ESR, and pelvic X-ray (SI joints); if X-ray normal but suspicion high, order MRI of sacroiliac joints to detect non-radiographic axial SpA. Refer to rheumatology before initiating biologics.

Early recognition matters: delay to diagnosis averages 7–10 years, and TNF inhibitors slow structural progression when started early.

Presentation Patterns and Key History

— Male predominance (~2–3:1), peak onset late teens to 30s

— Gradual low back and buttock pain, often alternating buttock pain (suggests sacroiliitis)

— Morning stiffness >1 hour, improves with movement

— Progresses cephalad: lumbar → thoracic → cervical fusion ("bamboo spine")

— Reduced chest expansion from costovertebral involvement

— Skin psoriasis precedes arthritis in ~70%, but 15% have arthritis first

— Ask about nail pitting, onycholysis, scalp/umbilical/gluteal cleft plaques

— DIP joint involvement, dactylitis (whole-digit swelling from tenosynovitis + arthritis)

— Family history of psoriasis common

— 1–4 weeks after GU infection (Chlamydia trachomatis) or enteric infection (Salmonella, Shigella, Yersinia, Campylobacter)

— Classic triad ("can't see, can't pee, can't climb a tree"): conjunctivitis, urethritis, arthritis — full triad in minority

— Asymmetric lower-extremity oligoarthritis, heel pain (enthesitis), dactylitis

— Mucocutaneous: keratoderma blennorrhagicum (palms/soles), circinate balanitis, painless oral ulcers

— Type 1 (pauciarticular, <5 joints): tracks with bowel flares, self-limited

— Type 2 (polyarticular, symmetric): independent of bowel activity

— Axial disease (sacroiliitis/spondylitis) is independent of GI activity — treating the gut does not fix the spine

Ankylosing spondylitis:

Psoriatic arthritis:

Reactive arthritis:

IBD-associated arthritis:

Key distinction: Inflammatory back pain improves with activity and worsens with rest; mechanical back pain does the opposite. This single history element is the highest-yield screen.

Board pearl: Always ask about eye redness/pain — acute anterior uveitis occurs in 30–40% of AS patients and is often the presenting complaint that brings them to ophthalmology before rheumatology. HLA-B27–associated uveitis is unilateral, recurrent, alternating, with hypopyon.

Step 3 management: Document symptom duration; SpA classification requires ≥3 months of back pain with onset before age 45.

Physical Exam Findings (and Functional Assessment)

— Schober test: mark L5 and 10 cm above; with forward flexion, distance should increase to ≥15 cm. <5 cm increase = reduced lumbar flexion

— Occiput-to-wall distance: patient stands heels/back to wall; inability to touch occiput indicates cervical/thoracic kyphosis

— Chest expansion: measured at 4th intercostal space; <2.5 cm is abnormal (costovertebral involvement)

— FABER (Patrick) test and sacroiliac compression reproduce SI joint pain

— Loss of lumbar lordosis, exaggerated thoracic kyphosis ("question mark posture")

— Dactylitis: uniform sausage-like swelling of an entire digit (toe > finger)

— Enthesitis: tenderness at tendon insertions — Achilles, plantar fascia insertion, patellar tendon, iliac crest

— Asymmetric large-joint synovitis, typically lower extremity

— PsA: DIP involvement, nail pitting (>20 pits highly suggestive), onycholysis, oil-drop sign

— Psoriatic plaques (scalp, extensor surfaces, umbilicus, gluteal cleft, nails)

— Keratoderma blennorrhagicum (hyperkeratotic papules on soles) and circinate balanitis in ReA

— Painless oral ulcers

— Slit-lamp: cells/flare in anterior chamber for acute anterior uveitis

— Aortic regurgitation murmur (aortitis affects root)

— Conduction blocks on auscultation/ECG cues (bradycardia)

— Restrictive pulmonary pattern from thoracic ankylosis; apical pulmonary fibrosis (rare, late)

Axial exam (AS, axial PsA):

Peripheral exam:

Mucocutaneous/ocular:

Cardiopulmonary (advanced AS):

Board pearl: A young man with chronic back pain + early diastolic murmur = AS with aortitis until proven otherwise. Get an echo and ECG.

Key distinction: RA spares the DIP and the axial skeleton (except C1–C2); SpA loves the DIP, SI joints, and entheses. Symmetric MCP/PIP synovitis with morning stiffness in a middle-aged woman → think RA, not SpA.

Step 3 management: Document Schober, chest expansion, and occiput-to-wall at baseline to monitor disease progression objectively over years.

Diagnostic Workup — Initial Labs and Imaging

— CRP and ESR: elevated in ~50–70% of active SpA; normal values do not rule it out

— CBC: normocytic anemia of chronic disease, mild thrombocytosis in active inflammation

— RF and anti-CCP: should be negative (seronegative); positive results redirect toward RA

— ANA: generally negative; helpful to exclude lupus

— HLA-B27: present in ~90% of AS, 50–70% of ReA, 50% of IBD-associated axial disease, ~25% of PsA

— Uric acid: to exclude gout in monoarthritis

— Synovial fluid analysis if monoarthritis: inflammatory (WBC 2,000–50,000, PMN-predominant), sterile cultures, no crystals

— Chlamydia NAAT (urine or urethral/cervical)

— Stool culture if recent diarrhea (Salmonella, Shigella, Campylobacter, Yersinia)

— HIV testing — especially before initiating immunosuppression

— Hepatitis B/C screening before biologics

— TB screen (IGRA or PPD) mandatory before any TNF inhibitor

— Plain pelvic X-ray (AP view of SI joints) is first-line: look for erosions, sclerosis, joint-space narrowing, ankylosis of SI joints

— Modified New York criteria require bilateral grade ≥2 or unilateral grade ≥3 sacroiliitis on X-ray for radiographic AS

— Lumbar spine: shiny corners (Romanus lesions), squaring of vertebrae, syndesmophytes, eventually bamboo spine

Laboratory studies:

Infectious workup for reactive arthritis:

Imaging — axial:

Board pearl: A negative HLA-B27 does not exclude SpA, especially in PsA and IBD-associated disease. Conversely, HLA-B27 has ~8% population prevalence — don't diagnose AS on B27 alone.

Key distinction: Syndesmophytes in AS are thin, vertical, marginal; osteophytes in degenerative disease are horizontal, bulky. PsA produces non-marginal, chunky, asymmetric syndesmophytes ("comma-shaped").

Step 3 management: Order CBC, CMP, ESR/CRP, HLA-B27, RF, anti-CCP, and AP pelvis X-ray as the initial outpatient panel. Plan TB and hepatitis screening before referring for biologic therapy — anticipate the rheumatologist's needs.

Diagnostic Workup — Advanced and Confirmatory Studies

— Indicated when plain films are normal but suspicion remains high (non-radiographic axial SpA)

— STIR/T2 fat-suppressed sequences show bone marrow edema at SI joints — the hallmark of active inflammation

— Detects sacroiliitis years before X-ray changes

— Also identifies enthesitis, capsulitis, synovitis

— Romanus lesions (anterior corner edema), Andersson lesions (discovertebral inflammation), fatty metaplasia (chronic)

— Helpful when SI joints already fused and disease activity needs assessment

— Power Doppler detects enthesitis (Achilles, plantar fascia) and subclinical synovitis

— Useful for distinguishing dactylitis from cellulitis

— ASAS axial SpA criteria: back pain ≥3 months + age <45 + either (imaging arm: sacroiliitis on imaging + ≥1 SpA feature) or (clinical arm: HLA-B27 + ≥2 SpA features)

— SpA features: IBP, arthritis, enthesitis, uveitis, dactylitis, psoriasis, IBD, good response to NSAIDs, family history, HLA-B27, elevated CRP

— CASPAR criteria for PsA: inflammatory articular disease + ≥3 points from psoriasis (current 2, history 1, family 1), nail changes, negative RF, dactylitis, juxta-articular new bone formation

— Slit-lamp exam if any eye symptoms — refer to ophthalmology urgently for suspected uveitis

— Colonoscopy if GI symptoms or unexplained anemia/iron deficiency to evaluate for occult IBD

— Echocardiogram if murmur or longstanding AS — screen for aortic regurgitation

— DEXA scan — AS patients have paradoxically high osteoporosis risk despite ankylosis; bone is fragile

MRI of sacroiliac joints:

MRI of the spine:

Ultrasound:

Classification criteria (for reference, not strict diagnosis):

Specific testing:

Board pearl: MRI bone marrow edema at SI joints is the single most important advanced imaging finding for non-radiographic axial SpA — it lets you diagnose and treat before irreversible structural damage.

Step 3 management: When ordering MRI SI joints, specify "STIR/fat-suppressed sequences without contrast" — gadolinium adds little and is unnecessary.

CCS pearl: Document baseline BASDAI or ASDAS scores on initial rheumatology evaluation to track response objectively.

Risk Stratification and First-Line Management Logic

— Relieve pain and stiffness

— Preserve function and posture

— Prevent structural damage (syndesmophytes, joint erosions)

— Treat extra-articular manifestations (uveitis, psoriasis, IBD)

— Address cardiovascular risk (chronic inflammation = accelerated atherosclerosis)

— Target = remission or low disease activity (ASDAS <2.1 for axial SpA, minimal disease activity for PsA)

— Reassess every 3 months until target reached, then every 6–12 months

— Adjust therapy if target not met

— Step 1: NSAIDs continuously (not PRN) for ≥2–4 weeks at full dose; try ≥2 different NSAIDs over 4 weeks total before declaring failure

— Step 2: If inadequate response → TNF inhibitor (adalimumab, etanercept, infliximab, golimumab, certolizumab) or IL-17 inhibitor (secukinumab, ixekizumab)

— Step 3: Switch within or between classes; consider JAK inhibitor (tofacitinib, upadacitinib)

— DMARDs (methotrexate, sulfasalazine) do NOT work for axial disease but may help peripheral arthritis

— Mild peripheral: NSAIDs ± intra-articular steroids

— Moderate-severe peripheral: methotrexate, sulfasalazine, leflunomide; advance to biologics

— Axial PsA: same as AS (NSAIDs → biologics; skip MTX)

— Enthesitis/dactylitis-predominant: biologics earlier

— NSAIDs first-line; usually self-limited (3–12 months)

— Treat the triggering infection if Chlamydia detected (doxycycline or azithromycin) — and treat sexual partners

— Persistent disease: sulfasalazine; refractory: TNFi

— Peripheral: treat the IBD (5-ASA, steroids, anti-TNF); arthritis often follows bowel

— Axial: TNFi (infliximab, adalimumab); avoid IL-17 inhibitors — they can worsen IBD

— Avoid systemic NSAIDs in active IBD (can flare colitis); use selective COX-2 cautiously

Goals of therapy:

Treat-to-target framework:

Stepwise approach — axial SpA (AS):

Stepwise approach — PsA:

Reactive arthritis:

IBD-associated arthritis:

Board pearl: IL-17 inhibitors (secukinumab, ixekizumab) are contraindicated/avoided in IBD — they can precipitate or worsen colitis. In a patient with both axial SpA and IBD, infliximab or adalimumab is the answer.

Step 3 management: Before starting any biologic, complete TB screen, hepatitis B/C, HIV, age-appropriate vaccinations (no live vaccines on biologics).

Pharmacotherapy — First-Line Drug Regimen

— Naproxen 500 mg BID, indomethacin 50 mg TID, or celecoxib 200 mg daily

— Continuous dosing superior to PRN for axial SpA — may slow radiographic progression

— Trial: full dose × 2–4 weeks; if no response, switch to a second NSAID for another 2 weeks

— Add PPI if cardiovascular/GI risk factors

— Monitor BP, renal function, GI symptoms

— Methotrexate 15–25 mg weekly + folic acid 1 mg daily; baseline CBC, LFTs, creatinine, hepatitis serologies; check labs q4–8 weeks

— Sulfasalazine 2–3 g/day — useful in peripheral PsA, peripheral AS, ReA; check G6PD; monitor CBC, LFTs

— Leflunomide 10–20 mg daily for PsA

— No efficacy for axial disease — don't expect MTX to fix sacroiliitis

— Adalimumab 40 mg SC q2 weeks; etanercept 50 mg SC weekly; infliximab 5 mg/kg IV q8 weeks; golimumab; certolizumab pegol (preferred in pregnancy — minimal placental transfer)

— Effective for axial disease, peripheral arthritis, enthesitis, dactylitis, uveitis (monoclonal antibodies > etanercept for uveitis and IBD), psoriasis, IBD

— Etanercept is less effective for uveitis and IBD — don't use it when those are dominant

— Avoid systemic steroids in AS — generally ineffective for axial disease and worsen osteoporosis

— Useful as intra-articular injections for mono/oligoarthritis or enthesitis

— Short systemic courses for severe PsA flares (caution: tapering can precipitate pustular psoriasis flare)

NSAIDs (cornerstone for axial disease):

Conventional synthetic DMARDs (for peripheral disease only):

TNF inhibitors (first-line biologic for axial SpA and PsA):

IL-17 inhibitors: secukinumab, ixekizumab — excellent for AS, PsA, psoriasis; avoid in IBD

IL-12/23 (ustekinumab) and IL-23 (guselkumab, risankizumab): strong for PsA skin and joint; less robust for axial disease

JAK inhibitors (tofacitinib, upadacitinib): oral option; black-box warnings for MACE, malignancy, thrombosis — reserve after TNFi failure, especially in patients <50 without CV risk

Glucocorticoids:

Board pearl: Certolizumab pegol is the TNFi of choice during pregnancy because its Fc-free structure minimizes placental transfer.

Step 3 management: Before any biologic — TB screen (IGRA preferred), HBV (HBsAg, anti-HBc, anti-HBs), HCV Ab, HIV, update vaccines (especially inactivated influenza, pneumococcal PCV20, recombinant zoster, hepatitis B); no live vaccines on biologics.

Adjunctive Treatments and Non-Pharmacologic Management

— Cornerstone of AS management — daily stretching, postural exercises, deep breathing

— Supervised group exercise > home exercise alone

— Swimming and aquatic therapy preserve flexibility while minimizing axial load

— Posture training: maintain extension; avoid prolonged flexion

— Smoking cessation — smoking accelerates radiographic progression in axial SpA

— Corticosteroid injection for mono/oligoarthritis (knee, ankle)

— Sacroiliac joint steroid injection (CT or fluoroscopy-guided) for refractory SI pain

— Entheseal injections cautiously (Achilles — avoid direct tendon injection, rupture risk)

— Total hip arthroplasty for severe hip involvement (AS commonly affects hips)

— Spinal osteotomy for severe, fixed kyphosis impairing forward gaze

— Cervical fusion stabilization after fracture (advanced AS spine fractures with minimal trauma — high-risk)

— Acute anterior uveitis → ophthalmology same-day → topical glucocorticoids + cycloplegic (cyclopentolate, homatropine)

— Recurrent/refractory: TNFi (adalimumab, infliximab) systemically

— Etanercept and IL-17 inhibitors less effective for uveitis

— Dermatology co-management for severe skin disease

— Topical steroids, calcipotriene, phototherapy for limited disease

— Systemic therapy choice should cover both skin and joints when possible

— Gastroenterology co-management

— Choose joint therapy that doesn't flare IBD: infliximab or adalimumab preferred; avoid IL-17 inhibitors and avoid chronic systemic NSAIDs

— Chronic inflammation = elevated MI/stroke risk

— Statin if indicated by ASCVD risk; aggressive BP and lipid management

— Smoking cessation counseling at every visit

— DEXA at diagnosis and every 2 years

— Calcium 1000–1200 mg/day, vitamin D 800–2000 IU/day

— Bisphosphonate if osteoporosis or vertebral fracture

Physical therapy and exercise:

Intra-articular and local therapy:

Surgical considerations:

Uveitis management:

Psoriasis management coordination:

IBD management coordination:

Cardiovascular risk reduction:

Bone health:

CCS pearl: Order PT consult, ophthalmology referral (if any eye symptoms), DEXA scan, vaccination update, and smoking cessation counseling at the diagnostic visit — these get full credit on CCS and reflect real comprehensive care.

Board pearl: Advanced AS spine fractures occur with trivial trauma through fused brittle vertebrae; any new neck/back pain after a fall warrants CT spine, not just X-ray.

Special Populations — Elderly and Renal/Hepatic Impairment

— Late-onset SpA exists but is uncommon; new "inflammatory back pain" in a patient >50 should also raise concern for PMR, crystal disease, infection, malignancy (metastatic), or vertebral fracture

— Established AS in elderly: focus shifts to managing complications (osteoporotic fractures, cardiovascular disease, restrictive lung disease)

— Polypharmacy concerns — review NSAID risk profile carefully

— Increased GI bleeding risk → add PPI, prefer COX-2 selective (celecoxib)

— Increased renal toxicity — monitor creatinine, avoid in CKD stage 4–5

— Increased BP elevation and heart failure exacerbation

— Avoid indomethacin in elderly (Beers criteria — CNS side effects)

— eGFR <30: avoid NSAIDs entirely; use acetaminophen, intra-articular steroids, biologics

— eGFR 30–60: short-course NSAIDs only, monitor closely

— Methotrexate contraindicated if eGFR <30 (accumulates, increases pancytopenia and pulmonary toxicity); reduce dose if eGFR 30–60

— Sulfasalazine: reduce dose, monitor for crystalluria; adequate hydration

— Biologics generally safe in renal impairment — no dose adjustment for TNFi, IL-17i

— JAK inhibitors: dose-adjust in moderate-severe CKD

— Methotrexate contraindicated in active hepatitis, cirrhosis, heavy alcohol use; check baseline and serial LFTs

— Leflunomide hepatotoxic — avoid in liver disease

— Sulfasalazine — caution, monitor LFTs

— Screen HBV before any biologic or MTX; HBV reactivation risk with TNFi → coordinate antiviral prophylaxis (entecavir/tenofovir) if HBsAg positive or anti-HBc positive with detectable DNA

— TNF inhibitors contraindicated in NYHA III–IV heart failure (worsened outcomes in trials)

— Choose IL-17 inhibitor or other alternative

Elderly patients with SpA:

NSAID adjustments in elderly:

Renal impairment:

Hepatic impairment:

Pre-existing heart failure:

Board pearl: A patient on infliximab who develops cough, dyspnea, and fever — think reactivated TB, opportunistic fungal infection (histoplasmosis, coccidioidomycosis), or heart failure exacerbation, not just community-acquired pneumonia.

Step 3 management: In CKD stage 4 with active AS, the answer is usually TNF inhibitor, not "increase NSAID dose."

Special Populations — Pregnancy, Pediatrics, and Other Subgroups

— Disease activity is variable — AS often persists or worsens (unlike RA, which typically improves); PsA tends to improve

— Plan pregnancy during low disease activity

— Pre-conception counseling: review and adjust medications

— Safe/preferred: sulfasalazine (add folic acid 5 mg), hydroxychloroquine, low-dose prednisone (<20 mg), certolizumab pegol (minimal placental transfer — preferred TNFi throughout pregnancy)

— Other TNFi (adalimumab, infliximab, etanercept, golimumab): generally continued through second trimester; consider stopping in third trimester (placental transfer); avoid live vaccines in infants <6 months exposed in utero

— NSAIDs: avoid after 20 weeks (renal/oligohydramnios); contraindicated after 30 weeks (premature ductus closure)

— Contraindicated: methotrexate (teratogen — neural tube, craniofacial defects; stop 3 months before conception in both partners), leflunomide (long half-life — cholestyramine washout required), JAK inhibitors

— Severe AS with cervical/lumbar ankylosis → difficult intubation and challenging neuraxial anesthesia — alert anesthesia early

— Hip involvement may limit lithotomy positioning

— Often presents as enthesitis-related arthritis (ERA) subtype of JIA

— Boys >8 years, lower-extremity oligoarthritis, enthesitis, family history, HLA-B27

— Higher risk of progressing to AS in adulthood

— Acute symptomatic uveitis (vs. asymptomatic uveitis in oligoarticular JIA)

— Mandatory while on methotrexate, leflunomide, JAK inhibitors

— Avoid estrogen-containing contraceptives if active inflammation increases thrombotic risk (especially with JAK inhibitors)

Pregnancy in SpA:

Medication safety in pregnancy:

Lactation: TNFi compatible with breastfeeding; sulfasalazine generally safe; methotrexate contraindicated

Delivery considerations:

Pediatric SpA (juvenile-onset):

Contraception counseling:

Board pearl: Certolizumab pegol is uniquely safe across all three trimesters because its pegylated, Fc-free structure does not undergo active placental transfer — the go-to answer for severe SpA in pregnancy.

Key distinction: AS typically persists or worsens in pregnancy; RA typically improves. Don't assume rheumatic disease automatically improves with pregnancy.

Step 3 management: A patient on methotrexate planning pregnancy → stop MTX 3 months before conception, continue folic acid, transition to a pregnancy-compatible agent (sulfasalazine, certolizumab) if needed.

Complications and Adverse Outcomes

— Vertebral fractures — paradoxically high in ankylosed spine; trivial trauma can cause unstable transverse fractures through fused segments; high spinal cord injury risk

— Osteoporosis despite radiographic ankylosis (disuse + inflammation)

— Atlantoaxial subluxation (less common than RA)

— Cauda equina syndrome (rare, late AS)

— Aortic regurgitation from aortic root dilation (aortitis) — up to 10% in long-standing AS

— Conduction abnormalities — AV block, bradyarrhythmias (fibrosis of conduction system)

— Accelerated atherosclerosis → increased MI/stroke risk (chronic inflammation)

— Pericarditis (uncommon)

— Restrictive lung disease from thoracic ankylosis and reduced chest expansion

— Apical pulmonary fibrosis (rare, late) — mimics TB radiographically; cavitation may be secondarily infected with Aspergillus

— Sleep apnea

— Acute anterior uveitis — up to 40% of AS; risk of synechiae, glaucoma, vision loss if untreated

— Cataracts from chronic steroid eye drop use

— Subclinical gut inflammation common in all SpA; clinically apparent IBD in ~5–10% of AS

— NSAID-induced gastritis/PUD

— IgA nephropathy associated with AS

— Secondary AA amyloidosis in long-standing inflammation — proteinuria, nephrotic syndrome (now rare with effective therapy)

— NSAID-induced AKI, analgesic nephropathy

— Arthritis mutilans — destructive resorption of phalanges ("telescoping digits, opera-glass hand")

— Severe nail dystrophy

— Higher CV risk from psoriasis itself

— Chronic disease in 15–20% — persistent arthritis, enthesopathy

— Cardiac conduction abnormalities (rare)

— TNFi: serious infections, TB reactivation, demyelination, lupus-like syndrome, infusion reactions, lymphoma risk (small)

— JAK inhibitors: MACE, VTE, malignancy, herpes zoster reactivation

— NSAIDs: GI bleeding, AKI, CV events, hypertension

Skeletal complications:

Cardiovascular complications:

Pulmonary complications:

Ophthalmologic:

Gastrointestinal:

Renal:

Psoriatic-specific:

Reactive arthritis:

Treatment-related:

Board pearl: A patient with long-standing AS who develops new neck pain after a minor fall — CT cervical spine immediately. Plain films miss fractures through ankylosed segments, and missed unstable fractures lead to devastating spinal cord injury.

Step 3 management: Annual cardiovascular risk assessment, lipid panel, BP, and DEXA every 2 years in established AS.

When to Escalate Care — Consults and Inpatient Triage

— New back/neck pain after trauma in AS (even trivial) → ED, CT spine, neurosurgery/orthopedic spine consult; treat as unstable until proven otherwise

— Acute red painful eye + photophobia → same-day ophthalmology for uveitis evaluation

— Cauda equina syndrome (saddle anesthesia, bowel/bladder dysfunction, bilateral leg weakness) → emergent MRI, neurosurgery

— Acute monoarthritis with fever → arthrocentesis to rule out septic arthritis before assuming flare; immunosuppressed SpA patients are at higher risk

— Suspected septic joint

— Severe spine fracture

— New AV block or symptomatic bradyarrhythmia

— Severe IBD flare with arthritis

— Serious infection while on biologic (sepsis, opportunistic infection, reactivated TB)

— Rheumatology: all confirmed/suspected SpA for diagnosis confirmation, biologic decisions, treat-to-target

— Ophthalmology: any uveitis symptom, baseline if on hydroxychloroquine (rare in SpA)

— Dermatology: moderate-severe psoriasis, coordinate biologic choice

— Gastroenterology: suspected or confirmed IBD; chronic diarrhea, hematochezia, weight loss, iron deficiency

— Cardiology: murmur of AR, conduction abnormalities, accelerated atherosclerosis management

— Orthopedic surgery: severe hip disease (THA), spinal deformity, fracture

— Physical therapy: all axial SpA at diagnosis

— Infectious disease: TB screening positivity before biologic initiation; opportunistic infections on therapy

— Inflammatory back pain in <45 y/o, especially with elevated CRP/B27 positive

— Failure of 2 NSAIDs over 4 weeks total

— Any extra-articular manifestation

— Suspected PsA: any psoriasis patient with new joint symptoms

Emergent/urgent escalation:

Inpatient triage:

Specialty consultation framework:

Outpatient escalation triggers (refer to rheumatology):

CCS pearl: On the CCS case of a young man with chronic back pain and a positive B27 — order pelvic X-ray, CRP, MRI SI joints if X-ray negative, ophthalmology referral for uveitis history, PT consult, and rheumatology referral. Start scheduled NSAID immediately; do not wait for the rheumatologist visit to begin treatment.

Board pearl: Don't anchor on "AS flare" in a patient on TNFi with new monoarthritis and fever — tap the joint. Septic arthritis on immunosuppression presents atypically.

Key Differentials — Same-Category (Other Inflammatory Arthritides)

— Symmetric, polyarticular, small joints (MCP, PIP, wrists), spares DIP

— RF and/or anti-CCP positive

— Cervical spine involvement (C1–C2 subluxation) but no sacroiliitis

— Morning stiffness >1 hour

— Erosive on hand X-rays at MCP/PIP

— Age >50, shoulder and hip-girdle pain and stiffness

— Markedly elevated ESR (often >50)

— Dramatic response to low-dose prednisone (15 mg)

— No true synovitis; no sacroiliitis

— Gout: sudden monoarthritis (1st MTP — podagra), tophi, hyperuricemia; MSU crystals (needle-shaped, negatively birefringent)

— CPPD: knees, wrists; chondrocalcinosis on X-ray; rhomboid, positively birefringent crystals

— Acute monoarthritis with fever; synovial WBC >50,000, positive Gram stain/culture

— Must rule out before steroid injection or assuming SpA flare

— Disseminated gonococcal infection: young, sexually active patient with tenosynovitis + dermatitis + migratory polyarthralgia — important mimic of reactive arthritis

— Symmetric, non-erosive, Jaccoud arthropathy (reducible deformities)

— ANA, anti-dsDNA, low complement

— Recurrent oral and genital ulcers, uveitis (panuveitis, not just anterior), pathergy, vascular disease

— Joint involvement non-erosive

— Löfgren syndrome: bilateral hilar lymphadenopathy + erythema nodosum + ankle arthritis; good prognosis

— ERA subtype overlaps with adult-onset axial SpA

Rheumatoid arthritis (RA):

Polymyalgia rheumatica (PMR):

Crystal arthropathies:

Septic arthritis:

SLE arthritis:

Behçet disease:

Sarcoid arthritis:

Juvenile idiopathic arthritis (in young adults previously diagnosed):

Key distinction: DIP involvement + nail pitting + dactylitis = PsA, not RA. Symmetric MCP/PIP + RF/anti-CCP = RA. Mixing these up is the most common board trap.

Board pearl: Gonococcal arthritis can mimic reactive arthritis (young, sexually active, oligoarthritis, skin findings) but features tenosynovitis (back of hand/wrist) and pustular skin lesions rather than keratoderma blennorrhagicum, and synovial fluid culture/NAAT confirms it. Treat with ceftriaxone.

Step 3 management: When monoarthritis is the presentation, arthrocentesis first — synovial WBC, crystals, Gram stain, culture — before committing to a diagnosis of SpA flare.

Key Differentials — Other-Category Causes of Back/Joint Pain

— Worse with activity, better with rest

— No morning stiffness or stiffness <30 min

— No systemic symptoms; CRP/ESR normal

— Imaging negative for sacroiliitis

— Radicular pain (dermatomal), positive straight leg raise

— Sensory/motor deficits

— MRI shows disc pathology, not SI joint inflammation

— Older patients, neurogenic claudication (pain with walking, relieved by sitting/bending forward)

— Imaging shows canal narrowing

— Acute back pain, point tenderness, height loss

— Risk factors: osteoporosis, glucocorticoids

— X-ray/MRI confirms

— Older patients (often diabetic, obese)

— Flowing osteophytes ("dripping candle wax") along anterolateral spine — at least 4 contiguous vertebrae

— SI joints and disc spaces preserved (key distinction from AS)

— Stiffness without significant inflammation; CRP normal

— Vertebral osteomyelitis/discitis: fever, focal tenderness, elevated ESR/CRP, often S. aureus or TB (Pott disease); MRI confirms

— Brucellosis — sacroiliitis in occupational/dietary exposure

— Metastatic disease (breast, prostate, lung, kidney, thyroid, multiple myeloma)

— Night pain, weight loss, age >50, no relief with rest, neurologic deficits

— Bone scan, MRI, SPEP/UPEP

— Widespread pain, fatigue, sleep disturbance, cognitive complaints

— Normal inflammatory markers, no synovitis, no imaging findings

— Can coexist with SpA and complicate disease activity assessment

— Groin pain with weight-bearing, limited internal rotation

— Imaging: joint-space loss, osteophytes, subchondral sclerosis

Mechanical low back pain:

Lumbar disc herniation/radiculopathy:

Spinal stenosis:

Vertebral compression fracture:

Diffuse idiopathic skeletal hyperostosis (DISH):

Infectious causes:

Malignancy:

Fibromyalgia:

Hip osteoarthritis:

Key distinction: DISH vs. AS — both have spinal "fusion" appearance but DISH preserves SI joints and disc spaces, has flowing anterior osteophytes (not thin marginal syndesmophytes), occurs in older obese/diabetic patients, lacks inflammation (normal CRP), and does not respond to NSAIDs the way AS does.

Board pearl: "Inflammatory back pain" features (age <40, insidious, >3 months, morning stiffness, improvement with exercise, nocturnal awakening) reliably separate SpA from the vastly more common mechanical/degenerative causes — memorize these.

Step 3 management: Red flags (age >50, weight loss, fever, night pain, neurologic deficits, history of malignancy) → expand workup with MRI, labs (CBC, ESR/CRP, SPEP/UPEP), and consider biopsy before settling on SpA.

Secondary Prevention, Discharge Planning, and Long-Term Strategy

— Maintain treat-to-target: ASDAS <2.1 or BASDAI <4 with normal CRP

— Continue biologic indefinitely if effective; dose tapering may be considered after sustained remission ≥6 months (specialist decision)

— Continuous NSAID may slow structural progression in axial SpA but balance against CV/GI/renal risks

— Inactivated influenza annually

— Pneumococcal: PCV20 (or PCV15 + PPSV23) per ACIP

— Recombinant zoster (Shingrix) — 2 doses, all immunosuppressed adults ≥19

— Hepatitis B series if not immune

— HPV through age 45 if not vaccinated

— COVID-19 per current ACIP

— No live vaccines while on biologics (MMR, varicella, yellow fever, live zoster, oral typhoid, intranasal flu)

— Time live vaccines ≥4 weeks before starting biologic or per agent-specific washout after stopping

— Annual lipid panel, BP, glucose, ASCVD risk calculation

— Statin per ASCVD guidelines (consider lower threshold given inflammation)

— Aggressive smoking cessation (smoking worsens both AS progression and CV risk)

— Aspirin only if standard primary/secondary prevention indications

— Calcium 1000–1200 mg/day, vitamin D 800–2000 IU/day

— DEXA at diagnosis, every 2 years

— Bisphosphonate or denosumab if osteoporosis or fragility fracture

— Counsel on fall prevention given fracture risk in fused spine

— Age-appropriate USPSTF screening (colorectal, breast, cervical, lung)

— Annual skin exam in psoriasis patients (esp. with phototherapy or biologic history) — increased non-melanoma skin cancer risk

— Lymphoma risk slightly increased with TNFi — clinical surveillance, no specific screening

— Depression and anxiety common in chronic inflammatory disease — screen with PHQ-9

— Sleep apnea screening if symptoms

— Cardiovascular and metabolic syndrome screening (esp. PsA)

— Posture, daily exercise, smoking cessation

— Sick-day rules: hold biologic during serious infection; resume after resolution

— Recognize uveitis symptoms → seek same-day care

Disease-modifying long-term plan:

Vaccination program (essential before and during biologics):

Cardiovascular risk reduction:

Bone health:

Cancer screening:

Comorbidity management:

Patient education:

Step 3 management: At every visit, complete a "biologic safety bundle": review for infections, surgical procedures coming up (hold biologic perioperatively per guideline — typically one dosing cycle), vaccinations, and screen for new neurologic, cardiac, or skin findings.

Board pearl: Shingrix is recombinant (non-live) and indicated even in patients on biologics; ensure both doses are given.

Follow-Up, Monitoring Parameters, and Rehabilitation

— Active disease starting therapy: every 1–3 months until stable

— Stable on biologic: every 3–6 months

— Long-standing stable disease: every 6–12 months with rheumatology, with PCP visits interspersed

— ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score) — preferred composite

— BASDAI (patient-reported, 0–10)

— BASFI (functional index)

— Physical exam: Schober, chest expansion, occiput-to-wall, tragus-to-wall, lateral spinal flexion

— Tender/swollen joint counts, enthesitis index

— PASI for psoriasis severity

— CBC, CMP, ESR/CRP every 3 months on biologic

— Methotrexate: CBC, LFTs, creatinine every 4–8 weeks initially, then every 3 months

— Sulfasalazine: CBC, LFTs every 3 months

— JAK inhibitors: CBC, LFTs, lipids (cause hyperlipidemia), creatinine

— Annual TB screen (IGRA) on biologic therapy

— Repeat spine/pelvis X-ray every 2 years in axial SpA to track structural progression

— MRI as needed for new symptoms or assessment of inflammation

— Daily exercise program — central to AS management

— Supervised PT initially, then home program with periodic check-ins

— Aquatic therapy, yoga (carefully), Pilates

— Occupational therapy for hand involvement (PsA)

— Smoking cessation at every visit

— Posture awareness (sit/stand tall; avoid prolonged flexion)

— Ergonomic workplace setup

— Driving: limited neck rotation in advanced AS — use mirrors, consider modifications

— Sleep position: firm mattress, thin pillow to preserve cervical alignment

— Sexual health and family planning

— PCP: cardiovascular risk, bone health, vaccines, cancer screening, mental health

— Rheumatology: disease activity, medication management

— Subspecialists: ophthalmology, dermatology, GI as needed

Follow-up cadence:

Disease activity monitoring:

Laboratory monitoring:

Imaging follow-up:

Rehabilitation:

Counseling topics:

Coordination of care:

CCS pearl: Order annual influenza, ASDAS at each visit, repeat DEXA at 2 years, repeat X-ray at 2 years, and PHQ-9 screen — comprehensive longitudinal care wins points and reflects real practice.

Board pearl: A patient on biologic for 2 years with normal CRP and ASDAS <1.3 has inactive disease; do not stop the biologic unilaterally — dose reduction is a specialist decision, and full discontinuation often leads to flare.

Ethical, Legal, and Patient Safety Considerations

— Discuss serious infection risk (TB reactivation, opportunistic infections, sepsis), malignancy concerns (lymphoma, skin cancer), demyelinating disease, infusion reactions

— JAK inhibitors: specific black-box discussion of MACE, VTE, malignancy, mortality (especially in patients ≥50 with CV risk factors) — document

— Cost and insurance coverage are part of shared decision-making; biologics are expensive and require prior authorization

— Document discussion of live vaccine contraindication while on biologic

— Ensure patient understands need for inactivated influenza, pneumococcal, zoster (recombinant), hepatitis B

— Document contraception counseling before starting methotrexate, leflunomide, JAK inhibitors

— Methotrexate: discuss teratogenicity with both partners; document 3-month washout before conception

— Unintended pregnancy on MTX → urgent rheumatology and MFM consultation

— Hold biologic perioperatively typically for one dosing interval before major surgery; resume 14 days post-op if wound healing and no infection (per ACR/AAHKS guideline)

— Continue MTX through surgery

— Communicate explicitly with surgical team — transition errors (failing to coordinate biologic timing) are a common patient safety issue

— Stress-dose steroids if on chronic prednisone

— Advanced AS with limited neck rotation → counsel on driving safety; some states require physician reporting of medical conditions impairing driving (jurisdiction-dependent)

— Reactive arthritis from Chlamydia, Salmonella, Shigella, Campylobacter, gonorrhea — these underlying infections are reportable to public health departments; ensure reporting and partner notification for STIs

— TB diagnosed during biologic screening is reportable

— Diagnostic delay disproportionately affects women (AS historically underdiagnosed in women), patients of color, and those with limited access

— Biologic affordability — coordinate with social work and patient assistance programs

— Always document TB and hepatitis screening before initiating biologic — failure is a recurrent malpractice and quality issue

— Document discussion of all major risks and alternatives

Informed consent for biologics:

Vaccination consent and timing:

Pregnancy and contraception:

Perioperative management (transition-of-care safety):

Driving safety:

Mandatory reporting and public health:

Health system equity:

Documentation safety:

Step 3 management: Before scheduled joint replacement in a SpA patient on adalimumab q2 weeks, hold the dose so that surgery falls at the end of the dosing interval; resume ~14 days post-op once wound is healing and no infection. Communicate this plan to the surgeon in writing.

Board pearl: A young woman with reactive arthritis after culture-confirmed Chlamydia — report to public health, treat the patient with azithromycin/doxycycline, and treat the sexual partner(s) (expedited partner therapy where legal).

High-Yield Associations and Rapid-Fire Clinical Facts

HLA-B27 prevalence by phenotype: AS ~90%, ReA 50–70%, IBD-axial ~50%, PsA ~25%, general US population ~8%

Reactive arthritis triggers (memorize): Chlamydia trachomatis (GU); Salmonella, Shigella, Yersinia, Campylobacter, C. difficile (GI). Mnemonic: "She Sells YCC"

Reactive arthritis triad: conjunctivitis, urethritis, arthritis ("can't see, can't pee, can't climb a tree")

Keratoderma blennorrhagicum = hyperkeratotic palms/soles in ReA (looks like pustular psoriasis)

Circinate balanitis = serpiginous penile lesions in ReA

AS uveitis: unilateral, acute, anterior, recurrent, often alternating sides, may have hypopyon

PsA five patterns: asymmetric oligoarticular (most common), DIP-predominant, symmetric polyarticular (RA-like), spondylitis, arthritis mutilans

PsA nail signs: pitting (>20 pits), onycholysis, oil-drop sign, subungual hyperkeratosis

Pencil-in-cup deformity: classic PsA hand X-ray finding (DIP)

Dactylitis: "sausage digit" — uniform swelling of entire digit; SpA hallmark

Bamboo spine: late AS, vertebral fusion via syndesmophytes

Shiny corner sign (Romanus lesion): early AS vertebral inflammation

Anderson lesion: discovertebral inflammation in AS

Modified Schober: <5 cm increase = abnormal

Chest expansion: <2.5 cm at 4th ICS = abnormal

Tragus-to-wall and occiput-to-wall: tracks cervical/thoracic kyphosis

DISH vs AS: DISH spares SI joints/discs, flowing anterior osteophytes, older diabetic/obese patients, normal CRP

IL-17 inhibitors: avoid in IBD

Etanercept: less effective for uveitis and IBD vs. monoclonal TNFi

Certolizumab: preferred TNFi in pregnancy (no Fc, minimal placental transfer)

DMARDs (MTX, SSZ): ineffective for axial disease; work for peripheral

Cardiovascular AS: aortic regurgitation, AV block

Pulmonary AS: apical fibrosis (mimics TB), restrictive disease

Renal AS: IgA nephropathy, AA amyloidosis

Spine fracture in AS: trivial trauma, high cord injury risk, CT (not just X-ray)

Smoking: worsens axial SpA progression

Biologic pre-screen: TB (IGRA), HBV, HCV, HIV, vaccines

Live vaccines: contraindicated on biologic

TNFi contraindicated in: demyelinating disease, NYHA III–IV heart failure, active serious infection, active TB/HBV without treatment

Board pearl: "Young man, low back pain, morning stiffness, uveitis, AR murmur" = AS until proven otherwise. Get pelvic X-ray, HLA-B27, echo.

Key distinction: RA loves symmetric small joints + DIP-sparing + seropositive; SpA loves SI joints, DIP, entheses, seronegative.

Board Question Stem Patterns

Stem 1 (classic AS): 24-year-old man, 6 months of low back pain, worse in mornings, lasts 90 minutes, improves with exercise, awakens him at 4 AM. Exam: reduced lumbar flexion, chest expansion 2 cm. → Next step: AP pelvic X-ray (look for sacroiliitis). If normal but high suspicion → MRI SI joints.

Stem 2 (AS + uveitis): Young man with chronic back pain presents with unilateral red painful eye, photophobia. → Diagnosis: acute anterior uveitis associated with axial SpA. Management: same-day ophthalmology, topical steroid + cycloplegic; check HLA-B27, pelvic X-ray.

Stem 3 (PsA): Patient with psoriasis develops swelling of entire 3rd toe and DIP pain in hand, nail pitting present. → Diagnosis: PsA (dactylitis + DIP). RF and anti-CCP negative. Management: NSAIDs + MTX for peripheral; consider TNFi if inadequate response.

Stem 4 (Reactive arthritis): 25-year-old man, 2 weeks after diarrheal illness in Mexico, asymmetric knee and ankle pain, painless oral ulcers, conjunctivitis. → Diagnosis: reactive arthritis post-Shigella or Campylobacter. NSAIDs; treat triggering infection if active; partner notification if Chlamydia.

Stem 5 (Chlamydia ReA): Sexually active young man with urethritis, oligoarthritis, conjunctivitis. → Treatment: doxycycline or azithromycin for Chlamydia; treat partners; report to public health; NSAIDs for arthritis.

Stem 6 (IBD-associated): Crohn disease patient develops chronic inflammatory low back pain. Best therapy: anti-TNF monoclonal (infliximab or adalimumab) — covers both bowel and joints. Avoid IL-17 inhibitors (may worsen IBD).

Stem 7 (DISH mimic): 70-year-old obese diabetic man with stiff back, X-ray shows flowing anterior osteophytes over 4+ vertebrae, SI joints normal. Diagnosis: DISH, not AS.

Stem 8 (AS fracture): 55-year-old with long-standing AS, minor fall, new neck pain. Next step: CT cervical spine (not X-ray) — high concern for unstable fracture through fused spine.

Stem 9 (Pregnancy): AS patient on adalimumab planning pregnancy. Best choice: switch to or continue certolizumab pegol for minimal placental transfer; methotrexate must be stopped ≥3 months pre-conception.

Stem 10 (Pre-biologic): Before starting infliximab — mandatory tests: TB (IGRA), HBV (HBsAg, anti-HBc, anti-HBs), HCV, HIV, update inactivated vaccines.

Stem 11 (Septic joint on TNFi): SpA patient on adalimumab develops monoarthritis with fever. Next step: arthrocentesis with cell count, Gram stain, culture — don't assume flare.

Stem 12 (Cardiac AS): Long-standing AS patient with new dyspnea, early diastolic murmur. Diagnosis: aortic regurgitation from aortitis. Workup: echo, ECG (look for AV block).

Board pearl: Stems featuring inflammatory back pain + improvement with NSAIDs + young age virtually always lead to pelvic X-ray as the first imaging step. If "X-ray is normal," the next answer is MRI SI joints.

Step 3 management: When the stem describes a positive TB IGRA before biologic, the answer is complete latent TB treatment (isoniazid 9 months or rifampin 4 months) — may start biologic after 1–2 months of LTBI therapy in consultation with ID.

One-Line Recap

Spondyloarthritis is a family of HLA-B27–linked, seronegative, inflammatory arthritides (AS, PsA, ReA, IBD-associated) defined by inflammatory back pain, sacroiliitis, enthesitis, dactylitis, and extra-articular features (uveitis, psoriasis, IBD), treated with continuous NSAIDs first-line and TNF/IL-17 inhibitors when NSAIDs fail — with biologic choice tailored to extra-articular disease (avoid IL-17i in IBD; use anti-TNF mAb for uveitis/IBD; certolizumab in pregnancy).

Diagnosis high-yield: Young patient (<45) + insidious back pain ≥3 months + morning stiffness + improvement with exercise + night pain → check HLA-B27, ESR/CRP, RF/anti-CCP (negative), AP pelvic X-ray; if X-ray negative but suspicion remains, MRI SI joints with STIR to detect bone marrow edema and diagnose non-radiographic axial SpA before structural damage.

Treatment high-yield: Scheduled (not PRN) NSAIDs for ≥4 weeks first; if inadequate → TNFi or IL-17i for axial disease; conventional DMARDs (MTX, SSZ) do not work on axial disease but help peripheral arthritis (especially PsA). Always complete TB, HBV, HCV, HIV screening and inactivated vaccines before biologic; no live vaccines on biologics; certolizumab pegol is the pregnancy-safe TNFi.

Differential high-yield: Distinguish SpA from RA (SpA spares serology, hits DIP and SI joints), from DISH (DISH preserves SI joints/discs, flowing osteophytes, older diabetics), from mechanical back pain (no inflammatory features), and from septic arthritis in any patient with monoarthritis + fever (always tap the joint, especially on biologics).

Long-term high-yield: Treat-to-target with ASDAS, aggressive cardiovascular and bone health management (osteoporosis paradoxically common despite ankylosis), annual flu/pneumococcal/Shingrix vaccination, low threshold for CT spine in any AS patient with new pain after trauma (unstable fracture risk), and same-day ophthalmology for any red painful eye to manage acute anterior uveitis before vision loss.