Sterile inflammatory arthritis triggered by a preceding gastrointestinal or genitourinary infection.
Also known as: reactive arthritis, ReA, Reiter syndrome (historical), post-infectious arthritis
Overview
A sterile inflammatory arthritis arising 1-4 weeks after an antecedent gastrointestinal or genitourinary infection. Part of the seronegative spondyloarthritis family, sharing HLA-B27 association, asymmetric oligoarthritis, enthesitis, and possible extra-articular features.
Epidemiology
Annual incidence approximately 30-40 per 100,000. Peak ages 20-40. Male predominance for genitourinary-triggered disease; gastrointestinal triggers affect both sexes equally. HLA-B27 positive in 30-50 percent and predicts more severe and chronic disease.
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Question 1MusculoskeletalMedium
A 30-year-old man presents with a 1-week history of pain and swelling in the right knee and left ankle, burning with urination, and bilateral red, gritty eyes. Three weeks earlier he completed treatment for a Chlamydia trachomatis urethritis. He denies fever, intravenous drug use, or new joint trauma. Examination shows an asymmetric lower-extremity oligoarthritis, sterile-appearing conjunctival injection, and a few painless erosions on the glans. Testing for HLA-B27 is positive. Which of the following is the most likely diagnosis?
AReactive arthritis
BGonococcal arthritis
CAnkylosing spondylitis
DSeptic arthritis
Reveal answer & full explanation
Correct answer: A — Reactive arthritis
AReactive arthritis✓
BGonococcal arthritis
CAnkylosing spondylitis
DSeptic arthritis
Why Reactive arthritis is correct
The triad of asymmetric oligoarthritis, urethritis, and conjunctivitis arising 1–4 weeks after a genitourinary infection is the classic presentation of reactive arthritis
Chlamydia trachomatis is the most common urogenital trigger; enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter) are the other classic triggers
HLA-B27 is positive in roughly 70–80% of cases and supports the diagnosis
Painless mucocutaneous findings (here, circinate balanitis) and a sterile, reactive joint process (rather than purulent fluid) are characteristic
Management targets the triggering infection plus NSAIDs for the arthritis
Why the others are wrong
Gonococcal arthritis — occurs in young sexually active adults but produces a purulent septic monoarthritis or a dermatitis-arthritis syndrome with pustular skin lesions, not a sterile post-infectious triad with conjunctivitis; buzzword-matching on 'sexually active male' sets this trap
Ankylosing spondylitis — also HLA-B27 associated, but causes chronic inflammatory low back pain and sacroiliitis, not an acute post-infectious peripheral triad; anchoring on HLA-B27 sets this trap
Septic arthritis — produces a single hot, swollen joint with fever and purulent fluid, not a sterile oligoarthritis with eye and urethral involvement; premature closure on 'swollen joint' sets this trap
Question 2MusculoskeletalEasy
A 25-year-old male has right knee pain, swelling, and warmth after a sexual contact 2 weeks ago. He also has urethritis and right eye redness. Synovial fluid shows 28,000 WBCs (70% polymorphonuclear leukocytes (PMNs)). Gram stain and culture are negative. Which of the following is the most likely diagnosis?
ALyme arthritis
BGonococcal arthritis
CReactive arthritis
DViral arthritis
Reveal answer & full explanation
Correct answer: C — Reactive arthritis
ALyme arthritis
BGonococcal arthritis
CReactive arthritis✓
DViral arthritis
Why Reactive arthritis is correct
Triggered by sexually transmitted infection (STI) — Chlamydia is the most common cause — or enteric infection (Salmonella, Shigella, Campylobacter, Yersinia)
Classic triad: arthritis (asymmetric, large joints, lower extremity), urethritis, conjunctivitis
Joint fluid is culture-negative and sterile, matching this patient's negative Gram stain and culture
Human leukocyte antigen B27 (HLA-B27) is positive in 75% of cases
Why the others are wrong
Lyme arthritis — caused by Borrelia burgdorferi tick bite, not STI; typically monoarticular large-joint (knee); no urethritis or conjunctivitis
Gonococcal arthritis — disseminated gonococcal infection produces migratory polyarthralgia, tenosynovitis, and pustular skin lesions without conjunctivitis, so the arthritis-urethritis-conjunctivitis triad here points elsewhere
Viral arthritis — parvovirus B19, hepatitis B, and acute HIV cause symmetric polyarthritis with lymphocyte-predominant, low-cell-count effusions, not a 28,000 PMN-predominant monoarthritis with conjunctivitis
Additional high-yield points
Treatment step 1: treat underlying infection — azithromycin 1 g single dose for Chlamydia
Treatment step 2: nonsteroidal anti-inflammatory drugs (NSAIDs) for arthritis
Treatment step 3: intra-articular corticosteroids for refractory joint
Treatment step 4: sulfasalazine or methotrexate for chronic reactive arthritis
Uveitis management: topical corticosteroids plus ophthalmology referral
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HIV infection (more severe and chronic reactive arthritis)
Pathophysiology
Molecular mimicry, persistent antigen, and aberrant immune response in genetically predisposed individuals. Bacterial antigens (particularly Chlamydia) may persist in joints despite negative cultures. HLA-B27 contributes through its role in antigen presentation and possible misfolding-related ER stress.
Clinical presentation
Symptoms
Asymmetric oligoarthritis of large lower extremity joints (knee, ankle) developing 1-4 weeks after triggering infection
Heel pain (Achilles enthesitis or plantar fasciitis)
Low back pain and stiffness (sacroiliitis)
Dactylitis (sausage digit)
Conjunctivitis or acute anterior uveitis
Urethritis or cervicitis (may be ongoing or recent)
Constitutional symptoms — fever, fatigue, weight loss in active disease
Signs / physical exam
Warm, swollen oligoarthritis predominantly of lower extremities
Sausage-shaped digits from dactylitis
Achilles or plantar fascia tenderness from enthesitis
Mucocutaneous: keratoderma blennorrhagicum (hyperkeratotic plaques on palms and soles), circinate balanitis, painless oral ulcers, nail changes
Conjunctival injection or anterior chamber inflammation
Sacroiliac tenderness with positive provocation tests
Classic findings
Young adult man with the classic triad of asymmetric oligoarthritis, conjunctivitis, and urethritis 2-4 weeks after a sexually acquired Chlamydia infection ('can't see, can't pee, can't climb a tree'); however, the full triad is present in only one-third of cases.
Crystal arthritis (gout, pseudogout) — Monoarticular, crystals on synovial fluid analysis, characteristic distribution
Psoriatic arthritis — Psoriasis (may precede arthritis), nail pitting and onycholysis, dactylitis, similar HLA-B27 association in axial disease
Inflammatory bowel disease-associated arthritis — Active or recent enteritis/colitis from IBD; oligoarticular peripheral arthritis or axial disease
Rheumatic fever — Migratory polyarthritis after streptococcal pharyngitis, carditis, chorea, erythema marginatum, elevated ASO/anti-DNase B
Diagnostic workup
Diagnostic criteria
Clinical diagnosis based on characteristic arthritis temporally associated with documented or strongly suspected GU or GI infection. ASAS criteria for spondyloarthritis can be applied; HLA-B27 supports but is not required.
Labs
CBC, ESR, CRP — elevated inflammatory markers
Stool culture and Chlamydia/Gonorrhea NAAT (urine, urethral, cervical, or rectal as appropriate) — even if asymptomatic
HLA-B27 — supports diagnosis and predicts chronicity
ANA, RF, anti-CCP — to exclude alternative diagnoses
HIV testing
Synovial fluid analysis (inflammatory but sterile, WBC 2,000-50,000, no crystals) to exclude infection and crystal disease
Imaging
Plain radiographs of affected joints — typically normal early; later may show enthesophytes, periostitis, asymmetric sacroiliitis
MRI or ultrasound to identify enthesitis and early sacroiliitis
Echocardiography for new murmur (rare aortic regurgitation)
Salmonella, Shigella, Yersinia, Campylobacter, C. difficile
1-4 weeks post-enteritis
Respiratory (less common)
Chlamydia pneumoniae
Variable
Common infectious triggers for reactive arthritis.
Treatment
First-line
NSAIDs at full anti-inflammatory doses (naproxen, indomethacin, diclofenac) — first-line therapy
Intra-articular corticosteroid injection for persistent monoarthritis or oligoarthritis after exclusion of infection
Antibiotics for active triggering infection: doxycycline or azithromycin for Chlamydia (treat partners); enteric infections are typically self-limited and antibiotics do not alter arthritis course
Physical therapy and joint protection
Second-line / adjunct
Sulfasalazine, methotrexate, or other conventional DMARDs for chronic disease (>3-6 months)
TNF inhibitors (etanercept, adalimumab, infliximab) for severe, refractory, or chronic disease, particularly with axial involvement
Topical glucocorticoids and cycloplegics for anterior uveitis (urgent ophthalmology referral)
Long-term doxycycline has been studied for chronic Chlamydia-induced disease but is not standard
Complications
Chronic arthritis or recurrence in 15-30 percent
Erosive joint disease in chronic HLA-B27 positive cases
Anterior uveitis with risk of visual loss if untreated
Sacroiliitis evolving into ankylosing spondylitis in some patients
Amyloidosis in chronic uncontrolled disease (rare)
PANCE pearls
Reactive arthritis follows infection — synovial fluid is inflammatory but sterile.
Chlamydia is the most common genitourinary trigger; partner treatment and STI testing are essential.
Acute anterior uveitis associated with reactive arthritis is a vision-threatening emergency — refer urgently to ophthalmology.
The term Reiter syndrome has been largely abandoned because of the eponym's Nazi history; reactive arthritis is preferred.
HLA-B27 is supportive but not required for diagnosis — its presence predicts more severe and chronic disease.
References
ACR — American College of Rheumatology clinical resources on reactive arthritis and spondyloarthritis
ASAS — Assessment of SpondyloArthritis International Society classification criteria for axial and peripheral spondyloarthritis (Rudwaleit et al., Ann Rheum Dis 2011)
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