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Key points
- Reactive arthritis: inflammatory arthritis post-GI or GU infection; classic triad (conjunctivitis, urethritis, arthritis) in only ~1/3 of cases.
- Aetiology: part of seronegative spondyloarthropathies; 30–50% HLA-B27 positive; triggered by Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia.
- Risk factors: HLA-B27, prior GI/GU infection, male sex (esp. in Chlamydia-induced ReA, M:F ratio 9:1).
- Clinical features: asymmetrical oligoarthritis (commonly knees), lower back pain, enthesitis, dactylitis, plus systemic symptoms (fever, fatigue).
- Extra-articular signs: conjunctivitis, iritis, urethritis, cervicitis, balanitis, keratoderma blennorrhagicum, aortitis.
- Investigations: ↑CRP/ESR, RF/anti-CCP negative, joint aspiration to rule out infection/crystals, stool/urine cultures, X-ray (enthesitis, joint space loss), MRI if unclear.
- Differentials: septic arthritis, RA, psoriatic arthritis, ankylosing spondylitis, gout, CPPD, gonococcal arthritis.
- Management: NSAIDs first-line; corticosteroids (intra-articular/systemic); DMARDs for chronic disease; antibiotics for acute Chlamydia infection only.
- Complications: chronic arthritis (30–50%), sacroiliitis, cataracts, urethral strictures, aortic regurgitation.
- Prognosis: most recover in <6 months; up to 50% risk of chronic ReA.
Introduction
Reactive arthritis (ReA) is an inflammatory arthropathy that often occurs after exposure to certain gastrointestinal and genitourinary infections. The classic triad of conjunctivitis, urethritis and arthritis are frequently described but only found in approximately one-third of cases and are not required for diagnosis.1
ReA is a rare condition and mainly occurs in adults. Males aged between 15 and 35 years are more commonly affected.1
Aetiology
ReA belongs to the group of seronegative inflammatory spondyloarthropathies commonly associated with the human leukocyte antigen B27 (HLA-B27).1
The prevalence of HLA-B27 in patients with ReA is 30 to 50% and is not a definite diagnostic criterion for acute ReA.
Patients often give a history of genitourinary or gastrointestinal infection 1 to 4 weeks before the onset of arthritis. The common causative organisms are Chlamydia trachomatis, Salmonella, Campylobacter, Shigella and Yersinia species; however, other bacterial infections have been seen.
Pathophysiology
ReA is an immune-mediated inflammatory process that affects the synovium. It is hypothesised to be multifactorial, including genetic susceptibility and environmental factors.2 The exact pathogenesis of ReA remains unclear. However, RNA and DNA of known infectious organisms have been found in the synovial tissue of patients and are thought to trigger the host’s immune response.1
Risk factors
Risk factors for ReA include:1-2
- HLA-B27 genotype
- Preceding genitourinary or gastrointestinal infection
- Male sex in Chlamydia-induced ReA (male-to-female ratio 9:1)
Clinical features
Symptoms usually begin within 1 to 4 weeks after the onset of a causative infection. The most recognised pattern of ReA is asymmetrical oligoarthritis, typically affecting the knee, although polyarthritis and monoarthritis can occur.
Classic triad in ReA
The triad of conjunctivitis, urtehtritis, and arthritis is commonly remembered as:
“Can’t see, can’t pee, can’t climb a tree/sore knee”
History
Typical symptoms of ReA include:1, 3
- Joint pain
- Joint stiffness, especially in the morning
- Non-specific lower back pain and stiffness, generally relieved by exercise
- Constitutional symptoms including fever, fatigue and weight loss
Clinical examination
Typical clinical findings of ReA can be divided into articular and extra-articular manifestations.
Articular manifestations
Articular manifestations of ReA include:1-3
- Tenderness and swelling of the affected joint (s): more common in larger joints of lower limbs, especially the knee
- Heel pain: due to enthesitis (inflammation at sites where tendons insert into bones) of Achilles’ tendon and plantar fascia at the calcaneus
- Lower back pain: due to axial arthritis, especially sacroiliitis
- Reduced range of motion due to pain and stiffness
- Dactylitis: swelling of entire digits
Extra-articular manifestations
Extra-articular manifestations of ReA include:1-3
- Genitourinary symptoms: urethritis, cervicitis, salpingo-oophoritis, cystitis, and prostatitis
- Ocular symptoms: conjunctivitis, iritis and uveitis
- Skin manifestation: keratoderma blennorrhagicum, circinate balanitis, aphthous ulcers
- Cardiac manifestations: aortitis causing aortic regurgitation
Differential diagnoses
Differential diagnoses to consider in suspected ReA include:1-2
- Septic arthritis
- Rheumatoid arthritis (RA)
- Psoriatic arthritis
- Ankylosing arthritis
- Osteoarthritis
- Gout
- Gonococcal arthritis
- Calcium pyrophosphate deposition disease (CPPD)
Investigations
Laboratory investigations
Relevant laboratory investigations include:1-2
- Inflammatory markers (ESR/CRP): usually elevated; however, they are non-specific
- Rheumatoid factor (RF): likely negative in seronegative arthropathy
- Anti-cyclic citrullinated peptide (anti-CCP): a specific marker for rheumatoid arthritis; if positive, would suggest RA rather than ReA
- Urogenital culture: if genitourinary infection is suspected
- Stool cultures: if gastrointestinal infection is suspected (cultures are usually negative at the onset of arthritis)
- Joint aspiration (arthrocentesis): tested for bacteria, viruses and crystals
Imaging
Relevant imaging includes:4
- X-ray (first-line radiological investigation): affected joints may show erosions, loss of joint space, soft tissue swelling and enthesitis. Sacroiliitis is typically asymmetrical.
- MRI: not commonly requested but can be helpful if the initial X-ray is inconclusive
Diagnosis
ReA is a clinical diagnosis based on history and examination. Laboratory and imaging investigations can help support or exclude other differential diagnoses.
Management
The main goal of treatment in inflammatory arthritis is symptomatic relief and prevention of further joint damage.
Conservative management
Conservative management with rest in the acute flare and early exercises with physiotherapy, once this has improved, is recommended.5
Medical management
Typical medical management includes:1, 3
- Non-steroidal anti-inflammatory drugs (NSAIDs): first-line drug for symptomatic relief, with consideration of renal function and risk of gastrointestinal bleeding
- Corticosteroids: in acute flare or if symptoms are unresponsive to NSAIDs. Intra-articular injections may provide short-term relief in monoarticular or oligoarticular involvement, systemic corticosteroids may be required in polyarthritis and ocular manifestation, and topical corticosteroids can treat skin manifestations.
- Disease-modifying antirheumatic drugs (DMARDs): in chronic and resistant ReA
- Biologics: monoclonal antibodies (anti-TNF, IL-6, IL-17a) that target specific immune response components. The management of biological agents is complex, and patients should be referred to a specialist for further evaluation.
- Antibiotics: indicated to treat the underlying infection in acute Chlamydia trachomatis infection. However, there’s no evidence treating enteric infection alters the course of reactive arthritis.6
Complications
Complications of ReA include:2
- Chronic arthritis or sacroiliitis
- Cataracts
- Urethral stricture
- Aortic root necrosis
Prognosis
Symptoms are expected to resolve within the first 6 months. About 30-50% of patients will develop chronic ReA.1
Reviewer
Dr Kim Ling Goh
Senior Registrar (Internal Medicine)
Editor
Dr Jamie Scriven
References
- BMJ Best Practice. Reactive Arthritis. 2022. Available from: [LINK].
- Vičić M, Massari LP. Reactive Arthritis. New England Journal of Medicine. 2022. Available from: [LINK].
- NHS. Reactive Arthritis. 2024. Available from: [LINK].
- Clopton D, Campos A, Knipe H, et al. Reactive arthritis. Radiopaedia. 2013. Available from: [LINK].
- Carter JD, Hudson AP. Reactive Arthritis: Clinical Aspects and Medical Management. 2009. Rheumatic Disease Clinics of North America. Available from: [LINK].
- Schmitt, SK. Reactive Arthritis. Infectious Disease Clinics of North America. 2017. Available from: [LINK]
Image references
- Figure 1. GerardM. Knee arthritis. License: [CC BY-SA 3.0].
- Figure 3. MRuniqat. Penis with balanitis circinata. License: [CC BY-SA 4.0].
- Figure 4. Noorus. Aphthous ulcers on lip. License: [CC BY-SA 3.0].
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