Reactive Arthritis (Reiter Syndrome)

Meet the patient

A 24-year-old man presents with a swollen, painful right knee and left ankle that appeared overnight, two weeks after a bout of bloody diarrhoea on a backpacking trip. He has a painless sore on the glans penis and has noticed his right heel hurts on waking. He is febrile and his right knee is hot and tense.[1][4]

Three questions decide his next 48 hours, and they decide every reactive-arthritis consult: is this joint septic? (aspirate before you assume reactive — the missed septic joint is the catastrophe), what was the trigger, and who else is at risk? (the preceding infection, the sexual contacts), and will this settle on NSAIDs, or is he heading for the chronic minority? (HLA-B27, hip involvement, polyarticular disease decide it). The temporal link — arthritis after a distant infection — is the single most important historical clue, so elicit it actively, never wait for it.[3][4]

What reactive arthritis is — a sterile arthritis that follows a distant infection

Reactive arthritis is the spondyloarthropathy that follows infection at a distant mucosal site. The joints are inflamed but sterile: the causative organism triggers the disease from afar and is not recoverable from the joint by standard culture. That single fact — a hot, inflamed joint that is culture-negative — is the defining pathological and diagnostic feature separating reactive arthritis from septic and gonococcal arthritis.[1][3]

The arthritis typically begins 1 to 4 weeks after a genitourinary or gastrointestinal infection and targets the entheses (tendon and ligament insertions into bone) as much as the synovium, producing the characteristic combination of asymmetric lower-limb oligoarthritis, enthesitis and dactylitis.[1][3]

A word on the eponym. "Reiter syndrome" is named for Hans Reiter, who described a soldier with the triad after dysentery in 1916. The eponym is now discouraged — both because Reiter's record under the Nazi regime is discredited and because the triad is an incomplete description. The preferred term reactive arthritis captures the essential concept: an immune-mediated arthritis reactive to a distant infection.[1]

The triggers — genitourinary, gastrointestinal, and the rare ones

Reactive arthritis is classified by its triggering infection, because the trigger decides the epidemiology, the public-health implications, and sometimes the phenotype.[2][4]

[2]

The family — the seronegative spondyloarthropathies

Reactive arthritis sits within the seronegative spondyloarthropathies (SpA), alongside ankylosing spondylitis, psoriatic arthritis, enteropathic (IBD-associated) arthritis and undifferentiated SpA. They share a unifying set of features that examiners reward as a group.[9]

• Inflammatory back pain and sacroiliitis (often bilateral in ankylosing spondylitis).
• Asymmetric, predominantly lower-limb oligoarthritis.
• Enthesitis — especially the Achilles tendon and plantar fascia insertions (heel pain).
• Dactylitis ("sausage digit").
• HLA-B27 association and a positive family history.
• Acute anterior uveitis.
• Mucocutaneous features (psoriasis, oral ulcers, keratoderma, balanitis, nail dystrophy).
• RF negative, ANA negative — the definition of "seronegative."[1]

The ASAS classification separates axial from peripheral SpA; reactive arthritis is the archetype of peripheral SpA with a known trigger, though it may coexist with axial (sacroiliitis, spondylitis) involvement.[9][10]

How common, who, and why HLA-B27 is necessary but not enough

Reactive arthritis most commonly affects young adults aged 20 to 40 years, with an overall incidence of 0.6 to 27 per 100,000 per year (the wide range reflects variable trigger prevalence and reporting). The post-genitourinary form predominates in young men (male-to-female ratio up to 9 to 1 for chlamydia-triggered disease, partly reflecting symptom reporting and ascertainment), while the post-enteric form has an equal sex ratio.[1][4]

The single most important host risk factor is HLA-B27 positivity, present in 30 to 50 percent of patients overall (higher in severe, chronic or axial disease) compared with roughly 4 to 8 percent of the general population. Among HLA-B27-positive individuals exposed to a triggering infection, the risk of developing reactive arthritis is 1 to 4 percent after chlamydia and 1 to 20 percent after certain enteric outbreaks — demonstrating that HLA-B27 is necessary but not sufficient for disease.[1][2]

[1]

Other risk factors: male sex (for chlamydia-triggered disease), HIV infection (reactive arthritis is more frequent and more severe, particularly axial and severe forms), a family or personal history of spondyloarthropathy, and bacterial virulence — not every strain triggers ReA; only certain Shigella flexneri and Yersinia strains are arthritogenic. Geographical variation in HLA-B27 prevalence (high in Scandinavia and certain Native American populations, low in African and Japanese) explains much of the global variation.[2][4]

Why a sterile joint hurts — antigen in the joint, organism at a distance

Reactive arthritis is an immune-mediated arthritis in a genetically susceptible host, triggered by bacterial antigens from a distant mucosal infection. Four linked stages explain the paradox of a hot, sterile joint.[1][2]

Stage 1 — mucosal infection at a distant site. The triggering organisms share a unifying feature: they are intracellular or facultatively intracellular bacteria that persist within host cells. Chlamydia trachomatis infects urethral or cervical epithelium; Campylobacter, Salmonella, Shigella and Yersinia invade the gut mucosa. The initial infection is often asymptomatic — chlamydial cervicitis is silent in up to 50 percent of women and 25 percent of men — which is why direct questioning and laboratory testing for the trigger is essential.[2][4]

Stage 2 — bacterial antigen traffics to the joint. Bacterial antigens, nucleic acid (DNA and especially rRNA), and lipopolysaccharide are detectable in the synovial fluid, synovial tissue and entheses, though viable, culturable organisms are usually absent. For chlamydia-triggered disease there is strong evidence that C. trachomatis persists in a metabolically active but non-culturable form within synovial macrophages — the engine of the ongoing immune response.[2]

Stage 3 — HLA-B27 and the IL-23/IL-17 axis. In an HLA-B27-positive host the response is dysregulated and excessive: molecular mimicry (bacterial peptides cross-reacting with self-peptides at the enthesis), the arthritogenic-peptide hypothesis (HLA-B27 presenting bacterial peptides to CD8 T cells), misfolding and the unfolded-protein response activating IL-23/IL-17, and surface homodimer signalling amplifying IL-17 at entheses. The IL-23/IL-17 axis is now the dominant inflammatory pathway — and enthesitis is the pathological hallmark.[1]

Stage 4 — a sterile, culture-negative inflammatory arthritis. The synovium shows a neutrophilic and mononuclear infiltrate; the enthesis shows inflammation at the fibrocartilage-bone interface with erosions, new bone formation (enthesophytes) and periostitis. Because the joint is sterile, cultures are negative and antibiotics treat the trigger and contacts but do not reliably shorten the established arthritis — the pivotal, frequently-tested point.[1][6]

[1]

The spondyloarthropathy signature — and the Reiter triad that is rarely complete

The presentation is acute, arising 1 to 4 weeks after a triggering GU or GI infection. The classic Reiter triad — arthritis plus urethritis plus conjunctivitis — is the exam-stem pattern, but it is complete in only about one third of patients. Most have some combination of features rather than the full triad. Examiners test both pattern recognition (the arthritis with a preceding infection) and the specific features.[3][4]

The musculoskeletal pattern is one of the highest-yield recognition cues in rheumatology. The arthritis is characteristically an asymmetric oligoarthritis (two to four joints), predominantly affecting the lower limbs — the knee, ankle and small joints of the foot are the commonest targets.[3]

• Asymmetric lower-limb oligoarthritis — knee and ankle effusions are typical; the arthritis is acute and may mimic septic arthritis in a single joint (hence the rule to aspirate).
• Enthesitis — tenderness at tendon and ligament insertions, most characteristically at the Achilles tendon insertion and the plantar fascia origin (calcaneal enthesitis), producing heel pain disproportionate to the visible swelling. The pathological hallmark of the spondyloarthropathies.
• Dactylitis (sausage digit) — uniform swelling of an entire finger or toe from combined synovitis and enthesitis; highly characteristic and examiner-rewarded.
• Sacroiliitis and spondylitis — low back and buttock pain from sacroiliac involvement, present in a minority at presentation but more common in chronic disease.
• Non-articular rheumatism — tendinitis, fasciitis and bursitis may accompany the arthritis.[1]

The extra-articular features — what completes the Reiter picture

The extra-articular features distinguish reactive arthritis from a generic inflammatory oligoarthritis. Examine for them actively — they are easily missed.[1][3]

[1]

Aspirate first — the septic joint is the killer

The pivotal diagnostic steps are pattern recognition and excluding septic arthritis by aspirating any acute hot joint. Reactive arthritis is seronegative (RF and ANA negative) and the synovial fluid is sterile, crystal-negative and inflammatory — which separates it from septic, gonococcal and crystal arthropathies.[1][3]

[1]

The discriminator line: asymmetric lower-limb oligoarthritis with enthesitis or a sausage digit, 1 to 4 weeks after a GU or GI infection. That pattern in a young adult is reactive arthritis until proven otherwise — and "proven otherwise" means aspirating the hot joint to exclude sepsis.[3]

The single most dangerous mimic is septic arthritis — a single hot joint with high fever and marked pain on movement must be aspirated before reactive arthritis is assumed, because sepsis can coexist with or mimic reactive disease and delays cause rapid joint destruction. Gonococcal arthritis is a close second: distinguished by its disseminated pustular rash, tenosynovitis and positive cultures or NAAT — it is a true infection, not a reactive process. And keratoderma blennorrhagicum and pustular psoriasis are clinically and histologically indistinguishable — the distinguishing clue is the history of a preceding infection and the distribution (soles in reactive arthritis; extensor surfaces and scalp in psoriasis).[3][4]

The synovial fluid — the pivotal investigation

There is no single diagnostic test for reactive arthritis. The diagnosis is clinical, supported by evidence of a preceding infection, a seronegative autoantibody profile, and a sterile, inflammatory, crystal-negative synovial fluid.[3][4]

Aspirate any acute hot joint. The synovial fluid in reactive arthritis is culture-negative (sterile) — the defining feature that distinguishes it from septic and gonococcal arthritis. It is crystal-negative (no monosodium urate or calcium pyrophosphate on polarised microscopy), and inflammatory — white blood cell count typically 2,000 to 50,000 per microlitre, predominantly neutrophilic.[1]

Gram stain and culture must always be sent even when reactive arthritis is suspected, because septic arthritis can coexist, and a culture-negative, crystal-negative inflammatory fluid with a compatible clinical story is the pattern that confirms reactive arthritis after sepsis is excluded.[4]

Finding the trigger — and excluding HIV

Identify the triggering infection because the trigger decides the treatment, the contact-tracing, and the prognosis.[1]

[1]

General laboratory tests. ESR and CRP are elevated (sometimes markedly) during active disease and trend with disease activity. The full blood count may show leukocytosis, neutrophilia, thrombocytosis and a normocytic anaemia of chronic inflammation. The seronegative profile — RF negative, ANA negative, anti-CCP negative — is the "seronegative" in seronegative spondyloarthropathy. HLA-B27 is supportive but not diagnostic — present in 30 to 50 percent of patients and 4 to 8 percent of the general population. It is most useful in prognostication (positivity predicts chronic, axial and recurrent disease), and it is not a screening test.[1][4]

Imaging is usually normal early. With chronic or recurrent disease, look for sacroiliitis, enthesophytes and erosions at tendon insertions (the "fluffy" or "fuzzy" periostitis at the calcaneus), periostitis, and in the spine syndesmophytes and squaring of vertebral bodies. MRI is more sensitive for early sacroiliitis (bone-marrow oedema on STIR) and enthesitis. A plain pelvic film and a heel X-ray (calcaneal enthesophyte) are high-yield classic findings in chronic disease.[1]

Treat the trigger and the contacts — then NSAIDs

Management is staged: treat the trigger first, then control symptoms with NSAIDs and local steroids, then escalate to DMARDs and biologics for the persistent minority. The ASAS-EULAR recommendations for spondyloarthritis management frame this approach, with reactive arthritis as the archetype of peripheral SpA.[5][10]

Step 1 — treat the trigger and the contacts

Treating the triggering infection addresses the source, prevents onward transmission, and prevents the reproductive complications of untreated chlamydia (pelvic inflammatory disease, infertility, ectopic pregnancy).[6]

[1]

For Chlamydia trachomatis, give azithromycin 1 g orally as a single dose, or doxycycline 100 mg orally twice daily for 7 days (14 days for epididymitis or pelvic inflammatory disease overlap). Treat all sexual partners of the preceding 60 days, and offer expedited partner therapy where available. For gastrointestinal triggers, the enteric infection has usually resolved by the time arthritis appears and antibiotics are not routinely needed — though specific treatment (for example oral vancomycin or fidaxomicin for C. difficile) follows the infective picture. Screen all sexually acquired reactive arthritis patients for HIV, syphilis, gonorrhoea and hepatitis B and C.[4]

Step 2 — NSAIDs are the cornerstone of first-line therapy

NSAIDs at full anti-inflammatory dose are the cornerstone of first-line therapy for the acute arthritis and enthesitis, continued for the duration of active disease (provided there are no contraindications — renal impairment, active peptic ulcer disease, anticoagulation, heart failure, aspirin-sensitive asthma).[3]

[1]

Naproxen 500 mg orally twice daily, ibuprofen 400 to 800 mg three times daily (maximum 2.4 g per day), or indomethacin 50 mg two to three times daily are the standard agents. Add a proton-pump inhibitor (omeprazole 20 mg daily) for patients at risk of NSAID gastropathy.[3]

Intra-articular corticosteroid — for an inflamed oligoarticular joint (a hot knee) inadequately controlled by NSAIDs or where NSAIDs are contraindicated. Triamcinolone acetonide 40 mg for a large joint, or a proportionate dose for smaller joints, after aspiration and confirmation that the fluid is sterile. Highly effective for mono- or oligoarticular disease.[3]

Topical corticosteroids for circinate balanitis, keratoderma blennorrhagicum and oral ulcers (clobetasol 0.05 percent cream to the soles; triamcinolone dental paste to oral ulcers; mild topical steroid to the glans). Uveitis demands urgent ophthalmology referral for topical, periocular or systemic corticosteroids and mydriatics (atropine 1 percent or cyclopentolate 1 percent) — untreated anterior uveitis threatens sight through synechiae, cataract and glaucoma. Physiotherapy rests the joint in the acute phase, then graded mobilisation and stretching (especially Achilles tendon and plantar fascia) preserve mobility.[3]

The antibiotics trap — they treat the trigger, not the arthritis

Prolonged antibiotics do not improve the arthritis course. This is the pivotal, frequently-tested point, and it trips candidates who reason "post-infectious, so give antibiotics."[6]

DMARDs and biologics for the persistent minority

For the 15 to 30 percent with disease persisting beyond 6 to 12 months, polyarticular or axial disease, or recurrent flares, disease-modifying antirheumatic drugs (DMARDs) are added.[3][5]

Sulfasalazine is the first-line DMARD: start at 500 mg orally twice daily and titrate to 2 to 3 g per day in divided doses over 4 to 8 weeks. Monitor full blood count and liver function (leukopenia, thrombocytopenia, transaminitis); screen for G6PD deficiency before starting (risk of haemolysis). Sulfasalazine has the best evidence of the conventional DMARDs for reactive arthritis and peripheral spondyloarthritis.[3]

Methotrexate is an alternative or add-on: 7.5 to 15 mg orally once weekly, titrating to 20 to 25 mg weekly, with folic acid 5 mg weekly. Monitor full blood count, liver and renal function; screen for and treat latent tuberculosis, hepatitis B and C before starting. Contraindicated in pregnancy. Short-course systemic corticosteroids — prednisolone 0.5 mg per kg per day orally, tapering over 2 to 4 weeks — bridge severe polyarticular flares unresponsive to NSAIDs.[5]

For the refractory minority — disease unresponsive to NSAIDs and DMARDs, especially with chronic axial spondyloarthritis — TNF inhibitors are the evidence-supported escalation.[5][10]

[1]

Screen for latent tuberculosis (interferon-gamma release assay or chest X-ray), hepatitis B and C and HIV before starting; ensure vaccinations are up to date and avoid live vaccines on therapy. IL-17 inhibitors (secukinumab, ixekizumab) and IL-23 inhibitors (ustekinumab) have a role in psoriatic and axial spondyloarthritis and are increasingly considered for refractory reactive arthritis, though the evidence base for reactive arthritis specifically is smaller than for ankylosing spondylitis and psoriatic arthritis.[5][10]

The subtypes — post-streptococcal, HIV-associated, and the chronic evolution

Post-streptococcal reactive arthritis is a separate entity from acute rheumatic fever. It follows group A streptococcal pharyngitis, lacks the major Jones criteria of acute rheumatic fever (no carditis, no chorea, no erythema marginatum, no subcutaneous nodules), and has a shorter latent interval (1 to 2 weeks rather than 2 to 4 weeks). It is not prevented by routine penicillin prophylaxis in the way acute rheumatic fever is, and does not carry the same cardiac implications. Management is NSAIDs; the role of long-term antibiotic prophylaxis is debated.[8]

HIV-associated reactive arthritis is more common and more severe, with florid skin and joint features — severe keratoderma blennorrhagicum, aggressive dactylitis and axial disease. The relationship is complex: HIV does not directly cause reactive arthritis, but the immune dysregulation it produces amplifies the spondyloarthropathy phenotype. HIV testing is mandatory in any sexually acquired reactive arthritis. Management principles are the same, though immunosuppression must be coordinated with antiretroviral therapy.[4]

Chronic and recurrent reactive arthritis — the 15 to 30 percent whose disease persists beyond 6 to 12 months, or recurs after remission. Predictors include HLA-B27 positivity, hip involvement, polyarticular disease at onset, and repeated triggering infections. This group may evolve into axial spondyloarthritis or ankylosing spondylitis over years and requires long-term follow-up, DMARDs and TNF inhibitors for refractory disease.[9][10]

Post-enteric reactive arthritis — triggered by Campylobacter jejuni (the commonest enteric trigger in many series), Salmonella, Shigella flexneri (particularly arthritogenic), Yersinia and C. difficile. Equal sex ratio, often follows food-borne outbreaks; the diarrhoea has usually resolved before arthritis onset, so antibiotics are rarely needed for the arthritis. Yersinia-triggered disease may be accompanied by erythema nodosum and can mimic inflammatory bowel disease.[2][4]

How reactive arthritis patients come to harm — the preventable list

• The missed septic joint — failing to aspirate a hot joint because "it is obviously reactive" is the catastrophic, avoidable error.[1]
• Conjunctivitis mislabelled when it is uveitis — the red eye with photophobia or visual change is acute anterior uveitis; delay risks synechiae, glaucoma, cataract and sight loss.[1]
• The omitted HIV test — missing co-infection that changes management and prognosis.[4]
• Untreated sexual contacts — allowing re-infection and onward transmission of chlamydia, with pelvic inflammatory disease, tubal infertility and ectopic pregnancy the downstream harms.[1]
• Prolonged antibiotics for the arthritis — they eradicate the trigger but do not shorten the course, and inappropriate prolonged use drives resistance.[6]
• Missing the diagnosis because the triad is incomplete — most patients have only some features; the pattern (asymmetric lower-limb oligoarthritis plus a recent infection) is the key.[3]
• Not examining the soles, palms and glans penis — keratoderma blennorrhagicum and circinate balanitis are pathognomonic when present but easily missed if not actively sought.[1]

Prognosis and disposition

Reactive arthritis is usually self-limiting, resolving within 3 to 12 months in the majority. The pivotal prognostic question is who will join the chronic or recurrent 15 to 30 percent, because that subgroup needs long-term DMARD or biologic therapy and rheumatology follow-up.[1][9]

The high-risk profile for chronicity: HLA-B27 positivity (predicts chronic, axial and recurrent disease), hip (coxofemoral) joint involvement at presentation, polyarticular or axial disease at onset, repeated triggering infections (recurrent chlamydia or enteric infections drive flares), male sex and young age in chlamydia-triggered disease, and elevated inflammatory markers that fail to normalise. Patients with the chronic phenotype may evolve into axial spondyloarthritis or ankylosing spondylitis over years; long-term follow-up is essential to detect this transition and escalate to TNF inhibitors when NSAIDs and DMARDs are insufficient.[9][10]

Disposition — most patients are managed in the ambulatory setting by rheumatology (or general medicine where rheumatology access is limited), with referral to ophthalmology (uveitis), genitourinary medicine or sexual health (STI treatment and contact tracing), physiotherapy (mobilisation, enthesitis management), dermatology (severe skin disease), cardiology (aortic regurgitation, conduction disease) and infectious diseases (HIV or complex enteric infection). Admission is rarely needed unless pain control is impossible, sepsis cannot be confidently excluded, or uveitis is severe.[3]

Monitoring and follow-up — review at 2 to 4 weeks to assess NSAID response and confirm trigger treatment; at 3 months to determine whether disease is settling or persisting (prompting DMARD escalation); and at 6 to 12 months to confirm remission or institute DMARD or biologic therapy. Counsel all patients on safe sex, food and water hygiene, and prompt treatment of any future triggering infection to reduce recurrence.[1][3]

Special populations

HIV-positive patients. Reactive arthritis is more frequent and more severe, with florid skin and joint features. HIV testing is mandatory in any sexually acquired reactive arthritis. Management is the same in principle (NSAIDs, DMARDs, TNF inhibitors), but immunosuppression must be coordinated with antiretroviral therapy, and infectious screening before biologics (latent TB, hepatitis B and C) is critical.[4]

Women. Chlamydia-triggered reactive arthritis is under-diagnosed in women because chlamydial cervicitis is frequently asymptomatic (silent in up to 50 percent). Maintain a low threshold for NAAT testing in a woman with an asymmetric oligoarthritis and any genital symptom or risk factor.[1]

Children and adolescents. Reactive arthritis is uncommon; when it occurs it usually follows a gastrointestinal infection (especially Yersinia and Campylobacter). Principles are the same, with weight-based dosing. Septic arthritis is a more prominent differential in a child with a hot joint, and aspiration is mandatory. Consider juvenile idiopathic arthritis (enthesitis-related arthritis) in chronic disease.[4]

Pregnancy. Use azithromycin (safe in pregnancy and breastfeeding) rather than doxycycline (contraindicated — tetracycline tooth discolouration and teratogenicity) for chlamydia-triggered disease. Avoid NSAIDs after 20 weeks' gestation and especially in the third trimester; paracetamol is the preferred analgesic, with short courses of oral or intra-articular corticosteroid for severe disease. Sulfasalazine is compatible with pregnancy (supplement folic acid 5 mg); methotrexate is absolutely contraindicated.[3]

Elderly. Less common and more readily misattributed to gout, osteoarthritis, septic arthritis or polymyalgia rheumatica. Weigh NSAID risks carefully (renal impairment, heart failure, peptic ulcer disease, anticoagulation) and prefer intra-articular corticosteroid injection for oligoarticular disease when NSAIDs are contraindicated.[3]

Evidence and regional deltas

The antibiotic evidence is the examinable core. The Barber 2013 systematic review and meta-analysis concluded that prolonged antibiotics do not improve the arthritis course overall (with a possible signal for chlamydia-triggered disease). The Carter 2010 double-blind, placebo-controlled trial of combination doxycycline plus rifampicin for chronic chlamydia-induced disease showed significant benefit over placebo — a nuanced finding highlighting persistent chlamydial antigen in a specific subset.[6][7]

The De Craemer 2022 study showed that peripheral manifestations (arthritis, enthesitis, dactylitis) are major determinants of phenotype and outcome in new-onset spondyloarthritis, with reactive arthritis as the archetype — supporting early aggressive management of peripheral disease to prevent chronicity.[9] The Zeng 2020 review summarised the evidence for biologic agents (principally TNF inhibitors) in refractory disease. The Ramiro 2022 (ASAS-EULAR) recommendations frame the management of the axial component: NSAIDs first-line for all, TNF or IL-17 inhibitors for inadequate responders, and conventional DMARDs for peripheral arthritis (sulfasalazine, methotrexate).[5][10]

The mantra, and the mnemonic

The mantra: sterile joint after a distant infection — aspirate first, treat the trigger and the contacts, NSAIDs lead, and never reach for prolonged antibiotics.[1][6]

Ward-round test — three stems, thirty seconds each

Stem 1 — the backpacker from the top of the topic (answer)

The 24-year-old with a hot swollen right knee and left ankle, heel pain, and a penile sore, two weeks after bloody diarrhoea. His right knee is hot and tense. What is the diagnosis, and what is the first action? Model: This is reactive arthritis — an asymmetric lower-limb oligoarthritis with enthesitis (heel pain) and circinate balanitis, arising 1 to 4 weeks after a gastrointestinal infection. But the first action is to aspirate the hot knee — to exclude septic arthritis (Staphylococcus aureus; WBC over 50,000, positive Gram stain and culture) before assuming reactive. Send fluid for cell count, Gram stain, culture and crystal microscopy. The expected reactive pattern is sterile, culture-negative, crystal-negative, inflammatory (WBC 2,000 to 50,000). Send stool culture (Campylobacter, Salmonella, Shigella, Yersinia), and start full-dose NSAIDs (naproxen 500 mg twice daily) once sepsis is excluded.[1][3]

Stem 2 — the red eye that is not conjunctivitis (answer)

A patient with proven reactive arthritis develops a red right eye with pain, photophobia and blurred vision. The registrar calls it "part of the Reiter triad — conjunctivitis" and plans no further action. What is the error, and what do you do? Model: This is acute anterior uveitis, not conjunctivitis — the pain, photophobia and blurred vision are the discriminators, and conjunctivitis is typically painless with discharge. Untreated anterior uveitis threatens sight through posterior synechiae, secondary glaucoma and cataract. Refer urgently to ophthalmology for slit-lamp examination and topical (or periocular or systemic) corticosteroids plus a mydriatic (atropine or cyclopentolate). The Reiter triad's eye is conjunctivitis; uveitis is the sight-threatening extra-articular complication that needs same-day ophthalmology.[1][4]

Stem 3 — the chronic minority (answer)

Eight months after chlamydia-triggered reactive arthritis, a young man still has polyarticular disease, hip involvement and a raised CRP, despite NSAIDs. HLA-B27 is positive. What is the prognosis, and what is the next step? Model: He has joined the chronic 15 to 30 percent — predicted by HLA-B27 positivity, hip involvement, polyarticular disease and inflammatory markers that fail to normalise. This group may evolve into axial spondyloarthritis or ankylosing spondylitis over years. The next step is a conventional DMARD — sulfasalazine, titrated to 2 to 3 g per day (screen for G6PD deficiency first) — and if that is insufficient, a TNF inhibitor (adalimumab 40 mg subcutaneously every 2 weeks, etanercept 50 mg weekly, or infliximab 5 mg per kg) after latent-TB and viral hepatitis screening. Long-term rheumatology follow-up is essential.[5][9][10]

References

1. [1]Bentaleb I, Abdelghani KB, Rostom S, et al. Reactive Arthritis: Update Curr Clin Microbiol Rep, 2020.PMID 33014690
2. [2]Zeidler H, Hudson AP. Reactive Arthritis Update: Spotlight on New and Rare Infectious Agents Implicated as Pathogens Curr Rheumatol Rep, 2021.PMID 34196842
3. [3]Jubber A, Moorthy A. Reactive arthritis: a clinical review J R Coll Physicians Edinb, 2021.PMID 34528623
4. [4]Schmitt SK. Reactive Arthritis Infect Dis Clin North Am, 2017.PMID 28292540
5. [5]Zeng H, Luo B, Zhang Y, Xie Z. Treatment of reactive arthritis with biological agents: a review Biosci Rep, 2020.PMID 32039436
6. [6]Barber CE, Kim J, Inman RD, Esdaile JM. Antibiotics for treatment of reactive arthritis: a systematic review and metaanalysis J Rheumatol, 2013.PMID 23588936
7. [7]Carter JD, Espinoza LR, Inman RD, et al. Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial Arthritis Rheum, 2010.PMID 20155838
8. [8]Bawazir Y, Towheed T, Anastassiades T. Post-Streptococcal Reactive Arthritis Curr Rheumatol Rev, 2020.PMID 31393253
9. [9]De Craemer AS, Renson T, Deroo L, Van Praet L, et al. Peripheral manifestations are major determinants of disease phenotype and outcome in new onset spondyloarthritis Rheumatology (Oxford), 2022.PMID 34850859
10. [10]Ramiro S, Nikiphorou E, Sepriano A, Ortolan A, et al. ASAS-EULAR recommendations for the management of axial spondyloarthritis: 2022 update Ann Rheum Dis, 2023.PMID 36270658