High Yield Overview

REACTIVE ARTHRITIS

Post-Infectious | Seronegative Spondyloarthropathy | Classic Triad

1-4 wksLatency after triggering infection

HLA-B27Positive in 60-80%

TriadArthritis + Urethritis + Conjunctivitis

KneeMost commonly affected joint

TRIGGERING INFECTIONS

Genitourinary

PatternChlamydia trachomatis (most common)

TreatmentAzithromycin or doxycycline

Enteric

PatternSalmonella, Shigella, Campylobacter, Yersinia

TreatmentOften self-limiting

Respiratory

PatternChlamydia pneumoniae (less common)

TreatmentAntibiotics if active

Other

PatternC. difficile, Ureaplasma

TreatmentTreat underlying infection

Critical Must-Knows

Classic triad: Arthritis + urethritis + conjunctivitis (full triad in only 30%)
Sterile joint - cultures negative despite inflammatory arthritis
Asymmetric oligoarthritis - typically lower limb predominance
Self-limiting in 50% within 6 months, but 30-50% develop chronic disease
Enthesitis and dactylitis are characteristic features

Examiner's Pearls

"
Cant see, cant pee, cant climb a tree = conjunctivitis, urethritis, arthritis
"
Keratoderma blennorrhagicum = psoriasiform skin lesions on palms/soles
"
Circinate balanitis = painless penile ulcers - pathognomonic
"
Septic joint excluded by negative cultures and crystal analysis

Clinical Imaging

Imaging Gallery

Sagittal T2-weighted MRI of the cervical spine demonstrates widening of the atlantodental interval, cervical canal stenosis without spinal cord signal changes, and pannus formation (arrow). — Sagittal T2-weighted MRI of the cervical spine demonstrates widening of the atlantodental interval, cervical canal stenosis without spinal cord signalCredit: Muscal E et al. via J Med Case Rep via Open-i (NIH) (Open Access (CC BY))

A) Lateral cervical spine X-ray showing an atlantodental interval (arrow) of less than 6 mm. B) Lateral cervical spine X-ray shows a progressive widening of the atlantodental interval (arrow) to more — A) Lateral cervical spine X-ray showing an atlantodental interval (arrow) of less than 6 mm. B) Lateral cervical spine X-ray shows a progressive widenCredit: Muscal E et al. via J Med Case Rep via Open-i (NIH) (Open Access (CC BY))

Coronal computed tomography of the cervical spine shows evidence of bony erosion at the tip of the odontoid (arrow).Credit: Muscal E et al. via J Med Case Rep via Open-i (NIH) (Open Access (CC BY))

A. Fibrous inflammatory granulation tissue in the tendon encompasses the fibrous connective tissue: fibrosis, scarce fibroblasts and slight blood vessels; B. degenerative changes within the tendon at — A. Fibrous inflammatory granulation tissue in the tendon encompasses the fibrous connective tissue: fibrosis, scarce fibroblasts and slight blood vessCredit: Sudoł-Szopińska I et al. via J Ultrason via Open-i (NIH) (Open Access (CC BY))

Critical Reactive Arthritis Exam Points

Exclude Septic Arthritis

Joint aspiration is mandatory in any acute monoarthritis. Reactive arthritis shows inflammatory fluid (WBC 10,000-50,000) but negative cultures and no crystals. Always exclude septic arthritis before attributing to reactive arthritis.

Triggering Infections

Chlamydia trachomatis is the most common trigger (GU route). Enteric pathogens include Salmonella, Shigella, Campylobacter, Yersinia. The triggering infection may be subclinical or have resolved by the time arthritis appears.

Extra-Articular Features

Mucocutaneous features are pathognomonic: Keratoderma blennorrhagicum (palms/soles), circinate balanitis (painless penile lesions), oral ulcers. Eye involvement: Conjunctivitis (most common) or anterior uveitis (more serious).

Differentiation from Other SpA

Unlike AS, axial involvement is asymmetric and not always present. Unlike psoriatic arthritis, skin lesions are different and triggered by infection. Temporal relationship to infection (1-4 weeks) is the key distinguishing feature.

Seronegative Spondyloarthropathies Comparison

Feature	Reactive Arthritis	Ankylosing Spondylitis	Psoriatic Arthritis
HLA-B27 association	60-80%	90-95%	40-50%
Triggering factor	GU or enteric infection	None identified	Psoriasis
Joint pattern	Asymmetric oligoarthritis	Axial predominant	Variable (DIP, dactylitis)
Sacroiliitis	Asymmetric if present	Bilateral symmetric	Asymmetric
Skin features	Keratoderma, balanitis	None	Psoriatic plaques, nail changes
Disease course	Often self-limiting	Chronic progressive	Chronic, variable

Mnemonic

CANT SEE, CANT PEE, CANT CLIMB A TREEClassic Triad

Cant See

Conjunctivitis or uveitis

Cant Pee

Urethritis (non-gonococcal)

Cant Climb a Tree

Arthritis (asymmetric oligoarthritis)

Memory Hook:The classic teaching mnemonic for reactive arthritis triad!

Mnemonic

SCCY-UTriggering Organisms

Salmonella

Enteric - food poisoning

Campylobacter

Enteric - common cause of gastroenteritis

Chlamydia

GU - most common trigger overall

Yersinia

Enteric - undercooked pork

Ureaplasma

GU - less common

Memory Hook:SCCY-U triggers reactive arthritis after infection clears!

Mnemonic

KUBOCExtra-Articular Features

Keratoderma blennorrhagicum

Psoriasiform lesions on palms and soles

Ulcers - oral

Painless oral ulcerations

Balanitis circinata

Painless penile lesions - pathognomonic

Onycholysis

Nail involvement

Conjunctivitis/uveitis

Eye inflammation - can be sight-threatening

Memory Hook:KUBOC - the mucocutaneous features of reactive arthritis!

Overview and Epidemiology

Reactive arthritis is an acute, sterile, inflammatory arthritis that develops following a distant infection, typically genitourinary or gastrointestinal. Previously known as Reiter syndrome (now deprecated due to historical associations), it is classified as a seronegative spondyloarthropathy.

Epidemiology:

Incidence: 30-40 per 100,000 following enteric infection, 4-8 per 100,000 following chlamydial infection
Male to female ratio: 3:1 for post-venereal, 1:1 for post-enteric
Peak age: 20-40 years
HLA-B27 positive in 60-80% of patients

Risk Factors:

Recent infection: GU or enteric 1-4 weeks prior
HLA-B27 positivity: Increases risk and severity
Male sex: Higher incidence of post-venereal form
Immunocompromised state: HIV increases risk

Terminology

The term "Reiter syndrome" is no longer used in most guidelines due to Hans Reiter's Nazi affiliations. The preferred term is now "reactive arthritis" or "post-infectious arthritis."

Pathophysiology

Understanding the pathophysiology of reactive arthritis is essential for both diagnosis and management. The condition involves an aberrant immune response to microbial antigens in genetically susceptible individuals.

Triggering Infections

Genitourinary triggers:

Chlamydia trachomatis (most common GU trigger)
Ureaplasma urealyticum
Mycoplasma genitalium

Enteric triggers:

Salmonella (typhimurium, enteritidis)
Shigella (flexneri most arthritogenic)
Campylobacter jejuni
Yersinia enterocolitica

Immunopathogenesis

Molecular mimicry and bacterial persistence:

Infection triggers initial immune response
Bacterial antigens or DNA persist in synovium (demonstrated for Chlamydia)
Cross-reactivity between bacterial and self-antigens
HLA-B27 may inefficiently present bacterial peptides
Th17 cells and IL-17/IL-23 axis drive synovial inflammation

HLA-B27 role:

Present in 60-80% of patients (vs 8% general population)
Associated with more severe and chronic disease
Associated with axial involvement
Mechanism: arthritogenic peptide presentation, protein misfolding, homodimer formation

Sterile Synovitis

Despite being triggered by infection, viable organisms are NOT present in the joint. However, bacterial DNA and antigens CAN be detected. This is why antibiotics for the triggering infection are important, but the joint itself is sterile.

Chronicity Factors

HLA-B27 positivity
Enteric rather than GU trigger (Yersinia especially)
Persistent infection (untreated Chlamydia)
Early sacroiliac joint involvement

Clinical Presentation

The Classic Triad

Arthritis (95-100%):

Appears 1-4 weeks after triggering infection
Asymmetric oligoarthritis (fewer than 5 joints)
Lower limb predominance (knee, ankle, feet)
May be additive (new joints over days/weeks)
Enthesitis: Achilles tendonitis, plantar fasciitis
Dactylitis: "sausage digit" - entire toe/finger swollen

Urethritis (90% of post-venereal):

May be mild or asymptomatic
Dysuria, urethral discharge
Can occur in enteric-triggered disease (sterile urethritis)
May precede arthritis

Conjunctivitis (30-60%):

Usually bilateral
Mild, self-limiting
May progress to anterior uveitis (15%) - more serious, requires ophthalmology

Mucocutaneous Features

Keratoderma blennorrhagicum:

Psoriasiform hyperkeratotic lesions
Palms and soles characteristic
Histologically identical to pustular psoriasis

Circinate balanitis:

Painless erythematous erosions on glans penis
Pathognomonic for reactive arthritis
May be missed if not specifically examined

Oral ulcers:

Painless aphthous-like ulcerations
Tongue, palate, buccal mucosa

Nail changes:

Onycholysis, subungual hyperkeratosis
Similar to psoriatic changes

Physical Examination

Inspection:

Swollen, erythematous joints (asymmetric)
Dactylitis ("sausage digits")
Skin lesions on palms, soles
Conjunctival injection

Palpation:

Tender joints and entheses
Achilles tendon tenderness
Plantar fascia tenderness

Investigations

Laboratory Studies

Inflammatory markers:

ESR and CRP elevated during acute phase
Useful for monitoring response

HLA-B27:

Positive in 60-80%
Supports diagnosis but not required
Predicts chronicity and axial involvement

Rheumatoid factor and anti-CCP:

Negative (seronegative spondyloarthropathy)

Infection screen:

Urethral swab or first-void urine for Chlamydia PCR
Stool culture if enteric trigger suspected
May be negative if infection has cleared

Synovial Fluid Analysis

Gold standard to exclude septic arthritis:

WBC: 10,000-50,000/microL (inflammatory)
Predominantly neutrophils
Gram stain and culture NEGATIVE
Crystal analysis NEGATIVE

Imaging

Plain radiographs:

Often normal early in disease
Periosteal reaction at entheses (fluffy periostitis)
Asymmetric sacroiliitis (if axial involvement)
Erosions in chronic disease

MRI:

Synovitis, enthesitis, bone marrow edema
Useful for sacroiliac joint assessment
Detects early axial involvement

Ultrasound:

Synovial thickening and effusion
Enthesitis at Achilles, plantar fascia
Power Doppler shows active inflammation

Management

Acute Phase Management

Treat triggering infection:

Chlamydia: Azithromycin 1g single dose OR Doxycycline 100mg BD for 7 days
Test and treat sexual partners
Enteric infections usually self-limiting

NSAIDs (first-line for arthritis):

Indomethacin 50mg TDS or naproxen 500mg BD
Continue for 2-4 weeks minimum
Usually effective for joint symptoms

Intra-articular corticosteroids:

For persistent monoarthritis after excluding infection
Provide good symptom relief
Can be repeated if needed

Local measures:

Rest during acute phase
Physiotherapy as symptoms settle
Orthotics for enthesitis

This section covers the acute management of reactive arthritis.

Surgical Management

Indications for Surgery

Surgical intervention is rarely required in reactive arthritis. Indications include:

Joint destruction: Rare, but end-stage arthropathy may require arthroplasty
Tendon rupture: Achilles tendon rupture from chronic enthesitis
Persistent effusion: Arthroscopic synovectomy in refractory cases

Joint Aspiration Technique

Indication:

All acute monoarthritis requires aspiration
Therapeutic and diagnostic

Knee aspiration:

Sterile preparation
Superomedial or superolateral approach
Aspirate as much fluid as possible
Send for: Cell count, Gram stain, culture, crystals

Interpretation:

WBC greater than 50,000 - septic until proven otherwise
WBC 10,000-50,000 - inflammatory (reactive, crystal, early septic)
Negative culture and crystals supports reactive arthritis

This section covers joint aspiration for diagnosis.

Complications

Disease Complications

Chronic arthritis: 30-50% develop chronic or recurrent disease
Ankylosing spondylitis: May evolve to AS in HLA-B27+ patients
Vision loss: From untreated uveitis
Cardiovascular: Aortitis and conduction defects (rare)
Amyloidosis: Secondary amyloidosis in chronic disease

Prognosis

Self-limiting: 50% recover fully within 6 months
Recurrent: 15-30% have recurrent episodes
Chronic: 15-30% develop chronic disease
HLA-B27: Associated with worse prognosis

Evidence Base

Prolonged Antibiotics in Reactive Arthritis

Carter JD et al. • Arthritis Rheum (2010)

Key Findings:

6-month combination therapy improved outcomes
Effect seen in Chlamydia-triggered cases
Not effective for enteric-triggered disease

TNF Inhibitors in Reactive Arthritis

III

Flagg SD et al. • J Rheumatol (2005)

Key Findings:

Clinical improvement with TNF inhibitors
Used in NSAID and DMARD refractory cases
Similar efficacy to other spondyloarthropathies

Natural History of Reactive Arthritis

Leirisalo-Repo M et al. • Clin Rheumatol (2003)

Key Findings:

50% recover completely within 6 months
30-50% develop chronic disease
HLA-B27 predicts worse prognosis

Role of HLA-B27 in Reactive Arthritis

Sieper J et al. • Ann Rheum Dis (2002)

Key Findings:

HLA-B27 present in 60-80% of cases
Associated with axial involvement
Predicts chronic disease course

Exam Viva Scenarios

Practice these scenarios to excel in your viva examination

VIVA SCENARIOStandard

Scenario 1: Acute Reactive Arthritis

EXAMINER

"A 28-year-old man presents with an acutely swollen right knee 3 weeks after an episode of urethral discharge. He also has a red eye. The knee is warm and tender with a large effusion."

EXCEPTIONAL ANSWER

Thank you. This presentation is classic for reactive arthritis with the triad of arthritis, preceding urethritis, and conjunctivitis appearing 3 weeks after the triggering infection. However, I must first exclude septic arthritis. I would aspirate the knee urgently and send fluid for cell count, Gram stain, culture, and crystal analysis. In reactive arthritis, I expect inflammatory fluid with WBC 10,000-50,000 but negative cultures and crystals. I would also test for Chlamydia with a urine PCR or urethral swab, and check HLA-B27, ESR, and CRP. If septic arthritis is excluded, I would treat the Chlamydia with azithromycin 1g or doxycycline, and treat the arthritis with NSAIDs. Partner notification and treatment is also important. The conjunctivitis usually settles spontaneously but I would refer to ophthalmology if there is concern for uveitis.

KEY POINTS TO SCORE

Classic triad: arthritis + urethritis + conjunctivitis

Must aspirate to exclude septic arthritis

Test for and treat Chlamydia

NSAIDs first-line for arthritis

COMMON TRAPS

✗Assuming reactive arthritis without aspiration

✗Not treating the triggering infection

✗Missing partner notification

LIKELY FOLLOW-UPS

"What if cultures grow Neisseria gonorrhoeae?"

"What is the prognosis?"

"What features suggest progression to chronic disease?"

VIVA SCENARIOStandard

Scenario 2: Post-Enteric Reactive Arthritis

EXAMINER

"A 35-year-old woman presents with painful swollen ankles and right knee 2 weeks after a bout of bloody diarrhea while travelling in Southeast Asia. She is HLA-B27 positive."

EXCEPTIONAL ANSWER

Thank you. This is post-enteric reactive arthritis following presumed bacterial gastroenteritis acquired during travel. Common triggers include Salmonella, Shigella, Campylobacter, and Yersinia. The asymmetric oligoarthritis affecting lower limbs is typical. Her HLA-B27 positivity suggests a higher risk of chronic disease and possible axial involvement. I would aspirate the knee to exclude septic arthritis, send stool for culture although it may be negative after 2 weeks, and check inflammatory markers. Management would include NSAIDs as first-line. Antibiotics are generally not indicated for post-enteric reactive arthritis as the infection has typically cleared. I would counsel her about the prognosis - approximately 50% recover within 6 months but her HLA-B27 status means she has a higher risk of chronic disease. I would monitor for sacroiliac involvement and progression to spondyloarthropathy.

KEY POINTS TO SCORE

Post-enteric reactive arthritis from travel-acquired GI infection

Aspiration to exclude septic arthritis

HLA-B27 predicts worse prognosis

Antibiotics not usually needed for post-enteric

COMMON TRAPS

✗Prescribing unnecessary antibiotics

✗Not considering HLA-B27 implications for prognosis

✗Missing axial involvement

LIKELY FOLLOW-UPS

"When would you start DMARDs?"

"What is the role of biologics?"

"How would you monitor for axial involvement?"

VIVA SCENARIOStandard

Scenario 3: Mucocutaneous Features

EXAMINER

"A 25-year-old man with known reactive arthritis presents with painless lesions on his penis and hyperkeratotic papules on his soles. He is concerned about an STI."

EXCEPTIONAL ANSWER

Thank you. These findings are characteristic extra-articular manifestations of reactive arthritis, not an acute STI. The penile lesions you describe are likely circinate balanitis - painless erythematous erosions on the glans penis that are pathognomonic for reactive arthritis. The sole lesions are keratoderma blennorrhagicum - psoriasiform hyperkeratotic papules that are histologically identical to pustular psoriasis. I would reassure him these are related to his reactive arthritis and not a new sexually transmitted infection. However, I would still screen for other STIs given the association with Chlamydia. Treatment is supportive - topical steroids may help. If he has ongoing active arthritis, we should ensure his NSAID therapy is optimised. These mucocutaneous features typically improve as the arthritis settles but can persist in chronic disease.

KEY POINTS TO SCORE

Circinate balanitis is pathognomonic for reactive arthritis

Keratoderma blennorrhagicum resembles pustular psoriasis

Reassure - not an acute STI

Treat underlying reactive arthritis

COMMON TRAPS

✗Misdiagnosing as STI

✗Not examining for mucocutaneous features

✗Missing opportunity to optimise arthritis treatment

LIKELY FOLLOW-UPS

"How would you differentiate from psoriatic arthritis?"

"What other skin/mucosal features occur?"

"How do you treat keratoderma?"

Australian Context

In Australia, reactive arthritis is encountered in both primary care and specialist settings. The most common trigger remains Chlamydia trachomatis, which is notifiable in all Australian states and territories. Notification and partner tracing are mandatory requirements.

PBS-listed medications:

NSAIDs: Various PBS listed for inflammatory conditions
Sulfasalazine: PBS listed for inflammatory arthropathies
Biologics: TNF inhibitors PBS listed for spondyloarthropathies (Authority Required)

Australian guidelines emphasize the importance of STI screening and partner notification in post-venereal reactive arthritis. Notifiable infections include Chlamydia, gonorrhoea, and enteric pathogens such as Salmonella and Campylobacter. Collaboration between rheumatology, sexual health, and infectious diseases services is important for comprehensive management.