Ophthalmology – Reactive Arthritis (Reiter Syndrome)

Basics

Description

Reactive arthritis (ReA) is an inflammatory seronegative spondyloarthritis that develops after certain genitourinary or gastrointestinal infections.

The traditional term:

Reiter syndrome

is now generally avoided; reactive arthritis is the preferred terminology.

The classic triad is:

• Arthritis
• Urethritis/cervicitis
• Conjunctivitis

However:

Most patients do not present with the complete triad.

Ocular involvement may include:

• Conjunctivitis
• Acute nongranulomatous anterior uveitis
• Episcleritis
• Rare keratitis or posterior-segment inflammation

The ophthalmically important complication is:

Recurrent anterior uveitis, which may threaten vision if inadequately treated.

Classification

Reactive arthritis belongs to the:

Spondyloarthritis spectrum

along with:

• Ankylosing spondylitis / axial spondyloarthritis
• Psoriatic arthritis
• Inflammatory bowel disease-associated arthritis

These disorders share associations with:

• HLA-B27
• Enthesitis
• Sacroiliitis
• Acute anterior uveitis

Epidemiology

Reactive arthritis typically affects:

• Adolescents
• Young adults

Historically, sexually acquired ReA has been reported more often in men.

The true incidence varies considerably according to:

• Population
• Triggering organism
• Diagnostic criteria
• Geographic region

HLA-B27

HLA-B27 is an important susceptibility and prognostic factor, but it is not required for diagnosis.

The frequency of HLA-B27 positivity varies substantially among cohorts and is generally lower than older estimates of 70–90%.

HLA-B27 positivity is associated with:

• More severe disease
• Sacroiliitis
• Recurrent disease
• Higher likelihood of acute anterior uveitis
• Greater risk of chronic spondyloarthritis phenotype

Important Diagnostic Principle

A positive HLA-B27 test:

Does not diagnose reactive arthritis.

A negative result:

Does not exclude it.

Testing is most useful when:

• Uveitis is recurrent
• Axial symptoms are present
• Spondyloarthritis is suspected
• Prognostic information is needed

Etiology

Reactive arthritis usually develops after infection with certain organisms.

The most important are:

Genitourinary

• Chlamydia trachomatis

Enteric

• Salmonella
• Shigella
• Campylobacter
• Yersinia

Other infectious triggers have been reported, but associations are less consistent.

Timing

Symptoms typically begin:

About 1–4 weeks after the triggering infection

The original infection may have:

• Resolved
• Been mild
• Gone unnoticed

by the time arthritis or uveitis appears.

Pathophysiology

Reactive arthritis is not usually caused by active organisms invading the joint.

Instead, it reflects:

Immune-mediated inflammation triggered by infection in a genetically susceptible host

Possible mechanisms include:

• Persistent bacterial antigens
• Innate immune activation
• Abnormal adaptive immune response
• HLA-B27-associated immune dysregulation

Sterile Arthritis

Joint inflammation is usually:

Culture-negative

hence the term:

Reactive arthritis

rather than septic arthritis.

However, septic arthritis must still be excluded when clinically suspected.

Chlamydia-Associated Disease

In Chlamydia-associated ReA, bacterial components may persist within host cells and contribute to prolonged immune activation.

Chlamydia remains one of the most important identifiable triggers of:

Sexually acquired reactive arthritis.

Enteric Reactive Arthritis

Reactive arthritis can follow gastroenteritis caused by:

• Salmonella
• Shigella
• Campylobacter
• Yersinia

The arthritis often begins after gastrointestinal symptoms have already improved.

Risk Factors

Important risk factors include:

• Recent Chlamydia infection
• Recent bacterial gastroenteritis
• HLA-B27
• Prior reactive arthritis
• Features of underlying spondyloarthritis

HIV

Reactive arthritis can occur in people living with HIV.

However, the relationship is complex because:

• Spondyloarthritis phenotypes overlap
• Infection patterns differ
• Effective antiretroviral therapy has altered epidemiology

HIV testing should be performed when clinically indicated, particularly in patients with:

• Sexually transmitted infection risk
• Unexplained systemic inflammatory disease

Systemic Clinical Features

Reactive arthritis typically causes:

Acute asymmetric oligoarthritis

predominantly affecting the:

• Knees
• Ankles
• Feet

Enthesitis

Inflammation at tendon or ligament insertion sites is characteristic.

Common sites include:

• Achilles tendon
• Plantar fascia

This may produce:

• Heel pain
• Achilles tenderness

Dactylitis

Some patients develop:

Dactylitis

or “sausage digit” swelling.

Axial Disease

Possible features include:

• Sacroiliitis
• Inflammatory back pain

Axial involvement is more likely in:

• HLA-B27-positive
• Recurrent/chronic disease

Genitourinary Manifestations

Symptoms may include:

• Dysuria
• Urethral discharge
• Urinary frequency
• Cervicitis

However, Chlamydia infection may be:

Asymptomatic

especially in women.

Mucocutaneous Findings

Characteristic findings include:

• Circinate balanitis
• Painless oral ulcers
• Keratoderma blennorrhagicum

Keratoderma Blennorrhagicum

This consists of:

• Hyperkeratotic
• Psoriasiform
• Sometimes pustular

lesions, commonly involving:

• Soles
• Palms

It may resemble psoriasis.

Ocular Manifestations

Ocular involvement is common enough to be clinically important.

The major manifestations are:

• Conjunctivitis
• Acute anterior uveitis

Less commonly:

• Episcleritis
• Scleritis
• Keratitis
• Posterior-segment inflammation

Conjunctivitis

Conjunctivitis often appears:

Early in the systemic illness

and may be:

• Bilateral
• Mild
• Self-limited

Symptoms include:

• Redness
• Irritation
• Tearing
• Mild discharge

It may resolve before the patient presents with arthritis.

Conjunctivitis Examination

Typical findings include:

• Diffuse conjunctival injection
• Mild papillary or follicular response
• Watery or mucoid discharge

Vision is usually:

Normal

unless another ocular complication is present.

Treatment of Conjunctivitis

Most uncomplicated conjunctivitis requires:

• Preservative-free lubricants
• Cold compresses

Topical antibiotics are not routinely required unless:

• Bacterial conjunctivitis is suspected separately

Acute Anterior Uveitis

The most important ocular manifestation is:

Acute nongranulomatous anterior uveitis

It resembles HLA-B27-associated uveitis seen in other spondyloarthropathies.

Typical Uveitis Pattern

Features include:

• Acute onset
• Usually unilateral at a given episode
• Pain
• Photophobia
• Ciliary injection
• Blurred vision
• Anterior chamber cells and flare

Disease may alternate between eyes over recurrent episodes.

Severe HLA-B27-Type Uveitis

More severe attacks may cause:

• Fibrin
• Hypopyon
• Posterior synechiae
• Marked anterior chamber reaction

A hypopyon in this setting is typically:

Sterile inflammatory material

but infectious endophthalmitis must be excluded when the clinical context is atypical.

Posterior Synechiae

Inflammation may cause adhesions between:

• Iris
• Anterior lens capsule

called:

Posterior synechiae

Cycloplegic/mydriatic therapy helps prevent or break early synechiae.

Uveitic Complications

Recurrent or poorly controlled inflammation may cause:

• Posterior synechiae
• Cataract
• Ocular hypertension
• Secondary glaucoma
• Cystoid macular edema
• Epiretinal membrane
• Vision loss

Keratitis

Corneal involvement is uncommon.

Reported findings include:

• Superficial punctate keratitis
• Peripheral inflammatory keratitis

Persistent focal ulceration should prompt investigation for:

• Infection
• Herpes simplex
• Other immune-mediated corneal disease

rather than automatically attributing it to reactive arthritis.

Diagnosis

Reactive arthritis is primarily a:

Clinical diagnosis

based on:

• Characteristic arthritis
• Compatible preceding infection
• Extra-articular findings

There is:

No single diagnostic laboratory test.

History

Ask about infection within the preceding several weeks.

Genitourinary History

Ask about:

• Dysuria
• Urethral/cervical discharge
• New sexual partner
• Known STI exposure

Gastrointestinal History

Ask about:

• Diarrhea
• Abdominal pain
• Foodborne illness
• Recent travel
• Similar illness among contacts

Musculoskeletal History

Ask about:

• Asymmetric joint swelling
• Knee or ankle pain
• Heel pain
• Morning stiffness
• Low back pain
• Buttock pain

Ophthalmic History

Ask about:

• Red eye
• Photophobia
• Eye pain
• Blurred vision
• Previous uveitis
• Alternating attacks between eyes

A patient with:

Pain + photophobia + reduced vision

requires assessment for uveitis rather than assuming simple conjunctivitis.

Physical Examination

Systemic examination should look for:

• Asymmetric oligoarthritis
• Enthesitis
• Dactylitis
• Sacroiliac tenderness
• Circinate balanitis
• Oral ulcers
• Keratoderma

Ophthalmic Examination

Perform:

• Visual acuity
• Pupils
• Slit-lamp examination
• IOP
• Dilated fundus examination when uveitis is present

Look specifically for:

• Anterior chamber cells
• Flare
• Fibrin
• Hypopyon
• Posterior synechiae
• Macular edema

Laboratory Evaluation

Tests should be targeted according to the suspected trigger and differential diagnosis.

Possible studies include:

• CBC
• CRP
• ESR

These may demonstrate inflammation but are:

Nonspecific.

Chlamydia Testing

The preferred test for suspected genital Chlamydia is:

Nucleic acid amplification testing (NAAT)

using:

• First-catch urine
• Vaginal/cervical swab
• Urethral specimen as appropriate

Gonorrhea Testing

Because sexually transmitted infections may coexist, testing commonly includes:

Neisseria gonorrhoeae NAAT

when sexually acquired disease is suspected.

Stool Testing

If gastrointestinal symptoms are:

• Recent
• Ongoing

stool culture or multiplex PCR may identify an enteric pathogen.

However, by the time arthritis appears, the gastrointestinal infection may already have cleared, so:

A negative stool test does not exclude post-enteric reactive arthritis.

HLA-B27 Testing

Consider HLA-B27 testing when:

• Recurrent anterior uveitis occurs
• Axial symptoms are present
• Diagnosis within the spondyloarthritis spectrum is uncertain
• Prognostic information is useful

It is not a screening test for every red eye or arthritis episode.

HIV and STI Screening

Depending on risk profile, consider:

• HIV testing
• Syphilis testing
• Other STI testing

particularly when Chlamydia-associated reactive arthritis is suspected.

Joint Aspiration

Synovial fluid analysis is important when the differential includes:

• Septic arthritis
• Crystal arthritis

Reactive arthritis usually shows:

• Inflammatory fluid
• Negative bacterial culture

Imaging

Imaging is not required for every acute case.

Depending on symptoms, studies may include:

• Plain radiographs
• Ultrasound
• MRI of sacroiliac joints

MRI is particularly useful when evaluating:

Early inflammatory sacroiliitis.

Differential Diagnosis

Important differentials include:

• Axial spondyloarthritis
• Psoriatic arthritis
• IBD-associated arthritis
• Septic arthritis
• Disseminated gonococcal infection
• Rheumatoid arthritis
• Crystal arthritis
• Lyme disease
• Sarcoidosis
• Behçet disease
• Systemic lupus erythematosus

Ophthalmic Differential Diagnosis

For acute red eye, consider:

• Conjunctivitis
• HLA-B27-associated anterior uveitis from another spondyloarthritis
• HSV/VZV anterior uveitis
• Syphilitic uveitis
• Sarcoid uveitis
• Behçet disease
• Infectious keratitis
• Scleritis

Treatment Principles

Treatment has three components:

1. Treat an active triggering infection when present
2. Control musculoskeletal inflammation
3. Treat ocular inflammation promptly

Antibiotic Treatment – Chlamydia

If active Chlamydia trachomatis infection is identified:

Treat according to current STI guidelines.

The goals are to:

• Eradicate infection
• Prevent transmission
• Prevent reinfection

Sexual partners also require:

• Evaluation
• Appropriate treatment

Antibiotics and Arthritis

An important distinction:

Antibiotics treat the infection, but they do not reliably terminate established reactive arthritis.

For post-enteric reactive arthritis after the infection has resolved:

Routine prolonged antibiotics are not recommended.

Chronic Chlamydia-Associated ReA

Prolonged combination antibiotic regimens have been investigated in selected chronic Chlamydia-associated disease, but this remains a:

Specialist and nonroutine strategy

rather than standard management for all reactive arthritis.

Musculoskeletal Treatment

NSAIDs

First-line treatment for acute arthritis is usually:

NSAID therapy

assuming no contraindication.

Examples include:

• Naproxen
• Ibuprofen
• Celecoxib
• Other appropriate NSAIDs

There is no requirement to use indomethacin specifically.

Local Corticosteroids

For persistent inflammation involving one or a few joints:

Intra-articular corticosteroid injection

can be effective after septic arthritis has been excluded.

Systemic Corticosteroids

A short systemic corticosteroid course may be considered for:

• Severe polyarthritis
• Major extra-articular inflammation

when NSAIDs are inadequate.

DMARD Therapy

Persistent or chronic arthritis may require:

• Sulfasalazine
• Methotrexate

under rheumatology supervision.

Other conventional immunosuppressants are individualized rather than routine first choices.

Biologic Therapy

For chronic refractory spondyloarthritis-like disease, biologic therapy may be considered.

Options include:

• TNF inhibitors

depending on:

• Axial vs peripheral phenotype
• Previous treatment
• Comorbidities

This should be managed by rheumatology.

Treatment of Anterior Uveitis

The standard initial ocular treatment is:

Topical corticosteroid + cycloplegic/mydriatic

Topical Corticosteroid

For significant anterior chamber inflammation, commonly:

Prednisolone acetate 1%

is used frequently initially.

Severe disease may require dosing:

• Hourly while awake

followed by a:

Slow taper according to inflammatory response.

The taper should be based on:

• Anterior chamber cell
• Flare
• Symptoms

rather than a fixed schedule.

Cycloplegia

Options include:

• Cyclopentolate
• Homatropine
• Atropine in severe cases

Cycloplegics:

• Relieve ciliary spasm
• Reduce pain
• Prevent posterior synechiae
• Help break early synechiae

Severe or Refractory Uveitis

If topical therapy is insufficient, treatment may escalate to:

• Periocular corticosteroid
• Systemic corticosteroid
• Steroid-sparing immunomodulatory therapy

depending on:

• Severity
• Recurrence
• Bilateral involvement
• Posterior involvement

Recurrent Uveitis

Frequent recurrent attacks may require coordination between:

• Ophthalmology
• Rheumatology

Systemic therapy used for the underlying spondyloarthritis can sometimes reduce ocular recurrences.

Biologic Therapy and Uveitis

When biologic treatment is required for associated spondyloarthritis, certain monoclonal anti-TNF agents such as:

• Adalimumab
• Infliximab

have evidence for reducing recurrent anterior uveitis.

Not all TNF inhibitors have equivalent efficacy for ocular inflammation.

Monitoring During Uveitis Treatment

Monitor:

• Visual acuity
• Anterior chamber inflammation
• IOP
• Posterior synechiae
• Lens clarity
• Macula

Long-term topical corticosteroids can cause:

• Cataract
• Steroid-induced ocular hypertension/glaucoma

Prognosis

Reactive arthritis is often:

Self-limited

with substantial improvement over:

Several months

However, some patients develop:

• Recurrences
• Persistent arthritis
• Chronic spondyloarthritis

Chronic Disease Risk

Chronicity is more likely with:

• HLA-B27 positivity
• Severe initial disease
• Recurrent attacks
• Sacroiliitis
• Persistent inflammatory symptoms

Ocular Prognosis

Simple conjunctivitis usually has:

Excellent prognosis

Anterior uveitis also generally responds well when treated promptly.

Poorer outcomes are associated with:

• Repeated severe attacks
• Delayed treatment
• Cystoid macular edema
• Cataract
• Secondary glaucoma

Referral

Ophthalmology

Urgent assessment for:

• Photophobia
• Eye pain
• Reduced vision
• Suspected anterior uveitis

Rheumatology

Appropriate for:

• Significant arthritis
• Persistent symptoms
• Sacroiliitis
• Recurrent uveitis
• Suspected chronic spondyloarthritis

Sexual Health / Primary Care

For:

• Chlamydia or gonorrhea testing
• STI treatment
• Partner management

Ophthalmology Pearls

• Reactive arthritis is the preferred term; “Reiter syndrome” is now largely historical terminology.
• The classic triad is arthritis + urethritis/cervicitis + conjunctivitis, but the complete triad is uncommon.
• Major infectious triggers are Chlamydia trachomatis and the enteric organisms Salmonella, Shigella, Campylobacter, and Yersinia.
• Symptoms typically begin 1–4 weeks after the triggering infection, which may already have resolved.
• HLA-B27 is neither required nor diagnostic; it is most useful as a susceptibility and prognostic marker.
• The typical arthritis is asymmetric oligoarthritis of the lower extremities, often accompanied by enthesitis.
• Characteristic systemic findings include circinate balanitis, painless oral ulcers, and keratoderma blennorrhagicum.
• Conjunctivitis is usually an early, mild, self-limited manifestation and may have resolved by the time arthritis is diagnosed.
• The major vision-threatening manifestation is acute nongranulomatous anterior uveitis.
• Reactive-arthritis uveitis usually resembles other HLA-B27 anterior uveitis: acute, painful, photophobic, often unilateral, and sometimes fibrinous or hypopyon-forming.
• Pain, photophobia, and reduced vision in a patient thought to have “conjunctivitis” should prompt slit-lamp examination for anterior uveitis.
• First-line treatment of anterior uveitis is intensive topical corticosteroid plus cycloplegia, with treatment tapered according to clinical response.
• Monitor uveitis patients for posterior synechiae, cataract, steroid-induced IOP elevation, glaucoma, and cystoid macular edema.
• NAAT is preferred for Chlamydia and gonorrhea testing when sexually acquired disease is suspected.
• Treat active Chlamydia infection and sexual partners appropriately, but antibiotics do not reliably cure established reactive arthritis.
• Routine prolonged antibiotics are not recommended for post-enteric reactive arthritis once the gastrointestinal infection has resolved.
• Persistent arthritis may require NSAIDs, intra-articular steroids, sulfasalazine or methotrexate, and occasionally biologic therapy.
• In patients requiring systemic biologic therapy who also have recurrent uveitis, monoclonal anti-TNF agents such as adalimumab or infliximab may reduce ocular recurrences.
• Most patients improve, but a subset develops recurrent uveitis or chronic spondyloarthritis, making coordinated ophthalmology–rheumatology follow-up important.

Classification Reactive arthritis belongs to the: Spondyloarthritis spectrum along with:  Ankylosing spondylitis / axial spondyloarthritis Psoriatic arthritis Inflammatory bowel disease-associated arthritis  These disorders share associations with:  HLA-B27 Enthesitis Sacroiliitis Acute anterior uveitis

Epidemiology Reactive arthritis typically affects:  Adolescents Young adults  Historically, sexually acquired ReA has been reported more often in men. The true incidence varies considerably according to:  Population Triggering organism Diagnostic criteria Geographic region

HLA-B27 HLA-B27 is an important susceptibility and prognostic factor, but it is not required for diagnosis. The frequency of HLA-B27 positivity varies substantially among cohorts and is generally lower than older estimates of 70–90%. HLA-B27 positivity is associated with:  More severe disease Sacroiliitis Recurrent disease Higher likelihood of acute anterior uveitis Greater risk of chronic spondyloarthritis phenotype

Important Diagnostic Principle A positive HLA-B27 test: Does not diagnose reactive arthritis. A negative result: Does not exclude it. Testing is most useful when:  Uveitis is recurrent Axial symptoms are present Spondyloarthritis is suspected Prognostic information is needed

Etiology Reactive arthritis usually develops after infection with certain organisms. The most important are: Genitourinary  Chlamydia trachomatis  Enteric  Salmonella Shigella Campylobacter Yersinia  Other infectious triggers have been reported, but associations are less consistent.

Timing Symptoms typically begin: About 1–4 weeks after the triggering infection The original infection may have:  Resolved Been mild Gone unnoticed  by the time arthritis or uveitis appears.

Pathophysiology Reactive arthritis is not usually caused by active organisms invading the joint. Instead, it reflects: Immune-mediated inflammation triggered by infection in a genetically susceptible host Possible mechanisms include:  Persistent bacterial antigens Innate immune activation Abnormal adaptive immune response HLA-B27-associated immune dysregulation

Sterile Arthritis Joint inflammation is usually: Culture-negative hence the term: Reactive arthritis rather than septic arthritis. However, septic arthritis must still be excluded when clinically suspected.

Chlamydia-Associated Disease In Chlamydia-associated ReA, bacterial components may persist within host cells and contribute to prolonged immune activation. Chlamydia remains one of the most important identifiable triggers of: Sexually acquired reactive arthritis.

Enteric Reactive Arthritis Reactive arthritis can follow gastroenteritis caused by:  Salmonella Shigella Campylobacter Yersinia  The arthritis often begins after gastrointestinal symptoms have already improved.

Risk Factors Important risk factors include:  Recent Chlamydia infection Recent bacterial gastroenteritis HLA-B27 Prior reactive arthritis Features of underlying spondyloarthritis

HIV Reactive arthritis can occur in people living with HIV. However, the relationship is complex because:  Spondyloarthritis phenotypes overlap Infection patterns differ Effective antiretroviral therapy has altered epidemiology  HIV testing should be performed when clinically indicated, particularly in patients with:  Sexually transmitted infection risk Unexplained systemic inflammatory disease

Systemic Clinical Features Reactive arthritis typically causes: Acute asymmetric oligoarthritis predominantly affecting the:  Knees Ankles Feet

Enthesitis Inflammation at tendon or ligament insertion sites is characteristic. Common sites include:  Achilles tendon Plantar fascia  This may produce:  Heel pain Achilles tenderness

Dactylitis Some patients develop: Dactylitis or “sausage digit” swelling.

Axial Disease Possible features include:  Sacroiliitis Inflammatory back pain  Axial involvement is more likely in:  HLA-B27-positive Recurrent/chronic disease

Genitourinary Manifestations Symptoms may include:  Dysuria Urethral discharge Urinary frequency Cervicitis  However, Chlamydia infection may be: Asymptomatic especially in women.

Mucocutaneous Findings Characteristic findings include:  Circinate balanitis Painless oral ulcers Keratoderma blennorrhagicum

Keratoderma Blennorrhagicum This consists of:  Hyperkeratotic Psoriasiform Sometimes pustular  lesions, commonly involving:  Soles Palms  It may resemble psoriasis.

Ocular Manifestations Ocular involvement is common enough to be clinically important. The major manifestations are:  Conjunctivitis Acute anterior uveitis  Less commonly:  Episcleritis Scleritis Keratitis Posterior-segment inflammation

Conjunctivitis Conjunctivitis often appears: Early in the systemic illness and may be:  Bilateral Mild Self-limited  Symptoms include:  Redness Irritation Tearing Mild discharge  It may resolve before the patient presents with arthritis.

Conjunctivitis Examination Typical findings include:  Diffuse conjunctival injection Mild papillary or follicular response Watery or mucoid discharge  Vision is usually: Normal unless another ocular complication is present.

Treatment of Conjunctivitis Most uncomplicated conjunctivitis requires:  Preservative-free lubricants Cold compresses  Topical antibiotics are not routinely required unless:  Bacterial conjunctivitis is suspected separately

Acute Anterior Uveitis The most important ocular manifestation is: Acute nongranulomatous anterior uveitis It resembles HLA-B27-associated uveitis seen in other spondyloarthropathies.

Typical Uveitis Pattern Features include:  Acute onset Usually unilateral at a given episode Pain Photophobia Ciliary injection Blurred vision Anterior chamber cells and flare  Disease may alternate between eyes over recurrent episodes.

Severe HLA-B27-Type Uveitis More severe attacks may cause:  Fibrin Hypopyon Posterior synechiae Marked anterior chamber reaction  A hypopyon in this setting is typically: Sterile inflammatory material but infectious endophthalmitis must be excluded when the clinical context is atypical.

Posterior Synechiae Inflammation may cause adhesions between:  Iris Anterior lens capsule  called: Posterior synechiae Cycloplegic/mydriatic therapy helps prevent or break early synechiae.

Uveitic Complications Recurrent or poorly controlled inflammation may cause:  Posterior synechiae Cataract Ocular hypertension Secondary glaucoma Cystoid macular edema Epiretinal membrane Vision loss

Keratitis Corneal involvement is uncommon. Reported findings include:  Superficial punctate keratitis Peripheral inflammatory keratitis  Persistent focal ulceration should prompt investigation for:  Infection Herpes simplex Other immune-mediated corneal disease  rather than automatically attributing it to reactive arthritis.

Diagnosis Reactive arthritis is primarily a: Clinical diagnosis based on:  Characteristic arthritis Compatible preceding infection Extra-articular findings  There is: No single diagnostic laboratory test.

History Ask about infection within the preceding several weeks. Genitourinary History Ask about:  Dysuria Urethral/cervical discharge New sexual partner Known STI exposure  Gastrointestinal History Ask about:  Diarrhea Abdominal pain Foodborne illness Recent travel Similar illness among contacts

Musculoskeletal History Ask about:  Asymmetric joint swelling Knee or ankle pain Heel pain Morning stiffness Low back pain Buttock pain

Ophthalmic History Ask about:  Red eye Photophobia Eye pain Blurred vision Previous uveitis Alternating attacks between eyes  A patient with: Pain + photophobia + reduced vision requires assessment for uveitis rather than assuming simple conjunctivitis.

Physical Examination Systemic examination should look for:  Asymmetric oligoarthritis Enthesitis Dactylitis Sacroiliac tenderness Circinate balanitis Oral ulcers Keratoderma

Ophthalmic Examination Perform:  Visual acuity Pupils Slit-lamp examination IOP Dilated fundus examination when uveitis is present  Look specifically for:  Anterior chamber cells Flare Fibrin Hypopyon Posterior synechiae Macular edema

Laboratory Evaluation Tests should be targeted according to the suspected trigger and differential diagnosis. Possible studies include:  CBC CRP ESR  These may demonstrate inflammation but are: Nonspecific.

Chlamydia Testing The preferred test for suspected genital Chlamydia is: Nucleic acid amplification testing (NAAT) using:  First-catch urine Vaginal/cervical swab Urethral specimen as appropriate

Gonorrhea Testing Because sexually transmitted infections may coexist, testing commonly includes: Neisseria gonorrhoeae NAAT when sexually acquired disease is suspected.

Stool Testing If gastrointestinal symptoms are:  Recent Ongoing  stool culture or multiplex PCR may identify an enteric pathogen. However, by the time arthritis appears, the gastrointestinal infection may already have cleared, so: A negative stool test does not exclude post-enteric reactive arthritis.

HLA-B27 Testing Consider HLA-B27 testing when:  Recurrent anterior uveitis occurs Axial symptoms are present Diagnosis within the spondyloarthritis spectrum is uncertain Prognostic information is useful  It is not a screening test for every red eye or arthritis episode.

HIV and STI Screening Depending on risk profile, consider:  HIV testing Syphilis testing Other STI testing  particularly when Chlamydia-associated reactive arthritis is suspected.

Joint Aspiration Synovial fluid analysis is important when the differential includes:  Septic arthritis Crystal arthritis  Reactive arthritis usually shows:  Inflammatory fluid Negative bacterial culture

Imaging Imaging is not required for every acute case. Depending on symptoms, studies may include:  Plain radiographs Ultrasound MRI of sacroiliac joints  MRI is particularly useful when evaluating: Early inflammatory sacroiliitis.

Differential Diagnosis Important differentials include:  Axial spondyloarthritis Psoriatic arthritis IBD-associated arthritis Septic arthritis Disseminated gonococcal infection Rheumatoid arthritis Crystal arthritis Lyme disease Sarcoidosis Behçet disease Systemic lupus erythematosus

Ophthalmic Differential Diagnosis For acute red eye, consider:  Conjunctivitis HLA-B27-associated anterior uveitis from another spondyloarthritis HSV/VZV anterior uveitis Syphilitic uveitis Sarcoid uveitis Behçet disease Infectious keratitis Scleritis

Treatment Principles Treatment has three components:  Treat an active triggering infection when present Control musculoskeletal inflammation Treat ocular inflammation promptly

Antibiotic Treatment – Chlamydia If active Chlamydia trachomatis infection is identified: Treat according to current STI guidelines. The goals are to:  Eradicate infection Prevent transmission Prevent reinfection  Sexual partners also require:  Evaluation Appropriate treatment

Antibiotics and Arthritis An important distinction: Antibiotics treat the infection, but they do not reliably terminate established reactive arthritis. For post-enteric reactive arthritis after the infection has resolved: Routine prolonged antibiotics are not recommended.

Chronic Chlamydia-Associated ReA Prolonged combination antibiotic regimens have been investigated in selected chronic Chlamydia-associated disease, but this remains a: Specialist and nonroutine strategy rather than standard management for all reactive arthritis.

Musculoskeletal Treatment NSAIDs First-line treatment for acute arthritis is usually: NSAID therapy assuming no contraindication. Examples include:  Naproxen Ibuprofen Celecoxib Other appropriate NSAIDs  There is no requirement to use indomethacin specifically.

Local Corticosteroids For persistent inflammation involving one or a few joints: Intra-articular corticosteroid injection can be effective after septic arthritis has been excluded.

Systemic Corticosteroids A short systemic corticosteroid course may be considered for:  Severe polyarthritis Major extra-articular inflammation  when NSAIDs are inadequate.

DMARD Therapy Persistent or chronic arthritis may require:  Sulfasalazine Methotrexate  under rheumatology supervision. Other conventional immunosuppressants are individualized rather than routine first choices.

Biologic Therapy For chronic refractory spondyloarthritis-like disease, biologic therapy may be considered. Options include:  TNF inhibitors  depending on:  Axial vs peripheral phenotype Previous treatment Comorbidities  This should be managed by rheumatology.

Treatment of Anterior Uveitis The standard initial ocular treatment is: Topical corticosteroid + cycloplegic/mydriatic

Topical Corticosteroid For significant anterior chamber inflammation, commonly: Prednisolone acetate 1% is used frequently initially. Severe disease may require dosing:  Hourly while awake  followed by a: Slow taper according to inflammatory response. The taper should be based on:  Anterior chamber cell Flare Symptoms  rather than a fixed schedule.

Cycloplegia Options include:  Cyclopentolate Homatropine Atropine in severe cases  Cycloplegics:  Relieve ciliary spasm Reduce pain Prevent posterior synechiae Help break early synechiae

Severe or Refractory Uveitis If topical therapy is insufficient, treatment may escalate to:  Periocular corticosteroid Systemic corticosteroid Steroid-sparing immunomodulatory therapy  depending on:  Severity Recurrence Bilateral involvement Posterior involvement

Recurrent Uveitis Frequent recurrent attacks may require coordination between:  Ophthalmology Rheumatology  Systemic therapy used for the underlying spondyloarthritis can sometimes reduce ocular recurrences.

Biologic Therapy and Uveitis When biologic treatment is required for associated spondyloarthritis, certain monoclonal anti-TNF agents such as:  Adalimumab Infliximab  have evidence for reducing recurrent anterior uveitis. Not all TNF inhibitors have equivalent efficacy for ocular inflammation.

Monitoring During Uveitis Treatment Monitor:  Visual acuity Anterior chamber inflammation IOP Posterior synechiae Lens clarity Macula  Long-term topical corticosteroids can cause:  Cataract Steroid-induced ocular hypertension/glaucoma

Prognosis Reactive arthritis is often: Self-limited with substantial improvement over: Several months However, some patients develop:  Recurrences Persistent arthritis Chronic spondyloarthritis

Chronic Disease Risk Chronicity is more likely with:  HLA-B27 positivity Severe initial disease Recurrent attacks Sacroiliitis Persistent inflammatory symptoms

Ocular Prognosis Simple conjunctivitis usually has: Excellent prognosis Anterior uveitis also generally responds well when treated promptly. Poorer outcomes are associated with:  Repeated severe attacks Delayed treatment Cystoid macular edema Cataract Secondary glaucoma

Referral Ophthalmology Urgent assessment for:  Photophobia Eye pain Reduced vision Suspected anterior uveitis  Rheumatology Appropriate for:  Significant arthritis Persistent symptoms Sacroiliitis Recurrent uveitis Suspected chronic spondyloarthritis  Sexual Health / Primary Care For:  Chlamydia or gonorrhea testing STI treatment Partner management

Ophthalmology Pearls  Reactive arthritis is the preferred term; “Reiter syndrome” is now largely historical terminology. The classic triad is arthritis + urethritis/cervicitis + conjunctivitis, but the complete triad is uncommon. Major infectious triggers are Chlamydia trachomatis and the enteric organisms Salmonella, Shigella, Campylobacter, and Yersinia. Symptoms typically begin 1–4 weeks after the triggering infection, which may already have resolved. HLA-B27 is neither required nor diagnostic; it is most useful as a susceptibility and prognostic marker. The typical arthritis is asymmetric oligoarthritis of the lower extremities, often accompanied by enthesitis. Characteristic systemic findings include circinate balanitis, painless oral ulcers, and keratoderma blennorrhagicum. Conjunctivitis is usually an early, mild, self-limited manifestation and may have resolved by the time arthritis is diagnosed. The major vision-threatening manifestation is acute nongranulomatous anterior uveitis. Reactive-arthritis uveitis usually resembles other HLA-B27 anterior uveitis: acute, painful, photophobic, often unilateral, and sometimes fibrinous or hypopyon-forming. Pain, photophobia, and reduced vision in a patient thought to have “conjunctivitis” should prompt slit-lamp examination for anterior uveitis. First-line treatment of anterior uveitis is intensive topical corticosteroid plus cycloplegia, with treatment tapered according to clinical response. Monitor uveitis patients for posterior synechiae, cataract, steroid-induced IOP elevation, glaucoma, and cystoid macular edema. NAAT is preferred for Chlamydia and gonorrhea testing when sexually acquired disease is suspected. Treat active Chlamydia infection and sexual partners appropriately, but antibiotics do not reliably cure established reactive arthritis. Routine prolonged antibiotics are not recommended for post-enteric reactive arthritis once the gastrointestinal infection has resolved. Persistent arthritis may require NSAIDs, intra-articular steroids, sulfasalazine or methotrexate, and occasionally biologic therapy. In patients requiring systemic biologic therapy who also have recurrent uveitis, monoclonal anti-TNF agents such as adalimumab or infliximab may reduce ocular recurrences. Most patients improve, but a subset develops recurrent uveitis or chronic spondyloarthritis, making coordinated ophthalmology–rheumatology follow-up important.