Orthopaedic Surgery - Reactive Arthritis

Basics

Reactive arthritis is an:

Inflammatory arthritis that develops after an infection elsewhere in the body

most commonly following:

Genitourinary infection

or

Gastrointestinal infection.

The joint itself is typically:

Sterile, meaning the triggering organism is not usually cultured from the affected joint.

Reactive arthritis was historically called:

Reiter syndrome.

The older term is now used less commonly.

Disease Group

Reactive arthritis belongs to the family of:

Seronegative spondyloarthritides.

Related conditions include:

Ankylosing spondylitis

Psoriatic arthritis

Enteropathic arthritis

These disorders share features such as:

Enthesitis

Axial involvement

HLA-B27 association

and typically negative:

Rheumatoid factor.

Classic Triad

The traditional triad consists of:

Urethritis or cervicitis

Conjunctivitis

Arthritis

However, all three features are present simultaneously in only a minority of patients.

Therefore, absence of the complete triad:

Does not exclude reactive arthritis.

Diagnostic Challenges

The diagnosis may be missed because:

Genitourinary symptoms may be mild

Conjunctivitis may be transient

Cervicitis may be asymptomatic

and the arthritis may resemble:

Other spondyloarthritides

or

Disseminated gonococcal infection.

Prevention

Preventive strategies focus on reducing exposure to triggering infections.

These include:

Barrier contraception

Safer sexual practices

Appropriate food handling

Good hygiene

Avoidance of contaminated food and water

Epidemiology

Reactive arthritis most commonly affects:

Young and middle-aged adults.

One historical series reported a mean age at onset of approximately:

38 years.

Incidence

The true incidence is uncertain and varies by:

Population

Triggering organism

Diagnostic criteria

HLA-B27 prevalence

Historical population studies reported rates such as approximately:

3.5 per 100,000 men younger than 50 years per year

in certain populations.

Sex

Sex distribution depends partly on the triggering infection.

Historically, sexually acquired reactive arthritis was recognized more commonly in:

Men

whereas post-enteric disease may affect both sexes.

Risk Factors

Important risk factors include:

Recent sexually transmitted infection

Recent bacterial gastroenteritis

HLA-B27 positivity

HIV infection

Exposure to enteric pathogens

Higher-risk sexual exposure

Genetics

Reactive arthritis does not follow a simple Mendelian inheritance pattern.

The major genetic association is:

HLA-B27.

HLA-B27

A substantial proportion of affected patients are:

HLA-B27 positive.

Older studies reported positivity in approximately:

50–80% of patients, although the proportion varies greatly by population and case definition.

Clinical Significance of HLA-B27

HLA-B27 appears to increase susceptibility to:

More severe disease

Axial involvement

and

Chronic or recurrent symptoms

but it is neither necessary nor sufficient for diagnosis.

A negative HLA-B27 test does not exclude:

Reactive arthritis.

Etiology

Reactive arthritis is believed to result from:

An immune response triggered by infection

rather than direct infection of the joint.

Genitourinary Triggers

The most important sexually transmitted trigger is:

Chlamydia trachomatis.

Other Chlamydia species have historically been investigated, including:

Chlamydia pneumoniae.

Enteric Triggers

Recognized gastrointestinal triggers include:

Salmonella

Shigella

Campylobacter

Yersinia

and other enteric infections.

Other Reported Organisms

Older literature has also reported associations with organisms such as:

Ureaplasma

and selected parasitic enteric infections including:

Giardia

and

Cryptosporidium.

The strength of these associations is less consistent than for the classic bacterial triggers.

Pathophysiology

The triggering infection activates an abnormal inflammatory immune response.

Microbial antigens may persist in host tissues and stimulate:

Synovial inflammation

Enthesitis

Axial inflammation

and

Mucocutaneous disease.

Associated Conditions

Reactive arthritis may occur in patients with:

HIV infection.

It may also overlap clinically with other:

Spondyloarthritides.

Diagnosis

Diagnosis is primarily:

Clinical.

There is no single definitive laboratory test.

The diagnosis is supported by:

Characteristic arthritis

Recent infection

Extra-articular manifestations

and exclusion of:

Septic arthritis

Gonococcal infection

and other inflammatory arthritides.

Timing

Symptoms usually begin approximately:

1–4 weeks after the triggering infection.

Genitourinary Manifestations

Urethritis is a classic feature.

Urethritis in Males

Men may develop:

Dysuria

Urethral discomfort

Mucopurulent urethral discharge

Symptoms may be mild.

Genitourinary Symptoms in Females

Women may develop:

Dysuria

Vaginal discharge

Cervicitis

Vaginitis

However, cervicitis may be:

Asymptomatic.

This can make recognition more difficult.

Ocular Manifestations

Conjunctivitis occurs in a substantial proportion of patients, historically around:

30–50%.

It is often:

Bilateral

Mild

and

Self-limited.

Mild Conjunctivitis

Some patients experience only:

Morning crusting

Mild redness

or

Eye irritation

and may not consider the symptom significant.

Uveitis

Less commonly, patients may develop:

Acute anterior uveitis.

This is more serious and may produce:

Severe eye pain

Marked redness

Photophobia

Blurred vision

and requires urgent ophthalmologic assessment.

Musculoskeletal Manifestations

The most characteristic joint pattern is:

Acute asymmetric oligoarthritis of the lower extremities.

Joint Findings

Affected joints may demonstrate:

Effusion

Marked tenderness

Warmth

Erythema

Pain with active and passive movement.

Joint Distribution

Commonly involved joints include:

Knees

Ankles

Feet

Upper-extremity joints may also be involved, but less commonly.

Number of Joints

Reactive arthritis often involves:

Only a few joints at a time.

Historical reports described an average of approximately:

Four joints

with one or two substantially more symptomatic than the others.

Axial Disease

Axial involvement may include:

Sacroiliitis

and

Spondylitis.

These are more common in:

Chronic disease.

Back and Buttock Pain

Inflammation of the sacroiliac joints may cause:

Low-back pain

Alternating buttock pain

and

Morning stiffness.

Hip Involvement

The hip is:

Less commonly involved

than the knees, ankles, and feet.

Enthesitis

Enthesitis is inflammation where a:

Tendon or ligament inserts into bone.

It is a characteristic manifestation of reactive arthritis.

Heel Pain

Common sites include the:

Achilles tendon insertion

and

Plantar fascia origin.

This produces characteristic:

Heel pain.

Dactylitis

Inflammation involving an entire digit may produce:

Dactylitis

or

Sausage digit.

This may involve the toes or fingers and also occurs in:

Psoriatic arthritis.

Tendon Involvement

Inflammation around the extensor tendons of the toes may contribute to:

Diffuse digital swelling.

Mucocutaneous Manifestations

Skin and mucosal findings may develop:

Several weeks after the triggering infection.

Keratoderma Blennorrhagicum

Keratoderma blennorrhagicum consists of:

Vesicular or pustular lesions

that evolve into:

Hyperkeratotic plaques

most commonly on the:

Palms

and

Soles.

These lesions may resemble:

Psoriasis.

Circinate Balanitis

Circinate balanitis produces:

Painless superficial lesions around the glans penis.

These lesions are usually:

Self-limited.

Oral Lesions

Patients may develop:

Small, shallow, painless oral erosions

usually affecting the:

Buccal mucosa

or other oral surfaces.

Nail Changes

Nails may become:

Thickened

Opaque

Brittle

and may resemble:

Fungal infection

or psoriatic nail disease.

History

Because the classic triad is present in fewer than one-third of patients at a single examination, careful history-taking is essential.

Important questions include:

Recent diarrhea

Recent urethral or genital symptoms

Recent sexual exposure

Eye irritation

Heel pain

Skin lesions

Oral lesions

Sexual History

A respectful sexual history is particularly important when:

Chlamydial infection

is suspected.

Physical Examination

A complete examination should include:

All symptomatic joints

Entheses

Spine and sacroiliac joints

Skin

Nails

Eyes

and, when clinically appropriate,

Genitourinary examination.

Joint Examination

Assess for:

Effusion

Warmth

Erythema

Tenderness

Pain with passive motion

Restriction of motion.

Spine Examination

Evaluate:

Lumbar motion

Sacroiliac tenderness

and signs of:

Inflammatory back pain.

Laboratory Tests

Laboratory studies are supportive rather than diagnostic.

Inflammatory Markers

Patients may demonstrate elevated:

ESR

and

CRP.

Blood Count

Possible findings include:

Leukocytosis

and

Mild anemia.

Autoantibodies

Reactive arthritis is usually:

Rheumatoid factor negative

and

ANA negative.

This is why it is categorized among the:

Seronegative spondyloarthritides.

HLA-B27 Testing

HLA-B27 testing may support the diagnosis in selected patients and may help characterize:

Risk of axial or chronic disease.

It is not required in every case.

Synovial Fluid

Joint aspiration may reveal:

Inflammatory synovial fluid

with elevated white blood cell count, often predominantly:

Neutrophils.

Synovial Culture

Synovial fluid cultures are generally:

Negative

in true reactive arthritis.

This helps distinguish it from:

Septic arthritis.

Joint Aspiration

Any acutely swollen joint in which infection is possible should be aspirated to evaluate for:

Septic arthritis

Crystal arthritis

and other causes.

Genitourinary Testing

Modern testing typically uses:

Nucleic acid amplification testing

for:

Chlamydia trachomatis

and other sexually transmitted pathogens when indicated.

Urinalysis

Sterile pyuria may occur.

A first-void urine specimen may demonstrate:

White blood cells without bacterial growth.

Stool Testing

If there has been recent diarrhea, stool testing may be useful early in the course to identify:

Enteric pathogens.

By the time arthritis develops, the gastrointestinal infection may already have resolved.

Imaging

Plain Radiographs

Radiographs may initially be:

Normal.

They become more useful in:

Persistent or chronic disease.

Chronic Radiographic Changes

Possible findings include:

Joint-space loss

Erosive change

Deformity

Sacroiliitis

Enthesitis

Periosteal reaction or bony proliferation may develop near:

Entheses

such as the:

Calcaneus.

MRI

MRI can be useful when evaluating:

Early sacroiliitis

Enthesitis

or persistent joint inflammation not apparent on radiographs.

Differential Diagnosis

The differential diagnosis includes other:

Seronegative spondyloarthritides

as well as infectious arthritis.

Psoriatic Arthritis

Psoriatic arthritis may also cause:

Dactylitis

Enthesitis

Nail changes

and asymmetric arthritis.

Evidence of:

Psoriasis

or characteristic nail disease supports that diagnosis.

Ankylosing Spondylitis

Ankylosing spondylitis more typically produces:

Chronic axial symptoms

Sacroiliitis

and inflammatory back pain.

Enteropathic Arthritis

Enteropathic arthritis occurs in association with:

Inflammatory bowel disease

such as:

Crohn disease

or

Ulcerative colitis.

Gonococcal Arthritis

Disseminated gonococcal infection is an important alternative diagnosis because it may present with:

Arthritis

Tenosynovitis

Skin lesions

and a history of sexual exposure.

Unlike reactive arthritis, this represents:

Active infection requiring antibiotic treatment.

Septic Arthritis

Any single severely inflamed joint must be evaluated for:

Septic arthritis

because delayed treatment can rapidly destroy cartilage.

Crystal Arthritis

Gout and CPPD may mimic acute reactive arthritis.

Joint aspiration with:

Crystal analysis

helps distinguish these disorders.

Treatment

General Principles

Treatment focuses on:

Controlling inflammation

Maintaining joint function

and

Treating any persistent triggering infection.

The arthritis itself is generally not caused by live organisms within the joint.

Activity

Prolonged bed rest should be avoided because it promotes:

Muscle atrophy

Joint stiffness

Contracture.

Activity should increase gradually as symptoms improve.

Physical Therapy

Physical therapy should emphasize:

Maintenance of range of motion

Progressive strengthening

Postural exercises

and, in axial disease,

Spinal mobility.

NSAIDs

NSAIDs are generally first-line treatment for:

Arthritis

Enthesitis

and pain.

Examples historically include:

Indomethacin

although other NSAIDs may be used.

Corticosteroid Injection

For persistent inflammation in one or a few joints, an:

Intra-articular corticosteroid injection

may be useful once infection has been excluded.

Topical Corticosteroids

Selected skin lesions may respond to:

Topical corticosteroids.

Systemic Corticosteroids

Systemic corticosteroids may occasionally be considered for:

Severe polyarthritis

or significant extra-articular inflammation when other treatments are inadequate.

Antibiotics

Antibiotic treatment is indicated when there is:

Active Chlamydia infection

or another identifiable treatable infection.

Effect of Antibiotics on Arthritis

Treating the active infection is important for:

Eradication

and

Prevention of transmission.

However, antibiotics do not reliably shorten established post-enteric reactive arthritis.

The role of prolonged antibiotics in chronic Chlamydia-associated reactive arthritis has been studied, but treatment should be individualized.

Treatment of Sexual Partners

When a sexually transmitted infection such as Chlamydia is identified, appropriate:

Partner evaluation and treatment

are important to prevent:

Reinfection

and further transmission.

Sulfasalazine

Sulfasalazine may be useful in:

Persistent peripheral arthritis

that does not respond adequately to NSAIDs.

Methotrexate

Methotrexate may be considered for:

Severe chronic inflammatory disease

that remains active despite simpler treatment.

Biologic Therapy

Biologic agents such as:

TNF inhibitors

may be considered in selected patients with:

Chronic, refractory spondyloarthritis-type disease

under specialist supervision.

Surgery

Surgery is rarely required.

In patients with severe chronic joint destruction, procedures such as:

Joint arthroplasty

may eventually be necessary.

Follow-Up

Follow-up frequency depends on:

Disease severity

Number of involved joints

Extra-articular manifestations

Treatment used.

Historically, patients with persistent disease have been reassessed every:

3–6 months.

Referral

Specialist referral is appropriate for:

Persistent inflammatory arthritis

Axial disease

Joint destruction

Recurrent uveitis

Diagnostic uncertainty

or need for:

Disease-modifying therapy.

Prognosis

Most patients experience substantial improvement over:

Several months.

Many recover completely within approximately:

6–12 months.

Chronic Disease

A minority develop:

Persistent or recurrent arthritis.

Historical series have reported chronic disease in approximately:

15% of patients, although estimates vary.

Chronic Symptoms

Chronic disease may present with:

Persistent joint discomfort

Recurrent inflammatory flares

Enthesitis

Sacroiliitis

or

Spondylitis.

Joint Damage

Long-standing uncontrolled inflammation may eventually cause:

Permanent joint destruction

Deformity

and functional impairment.

Complications

Potential complications include:

Chronic arthritis

Recurrent arthritis

Sacroiliitis

Spondylitis

Persistent enthesitis

Joint destruction

Recurrent uveitis

Patient Monitoring

Follow-up should assess:

Joint swelling and tenderness

Range of motion

Enthesitis

Axial symptoms

Eye symptoms

Skin and nail changes

Functional status

Patients taking disease-modifying or immunosuppressive medication require appropriate:

Laboratory and clinical monitoring.

Key Principle

Reactive arthritis is a sterile inflammatory arthritis that typically develops several weeks after a genitourinary or gastrointestinal infection.

The classic triad of:

Arthritis, urethritis or cervicitis, and conjunctivitis

is often incomplete.

The typical musculoskeletal pattern is:

Asymmetric lower-extremity oligoarthritis with enthesitis, sometimes accompanied by dactylitis, mucocutaneous lesions, or sacroiliitis.

Treatment focuses on:

NSAIDs, preservation of motion, treatment of any active triggering infection, and escalation to disease-modifying therapy when inflammation becomes persistent or chronic.