Dr. Kevin Yip

Dr Kevin Yip
Orthopaedic Surgeon
MBBS(UK), FRCS(EDIN), FAM(SING), FHKCOS(ORTHO)

Featured on Channel NewsAsia

Reactive Arthritis

Basics
Description
  • Reactive arthritis (previously called Reiter syndrome) is a form of reactive, inflammatory arthritis classically associated with urogenital, ocular, mucocutaneous, and musculoskeletal involvement.
  • This syndrome is categorized with the group of seronegative arthritides, along with AS, psoriatic arthritis, and enteropathic arthritis.
  • Diagnosis often is overlooked because of its variable presentation and the similarities with other seronegative arthritides and with gonococcal arthritis.
  • At examination, the classic triad of symptoms-urethritis (or cervicitis in females), conjunctivitis, and arthritis-often is not present or the symptoms of the urethritis or conjunctivitis are mild and not recognized or described by the patient.
  • Moreover, cervicitis often is asymptomatic, thus making the probability of missing the diagnosis in females even greater.
General Prevention
  • Barrier methods of contraception to prevent transmission of venereal disease
  • Proper food handling and preparation to prevent food-borne infection
Epidemiology
Mean age of onset in 1 study was 38 years.
Incidence
  • The incidence of reactive arthritis is unknown and appears to depend on the population studied.
  • Affects whites more than other racial groups because of the former’s higher frequency of the HLA-B27 gene.
  • In Rochester, MN, the incidence in males <50 years old was 3.5 per 100,000 .
Risk Factors
  • HIV
  • HLA-B27 haplotype
  • Poor hygiene with associated exposure to enteric pathogens
  • Increased sexual activity and thus wider exposure to sexually transmitted pathogens
  • Geographic location, although this may be related to hygienic conditions and sexual behavior of the population
Genetics
  • HLA-B27 gene: 60% of patients:
    • Persons with this gene are thought to be more susceptible to the disease.
    • 80% of affected individuals have this haplotype.
Etiology
  • The cause of the disease is thought to be an immune response to a sexually transmitted bacterial infection or to bacterial gastroenteritis.
  • Most cases are transmitted sexually, as opposed to enterically.
  • Organisms that have been associated with the disease include the following:
    • Chlamydia:
      • Chlamydia trachomatis and Chlamydia psittaci
      • Recent evidence shows that Chlamydia pneumoniae may be implicated.
    • Campylobacter fetus or Campylobacter fetus jejuni
    • Salmonella enteritidis, Salmonella heidelberg, or Salmonella paratyphi
    • Shigella flexneri
    • Ureaplasma urealyticum
    • Yersinia enterocolitica or Yersinia pseudotuberculosis
    • Giardia lamblia
    • Cryptosporidium
Associated Conditions
HIV syndromes
Diagnosis
Signs and Symptoms
  • The onset of the disease process generally occurs 2-4 weeks after enteric or sexually transmitted infection.
  • Urethritis (classic presentation):
    • Often the initial feature of the disease
    • Males experience mild dysuria and/or a mucopurulent urethral discharge.
    • Females may have dysuria, vaginal discharge, with or without purulent cervicitis/vaginitis.
    • Genitourinary symptoms may evolve after sexual or enteric exposure.
  • Conjunctivitis in 30-50% of patients:
    • Usually bilateral and can be as mild as onset of crusting of the eyelids each morning
    • As such, often unnoticed by patient and physician
    • Ocular involvement occurs along with urethral involvement, or within a few days of onset.
    • Less commonly seen but much more serious is unilateral, acute uveitis with associated severe ocular erythema and photophobia.
  • Articular involvement:
    • Most commonly includes acute oligoarticular arthritis with effusion, marked tenderness, and overlying erythema; a marked blue discoloration also appears sometimes.
    • Pain on active and passive ROM
    • The average number of joints involved is 4:
      • 1 or 2 joints have more severe involvement than do the others.
    • Typically involves lower extremities (knees, ankles, feet) asymmetrically, although upper extremity involvement may be present.
    • Axial involvement, with spondylitis or sacroiliitis:
      • Much more common in the chronic form
    • Rarely involves hip
    • Back pain and buttock pain are common.
  • Enthesopathies:
    • An enthesis is an insertion of a tendon or ligament into bone.
    • Very commonly involves the insertion of the Achilles tendon into the calcaneus or the plantar aponeurosis, causing characteristic heel pain
    • Involvement of the extensor hallucis longus or extensor digitorum longus tendons gives rise to sausage toes, a characteristic of reactive or psoriatic arthritis.
    • Although severe, the condition usually lasts only days to weeks before resolving.
  • Skin and mucous membrane involvement occur weeks after the inciting infection in 1 of several typical lesions.
    • In keratoderma blennorrhagica, clear vesicles erupt on the palms and soles, then crust, forming hyperkeratotic lesions that look similar to psoriasis.
    • Circinate balanitis is marked by small vesicles about the margins of the glans penis that are painless and self-limited.
    • Small, painless, shallow erosions occur in the buccal mucosa.
    • Fingernails and toenails are opaque and thickened, and can crumble and resemble mycotic infection.
History
  • The triad of urethritis, conjunctivitis, and arthritis is present in <1/3 of affected persons on examination.
  • Therefore, emphasis on the history, especially sexual history, is crucial!
Physical Exam
  • Given the often mild presentation, a thorough urogenital examination is important, especially in females.
  • All involved joints should be examined for the presence of effusion, surrounding erythema, and pain on passive and/or active ROM.
  • ROM of the lumbar spine
Tests
Lab
  • Positive HLA-B27 haplotype
  • Elevated ESR
  • Elevated C-reactive protein
  • Elevated C3 and C4 complement levels
  • Moderate leukocytosis with left shift
  • Mild anemia
  • Negative antinuclear antibody and rheumatoid factor
  • Joint fluid aspirate generally reveals an elevated white blood cell count with values from 500-50,000 with predominantly neutrophils.
  • Normal glucose and negative cultures, despite increased protein levels in the synovial fluid
  • Urethral swabs, cervical brushings, or fecal samples may be analyzed for chlamydial ribonucleic acid.
  • Sterile pyuria can be seen on 1st-voided morning urine sample.
Imaging
  • Radiographs are essential for documenting joint destruction: Obtain AP and lateral films.
  • Look for joint destruction, which may manifest as degenerative changes on either side of the involved joint and deformity.
  • Periosteal reactions indicating enthesitis can be seen at tendon insertions.
Differential Diagnosis
  • The differential diagnosis must include the other seronegative spondyloarthropathies: Psoriatic arthritis; AS; enteropathic arthritis
  • Psoriatic arthritis often presents with sausage digits, and enteropathic arthritis may be associated with gastrointestinal symptoms.
  • The differential diagnosis also must include gonococcal arthritis, which may present with urethritis and is associated with a positive sexual history.
Treatment
General Measures
Treatment is 2-fold, aimed at relieving the symptoms and eradicating the infection to prevent chronic reactive arthritis.
Activity
  • To prevent muscle atrophy or contractures, prolonged bed rest should be avoided.
  • Activity should be advanced as tolerated.
Special Therapy
Physical Therapy
A physical therapy program aimed at maintaining ROM should be instituted gradually.
Medication
First Line
  • NSAIDs:
    • Indomethacin (25-50 mg orally 4 times daily)
    • Sulfasalazine (2 g/day)
  • Steroids:
    • Intra-articular injection of steroids may be helpful.
    • Cutaneous lesions can be controlled with topical corticosteroids.
    • Limited scientific evidence suggests that long-term treatment with antibiotics is effective in shortening the acute course of the disease or in preventing chronic disease.
  • Antibiotics: Treatment of bacterial infections such as Chlamydia may help lessen chronic sequelae.
Second Line
  • Immunosuppressive agents:
    • Drugs such as methotrexate should be reserved for patients with severe, unremitting symptoms.
    • Disease-modifying agents such as TNF inhibitors may offer hope in the future for those affected with chronic disease.
Surgery
Occasionally, arthroplasty is necessary.
Follow-up
Patients are followed-up at 3-6-month intervals, depending on the severity of their symptoms.
Disposition
Issues for Referral
Joint destruction
Prognosis
  • The arthritis typically resolves over several months to a year and leaves no disability.
  • 15% of patients have chronic disease, typically marked by chronic joint discomfort with occasional exacerbations that are less severe than the initial presentation.
    • Chronic arthritis may lead to permanent joint destruction and deformity.
Complications
Chronic arthritis may occur.
Miscellaneous
Codes
ICD9-CM
099.3 Reiter syndrome
Patient Teaching
Prevention
  • Prevent sexually acquired disease by using condoms.
  • Prevent food-borne infection by following proper food-preparation techniques.
FAQ
Q: How often does reactive arthritis lead to chronic problems?
A: ~15% of people develop chronic disease; only 20% of those develop chronic arthritis.

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