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Reactive Arthritis

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Ovid: 5-Minute Orthopaedic Consult

Editors: Frassica, Frank J.; Sponseller, Paul D.; Wilckens, John H.
Title: 5-Minute Orthopaedic Consult, 2nd Edition
> Table of Contents > Reactive Arthritis

Reactive Arthritis
Chris Hutchins MD
Derek F. Papp MD
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 (1).
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 (2).
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 (3):
    • Persons with this gene are thought to be more susceptible to the disease.
    • 80% of affected individuals have this haplotype (4).
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 (5).
    • 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 (4):
    • 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 (6).
  • 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

P.357


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 (7).
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 (8).
    • Chronic arthritis may lead to permanent joint destruction and deformity.
Complications
Chronic arthritis may occur.
References
1. Savolainen
E, Kaipiainen-Seppanen O, Kroger L, et al. Total incidence and
distribution of inflammatory joint diseases in a defined population:
results from the Kuopio 2000 arthritis survey. J Rheumatol 2003;30:2460–2468.
2. Michet CJ, Machado EBV, Ballard DJ, et al. Epidemiology of Reiter’s syndrome in Rochester, Minnesota: 1950–1980. Arthritis Rheum 1988;31:428–431.
3. Ozgul A, Dede I, Taskaynatan MA, et al. Clinical presentations of chlamydial and non-chlamydial reactive arthritis. Rheumatol Int 2006;24:1–7.
4. Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Physician 2004;69:2853–2860.
5. Reveille
JD, Arnett FC, Keat A, et al. Seronegative spondyloarthropathies. In:
Klippel JH, ed. Primer on the Rheumatic Diseases,12th ed. Atlanta:
Arthritis Foundation, 2001:239–258.
6. Kiss
S, Letko E, Qamruddin S, et al. Long-term progression, prognosis, and
treatment of patients with recurrent ocular manifestations of Reiter’s
syndrome. Ophthalmology 2003;110:1764–1769.
7. Carter
JD, Valeriano J, Vasey FB. Doxycycline versus doxycycline and rifampin
in undifferentiated spondyloarthropathy, with special reference to
chlamydia-induced arthritis. A prospective, randomized 9-month
comparison. J Rheumatol 2004;31:1973–1980.
8. Colmegna I, Espinoza LR. Recent advances in reactive arthritis. Curr Rheumatol Rep 2005;7:201–207.
Additional Reading
Petersel DL, Sigal LH. Reactive arthritis. Infect Dis Clin North Am 2005;19:863–883.
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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