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DanNordström

Reactive Arthritis

Essentials

  • Reactive arthritis usually develops in response to an intestinal or sexually transmitted infection.
  • The majority of patients are HLA-B27 positive.
  • A sexually transmitted infection that precipitates reactive arthritis must always be treated with antimicrobials.
  • Other triggering microbes are usually not treated, if the patient is asymptomatic with respect to them.

Epidemiology

  • The annual incidence approximately 3 cases per 10 000 adults
  • The average age at disease onset is 20-30 years.
  • There is no sex predilection but symptoms are often more severe in men.
  • Pathogens considered certain to trigger reactive arthritis are Yersinia (picture 1), Salmonella, Shigella and Campylobacter. Uroarthritis is triggered by a chlamydial and gonococcal infection. Other microbes, such as Borrelia, E. coli, Chlamydia pneumoniae, Staphylococcus and Streptococcus have been associated with reactive arthritis as well. With the exception of Chlamydia pneumoniae, these are not equally clearly associated with HLA-B27 tissue type and hence the clinical picture may often be different. There is no difference between the occurrence rates of enteroarthritis and uroarthritis.
    • The synovial fluid is sterile in reactive arthritis, but Staphylococcus, Streptococcus, Salmonella, gonococci and Borrelia may also cause purulent arthritis.
  • At present, reactive arthritis that develops in response to Salmonella, Campylobacter or Chlamydia infection is the most common type. Reactive arthritis associated with Yersinia infection is now more rare.
  • 80% of patients with enteroarthritis and 60% of those with uroarthritis are HLA-B27 positive.

Clinical picture

  • The onset of reactive arthritis is often sudden about 1-4 weeks after the preceding infection. Fulminant disease is characterised by fever and a marked elevation of ESR and CRP levels. The involvement of several joints, the patient's age and the lack of underlying diseases best distinguish the condition from septic arthritis.
  • The preceding infection is symptomatic (diarrhoea or abdominal pain) in most, but not all, cases of enteroarthritis. The preceding genitourinary infection is often symptomatic in men (urethritis), but in women the infection may only have mild symptoms or is totally asymptomatic. A gonococcal infection may often cause inflammatory joint symptoms, but the so-called postgonococcal arthritis is probably most often precipitated by a concurrent infection with Chlamydia.
  • The inflammation almost always involves the large joints of the lower limbs
  • Joint inflammation of the upper limbs is seen in about 50% of patients
  • Extra-articular manifestations are frequent:
    • entesopathy, peritendinitis in 30-50%
    • symptomatic sacroiliitis in 20-30%
    • urethritis (may in association with an intestinal infection be reactive, i.e. sterile)
    • balanitis in 10-25% (circinate balanitis with annular lesions on the glans penis; picture 2)
    • conjunctivitis in 10-35%
    • iritis 2-4%
    • ECG changes in 5-15%
    • erythema nodosum Erythema Nodosum.

Diagnosis

  • There are no official diagnostic criteria, which is why the criteria for spondylarthritis may be relied on.
  • Synovial fluid analysis Investigation of Synovial Fluid
  • A stool culture and stool nucleic acid testing for Salmonella, Shigella, Campylobacter, Yersinia enterocolitica/pseudotuberculosis, Vibrio cholerae and E. coli strains that cause diarrhoea (EHEC, EAEC, EIEC, ETEC, EPEC), first-stream urine sample for nucleic acid testing of Chlamydia trachomatis and Neisseria gonorrhoeae, urinalysis, basic blood count with platelets, ESR, CRP, plasma creatinine, ALT, ALP and ECG should all be carried out during the first visit if reactive arthritis is suspected.
  • Crystal-induced arthritis should be considered as a diagnostic alternative especially in patients over 50 years of age.
  • The following tests are indicated at the first visit or within 1-3 weeks if the clinical picture and patient history are compatible with reactive arthritis:
    • anti-Yersinia antibodies
    • anti-Salmonella antibodies
    • anti-Campylobacter antibodies
    • anti-streptolysin if there is suspicion of rheumatic fever (in practice the disease is no longer encountered, and infections other than streptococcal may give false positive anti-streptolysin titres)
    • anti-staphylolysin (ASTA),anti-Borrelia antibodies Lyme Borreliosis (LB).
  • A chest x-ray should be taken to detect possible sarcoidosis. Radiographic findings of the joints are normal in early disease.
  • ECG should be recorded without much hesitation due to possible coexistence of (usually asymptomatic) carditis.
  • HLA-B27 testing aids the diagnosis in borderline cases, but there is no necessity to do the test, if the clinical picture is obvious and there is no doubt about the triggering infection.

Treatment Combination Antibiotics as a Treatment for Chronic Chlamydia-Induced Reactive Arthritis

  • Treatment of the infection
    • A sexually transmitted infection must always be treated with antimicrobials.
      • Chlamydia: azithromycin 1,000 mg as a single dose. Alternatively doxycycline 100 mg twice daily; the duration of treatment in primary infection is 14 days.
    • Enteroarthritis can be managed with a short course of antimicrobials (7-14 days) if diarrhoea is still present and the stool culture is positive.
  • Somewhat conflicting data exist on the benefit of antimicrobial therapy lasting for several months as regards the arthritis becoming prolonged or chronic. It may be beneficial in Chlamydia-induced arthritis, but a long course of antimicrobials is not the routine practice.
  • Treatment of an acute phase of arthritis

Prognosis

  • Reactive arthritis subsides in most cases within 6 months.
  • Approximately 15% of patients will develop chronic arthritis, more often in uroarthritis than in enteroarthritis.
  • Recurrent infections that activate the immune response, as well as HLA-B27 worsen the prognosis.

Prevention

  • The importance of avoiding infections with enteric bacteria or Chlamydia should be emphasised to a patient with a history of reactive arthritis.
    • It is advisable to use antimicrobial drugs if symptoms of gastrointestinal infection should occur when travelling abroad, but prophylactic antimicrobials to prevent gastrointestinal infections are not recommended Acute Diarrhoeal Disease in a Traveller.

References

  • Carter JD, Espinoza LR, Inman RD ym. Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial. Arthritis Rheum 2010;62(5):1298-307. [PubMed]

Evidence Summaries ⬆