Hospital Medicine

Reactive arthritis

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I. What every physician needs to know.

Reactive arthritis is a spondyloarthritis that develops after an infection elsewhere in the body. Symptoms of arthritis generally develop between 1 week and 1 month after the incident infection. By definition, the arthritis is aseptic (i.e. the pathogen cannot be recovered from synovial specimens).

Patients with reactive arthritis experience a mono- or oligoarticular arthritis that may be accompanied by enthesitis (inflammation at the site where tendons or ligaments insert into bone), such as Achilles tendonitis or plantar fasciitis. "Sausage digits" may also occur. Extraarticular manifestations may include conjunctivitis, uveitis, balanitis or a papular rash on the soles and palms called keratoderma blenorrhagicum. The triad of oligoarticular arthritis, urethritis and conjunctivitis, formerly known as "Reiter's syndrome", constitutes the narrowest definition of (what is now known as) reactive arthritis.

Reactive arthritis is an uncommon, typically self-limited, disease affecting younger patients of both genders. Approximately 30-80% of patients with reactive arthritis are HLA-B27 positive and these patients may be more likely to develop chronic arthritis. It is unclear why HLA-B27 predisposes to reactive arthritis.

Relatively few organisms are known to cause reactive arthritis:

  • Urogenital infections -Chlamydia trachomatis

  • Enteric infections -Campylobacter,Yersinia,SalmonellaandShigella, as well asClostridium difficile

These infections result in a well-defined form of "classical" reactive arthritis. Additionally, arthritis may follow other extra-articular infections (e.g. streptococcal, Lyme, etc.) however, these do not carry the HLA-B27 association and many authors distinguish these as "post infectious" arthritis.

The diagnosis of reactive arthritis is difficult as, by definition, the incident infection has often resolved prior to the onset of the arthritis. The goal of lab testing is to identify infection (current or recent) with a known causative organism and to exclude alternate diagnoses. For similar reasons, treatment is aimed at symptom relief rather than treatment of the underlying infection.

For most patients, symptoms resolve within 6 months though a small percentage will go on to develop chronic arthritis.

II. Diagnostic Confirmation: Are you sure your patient has reactive arthritis?

There is no gold standard or accepted diagnostic/classification criteria for reactive arthritis. The diagnosis relies on a compatible history, exam findings and exclusion of alternate diagnoses. Reactive arthritis should be considered in a patient with mono- or oligoarticular arthritis who also has a history of recent diarrheal or urogenital infection. Alternate diagnoses should be excluded.

A. History Part I: Pattern Recognition:

The typical patient with reactive arthritis will present with joint pain and swelling in one or a few joints. Though the lower extremity joints are most commonly affected, upper extremity joints may also be involved. The patient may give a history of recent urethritis or diarrheal illness, typically within the preceding month, or may have lab evidence of preceding/ongoing infection. Additional history may reveal eye problems (red eye, painful eye) or rashes of the skin and genitals.

B. History Part 2: Prevalence:

The prevalence of reactive arthritis is estimated to be 30-40/100,000 adults. The incidence varies with the inciting pathogen and the population studied. It is estimated that 1-3% of patients with chlamydial urethritis and 6-30% of patients with enteritis (from one of the organisms mentioned above) will go on to develop reactive arthritis. Cases are usually sporadic, though outbreaks may occur.

As indicated above, 30-80% of patients with reactive arthritis are HLA-B27 positive.

C. History Part 3: Competing diagnoses that can mimic reactive arthritis.

The differential diagnosis for reactive arthritis will vary depending on the specific presentation. For patients presenting with the syndromes listed, consider the following differential diagnoses:

  • Acute monoarticular arthritis - septic, gout, Lyme, etc.

  • Arthritis and enteritis- inflammatory bowel disease, Whipple's disease, Behçet's disease, celiac disease, parasitic infections, etc.

  • Arthritis and urethritis - disseminated gonococcal infection.

D. Physical Examination Findings.

Physical exam may reveal a mono- or oligoarticular arthritis (swelling, erythema and pain of the affected joint). The arthritis is typically asymmetric. Dactylitis ("sausage digit") or enthesitis (swelling and tenderness over the Achilles tendon or plantar fascia where it inserts into the calcaneus) may also be present.

Nonarticular exam findings may include conjunctivitis or uveitis (former being more common) and oral ulcers. Skin exam may reveal circinate balanitis (shallow erosions on the penis with a serpiginous border) and/or keratoderma blenorrhagicum; a papular, hyperkeratotic, psoriatic-appearing rash on the palms and soles.

E. What diagnostic tests should be performed?

There are no diagnostic tests that confirm a diagnosis of reactive arthritis. The goal of lab testing is to identify infection (current or recent) with a known causative organism and to exclude alternate diagnoses.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Diagnostic tests should include:

  • Stool cultures (even in absence of diarrhea)

  • Urine testing for chlamydia

  • Joint aspiration (to rule out septic or crystal-induced arthritis)

Additional serologic tests for the other organisms known to cause reactive arthritis may be warranted in select cases (e.g. following travel to an endemic region), but are not routinely warranted.

The value of HLA-B27 testing is unclear and should not be implemented for all patients. According to some authors it is probably most useful diagnostically for patients with an intermediate pre-test probability of disease, however this use has not been validated in large-scale studies.

Other routine blood tests such as complete blood count (CBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be indicated as part of a work-up for monoarticular arthritis, but are neither sensitive, nor specific for the diagnosis of reactive arthritis.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Routine imaging is not indicated in most cases.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

See above.

III. Default Management.

The main goal treatment is alleviation of pain from inflammation. To this end NSAIDs and corticosteroid injections are the mainstay of treatment. There is little role for antibiotics in patients found to have enteric infection. However, patients with C. trachomatis infection (and their sexual partners) should be treated.

A. Immediate management.

  1. NSAIDs: less than 2 weeks of continuous, high dose NSAID use may be warranted (e.g. indomethacin 50mg three times daily)

  2. Treatment ofC.trachomatis (for patients and their sexual partners)

  3. Corticosteroid injections or systemic corticosteroids may be considered

  4. DMARDs (disease-modifying anti-rheumatic drugs): Sulfasalazine has been shown to be beneficial (vs placebo) in patients who do not respond to the above measures. Some authors suggest 500mg twice daily, and up to a maximum of 1000mg twice daily for 3-6 months. Other DMARDs have not been adequately studied.

  5. Patient reassurance - most cases are self limited

B. Physical Examination Tips to Guide Management.

Monitor the number of swollen/tender joints and presence of enthesitis.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

Not applicable.

D. Long-term management.

Most cases of reactive arthritis will resolve within 6 months. Chronic persistent arthritis, by definition, lasting more than 6 months, occurs in only a small percentage of patients. Long-term antibiotic therapy for patients with chronic arthritis has been studied with mixed results. Current consensus is that long-term antibiotics do not improve outcomes and are therefore not warranted.

IV. Management with Co-Morbidities

N/A

A. Renal Insufficiency.

Avoid NSAIDs. Consider corticosteroid injections or systemic corticosteroids for symptomatic management.

E. Diabetes or other Endocrine issues

Avoid systemic corticosteroids if possible.

I. Gastrointestinal or Nutrition Issues

Avoid NSAIDs in patients with a history of peptic ulcer disease.

V. Transitions of Care

B. Anticipated Length of Stay.

There are no guidelines governing hospitalization for patients with reactive arthritis. Most patients will be treated on an outpatient basis. Admission may be required for diagnosis and symptom management. Discharge is dependent on symptom control.

1. When should clinic follow up be arranged and with whom.

Consider referral to a rheumatologist for outpatient follow-up. There is no defined interval for follow-up care.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

None

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

None

E. Placement Considerations.

None

F. Prognosis and Patient Counseling.

It is important to reassure patients that most patients with reactive arthritis can expect complete resolution of their symptoms within several months.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

None

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

None

What's the evidence?

Hannu, T, Inman, R, Granfors, K, Leirisalo-Repo, M. "Reactive arthritis or post-infectious arthritis? Best Practice &". Research Clinical Rheumatology. vol. 20. 2006. pp. 419-433.

Rihl, R, Klos, A, Kohler, L, Kuipers, JG. "Reactive arthritis". Best Practice & Research Clinical Rheumatology. vol. 20. 2006. pp. 1119-1137.

Svenungsson, B. "Reactive arthritis". BMJ. vol. 308. 1994. pp. 671-672.

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