Does this patient have reactive arthritis?
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. Traditionally, the arthritis has been described as “aseptic” (i.e. the living pathogen cannot be recovered from synovial specimens); however, bacterial DNA, antigenic proteins, and lipopolysaccharides may be detected within affected joints.
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. Dactylitis (“sausage digits”) may also occur. Extra-articular 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, but it is not a diagnostic test.
Relatively few organisms have been identified to cause reactive arthritis:
Urogenital infections – Chlamydia trachomatis
Enteric infections – Campylobacter, Enterobacteriae, Yersinia, Salmonella, Shigella, and Clostridium difficile
These infections can elicit a well-defined form of “classical” reactive arthritis. Arthritis may also follow other extra-articular infections (e.g. streptococcal, Borrelia, etc.), however, these do not carry the HLA-B27 association and in the case of spirochetal infections (Lyme, syphilitic arthritis) live organisms are present in the joints.
The diagnosis of reactive arthritis can be difficult as, by definition, the incident infection has often been treated and 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.
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. Somewhat uniquely, large knee effusions may occur, with only minimal other signs of inflammation (capsular tenderness, heat, redness).
Non-articular 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.
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, crystal associated, Lyme
Arthritis and enteritis- inflammatory bowel disease, Whipple’s disease, Behçet’s disease
Arthritis and urethritis – disseminated gonococcal infection
What tests to perform?
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. Although bacterial DNA may be detected in the synovial fluid, routine polymerase chain reaction testing of synovial fluid is not recommended as it will not change management.
Diagnostic tests should include:
Joint aspiration (to diagnose septic or crystal-induced arthritis)
Stool cultures (even in absence of diarrhea)
Urine testing for chlamydia (note that urethritis in reactive arthritis is often aseptic, and can follow GI infections)
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 recommended.
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 chronic arthritis, but are neither sensitive, nor specific for the diagnosis of reactive arthritis.
Routine imaging is not indicated in most cases; patients with chronic inflammatory low back pain should have imaging of their sacroiliac joints.
How should patients with reactive arthritis be managed?
The main goal treatment is alleviation of pain from inflammation. To this end NSAIDs and corticosteroid injections are the mainstay of treatment. Antibiotics are not used for the treatment of the arthritis and there is little role for antibiotics in patients found to have enteric infection. However, patients with prior C. trachomatis infection (and their sexual partners) should be treated in order to prevent future recurrences and urogenital complications, as well as to possibly minimize the symptoms of reactive arthritis following this specific infection.
NSAIDs: less than 2 weeks of continuous, high dose NSAID use may be warranted (e.g. indomethacin 50 mg three times daily or naproxen 500 mg twice daily).
Treatment of C. trachomatis (for patients and their sexual partners) with a regimen such as Azithromycin 1 gram orally (single dose) or Doxycycline 100 mg orally twice daily for 7 days.
Corticosteroid injections or systemic corticosteroids may be considered.
DMARDs (disease-modifying anti-rheumatic drugs): Sulfasalazine has been shown to be beneficial (vs. placebo) in patients with peripheral arthritis who do not respond to the above measures. Some authors suggest 500 mg twice daily, and up to a maximum of 1000 mg twice daily for 3-6 months. Other DMARDs have not been adequately studied.
Patient reassurance – most cases are self-limited.
What happens to patients with reactive arthritis?
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.
How to utilize team care?
Consider referral to a rheumatologist for outpatient follow-up. There is no defined interval for follow-up care.
Physical therapy referral might also be considered for these patients.
Are there clinical practice guidelines to inform decision making?
There are 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.
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.
What is the evidence?
Barber, CE, Kim, J, Inman, RD, Esdaile, JM, James, MT. “Antibiotics for treatment of reactive arthritis: a systematic review and metaanalysis”. J Rheumatol. vol. 40. 2013. pp. 916-928.
Carter, JD, Espinoza, LR, Inman, RD, Sneed, KB, Ricca, LR, Vasey, FB, Valeriano, J, Stanich, JA, Oszust, C, Gerard, HC, Hudson, AP. “Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial”. Arthritis Rheum. vol. 62. 2010. pp. 1298-1307.
Flores, D, Marquez, J, Garza, M, Espinoza, LR. “Reactive arthritis: newer developments”. Rheum Dis Clin North Am. vol. 29. 2003. pp. 37-59,vi.
Hannu, T, Inman, R, Granfors, K, Leirisalo-Repo, M. “Reactive arthritis or post-infectious arthritis?”. Best Pract Res Clin Rheumatol. vol. 20. 2006. pp. 419-433.
Manasson, J, Scher, JU. “Spondyloarthritis and the microbiome: new insights from an ancient hypothesis”. Curr Rheumatol Rep. vol. 17. 2015. pp. 1-8.
Morris, D, Inman, RD. “Reactive arthritis: developments and challenges in diagnosis and treatment”. Curr Rheumatol Rep. vol. 14. 2012. pp. 390-394.
Workowski, KA, Bolan, GA. “2015 Sexually transmitted diseases guidelines. Centers for Disease Control and Prevention”. MMWR Recomm Rep. 2015. pp. 64
Yli-Kerttula, T, Luukkainen, R, Yli-Kerttula, U, Möttönen, T, Hakola, M, Korpela, M. ” Effect of a three month course of ciprofloxacin on the late prognosis of reactive arthritis”. Ann Rheum Dis. vol. 62. 2003. pp. 880-884.
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- Does this patient have reactive arthritis?
- What tests to perform?
- How should patients with reactive arthritis be managed?
- What happens to patients with reactive arthritis?
- How to utilize team care?
- Are there clinical practice guidelines to inform decision making?
- Other considerations