Reactive arthritis is an inflammatory joint arthritis largely characterized by joint inflammation triggered by infection. To date, no diagnostic or classification criteria have been established, but in 2014, the American College of Rheumatology issued general treatment guidelines. In this article, we highlight a new review article on treatments for reactive arthritis.
Reactive arthritis is an inflammatory joint arthritis largely characterized by joint inflammation triggered by infection. To date, no diagnostic or classification criteria have been established, but in 2014, the American College of Rheumatology issued general treatment guidelines for the condition which is on the spondyloarthritis spectrum, which includes ankylosing spondylitis, psoriatic arthritis and arthritis associated with inflammatory bowel diseases.
Manuela Di Franco, M.D., of the University of Rome, Italy, outlines the pathogenesis, natural history, prognosis and treatment options in a review article published last month in the journal Clinical and Experimental Rheumatology. In this article, we cover the highlights.
THE PRESENCE OF INFECTION
Reactive arthritis includes any arthritis that is triggered by an infection. In this case, the most common infections include Chlamydia trachomatis and gastro-related infections, including Shigella, Salmonella, Yersinia and Campylobacter.
It is more common in men and in men and women who carry the HLA-B27 gene. It typically presents as sacroiliitis, enthesopathy and asymmetrical oligoarthritis of the lower limbs. But also includes other features often associated with rheumatic conditions, such as urethritis, iritis, conjunctivitis and mucocutaneous lesions (balanitis, keratoderma blenorrhagicum).
There is also “non-classical” reactive arthritis in which infections caused by Borrelia, Brucella, Haemophilus, Leptospira, Mycobacteria, Neisseria, Staphylococcus, Streptococcus, Ureaplasma, BCG and Vibrio spp. These infections can cause polyarticular joint pain, but they are not associated with the HLA-B27 gene.
The most common presentation of reactive arthritis is monoarthritis or asymmetric oligoarthritis of the lower extremities. Typically, the symptoms start days to weeks following the primary infection.
While large joints are most often involved, the small joints of the hands can be affected too. The presence of plantar fasciitis or Achilles’ tendon enthesitis should raise the suspicion for reactive arthritis. Axial involvement is more common in HLA-B27 positive patients.
Extra articular involvement including uveitis may also be present. Skin and mucous membrane inflammation are more rare and cardiac involvement even more so.
Because of the broad spectrum of clinical manifestations, developing a validated set of diagnostic criteria is difficult for reactive arthritis.
Reactive arthritis carries a good prognosis and a self-limiting course with full recovery in three to five months. A smaller portion of reactive arthritis patients will develop a chronic course with symptoms for more than six months.
A small portion of reactive arthritis patients will go on to develop ankylosing spondylitis or radiological sacroiliitis. Clinicians should identify those with chronic symptoms early and institute aggressive treatment to prevent debilitating manifestations.
Poor prognostic signs include specific infections, HLA-B27 positivity, positive family history for spondyloarthritis or ankylosing spondylitis, and the presence of chronic gut inflammation. Salmonella induced reactive arthritis has been associated with a chronic course, as has Yersinia and Shigella triggered disease.
Data suggest that the prognosis is better for enteroarthritis than Chlamydia-induced reactive arthritis. The frequency of HLA-B27 among reactive arthritis patients ranges from 30-80 percent, and HLA-B27 carriers are more likely affected by severe disease, with frequent spine involvement, extra-articular features and a chronic course of arthritis.
Persistent gut inflammation appears to play a significant role in determining the course and prognosis of reactive arthritis.
There are three primary goals of reactive arthritis treatment:
• The triggering infection should be promptly identified and treated.
• Symptoms should be addressed and relieved.
• The clinician should act to minimize disability in chronic forms of reactive arthritis.
Evidence suggests that prompt antimicrobial treatment of the triggering infection can prevent the initiation and persistence of the arthritis, especially for uroarthritis. The goal of early antibiosis is to halt the spread of the organism or it’s antigens.
In terms of a Chlamydia trachomatis infection, a higher rate of recurrence dictates a longer antibiotic course (four to 12 weeks). There is less evidence for treating post-enteric reactive arthritis with antibiotics. These findings suggest that in post-enteric reactive arthritis, the pathogenic events leading to arthritis occur very early in the course of the infection, so that the introduction of antibiotic therapy may be too late to influence the disease course. The exception to this appears to be salmonella where antibiotic treatment reduced the chance of musculoskeletal involvement.
MANAGEMENT OF ACUTE ARTHRITIS
NSAIDs are first line therapy for acute reactive arthritis. Due to individual responses to the different drugs it is suggested to attempt several NSAIDs for at least two to four weeks at full dose before shifting to another one. Treatment with glucocorticoids should be considered in case of inadequate response to NSAIDs or persistent active disease for more than four weeks and may be given via infiltration.
If patients develop chronic arthritis or acute arthritis resistant to NSAIDs or glucocorticoids, it is appropriate to treat them with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). Since reactive arthritis is often self-limiting, patients should be observed for several months before instituting DMARDs to prevent overtreatment. With the exception of sulfasalazine, the evidence for csDMARDs in reactive arthritis is scant. Otherwise, methotrexate and azathioprine have been used successfully in refractory reactive arthritis.
While TNF inhibitors have an impressive track record in the treatment of axial and peripheral manifestations of ankylosing spondylitis, there are few data on their use in reactive arthritis. A few case series have described the usefulness of etanercept and infliximab for reactive arthritis with positive clinical and histological results. It has also been shown that deficiencies in TNF alpha may influence the chronicity of reactive arthritis. Consideration should be taken with regards to biologics predisposing to other infections.
The use of long-term antibiotic treatment for patients with reactive arthritis is controversial. Tetracycline class drugs have shown promise in Chlamydial reactive arthritis utilizing a three-month course. Studies on long-term ciprofloxacin or azithromycin monotherapy showed lack of efficacy. While antibiotic therapy may be very helpful in HLA-B27 patients, a recent systematic review and meta-analysis showed no significant beneficial effect of antibiotics on remission and clinical features of the disease, while showing a significant increase in adverse events. Combination therapy with more than one antibiotic may emerge as an effective treatment for reactive arthritis.
Finally, targeted biologics such as tocilizumab have showed promise owing to their ability to mediate interleukins implicated in joint inflammation. Adequate clinical trials for the potential application of these agents in reactive arthritis are needed.
B. Lucchino, F. R. Spinelli, C. Perricone, et al. “Reactive arthritis: current treatment challenges and future perspectives.” Clinical and Experimental Rheumatology. May 22, 2019