Reactive Arthritis: An Evolving Role for Antibiotics?

August 3, 2010

How effective is antibiotic therapy for long-standing reactive arthritis?

How effective is antibiotic therapy for long-standing reactive arthritis?

Reactive arthritis, formerly called Reiter syndrome (that is, until the role of Hans Reiter as a Nazi war criminal was publicized), occurs in disparate situations, including some contingent on certain preceding infections. I used to teach about the microbial agents responsible for reactive arthritis with the mnemonic "SYC," which comprised a group containing 3 "S's" (Streptococci, Shigella, and Salmonella), a "Y" for Yersinia, and the "C" representing Campylobacter,Clostridium difficile, and Chlamydia.1-4 There may be other infectious agents responsible for other reactive arthritides, but the ones mentioned have been the major players.

So, why don't we obtain therapeutic benefit from antibiotics-the chronic arthritis is preceded by an infection-thereby successfully treating what can become a painful and crippling disease? Most of the later symptoms and signs of infection-related reactive arthritis are caused by "leftover" antigens and antibodies (as in rheumatic fever or poststreptococcal glomerulonephritis), not the intact organism itself. A recent study may have identified one situation-reactive arthritis after Chlamydia infection-wherein antibiotics do ameliorate the arthritis because the whole organism persists.5

A ROLE FOR ANTIBIOTICS IN CHLAMYDIAL REACTIVE ARTHRITIS

It appears that live Chlamydia organisms can persist in synovial tissues and peripheral blood mononuclear cells. Their continued presence can be detected by polymerase chain reaction (PCR) DNA-amplification techniques.6

Forty-two patients with chronic chlamydial reactive arthritis (proven by identification of Chlamydia DNA) were enrolled in the trial. There were 3 limbs in this study:

Patients who were taking doxycycline, 100 mg bid, plus rifampin, 300 mg/d.
Those randomized to azithromycin, 500 mg/d for 5 days and then twice weekly, plus rifampin, 300 mg/d.
The placebo group (no antibiotics).

Patients treated with antibiotics had a lower swollen joint count (P < .0001), a lower tender joint count (P < .0001), less low back pain (P < .002), less peripheral joint pain (P < .01), and a lower global assessment of disease activity (P < .008) than those who received placebo. In the placebo group, none of these outcome measures were improved at 6-month follow-up.

A STRIKING RESPONSE TO THERAPY

Bottom line, nearly two-thirds of those treated with antibiotics for chlamydial reactive arthritis responded to the antibiotic regimen, and 22% of these patients experienced a complete remission. These results are all the more striking in light of the fact that average disease duration in the study was 8.5 years. The study was not powered to detect a difference between the 2 antibiotic groups, however. More work will be required for this question as well as for optimum dosing.

Although the results are encouraging for 1 segment of the reactive arthritides, performing PCR evaluations in all persons with the syndrome is a financially daunting prospect. Further studies may clarify which patients are more likely to benefit.

References:

REFERENCES:

1.

Sarakbi HA, Hammoudeh M, Kanjar I, et al. Poststreptococcal reactive arthritis and the association with tendonitis, tenosynovitis, and enthesitis.

J Clin Rheumatol

. 2010;16:3-6.

2.

Schiellerup P, Krogfelt KA, Locht H. A comparison of self-reported joint symptoms following infection with different enteric pathogens: effect of HLA-B27.

J Rheumatol

. 2008;35:480-487.

3.

Söderlin MK, Alasaarela E, Hakala M. Reactive arthritis induced by

Clostridium difficile

enteritis as a complication of

Helicobacter pylori

eradication.

Clin Rheumatol

. 1999;18:337-338.

4.

Leirisalo-Repo M, Hannu T, Mattila L. Microbial factors in spondyloarthropathies: insights from population studies.

Curr Opin Rheumatol

. 2003;15:408-412.

5.

Carter JD, Espinoza LR, Inman RD, et al. Combination antibiotics as a treatment for chronic

Chlamydia

-induced reactive arthritis: a double-blind, placebo-controlled, prospective trial.

Arthritis Rheum

. 2010;62:1298-1307.

6.

Contini C, Grilli A, Badia L, et al. Detection of

Chlamydophila pneumoniae

in patients with arthritis: significance and diagnostic value.

Rheumatol Int

. 2010 Apr 10; [Epub ahead of print].

Dr Rutecki reports that he has no relevant financial relationships to disclose.