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Antibiotics, DMARDs have role in lyme arthritis.

BOSTON -- Antibiotic therapy decreases the duration of persistent joint inflammation in Lyme arthritis, and disease-modifying antirheumatic drugs can reduce its severity in individuals with antibiotic-refractory disease, reported Dr. Alan Steere at a rheumatology conference sponsored by Harvard Medical School, Boston.

Antibiotics continue to be the cornerstone of treatment for Lyme arthritis, with the majority of patients responding to a 1-month course of oral doxycycline or amoxicillin, said Dr. Steere of Massachusetts General Hospital, Boston. In patients with mild, residual joint swelling, the oral antibiotic regimen is repeated for an additional 30 days. When joint swelling is moderate to severe, an additional month of intravenous antibiotic therapy with ceftriaxone, cefotaxime, or penicillin is a standard course, he said.

Management options have been less clear-cut, however, for patients with proliferative synovitis that persists for months or years despite antibiotic treatment, he said.

According to Infectious Diseases Society of America practice guidelines, patients with persistent postantibiotic joint swelling--whose joint fluid test results are negative for Borrelia burgdorferi, the spirochete implicated in Lyme arthritis--should be treated with nonsteroidal antiinflammatory agents, intra-articular corticosteroid injections, or disease-modifying antirheumatic drugs (DMARDs). The guidelines also state that arthroscopic synovectomy should be considered for swelling that persists longer than 12 months (Clin. Infect. Dis. 2000;31:S1-14).

To evaluate postantibiotic treatment strategies in refractory patients and to compare treatment and disease course in antibiotic-responsive and -refractory patients, Dr. Steere and his colleagues reviewed the outcomes of 117 patients seen from November 1987 through May 2004. Of those, 50 were antibiotic responsive, and 67 had antibiotic-refractory Lyme arthritis.

All of the patients in the study met the Centers for Disease Control and Prevention criteria for Lyme arthritis as well as the Infectious Diseases Society of America guidelines for antibiotic treatment. The groups did not differ in age, sex, clinical presentation, duration of arthritis prior to diagnosis, or standard lab testing, according to Dr. Steere. Although the antibiotic-refractory patients tended to receive intra-articular steroids more often than the antibiotic-responsive patients did, "the majority of the refractory patients were not given this medication," he said.

Comparisons between the responsive and refractory groups identified potential risk factors for antibiotic-refractory arthritis, including specific human histocompatibility leukocyte antigen-DR alleles, greater immune reactivity with the outersurface protein A epitope, and treatment with intra-articular steroids prior to antibiotic therapy, Dr. Steere said.

In terms of treatment course, "in patients with antibiotic-responsive arthritis, a 1-month course of oral doxycycline was usually successful, while patients with refractory arthritis tended to have persistent disease even after 2 months of oral antibiotics and 1 month of IV ceftriaxone," Dr. Steere said, adding that type of therapy (oral antibiotics alone or combined with intravenous antibiotics) did not correlate with the postantibiotic duration of arthritis.

Patients in the refractory group underwent one of two different postantibiotic treatment strategies. Of the 67 patients, 22 were treated with NSAIDs or intra-articular corticosteroids. If their arthritis persisted for 12-24 months, they underwent arthroscopic synovectomy, In the remaining 45 patients, DMARD treatment (primarily hydroxychloroquine) was added to the previous regimen if polymerase chain reaction (PCR) testing was negative for B. burgdorferi. If the arthritis persisted, patients were given oral methotrexate for 3-4 months or two to four infusions of intravenous inifliximab, after which arthroscopic synovectomy was offered, if needed.

At follow-up, data for 20 of the 22 patients treated with NSAIDs or intraarticular corticosteroids showed that 11 patients had complete resolution of arthritis within a median of 11 months after the start of antibiotic therapy, whereas 9 patients underwent arthroscopic synovectomies. "Arthritis resolved in the all of the patients within a median of 14 months," Dr. Steere said.

Of the 42 patients treated with DMARDs for whom follow-up was available, 34 had resolution of arthritis within a median of 8 months after the start of antibiotic therapy. Three of the remaining eight patients who did not respond to treatment with hydroxychloroquine elected to have arthroscopic synovectomies, which was successful in only one patient, Dr. Steere said.

The two patients in whom the synovectomies failed, along with the remaining five with unresolved arthritis, received methotrexate or intravenous inifliximab, he said. Although both of the drugs induced responses, he said, "inifliximab resuited in particularly marked reductions in joint inflammation."

Overall, arthritis persisted in the group of 42 patients who received DMARDs for a median of 9 months, Dr. Steere said. One patient in this group experienced a breakthrough case of persistent infection.

Based on these findings, a "reasonable management plan" for Lyme arthritis that persists after 60 days of antibiotics (including 30 days of intravenous therapy) should include an additional month of oral antibiotic therapy if PCR testing for B. burgdorferi DNA is still positive; treatment with NSAIDs if PCR results for B. burgdorferi DNA are negative; and the addition of 200 mg oral hydroxychloroquine twice daily if arthritis still persists, Dr. Steere said. If arthritis persists for 3-6 more months, arthroscopic synovectomy should be considered, he added.

Although DMARDs stronger than hydroxychloroquine were used in the investigation, "we're reluctant to recommend them, both because our limited experience with them doesn't prove efficacy and because of the possibility that they may be given to patients in whom the infection is still active," Dr. Steere noted.

Because Lyme arthritis eventually resolves even without antibiotic therapy, Dr. Steere and colleagues also sought to determine whether antibiotic treatment altered the natural course of the disease in patients with antibiotic-refractory arthritis.

To do this, they compared the current findings to those of 21 patients treated for Lyme arthritis in the late 1970s "before the etiologic agent of Lyme disease was known," Dr. Steere said. That group of patients received NSAIDs and intra-articular steroids, but not antibiotics, and experienced episodes of arthritis for a median period of 43 months.

In contrast, the median total time of arthritis episodes for the antibiotic-responsive patients and the antibiotic-refractory patients in the current study was 4 and 16 months, respectively. The finding suggests "antibiotic therapy decreases the period of joint inflammation, even in patients with antibiotic-refractory arthritis," he said.


New England Bureau
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Title Annotation:disease modifying antirheumatic drugs
Author:Mahoney, Diana
Publication:Family Practice News
Geographic Code:1USA
Date:Nov 1, 2006
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