Post-Lyme Arthritis: More than Lyme?

Persistent joint symptoms may represent a new-onset autoimmune disease

Nancy Walsh 09.25.2016

Senior Staff Writer, MedPage Today

Action Points

Persistent arthritis following Lyme disease may represent a new-onset systemic autoimmune disease rather than refractory Lyme arthritis, and clinical findings can help differentiate the two, a retrospective study suggested.

Among 30 patients diagnosed with rheumatoid arthritis, psoriatic arthritis, or spondyloarthropathy following an episode of Lyme disease, the disease more commonly manifested with polyarthritis and with lower titers of IgG antibodies to Borrelia burgdorferi than in a group of 43 patients with established Lyme arthritis, reported Sheila L. Arvikar, MD, and colleagues from the Center for Immunology and Inflammatory Diseases at Massachusetts General Hospital in Boston.

For instance, among the 15 patients who were diagnosed with rheumatoid arthritis, all had at least three or four affected joints, and of the 13 patients with psoriatic arthritis, all had at least two affected joints. In contrast, among the Lyme arthritis group, only one had polyarticular disease.

Moreover, the mean titer of antibodies to B. burgdorferi was 1:486 in the systemic autoimmune group compared with 1:15,733 in the post-Lyme arthritis group (P<0.0001), the researchers reported online in Arthritis & Rheumatology.

Since Lyme disease was first recognized in the late 1970s, the challenge of post-Lyme complications has remained controversial, particularly for arthritis. "The majority of Lyme arthritis patients respond to appropriate oral or intravenous antibiotic treatment, but some patients have persistent proliferative synovitis in previously infected joints, usually a knee, after 2 to 3 months of such therapy, termed post-infectious, antibiotic-refractory arthritis," the researchers explained.

The challenge for clinicians when a patient develops inflammatory arthritis following Lyme disease, is to determine whether the patient has a persistent infection of the joint, post-infectious arthritis, or a new-onset separate inflammatory arthritis.

To help address this challenge, Arvikar and colleagues analyzed demographic data, reviewed antibody test results, and compared clinical findings for patients seen at their center during the previous 13 years.

They noted that the number of patients presenting with any type of post-Lyme arthritis had increased over the study period, as had the number of those found to have a systemic autoimmune disease. During the most recent years (2013 to 2015), approximately one-third had Lyme arthritis that was responsive to antibiotic treatment, another third had Lyme arthritis that was refractory to treatment, and the remaining third were diagnosed with another systemic autoimmune disease.

Of the 30 patients found to have a systemic autoimmune disease, mean age was 55, which was older than the group who had Lyme arthritis, whose age averaged 44 years (P=0.03). They were more often male, which is unusual for systemic autoimmune disease, had higher body mass index (29 versus 24 kg/m2, P<0.0006), and more often had a family history of autoimmunity (57% versus 16%, P=0.0004).

Before the onset of arthritis, 57% of the systemic autoimmune group had the typical erythema migrans skin rash, and an additional 23% had other typical Lyme disease symptoms during the summer such as fever and arthralgias. All 30 of these patients had been treated for Lyme disease with oral and intravenous antibiotics according to the recommendations of the Infectious Diseases Society of America.

In contrast, among the 43 patients with persistent Lyme arthritis, only two had reported the skin rash -- and those two had not received antibiotic treatment at the time. Another seven had experienced summertime flu-like symptoms, but also had not been treated with antibiotics.

Additional differences between the groups included higher erythrocyte sedimentation rates and C-reactive protein levels in the systemic autoimmune disease group, while the Lyme arthritis group had higher levels of Lyme disease-associated autoantibodies such as apolipoprotein B-100 and matrix metalloproteinase-10.

With regard to treatment, the researchers explained that they recommended anti-inflammatory treatment for patients in the systemic autoimmune disease group, with steroids, nonsteroidal anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs), and tumor necrosis factor (TNF) inhibitors.

For all those with systemic autoimmune diseases who received these treatments, the arthritis was controlled. "However, six patients (20%) were reluctant to accept the diagnosis of a systemic autoimmune disease, and sought further treatment for Lyme disease elsewhere with additional courses of antibiotic therapy," Arvikar and colleagues wrote.

Among the 43 patients with Lyme arthritis, 26% responded to a month of oral antibiotic therapy, and another 19% who had persistent arthritis responded to an additional month of intravenous antibiotics. The remainder had persistent symptoms that were treated with DMARDs such as methotrexate or TNF inhibitors, and all had "marked improvement" within months.

As to why patients might develop systemic autoimmune disease following Lyme disease, the researchers noted that it could be coincidental, or that the infection might be sufficient to trigger a preclinical autoimmune state to active disease.

"Numerous infections have been hypothesized to serve as triggers for initiating clinical expression of rheumatoid arthritis or psoriatic arthritis. In addition to antigen-specific activation of lymphocytes, microbes can provide the secondary signal necessary for the induction of a pathogenic autoimmune response, referred to as the adjuvant effect of the infection."

Regardless of the reason, they advised, the treatment of these patients should rely on DMARDs, not further antibiotic courses. They mentioned the example of one patient who was diagnosed with rheumatoid arthritis and responded well to methotrexate, but subsequently sought treatment elsewhere with long-term antibiotics.

"Three years later, he returned in a wheelchair with radiographic erosions and deformities and contractures in multiple joints. Given a choice between Lyme arthritis and a chronic illness that may require lifelong immunosuppressive therapy, it is not surprising that patients would find Lyme arthritis a more attractive diagnosis," the authors wrote.

Their findings add to the evidence supporting the use of early, aggressive DMARD treatment of inflammatory arthritis in these circumstances, both to improve the likelihood of remission and to prevent poor clinical outcomes, they concluded.

The authors have received support from the National Institutes of Health, the English, Bonter, Mitchell Foundation, the Ounsworth-Fitzgerald Foundation, the Littauer Foundation, the Lillian B. Davey Foundation, the Eshe Fund, and the Rheumatology Research Foundation.

                  Reviewed by F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner