When a patient presents with a history of Lyme disease and joint pain, it might be reasonable to assume that they're dealing with refractory Lyme arthritis. And in some cases, that's true. However, a new study(1) warns that systemic arthritis can also arise after Lyme disease, and that the Lyme history can confound the real diagnosis of an autoimmune disorder like rheumatoid arthritis or psoriatic arthritis.
"Making the distinction isn't always easy," said Sheila Arvikar, M.D., a rheumatologist at Massachusetts General Hospital.
Dr. Arvikar and her colleagues conducted a retrospective study of patients referred to the hospital's Lyme arthritis clinic between 2003 and 2015 and found 30 patients who were found to have a systemic autoimmune joint disease rather than Lyme arthritis. Compared to patients who did have Lyme arthritis, this group was older, more likely to have shown early symptoms of Lyme disease and more likely to have a family history of autoimmune disorders.
Lyme and arthritis
Lyme arthritis as a manifestation of Lyme disease has been well-known since the 1970s(2). As many as 60 percent of patients who aren't treated with antibiotics will experience Lyme arthritis(3). For most, treating the tick-borne Borrelia burgdorferi infection that causes Lyme also clears up the Lyme arthritis; a subset of patients, however, have antibiotic-refractory Lyme arthritis that requires treatment with anti-inflammatories.
Antibiotic-refractor Lyme arthritis appears to have an autoimmune component, Dr. Arvikar and her colleagues wrote online Sept. 16 in Arthritis & Rheumatology. It's associated with dysregulation of the CD4+ T effector/T regulatory ratio and with some HLA-DR alleles, for example. But Lyme arthritis is typically restricted to one joint (often the knee) and usually clears up with short-term treatment, Dr. Arvikar said.
Systemic arthritis, on the other hand, usually involves multiple joints and requires long-term treatment like any autoimmune disease. Prior research on systemic autoimmune arthritis after Lyme is minimal: One 1989 study (4) found that of 51 patients with reactive arthritis tested, 9 had antibodies for B. burgdorferi infection, indicating past Lyme. That study suggested that B. burgdorferi might be a potential trigger for autoimmunity, as other infections can be. In the intervening years, though, the link has not been proven.
The diagnosis of autoimmune disorders in patients with a history of Lyme could be a coincidence, Dr. Arvikar said. On the other hand, the median time from Lyme infection to new-onset joint symptoms in the autoimmune patients at Mass General's clinic was four months, which is similar to the timeframe for the development of Lyme arthritis.
"We think there may be a connection," Dr. Arvikar said.
Lyme arthritis versus systemic disease
Given that post-Lyme systemic autoimmunity can develop in a similar timeframe to Lyme arthritis, and that both conditions have overlapping symptoms, it's easy to misdiagnose, Dr. Arvikar said. She and her colleagues were motivated to study this patient group because they saw an increase of referrals to their clinic of patients thought to have Lyme arthritis who actually had rheumatoid arthritis, psoriatic arthritis, or spondyloarthritis.
"It seemed like they were suspected to continue to have Lyme disease or Lyme arthritis, so they kept being treated for those conditions rather than the appropriate treatment for the new type of arthritis," Dr. Arvikar said.
The researchers compared the 30 patients diagnosed with a systemic arthritic disorder to 43 patients enrolled in a Lyme arthritis cohort study from the same clinic. They discovered 15 cases of rheumatoid arthritis, 13 cases of psoriatic arthritis and 2 cases of spondyloarthritis. Compared with the Lyme arthritis cohort, the systemic autoimmune patients were older (median age 55 versus 44, p=0.03). They had higher body mass index measurements (P<0.0006), reflecting the known risk factor of obesity and elevated body weight for autoimmune disorders, particularly psoriatic arthritis. The systemic autoimmune patients were also more likely to have a first-order relative with an autoimmune disorder than the Lyme arthritis patients (P=0.0004).
Patients ultimately diagnosed with a systemic autoimmune were also more likely to have had early signs of Lyme Disease, including the characteristic bull's-eye rash and flu-like symptoms, compared with patients diagnosed with Lyme arthritis. This is consistent with Lyme arthritis as a manifestation of untreated disease, Dr. Arvikar said. As recognition of Lyme has become more widespread, those with early symptoms are likely to be treated and avoid Lyme arthritis.
Making the diagnosis
The key question is how to differentiate between three possibilities when joint pain emerges after Lyme disease, Dr. Arvikar said: Active joint infection (treatable with antibiotics), post-infectious Lyme arthritis (treatable with anti-inflammatories if previous antibiotic treatment was sufficient) and a secondary inflammatory arthritis emerging post-Lyme.
Family history of autoimmune disorders, elevated body mass index and older age are all demographic factors that might be red flags for the third possibility, Dr. Arvikar said. Doctors should particularly look for multiple joint involvement, as this is much more diagnostic of a condition like rheumatoid arthritis than Lyme arthritis. Many of the patients with psoriatic arthritis and spondyloarthritis had axial involvement, another red flag that may indicate that a patient does not have Lyme arthritis, she said.
Doctors should also ask about skin psoriasis, as that can be a strong indication that the problem is not Lyme arthritis, Dr. Arvikar said. Blood tests can reveal RA antibodies in many patients, though a subset will be seronegative, she said. A test for Lyme antibodies can be a useful test, as patients with Lyme arthritis typically have very high titers of Lyme antibodies. However, there is no commercially available test for Lyme antibody levels, Dr. Arvikar said, so this option is not widely available.
While antibiotic treatment is appropriate for patients with active joint infection, methotrexate is commonly used against post-infectious Lyme arthritis, she said. Thus, there is overlap between Lyme arthritis treatment and the first-line option against rheumatoid arthritis, but Lyme arthritis usually requires a shorter duration of treatment, she said.
Lyme cases are on the increase, Dr. Arvikar said, so it's quite likely that if there is a relationship between Lyme and later autoimmune disease, those post-Lyme disorders will rise, too.
"It's a possibility that [doctors] need to consider in people who develop arthritis after Lyme infection," she said.
1) Arvikar SL, Crowley JT, Sulka KB, Steere AC. Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthropathy, Following Lyme Disease. Arthritis & Rheumatology. 2016. doi:10.1002/art.39866.
2) Steere AC, Malawista SE, Snydman DR, Shope RE, Andiman WA, Ross MR, et al. Lyme arthritis: an epidemic of oligoarticular arthritis in children and adults in three Connecticut communities. Arthritis Rheum 1977;20:7-17
3) Steere AC, Schoen RT, Taylor E. The clinical evolution of Lyme arthritis. Ann Intern Med 1987; 107:725-31.
4) Weyand CM, Goronzy JJ. Immune responses to Borrelia burgdorferi in patients with reactive arthritis. Arthritis Rheum 1989; 32:1057-64.