Autoimmune Arthritides, Rheumatoid Arthritis, Psoriatic Arthritis, or Peripheral Spondyloarthritis Following Lyme Disease

Abstract

Objective: To describe systemic autoimmune joint diseases that develop following Lyme disease, and to compare their clinical features with those of Lyme arthritis (LA).

Methods: We reviewed records of all adult patients referred to our LA clinic over a 13-year period, in whom we had diagnosed a systemic autoimmune joint disease following Lyme disease. For comparison, records of patients enrolled in our LA cohort over the most recent 2-year period were analyzed. Levels of IgG antibodies to Borrelia burgdorferi and to 3 Lyme disease-associated autoantigens were measured.

Results: We identified 30 patients who had developed a new-onset systemic autoimmune joint disorder a median of 4 months after Lyme disease (usually manifested by erythema migrans [EM]). Fifteen had rheumatoid arthritis (RA), 13 had psoriatic arthritis (PsA), and 2 had peripheral spondyloarthritis (SpA). The 30 patients typically had polyarthritis, and those with PsA or SpA often had previous psoriasis, axial involvement, or enthesitis. In the comparison group of 43 patients with LA, the usual clinical picture was monoarticular knee arthritis, without prior EM. Most of the patients with systemic autoimmune joint disorders were positive for B burgdorferi IgG antibodies, as detected by enzyme-linked immunosorbent assay, but had significantly lower titers and lower frequencies of Lyme disease-associated autoantibodies than patients with LA. Prior to our evaluation, these patients had often received additional antibiotics for presumed LA, without benefit. We prescribed antiinflammatory agents, most commonly disease-modifying antirheumatic drugs, resulting in improvement.

Conclusion: Systemic autoimmune joint diseases (i.e., RA, PsA, SpA) may follow Lyme disease. Development of polyarthritis after antibiotic-treated EM, previous psoriasis, or low-titer B burgdorferi antibodies may provide insight into the correct diagnosis.

Figure 1

Duration from Lyme disease to onset of rheumatoid arthritis (RA), psoriatic arthritis or peripheral spondyloarthropathy (PsA/SpA). For comparison, the duration from erythema migrans, the initial skin lesion of the infection, to onset of Lyme arthritis (LA) is shown for historical patients seen in the late 1970s who were not treated with antibiotic therapy (4). Thus, the duration from erythema migrans to the development of arthritis was known.

Figure 2

The number of patients referred for presumptive Lyme arthritis over a 13-year period, according to the year of referral. The patients were stratified into 3 groups according to our diagnoses of post-Lyme systemic autoimmune joint diseases, antibiotic-refractory Lyme arthritis, or antibiotic-responsive Lyme arthritis.

Figure 3

Anti-Borrelia burgdorferi IgG antibody levels in post-Lyme systemic arthritis, rheumatoid arthritis, psoriatic arthritis or peripheral spondyloarthropathy, or antibiotic-refractory or antibiotic-responsive Lyme arthritis. Mean values and 1 standard deviation are shown. P=<0.0001 for the comparison of IgG antibody levels in the total Lyme arthritis group with each of the other 3 groups. The cut-off value for an equivocal Lyme IgG ELISA test in our laboratory is 400 units, and for a positive test is 800 units.

Figure 4

Levels of 3 Lyme-disease associated autoantibodies, endothelial cell growth factor (ECGF), apolipoprotein B100 (apoB100) and matrixmetalloproteinase-10 (MMP10), are shown for healthy controls (HC), patients with rheumatoid arthritis (RA) and psoriatic arthritis or spondyloarthropathy (PsA/SpA) who lacked a prior history of Lyme disease, patients with post-Lyme systemic autoimmune joint disorders (RA, PsA/SpA) and patients with Lyme arthritis, grouped by response to antibiotic treatment (responsive and refractory). Bars denote mean values. In the post-Lyme systemic arthritis group, white triangles represent patients with PsA/SpA, while black triangles represent RA patients. The shaded area represents values within 3 standard deviations of the mean value of the healthy control subjects. Statistical comparisons of antibody frequency between groups were performed using Fisher’s exact test.