Pediatric Antibiotic-refractory Lyme Arthritis: A Multicenter Case-control Study

Abstract

Objective: Few factors have consistently been linked to antibiotic-refractory Lyme arthritis (ARLA). We sought to identify clinical and treatment factors associated with pediatric ARLA.

Methods: We performed a case-control study in 3 pediatric rheumatology clinics in a Lyme-endemic region (2000-2013). Eligible children were aged ≤ 18 years with arthritis and had positive testing for Lyme disease by Western blot. Cases were 49 children with persistently active arthritis despite ≥ 8 weeks of oral antibiotics or ≥ 2 weeks of parenteral antibiotics; controls were 188 children whose arthritis resolved within 3 months of starting antibiotics. We compared preselected demographic, clinical, and treatment factors between groups using logistic regression.

Results: Characteristics positively associated with ARLA were age ≥ 10 years, prolonged arthritis at diagnosis, knee-only arthritis, and worsening after starting antibiotics. In contrast, children with fever, severe pain, or other signs of systemic inflammation were more likely to respond quickly to treatment. Secondarily, low-dose amoxicillin and treatment nonadherence were also linked to higher risk of ARLA. Greater antibiotic use for children with ARLA was accompanied by higher rates of treatment-associated adverse events (37% vs 15%) and resultant hospitalization (6% vs 1%).

Conclusion: Older children and those with prolonged arthritis, arthritis limited to the knees, or poor initial response to antibiotics are more likely to have antibiotic-refractory disease and treatment-associated toxicity. Children with severe symptoms of systemic inflammation have more favorable outcomes. For children with persistently active Lyme arthritis after 2 antibiotic courses, pediatricians should consider starting antiinflammatory treatment and referring to a pediatric rheumatologist.

Keywords: EPIDEMIOLOGIC STUDIES; LYME ARTHRITIS; PEDIATRIC ARTHRITIS; RISK FACTORS.

Figure 1.

Subject selection diagram ARLA, antibiotic-refractory Lyme arthritis; m, months; WB IgG, Western Blot immunoglobulin G This flow chart details the process of selecting 237 study participants (49 cases and 188 controls) after exclusion of 331 children without documented Lyme arthritis and 148 others who did not meet criteria for either cases or controls.