Daniel B Horton1,2, Alysha J Taxter3,4, Amy L Davidow3,4, Brandt Groh3,4, David D Sherry3,4, Carlos D Rose3,4. 1. From the Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey; Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, New Brunswick, New Jersey; Department of Biostatistics - Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey; Department of Pediatrics, Brenner Children's Hospital, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina; Department of Pediatrics, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University, Wilmington, Delaware. daniel.horton@rutgers.edu. 2. D.B. Horton, MD, MSCE, Division of Pediatric Rheumatology, Rutgers Robert Wood Johnson Medical School, and Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, and Rutgers School of Public Health; A.J. Taxter, MD, MSCE, Brenner Children's Hospital, Wake Forest Baptist Medical Center; A.L. Davidow, PhD, Rutgers School of Public Health; B. Groh, MD, Penn State Milton S. Hershey Medical Center; D.D. Sherry, MD, Children's Hospital of Philadelphia, Division of Pediatric Rheumatology, Perelman School of Medicine, University of Pennsylvania; C.D. Rose, MD, Division of Rheumatology, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University. daniel.horton@rutgers.edu. 3. From the Department of Pediatrics, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey; Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, New Brunswick, New Jersey; Department of Biostatistics - Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey; Department of Pediatrics, Brenner Children's Hospital, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina; Department of Pediatrics, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Department of Pediatrics, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University, Wilmington, Delaware. 4. D.B. Horton, MD, MSCE, Division of Pediatric Rheumatology, Rutgers Robert Wood Johnson Medical School, and Rutgers Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, and Rutgers School of Public Health; A.J. Taxter, MD, MSCE, Brenner Children's Hospital, Wake Forest Baptist Medical Center; A.L. Davidow, PhD, Rutgers School of Public Health; B. Groh, MD, Penn State Milton S. Hershey Medical Center; D.D. Sherry, MD, Children's Hospital of Philadelphia, Division of Pediatric Rheumatology, Perelman School of Medicine, University of Pennsylvania; C.D. Rose, MD, Division of Rheumatology, Nemours/A.I. duPont Hospital for Children, Thomas Jefferson University.
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.
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.
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