title: Epidemiology of Clostridium difficile Infection-Associated Reactive Arthritis in Children: An Underdiagnosed, Potentially Morbid Condition.
abstract: The incidence of Clostridium difficile infection has increased among children. The epidemiology of pediatric C difficile infection-associated reactive arthritis is poorly understood.
  
  
  
  To characterize the incidence, recognition, and distinguishing clinical features of pediatric C difficile infection-associated reactive arthritis among children with C difficile infection.
  
  
  
  In this cohort and nested case-control study using electronic health records from January 1, 2004, to December 31, 2013, across 3 geographically diverse pediatric health care networks, we screened for reactive arthritis among 148 children between ages 2 and 21 years with diagnostic or procedural codes suggesting musculoskeletal disease associated with C difficile diagnosis or positive testing. We identified 26 cases with acute arthritis or tenosynovitis within 4 weeks before to 12 weeks after confirmed C difficile infection with (1) no alternative explanation for arthritis and (2) negative synovial cultures (if obtained). Network-matched C difficile-infected controls without arthritis were randomly selected at the time of cohort member C difficile infections.
  
  
  
  Incidence of C difficile infection-associated reactive arthritis was calculated based on (1) pediatric source population and (2) children with C difficile infection. Characteristics of cases and controls were compared using conditional logistic regression.
  
  
  
  Based on the cases identified within the source population of the 3 hospital networks, we estimated that C difficile infection-associated reactive arthritis incidence was 5.0 cases per million person-years (95% CI, 3.0-7.8). Reactive arthritis affected 1.4% of children with C difficile infection yearly (95% CI 0.8%-2.3%). Joint symptoms began a median of 10.5 days after initial gastrointestinal symptoms, often accompanied by fever (n = 15 [58%]) or rash (n = 14 [54%]). Only 35% of cases of C difficile infection-associated reactive arthritis were correctly diagnosed by treating health care professionals (range across centers, 0%-64%). Five affected children (19%) were treated for presumed culture-negative septic hip arthritis despite having prior postantibiotic diarrhea and/or other involved joints. Compared with controls, cases of C difficile infection-associated reactive arthritis were less likely to have underlying chronic conditions (odds ratio [OR], 0.3; 95% CI, 0.1-0.8). Although all cases had community-onset C difficile infection and fewer comorbidities, they were more likely to be treated in emergency departments and/or hospitalized (OR, 7.1; 95% CI, 1.6-31.7).
  
  
  
  C difficile infection-associated reactive arthritis is an underdiagnosed, potentially morbid reactive arthritis associated with C difficile infection occasionally misdiagnosed as septic arthritis. Given the rising incidence of pediatric C difficile infections, better recognition of its associated reactive arthritis is needed.
authors.affiliation: Rutgers Biomedical and Health Sciences, New Brunswick, New Jersey2 Division of Pediatric Rheumatology, Department of Pediatrics, Nemours A.I. duPont Hospital for Children, Wilmington, Delaware3Center for Clinical Epidemiology and Biostatistics, Department.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Horton
authors.affiliation: Rutgers Biomedical and Health Sciences, New Brunswick, New Jersey3Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Strom
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Putt
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, Nemours A.I. duPont Hospital for Children, Wilmington, Delaware.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Rose
authors.affiliation: Division of Pediatric Rheumatology, Department of Pediatrics, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia.
authors.forename: David D
authors.initials: DD
authors.lastname: Sherry
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Infection Prevention and Control, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia.
authors.forename: Julia S
authors.initials: JS
authors.lastname: Sammons
mesh_terms: D000293:Adolescent; D016918:Arthritis, Reactive / Q000175:diagnosis / Q000453:epidemiology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003015:Clostridium Infections / Q000175:diagnosis / Q000453:epidemiology*; D003691:Delaware / Q000453:epidemiology; D003937:Diagnosis, Differential; D003951:Diagnostic Errors / Q000706:statistics & numerical data; D005260:Female; D005431:Florida / Q000453:epidemiology; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008297:Male; D015143:Philadelphia / Q000453:epidemiology; D012189:Retrospective Studies; D055815:Young Adult