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Original Investigation
July 5, 2016

Epidemiology of Clostridium difficile Infection–Associated Reactive Arthritis in ChildrenAn Underdiagnosed, Potentially Morbid Condition

Author Affiliations
  • 1Rutgers Biomedical and Health Sciences, New Brunswick, New Jersey
  • 2 Division of Pediatric Rheumatology, Department of Pediatrics, Nemours A.I. duPont Hospital for Children, Wilmington, Delaware
  • 3Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
  • 4Division of Pediatric Rheumatology, Department of Pediatrics, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia
  • 5Division of Infectious Diseases, Department of Pediatrics, Infection Prevention and Control, Perelman School of Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia
JAMA Pediatr. 2016;170(7):e160217. doi:10.1001/jamapediatrics.2016.0217
Abstract

Importance  The incidence of Clostridium difficile infection has increased among children. The epidemiology of pediatric C difficile infection–associated reactive arthritis is poorly understood.

Objective  To characterize the incidence, recognition, and distinguishing clinical features of pediatric C difficile infection–associated reactive arthritis among children with C difficile infection.

Design, Setting, and Participants  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.

Main Outcomes and Measures  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.

Results  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).

Conclusions and Relevance  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.

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