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Original Investigation |

Epidemiology of Clostridium difficile Infection–Associated Reactive Arthritis in Children An Underdiagnosed, Potentially Morbid Condition Online Only

Daniel B. Horton, MD, MSCE1,2 ,3; Brian L. Strom, MD, MPH1,3; Mary E. Putt, PhD, ScD3; Carlos D. Rose, MD2 ; David D. Sherry, MD4; Julia S. Sammons, MD, MSCE5
[+] 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.
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Published online

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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Figure.
Patient Selection for Clostridium Difficile Infection–Associated Reactive Arthritis and C Difficile Infection

aInternational Classification of Diseases, Ninth Revision, Clinical Modification(ICD-9-CM) Current Procedural Terminology codes suggesting arthritis.

bICD-9-CM code 008.45 and/or positive C difficile testing.

cNot mutually exclusive.

dCases were matched to up to 4 controls by network and time of C difficile infection within 3 months; 2 cases had only 2 to 3 matched controls.

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