Epidemiology of Clostridium difficile Infection-Associated Reactive Arthritis in Children: An Underdiagnosed, Potentially Morbid Condition

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.

Figure

Subject selection diagram for Clostridium difficile infection-associated reactive arthritis (cases) and Clostridium difficile infection (controls) ^a ICD-9-CM/CPT codes suggesting arthritis ^b ICD-9-CM code 008.45 and/or positive C difficile testing ^c Not mutually exclusive ^d Cases were matched to up to 4 controls by network and time of CDI ± 3 months; two cases had only 2-3 matched controls