After a couple of weeks of relatively minor illnesses — an ear infection, which was treated, followed by a bout of diarrhea — a child’s new complaint about pain in her joints and difficulty walking has her parents worried enough to take her to the emergency room. When the doctor learns the child is having pain in her hip, he treats her aggressively on suspicion of septic arthritis, an infection in the joint that can be debilitating if left untreated for too long. The girl’s hip is punctured and drained, and she takes a full new round of antibiotics to knock out the infection.
But a different diagnosis requiring less aggressive treatment might have been more appropriate for the child in this scenario: reactive arthritis. According to a recent study published in JAMA Pediatrics, clinicians are underdiagnosing reactive arthritis associated with the bacterial infection Clostridium difficile in children. The study is noteworthy as the first epidemiological study of C. difficile-associated reactive arthritis. Prior research on this condition in both children and adults has consisted of case reports and series.
The researchers advise clinicians to remain attuned to signs of this rare but possible complication to help reduce misdiagnosis of septic arthritis and unwarranted excess treatment.
“In our study, in pediatric patients, involvement of the hip seemed to be more common in patients with C. difficile-associated reactive arthritis,” said the study’s senior author, Julia Sammons, MD, MSCE, hospital epidemiologist and medical director of the Department of Infection Prevention and Control at The Children’s Hospital of Philadelphia and assistant professor of Clinical Pediatrics at the Perelman School of Medicine at the University of Pennsylvania.
The choice to treat a child’s hip pain aggressively is understandable because septic arthritis is a serious clinical concern that should receive prompt treatment, Dr. Sammons said. However, in many cases like in the scenario above, children also have other symptoms that are better explained by reactive arthritis, which would warrant less intensive intervention.
One such sign is recent prior illness with diarrhea following antibiotic medications. This is a classic indicator of C. diffficile infection, a cause of gastrointestinal illness which tends to take hold opportunistically after people take antibiotics for other infections.
Another sign is pain in multiple joints. Reactive arthritis, an inflammatory response that can be triggered by infection as well as several other causes, commonly affects multiple joints, or migrates to affect different joints at different times. In contrast, septic arthritis is most often isolated to a single joint.
In nearly half of cases, Dr. Sammons and her colleagues found, clinicians treating children with these symptoms still suspected and even treated for septic arthritis, when perhaps a more cautious and watchful suspicion of C. difficile-associated reactive arthritis was needed.
Dr. Sammons and colleagues identified this trend by examining electronic health records from CHOP, Nemours A.I. DuPont Hospital for Children in Delaware, and Nemours Children’s Hospital in Florida to find cases in which children had confirmed cases of C. difficile infection and who had musculoskeletal symptoms within a period of weeks after their C. difficile infection. Reviewing those records in detail, they identified 26 cases in which the symptoms were consistent with reactive arthritis and there was no other documented possible cause for joint pain. They compared these cases to matched control cases of children with C. difficile infections but no musculoskeletal complaints.
In 12 of the 26 cases that the researchers presumed to be reactive arthritis, the clinicians treating the child suspected septic arthritis, despite symptoms suggestive of reactive arthritis such as pain in multiple joints and/or recent post-antibiotic diarrhea. In only nine of the 26 cases cases (35 percent) did the clinician treating the child actually attribute the symptoms as a side effect of C. difficile.
Since they comprehensively reviewed population-based data from multiple children’s hospitals, the researchers were able to describe common features of presumed cases, noting that most children had pain, swelling, and limited movement in multiple joints. A majority also reported joint pain that migrated to different joints. Compared to the control cases of patients who did not have musculoskeletal pain, the children with presumed cases of reactive arthritis were less likely to have underlying chronic health conditions.
The study data indicated that 1 to 2 percent of children infected with C. difficile may experience an associated case of reactive arthritis. The rate of the complication increased over the study period, consistent with a rise in C. difficile infection itself.
“This is an underdiagnosed but potentially morbid condition,” Dr. Sammons said. “Part of the takeaway message to clinicians is to consider the diagnosis of C. difficile-associated reactive arthritis in patients with a recent history of post-antibiotic diarrhea, particularly if they have multiple or migratory joint involvement, and in these patients to consider observation and supportive management rather than more aggressive intervention.”
Dr. Sammons credits the collaborative environment at CHOP and Penn for building the partnership needed to conduct this study. The first author, Daniel Horton, MD, MSCE, now a postdoctoral research fellow at Rutgers, was a former CHOP resident who approached Dr. Sammons with the idea for this study while pursuing a master’s degree in clinical epidemiology at Penn and a fellowship in rheumatology at A.I. DuPont.