Necrotizing Fasciitis After Varicella: An Association with Ibuprofen Use?

Source: Zer DM, et al. A case-control study of necrotizing fasciitis during primary varicella. Pediatrics 1999; 103:783-790.

Zer and associates at the children’s hospital in Seattle were impressed with what appeared to be an increase in the number of invasive Group A streptococcal infections (GAS), including cases of necrotizing fasciitis (NF) complicating varicella that were seen in their institution in 1993-1995. Previous reports had shown an eight times increased frequency of the use of ibuprofen in children who developed invasive GAS infections compared to controls; however, this increase was not statistically significant.1

Nineteen children were admitted to their hospital with NF complicating primary varicella. Demographic data, clinical parameters, and possible risk factors in these 19 children were compared to a control group of 29 children hospitalized with soft tissue infections other than NF within three weeks of varicella. There was no difference between the groups in clinical manifestations such as fever, pain, swelling, and erythema; use of acetaminophen and antibiotics was also similar. However, 9/19 cases with NF had used ibuprofen prior to hospitalization compared to 4/29 controls. The association was even stronger in only those NF cases with documented GAS infections, where 8/16 cases used ibuprofen compared with 0/8 controls (P = 0.02).

Several reasons for this apparent association have been suggested. These include a masking of local symptoms that might delay diagnosis as well as effects of ibuprofen on suppressing neutrophil function and augmentation of inflammatory cytokine production.

Although proof of an association of ibuprofen use and invasive GAS infections including NF would require a large-scale study—similar to the ones that showed a causal link with aspirin use and Reye’s syndrome2—pediatricians should discourage the use of ibuprofen in children with varicella until more information is available. Acetaminophen is the best alternative. This serious syndrome is also further ammunition for advocating routine varicella immunization.

References

1. Peterson CL, et al. Risk factors for invasive group A streptococcal infections in children with varicella: A case control study. Pediatr Infect Dis J 1996;15:151-156.

2. Surgeon General’s advisory on the use of salicylates and Reye Syndrome. MMWR Morb Mortal Wkly Rep 1982;31:289-290.

In children with primary varicella, all of the following are correct except:
a. There may be a causal relationship between the use of ibuprofen and invasive GAS including NF.
b. Acetaminophen is the preferred analgesic/antipyretic.
c. Ibuprofen’s anti-inflammatory actions may delay diagnosis.
d. Children who have NF have more severe local manifestations than children with other soft tissue infections.