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Nonfever symptoms after IVIG in Kawasaki.

VANCOUVER, B.C. -- Children with Kawasaki disease who have persistence of symptoms other than fever after intravenous immunoglobulin treatment have sharply elevated odds of progressing to coronary artery abnormalities, a retrospective study showed.

In the study, 9% of children had resolution of fever but persistence of lip erythema, bulbar conjunctivitis, or both. These children were 18 times more likely to develop coronary artery abnormalities than their counterparts whose symptoms had entirely resolved.

"Persistence of symptoms other than fever is an independent risk factor for coronary artery abnormalities," lead author Dr. Sayaka Fukuda said in an interview. When it comes to identifying children with Kawasaki disease who have resistance to intravenous immunoglobulin (WIG) and need more treatment, clinicians typically watch for a fever that lingers. But the importance of persistence of other symptoms is unknown.


Using electronic medical records, they retrospectively studied the characteristics and outcomes of children hospitalized with Kawasaki disease who received aspirin (or the NSAID flurbiprofen) plus WIG as initial treatment. The children were classified into four groups according to persistence of fever in the 24-36 hours after initial WIG treatment (yes or no) and persistence of nonfever symptoms 1 month after initial IVIG treatment (yes or no).

Study results reported in a poster session were based on 77 children. Eight percent had persistence of both fever and nonfever symptoms, 9% had persistence of only nonfever symptoms, 18% had persistence of only fever, and 65% had resolution of all their symptoms. In the group with only nonfever symptoms, these symptoms were lip erythema and bulbar conjunctivitis, according to Dr. Fukuda, who is a pediatric fellow at the National Center for Child Health and Development in Tokyo.

The only significant difference among the four groups was the duration of hospitalization (P less than .01). The groups were similar with respect to age, sex, season of presentation, presenting symptom, fever duration, and more than a dozen laboratory measures of inflammation and coagulation.

All children with persistent fever had received a second course of WIG or an alternative treatment, whereas only one of the seven children with persistence of just nonfever symptoms had received further treatment.

Overall, 14% of the children developed coronary artery abnormalities as assessed by ultrasound 1 month after initial treatment. By group, the rate was highest (67%) in those with persistence of both fever and nonfever symptoms, but it was also high (43%) in those with persistence of only nonfever symptoms. The rate was lower in the groups with persistence of only fever (14%) or no symptoms at all (4%).

In an adjusted analysis, children with persistence of both fever and nonfever symptoms had 48-fold higher odds of developing coronary artery abnormalities than the symptom-free group (P = .001). But the children with persistence of only nonfever symptoms had 18-fold higher odds as well (P = .006). Those with persistence of only fever were not at significantly elevated risk.

"This classification's limitation is that persistence of symptoms was determined 1 month after initial WIG, so it is too late for [additional] treatment of Kawasaki disease," Dr. Fukuda noted.

"So we have to identify early factors associated with persistence of symptoms [such as] biomarkers,'" she said. Current candidates include the cytokines PRV1 (polycythemia rubra vera-1) and G-CSF (granulocyte colony-stimulating factor), and the transcription factor STAT3 (signal transducer and activator of transcription 3).


Major Finding: Children with Kawasaki disease who had persistence of only symptoms other than fever after initial IVIG treatment had 18-fold higher odds of developing coronary artery abnormalities relative to their symptom-free peers.

Data Source: A retrospective cohort study of 77 children with Kawasaki disease treated with tVIG and aspirin or the NSAID flurbiprofen.

Disclosures: None was reported.


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Title Annotation:NEWS; intravenous immunoglobulin
Author:London, Susan
Publication:Pediatric News
Article Type:Report
Geographic Code:1USA
Date:Jul 1, 2010
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