Of 199 subjects enrolled, one withdrew consent immediately after being randomized, so data were analyzed for 198 subjects. Study nurses recorded the occurrence of 93 types of associated symptoms, i.e., excluding the principal clinical criteria. Of these, nine symptoms occurred in more than 10% of study subjects in the ten days prior to diagnosis and form the basis of this report. Because none of the associated symptoms varied according to treatment assignment (e.g., IVMP versus placebo), our analyses are performed in the study cohort as a whole.
In the ten days prior to diagnosis, a history of irritability was noted in 98 (50%), vomiting in 88 (44%), decreased food/fluid intake in 73 (37%), cough in 55 (28%), diarrhea in 52 (26%), rhinorrhea in 37 (19%), weakness in 37 (19%), abdominal pain in 35 (18%), and joint pain (arthralgia or arthritis) in 29 (15%). When symptoms within ten days prior to diagnosis were grouped, 120 subjects (61%) had at least one gastrointestinal symptom and 69 (35%) had at least one respiratory symptom. The frequencies of symptoms from fever onset through completion of follow-up are described in .
Frequency of Symptoms over Time
We explored whether symptoms within the ten days prior to diagnosis were associated with abnormalities in laboratory measures prior to treatment. In univariate analysis, absolute neutrophil counts were higher in subjects with joint pain (p =.029) and abdominal pain (p =.019), and tended to be higher among patients with vomiting (p =.051). Median ALT was higher in patients with vs. without vomiting (median, range: 47 [5 – 300] unit/L vs. 28 [5– 885] unit/L, p =.028) and with vs. without abdominal pain (median, range: 64 [13 – 325] unit/L vs. 28 unit/L [5 – 885], p =.009). Adjusting for age at enrollment, mean IgA was significantly lower in patients with diarrhea (age-adjusted mean, 82.0 ± 8.7 vs. 105.4 ± 5.7 g/L, p =.026). Patients with a cough had a higher ESR at diagnosis (p =.017). Although univariate analyses suggested associations of lower hematocrit and IgA with irritability, as well as lower IgA with abdominal pain, these associations were no longer significant after adjusting for age. Interestingly, the degree of inflammation, as indicated by ESR and CRP, was not significantly associated with irritability. A greater number of symptoms was significantly associated with later illness day at diagnosis in univariate analyses (p =.005), but this relationship was no longer significant (p =.351) in multivariate analysis adjusting for center and age.
We analyzed the relationship of patient age to reporting of the most common symptoms within ten days prior to diagnosis (). Patients with irritability and rhinorrhea had a younger mean age than those without these symptoms (p <.001 and p =.032, respectively). Conversely, patients with symptoms of vomiting (p =.009), abdominal pain (p <.001), and arthralgia/joint pain (p =.016) were older than those without such symptoms. The overall prevalence of associated findings did not differ according to sex or day of illness at diagnosis. Patients with and without associated symptoms were similar with respect to the change in coronary dimensions from baseline to five weeks after randomization, expressed as z scores adjusted for body surface area.
Age of Patients According to Symptoms within the 10 Days Prior to Diagnosis