Factors predicting development of chronic disease in Nordic children with acute onset of idiopathic thrombocytopenic purpura

Bruin et al (2004) performed a prospective study of 60 Dutch children with typical acute idiopathic thrombocytopenic purpura (ITP), i.e. with onset of symptoms less than 14 d before presentation. They reported that chronic disease developed in 16 (27%) of the children and could be predicted by absence of previous infection, higher platelet count, and presence of the FCGR2B-232I/T genotype. In addition, they found that treatment with intravenous immunoglobulin (IVIG) reduced the risk of chronic disease (only one of 17 treated children), independently of the platelet count. The authors suggest that IVIG may prevent development of chronic disease by promoting expression of the Fc-gamma receptor IIb, the I/I isoform effectively signalling elimination of B-cells that produce autoantibodies. A possible protective effect of IVIG is of great clinical importance. The findings suggest that it might be beneficial to treat children with acute-onset ITP with IVIG, especially if the platelet count is relatively high and no preceding infection is reported. The findings, however, are not supported by previous studies: the frequency of chronic disease was not reduced in the IVIG arm in a Canadian randomised trial (Blanchette et al, 1993) or among treated children in the Intercontinental cohort (Kühne et al, 2001). We investigated whether the Dutch findings could be replicated in data from the prospective Nordic study of 506 children with newly diagnosed ITP (Rosthøj et al, 2003). In this study, there were 327 children with acute-onset ITP and with information on duration of disease. Fifty-four (17%) developed chronic disease. As in the Dutch study, the platelet count at diagnosis was significantly associated with outcome: the risk of chronic disease was 10·5% in children with counts below 5 × 109/l compared with 19·9% in children with higher counts [odds ratio (OR) 2·12, 95% confidence interval (CI) 1·05–4·31]. A previous infection, however, did not indicate a lower risk (OR 0·95, 95% CI 0·51–1·78), and neither age, gender or severity of bleeding were found to be predictive. Of the 327 children, 183 received treatment with IVIG within 14 d of diagnosis; some (n = 35) were also given corticosteroids. Twenty-eight (15%) of these children developed chronic disease, a slight but not statistically significant reduction in risk compared with untreated children (19%) (OR 1·27, 95% CI 0·71–2·27). The interaction between platelet count, IVIG therapy and outcome is shown in Table I. The treatment rate clearly depended on the platelet count, rising to 73% in children with a platelet count below 5 × 109/l. There were no significant differences in development of chronic disease when comparing treated and untreated children in any of the different platelet count strata. Thus, the slightly reduced frequency of chronic course after IVIG therapy must be ascribed to a higher fraction of children with very low platelet count rather than a protective effect. Children with insidious onset of disease, i.e. with symptoms for more than 14 d at presentation, are more likely to develop chronic disease than children with acute onset of symptoms (Zeller et al, 2005). We have no evidence to suggest that IVIG is protective in this group, either. Of 96 children with insidious onset, 44 were treated with IVIG: 25 (57%) developed chronic disease, compared with 21 (51%) of 41 untreated children. In summary, our data do not support the hypothesis that IVIG protects against chronic disease. The Dutch patient series (Bruin et al, 2004) was small, with only 17 children treated with IVIG, and the high percentage of children with chronic disease suggests that selection bias may have been at work. This may explain the divergence of findings from the much larger Intercontinental study (Kühne et al, 2001) and from the population-based Nordic cohort (Rosthøj et al, 2003). The observations are interesting, but in our opinion the evidence that treatment with IVIG may prevent chronic disease is limited.

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