Development and Validation of the FIP Score for the Screening of FIP1L1::PDGFRA-Associated Hypereosinophilic Syndrome.

Abstract

The FIP1L1-PDFGRA (F/P)-associated hypereosinophilic syndrome (HES) is a rare condition. The F/P fusion gene testing is one of the first-line investigations in patients with unexplained eosinophilia and yields poor diagnostic performance. To build and validate the factor interacting with PAPOLA and CPSF1 (FIP) score: a set of weighted criteria warranting testing for the F/P fusion gene. We merged data from 151 patients with F/P-associated HES and 320 patients with either F/P-negative HES (n = 279) or hypereosinophilia of undetermined significance (n = 41). Training and validation cohorts (comprising, respectively, 90% and 10% of all patients) were randomly dichotomized. Variables with a P value less than .20 in univariate analysis were included in the multivariable forward-backward logistic regression model to assess their independent contribution to testing positive for the F/P fusion gene. Beta coefficients from multivariable logistic regression were used to assign points for the construction of the score. Age younger than 66 years, male sex, splenomegaly, lymphomatoid papulosis, absence of gastrointestinal involvement, high serum vitamin B₁₂, high serum tryptase, and normal serum immunoglobulin E levels were the 8 variables retained in the model. The best cutoff value was greater than 48. The model yielded a sensitivity, specificity, positive predictive value, negative predictive value, and area under the curve, respectively, of 88.3%, 93.7%, 87.1%, 94.4%, and 0.962 in the training dataset and of 85.7%, 97.0%, 85.7%, and 97.0%, 0.986 in the validation dataset. The FIP score highlights the need for closely selecting patients with hypereosinophilia for whom F/P fusion gene testing should be performed, resulting in medical time reduction and substantial cost-savings.