FIGURE 1.

Diagnostic algorithm for patients with documented hypereosinophilia (HE). Patients with documented HE are examined for the presence of an underlying disease (etiology) and for the presence of eosinophil‐induced organ damage by applying basic diagnostics and specific staging investigations as well as specific molecular, laboratory, immunologic, hematologic, morphologic, and histopathologic investigations. The initial basic investigation includes a family history which may reveal familial HE (HE_FA). In a next step, clinical and laboratory features of a reactive process are documented or excluded. In the case of a secondary reactive HE (HE_R), the underlying disease process (inflammation, infection, tumor, others) needs to be defined. When no underlying reactive condition, no sign of clonality (neoplastic condition), and no signs of overt organ damage are found the provisional diagnosis is HE of unknown significance (HE_US). These patients must be carefully monitored over time. When neoplastic HE (HE_N) is detected, the final diagnosis of an underlying hematologic neoplasm must be determined by using WHO criteria and criteria provided by the ICOG‐EO group. When HE is accompanied by specific (HE‐induced) (multi)organ damage, the diagnosis of HES can be established. HES can occur in any type of HE and can present as secondary/reactive HES (HES_R), primary/neoplastic HES (HES_N), or idiopathic HES (HES_I).