Figure 3. Diagnostic algorithm for patients with hypereosinophilia.

After having established that HE is present, the cause and clinical significance of HE need to be explored. With regard to the cause, the patient is examined for signs of a reactive process (helminth infection, drug allergy or others), evidence of a myeloid or stem cell neoplasm (where eosinophils usually are neoplastic cells), or of other malignancies. In rare cases, familial HE is diagnosed. When no underlying condition and no signs of overt organ damage are found, the (provisional) diagnosis HE_US is established, and the patient is carefully monitored. In the case of secondary (reactive or paraneoplastic) HE or clonal (neoplastic) HE, the final diagnosis is determined using the WHO criteria and other established criteria. When HE is accompanied by specific (eosinophil-induced) organ damage, diagnosis of HES is established. HES can occur in any type of HE and can present as secondary (reactive) HES, primary (neoplastic) HES, or idiopathic HES. Rare syndromes presenting with eosinophilia, such as the CCS, Gleich’s syndrome and other syndromes, must also be considered based on clinical findings.

CCS: Churg-Strauss syndrome; HE: Hypereosinophilia; HE_N: Clonal/neoplastic HE; HE_R: Reactive HE; HE_US: HE of undetermined significance; HES: Hypereosinophilic syndrome; HES_N: Primary/neoplastic HES; HES_R: Reactive HES; NHL: Non-Hodgkińs lymphoma.