A retrospective cohort study of patients with eosinophilia referred to a tertiary centre

Eosinophilia (eosinophil count > 0.5 × 109/l blood) represents a clinical challenge that frequently requires detailed information about symptoms and a thorough examination combined with adequate diagnostic workup [1-3]. The incidence in the hospital setting varies by medical specialty and geographical region, reflecting the broad clinical spectrum of conditions associated with eosinophilia [4-6]. Eosinophilia was registered in 4% of all differential blood sample counts requested by general practitioners in unique, adult individuals in the Capital Region of Denmark during a ten-year period [7]. The eosinophilic granulocyte (eosinophil) possesses numerous physiological functions protecting against helminths and other infections and is involved in homeostatic activities [8]. However, uncontrolled activity of off-target eosinophils or constituents released from their granules may cause mono- or multiorgan dysfunction affecting any tissue [9, 10]. Three levels of eosinophilia have been arbitrarily defined; mild: 0.5-1.5 × 109/l, moderate: ≥ 1.5 × 109/l and severe: > 5 × 109/l. The specific term “hypereosinophilia” commonly refers to moderate or severe eosinophilia.

Eosinophilia is categorised as primary when reflecting a clonal haematological condition in which the production of eosinophils is driven by a genetic cause, intrinsic in haematopoiesis; and as secondary when the increase is reactive to factors with an extrinsic impact on the eosinopoiesis [1-3]. Secondary/reactive eosinophilia is driven, in particular, by the T-lymphocyte-produced cytokine interleukin (IL)-5 and is related to the differentiation and activation of eosinophils in interplay with other immunologically active cells associated with autoimmunity, inflammation, infection, malignancy and allergy including adverse reactions to various drugs [1, 5, 8, 11]. When neither primary nor secondary causes are demonstrable, patients with persisting eosinophil counts of at least 1.5 × 109/l are categorised as idiopathic hypereosinophilia (iHE, without symptoms) or idiopathic hypereosinophilic syndrome (iHES, with symptoms) [1-3], although clonality is likely involved in the pathobiology [12].

In the clinic, however, it may prove difficult to disentangle the diagnosis of iHES, primary or secondary eosinophilia due to the rarity of the syndromes and to overlapping manifestations including a heterogenous array of symptoms. Therefore, centralisation of management in tertiary referral centres has been established. The Centre for Eosinophilia (CEOS) is part of the Department of Haematology X, Odense University Hospital, and part of a National initiative for tertiary centres, since 2017 [3]. Patients are referred to CEOS for further diagnostic workup and for second opinion in case of unexplained eosinophilia. According to the national organisation of this tertiary centre in eosinophilia, collaboration within the CEOS encompasses general practitioners, departments at the Odense University Hospital or other departments at hospitals in the Southern Region of Denmark, five departments of haematology localized in the Region of Southern, Central or Northern Denmark (3.11 million inhabitants).

The aim of this retrospective observational study, based on cross-sectional analyses of adult patients referred to our multidisciplinary centre during a three-year period, aimed to benchmark our current performance with respect to diagnostic processes and treatment decisions