Idiopathic hypereosinophilic syndromes and rare dysimmune conditions associated with hyper-eosinophilia in practice: An innovative multidisciplinary approach

Abstract

Hypereosinophilic syndromes (HES) represent a group of rare dis-immune conditions characterized by blood hyper-eosinophilia and eosinophilic related burden. Especially the idiopathic subtype (I-HES) is particularly difficult to diagnose because of its heterogeneous clinical presentation, the lack of specific findings on physical exam, lab tools, and imaging informative enough to unequivocally confirm the diagnosis and the overlap with other entities, including eosinophilic organ-diseases or systemic dis-immune conditions other than I-HES (from atopy to eosinophilic granulomatosis with polyangiitis [EGPA], the last often extremely difficult to distinguish from HES). Taken together, all the features mentioned above account for an extremely difficult early recognition HES and on-time referral to a specialized centre. The referral itself is challenging due to a not univocal specialist identification, because of the variability of physicians managing HES in different settings (including allergist/clinical immunologist, haematologist, internal medicine doctors, pulmonologist, rheumatologist). Furthermore, the approach in terms of personalized treatment identification and follow-up plan (timing, organ assessment), is poorly standardized. Further translational and clinical research is needed to address the mentioned unmet needs, but on practical grounds increasing the overall clinicians' awareness on HES and implementing healthcare pathways for HES patients represent a roadmap that every clinician might try to realize in his specific setting. The present review aims at providing an overview about the current challenges and unmet needs in the practical approach to HES and rare hypereosinophilic allergo-immunological diseases, including a proposal for an innovative multidisciplinary organizational model.

Keywords: Benralizumab; HES; Hypereosinophilic syndrome; Mepolizumab; Multidisciplinary; Precision medicine.

Fig. 1

Overview of the most relevant immunological conditions sharing a T2-eosinophilic inflammation in their pathobiological background still with different clinical manifestations and burden. Red colour indicates systematic association with blood hypereosinophilia. ABPA: allergic bronchopulmonary aspergillosis. CRSwNP: chronic rhinosinusitis with nasal polyps. EGPA: eosinophilic granulomatosis with polyangiitis.

Fig. 2

Schematic description of eosinophils driven mechanisms in HES, their pathobiological implications and related patterns of clinical expression and of the most common symptoms and involved organs according to HES subtypes. I-HES: idiopathic hyperesoniphilic syndrome; L-HES: lymphocytic hyperesoniphilic syndrome; M-HES: myeloid hyperesoniphilic syndrome

Fig. 3

Overiew of treatment options for I-HES, according to the current regulatory setting and the reports in the literature related to the idiopathic subtype of hypereosinophilic syndrome

Fig. 4

Panel A. Structure of the organizational model related to rare dysimmune conditions with hyper-eosinophilia at Verona Integrated University Hospital, including the core Units contributing to the multidisciplinary group (vertical bars), the common services shared by all the Units (horizontal bar) and the hypereosinophilic conditions managed by Units subgroups (horizontal ovals). EGIDS: eosinophilic disorders of the digestive tract. EGPA: eosinophilic granulomatosis with polyangiitis. HES: hypereosinophilic syndromes. Panel B. Standardized roadmap driving the approach to patients according to red-flags and criteria shared by the GEos (multidisciplinary Group on rare dysimmune conditions with hyper-Eosinophilia) Units at Verona Integrated University Hospital