Managing Patients with Hypereosinophilic Syndrome: A Statement from the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC)

Abstract

Hypereosinophilic syndrome (HES) encompasses a heterogeneous and complex group of different subtypes within the wider group of hypereosinophilic disorders. Despite increasing research interest, several unmet needs in terms of disease identification, pathobiology, phenotyping, and personalized treatment remain to be addressed. Also, the prospective burden of non-malignant HES and, more in general, HE disorders is currently unknown. On a practical note, shortening the diagnostic delay and the time to an appropriate treatment approach probably represents the most urgent issue, even in light of the great impact of HES on the quality of life of affected patients. The present document represents the first action that the Italian Society of Allergy, Asthma, and Clinical Immunology (SIAAIC) has finalized within a wider project aiming to establish a collaborative national network on HES (InHES-Italian Network on HES) for patients and physicians. The first step of the project could not but focus on defining a common language as well as sharing with all of the medical community an update on the most recent advances in the field. In fact, the existing literature has been carefully reviewed in order to critically integrate the different views on the topic and derive practical recommendations on disease identification and treatment approaches.

Keywords: eosinophils; hypereosinophilia; hypereosinophilic syndrome; management; mepolizumab; network; precision medicine.

Figure 1

SIAAIC proposal for a revisited classification of hypereosinophilic disorders. ABPA: allergic bronchopulmonary aspergillosis; AD: atopic dermatitis; CEP: chronic eosinophilic pneumonia; CRwNP: chronic rhinosinusitis with nasal polyps; DRESS: drug rash with eosinophilia and systemic symptoms; EGIDs: eosinophilic disorders of the digestive tract; EGPA: eosinophilic granulomatosis with polyangiitis; HE: hypereosinophilia; HES: hypereosinophilic syndrome; HEus: hypereosinophilia of unknown significance; IEI: inborn errors of immunity.

Figure 2

Mandatory and optional assessment following the detection of blood hypereosinophilia suggestive of HES. ANA, antinuclear antibody; ANCA, anti-neutrophil cytoplasmic antibodies; CRP, C-reactive protein; CT, computed tomography; ECG, electrocardiogram; ESR, erythrocyte sedimentation rate; FGFR1, fibroblast growth factor receptor 1; FIP1L1, factor interacting with PAPOLA and CPSF1; JAK2, Janus kinase 2; MRI, magnetic resonance imaging; PDGFRA, platelet-derived growth factor receptor alpha; PET, positron emission tomography.

Figure 3

Skin manifestations of hypereosinophilic syndrome. Well-delineated maculopapules, eczematous lesions, and excoriated eruptions localized at the upper limbs (A), trunk, and abdominal skin (B).

Figure 4

Overview of conventional, new, and developing drugs for hypereosinophilic syndrome (HES) management. ETV6, ETS variant transcription factor 6; FGFR1, fibroblast growth factor receptor 1; FLT3, Fms-related receptor tyrosine kinase 3; IL-5, interleukin 5; IL-5R, interleukin 5 receptor; IgE, immunoglobulin E; JAK2, Janus kinase 2. Created with BioRender.com.

Figure 5

SIAAIC proposed recommendations for a hypereosinophilic syndrome (HES) therapeutic approach according to disease stage and clinical presentation. BEC, blood eosinophil count; CyC, cyclophosphamide; JAK, Janus kinase; Peg-INF-α, peginterferon-α; PDGFRA/B, platelet-derived growth factor receptor A/B; RTX, rituximab. * in the case of severe life-threatening eosinophilic respiratory, vascular, cardiac, or neurological involvement, even in the case the differential diagnosis within the HES subtypes has not been confirmed, the initial management is based on a corticosteroid therapy with 1 mg/kg/day prednisone, preceded by the intravenous pulses of methylprednisolone 5–15 mg/kg/day up to a maximum of 1000 mg for 3 days. ** especially in patients with PDGFRA/B-rearranged eosinophilic neoplasm.