French guidelines for the etiological workup of eosinophilia and the management of hypereosinophilic syndromes

Abstract

Eosinophilic-related clinical manifestations are protean and the underlying conditions underpinning eosinophilia are highly diverse. The etiological workup of unexplained eosinophilia/hypereosinophilia can be challenging, and can lead sometimes to extensive, inappropriate, costly and/or invasive investigations. To date, guidelines for the etiological workup and management of eosinophilia are mainly issued by hematologists, and thus mostly cover the scope of clonal hypereosinophilic syndromes (HES). Here, thanks to an extensive literature review, and thanks to the joint work of a large panel of experts involving physicians from both adult and pediatric medicine and from various subspecialties (as well as a representative of a patients’ association representative), we provide recommendations for both the step-by step diagnostic workup of eosinophilia (whether unexplained or within specific contexts) as well as the management and follow-up of the full spectrum of eosinophilic disorders (including clonal, reactive, lymphocytic and idiopathic HES, as well as single-organ diseases). Didactic prescription summaries intended to facilitate the prescription of eosinophil-targeted drugs are also provided, as are practical diagnostic and therapeutic algorithms. Lastly, this set of recommendations also includes a summary intended for general practitioners, as well as an overview of the therapeutic patient education program set up by the French reference center for HES. Further updates will be mandatory as new validated information emerges.

Ophthalmic vascular manifestations in eosinophil-associated diseases: a comprehensive analysis of 57 patients from the CEREO and EESG networks and a literature review

“…As eosinophils seem to have a prominent role in the genesis of ophthalmic vascular manifestations, prompt initiation of eosinophil-targeted treatments is advisable to curb the deleterious pathophysiological process and to prevent the advent of other manifestations related to eosinophilia-related vascular toxicity. Corticosteroids are the cornerstone of the management of most eosinophilia-associated diseases ( 38 – 40 ). Here, 84% of patients received corticosteroids, which are rapidly effective in most cases (91%) except in a very limited number of well-defined conditions, including drug-hypersensitivity, clonal HES, and paraneoplastic eosinophilia ( 18 ).…”

“…The use of corticosteroids has also seldom been reported in Purtscher’s retinopathy or CRVO, as evidence is lacking ( 33 , 35 ). Although more than one third of patients received immunosuppressants, it should be emphasized that, in both HES and EGPA, there is no evidence that the adjunction of either cytotoxic drugs or anti-interleukin 5 biologics to corticosteroids is superior to corticosteroids alone at the acute phase ( 38 , 40 ). Nevertheless, as mepolizumab has demonstrated clinical efficacy and substantial steroid-sparing effect in both EGPA and HES, it is likely that such treatment is beneficial on the long run in patients with high dose steroid dependency and/or steroid-related side effects ( 41 – 43 ).…”

Involvement of the JAK‐STAT pathway in the molecular landscape of tyrosine kinase fusion‐negative hypereosinophilic syndromes: A nationwide CEREO study

“…In line with the French guidelines for managing HE/HES, eosinophil-induced organ damage was retained either in case of histological evidence of eosinophilic infiltration, and/or when all of the following criteria were met: (i) HE >1.5 Â 10 9 /L; (ii) organ involvement consistent with eosinophil-related toxicity; (iii) the absence of alternate diagnoses for organ involvement; (iv) parallelism of evolution between organ involvement and eosinophilia. 14 Cytogenetic and molecular risk stratification were performed using the revised international prognosis scoring system (IPSS-R) and the molecular international prognosis scoring system (IPSS-M) for myelodysplastic syndromes (MDS), respectively. 15,16 Studied outcomes included hematologic responses (with complete (CHR) and partial (PHR) hematologic responses being defined as the normalization of absolute eosinophil counts (AEC) or the decrease in more than 50%…”

Eosinophilic Granulomatosis with Polyangiitis: Latest Findings and Updated Treatment Recommendations

“…Relatively common differential diagnoses of blood eosinophilia include parasitic and fungal infections, allergies including drug allergies, and atopic diseases. Hematological disorders (e.g., eosinophilic leukemia and malignant lymphoma), solid tumors (e.g., lung and colon cancer), chronic graft-versus-host disease, chronic inflammatory disease (e.g., inflammatory bowel disease), and autoimmune diseases are relatively rare but should be considered [ 42 , 43 , 44 ].…”

“…If the total scores of the seven items are six or more, it is possible to classify a patient as having EGPA [ 41 , 84 ]. However, the histological proof is not always obtained in clinical practice and overlap with HES is likely the case for some patients [ 5 , 10 , 42 ].…”