Research Article: Hypereosinophilia: Biological investigations and etiologies in a French metropolitan university hospital, and proposed approach for diagnostic evaluation

Date Published: September 26, 2018

Publisher: Public Library of Science

Author(s): Martin Peju, Alban Deroux, Hervé Pelloux, Laurence Bouillet, Olivier Epaulard, Mark Simonds Riddle.


We aimed to evaluate the usefulness of biological investigations in cases of eosinophilia in our area (French Alps).

We retrospectively included all adult patients attending the infectious disease and internal medicine units between 2009 and 2015 with eosinophilia ≥1 G/l.

We identified 298 cases (129 women and 169 men). In 139 patients, eosinophilia had not been addressed. In the 159 others, the cause of eosinophilia was identified in 118 (74.2%). The main identified causes at the time were drug reactions (24.5%, mostly β-lactams and allopurinol), infectious diseases (17.0%), vasculitis (8.2%), autoimmune diseases (6.9%), and malignant diseases (6.2%). In patients with a skin rash, eosinophilia was significantly more often investigated, and a diagnosis significantly more often made. Helminthosis were mainly diagnosed in tropical travelers (18/24) excepting toxocariasis (3 non-travelers). Stool examination for helminthosis was positive in 5/76 patients (6.6%) (all tropical travelers); 391 helminth serologies were performed in 91 patients, with 7.9% being positive (all but 3 positive cases were travelers). Anti-neutrophil cytoplasmic antibodies (ANCA) were positive in 26/112 patients (23.2%), with 9 cases of vasculitis identified.

Drug-related eosinophilia is the main etiology. Search for helminthosis is not recommended among non-travelers (excepting toxocariasis). ANCA should be performed early so as not to overlook vasculitis.

Partial Text

Blood eosinophilia is defined as a level of eosinophilic granulocytes above 0.4 or 0.5 G/l (1 G/l = 109 cells per liter) on the blood count; the levels of blood eosinophilia may be described as mild (0.5–1.5 G/l), moderate (1.5–5 G/l), or severe (>5 G/l) [1]. Eosinophils are key effectors of innate immunity against helminth parasites and as part of the allergic inflammation. After being produced in bone marrow, they circulate for only a few hours before being recruited in tissue where they act in diverse ways: degranulation (sudden release of the highly reactive content of their granules), cytokine production, and phagocytosis; blood eosinophilia is not strictly correlated with tissue infiltration by these cells. The incidence of eosinophilia can dramatically change depending on the world region or the existence of a recent travel history. In large transversal studies of routine medical samples, blood eosinophilia has been estimated to affect 0.4 to 4% of all blood counts [2,3], whereas it has been found in 4 to 27% of returning travelers or arriving refugees [4,5]. When eosinophilia is present, the suspected diagnoses may vary depending on the conditions: for example, in returning travelers, 18.9 to 53.7% of eosinophilia cases are related to an helminth infection [4,6]. However, eosinophilia is associated with a broad variety of non- helminth diseases (including hematological malignancy, vasculitis, allergic diseases, and hypereosinophilic syndrome). Because of this diversity, the diagnostic approach may become complex. Several authors have reviewed the diagnoses associated with blood eosinophilia [7–11], although the diagnostic strategy, which is strongly dependent on the clinical condition and circumstances, is less often detailed. Indeed, recommended examinations may differ from one publication to another.

All patients with an eosinophilia ≥1 G/L who attended the internal medicine or infectious disease units of Grenoble University Hospital between 2009 and 2015 were included. The subjects may have consulted or been hospitalized. We choose this threshold (1 G/L) by assuming that a high proportion of cases of eosinophilia between 0.5 and 1 G/L might have been overlooked by clinicians.

In our center, etiologies associated with an eosinophilia were dominated by drug reactions and helminth diseases. Strikingly, 46.6% of the 298 eosinophilia cases were probably neglected (and not even mentioned in the medical records) despite the fact that the level of eosinophils chosen for the selection of patients was high (≥1 G/l). A higher level of eosinophils was significantly more often taken into account. Thus, although the normal value of eosinophils is less than 0.4 or 0.6 G/L, this would suggest that most physicians do not pay attention to a transitory mild eosinophilia, unless it is associated with clinical or non-clinical disorders. The proportion of neglected cases would probably have been higher if we had retained a lower threshold value.

Mild eosinophilia is often neglected. A diagnosis of drug-related reaction is frequently identified, particularly in case of rash. Apart from toxocariasis, helminth infections should be searched for (mostly by serology or stool examination) in travelers. ANCA should be performed early, as potentially severe vasculitis is not uncommon. Determination of serum IgE level is weakly informative.




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