Journal Pre-proof

Pediatric Eosinophilia: A Review and Multi-Year Investigation into Etiologies

Tara E. Ness, MD, MPH, Timothy A. Erickson, Veronica Diaz, MD, Amanda B.
Grimes, MD, Ryan Rochat, MD, PhD, Sara Anvari, MD, MS, Joud Hajjar, MD, MS, Jill
Weatherhead, MD, PhD

PII: S0022-3476(22)00870-8
DOI: https://doi.org/10.1016/j.jpeds.2022.09.048
Reference: YMPD 13212

To appear in: The Journal of Pediatrics

Received Date: 11 May 2022

Revised Date: 26 September 2022
Accepted Date: 28 September 2022

Please cite this article as: Ness TE, Erickson TA, Diaz V, Grimes AB, Rochat R, Anvari S, Hajjar J,
Weatherhead J, Pediatric Eosinophilia: A Review and Multi-Year Investigation into Etiologies, The
Journal of Pediatrics (2022), doi: https://doi.org/10.1016/j.jpeds.2022.09.048.

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© 2022 Published by Elsevier Inc.

Title: Pediatric Eosinophilia: A Review and Multi-Year Investigation into Etiologies

Author listing. Tara E. Ness*a,, MD, MPH, Timothy A. Erickson*b, Veronica Diaz, MDc, Amanda
B. Grimes, MDd, Ryan Rochat, MD, PhDa, Sara Anvari, MD, MSc, Joud Hajjar, MD, MSc, Jill
Weatherhead, MD, PhDa,b,e,f

*Contributed equally

Affiliations
a. Department of Pediatrics, Division of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA
b. Department of Pediatrics, Division of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA
c. Department of Pediatrics, Division of Allergy and Immunology, Baylor College of Medicine, Houston, TX,
USA

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d. Department of Pediatrics, Division of Hematology/Oncology, Baylor College of Medicine, Houston, TX,
USA
e. Department of Medicine, Section of Infectious Diseases, Baylor College of Medicine, Houston, TX, USA

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f. National School of Tropical Medicine, Baylor College of Medicine, Houston, TX, USA

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Corresponding Author.
Tara E. Ness
BCM-Feigin Center
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1102 Bates St.
Houston TX 77030
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Phone: 4063704731
Email: tara.ness@bcm.edu
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Word count: 3000

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Conflict of Interest Disclosures: The authors declare no conflicts of interest.

Funding/Support: No specific funding or support was received for this project.
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Abstract

Objectives: To identify the etiology of peripheral eosinophilia in a large pediatric population and

to develop a diagnostic algorithm to help guide diagnosis and management of peripheral

eosinophilia in the outpatient pediatric population.

Study design: We performed a retrospective chart review of children presenting to Texas

Children’s Hospital in Houston, TX with peripheral eosinophilia from January 1st, 2011-December

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31st, 2019. Eosinophilia was classified as mild (absolute eosinophilia count or AEC > 500 and

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<1500), moderate (AEC >1500 and < 4500) and severe eosinophilia (AEC > 4500). Demographic

information and diagnostic workup were collected.

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Results: 771 patients under 18 years were evaluated. The most common cause of eosinophilia was
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allergy (N=357, 46%), of which atopy (N=296) and drug reaction (N=54) were the most common

sub-causes. This was followed by unknown etiology (N=274, 36%), infectious causes (N=72, 9%),
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and eosinophilic disorders (n=47, 6%). Many unknown cases (N=202, 73%) had limited or no
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follow up testing.

Conclusions: More information about the etiology of pediatric eosinophilia and work up could

help identify the causes. This study provides important information regarding the evaluation of

eosinophilia in pediatric populations in the United States, including a diagnostic algorithm to guide

primary care pediatricians.

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Introduction

Eosinophils are a primarily tissue dwelling white blood cell with a half-life of 8 to 18 hours

in the bloodstream.1 Eosinophilia is an increase in the absolute cell count of eosinophils over 500

cells per microliter in the peripheral blood stream, though laboratories and institutions vary slightly

in their cut-off values.2 Eosinophilia can be seen in a myriad of conditions, including allergy

disorders (including drug reactions and atopies), infections (such as helminths, fungi, protozoans),

and neoplastic disorders such as leukemia or lymphoma.3 Furthermore, eosinophilia alone can lead

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to end-organ damage including lung disease, heart disease and skin disease.4 Although the severity

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of eosinophilia has not been proven to predict the amount of organ damage, certain conditions are

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associated with higher eosinophil counts (drug hypersensitivity) and others are associated with
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lower eosinophil counts (asthma and other atopies).5
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The etiologies of pediatric-specific eosinophilia are poorly characterized. Although studies

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of pediatric eosinophilia exist, these studies include small patient numbers limiting their use to

robustly identify common eosinophilic conditions in children.6 Furthermore, there are also
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algorithms published for the initial evaluation of eosinophilia, however these algorithms are
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largely based on adult literature leaving pediatricians to determine their own pediatric-directed

workup.7,8 Because of these limitations, this study sought to investigate the cause of eosinophilia

using a large cohort of children presenting with eosinophilia to date.

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Methods

This study was approved by the Institutional Review Board at Baylor College of Medicine.

A list of potential patients was acquired by identification of patients (under 18 years of age) with

“Eosinophilia” ICD-9/10 codes presenting to Texas Children’s Hospital from January 1, 2011-

December 31, 2019. ICD 9/10 codes were used to capture patients with eosinophilia that were

recognized by medical providers. Patients were screened to ensure they met the definition of

eosinophilia (absolute eosinophils ≥ 500), and all others were excluded. For included patients, all

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complete blood counts (CBC) were reviewed. Patients with 500-1499 eosinophils were classified

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as mild, patients with values ≥ 1500 up to 4499 were classified as moderate and patients with

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values ≥ 4500 were classified as severe. Patients lacking information on absolute eosinophils, or
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the variables required to create this field (absolute eosinophilia being equal to CBC white blood
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cells//microliter * eosinophil percent) were excluded. When multiple eosinophil values existed,
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the maximum eosinophil value was utilized to define the eosinophilia category. Patient

demographics and diagnostic tests were extracted.

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Patient cause(s) of eosinophilia were acquired from the medical record. Each patient was
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reviewed by at least two independent, pediatrician authors to ensure accuracy. If the cause of

eosinophilia was not explicitly stated in the encounter by a medical provider, patients were

assigned an etiology based on review and interpretation of the medical chart. Overall categories

included allergy, autoimmune, eosinophilic disorders, infections, immunodeficiencies,

malignancies, and unknown. Within these categories, sub-classes were defined to provide more

specific data analysis. If a patient reported a history of allergic rhinitis, food, or environmental

allergies, asthma, or eczema and had eosinophilia with no other cause of eosinophilia identified,

allergy was considered the cause. Eosinophilic disorders included gastrointestinal eosinophilia

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(e.g., eosinophilic esophagitis with at least 15 eosinophils/high power field on biopsy),

eosinophilic granulomatosis with polyangiitis, Duchenne’s muscular dystrophy, Kimura disease,

eosinophilic pneumonia (>5% eosinophils on bronchoalveolar lavage), eosinophilic myositis

(diagnosed via muscle biopsy), or Well’s syndrome/eosinophilic cellulitis (diagnosed via skin

biopsy and other clinical features). Autoimmune causes included inflammatory bowel diseases

(e.g., Crohns disease, diagnosed via biopsy and clinical features), bullous pemphigoid

(characteristic skin features in addition to peripheral eosinophilia), primary biliary cirrhosis, and

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autoimmune thyroiditis. Immunodeficiencies were those specifically associated with elevated

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eosinophils, including Hyper IgE syndrome, hypereosinophilic syndromes, and

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hypogammaglobulinemia. Eosinophilia was considered secondary to an infectious agent if
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confirmed by an appropriate diagnostic test. Patients were either diagnosed via serology (for
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Toxocara or Strongyloides) or via stool ova and parasite (O&P) examination (for Giardia,
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Dientamoeba, Blastocystis, Enterobius, Ascaris, etc.). As O&P and the identified serologic assays

have minimal overlap in the initial evaluation of eosinophilia in children living in the US, they are
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utilized in this setting as complimentary diagnostics. Although it is possible to diagnose

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Stronglyoides via stool, this requires additional stool samples to provide adequate sensitivity, so

serology remains the gold standard. Patients with observation of pinworm (either physical or in

colonoscopy) were considered cases caused by pinworm, and patients with a positive stool

identification of protozoa were considered cases caused by these organisms if no other causes were

identified and if symptoms and eosinophilia resolved with targeted therapy. When cause was not

readily clear or questionable or if no work up had been completed, “unknown” was assigned as

the cause.

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 Statistical analysis was performed using Stata version 14.2 (Statacorp, College Station,

Texas). Chi-square analyses were performed to compare categorical variables, with Fishers exact

test employed for instances with < 5 observations in a cell. Kruskall-Wallis testing was used for

continuous variables. Statistical significance was set at the p<0.05 level.

Results

Description of causes of eosinophilia

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A total of 996 patients with ICD codes corresponding to eosinophilia were identified. Of

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these, 16 (2%) had restricted data and could not be accessed; 27 (3%) were older than 18 years of

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age when the eosinophilia was documented, and 182 (18%) were missing data on eosinophil count
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or did not meet criteria for eosinophilia. The remaining 771 were retained for analysis. Table I
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provides demographic information for the cohort. Overall, there was a slight male predominance
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(57% overall) except in the infectious category (43% male). The median age of the cohort was 8.6

(range 0 to 17.9) years and stable across all categories with no significant age difference identified
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in subcategories. Approximately 32% of the cohort was White (non-Hispanic), 38% White-
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Hispanic, 14% Black, 9% Asian, and 7% mixed race, other, or unknown.

The median eosinophil count as well as the percentage of children within each category

that had mild, moderate, and severe eosinophilia were reported (Table II, Figure 1). The most

common cause of eosinophilia was allergy conditions (N=357, 46%). Within this category, there

was significant overlap of causes in that a single patient may have asthma as well as allergic rhinitis

and eczema. Allergic rhinitis was the most common diagnosis for patients in this group, followed

by asthma and then eczema. For those with only allergic rhinitis (no other identified atopies), the

majority were mild eosinophilia (65%), and none were classified as severe eosinophilia. Several

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children also experienced drug-induced eosinophilia (N=54) including DRESS (N=11, 20%). The

most common drug associated with eosinophilia in this cohort was tacrolimus, however previous

research into tacrolimus associated peripheral eosinophilia has designated this as a sensitization

reaction and not a “true allergy” in its mechanism.9 Other common causes of drug-induced

eosinophilia (antibiotics, anti-epileptics) were not frequently identified. Most children with drug-

induced eosinophilia had moderate or severe eosinophilia (N=35, 65%), with the median count

being substantially higher than other causes in the allergy category (median 2230, range 667-

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30448).

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The second most common category of patients were those with eosinophilia of unknown

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etiology (N=274, 36%). In many cases (N=163, 59%), these patients consisted of persons with
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mild eosinophilia (median 1297, range 511-39040); although some had moderate (N=90, 33%) or
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severe eosinophilia (N=21, 8%). Many of the cases of eosinophilia of unknown etiology had an
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incomplete workup. Of those patients with unknown etiology, only 73.7% (N=202) had a follow

up CBC performed after their initially identified eosinophilia and of those with a repeat CBC,
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66.3% (N = 132) had persistent eosinophilia without an etiology ever identified. Testing for
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parasitic causes of disease (stool ova and parasite examination(s)) was done on only 44% of those

with a final diagnosis of unknown etiology (p<0.001, OR 2.69, 95% CI 1.51-4.89). Only 12% of

those with an unknown etiology had a Toxocara antibody test administered. There was a

statistically significant association between being tested for Toxocara and having an infectious

disease identified; p<0.001, OR 15.53, 95%CI 8.06-30.19).

Infections were also a common etiology for eosinophilia (N=71, 9%) in children, although

only 45% of children with eosinophilia were tested for infectious causes like parasites. With

exception of one bacterial infection (Bartonella henselae), all infectious causes of eosinophilia

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were parasites. It was unclear whether Bartonella henselae infection was truly related to the

eosinophilia as patient was subsequently lost to follow up however no other etiology was identified

during patient’s workup. Helminthic (N=48, 67% of infectious diseases in total) diseases were

more common than protozoa only (N=18, 25% of infectious diseases in total). Four cases (6%)

had both protozoa and helminth infections. Patients with parasitic infections were strongly

eosinophilic when compared with other causes, with a median value in the moderate range (median

1961, range 512-34029), and were frequently moderate or severe eosinophilia (N=47, 65%).

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Patients with helminthic infections had higher eosinophilia (median 2663.4) than those with only

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protozoa identified (median 1147). Although there was no difference in the types of testing patients

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received (17% tested for Toxocara vs 15% for Strongyloides), Toxocara cases were more likely to
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be positive (31 positive patients out of 129 tests conducted (24%)), vs 15 positive patients out of
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119 tests conducted for Strongyloides (13%, p=0.02, OR 2.19, 95%CI 1.07-4.63). Five of these
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patients had positive serologies for both Toxocara and Strongyloides during the same time interval.

More rarely, pinworms were observed in the setting of eosinophilia (9 patients) with no other
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identifiable cause and resolution of eosinophilia after targeted treatment.

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In the setting of eosinophilia, 18 patients were diagnosed with only protozoal infections.

The most common was Dientamoeba fragilis (N=9), followed by Giardia species (N=7),

Endolimax nana (N=4), Blastocystis species (N=5), Toxoplasma (N=1) and Iodamoeba butschlii

(N=1). The majority of these patients were infected with only a single organism (N=13); one was

infected with a pair of organisms, three with three organisms, and a single patient had four

organisms isolated from a single stool sample (Dientamoeba fragilis, Blastocystis hominis,

Endolimax nana, and Iodamoeba butschlii). Several patients with protozoal infections also had

helminths identified and were classified separately (two patients with Toxocara had infections with

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Blastocystis hominis and Endolimax nana recorded, and a patient with Strongyloides had a Giardia

lamblia coinfection).

Eosinophilic disorders were identified in 47 cases, the majority of which were

gastrointestinal eosinophilia (N=40) including eosinophilic esophagitis, eosinophilic

gastroenteritis, and eosinophilic colitis. Gastrointestinal eosinophilia had a moderate median

eosinophilia (1716, range 584-24,230) with 38% (N=15) of cases in the moderate range and 20%

(N=8) of cases in the severe eosinophil range. There were two cases of eosinophilic pneumonia,

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and one case each of Kimura disease, eosinophilic myositis, eosinophilic urticaria, and

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eosinophilic cellulitis. One patient was identified with Duchenne Muscular Dystrophy which has

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been shown to be associated with tissue eosinophilia in muscles10 and may represent a new finding
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to be explored further as no other cause of eosinophilia was identified in the individual.
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Immunodeficiency was the cause of eosinophilia in 9 cases. Hyper IgE mutation was found
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in 3 individuals (two with STAT3 mutation, one without a genetic diagnosis),

hypogammaglobulinemia in 3 cases without other identified immunodeficiency, and one case each
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of hypereosinophilic syndrome (not otherwise defined), severe combined immunodeficiency, and

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lymphocytic variant hyereosinophilic syndrome. Due to the lack of sufficient data, further

investigation into the association between hypogammaglobulinemia and eosinophilia is warranted.

These patients were all provided a diagnosis by the Allergy and Immunology service with whom

they were well-established.

Malignancy (hematologic or solid tumor was considered) was identified as the cause of

eosinophilia in 6 cases. This included 4 individuals who had undergone bone marrow transplant

but were not on medications at the time eosinophilia was documented. The other 2 individuals had

chronic myelocytic leukemia and acute lymphocytic leukemia. Those with malignancy were more

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likely to have moderate (N=2, 33%) or severe eosinophilia (N=3, 50%), however this trend was

hard to interpret due to the small sample size.

An autoimmune etiology was determined in 6 cases. This included one case of autoimmune

thyroiditis which is not a previously established association except as a late association of

DRESS,11 two cases of autoimmune disease not otherwise specified, one case of eosinophilic

granulomatosis with polyangiitis, and two cases of inflammatory bowel disease (one specifically

identified as Crohn’s Disease). Three of these cases had moderate eosinophilia (50%) and one had

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severe eosinophilia (17%).

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Based on the relative distribution of causes of eosinophilia (Figure 2; available at

www.jpeds.com) and the author’s

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expertise in Pediatric Infectious Diseases,
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Hematology/Oncology and Allergy/Immunology, a diagnostic algorithm (Figure 3; available at
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www.jpeds.com) was constructed to aid in diagnosis of common etiologies of pediatric

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eosinophilia. Although this algorithm is not exhaustive, it serves as an initial guide in diagnostic

evaluation of peripheral eosinophilia in children for the primary care pediatrician.

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Discussion

Our results show that allergy (and specifically atopy) is the most common cause of

peripheral eosinophilia in children, followed by eosinophilia with unknown cause, infections,

eosinophilic disorders, immunodeficiency, malignancy, and autoimmune diseases. Allergy had a

lower median eosinophil count than other causes and the number of cases decreased in frequency

with increasing eosinophilia severity. In comparison, the frequency of infection, eosinophilic

disorders, and malignancy increased with increasing eosinophilia severity. Due, in part, to lack

of consistent testing, the cohort included a large proportion of unknown cases. Use of a

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diagnostic evaluation protocol may aid in overcoming the diagnostic deficiency observed in the

unknown cases.

The current cohort had more allergy cases identified (46%), most commonly atopy such

as eczema and allergic rhinitis. In contrast, the previous study identified only 18% of patients

with atopy. This percentage difference could be due to characteristics of the cohort itself, data

collection methods, geographic differences or difference in physician interpretation of medical

charts. There were a large number of “unknown” etiologies in both cohorts due to a lack of

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complete diagnostic workup. In the current study, 26% of patients with an unknown cause did

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not have a repeat CBC. Furthermore, in the previous study parasites were investigated (via stool

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or antigen testing) in < 10% of patients while in the current study the frequency of parasite
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testing increased in patients with higher eosinophil counts. Another study including 37 children
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with eosinophilia identified 17 children with idiopathic hypereosinophilic syndrome, 5 with

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eosinophilic gastrointestinal disease, and 3 with parasitic helminth infection, specifically visceral

larva migrans caused by Toxocara spp.12 Several case reports, case series, or reviews have been
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published on pediatric eosinophilia including 34 cases of hypereosinophilic syndrome,13 one

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idiopathic,14 and two malignancies.15

Common infectious causes of eosinophilia include parasitic infection (specifically

helminths and ectoparasites), endemic mycosis and HIV. Helminths, such as Toxocara and

Strongyloides, typically cause eosinophilia during tissue migratory stages. Interestingly, in the

current study there were several pinworm infections associated with eosinophilia which is

unusual given the lack of intra-tissue parasite migration. Furthermore, there were several patients

with protozoa associated eosinophilia which also do not classically cause eosinophilia (with the

exception of Cystoisospora). For each of these cases, eosinophilia resolved with use of targeted

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anti-parasitic therapy. It is possible that co-infections with other parasites were present but were

not diagnosed at the time of treatment and were treated with the antiparasitic therapy, or these

individuals had other causes (e.g., atopy) that were not recognizable from their medical chart.

Based on our findings, future studies investigating pinworm and protozoa and observing

frequency of eosinophilia is warranted. We were unable to determine the sequential nature of

stool samples submitted by patients to investigate the sensitivity of first sample vs third stool

samples for diagnosis of parasites in this particular study. Although a reduced number of stool

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samples for O&P analysis may be sufficient in patients from regions with parasitic prevalence

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>20%, general practitioners in the US will be evaluating children from regions with varying

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prevalence (such as autochthonous cases in the US, a low endemic region) where studies show
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additional, independent stool samples increases likelihood of detection. As a result, in general, at
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least three stool samples provide the appropriate sensitivity. 16,17 Lastly, this study did not
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identify any fungal etiologies of eosinophilia such as endemic mycoses (e.g.

coccidioidomycosis) or aspergillosis that are classically associated with eosinophilia. The lack of
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fungal etiologies may reflect the study population, geographic location, or the lack of diagnostic
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testing.

The first step in evaluation of eosinophilia is determining whether the value is a one-time

sporadic value or is persistent and if the value has the potential to cause organ damage. Further

investigation is often guided by travel and exposure history, immune status of the patient, and

whether the patient has possible known benign causes to which the eosinophilia can be attributed

(e.g., atopies). A variety of specialties may be tasked with investigation into eosinophilia,

including primary care, hematology, infectious diseases, and allergy/immunology providers.

Despite being common, there is often not a clear diagnostic algorithm or point at which a referral

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is warranted. A review aimed at hematologists contained a wide breadth of differential diagnoses,

however workup focused largely on neoplastic causes.18 The World Health Organization provided

a diagnostic algorithm that focused on evaluation of eosinophilia after other secondary causes had

been ruled out but did not provide a standard algorithm for initial studies.19 These publications did

not define age ranges and their recommendations were based largely on adult population studies.20

severe eosinophilia should be evaluated immediately due to risk of life-threatening disorders like

malignancy and other hematologic conditions. Given that hematological disorders can have

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variable, and sometimes nonspecific presentations, we recommend having a low threshold for

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considering malignancy and hematological disorders in the work up of eosinophilia, even though

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the frequency of malignant drivers of pediatric eosinophilia are low (<1% in our cohort). We
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suggest measuring serum vitamin B12 and tryptase in patients with moderate and severe
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eosinophilia, if the patients had any cytopenia, abnormal blood smear, splenomegaly, or symptoms
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consistent with systemic mastocytosis (urticaria, anaphylaxis, flushing, or abdominal symptoms),

as these findings may suggest an underlying hematologic disorders or malignancy.

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There are several limitations worth addressing in this study. As with all chart reviews,
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errors inherent in the original records could not be addressed and form a source of potential bias.

Our status as a large referral hospital may have resulted in some bias in the etiology of patients

admitted, though our cohort included both children evaluated in inpatient as well as outpatient

clinics throughout the Houston area. A lack of follow up for some cases, which would include

repeat values, limited our study and contributed to the large number of unknown cases. Taking

the maximum eosinophil count for each patient was chosen to ensure standardization as

frequency or timing of eosinophil draw in relation to symptoms was not consistent. This provides

a larger average value than would have been obtained if we had taken a patients median

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eosinophil value or for each patient chosen one random eosinophil value over 500, however it

was determined this would best encompass trends to inform max eosinophil values found in the

different eosinophilic entities. For our study design we chose to identify patients with

eosinophilia based on ICD-10 codes which may have limited our study numbers or skewed the

type of etiologies captured. ICD-10 codes were specifically chosen to increase the chances

providers who physically saw the patients provided an assessment or specific diagnosis for the

etiology of eosinophilia rather than our chart reviewers making a diagnosis without physically

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assessing the patient.

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Further work investigating large cohorts of pediatric eosinophilia could provide even more

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clarity, especially when conducted in different geographic locations.
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Although allergy was the most common diagnosis for children presenting with
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eosinophilia, unknown causes were the second most common and were noted to have decreased
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rates of follow up testing. It is possible that the lack of complete work up for these unknown

cases is secondary to a lack of diagnostic recommendations for pediatric populations in the US

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presenting with eosinophilia.

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Acknowledgments

None

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92: 1243-1259.
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20. Klion A.D. Eosinophilia: a pragmatic approach to diagnosis and treatment. Hematology
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2014, the American Society of Hematology Education Program Book. 2015 Dec 5; 2015:

92-7.
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Table I: Demographics, Exposures, and Comorbidities of Eosinophilic Patients by Three Most
Common Etiologies and Unknown*Percentages were rounded to the nearest value

Table II: Causes of eosinophilia

Classes are noted with light green shading with sub-classes within the category noted directly
underneath and with slight indent.
For those categories or subcategories with only one patient, ranges were not provided.

Figure 1: Distribution of eosinophils by cause, showing malignancy with the overall highest
ranges of eosinophilia values, followed by immunodeficiency. Allergy had a huge range but a
lower overall median than other causes of eosinophilia.

Figure 2. Distribution of causes of eosinophilia within mild, moderate, and severe categories. As

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eosinophilia increases, allergic causes become less likely and eosinophilic disorders, infectious
causes, and malignancy make up a greater proportion of the cases.

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Figure 3. Outpatient diagnostic algorithm for eosinophilia workup

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 Eosinophilic Unknown
Allergic (n=357) Infectious (n=72) Total (n=771)
disorders (n=47) (n=274)
Male sex (%) 214 (60%) 31 (43%) 29 (62%) 154 (56%) 439 (57%)
Age in years, median (range) 8.7 (0.1 to 17.9) 7.2 (1.1 to 17.6) 7.7 (1 to 17.6) 7.3 (0 to 17.9) 8.6
Race/Ethnicity
White non-Hispanic 109 (31%) 23 (32%) 23 (49) 86 (31%) 248 (32%)
White-Hispanic 138 (39%) 31 (43%) 10 (21%) 104 (38%) 292 (38%)
Black 63 (18%) 3 (42%) 3 (6%) 34 (12%) 106 (14%)
Asian 26 (9%) 8 (11%) 6 (13%) 32 (14%) 72 (9%)
Other, multiple (e.g., Black/Hispanic), missing 16 (4%) 5 (7%) 5 (11%) 12 (4%) 53 (7%)
Stool O & P test administered 134 (37%) 52 (72%) 33 (70%) 121 (44%) 349 (45%)
Toxocara IgG test administered 32 (9%) 49 (68%) 12 (26%) 32 (12%) 129 (4%)
Strongyloides IgG test administered 34 (10%) 40 (56%) 12 (26%) 37 (14%) 127 (16%)
*Percentages were rounded to the nearest

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 Median eosinophil Moderate Severe
Cause N
count, range eosinophilia (%) eosinophilia (%)
Allergic 357 1310 (500-30448) 121 (34%) 26 (7%)
Allergic Reaction (specific event) 1 599 0 0
Contact Dermatitis 1 900 0 0
Atopy (including asthma, eczema,
allergic rhinitis, food allergies 276 1193.5 (500-18795.9) 97 (33%) 12 (4%)
without specific event)
Drug reaction 54 2230.37 (667-30448) 23 (43%) 12 (24%)
Food allergy 1 1326 0 0

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ABPA 4 2720 (764-6561) 1 (25%) 1 (25%)
Autoimmune 6 2003.21 (1098-8195) 3 (50%) 1 (17%)

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Immunodeficiency 9 2548.46 (845-12116) 6 (67%) 1 (11%)

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Infectious 71 1961.2 (512-34029) 32 (44%) 15 (21%)
Helminthic 48 2663.4 (511.6-34029) 21 (44%) 15 (31%)
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Protozoan 18 1205 (658-5085) 6 (33%) 2 (11%)
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Other, mixed 5
Eosinophilic Disorders 47 1723 (584-32362) 18 (38%) 11 (23%)
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Gastrointestinal eosinophilia 40 1716 (584-24230) 15 (38%) 8 (20%)

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Duchennes muscular dystrophy 1 2883 1 (100%) 0

Kimura Disease 1 2955 1 (100%) 0
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Eosinophilic cellulitis 1 32362.8 0 1 (100%)

Eosinophilic pneumonia 1 6354.8 0 1 (100%)
Eosinophilic myositis 1 5299.8 0 1 (100%)
Malignancy 6 5243 (1282-43080) 2 (33%) 3 (50%)
Unknownn 274 1297 (511-39040) 90 (33%) 21 (8%)
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Mild Eosinophilia (500-1500) Moderate Eosinophilia (1500-4999) Severe Eosinophilia (>4500)

Incidentally Clinically ill or Incidentally Clinically Clinically ill Either incidentally identified
identified, in clinically identified, in stable and and/or or in the setting of acute
well child, stable + other well child, other unstable, clinical illness
with laboratory or with laboratory or requiring
otherwise clinical otherwise clinical immediate
normal CBC abnormalities normal CBC abnormalities evaluation

Thorough • Thorough clinical history Off algorithm: urgent

history and and physical exam clinical evaluation indicated
physical • Further laboratory (requires evaluation for
exam; investigation: cardiovascular, respiratory,
Repeat CBC - Repeat CBC and gastrointestinal end

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- Peripheral smear organ damage)
- IgE

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Eosinophilia - Liver enzymes
• Directed work-up in the

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resolved?
setting of focal findings:
- Chest x-ray
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Yes No - Echocardiogram
- Abdominal imaging
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Persistent eosinophilia with

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Eosinophilia resolved? no clear etiology:

No further
1. Supplemental labs
work-up including IgE; peripheral
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needed Yes No smear; tryptase and B12 (in

evaluation for systemic
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Evaluate for allergic causes Evaluate for
(atopies such as asthma, infectious causes,
eczema, allergic rhinitis) based on travel and
exposure history:
- Ova and parasite (x3)
Does eosinophilia coincide - Toxocara Ab test
with atopic “flares”? - Strongyloides Ab test
- Consider referral to ID if
- Optimize management travel or exposure history
(including A&I referral if needed)
outside expertise level
Eosinophilia improved?
No further work-up needed Yes No
mastocytosis); if not
Review medications already done
for possible drug 2. Refer to Allergy/
hypersensitivity Immunology if immune
disorder is suspected
3. Refer to Hematology/
Discontinue Oncology if other
medications with cytopenias, hepato-
the potential to splenomegaly,
cause eosinophilia lymphadenopathy, or other
concern for malignancy
4. Refer to Gastroenterology
if GI eosinophilia is
suspected
5. Refer to ID if persistent
infectious source is
suspected