Int J Clin Exp Med 2018;11(9):10150-10155

www.ijcem.com /ISSN:1940-5901/IJCEM0071893

Case Report
A case of severe hypereosinophilia in a term infant
Juan He, Wei Zhou, Hui Lv, Li Tao, Xiao-Wen Chen, Ping Wang

Department of Neonatology, Guangzhou Women and Children’s Medical Center, Guangzhou 510623, Guangdong,
China
Received February 27, 2017; Accepted June 12, 2018; Epub September 15, 2018; Published September 30,
2018

Abstract: Eosinophilia is common in premature infants, but severe hypereosinophilia is rare in the neonatal period,
and a sustained or progressive form is particularly uncommon. We describe the clinical characteristics and course
of severe hypereosinophilia in a full-term male neonate. The patient exhibited substantial abnormalities in periph-
eral blood leukocytes and polypnea at birth, followed by a progressive increase in peripheral blood leukocyte count
and Ec ratio, reaching 32% of monocytes and an absolute value of 27.1×109/L. All related etiological examinations
(for viral, bacterial, fungal, immunodeficiency, and immune diseases, hyper IgE syndrome, hematological malig-
nancies, and bone marrow hyperplasia syndrome) and blood biochemistry results were normal. Biopsy revealed
proliferative bone marrow with eosinophil fraction at 25%, consistent with severe hypereosinophilia. Anhelation was
relieved by oxygen, atomization, and anti-infection treatments. Blood was reexamined one and three months after
discharge. By three months, absolute Ec was reduced to 1.18 and absolute count to 1.02×109/L. At six months, Ec,
motor function, and mental development were normal. Most cases of severe hypereosinophilia in neonates have
unknown etiology but good prognosis. Comprehensive clinical and laboratory assessments are usually required to
identify the etiology. Non-specific treatment was chosen in our case because of the unclear etiology. Serious cases
necessitate blood transfusion, and all require careful monitoring of eosinophil count and organ function until at
least 6 months after birth.

Keywords: Hypereosinophilia, hypereosinophilic syndrome, neonate, infant

Introduction mature rupture of fetal membranes. Amniotic

fluid, umbilical cord, and placenta were normal,
Hypereosinophilia (HE) is defined as an abso- and 1-5-10 min Apgar scores were all 10. The
lute value of oxyphil cells in neonatal peripheral mother has gestational diabetes, but no history
blood > 0.5×109/L, but without organ injury of drugs associated with reactive HE. The
[1]. Cases are classified as mild, moderate, or patient exhibited an abnormal increase in
severe according to differential counting (mild, umbilical cord blood leukocytes at birth, and an
Ec differential count 0.07-0.15, absolute value ensuing increase in peripheral blood leukocyte
0.5-1.5×109/L; medium, 0.15-0.50, 1.5-5.0× count and Ec ratio (Figure 1). Granulocyte and
109/L; severe, 0.50-0.90, > 5.0×109/L). Yen et lymphocyte ratios were reduced, immature
al. [2] report mild to moderate HE in 14%-76% granulocytes and erythrocytes were non-uni-
of preterm neonates during hospitalization. In form in size and large platelets were found
contrast, severe HE in neonates is rare, with occasionally on blood examination. The patient
only one case reported in 2011 [3]. We report a was given ceftriaxone sodium, imipenem, and
case of neonatal severe HE admitted to Guang-
cilastatin sodium (tienam) for anti-infection by
zhou Women and Children Medical Center
the local hospital due to the significant abnor-
in January, 2015, and reviewed the relevant
malities in peripheral blood leukocytes and
literatures.
polypnea. With oxygen uptake, atomization,
Case report and other treatments, the patient’s anhelation
was relieved, but routine blood test results
Clinical data and results were still abnormal, and he was admitted to our
hospital 6 days after birth (January 21, 2015).
The case patient was male with full-term nor- Physical examination at our hospital revealed
mal delivery, birth weight 3220 g, without pre- stable vital signs and age-appropriate respons-
 Hypereosinophilia in a term infant

nosis was hypereosinophilia (severe) of unkno-

wn etiology. The patient’s guardians requested
discharge against medical advice 13 days after
admission.

Blood was reexamined at one month and three

months after discharge. Absolute Ec was redu-
ced to 1.18 and absolute value to 1.02×109/L.
measure is normal at six months, at which time
the patient’s movement and mental develop-
ment were also normal.

Figure 1. Changes in absolute leukocyte and eosino- Discussion

phil counts in a case of severe neonatal hypereosino-
philia. Increased Ec in neonates may be related to
anabolism, drug reaction, allergy, bronchopul-
es, but flush complexion, loud crying, and slight monary dysplasia (BPD), hemopoietin therapy,
xanthochromia. There were no skin rashes or intravenous nutrition, or infection [4-8]. Hype-
swelling of superficial lymph nodes. Bregma reosinophilia is common in premature infants,
was flat and soft, breath sounds from both frequently related to infection, necrotizing en-
lungs were clear with no rales. Heart rate was terocolitis, and BPD, but etiology is also often
regular at 148 beats/min, and heart sounds unclear, mostly in mild and moderate cases.
were strong with no audible murmurs from Severe HE in neonates is rare in clinical prac-
valve areas. The abdomen was soft with slight tice. For neonates with HE, both benign and
bulging, but there was no swelling of the liver or reactive factors are considered as causes, for
spleen. Nervous system function was normal example allergy, infection, and drug reactions.
on physical examination. Routine blood test Other diseases or syndromes associated with
results were as follows: leukocytes 31.8× HE are then considered, such as hyper-IgE syn-
109/L, hemoglobin 120 g/L, blood platelet drome, Omenn syndrome, hematological malig-
356×109/L, Ec 29%, and Ec absolute value nant diseases (e.g., chronic eosinophilic leuke-
9.3×109/L. Blood biochemistry results revealed mia), and immune diseases (e.g., systemic
normal liver, heart, and kidney function, and all lupus erythematosus, vasculitis). Bone marrow
related etiological examinations were normal aspiration, flow cytometry immunoassay of B
(Table 1). The use of Tienam was continued and T cells, auto-antibody detection, and chro-
for 7 days after admission. Lumbar puncture mosome analysis should be conducted. If Ec
examination was negative, hypersensitive C-re- rises repeatedly or is sustained, idiopathic/
active protein and procalcitonin were normal, clonal hypereosinophilic syndrome(HES) should
and the child exhibited no vomiting or diarrhea, be considered.
anhelation, cough or wheeze, somnolence, or
tic. Severe HE (HES) is a group of diseases charac-
terized by markedly increased peripheral blood
The patient was reexamined on the ninth day Ec and organ function impairment caused by Ec
after admission (15 days after birth). Leukocyte invasion. Clinical manifestations of HES vary,
count was reduced to 12.7×109/L and Ec abso- but mainly involve the heart, skin, lungs, and
lute value to 4.0×109/L (Table 2). Bone marrow nervous system. In 1975, Chusid et al. [9] pro-
aspiration revealed proliferative bone marrow posed diagnostic criteria as follows: Ec abso-
and a substantially elevated of eosinophil ratio lute value of peripheral blood > 1.5×109/L, last-
of 25%, left moving nuclei with paramorphia, ing 6 months or more, with organ or tissue
hemophagocytes, and signs of infection associ- involvement. HE caused by other reasons are
ated hemophagocytic syndrome and hypereo- excluded. Crane et al. [10] reported that the
sinophilia. Plasma amino acids analysis show- incidence of HES is about 0.036/100 000, and
ed increased glutamine because of high blood is diagnosed mainly in adults 20 to 50 years
ammonia, but blood amminia is normal (43.9 old, but rarely in children. In one clinical report
mmol/L). Urine GC-Ms was negative. Karyotype from Europe, the case patient was 5 months
was normal (46 chromosomes, XY). Final diag- old [11], while a report from China documented

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 Hypereosinophilia in a term infant

Table 1. Examination results on related causes and complications in a case of severe neonatal hype-
reosinophilia
Causes and complications Items Results
Viruses Herpes simplex (blood, cerebrospinal fluid, CSF) Negative
Cytomegalovirus (CMV) (blood, CSF) Negative
Rubella (blood) Negative
MicrovirusB19 (blood) Negative
Coxsackie (blood) Negative
EB virus - four items (blood) Negative
Respiratory syncytial (blood) Negative
Influenza (blood) Negative
Adenovirus (blood) Negative
Bacteria High sensitive C-reactive protein (blood) Normal
Procalcitonin (blood) Normal
Blood culture Negative
Cerebrospinal fluid culture Negative
Throat swab culture Negative
Fungi Anaerobe (blood) Negative
Fungal dextran Normal
Chlamydia (blood) Negative
Mycoplasma (blood) Negative
Others Mycobacterium tuberculosis Antibodies (blood) Negative
Acid-fast bacilli (phlegm) Negative
Immunodeficiency disease or immune disease Immune items (IgA, IgG, IgM, C3, C4) Normal
Cellular immune function (flow cytometry) Normal
Auto-antibodies (8 items) Negative
Hyper-IgE syndrome IgE Normal
Fecal lactose intolerance Negative
Peripheral blood cell count No abnormalities
Hematological malignancies and bone marrow hyperpla- Bone marrow aspiration cytology Proliferative bone marrow image
sia syndrome Abdominal sonography No swelling of liver and spleen
Bronchopulmonary dysplasia and thoracic complications Chest radiograph Normal
Heart complications UCG Normal
ECG Normal
Cerebral complications Head ultrasound Bilateral periventricular paren-
chyma echo enhancement, bilateral
subependymal hemorrhage

HES in a 2-month-old infant [12]. If PDGFRA, tectotype HE, with organ damage by other cau-
PDGFRB, and FGFRI fusion genes or BCR/ABL1, ses [13] excluded. In this current case, Ec ratio
or JAK2V617F+ gene mutation is detected, HES of 25% of all karyocytes in bone marrow smear,
can be considered idiopathic/clonal HES. so Ec was severely increased with invasion of
myeloid tissue, but without other significant
The consensus statement on HE and related organ lesions, consistent with a diagnosed of
syndromes in 2012 defines HE as peripheral severe HE. More pathological results are re-
blood Ec > 1.5×109/L on two examinations sep- quired to determine whether it is tectotype or
arated by at least one month, with or without not.
tectotype, which defined as: an Ec ratio of more
than 20% of all karyocytes in bone marrow HE is divided into three categories according to
smear, or (and) pathology consistent with Ec the Chinese classification system: reactive HE,
infiltration of tissue, or (and) significant granin HES, and chronic eosinophilic leukemia (CEL).
deposition of Ec (with or without tissue infiltra- HE is observed in about one third of neonates,
tion of Ec). HES not only meets the peripheral but etiology and mechanism are generally un-
blood-related diagnostic criteria of HE, but in clear. Possible explanations include 1) reduced
addition requires organ dysfunction caused by secretion of adrenal hormone with feedback

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 Hypereosinophilia in a term infant

Table 2. Literature review

Term/ Ec Ec ascending Ec back to
Writer Clinical data Causes Complications Treatment Prognosis
preterm (severe) time nomal time
Wang Y-J et al. [15] Term None 2/24 0-20 d 2-21 d Infection None Antibotics Normal
Rui-X et al. [16] Term None 6/28 0-12 d - Infection 1/28 None Antibotics Normal
ABOhemolysis 4/28
HIE3/28 drug reaction 2/28
Yen J-M et al. [2] Preterm None 17/142 3w 5w No spefic None - Normal
Shahein AR et al. [3] Preterm Nec 1 23 d 3m Unknown None Antibotics, Normal
exchange
transfusion
Juul SE et al. [4] - None 50/1652- 3.3 d - Infection None Antibotics Normal
Aguiar A et al. [17] Preterm Vomiting and abdominal distention 1 - - - Hydrolyzed milk formula Dietry Normal
Krous HF et al. [18] - Fussy and feeding poorly 1 -- - Unexplained Endomyocardias - Dead
Manoura A et al. [19] Both None - 10.2±0.8 d - Infection None Antibotics Normal
Immunoglobulin

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 Hypereosinophilia in a term infant

Table 3. The treatment and results of blood leukocyte and Ec tion results were normal. This
ratio case, blood exchange was imple-
Date after WBC Ec mented, and absolute peak was
Symptom Treatment reduced to 47.28×109/L, eventu-
birth ×10 /L ×10 /L
9 9

1d Anhelation Ceftriaxone sodium, tienam 84.7 27.10 ally returning to normal 80 days
after birth with favorable progno-
2d Anhelation Ceftriaxone sodium, tienam 60.9 19.19
sis [3]. In our case polypnea and
3d Anhelation Ceftriaxone sodium, tienam 50.2 15.06
jaundice appeared in the full-term
4d Anhelation Ceftriaxone sodium, tienam 30.2 9.66
infant after birth, and antibiotics
6d Jaundice Ceftriaxone sodium, tienam 27.1 7.80 (Ceftriaxone sodium, tienam) was
8d Jaundice Tienam 31.8 9.30 used during hospitalization. The
10 d Jaundice Tienam 24.0 7.55 absolute value of Ec reahed a pe-
12 d Jaundice 16.4 5.05 ak 27.1×109/L and WBC reached a
15 d No 12.7 4.00 peak 84.7×109/L on the day of
1m No 11.7 1.18 birth. The absolute Ec value was
3m No 12.8 1.02 reduced to 5.05×109/L after 12
6m No 16.0 0.15 days, and slowly to normal level six
month after birth. (see Table 3) Ec
infiltration and hemophagocytes
Ec increase after birth, 2) establishment of a were found in bone marrow aspiration, but the
positiive nitrogen balance indicated by steady patient had no three series decrease or other
weight gain. 3) removal of external antigen cau- symptoms, and no hemophagocytic syndrome.
sing an increase in Ec of the alimentary canal Consistent with reactive HE, with favorable
and respiratory tract, and 4) intake of trypto- prognosis.
phan supplements during pregnancy [14]. Cur-
rent research suggests that reactive HE is HE may manifest with skin lesions and neoplas-
caused by Ec or precursor cell cytokine activa- tic diseases. HE is associated with a variety
tion (IL3, IL-5, GM-CSF), resulting in Ec prolifer- of rashes. Organ involvement can be found
ation, while CEL/HES is primarily caused by as well, as evidenced by respiratory symptoms
hematopoietic disorders that induce cloning of (cough, anhelation, etc), while chest radiogra-
totipotent stem cells or hemopoietic stem cells phy can show a variety of invasive changes.
of the medullary system or lymphatic system. Possible digestive system symptoms include
stomachache, diarrhea, and nausea/vomiting.
Two retrospective studies have reviewed do- Severe cases may show intestinal obstruction
mestic cases of neonatal HE. In total, 52 cases or hemorrhage of the digestive tract. Endosco-
have been reported, of which only one case pic biopsy is recommended to confirm invasive
was severe HE, with peak absolute Ec of 9.02× lesions with eosinophils. Myocardial damage,
109/L. In this case, Ec returned to normal after endocardial and cardiac valvular changes, se-
20 days, with pneumonia and IgE increase, and vere heart failure, and arrhythmia are all possi-
no abnormality was found at follow-up, consis- ble cardiovascular outcomes, while nervous sy-
tent with reactive HE [15, 16]. Three case re- stem symptoms can indicate both central and
ports [3, 17, 18] and retrospective studies [2, 4, peripheral nervous system involvement. Prolife-
19] have been published on cases outside of ration of reticuloendothelial system (RES) cells
China. Most cases were moderate, occurring in and systemic symptoms are also observed in
premature infants (80.90%). Established cau- HE. Some child patients show fever, emacia-
ses included infection (39.27%), BPD (11.45%), tion, weakness, and lymphadenectasis of the
blood transfusion (16.18%), and necrotizing liver and spleen. Krous HF et al. [18]. reported
enterocolitis (4.73%), but a substantial propor- one case of neonatal death due to eosinophilic
tion were of unknown etiology (25.82%). (see myocarditis, and Xiaoran et al. [12] reported
Table 2) Clinical manifestations varied from one pediatric case of HES. Although Ec ratio
none to rash, with one case of neonatal death was only 12%, Ec absolute value was 0.9×
due to Ec myocarditis. One case study of a pre- 109/L, and clinical manifestations included
mature infant with severe HE reported in 2011 fever, rash, anemia, swollen liver and spleen,
absolute peak Ec of 91.48×109/L, but no organ cough, rales of both lungs, and weak heart
damage was found and bone marrow aspira- sounds. Pathology revealed bone marrow inva-

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 Hypereosinophilia in a term infant

sion and myocardial involvement. Thus, in clini- [5] Yamamoto C, Kojima T, Hattori K, Nogi S,
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Disclosure of conflict of interest [13] Sali Z, Chuanhui X and Rong M. Consensus on
the classification of hypereosinophilia and rel-
None. evant syndromes of 2012 edition. Chinese
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