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Clinical Brief

Hypereosinophilic Syndrome
C. Venkatesh, E. Mahender, S. Janani, S. Malathi, M. Vijayakumar and B.R. Nammalwar
Departments of Pediatrics, Pediatric Gastroenterology and Pediatric Nephrology, Kanchi Kamakoti CHILDS Trust
Hospital, Chennai.

Abstract. Hypereosinophilic syndrome is a leukoproliferative disease characterised by sustained overproduction of

eosinophils. The three diagnostic criteria for this disorder are (1) Eosinophilia of greater than 1500 cells/ml, persisting for longer
than 6 months, (2) lack of another diagnosis to explain the eosinophilia and (3) signs and symptoms of organ involvement. We
report a 15-year-old boy who was diagnosed as Hypereosinophilic syndrome based on these criteria.
[Indian J Pediatr 2006; 73 (3) : 237-239] E-mail : jananis_2000@yahoo.com.
Key words : Eosinophilia; End organ damage

Hypereosinophilic syndrome, (HES) first described by

Hardy and Anderson in 1968, is characterized by
sustained overproduction of eosinophils. It is a rare
disorder in children. The term Idiopathic
Hypereosinophilic syndrome as defined by Chusid et al
characterized by 3 criteria- eosinophil count greater than
1500 cells/mL persisting longer than 6 months and single
or multiple organ system dysfunction attributable to
cytotoxic injury by eosinophils, without an identifiable
etiology to explain the eosinophilia. 1 The mortality in
untreated patients 3years after diagnosis, can be as high as
75%.2 Cardiac involvement is the most common cause of
increased morbidity and mortality. 3 Early identification
and aggressive therapy is of paramount importance in
decreasing the morbidity and mortality associated with
this condition.
CASE REPORT
A 15-year-old previously healthy boy was brought for
fever and malaise of two months duration, itchy papular
skin rashes with scaling for one month, progressively
increasing dyspnoea, with jaundice and decreased urine
output of 1-week duration prior to admission. Earlier
there was no puffiness of face, abdominal distension or
pain, pedal edema, seizures, altered sensorium,
hematemesis, malaena, arthralgia, arthritis or mucosal
ulceration. His chest X-ray showed right basal
pneumonitis, sputum culture had grown Staphylococcus

Correspondence and Reprint requests : Dr. Janani Sankar, Senior

Consultant, Kanchi Kmakoti Childs Trust Hospital Chennai-600034.
Fax : 044-28259633

Indian Journal of Pediatrics, Volume 73March, 2006

aureus and was diagnosed to have staphylococcal

pneumonia .He was treated with parenteral vancomycin,
meropenem, netilmicin, oral cephalexin and doxycycline.
Clinically he was well built, afebrile with marked
pallor, icterus and extensive exfoliative skin rashes with
hyper pigmentation over his entire body. He had bilateral
cervical lymphadenopathy of size 1-1.5 cm. His
cardiovascular system examination was normal with
blood pressure of 100/60 mm of Hg. The respiratory rate
was 42/min with fine crackles and wheeze. There was a
soft hepato-splenomegaly. The neurological examination
was normal.
His investigations were as follows: Hemoglobin 6
gm%, PCV 18 %, total leukocyte count 27,600/mm3 with
shift to left (stab forms 20%), eosinophils 14%, absolute
eosinophil count (AEC) 3864/mm 3, platelet count 1.2
lakhs/mm3, ESR 150 mm in the 1st hour, reticulocyte count
4.7%, Direct Coombs test was negative. Serum total
bilirubin was 4.4mg/dL with direct fraction 3.8 mg/dl,
SGOT 113 IU/L (5-45IU/L), SGPT 68 IU/L (5-45IU/L),
serum alkaline phosphatase 1454 IU/L (130-525 IU/L),
serum total protein 7.6 gm/dL, albumin 2.8gm/dL,
increased globulin 4.8gm/dL, blood urea 75mg/dL,
serum creatinine 3.1 mg/dL, and normal serum
electrolytes. Urine showed 4+ proteinuria by dipstick and
spot protein/creatinine ratio of more than 3.0 without
cellular casts or erythrocyturia. C-reactive protein was
48mg/L, and cultures of blood and urine were sterile.
Serology for hepatitis A, B and E, leptospirosi s and HIV
were negative. Smear study for microfilaria and malarial
parasite was negative and repeated stool microscopy for
parasites did not reveal any ova, cysts or occult blood.
Chest X-ray and echocardiogram were normal. Ultra
sonogram of abdomen revealed hepatosplenomegaly and
bilateral renomegaly (11.8&12cm) with normal echo
texture and no free fluid in the abdomen.
Bone marrow aspiration revealed plasmacytosis and
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C. Venkatesh et al
increased eosinophilic precursors. Karyotyping was
normal. Serum protein electrophoresis revealed elevated
gamma globulin of 3.5gm/dl and immunoglobulin
profile showed elevated S.IgE>2000 IU/L (<87 IU/L) and
IgG 31.49 gm/L (7-16 gm/L), with normal IgM 0.9gm/L
(0.4-2.3gm/L) and IgA 3.85gm/L (0.7 4.0 gm/L). Anti
Nuclear Antibody (ELISA) was borderline positive but
antibody to double stranded DNA, rheumatoid factor and
Anti Neutrophilic Cytoplasmic Antibody were negative.
Renal histology showed mild mesangial proliferation
with significant IgA deposits with few tubules showing
Periodic Acid Schiff (PAS) positive eosinophilic material.
The differential diagnosis included drug induced
allergic reaction, hypereosinophilic syndrome and
autoimmune disorder. In view of high AEC, multisystem
involvement at onset and rapidly deteriorating renal
function, hypereosinophilic syndrome was strongly
suspected. He was started on intravenous
methylprednisolone (30 mg/Kg/day) for 5 days,
followed by oral prednisolone 1mg/Kg/day. Packed red
cells were transfused for anemia. Within 10 days of
initiation of corticosteroid therapy, his renal function
improved and at one month of therapy, there was
disappearance of skin rashes with clinical and subjective
improvement of pulmonary symptoms with normal renal
and hepatic functions.
In view of significant improvement in
symptomatology with fully recovered renal and hepatic
functions, he was discharged on oral prednisolone, which
was tapered and stopped over a period of 6 months.
However, his AEC continued to be over 1500/mm3. and
hence received di-ethyl carbamazine (DEC) for 6 weeks.
At 8 months follow up his AEC was 3075/mm 3. At 10
months follow up, his AEC was 882/mm3. His last AEC at
11 months follow up was 847/mm3 and ESR was only
8mm in 1st hr. His repeat echocardiogram and follow up
renal and liver function test continued to be normal and
there was no proteinuria during this period. He continues
to be symptom free till date. A diagnosis of
Hypereosinophilic Syndrome was made in view of high
AEC persisting for more than 6 months and multisystem
(dermatological, hematological, renal, pulmonary and
hepatic) dysfunction at onset.
DISCUSSION
Hypereosinophilic syndrome is a rare disease in children
and its exact incidence is uncertain. The presentation is
heterogeneous. It can be asymptomatic or may present as
a life threatening disease. The pathophysiology of this
disease is centered around eosinophil mediated tissue
damage causing organ dysfunction. Numerous cytokines
especially IL3, IL5, GM-CSF and proinflammatory
cytokines are involved in its pathogenesis. Eosinophilic
infiltration is necessary to cause tissue damage. Two
variants of this disease have been described recently, the
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myeloproliferative and the lymphocytic variants.

Multiple organ systems are usually affected but cardiac
involvement in the form of endomyocardial fibrosis,
valvular regurgitation, mural thrombosis, ischemia and
congestive cardiac failure results in significant morbidity
in children.4 Central nervous system involvement is seen
with peripheral neuropathies, hemiplegia, paraplegia
encephalopathy, memory loss and ataxia. Diarrhea,
hepatosplenomegaly, hepatic dysfunction, ascites, chronic
active hepatitis and sclerosing cholangitis are few
gastrointestinal manifestations. Renal manifestations
include acute renal failure, chronic renal failure,
immunotactoid
glomerulopathy,
crescentic
glomerulonephritis and membranous glomerulopathy.
Anemia, thrombocytopenia and thrombotic episodes are
the common hematological manifestations. Some have
underlying malignancy while others progress to
eosinophilic leukemia. Skin manifestations are
nonspecific. The rashes can be macular, papulo-vesicular
or maculopapular. Urticaria and angioedema may be
seen. Mucosal ulcerations are common HES is difficult to
differentiate from eosinophilic leukemia as both have
common features at presentation. However, eosinophilic
leukemia may be associated with clonality, abnormal
karyotyping and presence of more than 5% blasts in the
marrow and more than 25% immature eosinophils in
peripheral smear or marrow. 4,5 Treatment includes
glucocorticoids, hydroxyureas, and cyclosporin and
interferon alpha. Cardiac or neurological dysfunction at
onset results in aggressive clinical course and treatment
failure. Newer modalities of therapy include the use of
imatinib mesylate, monoclonal anti IL5 antibody and
stem cell transplantation after nonmyeloablative
conditioning.6-9
In the present case, multisystem dysfunction was
present at the onset in the form of renal, hematological,
cutaneous, pulmonary and hepatic dysfunctions. There
was no cardiac or neurological involvement. The renal
involvement seen in this patient has been reported in a
patient with eosinophilic fasciitis and IgA nephropathy.10
The favorable response to steroids seen can be due to
absence of cardiologic or neurological dysfunction at
onset.3 However, the persistence of high AEC beyond six
months of withdrawal of the suspected offending drug(s)
makes this diagnosis less likely and further we were not
able to identify any etiological factor in him. Although
this patient had borderline ANA positivity, autoimmune
disease was not considered in him because the clinical
and laboratory features were more in favour of HES and
did not fit into any known spectrum of autoimmune
diseases.
CONCLUSION
HES is a multisystem disorder secondary to eosinophilic
infiltration of unknown etiology. In the present case the
above documented features fulfill the criteria for the
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Hypereosinophilic Syndrome
syndrome of HES. What is interesting is not only the
rarity of the case, but the rewarding response in freeing
the child of symptoms and a possible cure.
REFERENCES
1. Chusid MJ, Dale DC, West BC Wolff SM. The
hypereosinophilic syndrome: analysis of fourteen cases with
review of the literature. Medicine (Baltimore) 1975; 54: 1-27.
2. Boxer LA. Hypereosinophilic syndrome. In Behrman RE,
Kliegman RM, Jenson HB, eds. Nelson textbook of Pediatrics. 17th
edn. Philadelphia; Saunders, 2004; 710.
3. Schooley RT, Flaum MA, Gralnick HR, Fauci AS. A clinico
pathologic correlation of the idiopathic hypereosinophilic
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4. Alfaham MA, Ferguson SD, Sihra B, Davies J. The idiopathic
hypereosinophilic syndrome. Arch Dis Child 1987; 62 : 601-613.
5. Bain BJ, Eosinophilic leukemias and the idiopathic

Indian Journal of Pediatrics, Volume 73March, 2006

hypereosinophilic syndrome. Br J Haematol 1996; 95 : 2-9.

6. Roufosse F, Bartholome E, Schandene L, Goldman M, Cogan
E.The idiopathic hypereosinophilic syndrome: Clinical
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8. Klion AD, Law MA, Noel P, Kim YJ, Haverty TP, Nutman TB.
Safety and efficacy of monoclonal anti interleukin 5 antibody
SCH 55700 in the treatment of patients with hypereosinophilic
syndrome. Blood 2004; 103 : 2939-2941.
9. Juvonen E, Volin L, Koponen A, Ruutu T. Allogeneic blood
stem cell transplantation following non-myeloablative
conditioning for hypereosinophilic syndrome. Bone Marrow
Transplantation 2002; 29: 457-458.
10. Takeda S, Takazakura E, Fukui Y. Tubulointerstitial nephritis
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