Idiopathic Hypereosinophilic Syndrome (HES) is a rare
condition with organ damage secondary to high eosinophilic counts and
marked eosinophilic tissue infiltration. The presentation is generally
in the adult age group. We report a child with this syndrome who along
with the usual features of the syndrome also had the unusual
presentation of pericardial effusion, which resolved after treatment.
Case Report
An 11-year-old boy was admitted with complaints of
low-grade continuous fever, along with non productive, non spasmodic
cough, bilateral diffuse chest pain increasing on coughing, generalized
weakness and dyspnea for a period of 2 months. There was no history of
any rash, ear discharge, burning micturition, orthopnea, paroxysmal
nocturnal dyspnea, wheezing, hematuria, anuria or dysuria. There was no
history of palpitation or swelling in any part of the body, jaundice or
any bleeding tendencies, joint pains, limitation of movements or any
history of worm infestation or allergic disorders. There was no history
of contact with a tuberculous patient. The child was not consuming any
medications and was on a vegetarian diet. There was no history of a
similar illness in the family.
At admission, the child was sick with a pulse rate of
116/min, respiratory rate of 44/min with subcostal and intercostal
retractions and a blood pressure of 104/80 mmHg. He had raised jugular
venous pressure. There was no pallor, icterus, cyanosis, clubbing, edema
or significant lymphadenopathy. The anthro-pometry was normal.
Examination of the chest revealed diminished chest excursions with a
dull percussion note at the lung bases, auscultation revealed bilateral
decreased air entery in the lower zones. Cardiac apex was at the left
5th intercostal space just outside the mid clavicular line with distant
heart sounds, though both heart sounds were normal and no murmurs could
be heard. Liver was palpable 2 cm below the costal margin in the mid
clavicular line. It was non tender, soft in consistency with a smooth
surface. Spleen was palpable 2 cm below the costal margin in the mid
clavicular line, it was non tender, firm in consistency. Fundus
examination was normal. Rest of the systemic examination was within
normal limits.
Investigations revealed: Hb: 12gm%, TLC: 39,600/mm3,
DLC: Polymorphs 14%, Lymphocytes 8%, Eosinophils 78%, Absolute
eosinophilic count (AEC) of 30,800/mm3 and a platelet count of 2.0 lac/mm3.
ESR was 90 mm/1st hour. Peripheral blood smear examination showed marked
eosinophilia with normal morphology of other cells. X-ray chest
revealed bilateral pleural effusion and bilateral perihilar opacities
with pericardial effusion; confirmed by echocardiography. Pleural tap
showed 9,600 eosinophils/mm3, Gram stain, cultures and staining for Acid
Fast Bacilli was negative. Pericardial tap also revealed mainly
eosinophils. Bacteriological and fungal cultures of the pericardial
fluid were negative. PCR for tuberculosis of the pericardial fluid was
also negative. Liver biopsy revealed a normal architecture but marked
eosinophic infilteration. SGOT, SGPT, Alkaline Phosphatase, Blood Urea,
Serum Creatinine were within normal limits. Mantoux test (administered
as 5 Tuberculin Units) was non-reactive. Stool examination was normal.
Peripheral smear for malarial parasite was negative. Filarial serology
as well as smears were negative. ELISA for Human Immunodeficiency Virus
(HIV) was non reactive. Rheumatoid factor and anti-nuclear antibodies
were negative. Ultrasound abdomen was within normal limits. Bone marrow
examination did not reveal any abnormal cells or parasites however there
was preponderance of eosinophils and eosino-philic precursors.
Hematological parameters of the parents were normal.
Child was started on albendazole and was given
ceftriaxone and ampicillin for a period of 2 weeks but there was no
change in the clinical, radiological or pleural tap findings. In view of
the persisting eosinophilia he was given a 21 day course of
diethylcarbazine (at 6 mg/Kg/day) but still there was no change in
clinical, radiological or hematological findings. Repeated stool
examinations for ova and cysts were negative for common parasitic
infections. Since there was no other cause to attribute to the above
findings and with persistence of hypereosinophilia, a diagnosis of
Idiopathic Hypereosinophilic Syndrome was made.
The child was subsequently put on prednisolone at
1mg/kg/day and followed up. After 1 week of this therapy, there was
clinical improvement with lowering of the absolute eosinophilic count to
1,100/mm3 and improvement in chest X-ray with resolution of
pericardial effusion. The child over the next two weeks developed
features of severe gastritis (documented on endoscopy) and therefore
steroids were tapered. Over the next week the child again had increased
eosinophilic counts (AEC 3000/mm3) and also developed erythematous
papulo-nodular swellings allover the body with predominance on the
trunk. Skin biopsy revealed marked infiltration of eosinophils. Steroids
were reintroduced and within 2 weeks ABC had fallen to 1,000/mm3. Child
remained stable for a period of 6 weeks. There was reduction in
hepatosplenomegaly (liver and spleen regressed to 1 cm each below the
costal margin). Subsequently, he developed pneu-monitis, which was
confirmed by a chest X-ray and due to which the steroids were
tapered. His pneumonitis improved after 2 weeks of IV Ceftazidine,
Amikacin and Ampicillin. His AEC again rose, this time to 6,250/mm3.
Steroids were again added but this time eosinophils showed only a
marginal reduction in numbers. At this point, hydroxyurea was added and
there was reduction in the eosinophilic counts over the next 15 days.
Presently, the child is being maintained on low dose steroids (0.5
mg/Kg) and hydroxyurea (at 20mg/Kg/day). After 2 months of starting
hydroxyurea, his AEC is 450/mm3. He is remaining asymptomatic on this
regime and is on regular follow up for the past 6 months.
Discussion
The defining characteristics of this rare entity were
first described by Chusid, et al.(1) as peripheral blood
eosinophilia >1500/µL persisting for more than 6 months; absence of
parasitic, allergic, or other causes of eosinophilia; and manifestations
of organ involvement or dysfunction. The syndrome is generally seen
after the second decade of life with very few reports in the pediatric
population. Acute eosinophilic leukemia should be kept in the
differential diagnosis. Some of the common causes of hyper-eosinophilia
should be ruled out before a diagnosis of Idiopathic Hypereosinophilic
Syndrome is made(2).
The clinical presentations include weakness, fatigue,
cough, dyspnea, myalgia, angioedema, rashes, fever, rhinitis. The
symptomatology of Idiopathic HES is due to the eosinophilic tissue
damage related to the release of major basic proteins, eosinophil
peroxidase, eosinophil cationic proteins and eosinophil-derived
neurotoxins(2-4). Al-though almost any organ may be involved, the heart,
skin, nervous system, lungs, spleen, liver, eyes and the GI tract are
typically affected. Cardiac involvement is the most prominent cause of
morbidity and mortality(5,6). The course of events of cardiac
involvement can be staged as the Acute necrotic stage (5.5 weeks):
Presenting as a clinically silent stage with damage to the endocardium
and infiltration of the myo-cardium with eosinophils and histopatho-logic
evidence of myocardial necrosis, eosino-philic degranulation and micro
abscesses. This is followed by the thrombotic Stage (10 months) with
evidence of thrombosis along the endocardium and valve leaflets. The
last stage is the fibrotic stage where there is progressive scarring
that may lead to entrapment of the chordae tendinae, causing Mitral or
Tricuspid regurgitation, endocardial fibrosis and features of
restrictive cardio-myopathy. Mural thrombi provide a source for systemic
or pulmonary emboli. At this stage patients often present with dyspnea,
chest pain, signs of heart failure or new onset murmurs. Our case also
had the unusual presentation of pericardial effusion. Cutaneous
manifestations include urticarial lesions, angioedema, purpuric papules
and nodules, cutaneous micro thrombi. Neuro-logical manifestations are
generally impaired cognition, altered behavior, spasticity and
occasionally ataxia, focal deficits from cardiac emboli and peripheral
neuropathy. Pulmonary manifestations include a chronic persistent,
generally nonproductive cough. Symptoms secondary to emboli, thrombosis
and cardiac failure are the other pulmonary presentations.
Hepatosplenomegaly, blurring vision and diarrhea are some of the less
common presentations. Our patient had hepatosplenomegaly and pulmonary
mani-festations.
The primary aim of the management is to keep the
eosinophilic counts low. Some of the treatment options as summarized by
Weller and Bubley(5) are as follows. Patients with no organ dysfunction
or symptoms despite high AEC, without defining features of HES need a
close 3 to 6 monthly follow up(2,5,7,8). Steroids started at lmg/Kg/day
are indicated in the symptomatic patient with subsequent tapering and
maintenance as per clinical and laboratory parameters. Those
unresponsive to steroids can be given hydroxyurea. Acute reductions in
eosinophilic counts can be brought about by vincristine. The onset of a
decrease in blood eosinophilia is within 1 to 3 days. Vincristine
treatment may become limited by its neurologic complications. Imatinib
mesylate is a promising drug in the treatment of Idiopathic
Hypereosinophilic Syndrome with response seen as early as one week after
starting treatment, though more data are awaited for its use in the
pediatric population(9).
Long term prognosis of patients with Idiopathic HES
continues to be rather poor with a 40% reported mortality at 10
years(5). With maintainence of low eosinophilic counts and aggressive
medical and surgical treatment (managing thrombo-embolism, mitral or
tricuspid valve replacements in severe regurgitation, endocardial
resection in marked cardiac fibrosis) significant reduction in morbidity
and mortality have been noted.
Contributors: AJ did the literature search and
prepared the manuscript. APD conceived the idea, revised the manuscript
and will act as the guarantor for the paper. AJ, APD and SS all were
involved in the treatment of the patient.
Funding: None.
Competing interests: None stated.
