Discussion
Hypereosinophilic Syndrome (HES) is defined by an abnormal
overproduction and deposition of eosinophils in the blood or peripheral
organs leading eosinophil - mediated organ damage or
dysfunction.4 HES has been further divided based on
etiology into primary (stem cell, myeloid or eosinophilic malignancy),
secondary (parasitic infections, solid tumors, T cell lymphoma), or
idiopathic.3 According to various sources idiopathic
HES is an extremely rare disease and its incidence ranges from 0.04 to
0.17 per 100,000 persons and the prevalence ranges from 0.15 to 0.89
cases per 100,000 persons.5 Due to advances in
diagnostic techniques, causes of eosinophilia can be identified in a
proportion of cases that in the past would have been classified as
idiopathic. However, due to the unavailability of services in Nepal,
some of the investigations of the indexed case were sent to India for
further evaluation. The hypereosinophilic syndrome reports male
predominance, with a male-to-female ratio of 9:1.5 HES
is commonly diagnosed in patients aged 20-50 years, with a peak
incidence in the fourth decade. This study also exemplified that 38
years-old male case presented with rare clinical manifestations of
hypereosinophilic syndrome.
The most common cause of eosinophilia in the United States is an
allergic reaction or allergic disease.6 Worldwide, the
most common cause of eosinophilia is parasitosis.7Several mechanisms have been proposed for the pathogenesis of
hypereosinophilic syndrome, including the overproduction of
eosinophilopoietic cytokines, their enhanced activity, and defects in
the normal suppressive regulation of
eosinophilopoiesis.8 Eosinophils amplify the
inflammatory cascade by secreting chemoattractants that recruit more
eosinophils.9 Organ damage-induced HES is due to the
eosinophilic infiltration of the tissues accompanied by the mediator
(major basic protein, eosinophil peroxidase, eosinophil-derived
neurotoxin, and eosinophil cationic protein) release from the eosinophil
granules.9 The case presented in this study was
suspected of the parasitic infestation and later further investigations
reported that the cause could be eosinophilic leukemia. A similar case
of hypereosinophilic syndrome case was presented with features of
dilated cardiomyopathy as a dilemma to approach and treatment, as our
case with the presentation of bilateral hydro pneumothorax as
presentation.10
HES is a heterogeneous disease process with multiple manifestations that
may occur simultaneously or individually.4 The
presentation can be sudden and dramatic, with cardiac, neurologic, or
thrombotic complications, but, more often, the onset is insidious. HES
can involve any organ system but commonly involves the respiratory
tract, skin, central nervous system, and cardiac.4Many patients experience fever and night sweats. Some sources identify
anorexia and weight loss as common presenting manifestations. Cardiac
involvement is the leading cause of mortality and common symptoms of
cardiac involvement include chest pain, dyspnea, or orthopnea. A
chronic, persistent cough, usually nonproductive, is the most common
respiratory symptom reported in hypereosinophilic syndrome. Rhinitis or
angioedema is sometimes a presenting feature. Dyspnea may occur in
cardiac or respiratory involvement. Embolic or thrombotic strokes or
transient ischemic episodes may occur and are often the initial
manifestations. Some patients with HES experience encephalopathy caused
by CNS dysfunction. Peripheral neuropathies account for about 50% of
all neurologic symptoms in HES.
Arthralgia, myalgia, pruritus, diarrhea, and fatigue are relatively
common manifestations of HES but are non-specific. However, the case in
this study demonstrated some of the abovementioned clinical such as
shortness of breath, dry cough, and chest pain.
The decision to use a drug for the treatment of HES depends partly on
the presence or absence of organ involvement.4 So, the
initial evaluation of the patient with eosinophilia should include tests
that facilitate the assessment of target organ damage. In asymptomatic
patients’ treatment is postponed till a diagnostic workup is completed
and a specific diagnosis is made. Early initiation of therapy is
reasonable in clonal eosinophilia associated with imatinib
mesylate—sensitive molecular markers (eg, FIP1L1-PDGFRA,
PDGFRB rearrangement, BCR-ABL ). In idiopathic HES no evidence to
support early drug treatment. Periodic follow-up with monitoring of
complications is reasonable (no evidence to support
this).2 Symptomatic patients with clonal HES imatinib
mesylate are the first drug to be considered in the presence ofFIP1L1- PDGFRA or PDGFRA/PDGFRB translocations. For
induction of remission and maintenance 100mg/d of Imatinib mesylate is
recommended. In the case of rare mutant FIP1L1-PDGFRA,
imatinib-resistant, other tyrosine kinase inhibitors or interferon-alpha
is sensitive for induction of remission. In refractory cases,
allogeneic hematopoietic cell transplant needs to be
considered.8 The case in this study firstly was
treated with oral antiparasitic medications and steroids, later he
underwent anti-tubercular therapy.
In 2018 RN Das et al reported the first case in Nepal of idiopathic HES
presented with fatal eosinophilic cardiomyopathy and
dysphagia.11 They reported the case of a farmer
presenting with symptoms of persistent fever, cough, dyspnea, and
refractory heart failure for 7 months with peripheral eosinophilia. They
found no cause for eosinophilia despite a thorough evaluation.12 In 1971, similarly Rickles et al reviewed 16 cases
of hypereosinophilic syndrome, most of which were doubtful eosinophilic
leukemia.13 In 2009, a multicenter study conducted by
Princess U Ogbogu in 161 patients with eosinophilia found FIP1L1-PDGFRA
test positive in 18 patients. 11
The strength of this case study is that this has reported a rare case,
and this has been reported in a tertiary care hospital in Nepal. This
case report has been presented with several limitations. This case
report reported only one case; thus, several such case studies would
help to provide us with comprehensive information. Due to the
limitations in the equipment and other resources, timely diagnosis has
been one of the major challenges. Many investigations were sent to India
due to unavailability in Nepal. So, the studies highlighting the
challenges might contribute to disseminating the information and filling
up the gap.