Keywords hypereosinophilia - gastroenteritis - cystitis - endocarditis
Introduction
A rare and diverse group of conditions known as hypereosinophilic syndromes (HES)
is defined as chronic and marked blood eosinophilia (> 1.5 × 10(9)/L for more than
six consecutive months) along with evidence of eosinophil-induced organ damage after
other causes of hypereosinophilia (HE), such as allergies, parasitic diseases, and
malignant disorders, have been ruled out.[1 ] Young to middle-aged patients with a variety of indications that can appear simultaneously
or separately are most susceptible to HES. The onset could be abrupt and severe, leading
to issues with the heart, gastrointestinal system, nervous system, or thrombosis.[1 ] Eosinophilic gastroenteritis is characterized by the triad of peripheral eosinophilia,
alterations in gastrointestinal function (such as dyspepsia, obstruction, diarrhea,
and ascites), and exclusion of other illnesses with peripheral eosinophilia (such
as parasite infections and drug-induced causes).[2 ]
The rare and poorly understood clinicopathologic condition known as eosinophilic cystitis
can also manifest in the postpartum period. It is characterized by a significant local
eosinophilic infiltration in all the three layers of bladder wall. Urinary frequency
(67%), dysuria (62%), gross/microscopic hematuria (68%), suprapubic discomfort (49%),
and urine retention (10%) are the most typical presenting symptoms, according to Neeman
et al.[3 ]
HE is a systemic disease that can show itself in several ways. Eosinophilic endocarditis,
a rare consequence of HE, results in endomyocardial eosinophil infiltration and degranulation,
causing fibrosis and constrictive ventricular filling. Left or biventricular involvement
occurs more commonly.
Eosinophils can harm target organs in a variety of ways, with the skin, heart, lungs,
gastrointestinal tract, genitourinary tract, and central and peripheral nervous systems
accounting for more than 50% of cases.[4 ]
[5 ] Other frequent side effects include hepato and/or splenomegaly, eosinophilic gastroenteritis,
and coagulation issues.[5 ]
Three young people who presented with eosinophilic gastritis, cystitis, and endocarditis
are emphasized in this case series.
Case1
We present a case of a 36-year-old male who came to our outpatient department with
complaints more than 20 episodes of diarrhea per day for 2 months that was at times
mixed with blood. The patient also had complaints of pain in the lower abdomen for
3 weeks with decreased appetite and nausea. He was initially taken to a private practitioner
and was given medication for his symptoms that provided no significant relief, so
he was referred to out hospital.
The patient was dehydrated at arrival, as evidenced by his low blood pressure of 90/60 mm
Hg and a heart rate of 140 beats per minute. His body temperature was normal. Clinical
examination showed only mild lower abdominal tenderness. Blood counts were sent that
revealed total leucocyte count of 43.0 × 103cells/mm3 with markedly raised level of eosinophils (absolute eosinophil count—2,236 /mm3 ). Other serum chemistries including liver and kidney function showed no abnormality.
Tests for viral hepatitis, human immunodeficiency virus (HIV), and autoimmune conditions
showed negative results. Stool microscopy confirmed the presence of blood but did
not show any presence of ova, cysts, or any sign of parasitic infestation. Blood culture
showed no growth of pathological organisms. Chest radiography and ultrasound of abdomen
were found to be normal. There were no serious food or medication allergies in the
patient's past. He also had no recent drug history and was not on any medications
prior to developing present complaints.
A coloscopy was planned after a gastroenterologist referral that revealed multiple
erosions with scattered ulcers involving entire colon, rectum, and extending up to
terminal ileum as shown in [Fig. 1 ]. Biopsy from ileum and colon was taken and sent for histopathological examination
that revealed inflammatory infiltrates predominantly eosinophils along with lymph
histiocytic infiltrates; section also shows unremarkable submucosal glands suggestive
of eosinophilic enteritis. As diagnosis was confirmed, so bone marrow examination
was not done.
Fig. 1 Colonoscopy showing multiple erosions.
Patient was started on oral prednisolone as per his weight suspecting eosinophilic
gastroenteritis. After 2 days, patient had dramatic relief in symptoms including complete
relief in diarrhea and improvement in his appetite. Biopsy results as shown in [Fig. 2 ] confirmed the diagnosis and discharge of the patient was done on oral prednisolone,
with the dosage gradually tapered. After 2 weeks of corticosteroid therapy, the patient
had no symptoms and repeat complete blood count showed a normal white blood cell count
with a normal eosinophil level. Patient was followed up after a period of 1 month
and was doing well.
Fig. 2 Sections stained with hematoxylin and eosin stain (high power view 40x) showing unremarkable
villi, deeper tissue showing fibro collagenous stroma with extensive acute on chronic
inflammatory infiltrates predominantly eosinophils along with lymph histiocytic infiltrates,
and section also showing unremarkable submucosal glands, suggestive of Eosinophilic
enteritis (empty arrow).
Case 2
A 41-year-old female patient presented to medicine outpatient department with a history
of abdominal pain for the last 7 days; pain was diffuse and dull aching and more around
the umbilicus and she had two to three episodes of vomiting for the last 2 days, which
was containing food particles and nonbilious and not containing blood. Patient also
had a history of fever that was subsided from past 3 days, which was low grade in
nature and not associated with chills or rigor. Patient did not have any history of
asthma, tuberculosis, diabetes mellitus, or systemic hypertension or any other co
morbidities. Patient denied of having any allergies to drugs and other substances.
Patient did not have any prior history of hospitalization. General condition at presentation
was stable, febrile on touch with temperature of 99 °F, pulse of 92 beats per minute,
blood pressure of 100/70 mm Hg, respiratory rate of 20/min, and abdominal examination
showed suprapubic tenderness and guarding with no rigidity or organomegaly. Respiratory
system examination and cardiac examination were within normal limits. Ultrasound of
abdomen was done which showed normal study.
Blood counts were sent that revealed total leucocyte count of 32.4 × 103 cells/mm3 with markedly raised level of eosinophils (absolute eosinophil count—6,500 /mm3 ) that is shown in [Fig. 3 ].
Fig. 3 Peripheral smear of the patient showed eosinophilia (empty arrow).
Peripheral smear examination was suggestive of absolute eosinophil count of 6,500.
Other biochemical and microbiological reports were normal. Patient was advised for
bone marrow but she denied to give consent for the same. Also, viral markers were
sent for ruling out hepatitis or HIV that came negative. Urine routine microscopy
was done that was suggestive of plenty of epithelial cells, no pus cells, or ova or
any parasites. We could not take biopsy from cystitis as patient was postpartum and
breastfeeding. Patient was started with antibiotics, steroid and supportive treatment.
Patient improved drastically by clinical profile and laboratory parameters. Patient
was discharged with eosinophil count of 4 and she was doing well on follow-up after
1 month with 5 mg of prednisolone.
Case 3
A 25-year-old tribal woman appeared with a widespread rash and 1 week of increasing
dyspnea on exertion. Her palms and soles were spared as the rash, which started on
her neck, moved down her body. In addition, she experienced dyspnea symptoms with
effort without any prior restrictions. She ruled out any recent travel or medical
encounters. The patient denied having any chest pain or a cough that was productive.
She had been on olanzapine for a year for schizophrenia and bipolar disorder, according
to her medical history, but no regular follow-up care was reported, so she kept taking
olanzapine once daily.
The patient was afebrile, with a blood pressure reading of 100/60 mm Hg, a pulse rate
of 114, an oxygen saturation of 94% on room air, and a respiratory rate of 26 breaths
per minute at the time of presentation. Her pulmonary examination was normal, and
her cardiovascular assessment revealed nothing unusual than tachycardia. She did not
have lower extremity edema or jugular venous distention. Lymphadenopathy was not present.
During her physical examination, a generalized, maculopapular rash that spared her
palms and soles were also noticeable. As indicated in [Fig. 4 ], laboratory tests revealed an eosinophil count of 4,500/L and a total blood count
significant for white blood cells of 34.2 × 103/L. Troponins I was normal.
Fig. 4 Peripheral smear of the patient showed eosinophilia (empty arrow).
For influenza A, our patient tested negative. The HIV was negative by voluntary counseling
and testing center. Panel for hepatitis was negative. It was negative for antinuclear
antibodies. Bone marrow examination was normal.
T-wave inversions and nonspecific ST-segment alterations were visible on the electrocardiogram.
As seen in [Fig. 5 ], transthoracic echocardiography revealed no left ventricular involvement and a dilated
right ventricle with a significant (2.9 × 2.8 cm) echo density fixed to the right
apex, consistent with Loeffler endocarditis. Transthoracic echocardiography additionally
revealed a flattened septum and mild tricuspid regurgitation.
Fig. 5 Transthoracic echocardiography demonstrating a dilated right ventricle.
Methylprednisolone was administered intravenously to this patient. Her dyspnea, rash,
and eosinophilia all subsided.
The etiology was endocarditis caused by olanzapine-induced HE, according to our workup,
which was described above. Our patient has been taking olanzapine for the past year
without routine follow-up. Olanzapine-induced HE is an uncommon and poorly understood
condition.
High-dose steroids helped help our patient's symptoms, and she was released with prednisone
taper instructions and appointments for follow-up care with our outpatient cardiology
clinic for serial echocardiography and hematology for additional workup. Additionally,
our case study emphasizes the significance of early disease detection. Patient was
doing well both clinically and biochemically (eosinophil count was 3) after 1 month
of follow-up.
Laboaratory parameter as complete blood counts of all the threes cases has been highlighted
in [Table 1 ]:
Table 1
Complete blood counts of all the three case
Investigation
Case 1
Case 2
Case 3
Hemoglobin
10 g/dL
11 g/dL
10.8 g/dL
White blood cells
43.0 × 103 /μL
32.4 × 103 /μL
34.2 × 103 /μL
Platelets
2.0 × 104 /μL
2.75 × 104 /μL
3.0 × 104 /μL
Eosinophils
2236 /μL
6500 /μL
4500 /μL
Neutrophils
30.0 × 103 /μL
20 × 103 /μL
22 × 103 /μL
Lymphocytes
15.8 × 103 /μL
13× 103 /μl
12× 103 /μL
Monocytes
4.3 × 103 /μL
0.2 × 103 /μL
1.8 × 103 /μL
Basophils
0.3 × 103 /μL
0.0 × 103 /μL
0.1 × 103 /μL
Absolute eosinophil ratio
1933 cells/cumm
6360 cells/cumm
2450 cells/cumm
Discussion
HES are characterized on the basis of (1) HE, more than 1,500 cells/mm3 on two independent
occasions separated by at least one month; (2) eosinophil-caused organ damage; and
(3) exclusion of other organ damage causes.[1 ]
HES is rare, with a frequency range of 0.36 to 6.3 per 1,00,000.[3 ] HES are often diagnosed between the ages of 20 and 50; however, cases in the senior
population, like those of our patient, have also been documented.[4 ] HES frequently have an impact on the skin, lungs, heart, spleen, and nervous system.[5 ] In the case of our patient, the patient reported having a temperature and experiencing
stomach pain, and an examination of the urine revealed many pus cells, which was indicative
of cystitis.
One of the standard HES criteria is eosinophilia, but this does not always indicate
how much an organ has been affected. Eosinophilic degranulation, as opposed to eosinophilia,
indicates obvious organ involvement and necessitates quick medical care. Studies both
in vivo and in vitro have shown that after being secreted, these cationic proteins
exert a variety of proinflammatory and cytotoxic effects.[3 ] Despite the fact that eosinophilic degranulation is typically thought to be a hallmark
of eosinophil activation, there have been no reports that show it to occur in eosinophilic
colitis (EC). It may be required to conduct more study on the pathophysiology of EC
and the role of eosinophilic degranulation, especially in patients who may have HES
as an underlying condition.[2 ] Eosinophilic degranulation in our patient was regarded to be a symptom of organ
damage.
We looked through the literature to find patients with EC who may have had HES. Most
of the individuals with either definite or probable HES were men. This is consistent
with the observation that the male-to-female ratio for EC was 9:1 for HES. However,
in our case series one patient was male and two patients were female, which may be
chance. The typical systemic HES symptoms of fatigue, coughing, dyspnea, rash, and
fever were not present in any of individuals.[6 ]
[7 ] Instead, dysuria and abdominal pain, both signs of cystitis and gastrointestinal
eosinophilic illness were the presenting symptoms. Just 4.5% of instances were considered
to involve an EC-related issue.[8 ] The patient's strange symptoms included ascites, granulomatous peritonitis involving
the pylorus, and hepatic nodules. The prognosis for EC is reportedly better than that
of HES. One case study included 83 adult EC patients, and 32 (or 39%) of them required
no treatment.[9 ] According to a different analysis, 91 (77%) of 118 EC patients received treatment
and recovered, with only 15 (13%) of them relapsing.[10 ]
We started treatment with prednisolone 30 mg/day. In a previous study of 188 individuals
with HES, the maximum daily dose of prednisolone was 40 mg. Lessening the symptoms
and maintaining low eosinophil counts were the goals of the treatment. Prednisolone
10 mg/day was the median maintenance dose in the same trial. Despite the fact that
the symptoms returned once after stopping prednisolone, they improved when prednisolone
was reintroduced at a lower dose together with an antiallergic drug. Mepolizumab,
hydroxyurea, or pegylated interferon is suitable choices for patients who do not respond
to the necessary dose of steroids.[10 ]
Conclusion
In the differential diagnosis of multisystem disorders, HES is infrequently used.
Before idiopathic HES, a thorough and methodical workup is necessary to rule out hypereosinophilia.
Most of the time, symptoms appear gradually, and eosinophilia may only be discovered
by chance in a tiny percentage of patients. Due to the quick development of cardiovascular,
genitourinary, and gastrointestinal problems, the initial signs are severe. The major
therapy for HES continues to be steroids.
