Idiopathic Hypereosinophilic Syndrome (IHES) is a rare disease that can be difficult to diagnose as the differential is broad. This disease can cause significant morbidity and mortality if left untreated. Our patient is a 17-year-old adolescent female who presented with nonspecific symptoms of abdominal pain and malaise. She was incidentally found to have hypereosinophilia of 16,000 on complete blood count and nonspecific colitis and pulmonary edema on computed tomography. She went into cardiogenic shock due to papillary rupture of her mitral valve requiring extreme life support measures including intubation and extracorporal membrane oxygenation (ECMO) as well as mitral valve replacement. Pathology of the valve showed eosinophilic infiltration as the underlying etiology. The patient was diagnosed with IHES after the exclusion of infectious, rheumatologic, and oncologic causes. She was treated with steroids with improvement of her symptoms and scheduled for close follow-up. In general patients with IHES that have cardiac involvement have poorer prognoses.
Hypereosinophilic Syndrome (HES) is a rare disease in childhood, usually occurring between 20 and 50 years of age, with the true prevalence unknown [
This is a 17-year-old female with a history of depression, anxiety, chronic abdominal pain, and heavy and painful menses for which she takes an oral contraceptive pill. She presented with a two-week history of worsening abdominal pain, described as a constant dull ache located in the pelvic region and accompanied by nausea with bilious emesis, and mild chest pain. She had been seen in her primary care physician’s office four days prior to admission and given hyoscyamine for her pain with minimal relief. No associated menstrual symptoms were noted.
The patient admits to smoking 5–7 cigarettes daily but denies any drug or alcohol use. Her last sexual encounter was 6 months prior to admission and she denies any prior pregnancy or sexually transmitted infections.
She presented to the Emergency Department and vital signs showed tachycardia and elevated blood pressure. Her cardiac examination was normal and there was no prior history of any murmur. Her abdominal exam showed diffuse tenderness in the lower quadrants and pelvic area, without distension. Cervical motion tenderness was elicited and white discharge was noted on pelvic exam. Wet prep was negative for trichomonas, yeast, and clue cells. Laboratory values were significant for leukocytosis of 30,850 and eosinophilia of 52.4%. Computed tomography (CT) of the abdomen showed thickening and edema of the wall of the duodenum and proximal jejunum, ascites in the upper abdomen, and appearance of a collapsed hemorrhagic cyst/corpus luteum in the left adnexa. The patient was given intravenous doxycycline, cefotetan, and analgesia prior to admission.
Gynecology was consulted and treatment was directed towards a ruptured ovarian cyst. No surgical intervention was recommended and plan was to treat patient for a possible culture negative pelvic inflammatory disease. Repeat complete blood count was unchanged with eosinophilia and leukocytosis and clinically patient was improving.
On day two of admission she had an acute decompensation with bilious emesis and severe hypotension. She became hypoxic and was transferred to the pediatric intensive care unit, for suspected septic shock, where she was emergently intubated and started on inotropic support. She was taken to the operating room for an exploratory laparotomy. The small bowel was edematous and thickened throughout the proximal jejunum with full thickness enteritis. Areas of serosal erosion and adherent omentum as well as an area of pale bowel with lymphadenopathy were noted. A diverting jejunostomy was performed to allow the inflamed bowel to decompress and a specimen was sent to pathology.
She continued to decompensate and was started on high frequency oscillatory ventilation with nitric oxide. Her chest X-ray showed worsening interstitial and alveolar edema (Figure
(a) Chest X-ray showing complete opacification of the thorax suspicion for complete lung consolidation secondary to edema. (b) Echocardiogram images showing flail mitral valve from a ruptured cord and severe mitral regurgitation.
Pathology specimens, peripheral smear, bone marrow, bowel, and heart valve all demonstrated marked eosinophilic infiltration (Figures
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HIV |
Nonreactive |
Hepatitis A, hepatitis B, and hepatitis C | Nonreactive |
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Negative |
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Negative |
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Negative |
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Negative |
Blood/fungus cultures | Negative |
Urine cultures | Negative |
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ANA (blood and abdominal fluid) | Negative |
DSDNA/SSA Ab | Negative |
Smith/RNP Ab | Negative |
ANCA | Negative |
C3 | 39 mg/dL |
C4 | 2 mg/dL |
IgG | 345 mg/dL |
IgA | 111 mg/dL |
IgM | 143 mg/dL |
IgE | 191 kU/L |
CD4 helper cells | 34.3% |
CD8 suppressor cells | 26.4% |
Total CD3 | 66.2% |
Total B-cells | 28.9% |
Natural killer cells | 3.2% |
CD4/CD8 ratio | 1.3 |
T-cell interpretation | Normal total B-cells |
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Beta hCG (urine) | Negative |
Cortisol |
13.4 |
Tryptase | 2.6 |
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PDGFRa (4q12) FISH | Normal |
PDGFRb (5q33) FISH | Normal |
FGFR1 (8p11) FISH | Normal |
BCR/ABL1/ASS1 t(9,22) FISH | Normal |
KIT (c-KIT) mutation | Not detected |
Next-Gen Sequencing myeloid disorders profile |
No evidence of mutation in any of genes tested. Low probability of myeloid neoplasm diagnosis (<10%) |
(a) Peripheral smear: marked eosinophilia (most eosinophils show intact cytoplasmic granules). (b) Bone marrow biopsy: normocellular marrow with mild megakaryocytic hyperplasia, eosinophilia, and no increase in blasts. No monoclonal B-cells or immunophenotypically abnormal T-cells are detected.
(a) Jejunum: diffuse marked eosinophilic infiltrate associated with ischemic tissue damage. (b) Mitral valve: benign endomyocardial tissue demonstrating myocardial necrosis and fibrinous endocarditis with mixed inflammatory infiltrate comprising of eosinophils, lymphocytes, and histiocytes.
She was diagnosed with IHES and received a single dose of ivermectin before she was started on solumedrol. She was discharged to inpatient rehabilitation on day 27 and then returned for ostomy reversal 5 days later.
HES is defined as an absolute eosinophil count of greater than 1,500/mm3 that is associated with end organ damage that cannot be explained by another cause aside from the eosinophilia [
HES among the pediatric population has a heterogeneous presentation, most commonly with fever, arthralgias, and rash [
IHES, which we believe our patient has, is a diagnosis of exclusion and can only be made once all secondary causes of hypereosinophilia have been excluded. There must be an absence of eosinophil blasts in the blood and bone marrow [
There may be a different underlying pathogenesis in IHES of pediatric patients as compared to adult patients. There is only a slight male predominance in the pediatric population, whereas adult males have a predominance of 9 : 1 [
Cardiac involvement carries the highest morbidity and mortality and classically occurs in stages. Degranulated eosinophils in peripheral blood smears can indicate endocardial disease [
Eosinophilic colitis with low ESR, as was present in our patient, is a common GI manifestation, as well as hepatitis, hepatosplenomegaly, cholangitis, and pancreatitis [
Neurologically the disease can present as hemiplegia (focal deficits), peripheral neuropathy, or an altered behavior or cognitive dysfunction. Most patients with IHES with neurologic involvement also have an associated endocarditis with emboli being a source of the CNS complications. Neurotoxins have also been found in eosinophils which may account for the diffuse altered mental status [
Dermatologic manifestations include mucocutaneous ulcers, pruritic papules, and nodules as well as a reported case of recurrent vesicular rash with necrotic crusting lesions [
The differential for causes of hypereosinophilia is vast and a thorough investigation is indicated [
The goal of treatment is to keep absolute eosinophil counts below 1,500. If patients are asymptomatic they may be observed but with serial echocardiograms and close follow-up. First-line treatment for IHES is corticosteroids [
Surgery including heart valve replacement for severe mitral regurgitation is not uncommon although it is usually not as emergent as in our patient whose regurgitation was caused by papillary muscle rupture. Endocardial decortication and heart transplant may also be warranted but not as commonly [
If untreated, the morbidity and mortality can reach 80% at 3 years for the IHES. With treatment the survival rate increases to 80% at 5 years and 42–60% at 10 years [
Idiopathic Hypereosinophilic Syndrome
Hypereosinophilic Syndrome
Extracorporal membrane oxygenation.
The authors declare that they have no conflict of interests regarding this paper.
Tiffany Tamse was involved directly in patient care, conducted a literature search of the topic of IHES, drafted the initial paper, and approved the final paper as submitted. Avind Rampersad was involved directly in patient care, reviewed and revised the paper, and approved the final paper as submitted. Alejandro Jordan-Villegas was involved directly in patient care, reviewed and revised the paper, and approved the final paper as submitted. Jill Ireland was involved directly in patient care, conducted a literature search of the topic of IHES, helped to draft parts of the initial paper, and approved the final paper. All authors approved the final paper as submitted and agree to be accountable for all aspects of the work.