Article ID: 2023-0009-CR
Eosinophilic gastroenteritis (EGE) can occur throughout the gastrointestinal tract, from the stomach to the colon. Typical known symptoms are abdominal pain, nausea, vomiting, and diarrhea. In addition, lesions in the intestinal mucosa may cause weight loss, protein-losing enteropathy (PLE), and other problems. A 6-month-old girl with no previous medical history was brought to our hospital after an afebrile 1-min clonic seizure. Blood tests showed low concentrations of serum calcium and albumin. After the correction of hypocalcemia with gluconic acid, there was no recurrence of seizure. Technetium-99m scintigraphy showed slight leakage of protein from the intestinal tract, which led us to conclude that the hypocalcemia and hypoalbuminemia were caused by PLE. Gastrointestinal endoscopy and biopsy performed to detect the cause of PLE revealed the presence of EGE. After starting administration of an amino acid-based formula, gastrointestinal symptoms of diarrhea or vomiting did not reappear. The serum albumin concentration normalized, and her weight gain improved. We report the first case of EGE in an infant who was diagnosed based on seizure. This case shows that infants with EGE may present with seizure resulting from hypocalcemia caused by PLE.
Eosinophilic gastroenteritis (EGE) is a chronic immune disorder characterized by eosinophil infiltration of the gastrointestinal tract. This disease is rare, with an estimated prevalence of 22–28 cases per 100,000 people in the United States.1 Patients are predominantly adults between the ages of 30 and 50 years. Common clinical manifestations of EGE are abdominal pain, vomiting, diarrhea, and dyspepsia.2 This study presents the first case of EGE in an infant who was diagnosed based on seizure.
The patient was a 6-month-old girl with no specific medical history. She was born at 40 weeks’ gestation (weight, 2904 g). She was exclusively breastfed and fed well. However, she had poor weight gain of 100 g between 4 and 6 months of age. On presentation, she had a 2-day history of vomiting two or three times daily and diarrhea several times daily, without fever. On the day of presentation, the patient experienced a symmetrical clonic seizure upon awakening, which spontaneously ceased within 1 min, followed by 5–10 min of unconsciousness. The patient was rushed to our hospital, and a symmetrical clonic seizure was observed upon arrival at the hospital. This seizure resolved spontaneously within 1.5 min.
The patient was afebrile with a heart rate of 154 beats/min, a respiratory rate of 36 breaths/min, and oxygen saturation (pulse oximetry) of 99% on ambient air. Her weight on admission was 6314 g (−1.3 SD for her age) and her height was 66.0 cm (−0.1 SD). Physical examination showed lower leg edema and increased intestinal peristalsis. Blood tests revealed low concentrations of serum calcium (5.1 mg/dL) and albumin (1.5 g/dL). Urinary calcium excretion was less than 2.0 mg/dL, and urine protein was negative (Table 1).
| Analysis | Result |
| Blood count | |
| White blood cells | 10200 /mm3 |
| Neutrophils | 89% |
| Lymphocytes | 3% |
| Eosinophils | 0% |
| Monocytes | 0% |
| Hemoglobin | 11.5 g/dL |
| Platelets | 579,000 /mm3 |
| Blood gas analysis | |
| pH | 7.366 |
| pCO2 | 39.5 Torr |
| HCO3− | 22.6 mmol/L |
| Ionized Ca | 0.81 mmol/L |
| Base excess | −2.7 mEq/L |
| Biochemistry | |
| Albumin | 1.5 g/dL |
| Blood urea nitrogen | 3 mg/dL |
| Creatinine | 0.14 mg/dL |
| Na | 138.8 mmol/L |
| K | 3.5 mmol/L |
| Cl | 109 mmol/L |
| Ca | 5.1 mg/dL |
| P | 3.5 mg/dL |
| Mg | 0.8 mg/dL |
| Urinalysis | |
| Na | 17 mmol/L |
| K | 41.9 mmol/L |
| Cl | 92 mmol/L |
| Ca | <2.0 mg/dL |
| Ca/creatinine | <0.04 g/g |
| P | 82.4 mmol/L |
| Mg | 0.3 mmol/L |
| Total protein | 9 mg/dL |
| Total protein/creatinine | 0.20 g/g |
| Creatinine | 44.7 mg/dL |
Reference values for Ca/creatinine ratio in infants younger than 6 months are typically <0.8 g/g. Reference values for Total protein/creatinine ratio in children younger than 24 months are typically <0.5 g/g.
The patient was admitted in a fasting state, and central venous nutrition was initiated. After correction of hypocalcemia with gluconic acid, there was no recurrence of seizure. Computed tomography of the head was performed to exclude gross intracranial lesions. The scan showed no intracranial occupying lesions and no hemorrhages in the left or right ventricles. Electroencephalography and head magnetic resonance imaging were not performed because seizures did not recur and the consciousness level did not decrease after correction of hypocalcemia. The serum calcium concentration quickly improved, and the serum albumin concentration gradually increased. The stool antitrypsin concentration was high (714 mg/dL), and a protein leak was suspected. Technetium-99m scintigraphy showed slight leakage of protein from the intestinal tract.
Based on these results, the combination of protein-losing enteropathy (PLE) and associated secondary malabsorption was suspected to be the cause of the hypoalbuminemia and electrolyte abnormality. An endoscopy was performed to investigate the underlying disease. Although no abnormality was observed in the upper gastrointestinal tract, we observed mild inflammation of the intestinal mucosa and easy bleeding in the lower gastrointestinal tract. Inflammatory bowel disease was ruled out by the absence of erosion or ulcers in the gut. A biopsy performed at the same time showed negative results for intestinal lymphangiectasia, and lower gastrointestinal tract biopsy showed inflammatory cell infiltration in the stroma. Eosinophil counts were 28/high-power field (HPF) in the terminal ileum, 39/HPF in the cecum, 39/HPF in the ascending colon, 43/HPF in the transverse colon, and 39/HPF in the splenic flexure.
A diagnosis of EGE was made based on the presence of eosinophil infiltrates (Fig. 1). Treatment for EGE was initiated with an amino acid-based formula, and a decision was made not to start systemic corticosteroids. The patient’s gastrointestinal symptoms of diarrhea or vomiting did not reappear. Serum albumin concentrations normalized, and her weight gain improved. The patient was discharged 31 days after admission. No fever was observed during hospitalization. Informed consent was obtained from the patient’s mother for publication of the details of the case.
Histopathology of the transverse colon.
Inflammatory cell infiltrate was observed in the stroma with an eosinophil count of 43/high-power field. Magnification: ×400.
In the presented case, PLE or malabsorption secondary to EGE resulted in hypocalcemia, while the patient remained afebrile. Two previous case reports described infants with severe PLE that was attributed to intestinal lymphangiectasia or an egg allergy; these infants presented with seizure caused by hypocalcemia and/or hypomagnesemia.3,4 However, to date, no report has documented a case of a patient with an EGE diagnosis in the setting of seizure.
Eosinophilic gastroenteritis can occur throughout the gastrointestinal tract, from the stomach to the colon. The pathogenesis of EGE remains unclear. Eosinophils are believed to be mobilized by cytokines, and inflammation occurs in response to food allergens and other factors.5 Symptoms vary according to the lesion site, but no specific symptoms have been defined for this condition. Typically, the known symptoms include abdominal pain, nausea and vomiting, early satiety, and diarrhea.6 In addition, lesions in the intestinal mucosa may cause weight loss, protein-losing enteropathy, and other problems.6
A national survey of Japan on the clinical manifestations of EGE showed that this condition is more likely to cause hypoproteinemia in infants than in older children or adults.7 Considering this association, infants may be more susceptible to PLE and secondary malabsorption from EGE. Furthermore, the Japanese study found that the prevalence of vomiting or abdominal pain in infants with EGE was less than 20%, and these symptoms occurred less often in infants than in older children and adults. The prevalence of bloody stools and diarrhea in infants was about 50%.6 Therefore, the diagnosis of EGE in infants is often difficult because of the lower frequency of gastrointestinal symptoms. In our patient, the only gastrointestinal symptoms were several episodes of vomiting and diarrhea over 2 days before presentation. No other significant symptoms, such as continuous vomiting, diarrhea, or bloody stools, were noted. In addition, the patient had shown poor weight gain during the 2 months before her emergency presentation at age 6 months; however, her weight was maintained without further loss because of the edema associated with hypoalbuminemia. Furthermore, the edema resulted in the maintenance of a plump appearance, and the parents were unaware that her poor weight gain was caused by pathological factors. For these reasons, the patient’s symptoms and the course of disease were masked, resulting in the development of PLE, malabsorption, hypocalcemia, and ultimately the occurrence of seizure.
Performing gastrointestinal endoscopy or biopsy in infants is a challenging task because this age group displays very low EGE frequencies. Invasive testing is necessary to diagnose underlying diseases, including EGE, in the presence of complications such as hypoproteinemia, failure to thrive, or severe anemia that cannot be explained by transient gastrointestinal disease or chronic gastrointestinal symptoms.
Malabsorption syndrome was first considered in the present case because of low levels of various electrolytes and albumin. Therefore, PLE and secondary malabsorption syndrome were diagnosed based on alpha 1-antitrypsin measurement in stool and gastrointestinal scintigraphy. Next, gastrointestinal endoscopy and biopsy were performed to search for underlying diseases including EGE.
Although international consensus is lacking on the cut-off value of the eosinophil count for diagnosis based on biopsy, this case showed eosinophilic infiltrates of more than 20/HPF, which aligns with the cut-off value in the Japanese diagnostic criteria for EGE.8 Biopsy ruled out inflammatory bowel disease and intestinal lymphangiectasia, and EGE was definitively diagnosed.
In the present case, successful treatment was based solely on intake of an amino acid-based formula. For the treatment of EGE, Japanese guidelines recommend systemic corticosteroids. However, to date, no report with a high level of evidence is available regarding the use of corticosteroids in this condition.7 In addition, systemic corticosteroids are often associated with long-term adverse effects. Furthermore, in a case series of children with EGE, a high rate of improvement was observed with dietary therapy without the use of corticosteroids.9
In conclusion, EGE manifests with a wide variety of symptoms in infants; therefore, it is necessary to assume that the disease may progress without apparent gastrointestinal symptoms. As shown in this case, infants with EGE may present with seizure resulting from hypocalcemia caused by PLE.
The authors declare no conflict of interest.
