Title : CMV - associated enterocolitis in neonates, case reports
Background: Intestinal CMV infection is associated with watery diarrhea in infants or necrotizing enterocolitis (NEC) in preterm neonates. The cases of CMV enterocolitis and necrotizing enterocolitis are presented. Two term infants about 6 weeks old developed severe watery diarrhea and bloody stool in one case. One preterm infant had NEC deterioration associated with primary postnatal CMV infection. Case 1: Previously healthy full term (3700/52; 8/9) breast fed boy developed enterocolitis with bloody stool, vomiting and irritate condition on 49 day of life (DOL). He was admitted in our hospital three days later. He had hyponatremia (Na-125 -129 mmol/l), normal leukocytosis (17,7x10^9) with increased bands level (17%). He was treated with ceftriaxone, salin, electrolytes and glucose infusion during a week. All bacteriology (Salmonella, Shigella, Campylobacter, E coli O157) and virology (Rota, Adeno-, Entero- and Norovirus) stool tests were negative. Blood real-time PCR was positive for CMV. Specific IgG and IgM were revealed (Table 1). Specific anti-CMV- intravenous immunoglobulin (IVIG) 0,1 g/kg was administrated. The boy’s condition was improved and therapy was stopped. Few days later he developed severe watery diarrhea 10 times a day. In the same time he had a febrile temperature during 3 days. He had increased leucocytes and bands levels in CBC. Abdomen ultrasound revealed intestine wall thickening with mesenteric lymph nodes enlargement. CMV infection was confirmed from a blood, urine, saliva and stool samples by PCR (Table 1). Acute CMV enterocolitis was treated with IV ganciclovir (5 mg/kg twice a day) during 2weeks. Specific IVIG (0,1 g/kg) and nonspecific IVIG (1g/ kg) were given additionally. The boy needed parenteral nutrition in 2 weeks. He totally recovered without complications. His body measurements and neurodevelopmental skills were good in his 6 months old. Table 1. Case 1. Ig and PCR results Case 2: Previously healthy full term (3210/50; 8/9) breast fed girl started to get formula because of breast milk insufficiency. Since first month she was suffered from cow’s milk protein allergy. On 51 DOL she developed enterocolitis with severe watery diarrhea, febrile temperature and seizures because of electrolytes disturbance. Her laboratory tests were markedly abnormal: hyponatremia (120 mmol/l). She had hepatosplenomegaly. Abdomen ultrasound revealed intestine wall thickening. Leukocytosis (38-46 x 10^3/mcl), increased myelocytes (12%), metamyelocytes (14%) and bands (15%) levels were diagnosed. CRP was 116 mg/l. CMV infection was confirmed from a blood by real-time PCR. AntiCMV IgM level was positive. Acute CMV enterocolitis was treated with antibiotics, salin, electrolytes and glucose infusion. IV ganciclovir (5 mg/kd twice a day) was started. Specific anti-CMV-IVIG was given (0,25g/kg). The girl was fed reduced volume of lactose free deep hydrolyzed protein formula. Stool watery loss achieved about 400 ml/day (100 ml/kg/d). Enteral nutrition was stopped. TPN was provided for 10 days. The girl was discharged in 3 months with good healthy condition. Her neurodevelopmental outcome and physical skills were good in her 1 year old. Case 3: A 9-week-old, former 27-week (920/35; 6/7) estimated gestational age premature boy had recurrent episodes of necrotizing enterocolitis. Last episode started in 70 DOL. Serum procalcitonin was 2,41 ng/ml. Abdomen ultrasound 23 SEPT. 2019, Monday - 12:20 Page 24 Pediatrics and Neonatology 2nd Edition of Euro-Global Conference on EPN 2019 revealed intestine wall thickening at 3,1 mm, gallbladder wall thickening at 1,5 mm and free fluid in lateral canals at 15mm. The infant was treated with antibiotics and TPN. Primary CMV infection was confirmed from a saliva and blood samples by real-time PCR (Table 2). That implicated cytomegalovirus as the etiology of the NEC deterioration. IV ganciclovir (5 mg/kd twice a day) was started. After 2 weeks of the treatment viral load did not decrease. Anti-CMV IgM level was positive (Table 2). Specific anti-CMV-IVIG was added (0,2g/kg) and ganciclovir continued. NEC symptoms were resolved. The boy was discharged at 3,5 months old. His weight was 2595 g (+ 575g during 32 days). Table 2. Case 3. Ig and PCR results. CSF – cerebrospinal fluid Results: These patients had postnatal intestinal CMV infection. Two term infants developed severe watery diarrhea. Preterm infant had NEC deterioration. They were treated with specific IV immunoglobulin and IV ganciclovir during 2-4weeks. They needed parenteral nutrition in 2-4 weeks. All of them totally recovered. Conclusions: Cytomegalovirus is frequently overlooked in the differential diagnosis of enterocolitis and chronic gastrointestinal symptoms in infants. In case of severe intestinal cytomegalovirus infection we recommend a complex therapy including specific intravenous immunoglobulin and intravenous ganciclovir.