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Congenital Cytomegalovirus associates with intestinal stricture and small bowel obstruction presented in early infancy

Sheikha A. Rabie¹, Ghazala Balhaj¹, Gabriel Ionescu², Sayenna A. Uduman¹
¹Department of Pediatrics, Faculty of Medicine and Health Sciences, United Arab Emirates University.
²Department of Pediatric Surgery, Tawam Hospital in affiliation with Johns Hopkins
Al Ain, Abu Dhabi, United Arab Emirates.

 

 

Correspondence

Ghazala Balhaj,
Department of Pediatrics,
Faculty of Medicine and Health Sciences, UAE University
Tel: 0097137137296
Fax: 0097137672022
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Abstract

The authors present an infant admitted to hospital with recurrent episodes of intestinal obstruction due to small bowel stricture as a presenting sign of congenital cytomegalovirus (CMV) infection. The growth retardation, intra cerebral calcifications, progressive hepatosplenomegally and failure to thrive were attributed to prenatal onset of CMV disease. Further, the CMV specific IgM antibody persistence was supportive of the etiologic cause. This case illustrate the importance of gastrointestinal involvement of this virus is more frequent than previously recognized.

Key words: congenital cytomegalovirus (CMV) infection, gastrointestinal involvement

 

 

Introduction

Symptomatic congenital CMV infection was at first phrased as “Cytomegalic Inclusion Diseases” and the clinical features are microcephaly, purpura, petichiae, jaundice and hepatosplenomegally. Other features are prematurity, intrauterine growth restriction (IUGR) intracranial calcification, chorioretinitis and sensorineural hearing loss (SNHL) [1].

Gastrointestinal (GIT) involvement is an unusual manifestation of congenital CMV infection and has been reported in the literature infrequently. They describe an infant presented with vomiting, diarrhea and abdominal distension of recurring nature due to intestinal stricture as the major sign of congenital CMV disease. Manifestations that are frequently presenting in symptomatic CMV disease such as IUGR and periventricular cerebral calcification prompted us to substantiate the CMV etiology as the cause for GIT obstruction in this case.

Case Report:

A 4 month old male child was born to a G2P1A1 mother by Emergency Caesarean section at 38 wks of gestation because of fetal distress. Pregnancy was uneventful. Birth weight was 2350 G (SGA) with an Apgar score of 9 at 1 & 5 minutes of age. The neonatal physical examination was normal and discharged home well on exclusive breast feeding

At the age of 40 days, he was admitted to Pediatric Intensive Care Unit for vomiting, diarrhea and progressive abdominal distension associated with laboratory evidences of septic shock. The abdominal X-ray showed mechanical bowel obstruction. The CSF & blood cultures were negative. The small bowel obstruction was treated conservatively with bowel rest and antibiotics. His growth parameter on admission was just below 3rd centile and anterior fontanel measured 5 x 4cm in size with wide metopic sutures. Liver and spleen were enlarged to 4 and 3cm respectively. The WBC counts were ranging from 31 to 62,000/cm3 with neutrophil count predominance’s. The child begun to tolerate oral feeding after 26 days of intensive medical management. He was discharged against-medical advice

The subsequent clinical course was complicated with recurrent bilious vomiting, progressively worsening GIT obstructive symptoms and respiratory infections requiring multiple admissions in several hospitals. He was readmitted to our hospital as an emaciated child for further clinical assessment and management. Weight was 2.8 kg, height 54 cm and head circumference of 35 cm (all growth parameter were below 3rd centiles). A sick, hypotonic infant with abdominal distension and the liver and spleen measured >5 cm’s below costal margins .He also presented a reducible right inguinal hernia. Investigation relevant to perinatal infection on this admission shown as CMV IgG 40 AU/ml (cutoff 4.0), CMV IgM 2.31 AU/ml (cutoff 0.7) and the total IgM was 1.8g/l (normal range 0.1-1.05). Mother’s serology revealed CMV IgG 40 AU/ml (cutoff – 4.0) and negative anti- CMV specific IgM antibodies.

During this admission, he continued to have leukemoid reactions, the WBC ranged from 35 000 to 62,000. All cultures for bacterial infection were negative. Bone marrow aspirate showed myeloid hyperplasia, increased myeloid granulation and prominent monocots consistent with reactive changes to infection. Brain CT showed multiple periventricular calcifications and mild ventricular dilatation consistent with intra-uterine CMV infection ( fig. 1). On ophthalmologic evaluations showed no retinopathy changes detected. A complete audiology evaluation including brainstem evoked potential (BAEP) testing showed no sensorioneural hearing loss. Sweat test was negative and the chromosomal study showed XY male karyotype which was normal. HIV was negative

Considering the clinical and the laboratory evidence of congenital CMV infection, treatment with intravenous ganciclovir (10 mg/Kg/day) was initiated and continued for 6 weeks. Her subsequent clinical course was relatively stable with adequate weight gaining and remarkable regression of the size of the liver and spleen. A standard CMV cell culture was reported to have no growth on urine specimen collected after 3 weeks of ganciclovir therapy. However urine cytology revealed, distinctly enlarged nuclei with intra-nuclear basophilic inclusions and prominence of the nuclear membrane, consistent with owl’s eye inclusion bodies of CMV ( fig. 2). CMV viral load assay (Abbott Real time PCR) both prior and after completion of ganciclovir treatment was reported to be 391 DNA copies/ml (assay sensitivity is 100 copies / ml) and 65.8copies /ml respectively.

cytomegalovirus 1 cytomegalovirus 2
Fig. 1. Cytomegalovirus (CMV) infection. Non-contrast CT scan of the head shows multiple areas of calcifications within the periventricular regions bilaterally (arrows) Fig. 2. CMV inclusion (owl’s eye) in urine (arrows)

 

Due to recurrence of small bowel obstruction, the child underwent exploratory laparotomy. The exploration showed a narrowed segment of small intestine measuring 4 cm in length and 1 cm in diameter. The narrowed intestinal segment with adjacent Meckel’s diverticulum was found and excised, followed by an end to end primary anastomosis. The histopathology section revealed focal transmural inflammatory changes with necrosis and increase in lymphocytes and plasma cells within the lamina propria of small intestine. Subsequent clinical course was complicated with recurrent chest infection and failure to thrive requiring ICU management and frequent hospital admissions.

Discussion

Majority of children who have congenital cytomegalovirus (CMV) infection shows no clinical manifestation of the disease at birth. Less than 10% of infants who have symptomatic infection, signs involving central nervous system, hepatobiliary and hematopoietic system predominate. The severity of illness detected at birth may vary widely ranging from one or two clinical abnormalities to a multitude of clinical signs. We report a rare case of congenital CMV disease who revealed no clinical signs of disease at birth. Latter he became symptomatic with major gastrointestinal manifestation.

Congenital cytomegalovirus although a major public health problem as congenital rubella infection, is now the most frequent congenital infection in humans [2]. The frequency of congenital CMV infection among different populations has been estimated to vary between 0.2% and 5.4% of all live births [3]. CMV can infect newborns in utero with maternal primary infections during pregnancy and the risk for fetal infection is high (30-50%). On rare occasion, newborns are infected during re-infection or reactivation in a mother who has sero immunity status or a history of primary CMV infection prior to conception [4].

Newborns not infected through in utero transplacental route, may acquire CMV perinatally especially the preterm infants from vertical transmission. About 15% of seropositive women excrete CMV in cervical and vaginal secretions and up to 50% of seropositive women who breastfeed their infants transmit CMV via human milk [1]. Preterm infants acquiring CMV through human milk and vaginal secretion can develop symptomatic illness of recurrent chest infection and CMV pneumonia. In contrast to preterm neonates, the term born infant born to sero-positive mother rarely acquire CMV infection during postnatal period and causes no apparent disease during infancy [5].

Our case presented initially with sepsis and diarrhea associated with leukemoid reactions suggesting CMV enteritis, a recurrence of manifestations at an early age and complicated with intestinal stricture. Ideally, it would have been best to have identified CMV DNA and/or inclusion bodies in stool samples or on the excised intestinal specimen [6]. The identification of cerebral calcification and other CMV associated congenital disease including the IgM specific antibodies persistence is very supportive for CMV etiology for the intestinal pathology in our case. This case adds to the clinical spectrum of prenatal onset CMV infection and may represent a more common scenario than is currently recognized.

CMV involvement of gastrointestinal system in the form of enteritis with ischemic necrosis is common and well recognized in patients with AIDS and immunocompromised transplant patients. There have been reports in the literature in which congenital CMV cases presented with intestinal obstruction and the operative findings in those cases included colonic stricture, illeal ulceration and perforation [7]. The histopathology of the colonic and illeal lesions in these case had shown mixed inflammation and presence of scattered CMV inclusion bodies within the endothelial cells suggestive of CMV enteritis [8, 9].

This case is unusual and presented with atypical clinical picture before identification of the classical CMV disease manifestations. In conclusion the gastrointestinal symptoms of congenital CMV infection may represent a more common clinical manifestation than is currently recognized. Clinicians should be aware of this unusual clinical manifestation for settling of an early diagnosis and make therapeutic interventions.

 

 

 

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