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Herpes simplex virus colitis in a neonate

Daley, Andrew J. M.B.B.S., B.App.Sc.(MLS), F.R.A.C.P., F.R.C.P.A.; Craven, Paul B.Sc.(Hons), M.B.B.S., M.R.C.P., F.R.A.C.P.; Holland, Andrew J. A. B.Sc.(Hons), M.B.B.S., F.R.C.S.(Eng), F.R.A.C.S.(Paed); Jones, Cheryl A. M.B.B.S., Ph.D., F.R.A.C.P.; Badawi, Nadia M.B.B.Ch, M.Sc., Ph.D., F.R.C.P.I., F.R.A.C.P.; Isaacs, David M.D., F.R.A.C.P., F.R.C.P.C.H.

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The Pediatric Infectious Disease Journal: September 2002 - Volume 21 - Issue 9 - p 887-888
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Involvement of the gastrointestinal tract in neonates with congenital herpes simplex virus (HSV) infection is rarely described. We report a case of a newborn with disseminated HSV infection associated with profuse hematochezia and late sigmoid colon perforation. Histologic examination showed patchy areas of ulceration with multinucleated giant cells, and HSV nucleic acid was detected by polymerase chain reaction in colonic tissue. No clinically apparent episodes of recurrent colitis occurred in the first year of life.

Herpes simplex virus (HSV) colitis has been described in adults, principally in the setting of underlying malignancy or immunosuppression, 1–5 but is rarely seen in neonates. We describe a newborn with severe colitis associated with profuse hematochezia and late sigmoid colon perforation. Diagnosis was made from histologic appearance and identification of HSV nucleic acid by PCR.

Case report.

A 4-day-old female infant, born at term by vaginal delivery without the use of forceps or other assistance, was admitted to hospital with a 24-h history of cyanosis, cough, vomiting and abdominal distension. She was febrile (38.7°C) and had a 3-mm crusted skin lesion at the vertex of the scalp that had been present since Day 2 of life. There was no history of genital herpes infection in either parent, although the mother had experienced perineal burning on the day before delivery and the father had a history of recurrent herpes labialis.

A chest radiograph showed right upper lobe consolidation and bilateral interstitial infiltrates. The baby’s total leukocyte count was 10.5 × 109/l with a normal differential cell count. Cerebrospinal fluid examination was normal (protein 0.63 g/l, glucose 2.6 mmol/l, no cells or organisms seen), and nucleic acid amplification assays for HSV and enteroviruses were negative. An immunofluorescence study of cells scraped from the base of the scalp lesion was positive for HSV type 1 (HSV 1), and HSV 1 was subsequently cultured from the scalp lesion and from a nasopharyngeal aspirate. The child was treated with intravenous acyclovir, ampicillin and gentamicin.

During the next 2 days she developed hepatitis, disseminated intravascular coagulation and acute renal failure (alanine aminotransferase 2048 units/l, activated partial thromboplastin time 95 s, international normalized ratio 2.9, platelets 79 × 109/l, creatinine 137 μmol/l). She had profuse rectal bleeding (>3000 ml in 48 h) managed with vitamin K and transfusion of packed red blood cells, fresh frozen plasma and cryoprecipitate.

She improved until Day 22 (Day 19 of acyclovir therapy) when she developed acute abdominal distension, respiratory failure and hypotension requiring reintubation and inotrope support. An upper gastrointestinal contrast study and follow through failed to demonstrate a suspected bowel perforation, but in view of her worsening condition a laparotomy was performed. An irregular 3.5-cm perforation was identified in the mid-sigmoid colon and she underwent sigmoid colectomy. She made a rapid recovery and was extubated 3 days later with recommencement of enteral feeding. Acyclovir therapy was stopped after 21 days. She was discharged from the hospital on Day 35. Reversal of the colostomy was performed at 10 months of age.

Histopathology of the excised colon showed patchy mucosal ulceration sharply demarcated from the normal bowel. There was a mixed inflammatory cell infiltrate with occasional multinucleated giant cells suggestive of HSV infection. These, however, failed to stain for HSV by immunohistochemistry. HSV nucleic acid amplification by PCR 6 performed on paraffin-embedded colonic tissue demonstrated the presence of HSV nucleic acid. Viral culture and electron microscopy were not attempted from fresh tissue because perforation secondary to HSV infection was not considered at the time of surgery.

Discussion.

Colonic involvement with neonatal HSV infection has rarely been reported. Lesions in the upper gastrointestinal tract such as the oral cavity and esophagus are seen in neonatal HSV infection resulting from ingestion of virus-containing amniotic fluid or maternal secretions at the time of delivery. Infection of the bowel can occur by a similar mechanism or by hematogenous seeding of the bowel during viremia. 6 Singer 7 described the autopsy findings of 23 infants with fatal HSV infection. Four cases had areas of focal necrosis in the stomach and/or bowel, and one infant who had been treated with corticosteroids had involvement of the entire gastrointestinal tract. Our infant had no oral or perianal herpetic lesions. Cytomegalovirus has been associated with enterocolitis in an immunocompetent 5-week-old infant with intractable diarrhea 8 and has been described as a coinfection with HSV in an immunocompromised adult with colitis. 1 Our infant had negative urine viral cultures and no serologic evidence of perinatal cytomegalovirus infection.

HSV colitis in adults has been described in patients with lymphoma, 1, 2 colonic adenocarcinoma 3 and Crohn’s disease 4 and after renal transplantation. 5 Alimentary tract HSV infections in human immunodeficiency virus-infected homosexual men present as painful perianal ulceration with tenesmus and constipation, and lesions rarely extend >15 cm into the rectum. 9 Presentation of HSV colitis in adults is principally with abdominal pain and severe watery, 2 mucoid 5 or bloody 1, 3 diarrhea. Early colonoscopy demonstrates diffuse erythematous or hemorrhagic changes 1, 3, 5 which progress to confluent ulceration 5 or a more patchy pathology with localized areas of ulceration. 1, 2 Histologic examination generally shows a mixed inflammatory cell infiltrate with multinucleated giant cell formation. 2, 5 Electron microscopy may demonstrate the cytoplasmic and intranuclear inclusions of HSV, 2 HSV may be isolated from colonic tissue 1 and HSV antigen may be demonstrated in feces by enzyme immunoassay. 5 Immunohistochemistry has been used to detect HSV proteins in colonic tissue of infected adults. 2

Our infant had culture-confirmed HSV 1 infection with multiorgan involvement and clinical and histologic evidence of colitis. The enteric hemorrhage was probably exacerbated by the coagulopathy, and the late colonic perforation may have been caused by HSV infection with some attenuation of the bowel wall. It was not surprising that the HSV immunohistochemistry was negative in our patient because the sigmoid colectomy was performed after 19 days of intravenous acyclovir therapy. We would not expect there to be significant viral replication or lytic gene expression after this period of treatment unless acyclovir-resistant mutants were present. PCR is more sensitive than other methods of virus detection but does not distinguish between acute and latent HSV infection. We were able to detect HSV DNA in a solubilized colonic tissue extract of our patient by PCR, but we cannot exclude the possibility that the specimen was contaminated with HSV DNA during surgery and subsequent handling.

Our infant did not have clinical evidence of recurrent colitis during the first year of life, but reactivation of cutaneous and central nervous system HSV during infancy is described. 10 It is not known whether the gastrointestinal tract is a common site of recurrence but abdominal symptoms occurring in survivors of disseminated neonatal HSV infection should be investigated for evidence of HSV-associated colitis.

Acknowledgments.

We thank Dr. A. Shanker, Dr. P. Barr and the staff of the Grace Neonatal Intensive Care Unit for medical care; Professor D. Cass and Dr. H. Martin for surgical management; Dr. M. Watson for infectious diseases opinion; I. Evans for PCR assay; and Dr. A. Kedziora for histopathology.

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Keywords:

Herpes simplex virus; colitis; neonatal infection

© 2002 Lippincott Williams & Wilkins, Inc.