Endgames Case Report

Skin rash in a preterm infant

BMJ 2012; 345 doi: http://dx.doi.org/10.1136/bmj.e5390 (Published 30 August 2012) Cite this as: BMJ 2012;345:e5390
  1. Nisar Mir, consultant paediatrician,
  2. Hulikere Satish, consultant paediatrician
  1. 1Neonatal Intensive Care Unit, Warrington and Halton Hospitals NHS Foundation Trust, Warrington WA5 1QG, UK
  1. Correspondence to: nisar.mir{at}whh.nhs.uk

A girl was born at 30 weeks of gestation by spontaneous vertex delivery. The pregnancy had been uneventful apart from detection of group B streptococcus at nine weeks of gestation. This was treated with a course of oral ampicillin for five days.

Although the mother’s membranes ruptured 26 hours before delivery, she remained well throughout labour (which lasted for one hour) and there were no signs of infection. The baby’s birth weight was 1440 g and she had Apgar scores of 9 and 10 at one and five minutes, respectively. Although she showed no signs of sepsis, because of the history of prolonged rupture of membranes, a septic screen was performed and she was started on intravenous amoxicillin and cefotaxime for 48 hours until the cultures were confirmed as negative; C reactive protein (CRP) and peripheral white cell count remained normal during this time. She needed supplemental oxygen, via nasal continuous positive airway pressure, for three days because of surfactant deficiency related respiratory distress syndrome. When she was 6 days old, she developed recurrent apnoea associated with oxygen desaturations, which required endotracheal intubation. Her chest radiograph was normal. A repeat septic screen was performed, including analysis of cerebrospinal fluid and further blood cultures, and she was started on cefotaxime and teicoplanin. Her blood CRP remained normal throughout and the cerebrospinal fluid sample (day 7) and postnatal blood cultures (days 1, 7, and 9) were all negative for bacterial infection.

At 9 days of age she developed 3-5 mm vesicular skin lesions, mainly on her face and chest. She continued to have further eruptions on her trunk and a few lesions on the hard palate during the second week. The skin lesions progressed from being clear vesicles to pustules, and during the second week some lesions were vesicular and some pustular with an erythematous base. The lesions soon eroded, leaving a shallow ulcer with an erythematous base. During the third and the fourth weeks the lesions showed signs of complete resolution without skin scarring.

Questions

  • 1 In light of these lesions and clinical history what is the most likely diagnosis you would consider and why?

  • 2 What is the common mode of transmission of the disease in neonates?

  • 3 What are the possible complications of the disease?

  • 4 How would you treat this infant?

Answers

1 In light of these lesions and clinical history what is the most likely diagnosis you would consider and why?

Short answer

The characteristic facial distribution of the rash and the presence of oral and buccal mucosal lesions make infection with herpes simplex virus (HSV) the most likely diagnosis.1

Long answer

In an unwell neonate the occurrence of a vesicular, vesicular-pustular, or frankly pustular rash (figure) merits a thorough search for cause and prompt initiation of appropriate treatment.

Although both varicella and staphylococcus infections in a neonate may present with systemic illness and vesicular-pustular skin lesions, mucous membrane lesions are rare in both of these conditions. The presence of lesions on the hard palate coupled with the pattern of cutaneous lesions make the diagnosis of HSV infection most likely.2

In postnatal acquisition of chicken pox, a history of contact with a person with active lesions is often present; rarely varicella infection may be congenital, with a history of maternal chicken pox infection during the third trimester of pregnancy. Varicella lesions leave a variable degree of residual scarring on the skin and buccal mucosal lesions are absent. Staphylococcal infection (impetigo) tends to cause localised vesicular-pustular lesions, which soon become crusty; the lesions are usually found in the groins, axillae, and periumbilical area. A potentially serious form of staphylococcal infection known as scalded skin syndrome or Ritter’s disease produces extensive generalised scald-like vesicles.

A vesicular-pustular rash may be seen in benign transient conditions, such as miliaria and erythema toxicum, although infants are otherwise well and healthy. As the name suggests, autoimmune bullous diseases produce large bullae with clear fluid rather than small vesicular-pustular lesions. In addition, the presence of fever or seizures in a neonate, with or without a rash, should also heighten the suspicion for HSV infection.

2 What is the common mode of transmission of the disease?

Short answer

Perinatal transmission.

Long answer

Most neonatal HSV infections (82-87%) are acquired from exposure to maternal genital HSV during vaginal delivery.3 However, 50-75% of affected neonates are born to women who are asymptomatic at the time of delivery.3 The risk of transmission is higher in women who acquire primary genital infection during pregnancy than in those who have had a previous HSV genital tract infection with reactivation at term (25-50% v <1%).3

Although in the past most neonatal HSV infections were caused by HSV-2, recent studies suggest that HSV-1 infection accounts for 30-50% of all cases of reported neonatal HSV infections.4

Evidence also suggests that the incidence of genital herpes in adults has increased over the past two decades; the isolation of HSV from the maternal genital tract at delivery increases the risk of neonatal herpes more than 300-fold.3 5

3 What are the possible complications of the disease?

Short answer

Disseminated disease, severe hepatitis, infection of the central nervous system (CNS), ocular disease, and neurodevelopmental sequelae.

Long answer

HSV infection localised to skin, eyes, and mucous membranes carries a good prognosis when promptly and adequately treated with antiviral agents.6 However, even with treatment, disseminated and CNS neonatal HSV infection carries a high mortality and considerable disability among survivors; the outcome for survival in infants is poor without treatment (15% in disseminated disease and 50% with infection of the central nervous system).3 5

Severe hepatitis caused by either HSV-1 or HSV-2 can cause potentially fatal acute liver failure in neonates with disseminated disease.6

A considerable proportion (20-30%) of neonates who survive disseminated HSV or infection of the CNS have residual neurodevelopmental abnormalities, such as developmental delay, hemiparesis, persistent seizures, and microcephaly. Neonates with ocular HSV involvement such as keratitis may be left with permanent blindness.6

Congenital HSV infection, although rare, presents with clinical abnormalities (as microcephaly, hydrocephalus, hepatitis, and chorioretinitis) at birth and shares the clinical features and poor outcome seen for other in utero infections.3

Most genital HSV infections in women, which are usually asymptomatic, are associated with viral shedding. However, less than 1% of infants delivered vaginally to women who are shedding HSV at term develop neonatal herpes, suggesting that transplacentally acquired antibodies protect against infection.3 This may also explain why preterm neonates are susceptible to developing disseminated disease when exposed to HSV even if the mother has previously been infected with HSV.7

4 How would you treat this patient?

Short answer

Intravenous aciclovir for three weeks for disseminated disease or infection of the CNS.

Long answer

Systemic antiviral agents reduce the high mortality and morbidity associated with neonatal herpes simplex infection.8 Treatment with aciclovir reduces mortality from 85% to 31% in disseminated disease and from 50% to 6% in CNS infection.6 Intravenous aciclovir at a dose of 20 mg/kg every eight hours should be used.3 The appearance of mucocutaneous lesions seems to follow the onset of systemic symptoms in most cases.4

In this neonate, both the cerebrospinal fluid and the skin lesions were positive for HSV-1, which is indicative of mucocutaneous and CNS infection; most cases of maternal-fetal transmission involve women with undiagnosed genital herpes infection. A high index of suspicion is therefore necessary in neonates who present with a sepsis-like syndrome. Aciclovir should be considered as an early expectant treatment for suspected neonatal HSV infection because skin and mucosal lesions may appear late or not at all. The highest fatality rate for neonatal HSV is associated with disseminated infection of multiple organs (such as lung, liver, and brain) that is clinically indistinguishable from bacterial sepsis. All sick neonates presenting with vesicular or vesicular-pustular lesions should be evaluated for HSV infection.3 Because laboratory facilities may vary, seek advice from the local microbiologist.

Patient outcome

Blood and cerebrospinal fluid were positive on polymerase chain reaction for HSV-1 and viral skin swabs from the cutaneous vesicular lesions were also positive for HSV-1. She was treated with high dose intravenous aciclovir for three weeks and made a full recovery, with complete clearance of the skin lesions by day 20. Cranial magnetic resonance imaging at 3 weeks of age was normal. She was discharged home at term when she was feeding well, was gaining weight, and had a normal physical examination. On further follow-up, at the gestation corrected age of 18 months, the neurological examination and developmental assessment were normal, with normal physical and cranial growth velocity.

Notes

Cite this as: BMJ 2012;345:e5390

Footnotes

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

  • Parental consent obtained.

References