Due to the increasing incidence of neonatal herpes infection and the exceptionally high mortality and morbidity of this disease, a high index of suspicion is imperative in all clinicians caring for neonatal patients. Because the clinical symptoms associated with neonatal herpes infection are often nonspecific, they may go unrecognized or may be attributed to another disease process, such as bacterial sepsis.[29,30] Such a delay in diagnosis dramatically increases the mortality and morbidity of infected infants, and therefore all clinicians caring for neonatal patients must be fully aware of the signs and symptoms consistent with neonatal herpes infection as well as the often subtle differences between the clinical presentation of bacterial and herpetic infection.
Neonatal HSV infection can be divided into three clinical groups. Skin, Eyes and Mouth disease (SEM) is a localized infection affecting the skin, eyes, or mouth. Central nervous system (CNS) disease is defined as encephalitis with or without SEM disease. Disseminated disease involves infection in multiple organ systems and can include hepatitis, pneumonitis, and disseminated intravascular coagulation (DIC).[2,6,31] Cutaneous lesions may be seen in all types and disseminated disease may occur with or without the presence of CNS disease. This classification system is predictive of both morbidity and mortality ( Table 1 ).[32,33]
The incubation period for neonatal herpes infection is 4 to 21 days after delivery. Infants typically begin to exhibit signs sometime between 6 and 21 days, with 30 to 40% of infants becoming symptomatic within the first week of life.[2,6,11] Signs are often consistent with those of bacterial sepsis and include fever, temperature instability, lethargy, poor feeding, respiratory distress, and cyanosis.[30,34] As the infection progresses, one may see DIC, hepatitis, pneumonitis, and seizures.[11,29,35] Since these signs may be initially mistaken for those associated with bacterial infection, treatment is often delayed until progression of the disease process occurs, leading to a dramatic increase in mortality and morbidity.
The presentation of neonatal herpes infection differs according to the type of infection. Vesicular skin lesions are the most predominant symptom consistent with neonatal herpes infection and, when lesions are present, herpes infection must be presumed until proven otherwise. These lesions begin as papules, which develop over a few days into ulcers. They are typically thin walled with an erythematous base, are 1 to 3 mm in diameter, and occur either as a single unit or in clusters (Fig 1). Vesicles may appear anywhere on the body but are most commonly seen on the presenting part, such as the head in a vertex presentation or the buttocks in a breech presentation.[30,36,37] They may also present on the face, the soles of the feet, the palms of the hand, and in the mouth. Scalp monitoring sites are notorious for becoming the primary site of infection. These sites must be meticulously examined and a culture taken if evidence of infection exists. If this culture result shows the absence of bacteria, the presence of a herpes infection must be considered.[29,37]
Vesicular lesions due to neonatal HSV infection. Reprinted with permission from Rudolph, AJ: Atlas of the Newborn, Vol. 4: Dermatology and Perinatal Infection. Ontario, Canada, B.C. Decker, 1997, p 123. (Color version of this figure can be viewed online @ www.sciencedirect.com).
Although vesicular lesions are the most frequent presentation, the absence of lesions should not preclude the consideration of neonatal HSV infection. If the diagnostic focus is centered on the observation of these lesions, many cases of neonatal herpes infection will not be promptly diagnosed. In fact, only approximately 68% of neonatal herpes infection will present with lesions and 17 to 39% of infants with confirmed herpes infection will never exhibit evidence of lesions during their illness.[2,29] Therefore, the astute clinician must be cognizant of the more subtle presentation of neonatal herpes infection.
Those infants with SEM disease are the most easily diagnosed since they usually present with obvious vesicular lesions. However 17% of infants with SEM disease never exhibit skin lesions. In these cases, the disease is limited to either the mouth or eyes and thus may be difficult to appreciate. Conjunctivitis, especially keratoconjunctivitis, is a classic finding consistent with herpes infection and must be carefully evaluated and appropriately treated.[2,29] Vesicles in the mouth may be difficult to appreciate especially in the intubated infant and thus a careful examination is warranted. Early diagnosis of SEM disease is imperative since early treatment is associated with a remarkably favorable prognosis. However, if SEM disease is left untreated, 70% of these infants will progress to either Central Nervous System (CNS) or disseminated disease, both of which are associated with an extremely poor outcome.[2,11,29]
Infants with CNS disease present with acute symptoms of meningitis, including a bulging fontanel, irritability, abnormal movements or positioning, and most commonly seizure activity. Generalized or localized seizures are the most common symptom associated with herpes meningitis and the diagnosis of herpes infection must be entertained in any infant presenting with seizures with no underlying etiology.
Finally, infants presenting with disseminated herpes disease typically present with symptoms very similar to those associated with bacterial infection. Although the diagnosis may be easily confused, disseminated herpes disease may often be distinguishable from bacterial infection by the presence of vesicular lesions, neonatal hepatitis of unknown etiology, and DIC. Disseminated herpes infection may have a component of CNS involvement and the infant may therefore exhibit symptoms consistent with encephalitis or meningitis.[11,29,38]
Although infants with a positive maternal history of herpes infection are often considered at risk for the development of neonatal herpes infection, these infants actually carry the lowest risk of infection. It is the infant who on first assessment appears to be without risk factors who is in the most danger of infection and in whom the diagnosis is often not promptly recognized. Since the most serious neonatal infections are due to a primary infection in the mother and 60 to 80%[2,27,28] of those primary infections are asymptomatic, there may be no history of maternal herpes infection. Therefore, the presence of a negative maternal and/or paternal history cannot reduce the level of suspicion related to neonatal herpes infection.
The clinical presentation of neonatal herpes may be very nonspecific, therefore a high index of suspicion must be present to reduce the mortality and morbidity associated with a delay in diagnosis. However, it is not feasible to initiate acyclovir as a routine therapy in the treatment of all newborns undergoing evaluation for sepsis. Certain situations must be identified in which the likelihood of HSV infection is increased. These situations may include infants with culture negative sepsis, infants with clinical evidence of sepsis that is not responding as expected to antibiotic therapy, and infants with culture negative pneumonia that continues to progress despite treatment with antibiotics. Seizures are also an important manifestation of herpes meningitis and the presence of generalized or focal seizures without evidence of a clear etiology must be considered herpes infection unless proven otherwise.
Not only is neonatal herpes infection of concern for those clinicians caring for infants in the newborn nursery or neonatal intensive care unit, those infants who are considered well newborns and have been discharged home are also at risk of infection. Since neonatal herpes infection can be seen up until four weeks of age, clinicians caring for newborns in clinics, offices, and emergency rooms must be familiar with the clinical manifestations of this disease process.[2,11] To illustrate the importance of knowledge and education related to neonatal herpes infection, it has been reported that, while parents are noting a change in their infant's condition and promptly bringing their infected infant to the attention of medical personnel, there is then a six- to seven-day delay on the part of the clinician in initiation of proper antiviral therapy, resulting in progression of the disease process.
Any delay in the diagnosis of neonatal HSV infection can have disastrous consequences. While the presence of SEM infection is associated with a 0% mortality rate, without prompt treatment, up to 70% of infants with SEM disease will progress to either CNS or disseminated disease both of which have an increased risk of death or permanent sequelae. Thus clinicians working in both the hospital setting and the outpatient arena must be acutely aware of the clinical manifestations of this disease and regard symptomatic infants with a high degree of suspicion.
NAINR. 2004;4(1) © 2004 W.B. Saunders
Cite this: Neonatal Herpes Infection: A Review - Medscape - Mar 01, 2004.