June 2003

An 11-day-old female infant was referred to the hospital for evaluation and treatment of a rash on her head and face. The rash first appeared on the back of the head sometime during the first six days of life, while her mother was recovering from a cesarean section. The mother had noted some erythematous spots on the back of the head right after delivery, where the scalp probe had been. She delivered by cesarean section because of placenta abruption — with a history of ruptured membranes for about one hour. She and the baby were discharged home on day 6. The rash was initially treated in the hospital with Bactroban (GlaxoSmithKline), and later with a triple-antibiotic ointment, but appeared to have not responded to either when her primary physician first saw her on day 11. At this point, there were additional lesions on the head and face that were predominantly pustular and/or vesicular. She was otherwise well and feeding normally with no other complaints.

Mother’s pregnancy was complicated by the abruptio placentae as mentioned above and by having a painful, pruritic vaginal rash during the second trimester. It is unclear if she had had this rash before that time. She tested positive for herpes simplex at that time, but had no rash and was culture negative a few days prior to delivery. Her pregnancy was otherwise unremarkable.

On examination, the baby was alert, active and feeding normally. The only positive finding was the rash. This consisted of pustular lesions on erythematous bases on the occiput, right parietal area, left frontal area and medial to the right eye as shown in figures 1 through 4. The eyes appeared normal. The mouth, vagina, anus and rest of the skin surface were normal, as was the rest of the exam, including the abdomen.

Lab tests included a normal complete blood count, urinalysis, cerebrospinal fluid (CSF) analysis (cells, protein, glucose and Gram’s stain), electrolytes and liver enzymes, as well as a chest radiograph. Cultures of blood, urine and CSF for bacteria and viral cultures of CSF and the occipital skin lesion are pending. A sample of CSF was also sent for herpes simplex polymerase chain reaction (PCR) testing.

What Would You Do Pending Cultures?

1. Consult an ophthalmologist
2. Begin therapy with IV acyclovir
3. Begin broad-spectrum antibiotics
4. Begin trifluoridine eye drops
5. Both A & B above

Answer

My answer was to begin IV acyclovir and consult an ophthalmologist to rule out any herpes simplex virus (HSV) infection of the eye. Even though the eye looked normal, I don’t trust my ability to rule this out. However, some may choose to not consult ophthalmology unless they see erythema of the conjunctivae. Then, of course, if there is evidence of HSV keratoconjunctivitis, trifluoridine drops should be added to the therapeutic regimen, and the patient should continue to be co-managed with an ophthalmologist.

There should be no question about beginning therapy with IV acyclovir. The chances of this rash being due to HSV are very high. Most experts would use a dose in the area of 60 mg/kg/day divided every eight hours. The duration of therapy depends on the extent of the infection. This patient had a positive HSV culture of the skin lesion, but all others were negative, as well as the HSV PCR of the CSF. This baby did well clinically, with rapid resolution of the lesions after beginning the acyclovir (figures 5 through 8 taken three days after admission showing drying & crusting of most lesions).

The patient fit into the skin–eye–mouth/other mucous membrane (SEM) category of neonatal herpes infection, and underwent 14 days of therapy. If she had had clinical or laboratory evidence of disseminated disease or CNS disease, her duration of therapy would be at least 21 days. One has to also remember that there can be toxicity with acyclovir. The main problem seen is neutropenia. Also, if the patient has any renal insufficiency, the dose and/or interval should be changed accordingly. We rely heavily on our clinical pharmacologists to help guide us with these issues.

There is good evidence in this case that the mother had recurrent disease by the time of delivery since she had a documented case during the second trimester. It puts the baby at less risk of severe disease, but the possibility still exists. Because of this, most experts recommend the above therapy regardless of whether the mother had primary or recurrent HSV infection. After the acute infection is successfully treated, some of these patients go on to have recurrent cutaneous disease, which may be associated with neurologic morbidity. Some of the leading experts in this field are studying the use of oral suppressive therapy with acyclovir in babies with recurrent cutaneous HSV infections. This study showed that suppressive therapy can prevent recurrences, but the effect on neurologic outcome is still being investigated (Kimberlin D. Pediatr Infect Dis. 1996).

From a practical standpoint, frequent recurrences can create significant social problems with the family. Most day care centers and some schools will send these children and babies home until the rash clears, thereby disrupting the usual routine of the family. (We do not recommend excluding children with simple mucocutaneous herpes infections from day care or school, but it seems to be a common practice.) If both parents work, it can become a big financial problem, not to mention the effect on the child. While there may be no official recommendations at this time for using suppressive therapy in babies and children with frequent recurrences (every four to eight weeks) of mucocutaneous HSV infections, I think it is reasonable to give it a try, especially if the recurrences are about the face or eye. I usually start with 20 mg/kg/day of acyclovir in two divided oral doses for six months to a year, depending on the patient. If more is needed, I usually add another 10 mg/kg as a third dose per day. One just has to weigh the risks of toxicity, both known (neutropenia) and unknown with the benefit of reducing these recurrences, and involve the parents in an informed way. However, in my experience, you virtually never have to talk them into it. Parents are always very frustrated with this situation and want (demand) something to be done.

Acknowledgement: I would like to thank Manzoor Farooqi, MD, a pediatrician in Killeen, Texas, for contributing this case.

For more information:

• Kimberlin D, et al. Administration of oral acyclovir suppressive therapy after neonatal herpes simplex virus disease limited to the skin, eyes and mouth: results of a Phase I/II trial. Pediatr Infect Dis J. 1996;15(3):247-254.