Skin Ulcerations in a Preterm Newborn

Abstract

A preterm female infant has had skin ulcerations since birthCongenital absence of skin(1):Skin biopsy and ocular, rectal, and oral swabs were positive for HSV-1 by polymerase chain reaction (PCR). Skin biopsy revealed abnormal hair follicles that had extensive dystrophic calcification and total loss of follicular epithelium. The placenta exhibited areas of acute necrotizing villitis as well as multinucleated giant cells with nuclear staining positive for HSV-1. Given the grave neurologic and overall prognosis, the infant’s care was redirected and she was allowed to die a natural death.Intrauterine HSV infection is a rare but devastating illness. Approximately 1,500 cases of neonatal herpes infection occur annually in the United States, affecting approximately 1 in 3,200 neonates. (2,3) Although most neonatal herpes infections are acquired at the time of delivery (85%) and postnatally (10%), a small percentage (<5%) are acquired in utero. (2,4) Intrauterine HSV is acquired from ascending infection or hematogenous transplacental spread and is more likely to occur with primary rather than recurrent infections due to higher viral loads and longer periods of viral excretion. (5,6) A recent study of 69 consecutive cases of intrauterine fetal death found that 5% resulted from intrauterine HSV infection. (7)Symptoms of intrauterine infection are present at delivery or within the first 48 hours of birth(8) and usually involve the skin (94%), brain (79%), and eyes (59%). (9) Cutaneous manifestations include vesicles, ulcerations, pustules, bullae, hypopigmented scarring, zosteriform skin denudation in dermatomal distributions, (10) lesions resembling epidermolysis bullosa, (11,12) or aplasia cutis congenita. (12,13) Although rare, infants without mucocutaneous lesions have been reported. (14) Among the central nervous system (CNS) manifestations are hydrocephalus, cystic lesions, (1) hydraencephaly, brain atrophy, (15) hemorrhage, and encephalomalacia; (16) unlike the predilection for the temporal lobe seen in older infants who have HSV encephalitis, neonatal HSV can involve any and multiple regions of the brain. (2) Eye findings include chorioretinitis, microphthalmia, and persistent fetal ocular vasculature. (15,17) Systemic involvement is common, with many infants exhibiting disseminated disease on autopsy, especially of the liver, lungs, and adrenal glands. (15) Radiographs of the long bones may reveal metaphyseal lucencies as well as soft-tissue densities consistent with cutaneous calcification (dystrophic calcinosis cutis). (18) Additional rare reported findings include hydrops fetalis (19) and limb hypoplasia. (20)HSV is diagnosed via PCR testing of blood, cerebrospinal fluid (CSF), or scrapings of lesions. Acyclovir remains the current treatment (60 mg/kg per day divided every 8 hours), and the length of therapy is 21 days for disseminated or CNS disease. (21) The dosing interval may need to be increased in preterm infants based on creatinine clearance. (22) All infants who have CNS involvement should undergo a repeat lumbar puncture at the end of therapy to determine that CSF is PCR-negative. (23)Most cases of intrauterine HSV infection are identified as HSV-2 (90%), (24) but several cases of intrauterine infection with HSV-1 have been reported. (8,14,25) Infants infected with HSV in utero are more likely to be born preterm (59%) and have lower birthweights and shorter lengths. (24) The prognosis for intrauterine HSV infection is dismal. In the largest series of intrauterine HSV infection, 4 of 13 infants died; 7 of 13 had severe impairment, including intellectual disability, severe developmental delay, seizures, blindness, and hearing deficits; and 2 of 13 were expected to have severe impairment. (15) A single report describes a term infant who had large areas of atrophic skin scarring, erythema, and dystrophic nails present at birth and developed vesicles 4 days later that were positive for HSV-1. (8) He was presumed to have intrauterine infection due to skin scarring present at birth, was treated with acyclovir, and remained healthy at 18 months of age.In summary, intrauterine HSV is a rare but devastating illness that most often manifests with skin findings present at birth. A high index of suspicion is necessary to attempt to ameliorate the disease process, but outcomes are nearly uniformly poor.JoDee M. Anderson, MD, Division of Neonatal Medicine, Oregon Health & Science University, Portland, OR