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Premature infant born to mother with chorioamnionitis
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A 32-week, 1,627-g newborn female, with premature and prolonged rupture of membranes, was delivered via cesarean section secondary to failure to progress and development of maternal fever with chorioamnionitis. The mother had good prenatal care with no risk factors, all infectious disease screening tests (HIV, VDRL, group B strep and hepatitis B) were negative, and no history of genital herpes or other sexually transmitted infections.
James H. Brien
The baby's Apgar scores were 9 and 9 at 1 and 5 minutes, respectively. Because of the maternal chorioamnionitis, the baby had blood cultures obtained and was treated empirically with ampicillin and gentamicin. Her exam was that of a vigorous preterm newborn in no distress. She did well until day 5 of life, when she developed some skin lesions on her lower back (Figure 1). The rest of her examination is normal for her age and gestation.
What's Your Diagnosis?
A. Neonatal lupus
B. Neonatal herpes
C. Langerhans cell histiocytosis
D. Neonatal candidiasis
Figure 1. The patient did well until day 5 of life, when she developed some skin lesions on her lower back.
Source: Brien JH
This is not much of a brain-buster, but some good teaching points can be made. A sample of fluid was obtained from the lesion (Figure 2) and sent for herpes PCR, which was positive (B). The herpes was no doubt acquired perinatally, despite mother's negative history (as they often are). The timing is also right (most appear between 5 and 14 days of age), and the appearance is characteristic. The baby had a full sepsis workup, ruling out disseminated and central nervous system herpes. Therefore, this patient was classified as having skin-eye-mouth (SEM) disease. She was treated with acyclovir at 60 mg/kg per day, divided every 8 hours, for 14 days. Treatment continued with oral acyclovir prophylaxis at a consistent dose of 300 mg/m2 every 8 hours for 6 months while periodically adjusting the dose with growth and monitoring for neutropenia, a common toxicity. Due to the work led by David W. Kimberlin, MD, showing improved neurodevelopmental outcomes in those treated with this protocol, this regimen of prophylaxis has become the standard of care after neonatal herpes infections.
This also seems like a good time to point out the new guidelines for managing asymptomatic newborns of mothers with known or suspected active genital herpes, at or near the time of birth, published last year by the AAP in Pediatrics. This was also derived from work led by Kimberlin, which hinges significantly on whether the mother has had genital herpes preceding pregnancy, which requires a previous diagnosis or the presence of herpes IgG antibodies on mother's blood. In either case, it also relies on multisite herpes cultures of the baby at or beyond 24 hours of age, as in the past. However, now, herpes PCR of blood is also encouraged to help with decisions.
A sample of fluid was obtained from the lesion (Figure 2). The typical discoid, annular erythematous plaques, with central scale that constitute the skin lesions (Figure 3).
I would advise that you copy the algorithm in the paper and post it near your nursery for ready reference. The details are beyond the scope and space of this column, but the entire document can be found at pediatrics.aap publications.org/content/131/2/e635.full.pdf.
Choice A, neonatal lupus, is a fairly uncommon condition seen in the newborns of mothers with circulating autoantibodies (ANA, mostly anti-Ro) with lupus or Sjögren ’s syndrome. Of all the skin problems I have seen in more than 30 years, I have seen only one case. The typical discoid, annular erythematous plaques, with central scale that constitute the skin lesions (Figure 3), are the main cutaneous manifestation. These babies can also have cardiac manifestations (heart block), which may persist for life, and should all be evaluated and followed by a cardiologist. The skin lesions, however, tend to resolve when mother's antibodies are eliminated; usually by 6 to 9 months. The skin lesions need no treatment. However, if the baby has evidence of heart block, he or she may need a pacemaker and obvious long-term cardiology follow-up.
Langerhans cell histiocytosis can be seen in the neonatal period from the day of birth, and on. The cutaneous manifestations can have various appearances; from discrete reddish/yellow scaling lesions (Figures 4 and 5) to papular/nodular lesions, to persistent and diffuse "diaper rash."First described by Paul Langerhans, a 19th century German physician, this condition was subsequently subdivided into three categories: Letterer-Siwe disease (the most severe); Hand-Schüller-Christian disease; and eosinophilic granuloma (terminology no longer used). Babies with the more severe form are usually treated by an oncologist with immunosuppressive agents, with varying results.
The cutaneous manifestations can have various appearances; from discrete reddish/yellow scaling lesions (Figures 4 and 5) to papular/nodular lesions, to persistent and diffuse “diaper rash.”
Neither of the two previous conditions results in vesicular lesions, making differentiation fairly easy. However, neonatal candidiasis is frequently associated with pustular lesions (Figure 6), which could be confused with herpes. A fungal stain of the material within the lesion will usually reveal the budding pseudohyphae to give a quick diagnosis. Neonatal candidiasis, like neonatal herpes infections, begins with colonization at the time of delivery. However, candidiasis will usually have skin lesions within a day or two after delivery, and respond well to fluconazole. For severe infections or pulmonary involvement, one might consider treatment with amphotericin B until improvement is documented. The congenial form of candidiasis is fairly uncommon, and usually more severe, and is likely to be symptomatic at the time of birth.
On another topic, I want to recognize those who correctly answered the question posed in the May issue, identifying the molecular structure on the cover of the new 20th edition of John D. Nelson's Pediatric Antimicrobial Therapy. François Boucher, MD, FRCPC, Chef du service d’Infectiologie pédiatrique, Sainte-Foy (Québec), was the first to come up with Colistin as the correct answer, literally within minutes of the column being posted online.
Neonatal candidiasis is frequently associated with pustular lesions (Figure 6).
Gregory M. Anstead MD, PhD, division of infectious diseases, department of medicine, University of Texas Health Science Center at San Antonio; Luis E. Garcia-Chacon, MD, PhD, department of pediatrics, Leonard M. Miller School of Medicine, University of Miami; and Andrew Osten, MD, CPT, MC, pediatric resident, Tripler Army Medical Center, Honolulu, also correctly identified the structure. I want to thank all who participated.
If you sent a correct response, and I missed including you, PLEASE re-send it. I sometimes receive more than 100 messages per day, and occasionally miss one now and then.
Editor's Note
To see more columnist comments from this month's "What's Your Diagnosis" and Dr. Brien, visit Healio.com/Medblog.
References:
Kimberlin DW. Pediatrics. 2013;131:635-646.
For more information:
James H. Brien, DO, is vice chair for education in the department of pediatrics at McLane Children's Hospital at Scott & White/Texas A & M College of Medicine in Temple, Texas. He is also a member of the Infectious Diseases in Children Editorial Board. Brien can be reached at: jhbrien@aol.com.
Disclosure: Brien reports no relevant financial disclosures.