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PubMed This is a summary of 13 peer-reviewed journal articles Updated
Pediatrics · Neonatal Herpes Simplex Virus

Symptoms and Stages of Neonatal HSV

At a Glance

Neonatal HSV is a serious newborn infection classified into three categories: Skin/Eye/Mouth (SEM), Central Nervous System (CNS), and Disseminated disease. Prompt treatment with IV acyclovir is critical. Many infected newborns will not develop a visible skin rash when they first become sick.

Neonatal herpes simplex virus (HSV) is not a single “look.” Because the virus can affect different parts of the body, doctors group the infection into three distinct categories, often called “stages” or “classifications.” Understanding these helps you and your care team monitor your baby’s progress and plan the right treatment.

The Three Classifications of Neonatal HSV

1. Skin, Eye, and Mouth (SEM) Disease

This is the most localized form of the virus. In SEM disease, the infection is limited to the body’s external surfaces [1][2].

  • Common Symptoms: Small, fluid-filled blisters (vesicles) that may appear in clusters, redness or discharge from the eyes (conjunctivitis), or sores inside the mouth [3][4].
  • The “Window”: Symptoms typically appear around day 8 of life on average, but can appear earlier or later [2].
  • Why it Matters: While SEM has the best outlook, it is a critical warning sign. If left untreated, about 75% of these cases will progress to more serious forms affecting the brain or internal organs [5].

2. Central Nervous System (CNS) Disease

This classification means the virus has crossed into the brain or spinal cord, causing inflammation (encephalitis) [6].

  • Common Symptoms: Seizures (which may look like rhythmic twitching or bicycle-pedaling movements), extreme sleepiness (lethargy), or irritability [6][7].
  • The “Window”: Symptoms often appear slightly later, usually around day 14 of life on average [2].
  • Note on Rash: Many babies with CNS disease (up to 60-70% in some studies) do not have a skin rash when they first get sick [2][8].

3. Disseminated Disease

This is the most severe form, where the virus acts like a whole-body infection (sepsis) and affects multiple internal organs [8][9].

  • Common Symptoms: Temperature instability (either fever or being dangerously cold), respiratory distress (trouble breathing), and signs of organ failure [2][10].
  • The “Window”: This form often appears early, typically averaging around day 6 of life [2].
  • Organ Involvement:
    • Liver: Inflammation (hepatitis) often leads to elevated liver enzymes or jaundice [11].
    • Lungs: Pneumonia or severe lung distress [12].
    • Heart: Inflammation of the heart muscle (myocarditis) [13].

The “Invisible” Infection

One of the most confusing parts for parents is that a baby can be very sick with HSV without having a single blister on their skin.

In fact, approximately 73.7% of babies with the disseminated (whole-body) form of HSV do not have skin lesions when they are first diagnosed [2]. Because of this, doctors must maintain a “high index of suspicion,” testing for HSV in any newborn who looks unwell or has signs of sepsis, even if their skin looks perfectly clear [2][8].

Feature SEM Disease CNS Disease Disseminated Disease
Typical Onset Average ~Day 8 Average ~Day 14 Average ~Day 6
Primary Location Skin, eyes, mouth Brain and spinal cord Multiple internal organs
Key Signs Blisters, red eyes Seizures, lethargy Trouble breathing, liver issues
Rash Present? Yes Sometimes (often no) Often no [2]

Promptly starting intravenous (IV) acyclovir is the standard of care for all three types to stop the virus from spreading further [3][5].

Common questions in this guide

Does a baby with neonatal HSV always have a skin rash or blisters?
No, many babies with neonatal HSV do not have a visible skin rash. In fact, nearly three-quarters of newborns with the most severe whole-body form of the virus have no skin lesions when they are first diagnosed.
What are the three stages or types of neonatal herpes?
Doctors classify neonatal HSV into three types based on where it affects the body: Skin, Eye, and Mouth (SEM) disease; Central Nervous System (CNS) disease involving the brain; and Disseminated disease, which acts like sepsis and affects multiple internal organs.
When do symptoms of neonatal HSV usually appear?
The timing largely depends on the type of infection. Disseminated disease usually appears around day 6 of life, SEM symptoms around day 8, and CNS symptoms around day 14. However, symptoms can appear earlier or later than these averages.
Why is early treatment important if the baby only has localized blisters?
Prompt treatment with intravenous (IV) acyclovir is crucial to stop the virus from spreading further. If a localized infection on the skin, eyes, or mouth is left untreated, the majority of cases will progress to severe forms that attack the brain or internal organs.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my baby's symptoms, which of the three categories (SEM, CNS, or Disseminated) is the primary diagnosis?
  2. 2.What were the results of the liver function tests (ALT/AST), and what do they tell us about organ involvement?
  3. 3.If there are no skin lesions, what led you to suspect HSV?
  4. 4.How are we monitoring for potential neurological changes or seizures?
  5. 5.Since SEM can progress to more serious forms, how frequently are we re-evaluating my baby's status?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

References (13)
  1. 1

    Neonatal herpes simplex virus infection: From the maternal infection to the child outcome.

    De Rose DU, Bompard S, Maddaloni C, et al.

    Journal of medical virology 2023; (95(8)):e29024 doi:10.1002/jmv.29024.

    PMID: 37592873
  2. 2

    Herpes simplex virus disease in infants younger than 90 days: a British Paediatric Surveillance Unit study.

    Dudley JRR, Shears A, Yan G, et al.

    Archives of disease in childhood 2026; (111(5)):423-429 doi:10.1136/archdischild-2025-329176.

    PMID: 40897403
  3. 3

    Neonatal herpes simplex presenting as a zosteriform eruption.

    Anderson E, Johns E, Conlon J, Saleh E

    BMJ case reports 2023; (16(1)) doi:10.1136/bcr-2022-252627.

    PMID: 36657819
  4. 4

    Congenital herpes simplex with ophthalmic and multisystem features: a case report.

    Pereira SM, Lima RV, Muniz MCR, et al.

    BMC pediatrics 2023; (23(1)):611 doi:10.1186/s12887-023-04423-1.

    PMID: 38044450
  5. 5

    Herpes Simplex Virus in the Neonate.

    Wang A, Wohrley J, Rosebush J

    Pediatric annals 2017; (46(2)):e42-e46 doi:10.3928/19382359-20170112-01.

    PMID: 28192576
  6. 6

    The Many Faces of Neurological Neonatal Herpes Simplex Virus Infection.

    Shahoud F, Rathore MH, Shah CC, Alissa R

    Cureus 2023; (15(7)):e41580 doi:10.7759/cureus.41580.

    PMID: 37559852
  7. 7

    Neonatal herpes simplex virus encephalitis with intracranial bleeding in a newborn baby with concurrent rhesus incompatibility.

    Clemence P, Mariki H, Mkony M, Manji KP

    BMJ case reports 2024; (17(3)) doi:10.1136/bcr-2023-255822.

    PMID: 38458763
  8. 8

    A Rare Case of Neonatal Disseminated Herpes Simplex Virus (HSV) With Concomitant Methicillin-Sensitive Staphylococcus aureus (MSSA) Bacteremia.

    Sykes SR, Sharpe EL

    Advances in neonatal care : official journal of the National Association of Neonatal Nurses 2022; (22(5)):400-407 doi:10.1097/ANC.0000000000000949.

    PMID: 34596088
  9. 9

    Epidemiology and Outcomes of Neonatal Hemophagocytic Lymphohistiocytosis.

    Balakumar N, Sendi P, Totapally BR

    Frontiers in pediatrics 2022; (10()):848004 doi:10.3389/fped.2022.848004.

    PMID: 35558361
  10. 10

    Bird's Eye View of a Neonatologist: Clinical Approach to Emergency Neonatal Infection.

    Huang FK, Chen HL, Yang PH, Lin HC

    Pediatrics and neonatology 2016; (57(3)):167-73.

    PMID: 26701838
  11. 11

    Severe Acute Liver Injury From Hemophagocytic Lymphohistiocytosis Related to Disseminated Herpes Simplex Virus Type 1 in a Young Immunocompetent Man.

    Seog WJ, Steinberg J, Ghafary I, et al.

    ACG case reports journal 2025; (12(1)):e01581 doi:10.14309/crj.0000000000001581.

    PMID: 39764152
  12. 12

    Herpes Simplex Pneumonitis Presenting As Acute Respiratory Distress Syndrome and Septic Shock.

    Pata R, Kosuru B, Kristeva J

    Cureus 2024; (16(12)):e75075 doi:10.7759/cureus.75075.

    PMID: 39759712
  13. 13

    Precision in Cardiovascular Care Using Targeted Neonatal Echocardiography in Lethal Neonatal Disseminated Herpes Infection: A Case Series.

    Bhattacharya S, McNamara PJ, Giesinger RE

    The Pediatric infectious disease journal 2021; (40(6)):566-570 doi:10.1097/INF.0000000000003071.

    PMID: 33470772

This page provides educational information about neonatal HSV classifications and symptoms. It does not replace professional medical advice; always seek immediate medical attention if your newborn shows signs of illness.

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