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Case Conference

Case Conference. Sheryl Kho, M.D. PGY-3. 15 year old female . Chief complaint: rash. HPI. 2 wks Genital area No itchiness, no foul smelling vaginal discharge +pain, burning sensation No fever, no malaise, no dysuria, no hematuria, no frequency, urgency, hesitancy

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Case Conference

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  1. Case Conference Sheryl Kho, M.D. PGY-3

  2. 15 year old female Chief complaint: rash

  3. HPI • 2 wks • Genital area • No itchiness, no foul smelling vaginal discharge • +pain, burning sensation • No fever, no malaise, no dysuria, no hematuria, no frequency, urgency, hesitancy • Applied topical antibiotic, no relief

  4. PMHx: noncontributory • PSHx: noncontributory • Imm:UTD • FHx: noncontributory • HEADS: lives with mother, father, sister, in 11th grade, average student, hangs out with friends, stay at home, denies drugs, EtOH, cigarettes, no suicidal/homicidal ideation, no body dysmorphic disorder, no anorexia, bulimia

  5. Sexual Hx • + boyfriend, 17 years old • + sexual activity, last 5 days ago • Seldom uses condoms, no other contraception • Never been tested for STD

  6. Gyn Hx • Menarche:12 yo • Interval: q 30 days • Duration: 5-6 days • Amount: 3 pads per day, medium soaked • Symptoms: no dysmenorrhea • LMP: ? 1 month ago

  7. Physical Exam • VS: T99.7 HR 78 RR 18 BP 110/75 • Gen: NAD, AAO • HEENT: NCAT, EOMI, PERRLA, intact TM, MMM, no exudates, supple neck • Lungs:CTA B/L, no W/R/R • Heart: NRRR, N S1/S2, no murmur • Abdo: soft, NT, ND, no HSM • Ext:good cap ref, pulses full&equal, no cyanosis, no edema • GU:+multiple shallow ulcers on both labia majora, no crusting, no vesicles, no discharge, tanner 4

  8. Labs: • Urine Preg Test: + • HSV Viral Culture: + HSV 2 • Quantitative B-HCG: 1400

  9. Neonatal Herpes Simplex Infections

  10. Herpes Simplex Virus • Herpesviridae family, DNA • Also known as HHV 1 and HHV 2 • HSV 1: establishes latency in the trigeminal ganglion • HSV 2: sacral ganglion at the base of the spine

  11. Neonatal Herpes Simplex Infection • High morbidity and mortality in the absence of therapy ~ 80% • Most infants surviving CNS or disseminated disease are neurologically impaired • TORCH infection

  12. Epidemiology of Neonatal HSV Infection • Differs between countries • Rare in UK, higher incidence in USA 1.65/100,000 live births vs. 20-50/100,000 live births • Infection can be from HSV 1 or 2

  13. Epidemiology • HSV 2--> genital herpes, ~85% of cases, involved in 70% of neonatal herpes • Incidence: one in every 3,000-20,000 live births • Of known infected infants, only 30% of mothers have symptomatic HSV or a partner with clinical infection

  14. Transmission to the Neonate • Most often occurs during delivery (intrapartum) • In utero (congenital) • Following delivery (postpartum)

  15. Transmission to the Neonate • Intrauterine • 5% • A. Ascending infection from cervix or vulva • B. Transplacental transmission • First 20 wks- spontaneous abortions, stillbirth, congenital malformations

  16. Transmission to the Neonate • Intrapartum • 85% • Transmitted during labor • Direct contact with maternal secretions in birth canal

  17. Transmission to the Neonate • Postpartum • 10% • Environmental source • Family member with orolabial herpes, herpetic whitlow or lesions at other sites e.g. breast

  18. Factors Influencing Transmission to the Neonate • Type of maternal genital infection at the time of delivery • First episode: 50% • symptomatic reactivation: 2-5% • asymptomatic virus shedding: 33% • Transmission of maternal transplacental antibodies • Quantity and quality of maternal Ab • Seroconversion of mother vs. absence of maternal anti HSV Ab

  19. Factors Influencing Transmission to the Neonate • Duration of ruptured membranes in the presence of active infection • More than 6 hours • Ascending infection • Use of fetal scalp monitor at delivery • Site of inoculation for virus • Young maternal age <25 years old

  20. Clinical Manifestations • 3 Categories: • disease localized to the skin, eyes, mucous membranes (SEM) • CNS disease (with or without SEM) • Disseminated infection- multiorgan

  21. Clinical Manifestations • HSV should be considered in all neonates who present with nonspecific symptoms ie. Poor feeding, fever, lethargy or seizures in the first month of life • HIGH INDEX OF SUSPICION!

  22. SEM Disease • Presents around 10-11 days of age • Localized to the SEM • Discrete vesicles and keratoconjunctivitis

  23. SEM Disease: Complications • Spastic quadriplegia, microcephaly, blindness: 30-40% • Neurological impairment can become apparent in the following 6-12 months • May appear normal but have subclinical infection of the CNS

  24. CNS Disease/ Encephalitis • Seizures, lethargy, irritability, tremors, poor feeding, temperature instability, bulging fontanelle • Neuronal spread • Unitemporal --> bitemporal --> panencephalitis • 50% present with seizures • 50% mortality due to brainstem involvement • 70% have neurological sequelae

  25. Disseminated Disease • 9-11 days of age • Worst prognosis • Multiple organ involvement • Irritability, seizures, respiratory distress, jaundice, bleeding, shock, vesicular exanthem • Brain infected via blood borne route

  26. Predictors of Mortality • Disseminated> CNS> SEM (57%>15%>0%) • Disseminated Disease: • Reduced level of consciousness • DIC • HSV Pneumonia

  27. Predictors of Mortality • CNS Disease • Semicomatose or comatose at therapy initiation • Prematurity • seizures

  28. Predictors of Morbidity • Disseminated Disease • 4 fold increase: semicomatose or comatose • CNS Disease • 3.4 fold increase: seizures • SEM Disease • 3 or more recurrences of SEM disease (HSV2) in the first 6 months were 21x likely to develop neurological impairment vs. those with less than 3 recurrences

  29. Presentation & Outcomes in Neonatal Herpes in the absence of antiviral therapy

  30. Diagnosis • May occur in the absence of skin lesions • High index of suspicion • Viral culture swabs from skin, oropharyngeal, conjunctiva, rectal, urine

  31. Diagnosis • Liver function tests- elevated • CBC • CSF analysis • CXR • Gold standard: HSV DNA PCRfor CNS disease

  32. Management

  33. Strategies To Prevent Neonatal Acquisition of HSV Infection • Primary Infection/Symptomatic Recurrent Infection • Acyclovir (200mg QID or 400mg TID x 10days) • Decreases the clinical recurrence rate • Lowers c-section rate in women with with recurrent genital herpes • Valacyclovir: Category B-no evidence of adverse effects in humans • Famciclovir • Prophylactic acyclovir in the 3rd trimester for pregnant women with frequent outbreaks

  34. Strategies To Prevent Neonatal Acquisition of HSV Infection • Delivery by Caesarean section • Not 100% protective, atleast 70% decrease in transmission • Suppressive therapy in the sero+ partner of a sero- gravid woman • Condoms: if used more than 70% of the time, transmission is reduced to 60% in the sero- partner • Antivirals ie. Valacyclovir

  35. In Summary • Neonatal herpes: HSV 1 or HSV 2 • Risk of transmission of HSV to the neonate is low in women with a hx of genital herpes in the absence of identifiable lesions (3%) but is increased to ~50% in pregnant women with a primary infection in the 3rd trimester • Delivery by CS decreases te risk of HSV infection in the presence of an active lesion

  36. In Summary • Early recognition and treatment of neonatal HSV to decrease morbidity and mortality • Diagnosis is thru viral cultures, CSF HSV DNA PCR • Disseminated/CNS Disease: treated for 21 days

  37. Questions ?

  38. 1. All the following situations are associated with an increased risk of vertical transmission of HSV infection, except: A. Prematurity
 B. Invasive fetal monitoring
 C. Cesarean delivery
 D. First episode of primary genital maternal HSV infection

  39. 1. All the following situations are associated with an increased risk of vertical transmission of HSV infection, except: A. Prematurity B. Invasive fetal monitoring C. Cesarean delivery D. First episode of primary genital maternal HSV infection

  40. 2. Which of the following regimens is the treatment for disseminated neonatal HSV infection? A. Acyclovir, 60 mg/kg daily in 3 divided doses for 21 days B. Acyclovir, 30 mg/kg daily in 3 divided doses for 21 days C. Acyclovir, 30 mg/kg daily in 3 divided doses for 14 days D. Acyclovir, 60 mg/kg daily in 3 divided doses for 14 days

  41. 2. Which of the following regimens is the treatment for disseminated neonatal HSV infection? A. Acyclovir, 60 mg/kg daily in 3 divided doses for 21 days B. Acyclovir, 30 mg/kg daily in 3 divided doses for 21 days C. Acyclovir, 30 mg/kg daily in 3 divided doses for 14 days D. Acyclovir, 60 mg/kg daily in 3 divided doses for 14 days

  42. 3. You are asked to review a case for morbidity and mortality conference. The infant was born at term to a 19-year-old gravida 1, para 1 woman by normal spontaneous vaginal delivery. The mother was known to be group B Streptococcus-negative, but she did have genital warts. The Apgar scores were 9 at 1 minute and 10 at 5 minutes. On the seventh postnatal day, the infant developed a temperature of 103°F (39.4°C) and was brought to the emergency department. At this time, the infant was in shock and required mechanical ventilation. Physical examination revealed scleral icterus and hepatosplenomegaly but no skin lesions. A lumbar puncture could not be performed. Laboratory results include

  43. White blood cell count of 2.34x10³/mcL (2.34x109/L), with 32% lymphocytes, 41% neutrophils, 8% bands, 15% monocytes, 3% eosinophils, and 1% basophils • Hemoglobin of 7.1 g/dL (71 g/L) • Hematocrit of 21% (0.21) • Platelet count of 40x10³/mcL (40x109/L) • Prothrombin time of 41.2 seconds • Activated partial thromboplastin time of >6 seconds • Aspartate aminotransferase concentration of 3,086 U/L • Alanine aminotransferase concentration of 456 U/L • Total bilirubin of 4.4 mg/dL (75.2 mcmol/L)

  44. The chest radiograph demonstrated diffuse interstitial infiltrates bilaterally. The patient did poorly over the next 3 days and died despite aggressive management in a pediatric intensive care unit.

  45. Of the following, the MOST likely cause of this patients' death is a. Adenovirus b. Escherichia coli c. Group B Streptococcus d. Herpes simplex virus e. Listeria monocytogenes

  46. Of the following, the MOST likely cause of this patients' death is a. Adenovirus b. Escherichia coli c. Group B Streptococcus d. Herpes simplex virus e. Listeria monocytogenes

  47. 4. A 1-week-old infant presents for his first newborn evaluation. He had been discharged apparently well and thriving at 48 hours of age. He now exhibits grouped vesicles on an erythematous base that were not present at birth. Wright stain of scrapings from the floor of the vesicles reveals multinucleated giant cells and balloon cells.

  48. Of the following, the MOST likely diagnosis is a. Bullous impetigo b. Congenital varicella c. Herpes simplex virus infection d. Incontinentia pigmenti e. Recessive dystrophic epidermolysis bullosa

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