What is the appropriate management for a newborn presenting with a rash?

Management of Neonatal Rash

Any neonate with a rash and systemic signs (fever, poor feeding, lethargy, irritability) requires immediate hospitalization, blood cultures, lumbar puncture with CSF PCR for HSV, and empiric parenteral antibiotics—do not delay treatment for diagnostic workup. 1

Immediate Risk Stratification

The first critical step is determining whether the infant requires emergent intervention:

• High-risk presentations requiring immediate systemic therapy: 1

  • Any systemic signs (fever, poor feeding, lethargy, irritability, loss of alertness)
  • Premature infants with any pustulosis
  • Neonates with central lines, prolonged antibiotic exposure, or recent surgery
  • Rapidly spreading pustules or suspected bony involvement

• Important caveat: Only 60% of neonates with CNS or disseminated HSV disease present with vesicular rash—absence of vesicles does not exclude serious infection. 2, 1, 3

Empiric Antibiotic Therapy for High-Risk Neonates

For any neonate requiring systemic treatment (age ≤28 days with systemic signs or high-risk features): 1

• Ampicillin 150 mg/kg/day IV divided every 8 hours PLUS
• Either ceftazidime 150 mg/kg/day IV divided every 8 hours OR gentamicin 4 mg/kg IV every 24 hours

For suspected staphylococcal/streptococcal infection: 1

• Nafcillin or oxacillin 50 mg/kg/dose IV every 6 hours

Critical contraindications: Avoid TMP-SMX (kernicterus risk) and cefalexin (contraindicated birth to 28 days). 1

Essential Diagnostic Workup for Suspected Infection

When infection is suspected, obtain: 1, 2

• Blood cultures (mandatory for extensive disease or systemic illness)
• Lumbar puncture with CSF PCR for HSV DNA (diagnostic test of choice for HSV encephalitis)
• Culture specimens from blood, skin vesicles, mouth/nasopharynx, eyes, urine, and stool/rectum if HSV suspected
• Direct immunofluorescence or Tzanck preparation from lesion scrapings 2

Maternal history is critical: Document maternal syphilis serology status—no infant should leave the hospital without documented maternal testing. 2

Management of Specific Infectious Etiologies

Congenital Syphilis

For infants born to mothers with reactive syphilis serology: 2

• Perform quantitative nontreponemal test (RPR/VDRL) on infant serum (not cord blood—contamination risk)
• Examine thoroughly for hepatosplenomegaly, jaundice, rhinitis, skin rash, pseudoparalysis
• If infant titer is fourfold greater than maternal titer OR abnormal physical exam OR positive darkfield test:
  • Aqueous crystalline penicillin G 100,000-150,000 units/kg/day IV (50,000 units/kg/dose every 12 hours for first 7 days, then every 8 hours) for 10 days total
  • OR Procaine penicillin G 50,000 units/kg/dose IM daily for 10 days

Invasive Candidiasis

For disseminated cutaneous neonatal candidiasis in premature/low birth weight infants: 2, 1, 3

• Amphotericin B deoxycholate 1 mg/kg/day OR liposomal amphotericin B 2.5-7 mg/kg/day 1
• Fluconazole 12 mg/kg daily is alternative if urinary tract involvement excluded 1
• Treatment duration: minimum 3 weeks 1
• Catheter removal is mandatory 1
• Consider dilated retinal exam and imaging of genitourinary tract, liver, spleen if sterile body fluid cultures persistently positive 1

Prophylaxis consideration: In nurseries with invasive candidiasis rates >12%, consider fluconazole prophylaxis 3-6 mg/kg twice weekly for neonates <1000g. 1

Herpes Simplex Virus

Clinical presentation varies by disease type (disseminated, CNS, or localized skin/eye/mouth), typically appearing at 9-11 days of age. 2

• Vesicular rash present in only ~80% with localized disease and ~60% with disseminated/CNS disease 2
• Grouped vesicles on erythematous base are characteristic 3
• Treatment requires systemic antiviral therapy (specific regimens beyond scope but urgent consultation needed)

Management of Low-Risk, Well-Appearing Term Infants

For full-term infants ≤30 days with localized pustulosis and no systemic signs: 1

• Topical mupirocin 2-3 times daily with close monitoring is appropriate
• Most benign neonatal rashes (erythema toxicum neonatorum, transient neonatal pustular melanosis, neonatal acne) are self-limited and require only reassurance 4, 5

Benign Transient Rashes (Observation Only)

These can be diagnosed clinically by appearance: 4, 5

• Erythema toxicum neonatorum: Erythematous macules with central pustules, typically appearing 24-48 hours after birth
• Transient neonatal pustular melanosis: Superficial pustules that rupture easily, leaving hyperpigmented macules
• Neonatal acne: Comedones and inflammatory papules on face, typically appearing at 2-4 weeks

Fungal Skin Infections (Localized, Non-Invasive)

For healthy full-term infants with localized fungal dermatitis: 6

• Topical nystatin, clotrimazole 1%, or miconazole 2% cream applied 2-3 times daily for 7-14 days 6
• Continue treatment for at least one week after clinical resolution to prevent recurrence 6
• Keep area clean and dry with frequent diaper changes 6
• Treat maternal nipple candidiasis if breastfeeding to prevent reinfection 6

For significant inflammation: Consider short-term (3-5 days maximum) combination therapy with topical antifungal plus hydrocortisone 1%. 6

Local Wound Care for Pustules/Vesicles

When local care is needed: 1, 2

• Gently cleanse with antimicrobial solution (e.g., aqueous chlorhexidine 0.05%) without initially rupturing 1
• If drainage needed, pierce at base with sterile needle, apply gentle pressure with sterile gauze 1
• Never deroof blisters or pustules 1, 2
• Apply nonadherent dressing as needed 1
• Monitor for signs of infection (extending erythema, warmth, systemic symptoms) 2

Critical Pitfalls to Avoid

• Never delay antibiotics for imaging or extensive workup in systemically ill neonates—treat first, investigate simultaneously 1
• Do not use high-potency topical corticosteroids on infant facial skin—increased systemic absorption risk, HPA axis suppression, and skin atrophy 3, 2
• Neonates under 2 weeks can deteriorate rapidly from localized to disseminated infection—maintain extremely high index of suspicion 1
• Premature infants require immediate escalation to systemic antibiotics with any clinical change—do not attempt topical therapy alone 1
• Absence of vesicular rash does not exclude HSV—40% of disseminated/CNS cases lack vesicles 2, 1, 3
• Do not test infant cord blood for syphilis serology—maternal blood contamination causes false positives; use infant serum 2

Supportive Care for All Neonates

Regardless of etiology: 3

• Bathe with water or nonsoap cleanser 2-3 times weekly followed by bland emollient application 3
• Maintain thermoregulation and adequate hydration
• Ensure close follow-up within 24-48 hours for any treated rash