A newborn with widespread pustules
A 5-day-old term male infant is brought to the emergency department with a 2-day history of a widespread eruption. He was born at 39 weeks by spontaneous vaginal delivery, birth weight 3.4 kg, and was discharged at 48 hours. He is feeding poorly and has a temperature of 38.1 °C. On examination there are numerous 2–4 mm pustules with surrounding erythema over the trunk, limbs, and face, some with a collarette of scale. There are also a few larger flaccid bullae on the abdomen. The mucous membranes are spared. His mother had a febrile illness with a rash in the third trimester, and her serology results are pending. He has not yet received the BCG vaccine.
1. What is your differential diagnosis for pustular and bullous eruptions in a 5-day-old, and which features mandate immediate investigation?
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Differential diagnosis
- Staphylococcal scalded skin syndrome (SSSS) - flaccid bullae, Nikolsky-positive, tender erythema, often starts around the mouth and flexures; caused by exfoliative toxin from Staphylococcus aureus. A neonate with fever and poor feeding is a medical emergency.
- Bullous impetigo - localised flaccid bullae with clear or turbid fluid; can generalise in neonates.
- Erythema toxicum neonatorum - benign, fleabite-like pustules on erythematous base, sparing palms and soles, usually appears in the first 48–72 hours; infant is well. The fever and poor feeding argue against this.
- Transient neonatal pustular melanosis - pustules present at birth, rupture leaving collarette of scale and hyperpigmented macules; infant is well.
- Neonatal herpes simplex virus (HSV) - grouped vesicles on erythematous base, often with sepsis-like illness; a maternal third-trimester febrile rash raises this possibility. This is the most important diagnosis not to miss.
- Varicella - vesicular lesions at different stages; maternal history relevant.
- Congenital syphilis - often presents with bullous lesions (pemphigus syphiliticus) on palms and soles, snuffles, hepatosplenomegaly; maternal serology pending.
- Listeriosis - neonatal sepsis with pustules; maternal febrile illness is a clue.
- Candidiasis - usually oral or napkin area, not widespread pustules in a neonate.
- Incontinentia pigmenti - vesicular stage at birth, but follows Blaschko's lines and is X-linked dominant (usually female).
Features mandating immediate investigation Fever, poor feeding, and flaccid bullae in a neonate are red flags for serious bacterial infection, HSV, or congenital syphilis. The infant should be investigated urgently with:
- Blood cultures, full blood count, CRP, and lactate.
- Surface swabs from pustules and bullae for Gram stain, culture, and HSV PCR.
- Blood HSV PCR and, if any vesicle, unroofed-vesicle PCR.
- Maternal serology for syphilis (RPR/TPHA), HIV, HSV, and varicella.
- Lumbar puncture if sepsis or HSV is suspected.
- Skin biopsy if the diagnosis remains unclear - histology can distinguish SSSS (subcorneal cleavage) from HSV (ballooning degeneration, multinucleated giant cells).
- Urine and stool cultures as part of sepsis screen.
Empirical intravenous antibiotics (e.g., flucloxacillin plus gentamicin, or per local neonatal sepsis protocol) and consideration of intravenous aciclovir should not be delayed pending results.
2. The baby is started on empirical antibiotics and aciclovir. How do you distinguish SSSS from bullous impetigo and from HSV, and what specific management follows if each is confirmed?
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Distinguishing the three
SSSS
- Caused by exfoliative toxins A/B from S. aureus at a distant site (umbilicus, nares, conjunctiva).
- Flaccid bullae and superficial peeling, Nikolsky-positive, with tender erythema and a 'scalded' appearance; mucous membranes spared.
- Histology: subcorneal cleavage with no organisms in the blister.
- Neonates are at particular risk because of immature renal clearance of toxin.
Bullous impetigo
- Also S. aureus, but toxin acts locally; flaccid bullae with turbid fluid, usually localised, with a collarette of scale.
- Histology: subcorneal cleavage with Gram-positive cocci within the blister.
- Less systemic toxicity than SSSS.
Neonatal HSV
- Grouped vesicles on an erythematous base, often at sites of trauma (scalp electrodes), with sepsis-like illness, lethargy, poor feeding, and possibly hepatitis or CNS involvement.
- Histology: ballooning degeneration, multinucleated giant cells, intranuclear inclusions; PCR is the diagnostic test of choice.
- Maternal third-trimester febrile rash is a strong clue.
Management if confirmed
SSSS: IV anti-staphylococcal antibiotics (flucloxacillin or, if MRSA suspected, vancomycin/clindamycin), aggressive fluid and electrolyte management, emollients and non-adherent dressings, analgesia, and isolation. Avoid topical steroids. Mortality is low with treatment but significant if delayed.
Bullous impetigo: Oral or IV anti-staphylococcal antibiotics depending on extent and systemic status; topical mupirocin for limited disease; hygiene measures and treatment of carriers if recurrent.
Neonatal HSV: IV aciclovir 20 mg/kg every 8 hours for 14 days (21 days if CNS disease), with renal monitoring, ophthalmology review, and lumbar puncture. Prognosis depends on prompt initiation; disseminated disease carries high mortality.
In this infant The combination of fever, poor feeding, flaccid bullae, and maternal febrile rash means empirical cover for both staphylococcal disease and HSV is appropriate until results return. Continue supportive care, monitor renal and hepatic function, and involve neonatology, infectious diseases, and dermatology. If HSV is confirmed, notify public health as appropriate and counsel the mother.