Do a complete family history looking for relatives with similar changes. Broad categories include infection (Staph, Herpes, Syphilis), inherited, autoimmune (e.g. neonatal phemphigus) and trauma.
The differential diagnosis of neonatal hand and feet bullae includes epidermolysis bullosa (simplex, junctional, hemidesmosomal, or dystrophic), epidermolytic hyperkeratosis, bullous impetigo, and neonatal herpes infection. Small vesicles would suggest herpes simplex. Intact bulla and no erosions argue somewhat against bullous impetigo.
Epidermolytic Hyperkeratosis (Bullous Congenital Ichthyosiform Erythroderma)
Congenital Cutaneous Candidiasis
Herpes Simplex, Congenital
Herpes Simplex, Neonatal
Linear IgA Bullous Dermatosis
Pemphigus Vulgaris, Neonatal Mom almost always known to have pemphigus.
Bullous Dermolysis of the Newborn
Congenital Self-Healing Reticulohistiocytosis Rarely, CSHR may present as a widespread blistering eruption at birth[CED 1994;19;350]
Neonatal Bullous Eruption 2 To Transient Porphyrinemia And Phototherapy JAAD 1995;33;333
Transillumination blisters in the neonate [JAAD 1999;41;264]. Discrete 4 mm vesicles or crusted, necrotic areas acrally at areas where a vessel might be noted is characteristic.