Residents’ Corner

Vesiculobullous and Pustular Diseases in Newborns

Author and Disclosure Information



Infants at a few weeks of life may present with a noncomedonal pustular eruption on the cheeks, forehead, and scalp commonly known as neonatal acne or neonatal cephalic pustulosis. The driving factor is thought to be an abnormal response to Malassezia and can be treated with ketoconazole cream or expectant management.2

Cutaneous candidiasis is the most common infectious cause of vesicles in the neonate and can present in 2 fashions. Neonatal candidiasis is common, presenting a week after birth and manifesting as oral thrush and red plaques with satellite pustules in the diaper area. Congenital candidiasis is due to infection in utero, presents prior to 1 week of life, exhibits diffuse erythroderma, and requires timely parenteral antifungals.5 Newborns and preterm infants are at higher risk for systemic disease, while full-term infants may experience a mild course of skin-limited lesions.

It is imperative to rule out other infectious etiologies in ill-appearing neonates with vesicles such as herpes simplex virus, bacterial infections, syphilis, and vertically transmitted TORCH (toxoplasmosis, other infections rubella, cytomegalovirus infection, and herpes simplex) diagnoses.6 Herpes simplex virus classically presents with grouped vesicles on an erythematous base; however, such characteristic lesions may be subtle in the newborn. The site of skin involvement usually is the area that first comes into contact with maternal lesions, such as the face for a newborn delivered in a cephalic presentation.2 It is critical to be cognizant of this diagnosis, as a delay in antiviral therapy can result in neurologic consequences due to disseminated disease. The other TORCH diagnoses may present with blueberry muffin lesions, which are blue to violaceous papules on the trunk, arms, and legs due to extramedullary hematopoiesis. Each disease process may lead to its own characteristic sequelae and should be further investigated based on the maternal history.

If the clinical picture of vesiculobullous disease in the newborn is not as clear, less common causes must be considered. Infantile acropustulosis presents with recurring crops of pustules on the hands and feet at several months of age. The most common differential diagnosis is scabies; therefore, a mineral oil preparation should be performed to rule out this common mimicker. Potent topical corticosteroids are first-line therapy, and episodes generally resolve with time.

Another mimicker of pustules in neonates includes deficiency of IL-1ra, a rare entity described in 2009.7 Deficiency of IL-1ra is an autoinflammatory syndrome of skin and bone due to unopposed action of IL-1 with life-threatening inflammation; infants present with pustules, lytic bone lesions, elevated erythrocyte sedimentation rate and C-reactive protein, and failure to thrive.8 The characteristic mutation was discovered when the infants dramatically responded to therapy with anakinra, an IL-1ra.

Eosinophilic pustular folliculitis is an additional pustular dermatosis that manifests with lesions predominately in the head and neck area, and unlike the adult population, it usually is self-resolving and not associated with other comorbidities in newborns.2

Incontinentia pigmenti is an X-linked dominant syndrome due to a genetic mutation in NEMO, nuclear factor κβ essential modulator, which protects against apoptosis.3 Incontinentia pigmenti presents in newborn girls shortly after birth with vesicles in a blaschkoid distribution before evolving through 4 unique stages of vesicular lesions, verrucous lesions, hyperpigmentation, and ultimately resolves with residual hypopigmentation in the affected area.

Lastly, neonatal Behçet disease can present with vesicles in the mouth and genital region due to transfer of maternal antibodies. It is self-limiting in nature and would be readily diagnosed with a known maternal history, though judicious screening for infections may be needed in specific settings.2


In summary, a vast array of benign and worrisome dermatoses present in the neonatal period. A thorough history and physical examination, including the temporality of the lesions, the health status of the newborn, and the maternal history, can help delineate the diagnosis. The 5-step method presented can further elucidate the underlying mechanism and reduce an overwhelming differential diagnosis list by reviewing each finding yielded from each step. Dermatology residents should feel comfortable addressing this unique patient population to ameliorate unclear cutaneous diagnoses for pediatricians.


A special thank you to Lawrence A. Schachner, MD (Miami, Florida), for his help providing resources and guidance for this topic.

Next Article: