Skip to Main Content


The development of vesicles, pustules, or bullae on the neonatal skin raises a broad differential, which includes infectious, inflammatory, autoimmune, or hereditary causes. The initial clinical presentation of many of these conditions may appear similar. Thus, it is helpful to identify and categorize based on primary morphologic changes (Table 65-1).

Table 65-1Differential Diagnosis of Neonatal Blistering Diseases

Vesicles are defined as a blister measuring less than 1 cm in size. Blisters larger than 1 cm are termed bullae. Pustules are vesicles with purulent fluid. Vesicles, pustules, and bullae may rapidly rupture, resulting in erosions and ulcerations as the predominant morphology. In other cases, the vesicles and pustules may be miniscule and difficult to discern.

While most of these conditions are benign and transient, there are a few serious, life-threatening conditions that require prompt diagnosis and treatment. Given the broad differential raised by the presence of neonatal blisters, it is helpful to identify the predominant morphology of the eruption and take into account a thorough history and physical.


Erythema Toxicum Neonatorum

Erythema toxicum neonatorum (ETN) is 1 of the most common transient, benign skin disorders in the neonatal period. It occurs in about 20% of term newborns,1, 2, 3, and 4 with some reports5, 6, 7, and 8 of frequencies as high as 40%–70%. These erythematous papules and pustules are usually not present at birth but will appear during the first day or 2 of life.8

The lesions of ETN are characterized by small papules and pustules overlying an erythematous macule or wheal. The lesions are most frequently found on the trunk and thighs but can also occur on the face and arms.1 The eruption spares the palms and soles.

The differential diagnosis of ETN includes transient neonatal pustular melanosis (TNPM), miliaria rubra, and eosinophilic pustular folliculitis.

The diagnosis of ETN is usually made clinically. In some instances, confirmation of the diagnosis can be obtained by Wright staining of a pustule, which would show numerous eosinophils.8,9 Peripheral eosinophilia can be seen in about 15% of patients with ETN, which correlates with the severity ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.