The diagnosis of vesicular and bullous diseases in childhood can be a difficult task. To better understand the defining characteristics of vesiculobullous disorders, a general knowledge of skin anatomy is helpful. Figure 59-1 illustrates normal skin histology. The numerous causes of blistering can be divided into those with neonatal versus childhood onsets. Additionally, secondary characteristics, such as distribution and morphology, can further limit the differential diagnosis.

It is important to have a clear understanding of the terminology used to describe vesicular or bullous lesions and their associated physical features. A vesicle is a fluid-filled, dome-shaped lesion of 0.5 cm or less; if such a lesion is greater than 0.5 cm, it is termed a bulla. The fluid inside may be clear or hemorrhagic in nature. If the material is purulent, the lesion is called a pustule. Secondary lesions, including crusting, excoriation, scaling, milia, and scarring, may also be noted. An erosion is a superficially denuded vesicle with damage confined to the epidermis. Ulceration is a deeper lesion, with loss of the entire depth of the epidermis. Secondary scarring does not usually result from erosion, except if secondary infection occurs, but is common with ulceration given the depth of the injury (Table 59-1; Figure 59-2). Milia (small, white, superficial epidermal cysts) may result from a healing blistering process.

Whether the vesicle or bulla is flaccid or tense, is another defining characteristic. A tense bulla suggests a deeper process in which the split in the epidermis lies below the level of the lamina lucida located in the basement membrane zone. This gives the lesion enough support to hold the fluid tense under pressure. In contrast, a flaccid bulla is a more superficial process that generally occurs higher in the epidermis, where skin tension may easily disrupt the lesion’s integrity (Figure 59-3). Helpful in differentiating a tense from a flaccid bulla are the Nikolsky and Asboe-Hansen signs. A positive Nikolsky sign occurs when a blister is induced by rubbing normal-appearing skin with the eraser of a pencil. The Asboe-Hansen sign is elicited by applying lateral pressure to the edge of a bulla away from the center. If the lesion extends, the split is higher up in the epidermis and the lesion is classified as flaccid. If the lesion does not extend, a deeper split is suggested, and the lesion is defined as tense.

The clinical presentation of the numerous vesiculobullous conditions varies tremendously, depending on whether the lesion is a primary process or a manifestation of an underlying illness. A complete history should include the duration of disease, previous or current infection, other family members affected, recent travel, environmental or household exposures, and associated symptoms. A thorough review of systems can help ascertain the severity of the illness, and systemic complaints such as fever, arthralgias, lethargy, and weight loss may help define a cause. Special care must be taken in the evaluation of neonates, because associated symptoms are not always well defined in this age group, and occult infection can easily be missed. If an adverse drug reaction is suspected, a detailed drug history is essential. Even regularly used over-the-counter medications, such as nonsteroidal anti-inflammatory drugs, can cause blistering reactions, including bullous fixed drug reactions, pseudoporphyria, or even toxic epidermal necrolysis. A detailed family history is vital to the diagnosis of many genetic vesiculobullous disorders, including various forms of epidermolysis bullosa simplex and Hailey-Hailey disease. A positive family history of autoimmune diseases may also assist in making a diagnosis.

Aside from identifying the nondermatologic features on physical examination, a clear description of the skin lesions is necessary, using the terms defined earlier. Delineating the nature of the lesions, the pattern of eruption, and its arrangement and distribution can be invaluable in differentiating among vesiculobullous diseases. Note whether the lesions are grouped or scattered, localized to a specific area or generalized, or linear or annular in configuration; note whether they follow the lines of Blaschko or occur in a dermatomal distribution. It is also important to identify the duration and timing of the lesions. The history should reveal whether the lesions are acute, subacute, or chronic in duration. Lesions may appear at the same time, in crops, or follow a cyclical pattern, with periods of activity followed by resolution. The lesions may appear to be recently erupted, resolving, or a mixed pattern. Attention to the mucosal surfaces is important, because many systemic blistering disorders involve the oral, genital, or ocular mucosal surfaces.

As noted above, the age of onset of a disorder is an important clue in the diagnosis of vesiculobullous disorders. The differential diagnoses of neonatal and childhood vesiculobullous disorders are described in Tables 59-2 and 59-3, respectively.^1-6 Lesions that appear in the neonatal period may be genetic, infectious, or even iatrogenic. Infectious causes should always be considered in a newborn with vesiculobullous findings. If the lesions are congenital, a genetic blistering disorder should be considered. Some autoimmune disorders can be transferred through the presence of maternal antibodies, up to about 6 months of age. Disorders in this category include neonatal lupus, neonatal pemphigus, and pemphigus foliaceus.