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.
Lesion | Definition |
---|---|
Primary | |
Vesicle | Fluid-filled lesion <0.5 cm |
Bulla | Fluid-filled lesion >0.5 cm |
Pustule | Blistering lesion filled with purulent exudate |
Secondary | |
Erosion | Partial loss of epidermis |
Ulceration | Complete loss of epidermis with extension into dermis |
Excoriation | Scratched primary lesions; may be linear or crusted |
Scaling | Dry, superficial accumulations of keratin |
Crusting | Dried serous, hemorrhagic, or purulent exudate (i.e. scabbing) |
Milia | Small 1- to 2-mm epidermal cysts |
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.
Disorder | Onset and Duration | Clinical Characteristics | Diagnosis |
---|---|---|---|
Benign, transient erythema toxicum neonatorum | 24–72 hr after birth; lasts 1 wk | Blotchy erythema with small central pustule; generalized, except palms and soles; full-term, healthy infants | Clinical, Gram stain: eosinophils |
Neonatal acne | Weeks to months | Erythematous papules and pustules on face and chest; healthy neonates | Clinical, stains mostly negative, but may see yeast forms |
Transient neonatal pustular melanosis | Birth; hyperpigmentation lasts months | Pustules without erythema; collarette when wiped away; heals, but hyperpigmentation lasts months; generalized, palms, and soles; healthy neonates; more common in darker pigmented skin types | Clinical, Gram stain: neutrophils |
Miliaria (rubra or crystal lina) | Days to months; lasts hours to days | Small erythematous papules (rubra) to clear vesicles (crystallina) on forehead, upper chest, and back; history of fever, overheating | Clinical, all stains negative |
Infantile acropustulosis | Days to months; may last 2–3 yr | Extremely pruritic vesicles and pustules occurring in crops on hands and feet | Clinical, biopsy Biopsy |
Eosinophilic pustular folliculitis | Birth to 1 yr; may last years | Pruritic follicular-based papules and pustules on scalp and face; very rare | Biopsy |
Congenital langerhans cell histiocytosis | Birth to days | Vesicles to crusted papules, petechiae; solitary to numerous; scalp, groin, flexures most common | Biopsy, electron microscopy |
Sucking blister | Birth or later | Noninflamed blister; usually solitary; most often on hands or wrists | Clinical, all stains negative |
Inflammatory mastocytosis | Birth to several months | Mastocytoma: solitary pink, tan, or brown macule to indurated plaque with overlying bullae | Clinical, all stains negative, biopsy showing mast cells |
Urticaria pigmentosa: multiple lesions as described for mastocytoma | |||
Diffuse cutaneous mastocytosis: peau d’orange (indurated yellowish orange skin) with vesicles and bullae at sites of trauma | |||
Infectious syphilis | Birth | Vesicles and bullae, often eroded; perioralo (snuffles), hands, and feet; may be localized or generalized; associated with hepatosplenomegaly and pseudoparalysis | Serology, DFA; darkfield examination |
Candidiasis, congenital | Birth to 24 hr; lasts 2 wk | Generalized erythema and pustules or vesicles | KOH: pseudohyphae |
Candidiasis, neonatal | Past 1 wk of age | Erythematous macules or papules with satellite pustules; diaper area and flexures most commonly affected | KOH: pseudohyphae |
Herpes simplex | Birth to weeks | Vesicles or pustules; erosions to scarring; localized to generalized | Tzanck, DFA, PCR, culture, or serology |
Varicella | Birth | Linear scarring, erosions; often affects extremities; fetal anomalies occur with first- or second-trimester infection | Tzanck, DFA, PCR, culture, or serology |
Scabies | Weeks | Vesicles to crusted papules, nodules with burrows; hands, feet, axilla, scalp | Mineral oil preparation |
Genetic incontinentia pigmenti | Birth | Linear and whorled vesicles along lines of Blaschko; progresses to verrucous lesions; localized to limb or generalized; may be associated with seizures, retinopathy, and eosinophilia | Biopsy, genetic testing (NEMO gene) |
Epidermolysis bullosa | Birth to teens (for certain forms such as Weber-Cockayne) | Noninflammmatory vesicles, bullae; often eroded; milia with dystrophic forms; extremities most often affected; severity depends on type; some forms associated with pyloric atresia, Gl involvement, failure to thrive | Biopsy, electron microscopy, genetic testing (keratins 5/14, plectin, laminin 5, collagen XVII, α6β4 integrin, collagen VII) |
Transient bullous dermolysis of the newborn | Birth; resolves within months | Extensive blistering due to transient defect in collagen VII | Biopsy, electron microscopy |
Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma) | Birth | Generalized erythema and scaling with bullae and erosions; evolves to generalized ichthyosis with flexural predominance | Biopsy, genetic testing (keratins 1/10) |
Ichthyosis bullosa of siemens | Birth | Milder blisters and erosions than epidermolytic hyperkeratosis; episodic superficial peeling | Clinical, biopsy; genetic testing (keratin 2e) |
AEC syndrome birth (Hay-Wells) | Birth | Associated with erosive scalp dermatitis | Clinical, genetic testing (p63 gene) |
Ectodermal dysplasia; skin fragility syndrome | Birth | Generalized erythema with superimposed bullae, erosions; perioral redness and desquamation; sparse hair and dystrophic nails; abnormal sweating | Biopsy, genetic testing (plakophilin) |
Congenital erosive and vesicular dermatosis | Birth; heals in weeks to months | Premature infants; diffuse vesicles, erosions, and crusting; palms, soles, face relatively spared; heals with reticulated scarring | Biopsy |
Kindler syndrome | Birth to months | Acral blistering that later develops poikiloderma | Biopsy, electron microscopy |
Metabolic acrodermatitis enteropathies | Birth to 6 mo | Copper-colored patches and plaques; perioral region, groin, hands, and feet; overlying vesicles and bullae | Low serum zinc level, low alkaline phosphatase |
Autoimmune herpes gestationis | Birth; resolves in weeks | Very pruritic, urticarial plaques with overlying tense vesicles, bullae; results from transfer of maternal antibodies; self-limited | Biopsy, direct and indirect immunofluorescence |
Neonatal pemphigus | Birth; resolves in a few weeks | Pruritic, urticarial plaques with flaccid bullae, erosions; occurs in infants of mothers with active pemphigus vulgaris or foliaceus due to transfer of maternal antibodies | Maternal history, biopsy, direct and indirect immunofluorescence |
![](https://freepngimg.com/download/social_media/63059-media-icons-telegram-twitter-blog-computer-social.png)
Stay updated, free articles. Join our Telegram channel
![](https://clinicalpub.com/wp-content/uploads/2023/09/256.png)
Full access? Get Clinical Tree
![](https://videdental.com/wp-content/uploads/2023/09/appstore.png)
![](https://videdental.com/wp-content/uploads/2023/09/google-play.png)
![](https://clinicalpub.com/wp-content/uploads/2023/09/banner1.png)