Primary vesicular-bullous skin lesions include vesicles, bullae, or pustules. Other distinguishing features include scales, crusts, milia, and scarring. These conditions are classified by depth of skin involvement.
Vesicles are circumscribed, fluid-filled epidermal elevations <1 cm in diameter that: 
Contain serous exudates or serum mixed with blood, or are seropurulent in character (vesicopustules)
Are discrete, grouped (e.g., herpetic infection), irregularly distributed, or linear as in rhus dermatitis (e.g., poison ivy)
Are short-lived, either breaking spontaneously or evolving into bullae through enlargement or coalescence.
Bullae are blisters >1 cm in diameter containing serous or seropurulent fluid. When bullae are located within the epidermis, they present with thin and flaccid walls, which rupture resulting in erosions, scale, and crusts. Erosions are the result of loss of the superficial layers of the epidermis and (in the absence of secondary infection) typically heal without scarring.
The fragility of a blister is related to body location (e.g., intraoral blisters typically present as erosions due to oral trauma, irrespective of localization within or below the epidermis).  Friction blisters occur subcorneally, but present as tense bullae due to the thick stratum corneum of acral skin.
Bullae located intraepidermally are flaccid and rupture easily. They may demonstrate the Nikolsky sign (pressure on unblistered skin in a bullous eruption with resultant shearing off of the epithelium) or the Asboe-Hansen sign (extension of blister into unblistered skin when pressure is applied to the top of the blister).  These signs serve to demonstrate that in some diseases (e.g., pemphigus vulgaris and severe bullous drug eruptions) the extent of blistering is greater than observed by simple inspection.
Bullae located subepidermally are tense. Subepidermal blisters may result in ulceration and scarring following rupture. Ulcers occur when both the epidermis and superficial dermis are lost, either as a consequence of the blistering process (e.g., epidermolysis bullosa), or resulting from secondary infection. Pigment is lost in the ulcer base as the melanocytes are lost in the blister roof.
Pustules, vesicles with purulent exudates, occur as a primary lesion or as secondary change in a vesicle or bulla.
Clinical features that should be noted when evaluating a patient with a blistering process are the presence of scales, crusts, milia, and scarring.
Scales are laminated masses of keratin.  They may indicate a superficial blistering process such as pemphigus, infection-mediated desquamations, and drug eruptions (e.g., toxic epidermal necrolysis).
Crusts are dried exudate composed of serum, cells, and often bacteria. They may be found overlying erosions in one of the subtypes of pemphigus.
Milia are white keratinous cysts 1 mm to 4 mm in diameter. When present in a blistering process they may suggest epidermolysis bullosa or porphyria cutanea tarda.
Scarring is due to a blister developing at either the dermal-epidermal junction or subepidermally (e.g., basement membrane zone). The presence of urticarial plaques and excoriations (even in the absence of blisters) may be an early indicator of autoimmune blistering diseases (e.g., bullous pemphigoid and dermatitis herpetiformis).
Blisters occur at various depths of the epidermis or dermis and may be classified based on the depth of skin involved. A broad classification divides blisters into those arising within the epidermis (intraepidermal, which includes subcorneal) and those that develop below the epidermis (subepidermal, which includes the basement membrane zone).
Assistant Clinical Professor
Departments of Dermatology and Pathology
University of California
Davis Medical Center
KLB declares that she has no competing interests.
Professor of Dermato-Epidemiology
Center of Evidence Based Dermatology
Nottingham University Hospitals
Queen's Medical Centre
HCW declares that he has no competing interests.
Head of Department
Department of Dermatology
St George Hospital
University of New South Wales
DFM declares that she has no competing interests.
Associate Professor and Clinical Director
Section of Dermatology
University of Chicago
VPR declares that she has no competing interests.
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