Some disorders can be either vesicular or bullous. Hence, the causes of these two types of primary lesions are addressed together.

A vesicle must not be confused with a molluscum contagiosum, a milia seed, or a cystic lymphangioma.

Vesicles are mainly caused by infectious diseases (i.e., viral and parasitic infections), dermatitis, and autoimmune bullous dermatoses such as dermatitis herpetiformis and linear IgA dermatosis. In viral diseases such as infections with Herpesviridae, lesions are often umbilicated, i.e., with a central depression or dell, and can be pruritic, but without oozing. Viral vesicles usually have a particular gray color, especially in initial stages. However, in dermatitis, lesions are always pruritic and oozing. Certain systemic diseases may rarely manifest as vesicles, which are then accompanied by other primary lesions, e.g., subacute cutaneous lupus erythematosus or acrodermatitis enteropathica.

Bullae resulting from intraepidermal fragility break easily. They then evolve towards more or less superficial and round erosions, lined by a collarette which allows retrospective diagnosis.

Common causes of bullae are an overly elevated hydrostatic pressure (e.g., an edema flare-up in the lower limbs), mechanical stress (e.g., foot blisters), infections (i.e., impetigo), hypersensitivities (i.e., bullous dermatitis, dyshidrosis, and drug eruptions), and pemphigoid in patients over 65. However, several diseases may have a usual or unusual bullous manifestation, which is then generally associated with other cutaneous signs, such as in infectious bullous cellulitis or in bullous morphea.