Vesiculobullous Disorders

1

What is the difference between a vesicle and a bulla?

Size. If a blister is less than 5 mm in diameter, it is referred to as a vesicle. If a blister is 5 mm or larger, it is called a bulla. Some dermatologists require bulla be 1 cm or larger. The term “vesiculobullous” may be used for blistering disorders, as it encompasses blisters of varying size.

2

How are the bullous diseases defined?

Bullous diseases are characterized by blisters (skin lesions that contain fluid) that may arise at various depths in the epidermis and dermis. Often, the depth at which a blister forms can be used to classify the disorder. “Intraepidermal” refers to blisters that arise within the epidermis, while “subepidermal” refers to blisters that arise beneath the epidermis ( Table 10.1 ). Some blistering disorders develop because of autoantibodies directed against a component of the epidermis or basement membrane zone (“autoimmune bullous conditions”), while others develop because of structural defects of skin components (“congenital blistering disorders”). Refer to Fig. 10.1 for the location of these components in normal skin, as they are discussed in the following questions.

3

What things cause vesicles and bullae?

Blisters of the skin may be caused by a wide variety of external agents and/or diseases, including trauma, infections, metabolic disorders, genetic deficiencies, and inflammatory diseases, to name a few. Blisters caused by infections are discussed in Chapters 25 (viral) and 27 (bacterial).

4

How do you approach a patient who presents with an acute onset of a vesiculobullous eruption?

History is important in the evaluation of a blistering skin disorder. Acute onset of blisters may suggest an exposure to a contact allergen, arthropod bites, phototoxic agents, or other drugs or chemicals, trauma, or infectious agents. Some chronic vesiculobullous diseases may have an acute onset, but then may persist or recur ( Table 10.2 ).

5

Which skin findings are helpful in evaluating a patient with blisters?

Important features of a blistering disorder include the skin distribution, assessment of symmetry, involvement of mucosal surfaces, and associated lesions (such as erosions, ulcers, and crusts). Other types of skin lesions, such as urticaria, should be sought. For example, in bullous pemphigoid (BP), urticarial lesions often precede the development of blisters. In some vesiculobullous diseases, such as dermatitis herpetiformis (DH), only excoriations may be present, without intact blisters.

Characteristics of the blister may be important. Flaccid blisters may indicate a more superficial blistering process than is seen with tense blisters, but the anatomic site must also be considered. Blisters on acral skin, with a thick stratum corneum, may appear tense, even if superficial. In some other diseases, like toxic epidermal necrolysis, full-thickness sloughing of the skin can make it challenging to recognize vesiculation.

6

Do particular vesiculobullous diseases occur in characteristic distributions?

DH is a disorder that affects chiefly the knees, elbow, buttock, and posterior scalp. Table 10.3 details some classic patterns of distribution.

7

Which tests are most useful in evaluating vesiculobullous diseases?

Diagnostic tests for vesiculobullous eruptions are often performed on the blister itself. When infectious causes are considered, appropriate cultures (aerobic bacteria, viruses, fungi) may be obtained. Provider-performed microscopy, such as a Tzanck smear, can reveal multinucleate keratinocytes in Herpes viridae family infections. For noninfectious vesiculobullous diseases, a skin biopsy is often a useful test.

8

How should a skin biopsy of a vesiculobullous eruption be performed?

An early lesion should be biopsied to avoid secondary changes that can confound histologic examination. A small, intact blister is ideal, as the entire lesion and some of the surrounding skin can be removed intact, using a saucerization or excision technique. If a punch technique is employed, it is best to sample from the edge of the blister overlapping onto normal skin. The specimen should be placed in 10% neutral-buffered formalin (NBF) unless direct immunofluorescence studies are desired (see below). Appropriate clinical information, including the age/sex of the patient, a clinical description of the appearance and distribution of lesions, associated symptoms, exacerbating factors or relieving treatments, and a solid clinical differential diagnosis should be provided with the specimen.

9

When are special tests necessary to diagnose blistering diseases of the skin?

A skin biopsy for direct immunofluorescence may be helpful in including or excluding immunobullous diseases ( Table 10.4 ). Direct immunofluorescent (DIF) technique uses special fluorescent antibodies directed against immunoglobulin G (IgG), IgA, IgM, C3, and fibrin that are detected in tissue with a special fluorescent microscope ( Fig. 10.2 ). Immunofluorescent mapping, electron microscopy, or genetic studies may be necessary to diagnose some blistering conditions. Other tests to consider in special circumstances may include urine, serum, or stool porphyrin tests when porphyria is being considered or zinc levels, glucagon levels, or hepatitis panels when necrolytic erythemas are suspected.

van Beek N, Zillikens D, Schmidt E. Diagnosis of autoimmune bullous diseases. J Dtsch Dermatol Ges. 2018;16:1077–1091. https://doi.org/10.1111/ddg.13637 .