Pathogenesis

BSLE is believed caused by circulating autoantibodies to type VII collagen. Type VII collagen is an important element of the anchoring fibrils that maintain adhesion at the epidermal-dermal junction by cross-linking the lamina densa and dermal matrix. Antibodies of patients with BSLE recognize epitopes in the region of the amino-terminal noncollagenous (NC1) domain of collagen VII. These epitopes are shared between BSLE and EBA, and further analysis with immunoblotting and enzyme linked immunoassay studies have shown that BSLE sera also react with the collagenous domain adjacent to the carboxyl-terminal non-collagenous (NC2) domain, as reactivity of a construct of this domain and NC2 abolished the reactivity.

There are several mechanisms through which these pathogenic autoantibodies could result in the development of bullae. Interference between type VII collagen and its extracellular matrix ligands could block or weaken connection of the anchoring fibrils to the lamina densa and anchoring plaques resulting in ineffective lamina densa–dermal adhesion. Autoantibodies bound to the collagenous region near the NC2 domain may interfere with the antiparallel dimer alignment of collagen VII disrupting adherence at the dermis. In vitro studies have demonstrated that antibodies to type VII collagen have the potential to activate complement and generate complement-dependent peptides, which precipitate neutrophil-mediated proteolysis at the epidermal-dermal junction. Furthermore the peribullous skin of BSLE patients has been shown to active complement and generate inflammatory mediators to a significantly greater degree than uninvolved skin from the same patients or SLE patients without bullous disease.

Autoimmunity to type VII collagen remains the central focus of the pathogenesis of BSLE; however, more recent studies have demonstrated that this may not be the exclusive target antigen. A study of BSLE patients also identified autoantibodies to other elements of the basement membrane, including laminin-5, laminin-6, and BP antigen I. Epitope spreading may account for this. The primary autoimmune insult against collagen VII could expose epitopes otherwise sequestered, leading to a secondary autoimmune response to the newly exposed targets, accounting for the increasing repertoire of autoantibodies observed in BSLE.

Although the exact mechanism of bullae formation in BSLE has yet to be elucidated, it is likely that the underlying pathogenesis revolves around immunoglobulin deposition causing dysadhesion of the lamina densa subregion of the basement membrane from the upper dermis.

Clinical features

The clinical presentation of BSLE is typically that of an acute, generalized vesicobullous eruption in patients who satisfy the American Rheumatism Association revised criteria for SLE. Typically patients are black women in the second or third decade of life, although BSLE may manifest in patients of either gender or of any race or age. Lesions may erupt anywhere, although there exists a predilection for the upper trunk, neck, and supraclavicular regions as well as axillary folds and the oral and vulvar mucosa. There is a tendency for areas of sun-exposed skin to be most often affected although several cases exist without any suggestion of photosensitivity. Bullae usually arise from erythematous macules and may be preceded by inflammatory plaques but can also arise from normal skin. Bullae may be large and tense, like those of BP ( Fig. 1 ), or small and grouped, like those of DH. The lesions evolve to erosions and typically heal without scarring although may progress to hypopigmented or, less commonly, hyperpigmented macules ( Fig. 2 ). Pruritus is not usually present. The mechanical fragility and healing with scars and milia, which are characteristic of EBA, are not typically present in BSLE. The clinical trajectory of BSLE lesions does not usually correlate with the systemic manifestations of a patient’s SLE. Furthermore, the primary lesions of SLE and discoid lupus are rarely observed in patients with BSLE.

Tense bullae typical of BLSE on a 21-year-old African American woman.

The vesicles and bullae in BLSE typically progress to erosions, then heal without scarring or milia, although pigmentary changes (typically hypopigmentation) are common in patients with darker skin types.

Clinical features

The clinical presentation of BSLE is typically that of an acute, generalized vesicobullous eruption in patients who satisfy the American Rheumatism Association revised criteria for SLE. Typically patients are black women in the second or third decade of life, although BSLE may manifest in patients of either gender or of any race or age. Lesions may erupt anywhere, although there exists a predilection for the upper trunk, neck, and supraclavicular regions as well as axillary folds and the oral and vulvar mucosa. There is a tendency for areas of sun-exposed skin to be most often affected although several cases exist without any suggestion of photosensitivity. Bullae usually arise from erythematous macules and may be preceded by inflammatory plaques but can also arise from normal skin. Bullae may be large and tense, like those of BP ( Fig. 1 ), or small and grouped, like those of DH. The lesions evolve to erosions and typically heal without scarring although may progress to hypopigmented or, less commonly, hyperpigmented macules ( Fig. 2 ). Pruritus is not usually present. The mechanical fragility and healing with scars and milia, which are characteristic of EBA, are not typically present in BSLE. The clinical trajectory of BSLE lesions does not usually correlate with the systemic manifestations of a patient’s SLE. Furthermore, the primary lesions of SLE and discoid lupus are rarely observed in patients with BSLE.

Tense bullae typical of BLSE on a 21-year-old African American woman.

The vesicles and bullae in BLSE typically progress to erosions, then heal without scarring or milia, although pigmentary changes (typically hypopigmentation) are common in patients with darker skin types.

Histopathology

Histologic findings in BSLE are relatively consistent across cases and resemble lesions seen in DH. Bullae demonstrate separation of the epidermis from the dermis at the BMZ. The epidermal roof is typically intact and the blister cavity contains fibrin and abundant neutrophils. There is also a neutrophil-dominated inflammatory infiltrate of the upper dermis and dermal edema. In some cases, the infiltrate is most pronounced in the dermal papillae, as seen in DH, and in other cases, it distributed evenly in a band beneath the BMZ, as seen in linear IgA disease. Some monocytes and eosinophils are normally present within the infiltrate and in some cases there is histologic evidence of necrotizing vasculitis demonstrated by leukocytoclasis, extravasation of erythrocytes, and vessel necrosis. Basal keratinocyte vacuolisation, BMZ thickening and epidermal atrophy characteristic of primary SLE lesions are generally absent in the lesions of BSLE.