Bullous systemic lupus erythematosus in females

Abstract

Bullous systemic lupus erythematosus (BSLE) is a rare blistering presentation of systemic lupus erythematosus, typically affecting women with the highest incidence in those of African descent. The key pathogenic insult includes the formation of autoantibodies against type VII collagen, which weaken the basement membrane zone and lead to the formation of subepidermal blisters. The acute vesiculobullous eruptions in BSLE generally tend to affect photo-distributed areas, although they can arise unrelated to sun exposure (eg, mucous membranes, axillae). The bullae can arise from erythematous macules, inflammatory plaques, or previously normal skin. Their appearance can range from small, grouped vesicles reminiscent of lesions in dermatitis herpetiformis to large, tense blisters, similar to bullous pemphigoid. Internal organ involvement occurs in up to 90% of those affected. This mostly includes lupus nephritis (classes III-V, lifetime prevalence of up to 90%), arthralgias/arthritis, and cytopenias, while serositis and neuropsychiatric involvement are rare. First-line management with dapsone should be considered in mild disease with stable underlying systemic lupus erythematosus. As discussed in this review, the off-label use of rituximab (an anti-CD20 B-cell depleting agent) has been shown to be safe and effective in several refractory cases of BSLE unresponsive to dapsone, glucocorticoids, or steroid-sparing immunosuppressants.

Keywords: Bullous lupus; bullous systemic lupus erythematosus; type VII collagen; vesiculobullous skin disease.

Fig. 1.

Tense bullae typical of BSLE on a 15-y-old female patient (Courtesy of Dr. Julia Rood, MD, PhD). BSLE, bullous systemic lupus erythematosus.

Fig. 2.

Routine histology (hematoxylin and eosin) shows a subepidermal blister, superficial and deep perivascular and periadnexal inflammation, with intradermal mucin deposition at scanning power (A). The bullae and papillary dermis show a neutrophilic infiltrate with associated cytoclastic debris. Occasional civatte bodies and melanophages are seen (B). The deep periadnexal inflammation is lymphocytic, with scattered neutrophils. Deep dermal mucin is seen interstitially, as well as periadnexally around eccrine coils (C).

Fig. 3.

PAS staining shows basement membrane thickening in skin that is adjacent to bullae. DIF demonstrates deposition of IgG, IgA, and C3 at the BMZ. BMZ, basement membrane zone; DIF, direct immunofluorescence; PAS, periodic acid-Schiff.

Fig. 4.

Proposed therapeutic ladder for BSLE. BSLE, bullous systemic lupus erythematosus; G6PD, glucose-6-phosphate dehydrogenase; RA, rheumatoid arthritis; SLE, systemic lupus erythematosus.