Clinical, histological, immunological presentations and outcomes of bullous systemic lupus erythematosus: 10 New cases and a literature review of 118 cases

Abstract

Background

Bullous systemic lupus erythematosus (BSLE) is a rare blistering condition associated with systemic lupus erythematosus (SLE).

Patients and methods

We conducted a multi-center retrospective study and literature review in order to describe the clinical, immunological, and histological presentations and outcomes of BSLE. The skin biopsies were centrally reviewed, and sera obtained during a flare of BSLE were analyzed for identification of circulating anti-basement membrane zone antibodies.

Results

Ten patients (all women, median age at SLE diagnosis of 22 years) were included, as well as 118 cases from a systematic review of the literature. Lupus nephritis was associated in 50% of the cases. BSLE presented as tensed bullae on normal or erythematous skin, predominantly localized on the trunk, arms, head, and neck. Urticarial lesions were associated in 31% of the cases, and mucous membrane involvement was seen in 51%. Histological analyses displayed subepidermal detachment, dermal infiltration of polynuclear neutrophils, alignment of these cells at the basal membrane zone and leukocytoclasis. The direct immunofluorescence was polymorphic, showing linear and/or granular deposits of IgG, IgA, IgM, and/or C3. Anti-type VII collagen antibodies were detected in 69% of cases. Dapsone was efficacious in 90% of cases.

Conclusion

BSLE is rather an autoimmune neutrophilic blistering disease associated with SLE than a cutaneous manifestation and may be associated with active extra-cutaneous manifestations of SLE. Dapsone is the first-choice option.

Introduction

Bullous cutaneous lesions may occur in the course of systemic lupus erythematosus (SLE). They may be directly linked to SLE through 3 pathogenic mechanisms [1]. The first mechanism, referred to as bullous SLE (BSLE), consists of subepidermal detachment with neutrophilic dermal infiltrates. The second mechanism is a blistering of primary lesions of cutaneous lupus, characterized by vacuolization of the basement membrane zone (BMZ) and mononuclear cell infiltrates in the upper dermis. The third mechanism consists of toxic epidermic necrolysis (TEN)-like bullous lupus, characterized by extensive sheet-like skin detachment and epidermal necrosis. Bullous lesions occurring during SLE may also be due to an associated blistering disease (AIBD), erythema multiforme, and porphyria cutanea tarda [2]. In 1983, Camisa and Sharma suggested the following diagnosis criteria for BSLE [3]: (1) a diagnosis of SLE based on the American College of Rheumatology (ACR) criteria; (2) vesicles and bullae arising upon but not limited to sun-exposed skin; (3) histopathology compatible with dermatitis herpetiformis (DH); (4) negative indirect immunofluorescence (IIF) for circulating BMZ autoantibodies; and (5) direct immunofluorescence (DIF) revealing IgG and/or IgM and often IgA at the BMZ. The diagnosis criteria were later revised by Camisa in 1986, based on the technique of IIF on split skin, and the fourth criterion was modified as follows: (4) “negative or positive IIF for circulating BMZ autoantibodies using separated human skin as substrate” [4], [5]. Finally, in 1995, Yell et al. [6] defined BSLE as “an acquired subepidermal blistering disease in a patient with SLE, with immune reactants at the BMZ on either DIF or IIF”. Thereafter, the epidermolysis bullosa acquisita (EBA) autoantibody directed against collagen VII (C7) was identified in BSLE [7], [8], [9].

However, BSLE remains a rare manifestation of SLE and has been described mainly in case reports or small series [1], [3], [4], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71].

We therefore conducted a multi-center retrospective study with a review of the literature to describe the clinical, immunological, and histological presentations and outcomes of BSLE.