INTRODUCTION

Bullous lupus is a rare manifestation of lupus erythematosus, classified as a nonspecific skin lesion. Different diagnostic criteria allow the differentiation of bullous lupus from other bullous dermatoses that may be associated with lupus disease. Herein, we report the case of a lupus patient who developed bullous lesions on the body, and whose definitive diagnosis was made after correlation between clinical, histological, and immunological findings.

CASE REPORT

A 42-year-old female patient presented to our department with a malar rash, photosensitivity, and positive antinuclear antibodies. A diagnosis of systemic lupus erythematosus was established. The initial systematization assessment was normal and the patient was put on synthetic antimalarials (SAMs). One month later, the patient developed multiple tense vesiculobullous lesions with serohemorrhagic content, distributed on erythematous skin with a herpetiform pattern, mainly affecting the trunk, neck, and roots of the limbs. The Nikolsky sign was negative (Fig. 1a). Oral and nasal mucosal involvement was also found. The diagnoses of bullous lupus or autoimmune bullous dermatosis associated with lupus, such as epidermolysis bullosa acquisita (EBA), dermatitis herpetiformis, or linear IgA dermatosis were considered. A skin biopsy was taken from a tense bulla and the perilesional skin. Histology revealed a subepidermal bulla, vacuolation of the basement membrane, and a polymorphic infiltrate in the dermoepidermal junction with filling of the papillae (Fig. 1b). Direct immunofluorescence (DIF) showed granular junctional deposits of IgG, IgM, and IgA. In light of these results, the diagnosis of bullous lupus was retained. A new systematization assessment revealed cardiac involvement: pericarditis, hematological abnormalities consisting of anemia and lymphopenia, and lupus nephritis confirmed by a renal biopsy, classified as stage II. Complete healing of skin lesions without milia formation, as well as significant improvement in cardiac and renal function, were observed under treatment with dapsone, prednisone, and APS. Follow-up has been three years.

Figure 1: (a) Multiple tense vesiculobullous lesions with a serohemorrhagic content, resting on erythematous skin producing a herpetiform appearance. (b) Histological image showing a polymorphic infiltrate of the dermal floor with filling of the papillae and vacuolation of the basement membrane.

DISCUSSION

Bullous lupus is an uncommon and often challenging cutaneous manifestation of systemic lupus erythematosus (SLE). It mainly affects women and may occur in both sun-exposed and non-sun-exposed areas. It presents clinically as tense bullae or vesiculobulla on normal or erythematous skin with a herpetiform pattern. The predilection areas include the upper trunk, neck, supraclavicular regions, axillary folds, and limb roots, with mucosal involvement, mainly the oral mucosa, as seen in our patient. Healing occurs without atrophic scarring or milia formation, unlike EBA, with occasional hyperpigmented scar [1,2].

There are different mechanisms for blister formation in bullous systemic lupus erythematosus (BSLE). Firstly, collagen type VII-related autoantibodies may interfere with the normal interactions between collagen and its basement membrane or papillary dermis ligands, weakening or blocking connections between anchoring fibrils and the lamina densa and anchoring plaques [3].

Furthermore, autoantibodies related to the non-collagenous domain 2 (NC2) may destabilize anchoring fibrils by interfering with the formation of collagen type VII dimers, leading to dermo-epidermal detachment [4].

The third possible mechanism for detachment is complement-dependent tissue aggression. In vitro studies have shown that antibodies directed against collagen type VII may activate the complement system and generate complement-derived peptides, leading to leukocyte activation, migration, and adherence to the basement membrane [5].

Bullous lupus has similarities mainly with EBA, which has similar immunopathological criteria with a similarity in the target of autoantibodies (collagen VII). In addition, dermatitis herpetiformis and linear IgA dermatosis may have histological similarities with bullous lupus. Among the distinctive criteria that help to establish the diagnosis, mucin deposits in the dermis, filling of the dermal papillae and vacuolation of the basement membrane in histology, as found in our patient. In IFD, we mainly observe granular deposits, Unlike EBA where the deposit is mainly junctional, of IgG, and less frequently of IgM and IgA, and rarely of complement components (C3, C4) [6]. An additional argument is obtained with ELISA tests, where the positivity of the IgG2 and IgG3 subtypes of collagen VII is observed in bullous lupus, unlike EBA which is characterized by the positivity of the IgG1 and IgG4 subtypes [3]. However, due to the high cost of this test and its unavailability, a correlation between the clinic, histology, and immunology allowed us to establish the diagnosis in our patient.

Bullous lupus is generally associated with acute and severe forms of systemic lupus, mainly with renal involvement, as observed in our patient. Bullae may be the first clinical sign of systemic lupus suggesting that they could be a marker of disease activity [7]. This hypothesis is consistent with our patient, in whom the systematization assessment performed after the appearance of the bullous lesions revealed a systemic involvement, initially absent.

The main treatment is dapsone alone in the absence of systemic involvement, often resulting in a rapid response with cessation of blister formation within 48 hours and resolution of the rash within a week [8]. In cases of associated systemic involvement, as in our patient, oral corticosteroids alone or in combination with an immunosuppressant are indicated. Methotrexate has also shown good results. In refractory cases, a favorable response to rituximab has been reported [9,10].

CONCLUSION

This case showed the importance of correlating clinical, histological, and immunological aspects of bullous dermatosis in a lupus patient. Rapid diagnosis of this pathology allows for appropriate treatments and prevention of severe cutaneous and systemic complications.

REFERENCES

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