Bullous Systemic Lupus Erythematosus as an Initial Manifestation of SLE

Bullous systemic lupus erythematosus (BSLE) is a rare subset of systemic lupus erythematosus that is often associated with autoimmunity to type VII collagen. We describe a 45-year-old woman with BSLE who presented with vesiculobullous lesions as an initial manifestation of SLE. The patient first noticed a widespread urticarial, erythematous eruption associated with tense blisters, erosions, and crusting. She was diagnosed with bullous pemphigoid and underwent a one-month course of treatment with betamethazone. Because of the appearance of marked proteinuria, a subsequent renal biopsy, and serological tests, the patient was diagnosed with rapidly progressive glomerulonephritis and systemic lupus erythematosus. The patient's IgG circulating antibodies labeled the dermal floor of salt-split skin and recognized type VII collagen in immunoblot studies. Although methylprednisolone pulse therapy for glomerulonephritis did not alleviate the vesicullobullous eruption, treatment with dapsone resulted in dramatic disappearance of the lesions. Cessation of dapsone therapy due to hemolysis with Heinz-body formation did not aggravate the bullous disease. Our case illustrates that a generalized vesiculobullous eruption can be the sole presenting manifestation of SLE. It also emphasizes the close temporal relationship between BSLE and lupus nephritis.     

Bullous systemic lupus erythematosus with lupus nephritis: a rare case of a subepidermal bullous disorder in a child

Bullous systemic lupus erythematosus (BSLE) is a rare subset of systemic lupus erythematosus (SLE) with bullous lesions in a case fulfilling the American Rheumatism Association (Atlanta) criteria, histologically characterized by a neutrophil-predominant infiltrate in the upper dermis with immunoglobulin (IgG, IgA, IgM) and C3 deposition at the basement membrane zone (BMZ). It often is associated with autoimmunity to type VII collagen (NC1 [noncollagenous domain 1] domain), although occasionally other antigens such as laminin 5, laminin 6, and BP230 (bullous pemphigoid antigen) have been described. Bullous systemic lupus erythematosus is extremely rare in children. We report here a case of a 9-year-old girl with BSLE as an initial presentation with lupus nephritis class III, a rare occurrence at such a young age. Despite the rarity, we suggest that BSLE should be considered in the differential diagnosis of subepidermal bullous diseases in children in view of associated potentially serious systemic manifestations.     

Widespread vesiculobullous eruption in a 16-year-old male

Bullous systemic lupus erythematosus (BSLE) is a rare but distinct disease, characterized by vesiculobullous skin eruptions and systemic lupus erythematosus (SLE). It can arise either before or after a diagnosis of SLE has been established. BSLE is characterized by a dermatitis herpetiformis-like histology and an autoimmunity to type VII collagen. It must be differentiated from other autoimmune vesiculobullous diseases such as epidermolysis bullosa acquisita, dermatitis herpetiformis, linear IgA disease, and bullous pemphigoid. A combination of clinical, histological, and immunofluorescence findings are necessary to establish a diagnosis of BSLE. We present a case of BSLE to illustrate and emphasize the need for an integrative diagnostic approach.     

An Atypical Case of Bullous Systemic Lupus Erythematosus in a 16‐Year‐Old Boy

Bullous systemic lupus erythematosus (BSLE) is a rare autoimmune subepidermal blistering disease with a female predominance characterized as an acute vesicobullous eruption in patients with systemic lupus erythematosus (SLE). Here we report a case of BSLE in a 16‐year‐old boy that does not adhere to the criteria originally established and suggest a new outlook on this condition.     

Bullous systemic lupus erythematosus

Bullous systemic lupus erythematosus (BSLE) is a rare bullous dermatosis in patients with systemic lupus erythematosus. It is characterized by clinical and histologic features, resembling either bullous pemphigoid or dermatitis herpetiformis, and a heterogeneous immunologic profile, characterized by autoimmunity to components of type VII collagen, much like epidermolysis bullosa acquisita. As understanding of the pathology of this interesting dermatologic condition has evolved, so too have criteria and profiling of BSLE. The distinct clinical, histologic, and immunologic features of BSLE represent a unique bullous disease phenotype.     

Bullous systemic lupus erythematosus: revised criteria for diagnosis

Summary Blistering in systemic lupus erythematosus has been divided into three groups.¹ A specific subgroup of ‘bullous systemic lupus erythematosus’ has been defined by Gammon et al. on the basis of a number of criteria.² From our experience of seven patients with bullous systemic lupus erythematosus, and after reviewing the literature, we suggest that the current classification is too narrow. Our patients displayed clinical and immunohistolegical (based on direct and indirect immunofluorescence and Western immunoblotting) heterogeneity. Sera from two patients bound to epidermal epitopes in sodium chloride-split skin, but immunoblotting was negative. In neither of these patients could the target antigen be type VII collagen, the only antigen identified as pathogenic in this disease. Patients with epidermal binding should not be excluded from a diagnosis of bullous systemic lupus erythematosus. SLE is a disease in which there is a genetic predisposition to form antibodies to type VTI collagen, along with other autoantibodies, many of which may be implicated in blistering. We suggest that the criteria for the diagnosis of BSLE should be revised. We define this disease as an acquired subepidermal blistering disease in a patient with SLE, in which immune reactants are present at the basement membrane zone on either direct or indirect immunofluorescence.     

Bullous Systemic Lupus Erythematosus: A Review and Update to Diagnosis and Treatment

Bullous systemic lupus erythematosus (BSLE) is a rare cutaneous complication of systemic lupus erythematosus (SLE). It is a heterogeneous disease that is caused by autoantibodies to the dermoepidermal junction, mainly type VII collagen. Similarities in histology and immunopathology exist between BSLE and other primary bullous dermatoses, namely dermatitis herpetiformis (DH) and epidermolysis bullosa acquisita (EBA), respectively. EBA and BSLE commonly share the same autoantibody to type VII collagen and heterogeneous clinical presentations, creating a diagnostic challenge. However, clinical presentation combined with histology, immunological testing, and concomitant diagnosis of SLE distinguish this entity from other similar dermatoses. Diagnosis of this disease is important given its coexistence with SLE and its many complications. New developments in IgG subtyping have shown subtle variations in IgG subtypes between EBA and BSLE. In addition, rituximab was recently found to be efficacious in recalcitrant cases of BSLE that do not respond to dapsone and immunosuppressants. We review the topic of BSLE with emphasis on clinical, histologic, and immunopathologic features, as well as new methods of diagnosis and treatment.     

Detection of anti-type VII collagen antibody in Sjögren's syndrome/lupus erythematosus overlap syndrome with transient bullous systemic lupus erythematosus

Bullous systemic lupus erythematosus (SLE) is a chronic, widespread, non-scarring, subepidermal blistering eruption associated with autoimmunity to type VII collagen. We describe a patient with Sjögren's syndrome/lupus erythematosus overlap syndrome who showed transient blistering eruptions over limited skin surface and in oral mucosa. At the time of aggravation, the patient's serum contained IgG autoantibodies that bound to the dermal side of 1 mol/L NaCl-split normal skin, as determined by an indirect immunofluorescence test, and that reacted to type VII collagen, as determined by immunoblotting on dermal extract. Our observations suggest that a chronic, widespread, blistering eruption is not a prerequisite for the diagnosis of bullous SLE, and a mild, transient, blistering eruption could be a manifestation of type I bullous SLE.     

Cutaneous lupus erythematosus: a review

This article will review and update information about the pathogenesis, clinical presentation, diagnosis, and treatment of cutaneous lupus erythematosus. Lupus erythematosus (LE) can present as a skin eruption, with or without systemic disease. Cutaneous LE is subdivided into chronic cutaneous LE, subacute cutaneous LE and acute LE. The prevalence of systemic lupus erythematosus (SLE) is 17-48/100,000 population worldwide. Skin disease is one of the most frequent clinical complaints of patients suffering from SLE. It has been found to occur in up to 70% of patients during the course of the disease. The most frequent mucocutaneous manifestations of SLE are malar rash (40%), alopecia (24%), and oral ulcers (19%). It has been suggested that risk factors that are more likely to signal transition of cutaneous into systemic LE are high ANA titers (> 1:320) and the presence of arthralgias. CLE patients who exhibit these symptoms should be monitored closely, since they may be at increased risk to develop SLE.     

Bullous Lupus: An Unusual Initial Presentation of Systemic Lupus Erythematosus in an Adolescent Girl

Abstract: Bullous systemic lupus erythematosus is a subepidermal blistering disease that occurs only rarely in a subset of patients with systemic lupus erythematosus and even less commonly in pediatric patients. Autoimmunity in bullous systemic lupus erythematosus is characterized by the presence of circulating anti‐type VII collagen antibodies. We report here a case of a child whose initial systemic lupus erythematosus presentation was a diffuse bullous eruption.     

The lupus band: do the autoantibodies target collagen VII?

BACKGROUND: Circulating autoantibodies directed against basement membrane zone (BMZ) components from patients with bullous pemphigoid and epidermolysis bullosa acquisita have been used to identify their target antigen in the skin and to confirm pathogenicity. Although the pattern of immunofluorescence in those diseases is similar to the lupus band, little is known about the origin and pathogenesis of the lupus band. Identifying the binding sites of the lupus band could provide a clue to the nature of the autoantigen that stimulates autoantibody formation in the skin of patients with systemic lupus erythematosus (SLE) and might provide valuable insight into the factors that influence the localization and pathogenicity of the lupus band. OBJECTIVES: To investigate the relation between the lupus band and the main BMZ components and to identify the target epitopes of autoantibodies deposited in the skin of patients with SLE. METHODS: Colocalization of the main components of the skin BMZ in nonlesional SLE skin with the lupus band was investigated using conventional immunofluorescence and confocal laser scanning microscopy. The effect of collagenase and pepsin on the expression of the lupus band was correlated with the differential sensitivity of these proteases on the collagenous and noncollagenous (NC) domains of collagen VII. Reactivity of sera from patients with SLE to a complete recombinant human NC1 domain of type VII collagen was then investigated by enzyme-linked immunosorbent assay (ELISA). RESULTS: Near complete colocalization of the lupus band with collagen VII was found in this study, and chemical degradation of the skin attenuated the expression of the lupus band. Collectively, the NC1 domain of collagen VII was suggested as the target antigen of the lupus band, but none of the sera from patients with SLE reacted with recombinant NC1 domain-coated ELISA plates. Alternative explanations for the results of the colocalization of the lupus band with collagen VII are discussed. CONCLUSIONS: The lupus band colocalized with collagen type VII. The findings of this study ruled out the NC1 domain of collagen VII as a target antigen for circulating autoantibodies in SLE patients with no clinical evidence of blistering. Further studies are required to determine if other regions of collagen VII or another BMZ component is the target antigen for the immunoglobulins of the lupus band.     

Lupus-like phototriggering in a young woman with benign summer light eruption

We report the case of a young woman with a single history of benign summer light eruption (BSLE) who developed delayed onset annular lupus-like lesions triggered by a polychromatic phototest, 6 weeks after the irradiation. BSLE of French authors is an idiopathic photodermatosis that corresponds to the minor form of polymorphic light eruption (PLE) of Anglo-Saxon authors. This patient may develop a true lupus erythematosus in the future as indicated by this lupus-like phototriggering and in view of the high prevalence of PLE in lupus patients.     

Studies on Criteria of the European Academy of Dermatology and Venerology for the Classification of Cutaneous Lupus Erythematosus

A group of 140 cases of various forms of lupus erythematosus (LE) were examined for 24 variables, including the 11 criteria of the American Rheumatism Association (ARA) for the classification of systemic lupus erythematosus (SLE), and 13 additional criteria suggested by the European Academy of Dermatology and Venerology (EADV) for studies of cutaneous LE with or without systemic involvement. The EADV study factors included skin histopathology and immunopathology, complement and IgG levels, and other laboratory tests, as well as selected clinical findings, most notably the papulosquamous and/or annular lesions that characterize subacute cutaneous LE (SCLE). The patients examined included 50 SLE, 35 SCLE, 30 discoid LE (DLE), 25 disseminated DLE (DDLE), and 17 polymorphous light eruption (PMLE) cases. Preliminary analyses of the data reveal the following: (1) The SCLE cases differed significantly from SLE, DLE, and DDLE in 10 of 11 ARA criteria (all but photosensitivity). (2) The frequencies of positive findings in SCLE also differed significantly for 11 of 13 EADV study factors. (3) While no significant differences appeared in the frequency of photosensitivity between the five study groups, photo-testing revealed significant increases in the frequency of persistence of the photo reactions for 10 days and their Koebnerization in the SCLE cases. (4) The presence of SS-A (Ro)/SS-B (La) antibodies had some predictive value for the appearance of systemic involvement in SCLE, as seen by the increased frequencies of five or more ARA criteria, although highly significant differences from SLE occurred in the absence of renal involvement and lower frequency of ANA and LE band test.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bullous systemic lupus erythematosus with autoantibodies recognizing multiple skin basement membrane components, bullous pemphigoid antigen 1, laminin-5, laminin-6, and type VII collagen.

BACKGROUND: Bullous systemic lupus erythematosus is a generalized subepidermal blistering skin eruption in patients suffering from systemic lupus erythematosus. Type VII collagen was initially identified as the target antigen. OBSERVATION: We studied an unusual patient who had bullous systemic lupus crythematosus. The patient fulfilled the criteria of systemic lupus with an antinuclear antibody titer of 1:5120. Immunopathological testing revealed in vivo deposition of all IgG subclasses, secretory IgA1, and both light chains at the patient's skin basement membrane. The in vivo-bound IgG and IgA were localized at the hemidesmosomes and lamina densa. The patient's IgG and IgA circulating autoantibodies labeled both the epidermal roof and the dermal floor of salt-split skin and recognized the hemidesmosomal protein BP230 as well as the full-length native form and the recombinant noncollagenous domain 1 of type VII collagen (anchoring fibril). In addition, the patient's IgG autoantibodies recognized the anchoring filament proteins laminin-5 and laminin-6 (alpha3 chain and gamma2 chain). CONCLUSIONS: We conclude that patients with bullous systemic lupus erythematosus may have autoantibodies to multiple basement membrane components critical for epidermal-dermal junctional adhesion. Possible pathogenic mechanisms in this patient's clinical diseases include provocation of organ-specific disease (bullous disease) by systemic autoimmunity (lupus) and the "epitope spreading" immune phenomenon.     

A Study of lupus erythematosus with particular reference to generalized discoid lupus

The classification of lupus erythematosus (LE) is difficult because of variable and multisystem involvement, occurrence of transitional forms, and overlapping with connective tissue disorders. One of the earliest attempts at classification was made by O'Leary (1934), who classified LE clinically into four main types: (1) chronic discoid lupus erythematosus (DLE), or fixed type with the typical erythematous, scaly, well-demarcated eruption, usually showing follicular plugging and atrophy, confined to the head region; (2) generalized DLE, or chronic disseminated type differing from the localized discoid type in that the erythematous plaques are found not only on the head area but also below the neck region (O'Leary considered that constitutional systems were generally lacking in these two types); (3) subacute disseminated LE; and (4) acute disseminated LE. The last two categories reflect what we now call systemic lupus erythematosus (SLE) of varying severity. Many authors have used O'Leary's clinical classification, but progress in laboratory medicine—in particular the discovery of the LE cell—has led to other schemes, the most widely accepted at present being that related to the American Rheumatism Association's (ARA) preliminary criteria for the diagnosis of SLE (Cohen et al., 1971). These criteria have been criticized by many authorities because they do not include important data, such as those relative to the antinuclear antibody test, serum anti-native-DNA, serum complement levels, many neurological abnormalities, renal biopsy changes, and cutaneous immunofluorescent (IF) findings. However, Dubois (1974b) pointed out that all categorizations of LE are arbitrary, and he accepted the ARA criteria as a successful method for differentiating LE. This report involves the clinical and laboratory findings in 123 patients with LE seen at the Mayo Clinic during the 3-year period 1971–1974 and an assessment of the validity and usefulness of O'Leary's classification.     

Epidemiology of cutaneous lupus erythematosus in a tertiary referral centre in Singapore

The aim of this retrospective study was to investigate the epidemiology, yield of investigations and proportion of patients who develop systemic lupus erythematosus (SLE) among the subsets of cutaneous lupus erythematosus (LE) in the Singapore Asian population. One hundred and twenty-five patients were diagnosed with cutaneous LE on clinico-pathological correlation, of which 73 had discoid lupus erythematosus (DLE), eight had subacute cutaneous LE (SCLE), 22 had acute LE lesions and the remainder had other less common forms of cutaneous LE. Histology was consistent with LE in 94.4% and suggestive in 4.8%. Direct immunofluorescence was positive in 61% of DLE, 86% of SCLE and 80% of acute LE cases. Antinuclear antibody (ANA) was present in the majority of acute LE (85%) and SCLE (88%) but only in 25% of DLE. Eight patients (11%) presenting with DLE had definite SLE at first presentation and two (2.7%) subsequently several months later. Of these patients, six had only mucocutaneous and serological criteria but two had major organ involvement. Five SCLE patients (63%) fulfilled the criteria for SLE, including two with major organ involvement.     

Characterization of the changes in matrix molecules at the dermoepidermal junction in lupus erythematosus

Electron microscopy has revealed that the deposition of immunoglobulin in the skin of lupus erythematosus (LE) patients occurs on and below the basal lamina of the basement membrane (BM). The composition of the BM is now to some extent known, and antibodies have been developed against several of its individual components. In this study, we attempt to elucidate the status of some matrix molecules in the dermoepidermal junction in LE. Lesional and nonlesional skin from LE patients was examined using immunofluorescence microscopy with monoclonal and polyclonal antibodies against 6 matrix molecules. Immuno-electron microscopy using monoclonal antibodies was used to discern changes in type IV and type VII collagen. By immuno-fluorescence microscopy, type IV collagen, type VII collagen, and fibronectin were altered in lesional skin. There was a statistically significant correlation between the presence of immunoglobulin and alteration of type IV collagen and type VII collagen in lesional skin. The alterations in type IV and type VII collagens were confirmed on immuno-electron microscopy which showed fragmentation of staining of both antigenic components, particularly type IV collagen.     

Bullous systemic lupus erythematosus in a 6‐year‐old boy

Bullous systemic lupus erythematosus (BSLE) is a rare subepidermal blistering disorder characterized by an acute vesiculobullous eruption in a subset of individuals with systemic lupus erythematosus. BSLE most commonly affects young women and only rarely affects children. Herein we report a rare case of BSLE in a 6‐year‐old boy.     

Systemic lupus erythematosus and coexisting bullous pemphigoid: immunofluorescent investigations

An 18-year-old black woman with systemic lupus erythematosus (SLE) who subsequently developed a bullous eruption is presented. Direct immunofluorescent studies of a bulla and peribullous skin demonstrated a tubular band at the dermoepidermal junction diagnostic for bullous pemphigoid (BP). However, an atrophic plaque clinically and histologically characteristic for lupus erythematosus (LE) also demonstrated a tubular band instead of one of the LE bands. Indirect immunofluorescent studies employing normal human skin revealed peripheral, homogeneous, and particulate antinuclear antibody patterns with anti-IgG but were negative for circulating anti-basal zone antibodies. Therefore BP was dominant cutaneously, whereas SLE prevailed serologically. This case illustrates the diagnostic problems of a bullous eruption in an SLE patient and points out some unusual immunofluorescent findings.     

The phenotypic profile of dermatomyositis and lupus erythematosus: a comparative analysis

Background: The mechanisms which regulate cutaneous inflammation in the setting of collagen vascular disease have been a topic of recent interest; emphasis has been placed on type I interferon‐associated recruitment of CXCR3+ lymphocytes in dermatomyositis (DM). Methods: On a total of 42 biopsies from patients with DM, systemic lupus erythematosus (SLE), discoid lupus erythematosus (DLE) and subacute cutaneous lupus erythematosus (SCLE) comprehensive phenotypic studies were performed to explore the practical value of phenotypic analysis in the subclassification of lesions of collagen vascular disease. Results: The infiltrate in DM was of mild intensity compared to lupus erythematosus (LE). The dominant mononuclear cell in DM exhibited a CD4/CXCR3‐positive phenotype while biopsies of SLE typically showed a dearth of CXCR3‐positive cells. CD8 and CD20 lymphocytes were greatest in SLE and DLE, respectively. CD123 plasmacytoid dendritic cells, seen in most cases, were most frequent in cases of SCLE; CD83 expression was minimal. Endothelial MXA expression was a characteristic feature of DM. CD123 and MXA expression within inflammatory cells and keratinocytes was most conspicuous in areas of interface injury. Cutaneous lymphocyte antigen (CLA) expression was diminished in the dermal infiltrate in most cases of DM and LE. T regulatory cells never exceeded 15% of the infiltrate and were the least in the setting of DM and LE. Conclusions: An interferon‐α‐inducible cytokine milieu is common in SLE, DLE, SCLE and DM. In addition, there are phenotypic differences as alluded to above that may be of some practical value in separating these distinctive subsets. Features not previously emphasized such as MXA endothelial cell staining in DM and the lack of staining for CD83 and CLA in lesions of collagen vascular disease may be of diagnostic value. Magro CM, Segal JP, Crowson AN, Chadwick P. The phenotypic profile of dermatomyositis and lupus erythematosus: a comparative analysis.