Bullous systemic lupus erythematosus with milia and calcinosis

Bullous systemic lupus erythematosus (SLE) is a rare skin manifestation of SLE. It shares many features with epidermolysis bullosa acquisita (EBA). We report on a patient with SLE who developed a vesiculobullous eruption followed by findings not typical in bullous SLE, namely milia, mild scarring, and calcinosis. We discuss the relationship between bullous SLE and EBA.     

A patient with both bullous pemphigoid and epidermolysis bullosa acquisita: an example of intermolecular epitope spreading

Bullous pemphigoid (BP) and epidermolysis bullosa acquisita are distinct autoimmune blistering disorders. BP is characterized by autoantibodies directed against the NC16A domain of collagen XVII, whereas patients with epidermolysis bullosa acquisita have autoantibodies against the NC1 domain of type VII collagen. We followed up a patient with BP for 9 years. During that time his clinical disease took on several features suggestive of epidermolysis bullosa acquisita. The objective of this study was to determine if the patient's autoantibody profile reflected the change in his clinical picture. Enzyme-linked immunosorbent assay and immunoblotting for detection and subclass determination of autoantibodies to type XVII and type VII collagen were performed on banked patient sera from the 9-year period. The patient's initial autoantibodies were exclusively IgG1 directed against collagen XVII. During the course of his illness, the subclass specificity of the patient's type XVII collagen autoantibodies shifted to the IgG4 subclass and during the same time interval the patient developed IgG2 autoantibodies directed against type VII collagen. This patient with BP exhibited both subclass shifting and development of a second autoantibody system that correlated with a change in the clinical appearance of the disease. The analysis of the patient's autoantibodies provides strong evidence for the involvement of epitope spreading in the evolution of his autoimmune disease.     

Vesiculo-bullous lupus erythematosus. Immuno-electronic study

The authors present a case suggesting either bullous systemic lupus erythematosus of dermatitis herpetiformis. An immunoelectron microscopic study located the immunoglobulin deposits beneath the cutaneous basement membrane zone. The nosological problem of possible relationship between systemic lupus erythematosus and epidermolysis bullosa acquisita is discussed.     

Autoantibodies to bullous pemphigoid and epidermolysis bullosa acquisita antigens in an infant

We describe a 1-year-old boy with multiple tense blisters on the skin, who showed circulating autoantibodies directed to both bullous pemphigoid and epidermolysis bullosa acquisita antigens. The patient's serum IgG antibodies bound to the 290-kDa epidermolysis bullosa acquisita antigen with immunoblot analysis of human dermal extracts. Immunoblot analysis also demonstrated that the patient's serum autoantibodies were reactive with recombinant NC16a domain of the 180-kDa bullous pemphigoid antigen. This study confirmed the presence of circulating autoantibodies directed to both bullous pemphigoid antigen and epidermolysis bullosa acquisita antigen.     

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.     

Epidermolysis bullosa acquisita. Incidence in patients with basement membrane zone antibodies

We examined the incidence of epidermolysis bullosa acquisita in patients with circulating basement membrane zone antibodies. Serum samples from 100 sequential patients with basement membrane zone antibodies were tested by indirect immunofluorescence against 1 mol/L sodium chloride split skin and by Western immunoblot against epidermal and dermal extracts of skin. Ninety-two (92%) serum samples stained only the epidermal side of split skin, 5 (5%) stained only the dermal side, and 3 (3%) stained both sides. Four of the 5 serum samples with dermal staining but none of the serum samples with epidermal or combined staining reacted with the 290-kd epidermolysis bullosa acquisita antigen by Western immunoblot. These results indicate that approximately 5% of unselected patients with basement membrane zone antibodies have epidermolysis bullosa acquisita or bullous lupus erythematosus rather than bullous pemphigoid.     

A case of epidermolysis bullosa acquisita with unusual clinical features

A 30‐year‐old woman developed epidermolysis bullosa acquisita (EBA) with unusual clinical features. Initially, only prurigo‐like nodules were seen, which lasted for > 2 years and then blisters appeared. Eruptions resembling the rash in systemic lupus erythematosus were also seen on the face. Histopathological examination of a biopsy specimen revealed subepidermal blisters containing eosinophils and neutrophils. Direct immunofluorescence examination, indirect immunofluorescence examination using skin split with 1 mol/L sodium chloride, and immunoblotting analysis using extracts of normal human dermis gave results compatible with EBA. This case shows that EBA can present with nodular lesions as seen in pemphigoid nodularis or epidermolysis bullosa pruriginosa.     

Systemic lupus erythematosus presenting as a bullous eruption in a child

An 8-year-old girl presented with a generalized bullous eruption clinically resembling bullous pemphigoid or chronic bullous disease of childhood. Further study revealed immunopathologic findings seen in patients with epidermolysis bullosa acquisita or bullous systemic lupus erythematosus (SLE). Although she did not fulfill the American Rheumatism Association (Atlanta) criteria for SLE at her presentation, one year later she went on to do so. As well as being the youngest patient reported with bullous SLE, our patient is noteworthy because the bullous eruption was the initial manifestation of her SLE. Bullous SLE should be considered in the differential diagnosis of children presenting with generalized bullous eruptions.     

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.     

Epidermolysis bullosa acquisita occurring in association with systemic lupus erythematosus

A 77-year-old retired male physician with a 6-year history of systemic lupus erythematosus (SLE) developed a mechanobullous eruption, the features of which were clinically and immunopathologically consistent with a diagnosis of‘classical’epidermolysis bullosa acquisita (EBA). As EBA shares immunopathological findings with a number of cases reported as the‘bullous eruption of SLE', the clinical findings commonly recognized as‘classical EBA’may, in patients with SLE, represent a specific subset of the bullous eruption of SLE rather than a separate diagnostic entity. There arc few reports in the literature describing classical EBA in patients with SLE. Findings in this patient add further support to the suggestion that EBA occurring in association with SLE, represents a subset of the bullous eruption of SLE, the clinical features of which may be modified by genetic susceptibility or disease activity.     

Autoantigene subepidermal Blasen bildender Autoimmundermatosen

The dermal-epidermal junction contains a network of structural proteins that link epidermis and dermis. A central component of this complex is the cell membrane-associated hemidesmosomal plaque. Formation of autoantibodies against different components of this hemidesmosomal anchoring complex can lead to subepidermal blisters. Such autoantibodies have been frequently used to characterize the target antigens at the molecular level. Autoimmune subepidermal blistering diseases include bullous pemphigoid, pemphigoid gestationis, lichen planus pemphigoides, linear IgA disease, cicatricial pemphigoid, anti-p450-, anti-p200- and anti-p105-pemphigoid, epidermolysis bullosa acquisita, bullous systemic lupus erythematosus and dermatitis herpetiformis Duhring. Differences in the clinical picture of these diseases can be attributed, at least in part, to the different specificity of the autoantibodies involved. The autoimmune response is further modulated by inflammatory cells and other inflammatory mediators. Native and recombinant forms of the autoantigens are increasingly used for the diagnosis of these diseases.     

Epidermolysis bullosa acquisita: an autoimmune disease with distinctive immunoultrastructural features

Epidermolysis bullosa acquisita is a subepidermal bullous disease of the skin with distinctive clinical, histologic, immunologic, and ultrastructural features. A case of epidermolysis bullosa acquisita is presented in which the onset of the disease was heralded by inflammatory blisters similar to herpes simplex or herpes zoster. The immunofluorescent findings were indistinguishable from bullous pemphigoid. Although some inflammatory blisters persisted throughout the evolution of the disease, the patient eventually developed noninflammatory blisters that healed with milia formation and scarring, lesions typical of classic epidermolysis bullosa acquisita. The diagnosis of epidermolysis bullosa acquisita was definitely made by electron and immunoelectron microscopy which showed a sub-lamina-densa blister cleavage plane and immune deposits beneath the lamina densa. This case illustrates that some cases of epidermolysis bullosa acquisita may have an inflammatory stage and immunofluorescent findings that make it difficult to distinguish from inflammatory bullous diseases. The value of electron microscopy and immunoelectron microscopy in making a firm diagnosis of epidermolysis bullosa acquisita is emphasized.     

Autoimmune blistering dermatoses as systemic diseases

Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the α5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement.     

Epidermolysis bullosa acquisita following bullous pemphigoid, successfully treated with the anti-CD20 monoclonal antibody rituximab

Epidermolysis bullosa acquisita is a rare autoimmune subepidermal blistering disease, often resisting current treatments, especially systemic corticosteroids. We report a patient having a bullous pemphigoid who relapsed with clinical and immunological features of inflammatory epidermolysis bullosa acquisita. An anti-CD20 monoclonal antibody (rituximab) was proposed because of resistance to high-dose steroids and other immunosuppressive agents. The disease dramatically improved within a few weeks following rituximab infusion allowing the decrease in steroid therapy. Our case illustrates also the possible evolution from bullous pemphigoid to epidermolysis bullosa acquisita that should be suspected when clinical atypia occurs or in case of corticosteroid resistance.     

大疱性系统性红斑狼疮的皮肤基底膜带相关抗原

免疫印迹和盐裂皮肤间接免疫荧光检测 ５例大疱性系统红斑狼疮（ＢＳＬＥ）血清，对照为 ５例获得性大疤性表皮松解症（ＥＢＡ）、２０例类天疱疮（ＢＰ）、２０例ＳＬＥ和１０例正常人血清。结果表明，３例（３／５）ＢＳＬＥ血清结合盐裂皮肤真皮侧和真皮提取物中２９０ ０００抗原，其中２例ＢＳＬＥ血清也结合表皮提取物中 １６５ ０００抗原，结果与 ＥＢＡ和部分ＢＰ血清相同。ＳＬＥ血清未结合 ２９０ ０００和 １６５ ０００抗原。提示ＢＳＬＥ血清中存在ＥＢＡ和ＢＰ抗体，推测ＥＢＡ和ＢＰ抗原可能是ＢＳＬＥ的皮肤基底膜带相关抗原。     

Serological diagnosis of bullous pemphigoid (BP): comparison of the sensitivity of indirect immunofluorescence on salt-split to immunoblotting

Specialized immunological assays are required for the accurate diagnosis of bullous dermatoses such as bullous pemphigoid (BP), epidermolysis bullosa acquisita and bullous lupus erythematosus. The aim of this study was to analyse and compare the sensitivity of indirect immunofluorescence (IF) on salt-split skin and immunoblotting for the detection of circulating autoantibodies in BP. Of the BP patients selected for the study, 74/79 (94%) had circulating autoantibodies detected by at least one of the two methods. Both methods had comparable sensitivity and detected BP-specific autoantibodies in 82-85% of the patients. Because 20% of the patients were found to be positive by only one of the methods, both methods should be used in the diagnosis of BP. Indirect IF on salt-split skin is easier to perform and is preferable in routine analysis, but Western blotting may be used as a complementary assay with sera showing no reactivity on salt-split skin.     

Basement membrane and fibroblast aberration in blisters at the donor, graft, and spontaneously healed sites in patients with burns.

BACKGROUND AND DESIGN--Blisters that developed on spontaneously healed wounds and grafts in 13 patients with burns were analyzed by light, fluorescence, and electron microscopy. RESULTS--Blisters developed on the dermal side of the dermoepidermal junction and occurred more frequently in donor site and healed mesh graft than in split-thickness sheet graft. The four major components of the basement membrane zone (bullous pemphigoid antigen, laminin, type IV collagen, and epidermolysis bullosa acquisita antigen) were reduced in quantity and irregularly deposited at blister sites. Immediately adjacent to the blisters, epidermolysis bullosa acquisita antigen appeared normal in quantity, while laminin, type IV collagen, and bullous pemphigoid antigen levels appeared slightly reduced. Mononuclear infiltrates and autoantibodies were not detected by light microscopy or direct-indirect immunofluorescence, respectively. Ultrastructurally, adjacent dermal fibroblasts demonstrated swollen rough endoplasmic reticulum and vacuolization. CONCLUSIONS--We speculate that blister development in patients with burns is related to defective reorganization of the basement membrane zone in association with dermal fibroblast aberration during wound healing.     

The spectrum of epidermolysis bullosa acquisita.

A patient has an acquired, scarring, bullous eruption. The severity of the cutaneous, ocular, esophageal, and laryngeal scarring was suggestive of cicatricial pemphigoid or the severely dystrophic forms of epidermolysis bullosa. Clinical features and histologic and immunofluorescence and electron microscopic study led to the diagnosis of epidermolysis bullosa acquisita. The spectrum of epidermolysis bullosa acquisita includes cases that closely approximate the severity of disease previously recognized only for the recessive form of epidermolysis bullosa dystrophica.     

Anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita: differentiation by use of indirect immunofluorescence microscopy

Binding of autoantibodies to laminin 5 and type VII collagen causes anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita, respectively. Differentiation between these two dermal-binding autoimmune bullous dermatoses is not yet possible by indirect immunofluorescence microscopy. In this study we tested whether two recently described immunofluorescence techniques, "knockout" skin substrate and fluorescent overlay antigen mapping, can differentiate between anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita. A total of 10 sera were tested: 4 with antilaminin 5, and 6 with antitype VII collagen autoantibodies, as characterized by either immunoblot or immunoprecipitation analysis. Differentiation between anti-epiligrin cicatricial pemphigoid and epidermolysis bullosa acquisita was possible in all 10 sera by indirect immunofluorescence using either knockout skin substrate or fluorescent overlay antigen mapping technique.     

Psoriasis bullosa acquisita

We report a 51-year-old man with a 20-year history of chronic plaque psoriasis who developed an autoimmune subepidermal blistering eruption that had clinical features of bullous pemphigoid, erythema multiforme and epidermolysis bullosa acquisita. Investigations revealed a 1 : 400 titre circulating and in vivo bound IgG autoantibody that mapped to the dermal side of 1 m NaCl-split skin and localized to the lower lamina lucida/upper lamina densa on immunogold electron microscopy. Immunoblotting, using dermal extracts, showed serum binding to antigens of approximately 200- and approximately 260 kDa. Indirect immunofluorescence microscopy, using the patient's serum on archival skin sections taken from selected individuals with different forms of inherited epidermolysis bullosa as substrate, showed normal basement membrane labelling on all samples apart from recessive dystrophic epidermolysis bullosa skin (with inherent mutations in the type VII collagen gene): in these cases there was a complete absence of immunostaining. Clinically, the patient responded rapidly to combination treatment with intravenous immunoglobulin and oral corticosteroids, dapsone and mycophenolate mofetil. Autoimmune subepidermal blistering has been reported in other patients with psoriasis, although no specific target antigen has ever been determined. Our study provides preliminary evidence that, for this patient at least, the autoantibody may be targeted against a skin component closely associated with type VII collagen (the epidermolysis bullosa acquisita antigen). Therefore, we propose the term 'psoriasis bullosa acquisita' for this and possibly other patients with similar skin eruptions.