Nutrition and bullous skin diseases

Autoimmune and nonautoimmune bullous diseases can both be associated with significant morbidity and mortality. Although our understanding of the pathogenic mechanisms of these diseases has increased tremendously, there is still much to learn about the various factors affecting their onset, course, and therapy. In recent years, increasing information has been published about the effect of vitamins, minerals, and other nutrients on bullous skin diseases. Some factors are believed to be inducers (thiol and phenol-containing foods in pemphigus), whereas others are believed to be protective (antioxidants in cutaneous porphyrias). This contribution reviews the evidence in the literature of the role of various dietary factors in bullous diseases, including the nonautoimmune and the deficiency dermatoses. Additional studies and new investigations are needed to provide a better understanding of the specific associations of dietary factors with bullous diseases and better management for patients affected by these conditions.     

Subepidermal bullous diseases

An approach to the light microscopic diagnosis of subepidermal bullous diseases is presented. The recent literature is reviewed for current research in these disoreders.     

Annular bullous diseases

Annular bullous dermatoses represent an etiologically diverse group of cutaneous phenomena that present with a figurate morphology in association with vesicles and bullae. This group of diverse conditions consists of bullous pemphigoid; pemphigoid gestationis; epidermolysis bullosa simplex, Dowling-Meara type; linear immunoglobulin A bullous dermatosis; chronic bullous disease of childhood; anti-p200 pemphigoid; subcorneal pustular dermatosis; and immunoglobulin A pemphigus. Astute examination of clinical, histopathologic, and serologic features is crucial in distinguishing these bullous dermatoses. We review the clinical presentation, pathophysiology, histopathology, and treatments for each bullous annular disease to aid physicians in their recognition, diagnosis, and management.     

Autoimmune bullous diseases associations

The presence of one autoimmune disorder helps lead to the discovery of other autoimmune conditions. It is thought that diseases in which autoimmunity is a feature tend to be associated together more often than one can ascribe to chance. A variety of diseases have been implicated in the onset of intraepidermal and subepidermal autoimmune diseases. The presence of one autoimmune disease should alert the physician to watch for a second immunologic disorder. A list of autoimmune bullous diseases associations includes autoimmune bullous diseases, pemphigus, pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis (Duhring), linear immunoglobulin A disease, and multiple autoimmune syndrome.     

Diagnosis of autoimmune bullous diseases

Autoimmune bullous disorders (AIBDs) are a heterogeneous group of rare diseases clinically characterized by erosions and/or blisters on the skin and mucous membranes. AIBDs can be categorized into two groups: pemphigus diseases, characterized by intraepidermal blistering and autoantibodies against desmosomal proteins such as desmoglein (Dsg) 1, Dsg3, members of the plakin family, and subepidermal AIBDs, comprised of pemphigoid diseases and dermatitis herpetiformis. Autoantibodies in dermatitis herpetiformis target transglutaminases 2 and 3, while in pemphigoid disease, autoantibodies are directed against structural proteins of the dermal‐epidermal junction. Although analysis of a perilesional biopsy with direct immunofluorescence (IF) microscopy is still the diagnostic gold standard, several assays have become widely available that allow serological diagnosis in the majority of patients. Standard serological diagnosis includes indirect IF on monkey esophagus and salt‐split human skin. Assays to further characterize autoantibody specificity include ELISA systems based on recombinant forms of the immunodominant regions of the target antigens as well as multivariant indirect IF microscopy tests with several miniature substrates. These serological assays are complemented by various in‐house assays using immunoblotting and ELISA, which are only available in specialized laboratories. Here we review new developments in the diagnosis of AIBDs and describe state‐of‐the‐art diagnostic procedures for this group of diseases.     

免疫球蛋白在自身免疫性大疱病的研究进展

免疫球蛋白作为人体内具有活性的免疫效应分子,在自身免疫性大疱病的发病、诊断及治疗中发挥着重要的作用。人免疫球蛋白可以分为IgG、IgA、IgM、IgD、IgE5大类,除IgD外其他都在自身免疫性大疱病的发病过程中存在并发挥不同的作用。IgG可通过激活补体、活化白细胞、释放蛋白水解酶等诱发水疱形成,其不同亚型也有所区别。IgA可引起粒细胞迁移从而导致水疱脓疱的发生。IgE与荨麻疹样红斑、嗜酸性粒细胞浸润相关。IgM多见于巴西落叶型天疱疮。这些都为自身免疫性大疱病的诊断和治疗提供了新的思路。     

Autoimmune bullous diseases in Austria

Autoimmune bullous diseases (AIBD) are chronic disorders associated with significant morbidity and even mortality, for which the 19 dermatologic departments in Austria?apply standard modalities to provide state-of-the-art diagnosis and treatment. Most of the affected individuals are initially treated on an inpatient basis, with follow-up done in specialized outpatient clinics or in private practices. A well-established system of care for AIBD patients is thus available nationwide. Considering the significant morbidity and mortality but also rareness of AIBD, national and international standardization of AIBD administration in registries is a major requirement of further improvement in patient care.     

Autoimmune bullous diseases in childhood

Autoimmune blistering disorders are a heterogeneous group of diseases that result from autoantibodies generated against target antigens found in the skin and mucous membranes. This process leads to a variety of disruptions in keratinocyte adhesion and cellular integrity, resulting in fluid accumulation and development of blisters. Physicians should have an appreciation and understanding of autoimmune blistering disorders in the pediatric population when formulating a differential diagnosis of a patient who presents with skin blistering. Early detection and discrimination between the varied autoimmune blistering disorders can change the course of treatment and outcome. Due to the similarity in clinical presentation among different diseases within this category, histopathologic evaluation and, especially, immunofluorescence studies are necessary to establish the definitive diagnosis.     

自身免疫性疱病与银屑病的相关性

自身免疫性疱病（AIBD）和银屑病的发病机制有部分相似性。近年来,多项研究报道银屑病与AIBD之间具有相关性,以大疱性类天疱疮多见,还包括寻常型天疱疮、红斑型天疱疮、线状IgA大疱性皮病等,多数AIBD在银屑病发病后发生,部分患者两病同时出现或AIBD先出现。本文综述AIBD与银屑病发病的相关性及可能存在的机制。     

Autoimmune bullous diseases: diagnosis and management

Bullous diseases constitute a wide group of disorders in which blistering of the skin and/or mucous membranes occurs. Patients may develop other lesions in addition to blisters. It is important for dermatology nurses to understand the pathogenesis of these disorders, the means for making an accurate diagnosis, and systemic and local management of the diseases.     

Autoimmune bullous diseases: diagnosis and management

Autoimmune bullous diseases are a heterogenous group of diseases characterized by cutaneous and mucosal vesicles and bullae. Diagnosis is based on a combination of clinical, histopathological, and immunofluorescence findings. Current treatment, including vigilant wound care, significantly reduces disease morbidity and mortality.     

Unusual subepidermal bullous diseases with immunologic features of bullous pemphigoid.

Sixty-seven patients with histologic and immunologic features of bullous pemphigold (BP) were evaluated. Eleven patients had a localized blistering disease that was predominantly confined to one area of the body, most commonly the lower extremities. Two patients displayed a dapsone-responsive blistering disease that was characterized by a flexural distribution of ten to 20 1-cm or less, intensely pruitic, subepidermal bullae and linear IgA basement membrane zone deposition. Two patients had a chronic recalcitrant generalized scarring, hyperkeratotic, subepidermal blistering eruption that demonstrated serologic and direct immunofluorescence (IF) findings of BP. One patient displayed grouped small vesicles surmounted on an erythematous base; the clinical diagnosis was dermatitis herpetiformis, but direct IF examination of the biopsy specimen showed features of BP. One patient with epidermolysis bullosa acquisita had serologic and direct IF features suggestive of BP.     

U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases

BACKGROUND: Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme-linked immunosorbent assay. OBJECTIVES: To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. METHODS: We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. RESULTS: We found three distinct 'linear' fluorescence patterns at the basement membrane zone: true linear, n-serrated and u-serrated. The true linear pattern, often seen in conjunction with either the n- or the u-serrated pattern, was found in any subepidermal immunobullous disease with nongranular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n-serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u-serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. CONCLUSIONS: Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease.     

Rituximab in refractory autoimmune bullous diseases

Treatment of autoimmune blistering diseases consists of systemic glucocorticosteroids usually in combination with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators such as dapsone, antibiotics, intravenous immunoglobulins, and immunoadsorption. In some patients, these treatment regimens are not sufficient to control disease activity and/or lead to intolerable adverse events. Rituximab, originally developed for the treatment of non-Hodgkin's lymphoma, is an anti-CD20 humanized monoclonal antibody leading to transitory B-cell depletion. For this indication, rituximab is widely employed, and severe side-effects rarely observed. Subsequently, the B-cell-depleting effect of rituximab has been exploited successfully in various autoimmune disorders, including autoimmune blistering diseases. Here, we review the effect of rituximab in such diseases. To date, application of rituximab has been reported in 26 treatment-resistant patients with the vulgaris, foliaceus, and paraneoplastic variants of pemphigus as well as in bullous pemphigoid and epidermolysis bullosa acquisita. All but a single patient showed clinical improvement with reduction of lesion formation. In about a third, a clinical remission requiring further immunsuppressive medication was achieved, and in about a quarter, complete remission was induced. In addition, the mode of action and adverse events of rituximab as well as adjuvant immunosuppressive treatments, and the effect on levels of circulating autoantibodies in these patients are discussed.     

Immunosuppressive therapy for autoimmune bullous diseases

Adjuvant immunosuppressive drugs are widely used to minimize corticosteroid-related adverse effects in the short-term and long-term management of cautoimmune bullous diseases. In bullous pemphigoid and pemphigus vulgaris, azathioprine and mycophenolate mofetil seem to be equally effective when used in combination with oral corticosteroids, but mycophenolate mofetil is less myelosuppressive and hepatotoxic. Due to a better safety profile, mycophenolate mofetil or enteric-coated mycophenolate sodium may gradually replace azathioprine as the first-line adjuvant of choice in the treatment of moderate to severe autoimmune bullous diseases, including epidermolysis bullosa acquisita and cicatricial pemphigoid. Cyclophosphamide still has a place in the treatment of severe relapsing autoimmune bullous diseases. Continuous oral cyclophosphamide provides optimal immunosuppression, but it also produces the highest cumulative dose. Several pulsed cyclophosphamide regimens have, therefore, been developed and are reported to be effective in severe forms of pemphigus. Randomized controlled studies are needed to compare the efficacy and safety of cyclophosphamide with newer treatment options, such as rituximab and immunoapheresis, and to define optimal dose ranges and duration of available immunosuppressive treatments in different stages of autoimmune bullous diseases.