Treatment conundrum: A case of recalcitrant Epidermolysis Bullosa Acquisita (EBA) in a 50-year-old Filipino male

Introduction@#Epidermolysis Bullosa Acquisita (EBA) is a rare autoimmune blistering disease which presents in the skin and mucous membranes. The decrease in anchoring fibrils in the basement membrane zone causes separation of the epidermis from the dermis, resulting in its blistering presentation. The treatment plan will depend on the severity of the disease. The first-line treatment for mild EBA includes topical corticosteroids and immunomodulators such as dapsone and colchicine; while severe cases of EBA may be given intravenous immunoglobulins, systemic steroids, and immunosuppressants such as azathioprine and cyclophosphamide. @*Case Report@#This is a case of a 50-year-old Filipino male who presented with a 2-year history of vesicles and tense bullae which evolved into papules, plaques and erosions with scarring and milia formation on the scalp and trauma-prone areas of the trunk and extremities. Clinical examination revealed multiple, well-defined, irregularly shaped erythematous papules and plaques with crusts, scales, erosions, pearl-like milia and scarring on the chest, back, upper, and lower extremities. The oral mucosa was moist with some ulcers on the tongue. Histopathologic examination using Hematoxylin and Eosin (H&E) stain revealed the absence of the epidermis with retention of dermal papillae suggestive of subepidermal clefting. Further examination with direct immunofluorescence (DIF) revealed monoclonal immunoglobulin (IgG) deposits demonstrating an intense linear fluorescent band at the dermoepidermal junction, consistent with Epidermolysis Bullosa Acquisita. Overall, the combined administration of prednisone, azathioprine, and colchicine resulted only in transient and incomplete resolution of lesions in this case of EBA.@*Conclusion@#The management of EBA is mostly supportive with the goal of minimizing complications. Combination treatments using steroids, colchicine, and azathioprine have been reported with various results. Its management remains challenging as most cases are refractory to treatment.

Consensus on the treatment of autoimmune bullous dermatoses: bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita - Brazilian Society of Dermatology

Abstract: Bullous pemphigoid, mucous membrane pemphigoid and epidermolysis bullosa acquisita are subepidermal autoimmune blistering diseases whose antigenic target is located at the basement membrane zone. Mucous membrane pemphigoid and epidermolysis bullosa acquisita can evolve with cicatricial mucosal involvement, leading to respiratory, ocular and/or digestive sequelae with important morbidity. For each of these dermatoses, a literature review covering all therapeutic options was performed. A flowchart, based on the experience and joint discussion among the authors of this consensus, was constructed to provide treatment orientation for these diseases in Brazil. In summary, in the localized, low-risk or non-severe forms, drugs that have immunomodulatory action such as dapsone, doxycycline among others may be a therapeutic option. Topical treatment with corticosteroids or immunomodulators may also be used. Systemic corticosteroid therapy continues to be the treatment of choice for severe forms, especially those involving ocular, laryngeal-pharyngeal and/or esophageal mucosal involvement, as may occur in mucous membrane pemphigoid and epidermolysis bullosa acquisita. Several immunosuppressants are used as adjuvant alternatives. In severe and recalcitrant cases, intravenous immunoglobulin is an alternative that, while expensive, may be used. Immunobiological drugs such as rituximab are promising drugs in this area. Omalizumab has been used in bullous pemphigoid.

Subepidermal blistering disorder in a 16-year-old female: Case report

@#Subepidermal blistering disorders (SBD) are diseases associated with antibodies that attack structural proteins of the skin. Blister formation with widespread distribution is common in these diseases. Diagnosis of SBD is established through the demonstration of immunoglobulin deposits in the dermoepidermal junction by direct immunofluorescence microscopy, and through the presence of circulating autoantibodies by serology. Systemic corticosteroids and other immunosuppressive drugs are used to treat SBD. We present the case of a 16-year old female with a 6-week history of intensely pruritic, erythematous plaques with generalized blister formation on the face, trunk, upper extremities, and inner thighs. We diagnosed the patient as having a subepidermal blistering disorder. We placed her on a course of prednisone and azathioprine, which successfully treated her lesions.

Subepidermal blistering disorder in a 16-year-old female: Case report

@#Subepidermal blistering disorders (SBD) are diseases associated with antibodies that attack structural proteins of the skin. Blister formation with widespread distribution is common in these diseases. Diagnosis of SBD is established through the demonstration of immunoglobulin deposits in the dermoepidermal junction by direct immunofluorescence microscopy, and through the presence of circulating autoantibodies by serology. Systemic corticosteroids and other immunosuppressive drugs are used to treat SBD. We present the case of a 16-year old female with a 6-week history of intensely pruritic, erythematous plaques with generalized blister formation on the face, trunk, upper extremities, and inner thighs. We diagnosed the patient as having a subepidermal blistering disorder. We placed her on a course of prednisone and azathioprine, which successfully treated her lesions.

Acute renal failure in a patient with epidermolysis bullosa acquisita

Abstract: Epidermolysis bullosa acquisita is a severe autoimmune subepidermal bullous disease. In this report, we described for the first time a patient with epidermolysis bullosa acquisita who developed acute renal failure. There is a possibility that epidermolysis bullosa acquisita and acute renal failure's pathogenesis shared some common autoimmune pathways. Moreover, acute blood volume reduction may be another cause of prerenal kidney failure. Further studies are needed to verify our hypothesis.

Fenômeno de epitope spreading: caracterização clínico imunológica em pacientes portadores de dermatoses bolhosas autoimunes / Epitope spreading" phenomena: clínical and immunopathological characterization in patients with bullous dermatosis

As dermatoses bolhosas autoimunes são um grupo heterogêneo de afecções da pele e/ou mucosas associadas à produção de autoanticorpos dirigidos às moléculas de adesão epitelial. Podem ser classificadas em dermatoses bolhosas intraepidérmicas (pênfigos) ou subepidérmicas (penfigóides, epidermólise bolhosa adquirida). Nos últimos anos, a transição entre dermatoses bolhosas autoimunes ou coexistência de autoanticorpos de diferentes dermatoses têm sido relatadas em alguns pacientes e atribuída ao fenômeno de epitope spreading (ES): a diversificação de epítopos reconhecidos pelo sistema imune evocaria uma reação secundária a antígenos distintos e não relacionados aos da doença primária. Neste trabalho avaliamos a ocorrência de fenômenos de ES em pacientes portadores de pênfigo. CASUÍSTICA E MÉTODOS: Inicialmente, foi realizada análise de dados clínicos e laboratoriais (exame histopatológico, de imunofluorescência direta-IFD, indireta IFI e ELISA) de 351 pacientes portadores de pênfigos acompanhados no Ambulatório de dermatoses bolhosas autoimunes do Departamento de Dermatologia da Faculdade de Medicina da Universidade de São Paulo no período de dezembro de 2002 a dezembro de 2012. Foram selecionados pacientes com quadro sugestivo de conversão à dermatose bolhosa distinta da doença primária. RESULTADOS: Nove pacientes apresentaram sinais sugestivos de fenômeno de ES e foram incluídos no estudo: 8 com a conversão de Pênfigo vulgar (PV) a foliáceo (PF) 2,3% (grupo1) e um de PF a Epidermólise bolhosa adquirida (EBA) 0,3% (grupo 2). No grupo 1 o intervalo mediano para a conversão foi de 3,5 anos. Cinco pacientes apresentaram modificação histopatológica de clivagem intraepidérmica na camada suprabasal para clivagem na camada subcórnea durante a suspeita de ES; 2 apresentaram clivagem na camada epidérmica média durante a transição e um manteve clivagem suprabasal, apesar de quadro clínico sugestivo de PF. Todos os pacientes apresentavam...

Autoimmune bullous skin diseases represent a heterogeneous group of disorders of skin and mucosa associated with autoantibodies against distinct adhesion molecules. They can be classified, based on the level of loss of adhesion in intraepidermal and sub epidermal dermatosis. The shift from an autoimmune blistering disease to another has been recently described and attributed to the "epitope spreading" (ES) phenomena. It occurs when a primary inflammatory/autoimmune process releases "hidden" epitopes which are recognized by the lymphocytes and evoke a secondary reaction to antigens distinct from, and non-cross-reactive, with the disease causing-epitope. This study attempted to characterize the occurrence of ES in pemphigus patients. METHODS: We analyzed data from 351 pemphigus patients treated ambulatorially at the Department of Dermatology, Faculty of Medicine, University of São Paulo, from December 2002 to December 2012. A careful search for clinical and laboratorial (histopathology, direct-DIF and indirect-IIF immunofluorescence, ELISA) changes suggestive of shift to a secondary bullous disease was performed. RESULTS: Nine out of 351 patients presented clínical shift and were included in the study: eight from pemphigus vulgaris (PV) to foliaceus (PF) 2.3% (group 1) and one from PF to epidermolysis bullosa acquisita (EBA) 0.3% (group 2). In group 1, median interval of disease shift was 3.5 years. Of 8 patients with clinical PF, five showed change of histopathology pattern from suprabasilar cleavage to subcorneal acantholysis, two had cleavage within the middle epidermal layer, and one sustained the suprabasilar acantholysis. One shifted back to PV after clinical and histopatological changes of PF. All patients showed intercellular IgG and/or C3 deposits during PV and PF diagnosis by DIF. IIF titers varied from 1:160 to 1:5120. ELISA index for Dsg1 varied from 22 to 319; and for Dsg3 from 0.4 to 224 (positive if > 20)....

A Case of Epidermolysis Bullosa Acquisita Associated with Psoriasis / 대한피부과학회지

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease characterized by the presence of circulating IgG autoantibodies to type VII collagen. Various types of autoimmune blistering disease have been reported in association with psoriasis. A 58-year-old man with a 5-year history of psoriasis vulgaris presented with painful and mildly pruritic erythematous multiple bullae and vesicles. Histopathologically, there was a subepidermal bulla with infiltration of inflammatory cells composed of neutrophils and eosinophils. The salt-split skin indirect immunofluorescence test showed IgG binding to the dermal side of the separation, and immunoblotting using normal human dermal extract revealed antibodies directed against a 290-kDa polypeptide. He was diagnosed with EBA and started medication of oral prednisolone and mycophenolate mofetil. Skin lesions were continuously regressed. Of all the autoimmune blistering diseases coexisting with psoriasis, bullous pemphigoid is the most frequent. However, a few cases of EBA associated with psoriasis have been reported in the literature. We report a rare case of EBA coexisting with psoriasis vulgaris.

Expression of transient receptor potential lvanilloidreceptor 4 protein in autoimmune bullous skin disorders / 南方医科大学学报

<p><b>OBJEVTIVE</b>To investigate the expression of transient receptor potential lvanilloidreceptor 4 (TRPV4) protein in pemphigus vulgaris (PV), bullous pemphigoid (BP), dermatitis herpetiformis (DH), and epidermolysis bullosa acquisita (EBA), and explore the role of TRPV4 in the pathogenesis of these diseases.</p><p><b>METHODS</b>TRPV4 protein in normal skin tissues and lesions of PV, BP, DH, and EBA were detected with immunohistochemistry.</p><p><b>RESULTS</b>The positivity rate of TRPV4 protein expression was 61.90% in PV, 81.81% in BP, 72.22% in DH, and 68.42% in EBA. TRPV4-positive rates in these lesions were significantly lower than the rate in normal skin tissues (93.33%) and also differed significantly among these lesions (PV<EBA<DH<BP).</p><p><b>CONCLUSIN</b>Low TRPV4 expressions may affect the formation and reconstitution of skin connection. TRPV4 may play an role in the occurrence and development of autoimmune bullous skin disorders.</p>

Assessment of the Quality of Life in Autoimmune Blistering Skin Disease Patients / 대한피부과학회지

BACKGROUND: Autoimmune blistering skin diseases such as pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid and epidermolysis bullosa acquisita substantially affect patients' daily life and psychosocial well-being. OBJECTIVE: The aim of this study was to evaluate the quality of life (QOL) in patients with autoimmune blistering diseases and to identify the factors that can influence their QOL by comparing them to healthy controls. METHODS: Forty patients with autoimmune blistering skin diseases and 40 healthy controls were interviewed using the Korean version of Skindex-29. The study assessed the clinical severity of the disease. RESULTS: The total, symptom, function, and emotion scores of Skindex-29 were significantly higher in patients with autoimmune blistering skin diseases (35.28, 40.78, 30.57, and 36.67, respectively) than in the healthy controls (6.90, 9.38, 5.47, and 6.60, respectively) (p<0.001). Higher disease severity had a negative correlation with QOL in patients with blistering skin diseases, and QOL was lower when patients had low levels of satisfaction with treatment. CONCLUSION: The results show that autoimmune blistering skin diseases can affect patients' QOL. In addition, disease severity and low satisfaction with treatment are important factors that reduce QOL. Development of new treatments should improve treatment efficacy and the QOL of patients with autoimmune blistering diseases.

Localized Epidermolysis Bullosa Acquisita Limited to the Face / 대한피부과학회지

No abstract available.

Imunoglobulina intravenosa para tratamento de epidermólise bolhosa adquirida grave refratária a terapia imunossupressora convencional / Intravenous immunoglobulin for treatment of severe acquired bullous epidermolysis refractory to conventional immunosuppressive therapy

A epidermólise bolhosa adquirida é doença bolhosa subepidérmica crônica e rara. Geralmente, inicia-se na fase adulta, sendo a etiologia desconhecida, embora vinculada à presença de anticorpos contra o colágeno tipo VII. Há formação de bolhas, espontaneamente ou após trauma, podendo causar complicações graves. O tratamento é desapontador e difícil. Além da terapia convencional com corticoides sistêmicos, recentemente, novas modalidades terapêuticas promissoras estão sendo utilizadas, dentre elas, a imunoglobulina intravenosa. Destaca-se, neste relato, o difícil manejo clínico desta doença, e a melhora importante com a imunoglobulina intravenosa.

Acquired bullous epidermolysis is a chronic and rare bullous subepidermal disease. It usually begins in adulthood and its etiology is unknown although it is associated with antibodies against type VII collagen. There are spontaneous and trauma induced formation of blisters that may cause serious complications. Treatment is disappointing and difficult. Apart from conventional therapy with systemic corticosteroid, new therapeutic modalities such as intravenous immunoglobulin are currently being used. This report highlights the extremely difficult clinical management of this rare disease and the important improvement provided by intravenous immunoglobulin.

Penfigoide ampollar en lactante / Bullous pemphigoid in an infant

El penfigoide ampollar es una enfermedad autoinmune rara en la niñez, que afecta usualmente a los adultos. Clínicamente puede ser indistinguible de otras dermatosis ampollares. Presentamos un caso de penfigoide ampollar en un niño de 6 meses de vida con ampollas generalizadas y revisamos los principales diagnósticos diferenciales en este grupo etario.

Bullous pemphigoid is an immunological disorder that predominantly affects the elderly. It may be clinically indistinguishable from other immunobullous dermatoses. We present a case of bullous pemphigoid in a 6-month-old boy who presented generalized bullae and review the main differential diagnoses.

Epidermólise bolhosa adquirida inflamatória: relato de caso / Inflammatory epidermolysis bullosa acquisita: case report

Apresenta-se caso de epidermólise bolhosa adquirida inflamatória. Paciente do sexo masculino, 53 anos, há seis meses com erupção vesicobolhosa pruriginosa sobre base eritematosa no tronco, axilas e membros. O exame anatomopatológico mostrou bolha subepidérmica com neutrófilos. A imunofluorescência direta revelou depósitos lineares de IgG, IgA, IgM e C3 na zona da membrana basal, sendo a imunofluorescência indireta e o Salt Split Skin indireto negativos. Anticorpos antinucleares não reagentes. Houve melhora do quadro com prednisona e cicatrização de algumas lesões com formação de milia. Trata-se de apresentação rara de epidermólise bolhosa adquirida, com lesões iniciais predominantemente inflamatórias.

We report a case of an inflammatory variant of epidermolysis bullosa acquisita in a 53-year-old male, with itching blistering eruption on the trunk, armpits and limbs for six months. The skin biopsy specimen showed subepidermal blister with neutrophils. Direct immunofluorescence revealed linear depositions of IgG, IgA, IgM and C3 at the basement membrane; indirect immunofluorescence and salt Split Skin were negative. Antinuclear antibodies were also negative. Improvement of the blisters followed treatment with systemic corticotherapy and some lesions healed with milia. This is a rare presentation of epidermolysis bullosa acquisita, with inflammatory lesions at first.

Successful Treatment of Localized Epidermolysis Bullosa Acquisita with Low-dose Dapsone and Topical Tacrolimus / 대한피부과학회지

A 52-year-old man had a twenty-five year history of recurrent bullous eruption that was localized to both cheeks. The diagnosis of epidermolysis bullosa acquisita was confirmed by means of direct immunofluorescence and salt-split direct immunofluorescence studies that were performed on the perilesional skin. The patient has been in partial remission state with the treatment of low dose dapsone (12.5~25 mg) and topical tacrolimus. Herein, we report on a case of EBA localized to the face, and it showed a favorable response to treatment with low-dose dapsone and topical tacrolimus.

Clinical and Epidemiological Studies of Patients with Autoimmune Bullous Diseases / 대한피부과학회지

BACKGROUND: Autoimmune bullous diseases (ABDs) are a rare significant group of dermatoses that pose great challenges to the dermatologist. So far, few epidemiological surveys for the whole spectrum of ABDs have been completed in Korea, though many epidemiological survey have focused on single ABDs. OBJECTIVE: The aim of this study was to evaluate the incidence and clinical findings of patients in the Chonnam Province of Korea with ABDs over a 5 year period. METHODS: A retrospective analysis was conducted on 52 ABDs patients from 2002 to 2006. ABDs were diagnosed chiefly by histopathologic findings, immunofluoresence (IF), and immunoblotting with epidermal and dermal human foreskin extract. For the exact diagnosis of ABDs, several additional diagnostic methods such as indirect IF with salt-split normal skin, immunoblotting (IB) with normal keratinocyte cells, enzyme-linked immunosorbent assay (ELISA) with recombinant proteins, immunoprecipitaion (IP) were also performed. RESULTS: Out of 52 patients diagnosed with ABDs during the study period, pemphigus vulgaris was observed to be the commonest ABD (38.5%) followed by bullous pemphigoid (29.8%), pemphigus foliaceus (17.8%), epidermolysis bullosa acquisita (5.8%), paraneoplastic pemphigus, pemphigoid gestationis (3.8%), and linear IgA bullous dermatoses (1.9%). CONCLUSION: This study showed the incidence of the ABDs in Chonnam-Gwangju province area were very low (52 cases over 5 years) and was stationary over this period. Pemphigus vulgaris and bullous pemphigoid were common diseases among many ABDs. The incidence of ABDs in Korea as a whole needs to be investigated.

An Ultrastructural Examination of the Epitope Expression at Each Domain of Type VII Collagen in Patients with Epidermolysis Bullosa Acquisita / 대한피부과학회지

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is an autoimmune disease characterized by circulating IgG autoantibodies which bind to the type VII collagen (C-VII). The major antigenic epitopes in C-VII, to which most EBA autoantibodies react, have been considered to be present in the N-terminal noncollagenous (NC1) domain. However, a novel EBA subgroup was recently identified with circulating antibodies, which target domain(s) other than or along with the NC1 domain of C-VII. These data suggest that there might be some heterogeneity in the autoantibody specificity to bind the domain-oriented epitopes in EBA. OBJECTIVE: The purpose of this study was to determine whether additional or independent epitopes exist in the C- terminal noncollagenous (NC2) and/or collagenous triple-helical (CTH) domain among Korean patients with EBA. METHODS: For this investigation, postembedding, indirect, immunogold electron microscopy was performed with the sera from 10 cases of EBA, having circulating autoantibodies against C-VII. The identification of the epitope and the relevant domain in each case were determined by ultrastructural localization of the immunogold particles. RESULTS: From 10 sera examined, all 10 cases showed deposits of gold particles confined to the area along the lamina densa (LD), without any other pattern of deposition. There was no case which revealed any independent/distinct deposits of the gold particles in the dermis below the LD. The ultrastructural locations of each domain (NC1, on the LD; NC2, 300~360 nm below the LD; CTH, between the area of NC1 and NC2) indicated that the epitopes recognized in all 10 Korean cases of EBA were expressed at the NC1 domain of C-VII. We did not find any additional or independent epitope in other domain. CONCLUSION: The results suggest that there may not be a wide heterogeneity in the domain-oriented topographic expression of antigenic epitopes in EBA; it is highly likely that the major epitopes present in Korean EBA cases reside within the NC1 domain of C7, similar to those observed with white population.

Possible Apoptotic Mechanisms in the Vesiculation Process of Pemphigus, Bullous Pemphigoid, and Epidermolysis Bullosa Acquisita / 대한피부과학회지

BACKGROUND: Apoptosis, or programmed cell death, may participate with pathogenesis of intercellular detachment and loss of cell-matrix interaction. Autoimmune bullous dermatoses is an entity charaterized by bullous lesions of the skin and mucosa, and autoantibodies to the specific tissue components. OBJECTIVE: The purpose of this study was to investigate the induction of apoptosis in the lesional skin of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). METHODS: Hoechst 33342 (bisbenzimide) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was performed to determine the induction of apoptosis in the lesional skin of each disease. RESULTS: In PV and PF, typical findings of apoptosis were observed in the lesional epidermis showing acantholysis. However, in BP and EBA, no apoptosis of the epidermis was observed. CONCLUSION: These results suggest that apoptosis is only associated with acantholysis of the epidermal keratinocytes, one of many components of pathogenesis in bullous disease, in patients with pemphigus.

Application of Confocal Laser Scanning Microscopy to the Differential Diagnosis of Bullous Pemphigoid and Epidermolysis Bullosa Acquisita / 대한피부과학회지

BACKGROUND: The differential diagnosis of bullous pemphigoid (BP) and epidermolysis bullosa acquisita (EBA) presents some difficulties since both diseases have overlapping clinical and histological features, as well as immunopathological findings. Confocal laser scanning microscopy (CLSM) has been developed and has shown to be a promising tool for dermatological investigations, giving a higher degree of resolution and available co-localization analysis. OBJECTIVE: The purpose of this study was to evaluate whether the new technique of CLSM could reliably identify and differentiate the binding sites of disease specific-autoantibodies (Abs) at the basement membrane zone (BMZ), with the sera from BP and EBA. METHODS: An indirect immunofluorescence (IF) assay was performed to localize the binding sites of circulating Abs from 5 cases of both BP and EBA, as well as the sites of 3 BMZ markers (integrin beta4, laminin-5, and type IV collagen). To facilitate identification and topographic differentiation between the two groups, patients' Abs were labeled with fluorescein isothiocyanate, whereas the BMZ markers were labeled with Texas red. The tissue specimens were observed under both conventional IF microscopy and CLSM. RESULTS: Owing to superposition of antigens and marker labels, double immuno-labeled sections under IF microscopy revealed limitations for the differentiation of patient's sera from BMZ markers even with high magnification (x1,000). However, CLSM was able to eliminate much of the antigen overlap. In BP, the circulating autoantibody' deposits were recognized on the epidermal side of laminin-5 and type IV collagen, and codistributed with integrin beta4. On the other hand, the binding of autoantibodies in EBA was on the dermal side from that of integrin beta4, laminin-5 and type IV collagen. These spatial relationships are compatible with their known microstructural locations. CONCLUSION: Our study indicates that CLSM examination may provide more precise localization of the antigens in BP and EBA than conventional IF microscopy. CLSM would not only be an efficient tool to identify circulating anti-BMZ autoantibodies for diagnosis and differential diagnosis of blistering diseases, but also a great addition to examining tissue specimens in patients who do not have detectable circulating Abs.