Bullous pemphigoid in an infant

An acral blistering eruption in a 10 week old baby was found on histology and direct immunofluorescence to be bullous pemphigoid. Circulating auto-antibodies were not detected. He responded quickly to oral prednisolone and there have been no sequelae.     

Bullous pemphigoid in adolescence

Bullous pemphigoid (BP) is the most common autoimmune blistering disease affecting the elderly but is quite rare in childhood. The majority of pediatric cases have been reported during early childhood. Adolescence is divided into three phases: early (10‐13 years), middle (14‐17), and late (18‐21). This review aimed to identify BP cases in adolescence and demonstrate their clinical features and course. Our literature search was performed in Medline with the terms “bullous pemphigoid in childhood and adolescence,” “childhood bullous pemphigoid,” “juvenile bullous pemphigoid,” and “autoimmune blistering and autoimmune bullous diseases in childhood.” The data extraction for late adolescence was limited by the fact that this age group is included in adult BP registries. We identified nine cases in early adolescence. Mucosa were affected in 5 of 9 cases. Treatment consisted of systemic prednisone (8/9), in combination with dapsone (2/9), azathioprine (2/9), or erythromycin/nicotinamide (1/9). Relapses were reported in 3 of 9 cases. We identified five cases occuring in middle adolescence. Mucosa were not affected. Treatment consisted of systemic prednisone (5/5), in combination with dapsone (3/5), azathioprine (2/5), doxycycline/nicotinamide (1/5), or mycophenolate mofetil (1/5). Relapses were reported in two of five cases. No case of BP in the late adolescence was included in the results, as only one case met the search criteria, and overlapped with pemphigus vulgaris. With only 14 cases found in our review, BP in adolescence appears even rarer than in earlier childhood. Despite its low prevalence, BP should be included in the differential diagnosis of autoimmune blistering diseases in adolescents.     

Bullous scabies mimicking bullous pemphigoid

Scabies is an infestation caused by Sarcoptes scabiei and characterised by polymorphous lesions that may include burrows, papules, nodules, excoriation and crusts. Vesicular and bullous lesions are rather rare. Several diseases may be confused with scabies. We report a case of bullous scabies which, on the basis of the clinical and histopathological picture, mimicked bullous pemphigoid. Direct and indirect immunofluorescence were negative. Bullae recurred and persisted despite systemic corticosteroids. The patient was successfully treated with 5% permethrin and remained disease free for up to 12 months of follow-up.     

Bullous pemphigoid in pregnancy: contrasting behaviour in two patients

Bullous pemphigoid (BP) is an increasingly common immunobullous disease of the elderly, and, due to the late age of onset, is rarely seen in women of fertile age. Consequently, to the best of our knowledge no cases of BP in pregnancy have been described. We present two cases of BP that have differed in disease behaviour during pregnancy.     

Bullous pemphigoid

Bullous pemphigoid is the most common autoimmune blistering skin disease. It typically affects elderly patients and is characterized by subepidermal bullae and in vivo deposition of autoantibodies and complement components and significant polymorphonuclear cell infiltrates along the epidermal basement membrane zone. Despite of its relatively benign course, an effective treatment should promptly be initiated to control and prevent the appearance of new blisters in a population of patients that is already commonly debilitated by concomitant chronic diseases. In this article we present our practical, yet comprehensive approach to the management of patients with bullous pemphigoid.     

幼儿大疱性类天疱疮1例

报道1例儿童大疱性类天疱疮。患儿男．1岁8个月。全身泛发大疱生皮损，疱壁紧张，不易破裂，疱液清澈，尼氏征阴性。皮肤组织病理检查见表皮下水疱，真皮层见以嗜酸粒细胞为主的浸润。皮肤免疫病理检查见表皮基膜带有IgM及C3沉积，患儿经皮质类固醇治疗，疗效满意。     

Bullous pemphigoid in Liguria: A 2-year survey

BACKGROUND: The epidemiology of bullous pemphigoid (BP) is not clear because of the heterogeneity of the disease, and its possible association with internal malignancies has been under debate for many years. We report the findings of a 2-year study on incident BP cases in the Liguria region of Italy. SUBJECTS AND METHODS: Thirty-two patients with BP were collected over the 2-year period. Diagnosis was made based on clinical findings and confirmed by histology, direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) with salt-split skin and monkey oesophagus, and immunoblotting (IB). All patients were thoroughly investigated for possible malignancies and all were followed up for 6 months to monitor the response to treatment. RESULTS: DIF showed linear deposits at the dermoepidermal junction in all but one patient. IIF gave positive findings for 15 sera tested with monkey oesophagus and 20 tested with salt-split skin. IB gave positive findings in 19 cases. There was a malignancy in six cases, but no clinical or immunological features that could be considered to predict this occurrence. CONCLUSIONS: The findings of this study are in accordance with most of the data found in the literature, including the fact that IgG serum levels did not predict the course of the disease. Contrary to previous indications, IgE levels were not indicative of disease course either. Mucosal lesions, erythema multiform-like lesions, negative IIF findings and antibodies to AgPB2 were not a prediction for the development of malignancy.     

Bullous pemphigoid in adolescence,a rare demographic

Bullous pemphigoid is rarely seen in adolescence, and its presentation, clinical course, and treatment can differ to that found in other age groups. We present a case of bullous pemphigoid in a 16‐year‐old with features of koebnerisation and oral mucosal involvement and provide a brief review of paediatric bullous pemphigoid.     

Amoxicillin-induced bullous pemphigoid in a child

The Authors describe the case of a 6-year old female child who presented a bullous dermatitis following the administration of amoxicillin, with clinical, histopathological and immunological features typical of childhood bullous pemphigoid. The peculiar aspects of drug-induced bullous pemphigoid are therefore reviewed, with particular reference to the hypotheses behind the relative induction mechanism.     

Bullous pemphigoid: serum antibody titre and antigen specificity

Abstract 2 antigens have been identified as possible targets for autoantibody depositions in bullous pemphigoid: a 230-kD protein (BP230) and a 180-kD protein (BP180). We studied the relationship of these 2 antigens with the immunofluorescence determined serum antibody titre. 2 groups of bullous pemphigoid patients were selected on the basis of immunoblot-determined antibody specificity. One group (13 patients) had antibody specificity for BP230 and not for BP180, while the other group (9 patients) had antibody specificity for BP180 and not for BP230. The immunofluorescence titres of the circulating antibodies determined on monkey oesophagus substrate displayed, for the BP230-specific group, a mean of 1:1102. The maximal observed titre was 1:5120. The mean titre in the BP180-specific group was only 1:29, with a highest titre of only 1:160. This result suggests that in routine indirect immunofluorescence of bullous pemphigoid sera, the contribution of the BP180-specific antibodies to the total anti-epidermal basement membrane zone antibody titre is relatively much lower than that of the BP230-specilic antibodies. Thus, at high dilutions, only the BP230-speeific antibodies contribute to the overall indirect immunfluorescence titre.     

Bullous pemphigoid with a prolonged prodrome

Bullous pemphigoid is an autoimmune blistering skin disease of the elderly that may be preceded by a pruritic, urticarial or eczematous eruption. We report a case of bullous pemphigoid preceded by prodromal eczematous eruptions that lasted an unusually long time of 11 years. Elderly patients with persistent pruritic or eczematous eruption of unknown etiology should be carefully followed, as bullous pemphigoid may be a potential diagnosis.     

A child with localized vulval pemphigoid and IgG autoantibodies targeting the C-terminus of collagen XVII/BP180

Localized vulval pemphigoid of childhood (LVPC) has previously been reported in six girls. Clinical features and immunopathological data have suggested it to be a morphological variant of bullous pemphigoid. Epitope targets of the autoantibodies of these patients have not been defined in detail. We describe a 9-year-old girl with possible cicatricial LVPC and circulating IgG antibodies directed against native collagen XVII/BP180, its 120-kDa soluble ectodomain and against the C-terminus of collagen XVII/BP180. No reactivity was detected towards the NC16A domain of collagen XVII/BP180. Linear IgG and C3 deposits were found along the cutaneous basement membrane zone. On 1 mol/L salt-split skin, IgG autoantibodies were shown to bind to the epidermis, and the HLA type II allele DQB1*0301, a marker with significantly increased occurrence in patients with ocular and oral cicatricial pemphigoid, was identified in this patient. Our data suggest that LVPC is a variant of bullous pemphigoid in which direct immunofluorescence microscopy combined with immunoblot analysis can deliver valuable diagnostic information for differential diagnosis. However, differentiation between the scarring and non-scarring course of the disease cannot be made with the present diagnostic markers and therefore careful follow-up of patients with LVPC is required.     

Bullous pemphigoid and burns: The unveiling of the attachment plaque?

Two patients with bullous pemphigoid (BP) associated with burns are described. The case with BP lesions that were localized is the first to be described in the literature and generalized BP has been described on only one occasion previously. Both cases exhibited the clinical features of BP and settled with the use of oral prednisolone. Many extrinsic precipitants of BP have been described; however, the precise trigger of the autoimmune process is not yet understood. The authors discuss the hypothesis that as burns expose BP antigen, the association of BP with advancing years arises through exposure of BP antigen during the process of involution of the basement membrane zone seen in the normal process of ageing. BP should be considered in cases of burns associated blistering, particularly blisters occurring at distant sites, but also involving affected skin.     

Bullous pemphigoid: role of complement and mechanisms for blister formation within the lamina lucida

Bullous pemphigoid (BP), an autoimmune subepidermal blistering skin disease, demonstrates tense blisters with or without widespread erythema, blistering along the lamina lucida, immunoglobulin G and/or complement deposits at the basement membrane zone, and the presence of circulating autoantibodies against hemidesmosomal molecules. These autoantibodies usually react against 180‐kDa and/or 230‐kDa proteins, designated as BP180 and BP230, respectively. The precise blistering mechanisms after autoantibodies bind to antigens are not fully understood. Immune complexes are thought to initially activate the complement cascade, which may induce activation of proteases and/or cytokines and cause dermal–epidermal separation. However, why does separation run specifically within the lamina lucida in a space as narrow as 500 nm wide? This review mainly focuses on the possible mechanisms of BP‐specific blistering and how separation occurs along the lamina lucida, based on existing evidence.     

Bullous pemphigoid with hyperkeratosis and palmoplantar keratoderma: Three cases

The clinical features of bullous pemphigoid are extremely polymorphous. Several atypical forms of bullous pemphigoid have been described, and the diagnosis critically relies on immunopathological findings. We describe three bullous pemphigoid patients characterized by palmoplantar keratoderma, diffused hyperkeratotic cutaneous lesions and extremely high levels of immunoglobulin E serum. The diagnosis of bullous pemphigoid should be taken into account in patients presenting diffused hyperkeratotic cutaneous lesions and palmoplantar keratoderma, even in the absence of blisters. Alteration of the keratinization process, that could occur in patients with genetic mutations in desmosomal and hemidesmosomal genes, may also be due to circulating autoantibodies against hemidesmosomal proteins in these bullous pemphigoid patients.     

Bullous Pemphigoid Associated with Shy-Drager Syndrome

We report a patient with Shy-Drager syndrome who developed multiple tense blisters mainly on the extremities. Circulating anti-basement membrane zone autoantibodies were detected by the indirect immunofluorescence method. Immunoblot analysis using normal human epidermal extracts demonstrated that this patient's serum reacted only with 230 kD bullous pemphigoid antigen (BPAG1). Concerning the pathoetiology of the association of bullous pemphigoid and Shy-Drager syndrome, we discuss a sequence similarity between BPAG1 and dystonin, a candidate gene for dystonia musculorum.     

大疱性类天疱疮并发原发性皮肤弥漫性大B细胞淋巴瘤

报告1例大疱性类天疱疮并发原发性皮肤弥漫性大B细胞淋巴瘤.患者男,80岁.全身水肿性红斑伴水疱、大疱,诊断为大疱性类天疱疮.在发病7个月后,右胫前出现多个暗紫红色结节,逐渐增多、增大,并扩展至右股内侧和背部.皮损组织病理检查示真皮全层及皮下脂肪小叶弥漫致密的淋巴细胞浸润,可见多数淋巴细胞体积增大,形态不规则,核大深染,可见核分裂相.免疫组化染色:CD20( ),bcl-2( ),bcl-6( ).诊断:原发性皮肤弥漫性大B细胞淋巴瘤.在肿瘤出现后1个月,患者大疱性类天疱疮的病情出现反复,通过CHOP方案治疗,病情明显好转.     

Bullous pemphigoid antigen II (BP180) and its soluble extracellular domains are major autoantigens in mucous membrane pemphigoid: the pathogenic relevance to HLA class II alleles and disease severity

BACKGROUND: Mucous membrane pemphigoid (MMP), a chronic autoimmune subepithelial blistering disease, is associated with circulating IgG and/or IgA autoantibodies against several basement membrane zone antigens. The heterogeneity of clinical presentation and diversity of target autoantigens have contributed to difficulties in characterizing this condition immunologically. OBJECTIVES: To analyse serum autoantibody profile and HLA class II alleles in MMP patients and to correlate this with the clinical presentation of disease. METHODS: Well-defined subgroups consisting of 124 patients with MMP were examined for IgG and IgA reactivity with immunoblotting using human epidermal, dermal and placental amnion proteins. The results were further analysed on the basis of detailed clinical (sites of involvement and disease severity) and immunopathological criteria (immunofluorescence study and HLA class II alleles). RESULTS: Immunoblot assay revealed that the majority of MMP patients had IgG (93 of 124, 75%) and/or IgA autoantibodies (63 of 124, 51%) to BP180 (including its soluble ectodomains, 120-kDa LAD-1 and 97-kDa LABD97 antigens). Other antigens targeted predominantly by IgG autoantibodies included: BP230 in 34 (27%), beta4 integrin in 26 (21%), and laminin 5 in three (2%). All the BP230+ sera and 23 (88%) beta4 integrin+ sera also reacted with at least one of the BP180 antigens. Over 85% of patients with reactivity to beta4 integrin had ocular involvement. In most cases of MMP, more severe clinical features were associated with antibody reactivity to multiple basement membrane zone antigens, as well as reactivity to multiple BP180 component antigens. Dual BP180/LAD-1 reactivity with IgG and IgA was associated with a more severe phenotype. In addition, the subset-dependent autoantibody reactivity correlated well with specific HLA class II alleles, DQB1*0301, DRB1*04 and DRB1*11. CONCLUSIONS: Our results confirmed that BP180 is a major autoantigen targeted by the sera of patients with MMP. The disease-prevalent HLA class II alleles and humoral autoimmune response against the particular subsets of antigenic epitope(s) within BP180 ectodomain may contribute to the clinicopathological significance and disease severity of MMP.     

Erythrodermic bullous pemphigoid

We report a case of erythrodermic type of bullous pemphigoid which is a rare variant of bullous pemphigoid. Our patient had a peculiar clinical presentation with bullae, erosions and extensive erythrodermic areas, and distinct direct immunofluorescent findings which included linear IgG and C3 deposits in the basement membrane and also IgG in the intercellular spaces. Very high levels of serum IgE were also detected in our patient.