Drug-induced bullous pemphigoid with dermal fluorescence on salt-split skin

The immunological features of drug-induced bullous pemphigoid appear to be similar to those of idiopathic bullous pemphigoid (BP), with presence of circulating and tissue-bound antibodies showing anti-basement membrane zone specificity. We describe a 28-year-old woman who developed a widespread blistering eruption with marked involvement of the mucous membranes shortly after commencing treatment with oral flucloxacillin. The eruption gradually cleared following drug withdrawal and treatment with oral corticosteroids. Indirect immunofluorescence showed circulating IgG anti-basement membrane zone (BMZ) antibody and C3 which bound to the dermal aspect of salt-split skin, and direct immunofluorescence (IMF) of perilesional skin showed a linear band of C3 at the BMZ. Western immunoblotting of the patient's serum showed positive reactivity with a 180 kDa antigen in epidermal extracts and no reactivity with dermal extracts. The dermal-binding pattern on indirect IMF with salt-split skin only occurs in a minority of patients with BP and has not been described previously in a drug-induced case.     

Suppressor-cell functions in bullous pemphigoid

Summary T Cells from 14 patients in the active stage of bullous pemphigoid and 10 patients in the inactive stage of the disease were studied with Leu-1, Leu-2, and Leu-3 monoclonal antibodies. The proportions of total T cells and T cells expressing either helper or suppressor phenotype in the peripheral blood of patients were not significantly different to those observed in normal subjects. In 15 patients with active disease, immunoregulatory mechanisms were functionally studied using an assay measuring the amount of total IgG synthesized in vitro. Peripheral-blood leukocytes were seearated into T- and B-cell fractions, and cultured in various combinations. In ten experiments, prior to culturing with B cells, the T cells were irradiated to remove their suppressor function. No statistically significant differences were observed in the amount of total IgG synthesized by B cells obtained from patients and normal subjects when they were cultured with untreated T cells or irradiated T cells obtained from patients or normal controls. These results indicate that, in patients with bullous pemphigoid, there is no loss of suppressor-cell function or increased helper-cell function as assessed by measuring the total IgG synthesized. Therefore, the immunoregulatory defect, if present, is a highly specific one and can only be studied using antigen-specific assays.     

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.     

药物相关性大疱性类天疱疮研究进展

药物相关性大疱性类天疱疮(drug-associated bullous pemphigoid, DABP)特指应用特定药物诱发的一种特殊类型的类天疱疮,其临床表现、组织学或免疫病理特征与特发性大疱性类天疱疮相同或相近。近年由药物导致大疱性类天疱疮的报道增多,本文就DABP的研究进展进行综述。     

大疱性类天疱疮临床评估指标的研究进展

大疱性类天疱疮是一类自身免疫性疱病。针对自身免疫性大疱病,有专门的评分指标用以评估病情的严重程度和对治疗的反应。常用的评价指标有自身免疫性疱病严重程度评分,专门针对大疱性类天疱疮的大疱性类天疱疮疾病面积指数评分,以及其他的一些评分方式。自身免疫性大疱病严重程度评分已经经过了效度检验,广泛地应用在寻常型天疱疮和其他一些自身免疫性疱病的评估中。大疱性类天疱疮疾病面积指数评分尚处于检验的过程中,应用该评分的临床试验较少。上述两种评分方式均对全身的皮肤、黏膜皮损情况,主观瘙痒程度进行了评分。     

Treatment of bullous pemphigoid

Bullous pemphigoid (BP) is the most frequent auto-immune blistering skin disease. Up to recently, it was treated with oral corticosteroids. High dose steroids are poorly tolerated in the elderly and probably contributed to the high mortality rates observed in several cohorts. For years, efforts have been devoted to looking for steroid sparing agents including immunosuppressive drugs, plasma exchanges, intravenous immunoglobulins, tetracycline. Many seemed useful in open series but proved ineffective or marginally effective when tested in randomized controlled trials. An important breakthrough was the demonstration by a large randomized trial that a "super-potent" topical corticosteroid (clobetasol propionate) was not only associated with a significant decrease in severe complications and mortality of BP patients but was also more effective than oral prednisone. New strategies for BP should include topical clobetasol propionate as the first line treatment and consider adjuvant therapy only in the very rare cases that are either resistant to or intolerant of this treatment.     

Plectin, an unusual target antigen in bullous pemphigoid

BACKGROUND: Bullous pemphigoid (BP) is a blistering disease associated with autoantibodies directed against two components of hemidesmosomes, BP180 and BP230. OBJECTIVES: To assess whether BP patients have autoantibodies targeting plectin, another hemidesmosomal component showing extensive homology to BP230. METHODS: Examination of sera from 16 patients with BP, using immunoprecipitation studies followed by immunoblotting. RESULTS: Serum of one of the 16 (6%) patients with BP contain autoantibodies binding to plectin, while no reactivity was found with sera from three control subjects. Sera from all 16 BP patients immunoprecipitated BP230 from extracts of biosynthetically radiolabelled human keratinocytes. CONCLUSIONS: Our results indicate that sera from BP patients might contain autoantibodies binding to plectin. Although this protein and BP230 are closely sequence-related, the occurrence of autoantibodies binding to plectin is a rare phenomenon in BP.     

Colloid body formation in bullous pemphigoid

Summary Thirty-eight biopsy specimens from 18 cases of bullous pemphigoid (BP) were observed using direct immunofluorescence (IF) techniques with fluorescein isothiocyanate (FITC)-labelled antisera against human serum factors. In addition to deposits of immunoglobulins and serum components at the basement-membrane zone (BMZ), 15 specimens from eight cases displayed homogeneous and globular fluorescent bodies in the uppermost dermis and/or the blisters when FITC-labelled antisera to human IgM and other serum factors were used. Using immunoperoxidase staining, haematoxylin/eosin (HE) and periodic acid-Schiff (PAS) staining, these immunoglobulin and/or complement-positive cell-sized bodies were shown to be slightly eosinophilic and PAS positive. Electron microscopy revealed entangled networks of microfilaments approximately 7–8 nm in diameter. These homogeneous, fibrillar bodies were histologically, immunohistologically and ultrastructurally indistinguishable from the colloid bodies found in lesional skins of lichen planus, lupus erythematosus, dermatomyositis and several other dermatoses. In BP, degenerated keratinocytes adjacent to the blister roof, may, after undergoing a filamentous change, drop off into the dermis and subsequently form homogeneous, fibrillar bodies in the uppermost dermis when reepithelization is completed.     

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.     

Dyshidrosiform bullous pemphigoid: trigger factors

This report presents 2 patients with a rare form of bullous pemphigoid on (heir palms and soles. To date, at least 16 cases of dyshidrosiform pemphigoid have been reported. The first case was accompanied by a bacterial fool infection, the second by contact dermatitis. The possibility that dyshidrosiform bullous pemphigoid was induced by these trigger factors is discussed.     

Trichophytic granuloma associated with bullous pemphigoid

A 69-year-old Japanese man developed multiple nodular granulomatous cutaneous lesions caused by Trichophyton rubrum during treatment of bullous pemphigoid. One and a half months after the initiation of oral corticosteroid therapy, the lesions appeared. He had suffered from tinea pedis for several decades. Oral ketoconazole was given for 6 weeks with remarkable improvement. Trichophytic granuloma is a rare but important complication of bullous pemphigoid.     

A population-based study of acute medical conditions associated with bullous pemphigoid

Background  Bullous pemphigoid is associated with poorly understood dramatically increased early mortality rates.
Objectives  To assess the incidence of acute events predisposing to early mortality.
Methods  Computerized medical records from the Health Improvement Network, a large population-based U.K. general practice database, were used to conduct a cohort analysis. Outcome measures were incidence rates of myocardial infarction, pulmonary embolism, pneumonia and sepsis compared with a matched control population.
Results  People with bullous pemphigoid were three times as likely to develop pneumonia, adjusted rate ratio 2·94 [95% confidence interval (CI) 2·01–4·31] or pulmonary embolism, adjusted rate ratio 3·12 (95% CI 1·37–7·12) compared with matched controls. No statistically significant increase was seen for myocardial infarction, adjusted rate ratio 1·24 (95% CI 0·66–2·33), or sepsis, adjusted rate ratio 2·02 (95% CI 0·78–5·21).
Conclusions  The risk of pulmonary embolism and pneumonia is increased following a diagnosis of bullous pemphigoid. It may be possible to reduce associated mortality through considering prophylaxis with either antithromboembolic measures or antibiotic therapy and vaccination.     

The distribution of IgG subclass autoantibodies in bullous pemphigoid analysed by immunofluorescence and immunoblotting

Summary The distribution of IgG subclasses in bullous pemphigoid (BP) autoantibodies in 14 BP sera and four biopsies was analysed by immunofluorescence (IF) and immunoblotting (IB). Three clones of monoclonal antibodies (MoAbs) to each IgG subclass were used. All 14 sera showed linear fluorescence in the basement membrane zone with IF, and 240 kDa and/or 180 kDa protein bands in human epidermal extract were detected by IB using a polyclonal antibody to total IgG. BP antibody in IgG₄ subclass was found to be predominant, as it was detected most frequently and intensively in all positive sera and lesions studied by both techniques. In the IgG₁ to IgG₃ subclasses, a range of proportions of positive sera was obtained among MoAbs to the same IgG subclass in both techniques. However, one MoAb could detect IgG₁ subclass BP antibody with a high frequency in both techniques. No difference in IgG subclass distribution of BP antibodies was observed during the course of the disease. In each serum, any IgG subclass of BP antibody recognized the identical BP antigen(s). These results suggest the predominance of IgG₄ subclass and the possible presence of IgG₁ subclass in BP antibodies.     

大疱性类天疱疮患者发根毛囊中抗体的检测

目的：通过检测大疱性类天疱疮患者拔出的头发上残留毛囊中大疱性类天疱疮抗体的沉积情况,建立一种快捷、损伤小的检测大疱性类天疱疮的方法。方法：直接免疫荧光方法测定35例大疱性类天疱疮患者拔出的头发上残留毛囊中类天疱疮抗体的沉积,10例健康人及20例天疱疮病人头发作为对照。结果：35例大疱性类天疱疮患者的毛发,其中阳性28例,阴性7例,阳性率80%;类天疱疮IgG和C3在毛囊表皮下的外毛根鞘外层与结缔组织鞘之间呈明显的线状沉积。10例正常人及20例天疱疮患者均无线状沉积。结论：本实验方法简单、快速、敏感,且具有较高特异性,有可能成为诊断和鉴别诊断大疱性类天疱疮的一种有效的方法。     

大疱性类天疱疮免疫发病机制的研究进展

大疱性类天疱疮作为常见的自身免疫性疱病,国内外学者一直进行其发病机制的研究.目前认为,IgG是大疱性类天疱疮患者血清中主要的致病性自身抗体类型,与BP180等自身抗原结合后可同定并激活补体,导致肥大细胞脱颗粒,激活浸润的炎症细胞并使其释放蛋白水解酶,引起真表皮连接部位的重要蛋白结构受损,最终导致表皮下水疱的发生.研究表明,体液免疫和细胞免疫均参与大疱性类天疱疮的发病过程,但大疱性类天疱疮自身抗体及可能存在的自身抗原的来源及嗜酸粒细胞在发病过程中的作用尚不完全清楚.

Abstract：

Bullous pemphigoid (BP) is a common autoimmune blistering skin disease. Studies on its immunologic pathogenesis have been always carried out at home and abroad. IgG autoantibodies, which are the predominant type of pathogenic autoantibodies, can bind to multiple BP180 epitopes, result in the fixation and activation of complement, degranulation of resident mast cells, activation of infiltrating inflammatory cells and release of proteinases followed by the loss of cell-matrix adhesion structure at the dermal-epidermal junction, and finally cause the formation of subepidermal blisters. Although studies have shown that both humoral and cellular immunity are involved, little is known about the resource of autoantibodies, probalble existent autoantigens, and the roles of eosinophils in the pathogenesis of BP.     

某些细胞因子与大疱性类天疱疮病情相关性的研究

目的：探讨大疱性类天疱疮（ＢＰ）病情的临床指标和实验室指标,并进一步分析细胞因子（ＣＫｓ）在发病机理中的作用。方法：应用ＥＬＩＳＡ试剂盒定量测量疱液和血清中,ＩＬ－５、ＩＬ－６和ＩＦＮ－γ的浓度。结果：１０例ＢＰ患者,水疱个数和受累面积呈正相关;〈２４小时水疱疱液中ＩＬ－５与水疱个数和受累面积相关性最大;血液中３种ＣＫｓ浓度与水疱个数和受累面积间无相关关系;随时间延长ＩＬ－５、ＩＬ－６浓度逐渐降低,ＩＦＮ－γ逐渐升高。结论：水疱计数可作为估计ＢＰ病情严重性的临床指标,并可以此确定治疗方案中皮质类固醇初始剂量。２４小时以内新起水疱中ＩＬ－５浓度可作为衡量临床病情严重性的实验室指标。ＩＬ－５在疾病的早期阶段参与水疱形成,随病情进展,皮损区浸润细胞由Ｔｈ２型向Ｔｈ１型细胞过渡,ＩＦＮ－γ逐渐替代ＩＬ－５、ＩＬ－６成为