大疱性类天疱疮与瘢痕性类天疱疮

通过大疱性类天疱疮与瘢痕性类天疱疮之间的比较,发现大疱性类天疱疮与瘢痕性类天疱疮之间存在相关性,表现在好发人群均为老年人、存在相同致病抗体、两者可同时合并肿瘤、间接免疫荧光显示致病抗体沉积在表皮侧等方面。近年来生物制剂如抗CD20抗体利妥昔等应用于大疱性类天疱疮与瘢痕性类天疱疮的临床治疗,具有一定疗效。瘢痕性类天疱疮的黏膜受累机制与大疱性类天疱疮180及层粘连蛋白332等自身抗体有关,发病机制尚待进一步研究。     

生物制剂和生物技术治疗天疱疮进展

天疱疮是一种慢性、复发性表皮内棘层松解性大疱性皮肤病,生物制剂和生物工程技术在天疱疮治疗中发挥一定作用。利妥昔单抗作为一种生物制剂,被国际专家共识推荐为天疱疮一线治疗方案。造血干细胞移植可重建患者的免疫系统,基于前期临床试验确切的疗效,造血干细胞移植已被应用于难治性天疱疮的治疗。调节性T细胞（regulatory T cells,Tregs）在维持自身免疫耐受和避免免疫反应过度损伤中发挥重要作用,应用Tregs过继回输治疗天疱疮前期试验疗效显著。本文综述了利妥昔单抗、干细胞技术以及Tregs过继治疗天疱疮的进展。     

抗CD20单克隆抗体治疗寻常型天疱疮研究进展

寻常型天疱疮是一种累及皮肤、黏膜,以泛发性水疱为特征的自身免疫性皮肤病,药物治疗寻常型天疱疮主要是通过抑制免疫系统,减少相关特异性抗体的产生,从而控制疾病的发展.目前糖皮质激素仍作为常规治疗的首选,而利妥昔单抗作为辅助治疗的一种抗CD20单克隆抗体,近年来已在寻常型天疱疮治疗中获得满意疗效.由于利妥昔单抗治疗可出现严重输液相关反应,增加感染风险,且价格昂贵、治疗累积时间长、易复发及耐药等缺点,临床上已减少了利妥昔单抗在寻常型天疱疮中的应用.新一代抗CD20单克隆抗体,克服了利妥昔单抗治疗的不良反应,有改善用药方式、减少治疗时间等优点,逐渐用于寻常型天疱疮治疗,新的研究成果给患者提供更多治疗选择.     

利妥昔单抗在天疱疮的应用

天疱疮是一种严重的自身免疫性大疱病,部分病例对传统治疗的疗效不佳.近几年临床研究发现,利妥昔单抗可明显提高天疱疮患者的临床治愈率,且可获得长期缓解,复发后再次治疗的安全性与临床缓解率仍较理想.利妥昔单抗不仅适用于重症难治性天疱疮,也有治疗轻至中度甚至儿童天疱疮的相关报道.目前已有较多关于利妥昔单抗不同单次治疗剂量或总剂量使天疱疮病情缓解的报道.利妥昔单抗可联合用药提高临床缓解率,其在安全剂量内仍会出现相关不良反应.     

利妥昔单抗治疗天疱疮六例并文献复习

目的：评价利妥昔单抗治疗天疱疮的疗效和安全性并对相关文献进行复习。方法：对采用利妥昔单抗治疗并随访至少1年的天疱疮患者的临床资料和国内外相关文献进行分析。结果：2013-2019年我院共应用利妥昔单抗治疗天疱疮6例，其中1例为初治患者，5例为病情复发的患者。剂量方案：1例采用淋巴瘤方案，5例采用类风湿关节炎方案。经过2~71个月随访，6例患者中停止治疗后完全缓解2例，治疗中完全缓解3例，出院后因肺部感染死亡1例。最新国内外指南和专家共识已经将利妥昔单抗列为天疱疮的一线治疗药物。结论：利妥昔单抗治疗顽固性天疱疮有效，可达到病情长期缓解的目的，但是需要警惕感染风险。     

抗CD20单克隆抗体在天疱疮治疗中的应用进展

天疱疮的传统治疗药物为糖皮质激素和免疫抑制剂,但副作用较大且易复发.利妥昔单抗是第一代人鼠嵌合型抗CD20的单克隆抗体,与B淋巴细胞跨膜抗原CD20结合后可通过多种机制将其清除.目前利妥昔单抗常用于中重度天疱疮患者的治疗,不仅有助于改善病情、减少复发,而且可以减少糖皮质激素用量从而减少激素相关不良反应.新一代人源化的抗...     

天疱疮的治疗现状

天疱疮是一种累及皮肤和黏膜的有潜在致命性的以水疱和溃疡为主要表现的自身免疫性疾病,系统应用糖皮质激素是其主要治疗方法,各种免疫抑制剂是其辅助治疗手段,近年来,新的治疗方法不断问世,其中包括静脉注射免疫球蛋白（IVIg）、血浆置换、免疫吸附、生物制剂利妥昔单抗（rituximab）等应用.     

生物制剂在大疱性类天疱疮治疗中的应用

近年大疱性类天疱疮(BP)新的治疗靶点不断出现,针对BP的致病性抗体、补体、辅助性T淋巴细胞2(Th2)及Th17轴细胞因子的新型生物制剂也陆续进入临床试验,其中靶向CD20的利妥昔单抗及靶向IgE的奥马珠单抗等已在临床中应用,并使部分难治性BP患者受益。本文综述BP生物制剂治疗策略相关的文献及临床试验,分析并讨论新型生物制剂在BP中的临床应用,为难治性BP的治疗提供新思路。     

小剂量利妥昔单抗联合激素治疗难治性大疱性类天疱疮1例

报告1例大疱性类天疱疮患者。该患者曾接受过大剂量糖皮质激素和多种免疫抑制剂的治疗,但是皮损控制不佳,治疗期间皮疹多次复发,同时伴有多种治疗相关并发症。后停用免疫抑制剂,予利妥昔单抗（每次500 mg,共2次,间隔2周）联合中剂量激素进行治疗,皮疹得到控制。在治疗过程中和治疗后未出现严重不良反应。因此,利妥昔单抗可以作为难治性大疱性类天疱疮的一种有效治疗手段。     

生物制剂治疗类天疱疮的研究进展

类天疱疮是一组自身免疫性表皮下大疱病,包括大疱性类天疱疮、黏膜类天疱疮、妊娠类天疱疮等.外用或系统应用糖皮质激素和免疫抑制剂是类天疱疮传统的治疗方法,长期使用易发生严重不良反应,近年来一些学者使用生物制剂治疗类天疱疮取得一定疗效,现将生物制剂治疗类天疱疮的研究进展进行综述.     

Dual diagnosis of Pemphigus and pemphigoid. Retrospective review of thirty cases in the literature.

BACKGROUND: Pemphigus and pemphigoid are two distinct groups of autoimmune blistering diseases. There are many reports of the simultaneous presence of clinical and serological features of both diseases in the same patient. OBJECTIVE: This study is a retrospective review of the present literature on reports of patients with features of both pemphigus and pemphigoid. We recommend that these patients be considered as having a dual diagnosis. METHODS: A review of the English language, peer-reviewed literature was conducted on patients described with features of pemphigus and pemphigoid. Available data on clinical profile, histology, immunopathology, treatment, follow-up and outcome were studied in 30 patients. They were divided into three groups: (1) bullous pemphigoid and pemphigus vulgaris, (2) mucous membrane or cicatricial pemphigoid and pemphigus vulgaris and (3) bullous pemphigoid and pemphigus foliaceus. RESULTS: In all three groups, most patients had a clinical phenotype resembling both diseases. In 17 patients with bullous pemphigoid and pemphigus vulgaris, 83% had a skin biopsy consistent with bullous pemphigoid, 70% had direct immunofluorescence studies typical of bullous pemphigoid and sera of 83% had antibodies typical of pemphigus vulgaris on indirect immunofluorescence. In 10 patients with mucous membrane or cicatricial pemphigoid and pemphigus vulgaris, a histology of mucous membrane pemphigoid was reported in 60% of the patients, direct immunofluorescence studies typical of mucous membrane pemphigoid were reported in 70% of the patients and in 80%, autoantibodies characteristic of pemphigus vulgaris were observed. In 3 patients with bullous pemphigoid and pemphigus foliaceus, the histologies were consistent with bullous pemphigoid, direct immunofluorescence was typical of pemphigus foliaceus and their sera had both autoantibodies. The majority of the 30 patients required long-term high-dose corticosteroids and immunosuppressive agents to control their disease. Three patients with bullous pemphigoid and pemphigus vulgaris (18%) died due to effects of prolonged immunosuppression. CONCLUSION: We characterize a group of patients who have clinical, histological and immunopathological features of bullous or mucous membrane or cicatricial pemphigoid with serological features of pemphigus. These patients did not achieve a prolonged clinical remission by conventional therapy. It is possible that early identification of these patients may improve their prognosis.     

Adjuvant high-dose intravenous gammaglobulin in the treatment of pemphigus and bullous pemphigoid: experience in six patients

At present, initial high-dose prednisone is the treatment of choice for patients with pemphigus and bullous pemphigoid. To reduce the risks associated with long-term corticosteroid treatment, other immunosuppressants are often given as steroid-sparing agents. Occasionally, the dose of steroids cannot be reduced. In this study, we report six patients with pemphigus vulgaris, pemphigus foliaceus and bullous pemphigoid, in whom the daily corticosteroid dose could only be tapered to acceptable, effective, maintenance levels following treatment with high-dose intravenous gammaglobulin.     

Functional involvement of urokinase-type plasminogen activator receptor in pemphigus acantholysis

Urokinase-type plasminogen activator (uPA) has been well documented in the development of pemphigus acantholysis. The function of its receptor (uPA-R) in pemphigus acantholysis has only recently attracted attention. Increased expression of uPA-R has been demonstrated in pemphigus vulgaris. In this study, we have further explored the functional involvement of uPA-R in pemphigus acantholysis. Our results show that uPA-R expression is significantly increased in acantholytic foci of pemphigus vulgaris and pemphigus foliaceus but not in bullous pemphigoid or normal skin specimens; the expression of uPA-R in cultured human keratinocytes is subjected to regulation by pemphigus vulgaris IgG but not by pemphigoid IgG or normal human IgG; furthermore, anti-uPA-R monoclonal antibody effectively inhibits pemphigus vulgaris IgG induced acantholysis in skin organ cultures. These data suggest that uPA-R may play an important role in the pathogenesis of pemphigus acantholysis.     

Efficacy of Dapsone in the Treatment of Pemphigus and Pemphigoid

Dapsone is a chemotherapeutic agent primarily used in treating leprosy, Pneumocystis jiroveci(previously carinii) pneumonia, and malaria. It is also used as an adjuvant in the treatment of pemphigus and pemphigoid. To assess the role of dapsone in the treatment of pemphigus and pemphigoid, a retrospective review of reports in the English-language literature was conducted. Information on the number of patients treated, their average age, prior therapies, indications for use, protocol (dose and interval) used, concomitant therapies, reported adverse effects, and clinical outcomes were analyzed. There were 35 case reports/series published describing the use of dapsone in a total of 427 patients. Data on 55 pemphigus patients were obtained from several case reports and some case series and one randomized controlled trial. Of these, 32 patients with pemphigus vulgaris and 14 patients with pemphigus foliaceus responded to dapsone. Data from 13 case series, each including at least five patients, accounted for 372 patients with pemphigoid. The overall response rates to dapsone, when given either alone or in combination with corticosteroids or immunosuppressive agents, were 84% in mucous membrane pemphigoid, and 81% in bullous pemphigoid. Hemolysis was the most common adverse effect observed. Dapsone is a promising and useful agent in patients with autoimmune mucocutaneous blistering diseases, especially in mucous membrane pemphigoid. It can be used as a corticosteroid-sparing agent. Therefore, its combined use with oral corticosteroids may be useful in pemphigus vulgaris and bullous pemphigoid. Adverse effects of dapsone are dose dependent and usually reversible. Hemolysis and concomitant anemia secondary to hemolysis are expected in most patients. In the opinion of the authors, dapsone is underutilized in the treatment of autoimmune mucocutaneous blistering diseases.     

Management of Bullous Pemphigoid

In 1953, Lever differentiated bullous pemphigoid from autoimmune pemphigus. The natural course of bullous pemphigoid is relatively benign, with a disease-related mortality rate of 24% compared with around 70% in pemphigus. In spite of the introduction of systemic corticosteroids, the mortality rates in bullous pemphigoid have generally not improved and vary between 0% and 40%. Higher doses of systemic corticosteroids seem to be associated with higher mortality rates, which led to the addition of corticosteroid-sparing agents to the treatment of bullous pemphigoid. However, many of these modalities are also accompanied by severe adverse effects and have not led to a significant decrease in the mortality rate. In recent years, there has been a move toward less toxic treatment options for a disease that is usually self-limited. A systematic review of the literature found that treatment with lower doses of systemic corticosteroids and potent topical corticosteroids is effective and accompanied by less serious adverse effects, including death. No benefit of the addition of plasmapheresis or azathioprine to systemic corticosteroids has been shown. The treatment of bullous pemphigoid with tetracyclines and niacinamide (nicotinamide) is effective and accompanied by less serious adverse effects. However, more randomized controlled trials are needed to confirm these results and to determine the best treatment for bullous pemphigoid.     

天疱疮282例和类天疱疮366例回顾性研究

目的 探讨天疱疮和类天疱疮诊断与治疗特点.方法 对2003-2007年天疱疮和类天疱疮648例患者的临床资料进行同顾性分析.结果 天疱疮平均发病年龄低于类天疱疮(P＜0.001),直接免疫荧光(DIF)确诊的175例天疱疮患者中IgG100%阳性,C3 92.0%阳性;类天疱疮223例患者中C399.1%阳性,IgG 51.12%阳性.两种大疱性疾病的诊断中,①天疱疮患者的临床诊断、病理检查与DIF三者一致率为68.8%.病理检查、DIF两者一致率为80.7%.②类天疱疮患者的临床诊断、病珲检查与DIF三者一致率为62.8%.病理检查、DIF两者一致率为78.1%.糖皮质激素是治疗两种疾病的主要手段,泼尼松(0.5～1.5)mg·kg-1·d-1可控制大部分患者病情.结论 临床和病理无法确诊的大疱疮和类天疱疮病例,DIF可以作为诊断该病的重要方法.在基层医院,临床怀疑天疱疮,DIF可主要检查IgG、C3,怀疑类天疱疮,可主要检查C3.     

Therapieoptimierung bei schweren bullösen Autoimmundermatosen

Autoimmune bullous diseases are a heterogeneous group of disorders that can be subdivided according to the level of split formation in the intraepidermal blistering pemphigus diseases and subepidermal bullous disorders, latter including pemphigoid diseases, epidermolysis bullosa acquisita (EBA), and dermatitis herpetiformis. In the majority of autoimmune bullous disorders, disease activity can be sufficiently controlled by systemic corticosteroids in combination with further immunsuppressants/-modulants such as dapsone, doxycycline, azathioprine, mycophenolate mofetil, or methotrexate. In contrast, in pemphigus, mucous membrane pemphigoid, and EBA, treatment is challenging and conventional immunosuppressive therapy induces clinical remission only in a minority of patients. Until recently, only cyclosphosphamide and high-dose intravenous immunoglobulin (IVIG) were available as potent second-line therapies. Meanwhile, immunoadsorption and the monoclonal anti-CD20 antibody rituximab have been established as further therapeutic options. The present review focuses on efficacy, adverse events, treatment protocols, and mechanisms of action of IVIG, immunoadsorption, and rituximab in the treatment of severe and/or refractory patients with bullous autoimmune diseases.     

Rituximab in autoimmune pemphigoid diseases: Indications,optimized regimens,and practice gaps

Rituximab is a monoclonal antibody targeting CD20 on B cells with proven efficacy for pemphigus vulgaris, now an FDA-approved indication. Other autoimmune bullous diseases can be challenging to treat and have significant associated morbidity and mortality, but data supporting the use of rituximab in pemphigoid group diseases remain limited. Although rituximab demonstrates efficacy for clinical improvement and remission in pemphigoid, concern for adverse events may also limit the use of this medication. We review the current evidence fo rthe use of rituximab in pemphigoid diseases, pertinent dosing schedules and laboratory monitoring, and the associated common and rare adverse events. Review of the literature to date not only supports consideration of rituximab for treatment of refractory pemphigoid group diseases but also reflects tolerability and an acceptable safety profile.     

Minocycline-induced hyperpigmentation in patients with pemphigus and pemphigoid

BACKGROUND: Immunosuppressive medications typically used to treat the immunobullous disorders pemphigus vulgaris, pemphigus foliaceous, and bullous pemphigoid can have serious adverse effects. The tetracycline family of antibiotic drugs has been shown to be effective in the treatment of these conditions with a more favorable side effect profile. Minocycline hydrochloride use has been associated with various forms of hyperpigmentation, and its incidence is well reported in acne vulgaris and rheumatoid arthritis. We examined a series of 9 patients treated with minocycline for pemphigus or pemphigoid, most of whom have developed cutaneous hyperpigmentation. OBSERVATIONS: Seven of 9 patients treated with minocycline, 50 mg daily (1 patient) or 100 mg twice daily (8 patients), for pemphigus vulgaris, pemphigus foliaceous, or bullous pemphigoid developed hyperpigmentation, which necessitated discontinuing therapy. Five of these patients had experienced notable clinical improvement of their immunobullous disease with minocycline therapy. The average duration of treatment was 8.2 months (range, 1-25 months). The second most common adverse effect in our group was oral candidiasis, which occurred in 2 patients. CONCLUSIONS: We found a favorable response to minocycline therapy in 5 of 9 patients. However, 7 patients developed localized hyperpigmentation as early as 1 month after starting medication use. This incidence of minocycline-induced hyperpigmentation is significantly higher in immunobullous disease than in acne vulgaris or rheumatoid arthritis. This increased incidence may be related to an increase in pigment deposition complexed with collagen during the remodeling process, subclinical inflammation, or glucocorticosteroid-induced skin fragility. The hyperpigmentation process was reversible, as most of our patients had fading of their pigmentation after minocycline cessation.