大疱性类天疱疮89例临床分析

目的 探讨大疱性类天疱疮患者的临床表现、实验室检查和治疗的特点。方法 回顾性分析89例大疱性类天疱疮患者的临床资料。结果 89例患者,男女之比1.07:1,平均发病年龄58岁。皮损除典型的水疱、红斑外,还有多形红斑、疱疹样皮炎样损害。33.7%的患者有口腔粘膜损害,6.7%的患者以口腔水疱、糜烂为首发症状。18%的患者尼氏征阳性。间接免疫荧光法检测阳性率74.4%,直接免疫荧光法检测阳性率94.9%.皮质类固醇以及皮质类固醇联合免疫抑制剂是治疗大疱性类天疱疮的主要手段,除接受冲击治疗的患者外,控制皮损所需的皮质类固醇剂量平均值为65.5mg(相当于泼尼松).结论 组织病理和免疫荧光检测是确诊的主要依据,控制皮损的皮质类固醇最大用量存在个体差异。     

23例中重度大疱性类天疱疮皮质类固醇激素用量分析

回顾分析23例中重度大疱性类天疱疮患者的临床资料,探讨中重度大疱性类天疱疮合理的治疗方案。结果：中度大疱性类天疱疮患者皮质类固醇激素控制量（相当于泼尼松剂量）为（57．43±11．58）mg／d,重度患者控制量为（87．26±14．52）mg／d。联合免疫抑制剂治疗,可减少皮质类固醇激素的用量,利于其较快减量,减少激素使用副作用的发生。     

天疱疮的治疗进展

天疱疮（pemphigus）是皮肤科较为常见的获得性表皮内大疱病，是一组较严重的慢性、复发性大疱性皮肤黏膜疾病。现已证实本病为一种自身免疫性疾病。应用皮质类固醇激素治疗，可使天疱疮预后大为改观。近年来皮质类固醇激素与免疫抑制剂联合应用以及在此基础上与血浆置换疗法，大剂量免疫球蛋白静脉滴注联合应用，使天疱疮得到有效控制，甚至长期缓解，使天疱疮的治愈成为可能。     

寻常型天疱疮联合冲击治疗后随访观察及疗效分析

近来年，我们应用大剂量皮质类固醇与环磷酰胺联合冲击疗法治疗了１１例重症泛发性寻常型天疱疮病人，并进行了随访观察，对该治疗方案的远期疗效作了初步分析。１临床资料寻常型天疱疮１１例，男６例，女５例。年龄２５～６９岁，平均５０．４岁，病程１年半～６年半，平均４１．５月；起病至冲击治疗时病程４月～３年，平均１６．７月；随访时间１年～６年，平均２年（２５个月）。２治疗方法２．１皮质类固醇冲击疗法：本组所有患者均采用大剂量地塞米松冲击疗法，地塞米松量为１００mg／d～１５０mg／d，连用３～５天。所有病人均只作１…     

环磷酰胺冲击联合皮质类固醇治疗寻常型天疱疮9例

应用大剂量环磷酰胺冲击联合常规剂量皮质类固醇治疗寻常型天疱疮９例。冲击方法：环磷酰胺８～１２ｍｇ·ｋｇ·ｄ，加入５％葡萄糖溶液中静滴，１～２小时滴完。每半月连续２天为一个疗程。结果经２个疗程（７例）或３个疗程（２例）冲击，环磷酰胺总量达２．０～３．６ｇ，达到临床痊愈。除胃肠反应外未见严重副作用。     

大剂量皮质类固醇激素联合环磷酰胺治疗重症天疱疮30例

采用大剂量皮质类固醇与环磷酰胺同时并用治疗重症天疱疮３０例。结果表明采用泼尼松相当量为６０ｍｇ／ｄ时控制病情者１２例，８０－１００ｍｇ／ｄ者８例，１２０－１５０ｍｇ／ｄ者６例，１８０ｍｇ／ｄ得１例，超过１８０ｍｇ／ｄ者３例。副作用包括血压升高、消化道出血、感染及精神症状，经上副作用经对症处理及皮质类固醇的迅速减量距减轻或消失。２６例患者近期痊愈，４例近期基本痊愈。结果证实联合用药具有疗效高。皮质类     

天疱疮治疗的某些近展

目前仍首选皮质类固醇治疗天疱疮,起始剂量常较大,一般在1月左右控制病情.天疱疮抗体可作为皮质类固醇用量及疗程的指标.其机理可能与抑制天疱疮抗体及纤溶酶原激活剂(PA)的产生,诱导PA抑制因子形成有关.但皮质类固醇治疗剂量大,疗程长,副作用多.血浆交换单独应用常可引起反跳现象,与皮质类固醇合用能更快地降低血中抗体滴度.免疫抑制剂亦需与激素合用.肝素治疗有一定疗效,但报道尚少.酶抑制剂治疗近年来报道较多,但临床上应用尚待进一步观察.     

大剂量皮质类固醇并环磷酰胺治疗重症天疱疮1例

大剂量皮质类固醇与免疫抑制剂同时并用(CSI)治疗天疱疮(PEM)可有效地降低该病的死亡率,并使近半数的患者停药缓解[1].我们在临床上采用CSI治疗了1例重症PEM患者,获得满意的疗效,现报告如下.     

静脉内大剂量滴注丙种球蛋白辅助治疗6例天疱疮、大疱型类天疱疮

目前,早期大量皮质类固醇激素是治疗天疱疮、类天疱疮的首选方法。但长期大剂量地使用激素可致严重副作用。近期发现,静脉内大剂量滴注丙种球蛋白有类激素作用。该文报道了6例应用此疗法辅助治疗的天疱疮、大疱型类天疱疮的有关情况。     

大剂量皮质类固醇冲击治疗难治性寻常型天疱疮三例

尽管常规大剂量皮质类固醇与免疫抑制剂联合可控制重症天疱疮的病情,但仍有少数病例反应欠佳。近来我们对３例平均泼尼松用量超过１８０ｍｇ／ｄ仍不能控制病情的天疱疮患者采用超大剂量皮质激素冲击疗法,获得满意疗效,报道如下。一、临床资料３例患者均为男性,年龄４２～５０岁,病期６～７个月,入院前经临床诊断为天疱疮,给予泼尼松３０～８０ｍｇ／ｄ治疗４～６个月不能控制病情。体检:一般情况尚可,各系统检查无异常发现;３例患者的四肢、躯干均布满大小不等的松弛性水疱,尼氏征阳性,其中２例胸背部受累较重,１例颈、腋窝及腹股沟等皱褶…     

Steroid sparing effect of intravenous immunoglobulin therapy in patients with pemphigus foliaceus

Pemphigus foliaceus (PF) is a rare autoimmune cutaneous blistering disease, with only skin involvement. Systemic corticosteroids and immunosuppressive agents are the mainstay of therapy. However, some patients develop multiple side effects to systemic corticosteroids, when they are used in high doses over prolonged periods. In some patients, immunosuppressive agents are not effective or contraindicated. In such patients, alternative treatment modalities are needed. The purpose of this study is to demonstrate the use of intravenous immunoglobulin (IVIg) therapy in seven patients with severe PF, who were steroid-dependent. The following information was recorded in each patient, before and after IVIg therapy initiation: total dose and total duration of prednisone therapy, and number of relapses. In addition, the highest dose and side effects of prednisone therapy, and duration of observation were documented. After the initiation of IVIg treatment, doses of systemic corticosteroids were gradually reduced and eventually discontinued over a mean period of 2.8 months. Thereafter, IVIg was used as monotherapy. A statistically significant difference was noted between pre-IVIg therapy and after the initiation of IVIg therapy in the total dose (p = 0.005), and total duration of prednisone treatment (p = 0.02), and the number of relapses (p = 0.002). In all seven patients, IVIg produced an effective clinical response and demonstrated a steroid-sparing effect. In patients with PF, who are steroid-dependent and in whom use of conventional immunosuppressive agents is contraindicated, IVIg appears a safe and effective agent to induce and maintain a prolonged clinical remission.     

Treatment of severe pemphigus with protein A immunoadsorption, rituximab and intravenous immunoglobulins

BACKGROUND: Pemphigus is a life-threatening autoimmune blistering disease usually treated with high-dose corticosteroids and other immunosuppressants. However, this regimen may prove inadequate in severe cases and cause dangerous side-effects. While protein A immunoadsorption (PAIA) induces a rapid remission in severe pemphigus, the disease usually recurs once the treatment is stopped. In contrast, anti-CD20 antibody rituximab has a delayed onset of action but may lead to a long-term remission of pemphigus. OBJECTIVE: To develop a treatment protocol combining the rapid remission induced by PAIA with the positive long-term effects of rituximab. PATIENTS AND METHODS: Five patients with pemphigus vulgaris and two patients with pemphigus foliaceus were treated with a combination of PAIA, rituximab and conventional immunosuppressants. Patients who failed to respond to this therapy subsequently received intravenous immunoglobulins (IVIg). RESULTS: All seven patients showed a sharp decline of circulating autoantibody levels and rapid improvement of cutaneous and mucosal lesions within 4 weeks of therapy. Long-term remission was induced in three patients and one further patient showed a partial improvement of his disease. The three remaining patients who could not be weaned off PAIA and remained resistant to rituximab treatment showed a good response to IVIg therapy. CONCLUSION: The combination of PAIA and rituximab induces a rapid and durable remission in a subset of patients with severe pemphigus. IVIg therapy appears to be a good treatment option for rituximab nonresponders.     

Intravenous immunoglobulin therapy in the treatment of patients with pemphigus vulgaris unresponsive to conventional immunosuppressive treatment

BACKGROUND: Severe pemphigus vulgaris (PV) is conventionally treated with high-dose oral prednisone, usually in combination with an immunosuppressive agent (ISA). Some patients experience significant side effects, which are sometimes fatal, from prolonged immunosuppression. OBJECTIVE: Intravenous immunoglobulin (IVIg) was administered to 21 patients with severe cutaneous and mucosal PV who had not responded to the prolonged use of oral prednisone and multiple ISAs. METHODS: A preliminary dose-determination study tested 7 additional volunteers to ascertain the optimal IVIg dose of 2 g/kg per cycle. Parameters to assess clinical outcome were recorded before and after IVIg therapy. Variables tested were highest dose, total dose, and duration of prednisone and ISAs, their side effects, frequency of recurrence and relapse, duration of IVIg therapy, clinical response, induction and duration of remission, number of hospitalizations, total days of hospital stay, and quality of life. RESULTS: Use of IVIg monotherapy resulted in effective control of disease and produced a sustained remission in the 21 patients. The patients became free of lesions and remained so after finishing IVIg therapy. IVIg had a steroid-sparing effect and produced a high quality of life. Serious side effects from the use of IVIg were not observed. IVIg needs to be gradually withdrawn after achievement of clinical control. CONCLUSION: In patients with PV who do not respond to conventional immunosuppressants, IVIg appears to be an effective treatment alternative. Its early use is of significant benefit in patients who may experience life-threatening complications from immunosuppression. IVIg is effective as monotherapy.     

Treatment of pemphigus with intravenous immunoglobulin

BACKGROUND: Intravenous immunoglobulin (IVIg) has recently been advocated as a treatment for pemphigus, but the results of published studies are in conflict. This study was conducted to re-examine the effectiveness of IVIg for the immediate control of active disease and to study the mechanisms of its action. METHODS: Six patients with active pemphigus vulgaris unresponsive to conventional therapy with high doses of corticosteroids were treated with IVIg (400 mg/kg per day for 5 days) and concurrently given cyclophosphamide (100-150 mg/d). The primary end points were healing of skin lesions and changes in the level of intercellular antibodies and steroid dose. RESULTS: New lesions ceased to form within 1 week of initiating IVIg therapy, and within 2 weeks the extent of existing skin lesions was reduced by 80% or more in all but one patient. Within 3 weeks, steroid doses were reduced by an average of 41%. The improvement was more rapid than that in patients previously treated with similar doses of steroids and cytotoxic agents at the same institution. Clinical improvement was associated with a rapid decline in pemphigus antibodies whose levels decreased by 72% within 1 week of initiation of IVIg therapy. The rapidity and extent of this decline were similar to those achieved with intensive plasmapheresis. The decline was not due to blocking the synthesis or the immunologic activity of intercellular antibodies by IVIg, suggesting that it resulted from increased immunoglobulin catabolism. CONCLUSIONS: These results indicate that IVIg can effectively and rapidly control active pemphigus unresponsive to conventional therapy and suggest that the mechanism of its action is decreasing serum levels of intercellular antibodies.     

Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients with pemphigus vulgaris

BACKGROUND: Pemphigus vulgaris (PV) is a rare, potentially fatal autoimmune mucocutaneous blistering disease. The prolonged use of systemic corticosteroids, though clinically effective in high doses, can result in multiple debilitating adverse effects. Immunosuppressive agents, used as adjuvants and as corticosteroid-sparing agents, are not effective in all patients and are contraindicated in some. Therefore, alternative treatment modalities are needed to provide effective control of PV in such patients. OBJECTIVE: To demonstrate the corticosteroid-sparing effect of intravenous immunoglobulin (IVIg) therapy in patients with moderate to severe PV. DESIGN: A retrospective analysis in a cohort of 15 patients with moderate to severe PV who were treated with IVIg therapy. All 15 patients were corticosteroid dependent, and the use of other systemic conventional immunosuppressive agents was contraindicated. The patients were followed up over a mean period of 6.2 years. SETTING: Ambulatory tertiary medical care facility of a university-affiliated hospital. INTERVENTION: All 15 patients received an IVIg dose of 1 to 2 mg/kg per cycle. MAIN OUTCOME MEASURES: The following information was documented in each of the 15 patients before and after the initiation of IVIg therapy: total dosage and total duration of prednisone therapy and number of relapses. Also, the highest dosage and adverse effects of prednisone therapy, as well as the total duration of observation, were recorded. RESULTS: All 15 patients had a satisfactory clinical response to IVIg therapy. The use of systemic prednisone was gradually discontinued over a mean period of 4.3 months. A statistically significant difference was noted in the total dose of prednisone (P =.004), total duration of prednisone therapy (P =.003), and number of relapses (P<.001) before and after the initiation of IVIg therapy. CONCLUSIONS: Intravenous immunoglobulin therapy has a demonstrable corticosteroid-sparing effect. It is a safe and effective alternative treatment modality in patients with PV who are dependent on systemic corticosteroids or who develop significant adverse effects as a result of their use.     

Treatment of pemphigus vulgaris with pulse intravenous cyclophosphamide.

BACKGROUND--Although corticosteroids have dramatically altered the prognosis in pemphigus vulgaris, morbidity and mortality from systemic corticosteroid side effects remains high. While immunosuppressive agents have been successfully used in pemphigus vulgaris, there is a high incidence of side effects with these agents as well. Particularly bothersome are reports of increased risk of malignancy with long-term use of immunosuppressive agents. For these reasons, we used a protocol that includes low-dose oral cyclophosphamide coupled with pulse intravenous cyclophosphamide in two patients with recalcitrant pemphigus vulgaris. OBSERVATIONS--Both patients responded well to monthly doses of intravenous cyclophosphamide with rapid decrease in the frequency and severity of blistering, resulting in resolution of their disease after 7 and 10 months, respectively. CONCLUSIONS--Pulse doses of immunosuppressive agents appear to be successful in the treatment of pemphigus vulgaris. High-dose steroid therapy can be tapered with the use of this treatment. Because monthly intravenous doses of cyclophosphamide lead to a substantially reduced cumulative dose, when compared with standard oral regimens, the risk of developing malignancy may also be reduced. Further studies using larger groups of patients are needed to evaluate the efficacy of pulse intravenous cyclophosphamide in pemphigus vulgaris. Long-term follow up will be necessary to compare the incidence of malignancy in patients receiving pulse doses of immunosuppressive agents with that in patients receiving continuous oral treatment.     

Role of intravenous immunoglobulin in the treatment of bullous pemphigoid: analysis of current data

BACKGROUND: Conventional therapy of severe bullous pemphigoid (BP) relies on the use of high-dose systemic corticosteroids with or without adjuvants, notably immunosuppressive agents. This approach can result in debilitating and potentially fatal side effects, hence the need to explore alternative therapies. Intravenous immunoglobulin (IVIg) therapy is emerging as one possibility. OBJECTIVE: Our purpose was to determine whether any preliminary conclusion can be drawn about the potential for the use of IVIg to treat patients with severe BP. METHODS: A literature search was done to identify reports, in English-language peer-reviewed journals, on the use of IVIg to treat patients with BP. Reports were examined for information on disease duration, severity, therapies used before and after IVIg, dose and frequency of IVIg administration, and its immediate and long-term effects. RESULTS: Data on treatment of 17 patients indicated that 12 patients (70%) experienced a beneficial clinical response to IVIg. In 5 patients (30%) no clinical benefit was observed. A minimum dose of 2 g/kg per cycle at monthly intervals for 3 months has been the most common approach. However, this should not be perceived as a "standard dose" at the present time. In some patients the use of IVIg appears to permit a systemic corticosteroid-sparing effect. Longer use has achieved sustained clinical remission in some patients. Lack of response was observed in patients who received low-dose IVIg or who received a single infusion only. Minimal side effects in the form of headaches and nausea and vomiting were observed in some patients. CONCLUSION: The present experience consists only of open uncontrolled trials in a few patients and does not allow for definitive conclusions. However, at this time IVIg appears to be a promising agent for the treatment of BP, especially for patients who do not respond to conventional therapy. Adequate doses for longer periods may be required to induce and maintain sustained clinical remissions. Large-scale controlled studies with defined entry criteria, objectives, end points, and long-term follow-up are necessary to determine the specific role of IVIg in the overall management of BP.     

Intravenous immunoglobulin therapy for patients with pemphigus foliaceus unresponsive to conventional therapy.

BACKGROUND: Pemphigus foliaceus (PF) is a chronic autoimmune blistering skin disease that is commonly treated with oral corticosteroids and immunosuppressive therapy. In some patients, PF can be refractory to treatment and the resultant side effects of prolonged immune suppression can be potentially fatal. Alternative therapies are needed. OBJECTIVE: The purpose of this study is to report treatment outcomes with IVIg therapy in 11 patients with severe PF refractory to prednisone and other immunosuppressive therapy. METHODS: Selection criteria included documentation of a biopsy and immunopathology in 11 patients who were resistant to treatment or experienced side effects to conventional therapy. IVIg was administered according to a defined protocol. The parameters used to assess clinical response to IVIg included time observed for effective control of disease, duration of IVIg maintenance therapy, total duration of IVIg, number of IVIg cycles, systemic drug therapy, and the frequency of recurrences and relapses. The pre-IVIg and post-IVIg data were statistically analyzed by means of the SAS UNIVARIATE and 2-sided Wilcoxon sign rank and sign tests. RESULTS: All patients had an effective clinical response and remained in clinical remission for a mean period of 18.6 months after discontinuation of IVIg therapy. Serious side effects from IVIg use were not observed. CONCLUSION: IVIg therapy appears to have potential as a biologic alternative agent in inducing and maintaining clinical remissions in patients with PF who are resistant to more standard conventional treatment. IVIg is effective as monotherapy and may be needed for a period of several months to achieve a long-term clinical remission.     

The role of IVIg treatment in severe pemphigus vulgaris

BACKGROUND: High-dose intravenous immunoglobulin (IVIg) has become a part of the treatment armentarium in pemphigus vulgaris (PV). Some consider IVIg as an adjuvant steroid sparing agent in PV, while others as disease modifying that can be used as monotherapy. METHODS: We report our experience with a series of 12 PV patients with severe disease treated with IVIg as an adjuvant therapy. RESULTS: Ten of 12 patients (83%) showed response to six cycles of IVIg, six (50%) having complete remission and four (33%) having a partial response. This response rate is concordant with previous reports. The therapy was well tolerated. In all 12 patients, treatment with IVIg allowed a gradual reduction of prednisone dose compared with baseline levels. CONCLUSION: IVIg treatment was beneficial as a steroid sparing agent in our series of patients with severe PV.     

The role of therapeutic plasma exchange in pemphigus vulgaris

Background The treatment of pemphigus, an autoimmune bullous disease, is based on the combination of corticosteroids and adjuvant therapies, such as immunosuppressive drugs, anti‐inflammatory drugs and immunomodulatory procedures, such as intravenous immunoglobulin and therapeutic plasma exchange (TPE). Objective This study aims to assess our experience with TPE as a steroid‐sparing modality in moderate and severe intractable pemphigus patients. Methods A retrospective evaluation for all intractable pemphigus patients treated by TPE in a university‐affiliated tertiary referral medical centre between the years 1998 and 2008. Treatment protocol included three TPE treatments weekly for 1–3 months, combined with monthly pulse therapy of dexamethasone and/or cyclophosphamide. Maintenance therapy was based on once/bi weekly TPE treatments or monthly intravenous immunoglobulin. Results Seven patients were included in the study, four with severe pemphigus vulgaris and three with moderate disease. Six of the seven patients responded to TPE: Four patients (57%) achieved complete remission and two patients (28%) achieved partial remission on minimal therapy. Mild adverse effects related to TPE were observed in two patients and included dizziness and mild headache. Conclusion TPE is a well‐tolerated effective steroid‐sparing agent in recalcitrant pemphigus patients.