重症寻常型天疱疮24例分析

目的探讨重症寻常型天疱疮的的临床特点、实验室特点以及合理的治疗方案。方法回顾分析24例重症寻常型天疱疮的临床资料。结果24例重症寻常型天疱疮患者中男女之比2.43:1,平均44.63岁,职业以农民和工人为主,患者均有躯干部受累,黏膜受累75%,尼氏征阳性19例,入院时并发症特别是感染发生率高,创面细菌培养阳性率41.7%,血培养阳性率25%,激素早期联合免疫抑制剂治疗取得满意疗效,总有效率为87.5%。结论本病多合并感染,激素联合免疫抑制剂是治疗重症寻常型天疱疮的首选治疗方案。     

自身免疫性大疱性皮肤病的临床研究

目的:探讨各种自身免疫性大疱病的临床特征和合适的治疗方法。方法:对135例自身免疫性大疱病进行回顾性分析。结果:天疱疮、类天疱疮和线状IgA大疱性皮病是自身免疫性大疱病中常见的3种疾病,分别易累及中年人、老年人和儿童。寻常型天疱疮伴发口腔黏膜受累多见(73.1%)。在病情得到控制的患者中,重症患者糖皮质激素用量泼尼松(78.7±23.9)mg/d显著高于轻、中症患者泼尼松(45.8±19.8)mg/d和(59.4±20.8)mg/d,P<0.001;寻常型、落叶型天疱疮糖皮质激素用量(66.2±24.3)mg/d、(73.0±14.9)mg/d显著高于红斑型(49.1±21.8)mg/d,P<0.05;寻常型天疱疮痊愈率(24.2%)显著低于红斑型(63.6%),P<0.05。接受相近剂量的糖皮质激素治疗,类天疱疮痊愈率(56.1%)明显高于天疱疮(35.5%),P<0.05。结论:应根据不同情况确定糖皮质激素合适的初始剂量。对于线状IgA大疱性皮病和IgA型大疱性系统性红斑狼疮,氨苯砜是首选治疗药物。     

寻常型天疱疮53例临床分析

通过对1996～2002年本院53例寻常型天疱疮住院患者的临床资料回顾性分析,以探讨寻常型天疱疮临床、组织病理、免疫病理和治疗方案及预后。结果28例单用糖皮质激素(简称激素)治疗,按轻、中、重三组激素控制剂量分别相当于泼尼松(60.0±19.6)mgd、(85.6±19.8)mgd、(112.5±39.4)mgd,平均(98.2±48.8)mgd。三组之间有统计学差异。18例患者激素联合免疫抑制剂治疗,激素控制剂量相当于泼尼松(102.1±41.4)mgd。与单用激素组无统计学差异。5例采用激素冲击疗法。2例患者死于激素副作用,死亡率为3.9%。寻常型天疱疮治疗首选激素,若控制不满意可用激素冲击疗法或联合免疫抑制剂。寻常型天疱疮预后较好,死亡率较低。     

联合冲击治疗天疱疮与常规疗法的比较分析

我们应用地塞米松与环磷酰胺（CTX）联合冲击疗法治疗8例寻常型天疱疮，并初步与常规方法治疗的8例寻常型天疱疮病人进行了疗效比较，根据治疗结果观察比较，我们认为与常规方法治疗寻常型天疱疮相比，皮质类固醇激素与CTX联合冲击疗法具有起效快，病情控制迅速，激素使用量相对较小、时间较短、激素副作用发生较少的优点，值得临床推广应用，尤其适用于病情较重的寻常型天疱疮。     

大剂量静脉注射免疫球蛋白治疗重症皮肤病的疗效观察

目的探讨大剂量静脉注射免疫球蛋白(IVIg)治疗寻常型天疱疮、系统性红斑狼疮、重症药物疹和重症过敏性紫癜等重症皮肤病的临床疗效和不良反应。方法对4例重症皮肤病患者采用免疫球蛋白0.4 g/(kg·d)静脉滴注,每个疗程时间均为连续(3~5)d。结果大剂量IVIg对这4例重症皮肤病均有疗效,无不良反应。结论大剂量IVIg治疗对某些重症皮肤病安全有效。     

大疱及疱疹性皮肤病

20053252自身免疫性大疱性皮肤病的临床研究/王培光(安徽医大一附院),杨森,林达…∥中国麻风皮肤病杂志.-2005,21(3).-163~165通过对135例自身免疫性大疱病进行回顾分析显示,天疱疮、类天疱疮和线状IgA大疱性皮病是自身免疫性大疱病中常见的3种疾病,分别累及中年人、老年人和儿童。寻常型天疱疮伴发口腔黏膜受累多见(73.1%)。在病情得到控制的患者中,重症患者糖皮质激素用量泼尼松显著高于轻、中症患者泼尼松(P<0.01);寻常型、落叶型天疱疮糖皮质激素用量显著高于红斑型(P<0.05);寻常型天疱疮痊愈率(24.2%)显著低于红斑型(63.6%,P<0.05)。…     

寻常型天疱疮患者的护理体会

寻常型天疱疮是以表皮内棘细胞松解为特点的大疱性皮肤病,好发于中青年,无性别年龄差异,发病机制与自身免疫有关。其病程长,易感染,性质严重,治疗中除早期足量的皮质类固醇激素、免疫抑制剂、支持疗法外,皮损的护理也十分重要,护理不当仍可危及生命。我科收治了1例重症寻常型天疱疮患者,经精心治疗和护理,住院17天,病情好转出院。     

天疱疮治疗的研究进展

天疱疮是一种罕见且可危及生命的自身免疫性大疱性皮肤病。依据临床及病理特征,天疱疮分为寻常型、增殖型、落叶型及红斑型四种类型。天疱疮治疗目的是尽快控制病情、修复松解的表皮,减少或延缓复发、预防感染、减少药物副作用、提高患者生活质量。对于病情轻中度的患者,外用或系统应用中强效糖皮质激素仍是首选,联合应用免疫抑制剂或生物靶向制剂治疗难治性天疱疮有望取得满意疗效,对于不能耐受激素和免疫抑制剂等治疗抵抗的患者,造血干细胞移植带来了新的希望。本文旨在归纳总结出针对不同病情、患者情况的个性化方案。     

PDCA及认知行为疗法在寻常型天疱疮治疗中的应用

目的应用戴明环(Plan-Do-Check-Action,PDCA)及认知行为疗法对寻常型天疱疮患者进行全面质量管理并进行评价。方法对入选的寻常型天疱疮患者应用认知行为疗法进行护理,并用PDCA质量管理办法制定监测计划与方案,解决治疗过程中新出现问题和上一循环遗留问题。结果出院后6个月和1年时,观察组与对照组患者比较,依从性(χ~2=9.32和7.94)、心理状况(χ~2=9.32和7.94)、不良反应(χ~2=12.00和12.27)及复发率(χ~2=11.89和7.94),差异有统计学意义(P均0.05)。结论采用PDCA联合认知行为疗法实施全面质量持续改进,可增加寻常型天疱疮患者的依从性,并能改善患者的心理状态和减少复发率。     

10例重型天疱疮皮质类固醇激素用量分析

一般资料 男6例,女4例,年龄35—65岁。寻常型天疱疮6例,落叶型天疱疮1例,红斑型天疱疮3例。皮损面积大于50％,诊断根据临床表现、组织病理及皮损直接免疫荧光检查确定。8例曾在入院前给予强的松等不规则治疗。 治疗与疗效 疗效判断标准:病情控制为皮损全部愈合,无水庖发生,尼氏征阴性,病情缓解为皮损大部分愈合,残存小片糜烂面,无或有少许新水疱发生。10例均给予皮质类固醇激素(以下简称激素)治疗。强的松首次用量(或相当于强的松等效剂量的地塞米松,甲基强     

Improved protocol for treatment of pemphigus vulgaris with protein A immunoadsorption

BACKGROUND: Pemphigus vulgaris is a life-threatening autoimmune blistering skin disease, usually treated with high-dose corticosteroids in combination with other immunosuppressants. However, this regimen may prove inadequate in severe cases and can cause dangerous side-effects. We have recently reported protein A immunoadsorption (PAIA) to be an effective adjuvant treatment for induction of remission in severe pemphigus. However, in a significant number of cases, the disease rapidly recurred once PAIA and immunosuppressive medication were tapered. AIMS: The aim of the present study was to develop a PAIA-based therapeutic regimen that would result in a more prolonged remission of pemphigus. METHODS: Nine patients with pemphigus vulgaris were treated with a modified protocol characterized by a combination of PAIA with a higher initial dose of systemic methylprednisolone (2 mg/kg). In addition, azathioprine or mycophenolate mofetil was administered as a steroid-sparing agent. RESULTS: In all nine patients treated with this regimen, we observed a sharp decline of circulating autoantibody levels and dramatic improvement of cutaneous and mucosal lesions within 4 weeks of therapy. The patients remained free of clinical disease for up to 26 months after PAIA treatment was discontinued. CONCLUSION: The improved treatment protocol appears to combine highly effective induction of clinical remission in severe or treatment-resistant pemphigus with a prolonged subsequent symptom-free interval.     

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.     

Treatment of severe pemphigus with rituximab: report of 12 cases and a review of the literature

BACKGROUND: Treatment of pemphigus vulgaris can be challenging. Systemic steroids associated with other immunosuppressant agents are the mainstay of therapy and have dramatically reduced morbidity and mortality from pemphigus vulgaris. In some patients, however, these agents are not able to control the disease or have severe adverse effects. Rituximab (MabThera; Roche, Basel, Switzerland), a chimeric monoclonal anti-CD20 antibody, induces depletion of B cells in vivo and has shown efficacy in patients with refractory antibody-mediated autoimmune disorders. We report 10 cases of pemphigus vulgaris and 2 cases of pemphigus foliaceous treated with rituximab--to our knowledge the largest series of patients so far--and review the existing literature on the topic. OBSERVATION: The 12 patients were selected for treatment with the anti-CD20 antibody. Rituximab was administered intravenously at a dosage of 375 mg/m(2) once weekly for 4 weeks. The treatment was well tolerated, and all 12 patients showed a good clinical response during an 18-month follow-up period, along with a consensual decline of the serum antidesmoglein titers. No infectious complications were observed. CONCLUSIONS: Rituximab is able to induce a prolonged clinical remission in patients with both pemphigus vulgaris and pemphigus foliaceous after a single course of 4 treatments. The preliminary experiences worldwide make rituximab a promising therapeutic option for patients with autoimmune diseases. The high costs and the limited knowledge of long-term adverse effects, however, limit its use to selected patients with treatment-resistant or life-threatening disease.     

Pemphigus vulgaris: a review of treatment over a 19-year period

BACKGROUND: Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes with a high mortality if left untreated. OBJECTIVE: We present a retrospective analysis of 159 patients with pemphigus vulgaris and pemphigus vegetans who were admitted to the Department of Dermatology and Venereology, Zagreb University Hospital Center (Zagreb, Croatia) from 1980 to 1998. RESULTS: Female to male ratio was approximately 2:1. The mean age was 53 years. During the war years in Croatia (1991-95) we noticed a low incidence of pemphigus vulgaris, and from 1996 to 1998 the incidence almost doubled. Diagnosis was based on histopathology [showing typical pemphigus vulgaris changes in 156 (98%) patients], indirect immunofluorescence [positive in 122 (77%) patients], direct immunofluorescence [positive in 141 (89%) patients], and blister smear cytology (Tzanck test) [positive in 115 (72%) patients]. High dosages of prednisone (100-150 mg) were given to 129 patients, which was combined with azathioprine. Patients with refractory pemphigus vulgaris were treated with intramuscular gold (14 patients) and plasmapheresis (five patients). All patients were treated with local ointments. The prolonged use of high doses of corticosteroids and immunosuppressants caused several complications, in particular, steroid diabetes (37 patients), skin infections (26 patients), arterial hypertension (23 patients), cardiorespiratory diseases (22 patients), sepsis (nine patients), etc. During the hospital treatment, 14 patients died, 10 during 1980-89 and only four during the 1990-98 period. The main causes of death were cardiorespiratory failure (six patients) and sepsis (five patients). CONCLUSIONS: Although pemphigus vulgaris is still a life-threatening disease, today it can be successfully treated with a combination of immunosuppressive agents. Early diagnosis and treatment of pemphigus vulgaris allow a better prognosis with lower mortality rates.     

Mycophenolate mofetil: A new therapeutic option in the treatment of blistering autoimmune diseases

Background: Mycophenolate mofetil (MMF), an ester of mycophenolic acid (MPA), was approved by the Food and Drug Administration in 1995 and is currently primarily indicated for the prophylaxis of rejection in renal transplant patients. The drug seems also to be of value in the treatment of psoriasis and rheumatic arthritis. Recently there have been 6 reported cases of successful treatment of blistering autoimmune diseases with MMF in combination with high dose prednisone therapy. Objective: On the basis of these reports we administered this new treatment regimen to several patients with blistering autoimmune diseases. Besides using a combination of MMF and high-dose prednisone we wanted to evaluate whether MMF monotherapy is also effective in the treatment of blistering autoimmune diseases. Methods: We administered MMF to 5 patients who had severe pemphigus vulgaris or bullous pemphigoid. Two patients received MMF in combination with high-dose prednisone therapy and 3 patients received MMF monotherapy. To our knowledge, this is the first report of successful treatment of pemphigus vulgaris and bullous pemphigoid with MMF monotherapy. Results: All patients were completely free of symptoms within 8 to 11 weeks of therapy. Patients who had received MMF monotherapy responded as well to treatment as those who received a combination of MMF and high-dose prednisone. Conclusion: Our experiences strongly suggest that MMF monotherapy may be effective for patients even with severe pemphigus vulgaris and bullous pemphigoid. In addition, MMF monotherapy, at least over the short term, offers the advantage of fewer side effects in comparison to immunosuppressive combination therapy and was well tolerated by our patients. (J Am Acad Dermatol 1999;40:957-60.)     

Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil

BACKGROUND: Mycophenolate mofetil is increasingly being used as a corticosteroid-sparing agent in immunosuppressive regimens. OBJECTIVE: To elucidate the effectiveness of mycophenolate as adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. DESIGN: Historical prospective study. SETTING: University hospital. PATIENTS: The study included 42 consecutive patients with pemphigus (31 with pemphigus vulgaris and 11 with pemphigus foliaceus) who had relapses during prednisone taper or had clinically significant adverse effects from previous drug therapy. RESULTS: Remission was achieved in 22 (71%) and 5 (45%) of patients with pemphigus vulgaris and pemphigus foliaceus, respectively. Partial remission was achieved in 1 (3%) and 4 (36%), respectively. The median time to achieve complete remission was 9 months (range, 1-13 months). The treatment was administered for a median of 22 months, and the median follow-up period was 22 months. Seventy-seven percent of patients had no adverse effect. Two patients had side effects severe enough to necessitate discontinuation of treatment, one because of symptomatic but reversible neutropenia and the other because of nausea. CONCLUSION: Mycophenolate is an effective and safe adjuvant in the treatment of both pemphigus vulgaris and pemphigus foliaceus.     

Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus

BACKGROUND: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are autoimmune blistering skin diseases usually treated with high-dose systemic corticosteroids and other immunosuppressants that may cause severe side-effects. Plasmapheresis also has been demonstrated to be of benefit in the treatment of pemphigus. In contrast to plasmapheresis, staphylococcal protein A immunoadsorption (PA-IA) specifically removes immunoglobulin from the circulation, allows treatment of larger plasma volumes, and does not require the substitution of plasma components. OBJECTIVES: To determine the effectiveness and side-effects of PA-IA in patients with severe pemphigus. METHODS: Five patients with severe pemphigus (PV, n = 4; PF, n = 1) were treated by PA-IA. Three of these patients had been refractory to various treatment regimens. In addition to PA-IA, methylprednisolone, 0.5 mg x kg-1 body weight day-1 was given initially and subsequently tapered. RESULTS: In all patients, a dramatic clinical improvement was seen within 2 weeks after initiation of therapy. Patients were free of lesions after 3, 4, 4, 10 and 21 weeks of treatment, respectively. Concurrently, autoantibody levels decreased rapidly. CONCLUSIONS: PA-IA is a rational, effective, and safe adjuvant therapy for severe pemphigus and warrants wider use for this indication. A controlled study should compare side-effects and effectiveness of PA-IA with other treatment options for pemphigus.     

Immunoablative high-dose cyclophosphamide without stem cell rescue in pemphigus foliaceus

BACKGROUND: There is growing evidence that immunoablative high-dose cyclophosphamide without stem cell rescue is effective and safe in patients with refractory autoimmune diseases such as paraneoplastic pemphigus, systemic lupus erythematosus, aplastic anemia, and more recently pemphigus vulgaris. METHODS: We report a 51-year-old patient with severe pemphigus foliaceus, which was recalcitrant to multiple medical regimes. The patient presented with multiple thick hyperpigmented and scaly, ill-defined plaques on the face. In addition, she had multiple superficial erosions and crusts on her scalp, thorax, upper and lower extremities. The patient also had a few discrete intact flaccid bullae. A skin biopsy and direct immunofluorescence was consistent with pemphigus foliaceus. The patient's circulating pemphigus autoantibodies were present at a titer of 1 : 2560. The patient received immunoablative high-dose cyclophosphamide (50 mg/kg/day) for 4 consecutive days, and tolerated the regime well. RESULTS: Approximately 3 months after therapy, the skin lesions had healed and her prednisone, which had been as high as 80 mg daily, was tapered to 30 mg daily. In addition, her circulating autoantibodies decreased after treatment. Nearly 10 months after treatment, the patient did relapse. However, her disease was less severe and more easily managed with lower doses of immunosuppressive therapy. CONCLUSION: This case contributes to the growing evidence of high-dose cyclophosphamide's efficacy without stem cell rescue in recalcitrant autoimmune diseases, including pemphigus foliaceus.     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

Successful treatment of corticoid-resistant pemphigus with high-dose intravenous immunoglobulins

INTRODUCTION: Pemphigus vulgaris is a serious autoimmune bullous disease, that may be difficult to control. Although corticosteroids have dramatically improved the outcome of the disease, this treatment may be complicated by unresponsiveness or serious side-effects. We report the case of a patient with pemphigus vulgaris refractory to corticosteroids who responded rapidly to the addition of high-dose intravenous immunoglobulins. CASE REPORT: A 38-year-old man presented with a 1-month history of widespread bullous lesions of the skin and oral mucosa. The diagnosis of pemphigus vulgaris was made on the results of histology and direct immunofluorescence of perilesional skin. Systemic corticosteroids were initially started, but cutaneous and mucosal lesions poorly responded after 6 weeks. Mensual cycled of intravenous immunoglobulins were then begun and led to a complete disappearance of the lesions after three cycles. Four courses of high-dose intravenous were administered, that allowed to reduce doses of steroids. The patient was in complete remission without treatment after a two-year follow-up. DISCUSSION: Pulse therapy with high-dose intravenous immunoglobulins has been occasionally used for the treatment of pemphigus vulgaris, especially in an attempt to reduce side-effects of immunosuppressive agents or when these therapies are ineffective. We report an additional case, suggesting in addition of recent data of literature, that immunoglobulins may be useful as an alternative treatment in pemphigus vulgaris.