糖皮质激素联合环磷酰胺治疗寻常型天疱疮疗效观察

目的 :　探讨糖皮质激素联合环磷酰胺 (CTX)治疗寻常型天疱疮近、远期疗效 ;方法 :　收集近 8年 5 9例在我科住院经临床、病理和直接免疫荧光确诊为寻常型天疱疮患者的详细资料 ,对糖皮质激素(对照 )和糖皮质激素联合环磷酰胺 (试验 )两组治疗后近、远期疗效进行评估 ;结果 :　近期疗效 ,对照组痊愈 78% (2 1 2 7) ,未愈 2 2 .2 % (6 2 7)。试验组痊愈 87.5 % (2 8 32 ) ,未愈 14 .8% (4 32 )。两组相近 ,差异无显著性 (P >0 .0 5 )。远期疗效 ,对照组痊愈 14 .8% (4 2 7) ,控制 37.0 % (10 2 7) ,未控制 4 8.1% (13 2 7)。试验组痊愈 31.2 5 % (10 32 ) ,控制 5 6 .2 5 % (18 32 ) ,未控制 12 .5 % (4 32 ) ,两组差异有显著性意义 (P <0 .0 5 )。结论 :　糖皮质激素联合CTX治疗寻常型天疱疮近期疗效与单用糖皮质激素相近 ,远期疗效明显优于单用糖皮质激素。     

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。     

自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例

目的观察自体外周血造血干细胞移植治疗难治性寻常型天疱疮1例的效果。方法患者男,45岁。口腔、头面部、躯干、四肢水疱、糜烂6年。诊断为寻常型天疱疮。经糖皮质激素和免疫抑制剂及抗CD20单克隆抗体治疗,疾病反复发作。同时合并糖尿病和高血压。半年前,全身水疱加重,行自体外周血造血干细胞移植。应用环磷酰胺、粒细胞集落刺激因子（G-CSF）进行动员。用环磷酰胺（CTX）＋磷酸氟达拉滨（Flud）＋抗胸腺细胞球蛋白（ATG）进行预处理。结果患者移植结束后,皮疹消退,自身抗体滴度明显降低。移植2个月后皮疹轻度反复,小量糖皮质激素联合甲氨蝶呤可以控制。目前移植后6个月,病情稳定。结论自体外周血造血干细胞移植治疗难治性寻常天疱疮疗效显著。可作为治疗难治性寻常型天疱疮的一种新方法。但其远期治疗效果需进一步观察。     

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。     

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)。…     

大疱及疱疹性皮肤病

20052479 副肿瘤性天疱疮1例，20052480 副肿瘤性天疱疮（继续医学教育），20052481 微波-免疫组化SP法在天疱疮诊断中的初步应用研究,20052482 糖皮质激素联合环磷酰胺治疗寻常型天疱疮疗效观察，20052483 寻常型天疱疮患娩出一天疱疮患儿。     

天疱疮43例临床资料分析

目的 探讨天疱疮各型的临床特征和治疗方法 .方法 对43例天疱疮住院患者的临床资料进行回顾性分析.结果 35.71%的寻常型天疱疮患者出现口腔、外阴黏膜损害,14.29%红斑型天疱疮患者出现口腔溃疡,1例增殖性天疱疮患者表现为近3年口腔黏膜破溃.直接免疫荧光确诊阳性72.72%.糖皮质激素治疗为首选,糖皮质激素联合免疫抑制剂治疗疗效好.结论 直接免疫荧光为诊断天疱疮的常用方法 ,天疱疮的分型是影响激素用量的重要因素,糖皮质激素联合免疫抑制剂是目前治疗此病的主要方法 .     

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。     

5-氨基酮戊酸光动力疗法联合CO_2激光治疗尖锐湿疣的临床观察

目的观察5-氨基酮戊酸光动力(ALA-PDT)疗法联合CO2激光与单纯使用ALA-PDT疗法和单纯使用CO2激光疗法治疗尖锐湿疣的临床疗效。方法将入选的120例尖锐湿疣患者随机分为3组,即ALA-PDT疗法联合CO2激光治疗组、单纯ALA-PDT疗法治疗组和单纯CO2激光治疗组,每组40例,均治疗结束3月后判定疗效。结果 ALA-PDT疗法联合CO2激光治疗组清除率为100%(40/40),痊愈率为90%(36/40),复发率为10.00%(4/40);单纯使用ALA-PDT疗法组痊愈率为42.50%(17/40),复发率为29.17%(7/24);单纯使用CO2激光治疗组一次性清除率为100%(40/40),痊愈率为37.50%(17/40),复发率为62.50%(25/40)。三组患者的痊愈率和复发率比较,ALA-PDT疗法联合CO2激光治疗组均优于单纯ALA-PDT疗法治疗组和单纯CO2激光治疗组,差异均有统计学意义(P均0.001)。结论 ALA-PDT疗法联合CO2激光疗法治疗尖锐湿疣的疗效确切,复发率较低,其疗效优于单纯使用ALA-PDT疗法组和单纯使用CO2激光治疗组,值得临床应用。     

氟芬那酸丁酯软膏联合卤米松乳膏序贯疗法治疗寻常型银屑病的随机对照研究

目的观察氟芬那酸丁酯软膏联合卤米松乳膏序贯疗法治疗寻常型银屑病的疗效和安全性。方法将120例患者随机分为治疗组(氟芬那酸丁酯软膏联合卤米松乳膏组)和对照组(他卡西醇软膏联合卤米松乳膏组),采用序贯疗法进行治疗,疗程8周。评价患者的银屑病面积和严重程度指数(PASI)评分并进行组间比较。结果治疗4周(66.7%vs 61.7%),8周(86.7%vs 88.7%)及治疗结束后4周(95.0%vs 93.7%)2组有效率(痊愈率加显效率)差异无统计学意义(P0.05),2组患者均未发生严重不良反应。结论氟芬那酸丁酯软膏联合卤米松序贯疗法治疗寻常型银屑病安全有效。     

A comparison of oral methylprednisolone plus azathioprine or mycophenolate mofetil for the treatment of pemphigus

OBJECTIVE: To investigate the safety and efficacy of oral methylprednisolone combined with azathioprine sodium or mycophenolate mofetil for the treatment of pemphigus. DESIGN: A prospective, multicenter, randomized, nonblinded clinical trial to compare 2 parallel groups of patients with pemphigus (pemphigus vulgaris and pemphigus foliaceus) treated with oral methylprednisolone plus azathioprine or oral methylprednisolone plus mycophenolate mofetil. Settings Thirteen departments of dermatology in Germany. Patients We included patients with pemphigus vulgaris (n = 33) or pemphigus foliaceus (n = 7) evidenced by clinical lesions suggestive of pemphigus, intraepidermal blistering on histological analysis of skin biopsy specimens, intercellular deposition of IgG within the epidermis, and immunoblot analysis findings for antidesmoglein 3 and/or antidesmoglein 1 autoantibodies. MAIN OUTCOME MEASURES: The cumulative total methylprednisolone doses and rate of remission. Secondary outcome measures were safety profiles and duration of remission. RESULTS: In 13 (72%) of 18 patients with pemphigus receiving oral methylprednisolone and azathioprine, complete remission was achieved after a mean +/- SD of 74 +/- 127 days compared with 20 (95%) of 21 patients receiving oral methylprednisolone and mycophenolate mofetil in whom complete remission occurred after a mean +/- SD of 91 +/- 113 days. The total median cumulative methylprednisolone dose used was 8916 mg (SD, +/-29 844 mg) in the azathioprine group compared with 9334 mg (SD, +/-13 280 mg) in the mycophenolate group. In 6 (33%) of 18 patients treated with azathioprine, grade 3 or 4 adverse effects were documented in contrast to 4 (19%) of 21 patients who received mycophenolate mofetil. Conclusion Mycophenolate mofetil and azathioprine demonstrate similar efficacy, corticosteroid-sparing effects, and safety profiles as adjuvants during treatment of pemphigus vulgaris and pemphigus foliaceus.     

Efficacy and Safety of Cyclophosphamide, Azathioprine, and Cyclosporine (Ciclosporin) as Adjuvant Drugs in Pemphigus Vulgaris

Background:Pemphigus vulgaris is a potentially life-threatening, autoimmune bullous disease of the skin and mucous membranes. Most commonly, the disease is treated with prednisone in combination with an immunosuppressant agent, frequently referred to as adjuvant drug. However, there is no consensus regarding the first-choice adjuvant drug for the treatment of pemphigus vulgaris or the recommended dosage. Objective:To evaluate the efficacy and safety of prednisone as monotherapy and in combination with the three most popular adjuvant agents — azathioprine, cyclosporine (ciclosporin), and cyclophosphamide in the treatment of pemphigus vulgaris time to immunologic remission (non-detectable circulating pemphigus vulgaris antibodies), proportion of patients who remained free of clinical relapse within 5 years after discontinuation of therapy, time from treatment discontinuation until first relapse, and incidence of adverse effects. Results:The average (± SD) time to clinical remission was 7.2 ± 13.1 months in patients who received prednisone monotherapy, 6.8 ± 10.5 months in patients receiving additional azathioprine, 8.1 ± 11.8 months in the cyclosporine group, and 4.9 ± 6.9 months (which was significantly shorter than all other treatment groups, p < 0.05) in patients receiving cyclophosphamide. The average (± SD) times to immunologic remission were 33 ± 27 months, 28 ± 24 months, 30 ± 21 months, and 23 ± 17 months for prednisone monotherapy, azathioprine, cyclosporine, and cyclophosphamide, respectively. The proportions of patients who remained free of clinical relapse within 5 years after discontinuation of therapy were 55%, 50%, 43%, and 69% for prednisone monotherapy, azathioprine, cyclosporine, and cyclophosphamide, respectively. In patents who experienced relapse, the average (± SD) time from treatment discontinuation to clinical relapse was 10.50 ± 6.86 months in patients receiving prednisone monotherapy, 16.40 ± 17.36 months in the azathioprine group, 12.44 ± 6.48 months in the cyclosporine group, and 21.16 ± 20.13 months in the cyclophosphamide group. The safety profiles of all treatment regimens were comparable. Conclusion:Oral prednisone with cyclophosphamide is the most effective treatment for pemphigus vulgaris. All therapy regimens had a similar safety profile. In our opinion, cyclophosphamide at a dose of 1.1–1.5 mg/kg/day should be the adjuvant drug of choice in the treatment of moderate-to-severe pemphigus vulgaris.     

Remisión clínica completa prolongada en pacientes con pénfigo vulgar grave después del tratamiento con ciclos intravenosos de ciclofosfamida

BackgroundCorticosteroids are the systemic treatment of choice in patients with pemphigus vulgaris, but chronic administration is associated with side effects. Intravenous treatment with cyclophosphamide can improve the clinical signs of pemphigus vulgaris.Material and methodsWe prospectively studied 8 patients diagnosed with pemphigus vulgaris. Six of these had mucocutaneous pemphigus vulgaris and 2 had mucosal pemphigus vulgaris. Treatment consisted of 10 cycles of cyclophosphamide at a dose of 10-15 mg/kg separated by 15 days, while maintaining the initial corticosteroid and immunosuppressant dose. Clinical efficacy was assessed and the anti-epidermal intercellular substance (EIS) and anti-desmoglein (DSG) 3 and 1 antibody titers were monitored (by indirect immunofluorescence and enzyme-linked immunosorbent assay, respectively).ResultsAll patients with pemphigus vulgaris responded excellently to treatment. Five of the 8 patients achieved complete remission of pemphigus lesions after 10 cycles of cyclophosphamide. In the other 3 patients, the skin lesions disappeared a few weeks after the last cycle of cyclophosphamide. A substantial reduction in immunosuppressant dose was possible in all patients. Furthermore, an improved immunologic response was observed in all cases after cyclophosphamide treatment, with decreased anti-DSG1 and anti-DSG3 antibody titers and well as decreased circulating anti-EIS antibody titers. During the mean 15.1 month follow-up (range, 1-25 months), no new lesions appeared and no side effects of cyclophosphamide therapy were reported.ConclusionsFortnightly cycles of intravenous cyclophosphamide may be a useful therapeutic option in patients with severe pemphigus vulgaris. A reduction of corticosteroid dose was possible with this therapeutic approach and the cumulative cyclophosphamide dose was lower than with daily oral administration. Our findings also show that the therapeutic approach induces clinical and immunologic remission in most patients.     

Intravenous dexamethasone‐cyclophosphamide pulse therapy in comparison with oral methylprednisolone‐azathioprine therapy in patients with pemphigus: Results of a multicenter prospectively randomized study

Background: Pemphigus is a potentially life‐threatening autoimmune blistering skin disease usually treated with high‐dose corticosteroids in combination with immunosuppressive drugs. In a multicenter, prospectively randomized study we compared efficacy and side effects of a dexamethasone‐cyclophosphamide (D/C) pulse therapy with a methylprednisolone‐azathioprine (M/A) therapy in 22 patients with newly diagnosed pemphigus vulgaris and pemphigus foliaceus. Patients and methods: The 11 patients of the M/A group were treated with daily doses of methylprednisolone (initially 2 mg/kg body weight) and azathioprine (2 – 2,5 mg/kg body weight) which were subsequently tapered. D/C pulse therapy in 11 patients consisted of intravenous administration of 100 mg dexamethasone/d on 3 consecutive days along with cyclophosphamide (500 mg) on day one. Pulses were initially repeated every 2 – 4 weeks and then at increasing intervals. In between the pulses, oral cyclophosphamide (50 mg) was given daily for 6 months. Results: Within 24 months after treatment initiation, 5/11 patients of the D/C group had a remission (complete remissions after discontinuation of therapy in 3 patients) and 6/11 patients had a progression. In the M/A group, there were remissions in 9/11 patients (complete remissions after discontinuation of therapy in 3 patients) and progression in 1/11 patients. There were more relapses in M/A therapy after remission than in D/C therapy. Side effects were more common in the M/A group. These differences were not significant (p > 0,05). Conclusion: Because of the high number of progressions in patients treated with D/C therapy, we can not confirm the encouraging results of earlier reports about pulse D/C therapy. Nevertheless D/C therapy seemed to be better tolerated and, in case of primary efficacy, was associated with fewer recurrences than M/A therapy.     

Use of cyclophosphamide in azathioprine failures in pemphigus

Four patients with pemphigus vulgaris are presented in which diagnosis was confirmed histologically and immunopathologically. Although these patients responded to high-dose prednisone therapy during the initial stages of acute disease, the addition of azathioprine failed to allow lower steroid doses and did not result in prolonged, complete remission. Indeed, the disease was exacerbated during azathioprine therapy, and significant side effects from prolonged high-dose steroid therapy were observed. Both clinical and serologic remission resulted from the addition of cyclophosphamide and dapsone to prednisone therapy. Thus, when azathioprine fails to produce remission or a steroid-sparing effect, cyclophosphamide may be an effective alternative. During a prolonged follow-up period, no recurrences of pemphigus have been observed, and no significant side effects of cyclophosphamide (Cytoxan) have been encountered. The addition of dapsone produced enhanced anti-inflammatory effects without increasing the existing or potential side effects of steroid therapy. Dapsone was easily withdrawn at the onset of remission. Thus the anti-inflammatory effect of dapsone may prove valuable in patients for whom steroids are contraindicated, who develop significant side effects during long-term steroid therapy, or for whom increases of dose threaten to enhance the possibility of catastrophic side effects.     

A Comparative Effectiveness Research of Azathioprine and Cyclophosphamide on the Clinical and Serological Response in Pemphigus Vulgaris

Context:A prospective study was carried out to examine the efficacy of cyclophosphamide and azathioprine in pemphigus vulgaris.Aims:To compare the clinical and serological effect of azathioprine and cyclophosphamide in pemphigus patients.Results:Azathioprine had a slower onset of action with a statistically significant improvement seen by 6 months (P = 0.016). Cyclophosphamide had a faster onset of action (3 months) though there was no statistical difference in the efficacy between the two at the end of 6 months. The (RonT) was 33.3–44.4% for azathioprine and 28.8–42.9% for cyclophosphamide at 6 months. Though ELISA had a high sensitivity and specificity for diagnosis, as a tool for assessing therapeutic response a significant decrease was seen only till 3 months. This was restricted to Dsg1 for the azathioprine group and both Dsg3 and Dsg1 levels for the cyclophosphamide group. There were two deaths, both in the cyclophosphamide group.Conclusions:Azathiorpine and cyclophosphamide are equally effective for mucosal and cutaneous disease in pemphigus after 6 months of therapy. Dsg ELISA is useful for diagnosis of pemphigus but is not a useful tool for monitoring response to therapy.     

Inguinal pseudotumor: relapse of a pemphigus after 15 years' remission

INTRODUCTION: Pemphigus vegetans (PV) is a rare type of pemphigus vulgaris. We report a patient with pemphigus vulgaris relapsing as an isolated vegetative tumour. CASE REPORT: A 59-year-old man was seen in February 2001 for a tumour on the right groin. He had received systemic corticosteroids and cyclophosphamide for pemphigus vulgaris from 1974 to 1985, and he had been in complete remission since 1985. At the time of evaluation, a 10 x 5 x 5 cm, smooth vegetative tumour was seen on the right groin. Biopsies showed spongiosis, acanthosis and some acantholysis. Direct immunofluorescence showed strong deposition of immunoglobulin G within the intercellular substance of the epidermis. Indirect immunofluorescence revealed anti-intercellular antibodies at a titer of 1/800. Immunoblot analysis showed reactivity with the 130 kD pemphigus vulgaris antigen. PVg was diagnosed. Local corticosteroid treatment was initiated. The patient was disease-free at follow-up three years later. DISCUSSION: Localised forms of pemphigus are very rare. Twenty four other cases have been reported among them just one case of localised PV. Our case report is very unusual because of the variability of the expression of the disease, the high antibody level, the absence of trigger factors, and the efficacy of the local corticosteroid treatment.     

Childhood pemphigus

BACKGROUND: Five children with pemphigus are reported: three with pemphigus vulgaris, one with pemphigus vegetans, and one with pemphigus foliaceus. Only one case of juvenile pemphigus vegetans has been published in the literature. MATERIALS AND METHODS: All three patients with pemphigus vulgaris were treated with oral corticosteroid; in two cases, azathioprine was added for steroid-sparing effect. The patient with pemphigus vegetans had a clinical presentation resembling pemphigus vulgaris, but the lesions in the perianal area healed as hypertrophic granulation tissue. He was treated with oral corticosteroid, azathioprine, and intralesional corticosteroid. The patient with pemphigus foliaceus presented with exfoliative dermatitis, and was treated with oral corticosteroid; methotrexate was added later for steroid-sparing purposes RESULTS: The patients were followed up for 1-4 years; the prognosis of childhood pemphigus is good. CONCLUSIONS: Long-term follow-up is needed to detect flaring of the disease and the side-effects of immunosuppressive drugs.     

Evaluation of cyclophosphamide pulse therapy as an adjuvant to oral corticosteroid in the management of pemphigus vulgaris

Corticosteroids are the mainstay of treatment for pemphigus. However, despite the introduction of adjuvant therapy for PV, the mortality rate has remained static over the past 2 decades, and consequently, a new adjuvant therapy that is both safe and effective is needed. Intravenous pulse cyclophosphamide has shown encouraging results in few studies, with a better safety profile than the oral formulation, and with better treatment compliance. We undertook a randomized, prospective, non‐blinded trial to assess the efficacy of cyclophosphamide pulse therapy (CPT) as an adjuvant to oral corticosteroid in pemphigus vulgaris (PV). We enrolled 60 patients with mild to moderate active disease to receive either daily oral prednisolone or intravenous CPT prednisolone for 1 year, and they were then followed up for another year. At the end of the study period, the time taken to initiate response was similar in both groups, but in the group who received pulse cyclophosphamide, there was a reduced time to remission, a greater proportion of cases who achieved remission, a lower number of patients who relapsed while on treatment or after stopping treatment, and a lower cumulative dose of corticosteroid. Hence, the overall trend was in favour of CPT, although this was not significant. CPT also had a good safety profile. Based on the results of this trial, CPT may be a useful adjuvant in PV in terms of reducing time to remission, relapse rates and cumulative dose of steroid, and it has a good safety profile.