刘传慧 刘璐 潘建康
【摘 要】意图:调查环孢素A与利可君序贯医治原发性枯燥综合征兼并外周血白细胞削减的临床作用。办法:选取60例原发性枯燥综合征患者,入院实验室查看外周血白细胞(2.5~3.5)×109·L-1,随机分为A组和B组,每组30例。A组给予利可君每日60 mg,1个月后复查外周血白细胞;若升至3.5×109·L-1以上,给予环孢素A每日50 mg,医治3个月后复查外周血白细胞。B组给予醋酸泼尼松每日15 mg,1个月后复查外周血白细胞;若升至3.5×109·L-1以上,给予环孢素A每日50 mg,医治3个月后复查外周血白细胞。2组患者在3个月内逐渐减停利可君或醋酸泼尼松。成果:1个月后,A组26例、B组27例外周血白细胞升至3.5×109·L-1以上,均给予环孢素A每日50 mg医治;3个月后,A组21例、B组23例外周血白细胞保持在3.5×109·L-1以上。定论:利可君医治原发性枯燥综合征兼并外周血白细胞削减有用。
【关键词】 原发性枯燥综合征;利可君;环孢素A;外周血白细胞
【ABSTRACT】Objective:To investigate the clinical efficacy of cyclosporine A and Leucoson Tablets sequential therapy in the treatment of primary Sj?gren's syndrome complicating peripheral leukocyte reduction.Methods:Sixty patients with primary Sj?gren's syndrome were selected and randomly divided into group A and group B after their peripheral blood leucocytes(2.5~3.5)×109·L-1 were examined in the laboratory,with thirty cases in each group.Group A was given Leucoson Tablets(180 mg)daily.If their peripheral blood leukocytes were no less than 3.5×109·L-1,they would be given cyclosporine A(50 mg)daily and reexamined after three months of treatment.Group B was given 15 mg of prednisone per day,and 1 month later,the peripheral blood leukocytes were reexamined.If their peripheral blood leukocytes were up to 3.5×109·L-1,50 mg of cyclosporin A would be given each day.The peripheral blood leukocytes were reviewed after 3 months of treatment.During the 3 month,patients in the two groups were gradually given less or stopped taking Leucoson Tablets or prednisone.Results:One month later,peripheral blood leukocytes in 26 cases of group A and 27 cases of group B rose no less than 3.5×109·L-1.They were all treated with cyclosporine A(50 mg)per day.Three months later,peripheral blood leukocytes in 21 cases of group A and 23 cases of Group B were no less than 3.5×109·L-1.Conclusion:Leucoson Tablets are effective in treating primary Sj?gren's syndrome complicating peripheral leukocyte reduction.
【Keywords】 primary Sj?gren's syndrome;Leucoson Tablets;cyclosporine A;peripheral blood leucocytes
原發性枯燥综合征(primary Sj?gren's syndrome,pSS)是一种以侵略泪腺、唾液腺等外排泄腺体为主的缓慢本身免疫性疾病,又称为本身免疫性外排泄腺体病。pSS患者临床除有唾液腺和泪腺受损功用下降而呈现口干、眼干外,尚有其他外排泄腺及腺体外其他器官劳累而呈现的多体系危害症状,其血清中存在多种本身抗体和高免疫球蛋白。原发性胆汁性肝硬化是pSS常见的脏器危害之一。
外周血白细胞下降是pSS最常见的体系危害之一,严峻的外周血白细胞下降患者可继发感染乃至危及生命。以往关于pSS兼并外周血白细胞下降的患者多选用糖皮质激素医治,待血惯例康复后给予环孢素A保持,但糖皮质激素或许导致的骨质疏松及其他不良反应不行忽视。本研讨选用利可君对症医治,讨论该药物代替糖皮质激素短时刻内升高外周血白细胞的或许性。
1 临床材料
1.1 一般材料 选取2011年1月至2015年12月在郑州市骨科医院就诊的门诊和住院pSS患者60例,依照随机数字表法分为A组和B组,2组患者在性别、年纪、病程等方面比较,差异无统计学含义(P > 0.05),具有可比性。见表1。
1.2 确诊规范 依照2002年pSS世界分类规范[1]。
1.3 归入规范 ①契合上述确诊规范;②外周血白细胞在(2.5~3.5)×109·L-1;③入组前未运用糖皮质激素。
1.4 扫除规范 ①兼并其他血液体系疾病者;②兼并有其他疾病者。
2 方 法
2.1 医治办法 A组给予利可君(江苏吉贝尔药业股份有限公司,国药准字H32025444,规范20 mg),每次20 mg,每日3次,口服。1个月后复查外周血白细胞,若升至3.5×109·L-1以上,给予环孢素A(杭州中美华东制药有限公司,国药准字H10960123,规范25 mg),每次25 mg,每日2次,口服。B组给予醋酸泼尼松(浙江仙琚制药股份有限公司,国药准字H33021207,规范5 mg),每次5 mg,每日3次,口服。1个月后复查外周血白细胞,若升至3.5×109·L-1以上,给予环孢素A每日50 mg。
2.2 调查目标 2组患者医治3个月后均复查外周血白细胞;2组患者在3个月内逐渐减停利可君或醋酸泼尼松,并复查血脂、血糖、骨密度。
2.3 统计学办法 选用SPSS 16.0软件进行统计分析。计量材料以标明,选用成组规划t查验;计数材料选用χ2查验。以P < 0.05为差异有统计学含义。
3 结 果
3.1 2组患者医治后外周血白细胞状况比较 1个月后复查外周血白细胞,A组26例、B组27例外周血白细胞升至3.5×109·L-1以上,2组比较,差异无统计学含义(P = 0.112 > 0.05)。上述患者均给予环孢素A医治,2组患者在3个月内逐渐减停利可君或醋酸泼尼松。医治3个月后复查外周血白细胞,A组21例、B组23例外周血白细胞升至3.5×109·L-1以上。且2组比较,差异无统计学含义(P = 0.214 > 0.05)。
3.2 2组患者医治期间并发症状况 2组患者在医治过程中,环孢素A相关的不良反应,A组2例,B组3例,体现为厌恶、吐逆、腹胀等。A组未呈现与利可君相关的不良反应,B组有6例呈现高血压、血糖反常等与醋酸泼尼松相关的不良反应。
2组不良反应比较,差异无统计学含义(P > 0.05)。
4 讨 论
pSS是一种侵略外排泄腺,尤其是侵略唾液腺和泪腺为主的缓慢本身免疫性疾病。它不只侵略外排泄腺体形成口干、眼干,还可累及肾、肺、神经体系、消化体系等多个体系,引起全身器官劳累,其间血液体系危害是其主要体现之一。本病可呈现白细胞计数削减或(和)血小板削减[1-6]。近年来,国内外多篇文献具体介绍了现在对pSS的知道及医治发展,可是pSS所触及的血惯例改变,尤其是兼并外周血白细胞削减的医治仍存在许多
短缺[1-3]。
现在,惯例医治pSS兼并外周血白细胞削减的计划是运用小剂量糖皮质激素使白细胞升至正常水平,后给予免疫抑制剂环孢素A。环孢素A具有必定影响骨髓增殖的作用,长期服药能够保持血惯例在抱负水平[4]。糖皮质激素的不良反应较多,较短时刻运用小剂量仍会呈现骨质疏松、血压和血糖反常等严峻问题[5],长期运用会导致血脂反常、股骨头坏死、肱骨头坏死等严峻并发症。因而,能否给予其他具有升高外周血白细胞的药物代替糖皮质激素成为人们重视的问题。
利可君为半胱氨酸的衍生物,口服后在十二指肠碱性条件下与蛋白结组成可溶性物质敏捷被肠所吸收[6-7]。利可君可促进白细胞增生,防备和医治白细胞削减及血小板削减有必定的作用[8]。本研讨成果显现,口服利可君可在短时刻内升高外周血白细胞,与服用醋酸泼尼松比较差异无统计学含义(P > 0.05)。标明利可君联合环孢素A医治与醋酸泼尼松联合环孢素A医治的作用根本共同,即均可长期有用地保持外周血白细胞在根本正常规模。本研讨提示,利可君能够在短时刻内代替糖皮质激素医治轻度外周血白细胞下降。但本研讨病例数少,调查时刻短,还需大样本长期的进一步探究。
5 参考文献
[1] 董怡.论2002年修订的枯燥综合征分类(确诊)规范[J].中华风湿病学杂志,2002,7(1):1-2.
[2] BALDINI C,PEPE P,QUARTUCCIO L,et al.Primary Sj?gren's syndrome as a multi-organ disease:impact of the serological profile on the clinical presentation of the disease in a large cohort of Italian patients[J].Rheumatology,2014,53(5):839-844.
[3] QIAO L,LUO Y,ZHANG LL,et al.The clinical characteristics of primary Sj?gren syndrome with neuromyelitisoptica[J].Zhonghua Nei Ke Za Zhi,2013,52(9):745-748.
[4] WU JJ,CARSONSSE.Management of extraglandular manifestations of primary Sj?gren's syndrome[J].Oral Maxillofac Surg Clin North Am,2014,26(1):101-109.
[5] ALUNNO A,BISTONI O,BARTOLONI BOCCI E,et al.IL-17-producing double-negative T cells are expanded in the peripheral blood,infiltrate the salivary gland and are partially resistant to corticosteroid therapy in patients with Sj?gren's syndrome[J].Reumatismo,2013,65(4):192-198.
[6] ST CLAIR EW,LEVESQUE MC,PRAK ET,et al.Rituximab therapy for primary Sj?gren's syndrome:an open-label clinical trial and mechanistic analysis[J].Arthritis Rheum,2013,65(4):1097-1106.
[7] Mariette X,Seror R,Quartuccio L,et al.Efficacy and safety of belimumab in primarySjogren's syndrome:results of the BELISS open-label phase Ⅱstudy[J].Ann Rheum Dis,2013,74(3):526-531.
[8] 鄭修文,钱文,高瑞银,等.HPLC测定利可君原料药中主药含量和有关物质[J].我国药学杂志,2006,41(14):1105-1108.