我国类风湿关节炎患者羟氯喹使用的现状调查

目的 了解我国类风湿关节炎(RA)患者羟氯喹使用的现状及特点.方法 现场调查全国20家大型医院风湿科就诊的858例RA患者,记录患者的一般人口学特征、临床病情活动度、羟氯喹用药情况以及不良反应等.采用SPSS 20.0软件根据不同数据特点进行Mann-Whitney U检验、x2检验及回归分析等.结果 ①羟氯喹在我国RA患者中使用方案较规范,使用率为19.5％(167/858),64.7％(108/167)达到足疗程,77.8％(130/167)达到推荐剂量,94.6％(158/167)为联合用药,最常用的联合药物为甲氨蝶呤和来氟米特.②足疗程使用羟氯喹的RA患者多项疾病活动指标得到明显改善,包括晨僵时间(U=1 670.5,P＜0.05)、压痛关节数(U=1 380.5,P＜0.01)及肿胀关节数(U=67 974.5,P＜0.01)、患者视觉模拟评分(VAS)疼痛评分(U=2 086.0,P=0.01)、患者VAS疾病活动评分(U=2 181.5,P＜0.05)、医生VAS疾病活动评分(U=2 086.5,P＜0.05)、28个关节疾病活动指数(DAS28)评分(U=827.5,P＜0.01)、斯坦福健康评定量表(HAQ)评分(U=1 855.5,P＜0.01)、红细胞沉降率(U=1 231.0,P＜0.05).③羟氯喹总体不良反应发生率为5.4％(9/167),最常见眼部受累(包括眼底黄斑变性、眼前闪光、眼异物感)及过敏反应、发生率分别为1.8％(3/167)及1.2％(2/167).结论 在我国大型医院就诊的RA患者中有19.5％使用羟氯喹,其中94.6％为联合用药.羟氯喹足疗程使用疗效肯定,总体不良反应发生率低,无严重不良反应.     

羟氯喹抑制紫外线诱导的系统性红斑狼疮CD4+T细胞白细胞介素-10和干扰素-γ的表达

目的 研究紫外线对系统性红斑狼疮(SLE)CD4+T细胞因子的影响和羟氯喹的抑制作用.方法 选择SLE 30例,健康对照10名.磁珠分选SLE患者和健康人的CD4+T细胞,紫外线311 nm窄谱中波紫外线暴露,加入羟氯喹共培养,酶联免疫吸附试验(ELISA)检测培养上清白细胞介素(IL)-10和干扰素-γ的表达水平.采用t检验进行统计学分析.结果 SLE患者CD4+T细胞IL-10表达高于健康对照[(27±4)和(18±3) pg/ml,P=0.011];经45、100 mJ/cm2紫外线暴露后,SLE活动患者CD4+T细胞IL-10表达升高[(27±4)和(77±42) pg/ml,(40±18)和(77±42) pg/ml,P=0.022,P=0.048],经100 mJ/cm2紫外线暴露后,活动患者CD4+T细胞IL-10表达高于稳定患者[(77±42)和(24±4)pg/ml,P=0.029];羟氯喹降低SLE活动患者CD4+T细胞IL-10和干扰素-γ表达[(2.6±4.0)和(17.9±2.3)pg/ml,P=0.018,P=-0.017)];羟氯喹降低经45,100 mJ/cm2紫外线暴露后SLE活动患者T细胞IL-10表达[(40±18)和(22±6)pg/ml,(77±42)和(21±5) pg/ml,P=0.037,P=0.04];羟氯喹降低经100 mJ/cm2紫外线暴露的SLE活动和稳定患者T细胞干扰素-γ表达[(18±3)和(13±14) pg/ml,(19±7)和(12±5) pg/ml,P=0.013,P=0.049].结论 紫外线加重SLE患者体内Th1/Th2细胞因子的比例失衡;羟氯喹抑制了紫外线诱发SLE患者干扰素-γ和IL-10的表达.

Abstract：

Objective To explore the role of hydroxychloroquine (HCQ) in ultraviolet B (UVB)- induced expression of interleukin (IL)-10 and interferon (IFN)-γ from CD4+T cells in patients with systemic lupus erythematosus (SLE). Methods Thirty patients with SLE and 10 healthy controls were enrolled in the study. CD4+ T cells were isolated using magnetic beads from SLE patients and healthy controls. HCQ was added in culture media before and after irradiation with UVB 311 nm narrow band ultraviolet B (NB-UVB). The levels of IL-10 and IFN-γ in the supernatant were detected with enzyme-linked immunosorbent (ELISA). Comparisons between groups were performed by t-test. Results The level of IL-10 was higher in SLE patients [(27±4) pg/ml] than that in healthy controls [(18±3) pg/ml, P=0.011]. After exposure of CD4+T cells to UVB in 45 or 100 mJ/cm2 dosages, the level of IL-10 was increased significantly in patients with active disease (P=0.022, P=0.048). After exposure of CD4+T cells to UVB in 100 mJ/cm2 dosages, the levels of IL-10 was higher in patients with active disease [(77±42) pg/ml] than patients with stable disease [(24± 4) pg/ml, P=0.029]. When CD4+ T cell were cultured with HCQ, IL-10 and IFN-γ levels in patients with active disease [(2.6±4.0), (17.5±2.3) pg/ml] were decreased significantly (P=0.018, P=0.017). HCQ reversed UVB-induced IL-10 expression in active SLE patients after exposure of CD4+T cells to UVB in 45 or 100 mJ/cm2 dosages (P=0.037, P=0.04). HCQ also reversed UVB-induced IFN-7 expression in active SLE patients and stable SLE patients after exposure to CD4+T cells with UVB in 100 mJ/cm2 dosages (P=0.013, P= 0.049). Conclusion UVB can aggravate the imbalance of Th1 and Th2 cytokines. HCQ inhibits UVB-induced IL-10 and IFN-7 expression of CD4+T cells in patients with SLE, especially in patients with active disease.     

Detection of the regression on hydroxychloroquine retinopathy in optical coherence tomography

Hydroxychloroquine (HCQ) that is widely used in the treatment of the connective tissue disorders can cause retinopathy. The fundus examination of a patient with systemic lupus erythematosus receiving HCQ revealed left incomplete bull's eye and pigmentary changes in macula in the right eye. Repeated visual field tests showed the paracentral and peripheral defects in the right eye and the pericentral ring scotoma in the left eye. Optical coherence tomography (OCT) scans revealed the photoreceptor loss, retina pigment epithelium (RPE) irregularities, and a cyst-like hypo reflective space over RPE layer on the nasal perifoveal region in the left eye. On the ophthalmoscopic examination, the perifoveal pigmentation was not altered after the discontinuation of HCQ. However, the bilateral visual field defects were improved and the photoreceptor destruction and cyst-like hyporeflective space disappeared in the left eye. Mild RPE irregularities remained in both eyes as revealed by OCT scans. Even if OCT is used to evaluate the regression of HCQ retinopathy, it only shows advanced stage of retinopathy.     

羟氯喹对痛风患者血尿酸及血脂的影响

目的探讨羟氯喹治疗对痛风患者血尿酸(UA)和血脂的影响及其安全性。方法将2009年1月—2010年4月治疗的原发性痛风患者43例随机均分为治疗组和对照组,治疗组25例采用一般治疗+控制尿酸药+羟氯喹治疗,对照组18例采用一般治疗+控制尿酸药+小剂量秋水仙碱治疗,观察期6个月,比较2组血清尿酸和血脂的变化。结果 (1)血UA:2组治疗后3、6个月末较治疗前比较差异有统计学意义(P<0.05或P<0.01),且治疗组尿UA降低较对照组同时点明显(P<0.05或P<0.01)。(2)血脂:治疗组治疗后3、6个月末TC、LDL-C、HDL-C水平较治疗前比较差异有统计学意义(P<0.05或P<0.01),而对照组治疗前后变化不明显(P>0.05);治疗组治疗后3、6个月末TC、LDL-C、HDL-C水平较对照组同时点有显著差异(P<0.05或P<0.01)。急性痛风性关节炎复发次数减少,差异无统计学意义(P>0.05)。结论羟氯喹可减少痛风关节炎的发作次数及降低血尿酸、血脂,具有较好耐受性和安全性。     

羟氯喹治疗系统性红斑狼疮合并妊娠24例临床研究

目的 评价羟氯喹治疗系统性红斑狼疮(SLE)患者合并妊娠的疗效与安全性.方法 回顾性分析2006年5月至2011年2月中日友好医院风湿免疫科收治的24例妊娠期间使用羟氯喹治疗SLE患者的疾病控制和新生儿安全情况,并对其子代进行随访.结果 24例患者中22例在妊娠期间持续应用羟氯喹治疗,21例患者SLE病情平稳,无复发.2例患者妊娠后停用羟氯喹,在妊娠中期出现SLE活动,增加糖皮质激素剂量并再度加用羟氯喹,SLE病情稳定至分娩和产后.3例患者诊断妊娠高血压,3例患者早产.副作用:2例患者在妊娠期加用羟氯喹后,分别出现一过性厌食和脱发,未予特殊治疗,症状大约持续3周后自行缓解.所有患者均未出现眼部不适及视野缺损症状.至目前为止,患者在我院眼科门诊定期复查视野及眼底均无异常发现.新生儿听力筛查和身高、体重均在正常范围内,未发现心肺异常及生长发育异常.结论 羟氯喹对SLE妊娠期妇女及胎儿具有良好的安全性,应在妊娠期间持续使用.     

Hydroxychloroquine is a novel therapeutic approach for rosacea

Rosacea is a chronic inflammatory disease in face. Hydroxychloroquine (HCQ), an anti-malaria drug, was reported to have anti-inflammation activities. However, the role of HCQ on rosacea remains unclear. In this study, we revealed the potential molecular mechanism by which HCQ improved rosacea in rosacea-like mice and mast cells (MCs). Moreover, the effects of HCQ treatment for rosacea patients were investigated. In this study, we found HCQ ameliorated the rosacea-like phenotype and MCs infiltration. The elevated pro-inflammatory factors and mast cell protease were significantly inhibited by HCQ treatment in rosacea-like mice. In vitro, HCQ suppresses LL37-induced MCs activation in vitro, including the release of inflammatory factors, chemotaxis, degranulation and calcium influx. Moreover, HCQ attenuated LL37-mediated MCs activation partly via inhibiting KCa3.1-mediated calcium signaling. Thus, these evidences suggest HCQ ameliorated rosacea-like dermatitis may be by regulating immune response of MCs. Finally, the 8-week HCQ treatment exerted satisfactory therapeutic effects on erythema and inflammatory lesions of rosacea patients, indicating that it is a promising drug for rosacea in clinical treatment.     

Hydroxychloroquine retinopathy: A review of imaging

Hydroxychloroquine (HCQ) retinopathy can result in permanent vision loss. In early stages of HCQ retinopathy, patients are usually asymptomatic with preservation of visual acuity. We aspire that our review, in conjunction with the American Academy of Ophthalmology screening guidelines, shall shed light on effective screening measures utilizing multimodal imaging techniques to detect early signs of HCQ retinopathy before advanced changes manifest clinically.     

Spectral domain optical coherence tomography–based prevalence of hydroxychloroquine maculopathy in Indian patients on hydroxychloroquine therapy: A utopia of underdiagnosis

BackgroundSpectral domain optical coherence tomography (SD-OCT) detects early structural damage to macula in patients on Hydroxychloroquine (HCQ) therapy. The current screening protocols emphasize concurrent use of both SD-OCT and Visual field analysis (VFA) which detects functional damage to detect Hydroxychloroquine maculopathy. However, VFA is a time-consuming and subjective test which is often neglected. This study gives the prevalence of Hydroxychloroquine maculopathy using SD-OCT alone which often fails to detect macular damage in peri-foveal and extra-foveal area of the retina.MethodsThree hundred thirty four eyes of 167 patients taking systemic Hydroxychloroquine were studied with SD-OCT macular cube 512 x 128 to diagnose structural macular damage to detect prevalence of Hydroxychloroquine maculopathy.ResultsOut of 167 patients, only four patients showed features suggestive of Hydroxychloroquine maculopathy. One patient had ELM loss, two had para-foveal and one had peri-foveal IS-OS disruption. The SD-OCT gave prevalence as 2.4%.ConclusionSD-OCT alone can underdiagnose burden of Hydroxychloroquine maculopathy (prevalence = 2.4%) when compared to studies which use both SD-OCT and Visual field analysis (prevalence = 7.5%).