Electroanatomic mapping and ablation of ventricular tachycardia associated with systemic sclerosis.

Two cases of systemic sclerosis with sustained ventricular tachycardia (VT) are presented. The first patient received hydroxychloroquine for skeletal muscle disease coexisting with cardiac involvement. In both cases, 3D-electroanatomic mapping showed low-voltage areas in the right ventricle. In the first patient the tachycardia was mapped and a protected isthmus suggesting reentry was delineated and ablated. Other substrate locations were indirectly identified by pacemapping on the right and left ventricular endocardium in the second patient. VT did not reoccur during follow-up. Radiofrequency catheter ablation is safe and effective and electroanatomic mapping may be helpful in patients with systemic sclerosis.     

Low-dose oral hydroxychloroquine led to impaired vision in a child with renal failure: Case report and literature review

Introduction:Hydroxychloroquine (HCQ) has received much attention in the treatment of coronavirus disease 2019 recently. However, it can cause irreversible vision loss. Few cases have been reported in pediatric patient with HCQ-related adverse reactions. Appropriate administration and early disease recognition are important for reducing the adverse drug reactions of HCQ.Patient concerns:We report a case of a 14-year-old Chinese girl who sought treatment for rapidly decreasing vision in the left eye over 3 days. The simulation results of the population pharmacokinetic model of HCQ revealed that the plasma concentration of HCQ abnormally increased before the visual acuity of the eye decreased.Diagnosis:She was diagnosed as HCQ related drug adverse reaction.Interventions:The daily dose of HCQ for this patient was adjusted from 100 mg/d to 50 mg/d.Outcomes:Follow-up for 6 months showed no more vision loss recurrence. However, the existing decreased visual acuity of the eye did not recover either.Conclusion:Although decreased visual acuity is an infrequent symptom, ophthalmologists should be aware of the possibility of HCQ concentration enrichment and consider minimizing HCQ use when a child with renal hypofunction seeks treatment for shortsightedness.     

羟氯喹联合利妥昔单抗治疗系统性红斑狼疮的临床研究

目的 研究羟氯喹联合利妥昔单抗治疗系统性红斑狼疮的临床疗效。方法 选择2017年1月—2019年12月榆林市第二医院的系统性红斑狼疮患者71例作为研究对象。用抽签法随机将患者分为对照组（36例）和观察组（35例）。对照组iv利妥昔单抗注射液,100 mg/次,1次/周。观察组在对照组基础上口服硫酸羟氯喹片,0.4 g/次,2次/d。两组均治疗4周。观察两组患者的临床疗效,同时比较两组治疗前后的系统性红斑狼疮疾病活动指数（SLEDAI）评分、24 h尿蛋白、血肌酐、血清白蛋白和炎性因子水平。结果 治疗后,观察组的有效率为91.43%,明显高于对照组的69.44（P<0.05）。治疗后,两组的SLEDAI评分、血肌酐及24 h尿蛋白水平明显降低,血清白蛋白水平明显升高（P<0.05）;且观察组的SLEDAI评分、血肌酐及24 h尿蛋白水平明显低于对照组,血清白蛋白水平明显高于对照组（P<0.05）。治疗后,两组血清白细胞介素（IL）-4、IL-17和单核细胞趋化蛋白-4（MCP-4）水平明显降低（P<0.05）,且观察组的血清IL-4、IL-17和MCP-4水平明显低于对照组（P<0.05）。结论 羟氯喹联合利妥昔单抗能改善系统性红斑狼疮患者的免疫功能,降低血清IL-4、IL-17和MCP-4水平,具有一定的临床推广应用价值。     

短期使用氯喹/羟氯喹引起不良反应的病例报道分析及合理应用建议

目的检索与分析短期应用氯喹/羟氯喹(CQ/HCQ)可能导致的药品不良反应(ADR)及分析相关影响因素,为临床合理应用提供参考。方法通过检索PubMed、中国期刊全文数据库(CNKI)、万方数据库从建库至今CQ/HCQ引起的药品相关不良反应的个案报道的相关文献,设定单次服药至服药3个月内出现的ADR情况,分析CQ/HCQ可能引起的ADR及容易诱发ADR的相关因素,进行分析总结。结果共检索到文献1280篇,最终纳入42篇。其中心脏ADR共7篇10例,主要为心律失常,包括房室传导阻滞4例、Q-T间期延长4例;其中3例死亡,7例停药后恢复,服药1 g/d以上出现心脏毒性更快。视觉相关ADR文献4篇5例,其中应用CQ的1例,为单次用药后出现视力下降。HCQ的4例,出现黄斑病变1例,视物模糊1例,结膜充血2例。出现视物模糊与黄斑病变的患者停药后未恢复。皮肤ADR纳入21篇,严重的可引起Stevens-Johnson综合征2例,急性或泛发性脓疱病10例。其他严重ADR共10篇,主要表现为神经精神系统ADR。结论CQ/HCQ可引起严重ADR,对既往有心脏疾病、合并使用有相互作用的药物应进行严密监测,制定新型冠状病毒肺炎治疗的合理剂量,还应考虑患者疾病严重程度、肝肾功能情况,选择不同的药物与给药方案。     

Hydroxychloroquine-induced Phospholipidosis in a Case of SLE: The Wolf in Zebra Clothing

Abstract

A 30 year old lady patient of SLE on steroid and hydroxychloroquine therapy presented with lupus nephritis and later developed cardiac symptoms. Her renal biopsy revealed features of Class III lupus nephritis. Also seen was typical lamellated myelinoid material in the glomerulus. The alpha-galactosidase A activity was normal. The clinical morphological and biochemical findings were consistent with Lupus nephritis showing changes of hydroxychloroquine induced phopholipidosis. Electron microscopy along with careful clinical examination and follow up status was instrumental in the diagnosis of the latter.     

基于FDA不良事件数据库和指定医疗事件对氯喹和羟氯喹不良反应信号的检测与评价

目的： 挖掘和评价新型冠状病毒肺炎治疗方案（试行第七版）中加入的药物"磷酸氯喹"和《上海市2019冠状病毒病综合救治专家共识》中推荐加入的"硫酸羟氯喹"上市后的安全信号,为临床合理用药提供参考。方法： 检索美国FDA不良事件报告系统（FDA adverse event reporting system,FAERS）数据库2004年1月1日-2019年12月31日收录以"氯喹"及"羟氯喹"为怀疑对象的不良事件（adverse drug events,ADEs）报告,提取排名前200位药物不良反应（adverse drug reaction,ADR）报告进行指定医疗事件（designated medical event,DME）筛选,采用报告比值比法（ROR）和比例报告比值比法（PRR）检测ADR信号,重点评估和比较出现DME的系统器官分类（SOC）中的安全信号,并对DME进行分析。结果： 提取FAERS数据库得到氯喹与羟氯喹ADEs报告数量分别为1 128例和29 639例;氯喹严重不良事件（serious adverse event,SAE）占比57.89%,羟氯喹占比26.60%。经DME筛选,共涉及7种SOC,其中眼部疾病与呼吸系统相关ADR中,羟氯喹检出的信号较多;皮肤和皮下组织类疾病,2种药物信号检出数量大致相等;心脏、血液及肝胆系统相关ADR中,信号主要集中在氯喹;耳部系统相关ADR中,信号检出较少。另外,氯喹检出的7种DME中尖端扭转型室速信号值最高,羟氯喹检出的4种DME中中毒性表皮坏死松解症信号值最高。结论： 基于真实世界的ADR信号检测有助于新冠疫情中氯喹与羟氯喹的安全性评价,降低临床用药风险。     

Early induction of apoptosis in B-chronic lymphocytic leukaemia cells by hydroxychloroquine: activation of caspase-3 and no protection by survival factors

We have investigated the effect of hydroxychloroquine (HCQ), an anti-rheumatic drug, on malignant B cells from 20 patients with B-chronic lymphocytic leukaemia (B-CLL). HCQ induced a decrease in cell viability in a dose- and time-dependent manner. The mean IC50 was 32 +/- 7 microg/ml (range, 10-75 microg/ml) for 24 h of exposure. This cytotoxic effect was owing to apoptosis, as demonstrated by morphological changes, annexin V binding capacity and DNA fragmentation (28 +/- 4% of apoptotic cells as early as 5 h post incubation, increasing to 82 +/- 4% at 18 h post treatment). The apoptosis was associated with caspase-3 activation because the cleavage and activity of caspase-3 were increased by HCQ. The amount of bcl-2 protein was reduced during apoptosis, evidenced using quantitative flow cytometry. As early as 1 h post-HCQ treatment, a reduction of the mitochondrial transmembrane potential was measured by 3,3'-dihexyloxacarbocyanine iodide. Interestingly, the HCQ effect was not affected by exposure to interleukin-4 or co-culture with bone marrow stromal cells. Our observations suggest that HCQ may offer a new therapeutic tool in the treatment of B-CLL patients.     

Chronic ulcerative stomatitis: A comprehensive review and proposal for diagnostic criteria

Chronic ulcerative stomatitis (CUS) is an immune‐mediated disorder characterized by oral erosions and ulcers usually refractory to conventional treatments. The disease often involves middle‐aged and older women with painful lesions sometimes resembling those of erosive oral lichen planus (OLP). The most affected sites are the buccal mucosa, the gingiva and the tongue, but the skin is involved in 22.5% of cases. Histopathologic features in CUS are non‐specific and indistinguishable from those of OLP, with the exception of the presence of a mixed infiltrate composed of lymphocytes and plasma cells. Direct immunofluorescence (DIF) analysis reveals the presence of stratified epithelium‐specific antinuclear antibodies (SES‐ANA) in the lower third of the epithelium. The IgG antibodies detected on DIF are directed against the ?Np63α isoform of p63 expressed in the nuclei of the epithelial basal cells. A distinguishing feature of CUS is the low response to conventional corticosteroid therapy and the good outcome with hydroxychloroquine at the dosage of 200 mg/day or higher dosages. This paper presents a comprehensive review of CUS and is accompanied by a new case report (the 73rd case) and a proposal for updated diagnostic criteria.