ERG findings in patients using hydroxychloroquine

PURPOSE: To examine the electroretinographic findings derived by full-field electroretinography (ERG) and multifocal electroretinography (mfERG) in patients taking HCQ for different periods of time, including those without clinically visible evidence of toxicity. METHODS: The records for 26 consecutive patients (51 eyes, age 19-79) who had used HCQ for 1-30 years and who had an ERG and/or mfERG were reviewed. RESULTS: The patients fell into 5 groups, according to the results from their electrophysiological and clinical evaluation: no abnormalities (n = 13), cone b-wave delay (n = 2), decreased ERG amplitude (n = 6), borderline toxicity (n = 2) and toxicity (bull's-eye maculopathy; n = 3). Oscillatory potential (OP) amplitudes were decreased in many of the patients, even in the absence of any other clinical or ERG abnormality. MfERGs were normal in these patients without other abnormalities, but showed a bull's eye pattern of damage in a patient with clear toxicity. The full-field ERG parameters (including OPs) showed little relationship to the duration of HCQ usage or the cumulative dose. CONCLUSIONS: A substantial subgroup of patients showed varying degrees of diffuse ERG abnormality despite having no clinical signs (visual or fundus changes) of toxicity, and despite a range of cumulative doses. The mfERG showed toxicity, but its sensitivity in detecting early change remains to be determined. Further work is needed in order to separate pharmacological actions of the drug, retinopathy from the systemic disease, and potential toxic effects.     

Ocular Toxicity Due to Chloroquine and Hydroxychloroquine: Electrophysiological and Visual Function Correlates

Chloroquine (CQ) and hydroxycholorquine (HCQ) have been used widely for the treatment of rheumatoid arthritis and other similar inflammatory diseases since the early 50s. They remain the treatment of choice for many patients even today. Significant, either reversible or irreversible central visual loss associated with the drugs is very rare, but an important side effect that can warrant discontinuation of therapy. Early diagnosis of toxicity and evaluation of the visual function are, therefore, important parts of the treatment process. Various electrophysiological and psychophysical tests have been and are used for the detection, follow-up and prognosis of drug-associated central visual loss. A summary and comment on the tests, with emphasis on the use of more recently developed methods, such as the multifocal electroretinography (mfERG), are presented in this review.     

Digoxin-Hydroxychloroquine Interaction?

ABSTRACT. Interaction between digoxin and the natural cinchona alkaloid quinidine is well documented. A possible interaction between digoxin and the semisynthetic cinchona derivative hydroxychloroquine is reported in this communication.     

抗疟药在皮肤科的临床应用及其监测

抗疟药治疗皮肤病的历史可回朔到Ｐａｖｎｅ于 1894年用奎宁和Ｐａｇｅ于 195 1年用阿的平治疗红斑狼疮 (ＬＥ) ,目前已广泛用于治疗ＬＥ、多形性日光疹和迟发性皮肤卟啉病 (ＰＣＴ)等〔1～ 5〕。皮肤科目前应用的主要为氯喹 (ｃｈｌｏｒｏｑｕｉｎｅ ,Ａｒ ａｌｅｎ)、羟氯喹 (ｈｙｄｒｏｘｙｃｈｌｏｒｏｑｕｉｎｅ ,Ｐｌａｑｕｅｎｉｌ)和阿的平(ｑｕｉｎａｃｒｉｎｅ ,Ａｔａｂｒｉｎｅ) ,其中羟氯喹用于 90 %病例 ,阿的平已基本淘汰〔1～ 3〕。1　药理特性〔1～ 3〕1 1　阿的平　是具有 1个外苯环的吖啶化合物。口服后迅速吸收 ,8～ 12…     

Antimalarials

ABSTRACT: Over the last century, antimalarial medications have become the parenteral drugs of choice for treating the cutaneous manifestations of lupus erythematosus. The effects of immune modulation with the concomitant preservation of host immune response to exogenous antigens procures these agents as powerful tools in a wide range of conditions. With prudent dosage and monitoring, antimalarials can be used safely and effectively in the treatment and management of autoimmune connective tissue disease.     

氯喹和羟氯喹抗病毒药理及临床研究进展

病毒感染性疾病致病率高、传染性强、危害性大,对人类健康乃至社会发展造成很大威胁,因此寻找预防及治疗药物一直是关注的重点。氯喹、羟基氯喹是美国食品药品管理局批准的治疗疟疾、风湿免疫病的常用药,药品的成本低、安全性高。回顾了多项氯喹、羟氯喹抗病毒的药理研究及临床试验,归纳了二者对于人冠状病毒（HCoVs）、人免疫缺陷病毒（HIV）、寨卡病毒、肠道病毒71型（EV-A71）、朊病毒等多类病毒的作用,其具有广谱抗病毒作用,在临床上有较好的应用前景。     

Azithromycin and COVID‐19: Prompt early use at first signs of this infection in adults and children,an approach worthy of consideration

The devastating effects of the coronavirus designated severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have led to urgent attempts to find effective therapeutic agents for inpatient and outpatient treatment of COVID‐19. Initial enthusiasm for the combination of hydroxychloroquine and azithromycin has abated. However, as a result of positive clinical experience with azithromycin used alone during the first few days of the flu‐like illness caused by this coronavirus, we recommend formal clinical trials using azithromycin early in the course of a COVID‐19 infection. There is one clinical trial initiated, the individually randomized, telemedicine‐based, “Azithromycin for COVID‐19 Treatment in Outpatients Nationwide” based at the University of California San Francisco. This placebo‐controlled trial is designed to determine the efficacy of a single 1.2‐g dose of oral azithromycin to prevent COVID‐19 patient progression to hospitalization. We recommend formal clinical trials of azithromycin in its prepackaged form at the first sign of COVID‐19 infection in adults and children, using an initial adult dose of 500 mg followed by 250 mg per day for 4 days, a total cumulative dose of 1.5 g, and for children 5 to 18 years of age, 10 mg/kg on the first day followed by 5 mg/kg for 4 days.     

Additive immunosuppressive effect of leflunomide and hydroxychloroquine supports rationale for combination therapy for Sjögren’s syndrome

ABSTRACT

Objective: Effective treatment for primary Sjögren’s syndrome (pSS) is not available. pSS immunopathology involves a variety of immune-cells and dysregulated pathways; targeting several pathways instead of only one could therefore be effective. Treatment with leflunomide (LEF) and hydroxychloroquine (HCQ) might be successful given their unique immunosuppressive properties. We aimed to study the in vitro effects of LEF, HCQ and their combination on T- and B-cell proliferation, cytokine and immunoglobulin production by activated PBMCs.

Methods: PBMCs of six healthy individuals and nine pSS patients were stimulated with superantigen and TLR9 agonist to mimic the hallmark features. LEF, HCQ and their combinations were tested at clinically observed concentrations and proliferation, cytokine and immunoglobulin production were measured.

Results: TCR/TLR9 activation of PBMCs induced strong proliferation of T and B-cells and production of CXCL13, IFN-α, IFN-γ, IgG and IgM. LEF dose-dependently inhibited all measured parameters, where HCQ potently and dose-dependently decreased B cell proliferation, CXCL13, IFN-α, IgG and IgM production. At different concentration combinations, HCQ and LEF inhibited several immune hallmark features more potently than each single compound.

Conclusion: A combination of LEF and HCQ at clinically applicable concentrations additively inhibits immune activation, supporting a potential implementation of this drug combination in pSS treatment.     

Hydroxychloroquine in lupus: emerging evidence supporting multiple beneficial effects

Due to multiple beneficial effects, including control of disease activity, reduction in cardiovascular events and improved survival, hydroxychloroquine is now recommended long‐term for all patients with systemic lupus erythematosus. However, patients must be made aware of the possible risk of retinal toxicity and have eye examinations to monitor for this complication. As hydroxychloroquine becomes more widely used in systemic lupus erythematosus, physicians must also be aware of rare but serious adverse effects, including neuromyotoxicity and cardiotoxicity.     

来氟米特及甲氨蝶呤对早期严重类风湿关节炎的治疗作用

目的研究来氟米特及甲氨蝶呤联合运用对早期严重类风湿关节炎临床症状，特别是对关节损害的作用。方法108例早期严重类风湿关节炎患者随机分为来氟米特组、来氟米特＋甲氨蝶呤组及来氟米特＋羟氯喹组，治疗前作相应的临床、实验室及影像学检查，以来氟米特30mg／d，连续2天后改为20mg／d，甲氨蝶呤10mg／w，羟氯喹400mg／d治疗12个月后，再评价患者临床、实验室及影像学的改变。结果来氟米特组、来氟米特＋甲氨蝶呤组及来氟米特＋羟氯喹组治疗12个月后，关节疼痛数明显减少，关节肿胀亦得到明显改善，晨僵时间显著缩短，其中尤以来氟米特＋甲氨蝶呤效果明显。关节侵蚀及Larsen-Dale积分在来氟米特＋甲氨蝶呤组改善亦较其他两组显著。但血沉及C反应蛋白改变不显著。结论来氟米特及甲氨蝶呤联合运用对早期类风湿关节炎的临床症状及关节损害的改善具有明显的效果。