Hydroxychloroquine retinopathy is an ocular lesions that develops following long-term or excessive use of hydroxychloroquine. The early clinical presentation of this lesion is nonspecific and is often detected when severe central vision impairment occurs in late stage. It currently mainly includes hydroxychloroquine binding to melanin, inducing degeneration of the retinal pigment epithelium, increasing the pH of lysosomes in the retinal pigment epithelium and interfering with the visual cycle. In recent years, with the development of retinal imaging technology and the in-depth study of hydroxychloroquine retinopathy, characteristic fundus structural changes such as retinal and choroidal thickness and blood vessels may occur in the early stage. This not only provides an important basis for the early diagnosis of hydroxychloroquine retinopathy, but also provides important clues for investigating its pathogenesis. Clinicians' proficiency in relevant fundus changes and pathogenesis will facilitate early diagnosis and treatment, while also minimizing irreversible central vision impairment in patients.
Objective To investigate the effects and mechanisms of hydroxychloroquine sulfate (HCQ) on pulmonary fibrosis through the PI3K/AKt/mTOR signalling pathway. Methods Paraquat intraperitoneal injection was used to establish a mouse model of pulmonary fibrosis. Thirty-six SPF C57BL/6J female mice were randomly divided into a blank group, a paraquat group (20 mg/kg) and a HCQ intervention group. The HCQ intervention group was divided into two subgroups (10 mg/kg and 30 mg/kg) according to different doses. The general condition and body weight changes of mice were observed. twenty-one days later, lung tissues were stained with hematoxylin-eosin and Masson’s pathological staining, and the content of inflammatory factors (IL-1β, IL-6, TNF-α) and hydroxyproline (HYP) were detected by ELISA. Alpha-smooth muscle actin (α-SMA), E-cadherin (E-cad), the expression levels of PI3K/Akt/mTOR pathway-related proteins, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKt), and mammalian target of rapamycin (mTOR) were detected by Western blot. The gene expression levels of α-SMA and E-cad were detected by q-PCR. Results Compared with the blank group, the mice in the paraquat group had lower body weight, worse general condition, higher serum levels of inflammatory factors, increased lung structure destruction and collagen deposition, significantly increased HYP content, and higher expression level of PI3K/AKt/mTOR signaling pathway related proteins (all P<0.05). The expression levels of E-cad protein and gene decreased, α-SMA protein and gene increased (all P<0.05). While the HCQ intervention group improved the degree of pulmonary fibrosis in different degrees, and the relevant indexes of PI3K/AKt/mTOR signaling pathway decreased compared with the paraquat group (all P<0.05). Conclusion HCQ can ameliorate paraquat-induced pulmonary fibrosis by inhibiting the PI3K/AKt/mTOR signaling pathway.
ObjectivesTo systematically review the efficacy and safety of hydroxychloroquine (HCQ) and chloroquine (CQ) for oral lichen planus (OLP).MethodsPubMed, The Cochrane Library, Web of Science, CNKI, CBM, VIP and WanFang Data databases were electronically searched to collect randomized controlled trials (RCTs) of HCQ and CQ for OLP from inception to September, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 10 RCTs involving 726 patients were included. The results of meta-analysis showed that: HCQ or CQ were more effective than placebos (P<0.05). Nevertheless, they were inferior to oral traditional Chinese medicine (RR=0.75, 95%CI 0.69 to 0.82, P<0.000 01). In addition, the ratio of CD4+/CD8+ T cell increased significantly in peripheral blood of OLP patients after treatment with HCQ or CQ (MD=–0.28, 95%CI –0.44 to –0.13, P=0.000 3). The incidences of adverse reaction of HCQ or CQ were higher than orally traditional Chinese medicine (RR=11.80, 95%CI 4.85 to 28.68, P<0.000 01), and the difference was statistically significant.ConclusionsCurrent evidence shows that the efficacy of HCQ or CQ for OLP were significantly superior to placebo, while inferior to orally traditional Chinese medicine. The possible therapeutic mechanism of HCQ or CQ for OLP may be related to the regulation of the ratio of CD4+/CD8+ T cells and cellular immunity of OLP patients. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusion.
ObjectiveTo investigate the protective effects of different concentrations of chloroquine on RGC in n-methyl-d-aspartate (NMDA) injured mice and its possible mechanisms.MethodsFifty-four healthy male C57/BL6 mice were randomly divided into three groups, 18 in each group. The mice in low-dose chloroquine group were intraperitoneally injected with chloroquine solution at a dose of 10 mg/kg daily. Mice in high-dose chloroquine group were intraperitoneally injected with chloroquine solution at a dose of 100 mg/kg, and the mice in control group were intraperitoneally injected with the same volume of PBS. NMDA intravitreal injection was performed 2 days after intraperitoneal injection, 5 nmoles NMDA was injected into the left eye, and the same volume of PBS was injected into the right eye as a control. The RGC staining of retinal plaques were performed 7 days after NMDA injection, and the number of alive RGC was calculated. The visual acuity and electroretinogram were used to evaluate the electrophysiological functions of RGC at 9 and 10 days after modeling. Real-time quantitative PCR and retinal frozen sections and glial fibrillary acidic protein (GFAP) immunofluorescence staining were performed 11 days after NMDA injection to evaluate the glial activation of the retina. The density, visual acuity, and the amplitude of PhNR-wave of RGC between groups were compared by one-way analysis of variance.ResultsAt 7 days after NMDA injection, the density of RGC in retinal patch of low-dose chloroquine group was significantly higher than that of intraperitoneal injection of PBS control group (F=54.41, P＜0.01). The density of RGC in retinal patch of high-dose chloroquine group was lower than that of control group (F=1.18, P＞0.05). The visual acuity was higher than control group, and the difference was statistically significant (F=9.10, P＜0.05). The amplitude of PhNR-wave was significantly higher in low-dose chloroquine group than that of the control group (F=17.60, P＜0.01). The mRNA level of inflammatory factor and GFAP positive signal was also significantly lower than that of the control group (F=23.66, P＜0.05). The amplitude of PhNR-wave, the expression of GFAP (F=110.20, P＜0.01) and the mRNA level of inflammatory factors (F=167.60, 17.78; P＜0.01) in the high-dose chloroquine group were higher than the other two groups, and the differences were statistically significant.ConclusionsIn NMDA injury retinal model, low-dose chloroquine significantly increased the survival and physiological function of RGC, and the mechanism may be related to the inhibition of glial activation and inflammatory response. High-dose of chloroquine would aggravate the apoptosis of RGC.
Hydroxychloroquine is widely used in a variety of autoimmune diseases. However, long-term use of hydroxychloroquine can cause severe retinopathy, which has a complex pathogenic mechanism and diverse clinical manifestations, mainly manifested as photoreceptor and retinal pigment epithelial damage and irreversible vision loss. Identifying damage before retinitis pigment epithelium lesions preserve central vision, so early detection is crucial to slow disease progression and reduce vision loss. The development of multimodal imaging technology and the issuance of the latest treatment guidelines provide a powerful tool for the early screening and treatment of hydroxychloroquine retinopathy. Proficient in the latest guidelines for the treatment of hydroxychloroquine can better guide clinicians to do a good job in disease screening and management, recommend risks, safe dosages and appropriate screening procedures to patients and strengthen the prevention of hydroxychloroquine retinopathy, which will help save the vision of more patients and reduce the waste of medical resources.
ObjectiveTo observe the efficacy of low-dose methylprednisolone combined with hydroxychloroquine and methotrexate in the treatment of rheumatoid arthritis (RA).
MethodsBetween January 2011 and May 2013, 60 RA patients on their first treatment with a disease course of less than or equal to 2 years were randomly divided to control group and treatment group Ⅰ with 30 patients in each. Patients in both the two groups were given hydroxychloroquine and methotrexate therapy, while the control group was treated with meloxicam (7.5 mg/time, 2 times/d) in addition, and the treatment group one was given methylprednisolone (4 mg/time, 2 times/d) in addition. Another 30 RA patients with a disease course of more than 5 years with no standardized treatment were designated into the treatment group Ⅱ. They accepted the same treatment scheme as treatment group Ⅰ. All the patients were evaluated one week after treatment to assess their clinical symptoms. Twelve weeks before and after treatment, the patients were evaluated on their clinical indicators and immunological indicators.
ResultsThe clinical symptoms of patients in treatment group Ⅰ and Ⅱ were rapidly relieved within one week after treatment, and the curative effect was significantly higher than that in the control group (P<0.05). Twelve weeks after treatment, the treatment groups were significantly improved compared with the control group in clinical symptoms and DSA28 (P<0.05). The improvement of clinical symptoms and immunological tests in treatment group Ⅰ was more obvious than that in treatment groupⅡ.
ConclusionLow-dose methylprednisolone combined with hydroxyl chloroquine and methotrexate can quickly and effectively relieve the clinical symptoms of the patients with RA, and patients with a shorter course of the disease have better clinical efficacy.
Hydroxychloroquine is widely used in the treatment of autoimmune diseases and skin diseases, mainly for the treatment of diseases such as systemic lupus erythematosus, rheumatoid arthritis and other diseases. Hydroxychloroquine has many benefits to patients, but long-term use of the drug may lead to retinal chronic toxicity changes, seriously affect the patient’s vision and quality of their lives. However, there are few studies on retinal toxicity of hydroxychloroquine in the world, easy to miss diagnosis and misdiagnosis clinically. ophthalmologists should increase the knowledge with the etiology and pathology of hydroxychloroquine retinal toxicity, through relevant auxiliary check early detection of the drug to the retina and timely suggest patients to stop. This can effectively reduce the risk of vision loss caused by retinal toxicity, and reduce the adverse effects of hydroxychloroquine on the retina while patients get a good treatment effect.
