Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft‐versus‐host disease

Bolaños-Meade, Javier; Zhou, Lan; Höke, Ahmet; Corse, Andrea M.; Vogelsang, Georgia B.; Wagner, Kathryn R.

doi:10.1002/ajh.20294

Cited by 41 publications

(20 citation statements)

References 16 publications

(25 reference statements)

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“…However, recent studies provided compelling evidence that autophagy protected against neurodegenerative diseases and the accumulation of autophagosomes primarily represented the activation of beneficial physiological process [15,16]. Danon disease, which is a kind of genetic myodegenerative disease, was characterized by the extensive accumulation of autophagosomes [17]. As a result, a general point of view seems to emerge that the autophagy pathway apparently improves survival via clearance of aggregate-prone proteins [18].…”

Section: Discussionmentioning

confidence: 99%

Modulating Autophagy Improves Cardiac Function in a Rat Model of Early-Stage Dilated Cardiomyopathy

Xie

Jin²,

Li³

et al. 2013

Cardiology

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Objectives: Previous studies reported that autophagy is activated in human dilated cardiomyopathy (DCM). It is still unknown whether modulating autophagy can improve cardiac function of the failing heart. Methods: We immunized rats with porcine cardiac myosin to set up a model of DCM. Rapamycin, a kind of mTOR inhibitor upregulating autophagy, was given to rats weeks after the immunization at low (1 mg/kg · day i.p.), intermediate (2 mg/kg · day i.p.) and high dose (4 mg/kg · day i.p.) for 2 weeks. Results: Compared to the control group (ejection fraction, EF = 81.3 ± 3.8%), the average EF decreased in both the DCM group (EF = 56.1 ± 3.3%) and the high-dose rapamycin group (EF = 55.9 ± 3.6%), but recovered in the low-/intermediate-dose rapamycin groups (EF = 64.9 ± 4.6/69.4 ± 4.4%). Phosphorylation of p70s6k and 4E-BP1 decreased and the expression of LC3BI/II increased in all rapamycin groups. Autophagic vacuoles were easily found in these groups. However, body weight was significantly reduced in the rapamycin groups. Furthermore, mortality was increased in the high-dose rapamycin group. Conclusions: Rapamycin could improve cardiac function of early-stage DCM, but the effect of rapamycin turned out to be biphasic and the effective range appeared narrow.

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Section: Discussionmentioning

confidence: 99%

Modulating Autophagy Improves Cardiac Function in a Rat Model of Early-Stage Dilated Cardiomyopathy

Xie

Jin²,

Li³

et al. 2013

Cardiology

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“…5,6 The development of this side-effect does not appear to be dose-dependent. 4 No report of myopathy from the quinines has been reported before 6 months of continued intake.…”

Section: Sirmentioning

confidence: 94%

Chloroquine-induced myopathy

Posada

García-Cruz

García‐Doval

et al. 2011

Lupus

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“… Pre-existing myopathy and/or neuropathy, due to the potential risk of HCQ-induced neuromyotoxicity. (58)(59)(60)(61)(62)(63)  Glucose-6-phosphate dehydrogenase (G6PD) deficiency, due to the potential increased risk of HCQ-related hemolysis crisis. (64) Interestingly, Heymann et al (65) found a significantly higher proportion of G6PD-deficient patients among the diabetic population aged 45-64 years.…”

Section: Accepted Articlementioning

confidence: 99%

Antihyperglycemic properties of hydroxychloroquine in patients with diabetes: Risks and benefits at the time of COVID‐19 pandemic

Infante

Ricordi

Fabbri

2020

Journal of Diabetes

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The antimalarial drug hydroxychloroquine (HCQ) has long been used as a disease-modifying antirheumatic drug for the treatment of several inflammatory rheumatic diseases. Over the last three decades, various studies have shown that HCQ plays also a role in the regulation of glucose homeostasis. Although the mechanisms of action underlying the glucose-lowering properties of HCQ are still not entirely clear, evidence suggests that this drug may exert multifaceted effects on glucose regulation, including improvement of insulin sensitivity, increase of insulin secretion, reduction of hepatic insulin clearance and reduction of systemic inflammation. Preliminary studies have shown the safety and efficacy of HCQ (at a dose ranging from 400 to 600 mg/day) in patients with type 2 diabetes over a short-term period. In 2014, HCQ has been approved in India as an addon hypoglycemic agent for patients with uncontrolled type 2 diabetes. However, large randomized controlled trials are needed to establish the safety and efficacy profile of HCQ in patients with type 2 diabetes over a long-term period. With regard to the COVID-19 pandemic, several medications (including HCQ) have been used as off-label drugs due to the lack of proven effective therapies.However, emerging evidence shows limited benefit from HCQ use in COVID-19 in general. The aim of this manuscript is to comprehensively summarize the current knowledge on the antihyperglycemic properties of HCQ and to critically evaluate the potential risks and benefits related to HCQ use in patients with diabetes, even in light of the current pandemic scenario. Highlights Hydroxychloroquine (HCQ) has been shown to exert antihyperglycemic properties by virtue of potential multifaceted effects on glucose homeostasis, including improvement of insulin sensitivity, increase of insulin secretion and reduction of systemic inflammation. This article is protected by copyright. All rights reserved. Accepted Article Preliminary studies have shown the safety and efficacy of HCQ as an antihyperglycemic agent in type 2 diabetes over a short-term period. A careful risk-benefit assessment of HCQ is critical for a cautious use of this drug in diabetic patients, particularly in light of the current COVID-19 pandemic.

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Hydroxychloroquine causes severe vacuolar myopathy in a patient with chronic graft‐versus‐host disease

Cited by 41 publications

References 16 publications

Modulating Autophagy Improves Cardiac Function in a Rat Model of Early-Stage Dilated Cardiomyopathy

Modulating Autophagy Improves Cardiac Function in a Rat Model of Early-Stage Dilated Cardiomyopathy

Chloroquine-induced myopathy

Antihyperglycemic properties of hydroxychloroquine in patients with diabetes: Risks and benefits at the time of COVID‐19 pandemic

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