Hydroxychloroquine (Plaquenil) Myopathy: A Rare but Incompletely Understood Side Effect

Does hydroxychloroquine cause muscle injury?

Hydroxychloroquine (Plaquenil) is a medication that is prescribed to treat a range of autoimmune diseases. For physicians who treat hair loss, hydroxychloroquine is an off label treatment option for a variety of immune mediated conditions including lichen planopilaris, frontal fibrosing alopecia, systemic lupus erythematosus and discoid lupus.

We have discussed the side effect of ‘myopathy’ from hydroxychloroquine and chloroquine in prior articles.

ARTICLE 1: Muscle Injury from Hydroxychloroquine: Are We Screening Appropriately?

ARTICLE 2: Muscle Injury from Hydroxychloroquine: What Muscles Exactly?

ARTICLE 3: What Side Effects Prompt Patients to Stop Hydroxychloroquine?

New Study Highlights Myopathy As A Side Effect of Hydroxychloroquine

In 2021, Biguetti and colleagues set out to perform qualitative and quantitative analysis on the toxic effects of chloroquine (CQ) and hydroxychloroquine (HCQ) on skeletal muscles.

The authors assessed a variety of case reports and observational studies. From case reports, a total of 21 patients presented muscle weakness and confirmatory biopsy for antimalarial induced myopathy. From observational studies, 37 patients out of 1,367 patients from five studies presented muscle weakness related to the use of these 2 antimalarial drugs, and 252 patients presented elevated levels of muscle enzymes (aldolase, creatine phosphokinase, and lactate dehydrogenase). Four studies presented data on 34 patients with confirmatory biopsy for drug-induced myopathy.

Overall, the authors highlight data that chronic use of CQ/HCQ may be a risk for drug-induced muscle injury (myopathy).

If Possible, Stopping HCQ Gives Potential for Some Degree of Muscle Improvement.

Stopping antimalarial medications may lead to an improvement in muscle weakness in many patients diagnosed with antimalarial induced myopathy. Drugs were discontinued in 7 from 22 patients with severe muscle weakness in a study by Casado et al with complete recovery for 5 patients. In a study previously discussed by Wang et al, 2 patients presenting with proximal muscle weakness had significant clinical improvement 2 months after antimalarial discontinuation.

Conclusion

This is an interesting study that highlights an area that really needs additional attention from the research world. Despite the use of chloroquine and then hydroxychloroquine for over 65 years to treat several inflammatory conditions, only a limited number of studies have addressed antimalarial induced myopathy. This includes the 5 clinical studies and 17 case reports that the authors of this study have carefully analyzed.

It’s clear now that hydroxychloroquine can cause a myopathy (muscle injury) in a small proportion of long term-users but exactly how common this is will need more studies. Estimates suggested it ranges from 1% to 13% of rheumatology patients and seems to be more common in women. Age may be a risk factor as most patients with antimalarial myopathy are older than 50 years. We will also need to understand if the risks are similar in our scarring alopecia patients who use these drugs as their baseline risks may be different than those of rheumatology patients. The muscles of interest are the skeletal muscles and the heart muscle and so further studies are needed to address both these issues.

Antimalarial induced Cardiomyopathy (heart muscle injury) has been reported as a very rare side but very serious effect of hydroxychlorquine use. Although rare, it is another important muscle for us to consider as we talk about the general concept of hydroxychloroquine’s effects on muscle tissue. To date, there are only about 50 cases reported in the published literature. Most patients with antimalarial induced cardiomyopathy have been on the drug a long time (10-20 years). Such a duration is not uncommon for rheumatology patients. This long duration is atypical for our scarring alopecia patients. Interestingly, most patients with antiamalarial induced cardiomyopathy a history of elevated CPK and CK before the diagnosis of cardiomyopathy which underscores the importance for us to consider checking these labs at baseline.

It is probably important for us to consider ordering baseline CK, LDH prior to starting hydroxychloroquine and screen for dysphagia, skeletal muscle weakness, respiratory symptoms and neck weakness at baseline as well. These can be re-assessed at follow up visits. Patients with elevated muscle enzymes or muscle related symptoms (swallowing, neck weakness, skeletal muscle weakness, respiratory muscle issues) will likely require dose adjustment (or stopping) and may require further EMG and muscle biopsy studies. Patients on hydroxychloroquine for more 3-4 years might benefit from ECG studies to better assess the QT interval, but good studies to guide these sorts of recommendations have not been done. It is likely that a muscle biopsy will be strongly considered for patients with clinical manifestations of myopathy combined with chronically elevated muscle enzyme disturbances, such as aldolase (ALD), creatine phosphokinase (CK or CPK) and lactate dehydrogenase (LDH).

REFERENCE

Biquetti et al. The toxic effects of chloroquine and hydroxychloroquine on skeletal muscle: a systematic review and meta-analysis. Sci Rep. 2021 Mar 23;11(1):6589.

Casado, E. et al. Antimalarial myopathy: An underdiagnosed complication? Prospective longitudinal study of 119 patients. Ann. Rheum. Dis. 65, 385–390.

Tselios et al. Antimalarial-induced Cardiomyopathy in Systemic Lupus Erythematosus: As Rare as Considered?J Rheumatol. 2019 Apr;46(4):391-396.

Wang, C. et al. Discontinuation of antimalarial drugs in systemic lupus erythematosus. J. Rheumatol. 26, 808–815 (1999).