Hydroxychloroquine is a widely used medication for various autoimmune conditions, and while generally considered safe, understanding its potential side effects, particularly retinopathy, is crucial for patients and clinicians alike.

Hydroxychloroquine (HCQ) is a medication primarily known for its historical use in treating and preventing malaria. However, it has also become a cornerstone in the management of several autoimmune diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), antiphospholipid syndrome, and primary Sjögren's syndrome [1], [2]. While generally considered safe, healthcare providers carefully monitor patients for potential adverse reactions during treatment [1].

How Hydroxychloroquine Works

The precise mechanisms by which hydroxychloroquine exerts its therapeutic effects in autoimmune conditions are still being fully elucidated [1], [3]. Researchers understand that HCQ, a weak base, has a characteristic 'deep' volume of distribution and a long half-life of approximately 50 days [3].

At a cellular level, HCQ interferes with various pathways. It is known to affect lysosomal activity and autophagy, interact with cell membrane stability, and alter signaling pathways and transcriptional activity [3]. These actions can lead to the inhibition of cytokine production and modulation of certain co-stimulatory molecules, which are key processes in immune regulation [3]. These complex modes of action are believed to explain both the clinical effectiveness of HCQ and its known side effects, such as retinopathy [3].

Potential Side Effects of Hydroxychloroquine

While HCQ is effective for many patients, it is important to be aware of its potential side effects. Clinicians are advised to carefully monitor patients with rheumatic diseases when prescribing these drugs to manage any adverse reactions [1]. The risk of side effects often depends on factors like the daily dose and the duration of treatment [4].

Retinopathy: A Key Concern

One of the most well-known and significant adverse effects associated with long-term hydroxychloroquine use is retinopathy, a condition affecting the retina of the eye [3], [4]. The damage can occur in different patterns; in many eyes, it is parafoveal (near the center of vision), but in some Asian patients, an extramacular pattern of damage may be observed [4].

To minimize the risk of retinopathy, current recommendations suggest a maximum daily HCQ dose of ≤5.0 mg/kg of real body weight, as this correlates better with risk than ideal weight [4]. The risk of developing retinopathy is low in the initial years of treatment but increases over time:

The risk of toxicity is under 1% for up to 5 years of use [4].
This risk rises to under 2% for up to 10 years of use [4].
After 20 years of treatment, the risk can increase to almost 20% [4].

However, even after 20 years, a patient who has not developed toxicity has only about a 4% risk of developing it in the subsequent year [4]. Regular eye screenings are crucial for early detection and management of this rare but serious complication [4].

Hydroxychloroquine Use During Pregnancy

Many autoimmune diseases commonly affect women of child-bearing age, leading to concerns about the safety of medications like HCQ during pregnancy [2]. Research indicates that hydroxychloroquine does not appear to be associated with an increased risk of congenital defects or spontaneous abortion [2]. However, it is important to note that comprehensive data regarding the full safety profile of HCQ throughout pregnancy may still be limited [2]. Patients who are pregnant or planning to become pregnant should discuss their treatment options thoroughly with their healthcare provider.

Monitoring and Management

Given the potential for adverse effects, particularly retinopathy, careful and ongoing monitoring is an essential part of HCQ treatment [1], [4]. Regular follow-ups with your rheumatologist and ophthalmologist are vital to ensure the medication's benefits continue to outweigh its risks. Patients should always adhere to their prescribed dosage and report any new or worsening symptoms to their doctor promptly.

Sources

[1] Hydroxychloroquine: A double‑edged sword (Review). https://pubmed.ncbi.nlm.nih.gov/39981928/
[2] Hydroxychloroquine in systemic lupus erythematosus and rheumatoid arthritis and its safety in pregnancy. https://pubmed.ncbi.nlm.nih.gov/21417950/
[3] Mechanisms of action of hydroxychloroquine and chloroquine: implications for rheumatology. https://pubmed.ncbi.nlm.nih.gov/32034323/
[4] Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). https://pubmed.ncbi.nlm.nih.gov/26992838/

This article summarises published research for a general audience. It is not medical advice — talk to a qualified clinician about your own situation. Need help finding one? Browse doctors.