Hydroxychloroquine: mechanism and retinopathy screening
Hydroxychloroquine is an antimalarial drug that dampens the immune system; its key long-term risk is retinopathy, damage to the retina (the light-sensing layer at the back of the eye).
Remember
The key long-term risk of hydroxychloroquine is retinopathy, which is irreversible, so patients need regular eye screening: annually after 5 years of use, or from 1 year if extra risk factors are present.
Hydroxychloroquine is an antimalarial drug that also dampens the immune system and is used as a DMARD (disease-modifying anti-rheumatic drug, a medicine that slows an autoimmune disease rather than just easing its symptoms). It is used in mild rheumatoid arthritis and in systemic lupus erythematosus (SLE, an autoimmune disease that can affect the skin, joints and other organs), particularly for skin and joint disease.
Its exact mechanism is still incompletely understood. It is thought to raise the lysosomal pH: lysosomes are acid-filled compartments inside cells that break down material and help process antigens (fragments of proteins that the immune system learns to recognise), so a higher pH is thought to impair that processing. It is also thought to reduce Toll-like receptor signalling. These receptors sit on immune cells, recognise signs of germs or damaged cells and switch on inflammation, so turning them down is thought to help calm the overactive immune response of lupus.
The key serious long-term adverse effect is retinopathy. It is rare, but it is irreversible, and the loss of vision can even progress after the drug is stopped. Early damage is usually symptomless and the retina often looks normal for years before toxicity appears, so patients are screened rather than waiting for symptoms. Retinal toxicity can cause constant blurred vision, changes in colour vision or sensitivity to light.
The risk rises with a higher daily dose (above 5 mg/kg), longer use, kidney disease and tamoxifen (a breast cancer drug). Annual eye review with retinal imaging (scans of the retina) is recommended after 5 years of use, or from 1 year if extra risk factors are present.
Key facts
- Drug type
- an antimalarial with immune-dampening effects, used as a DMARD.
- Mechanism
- incompletely understood, but thought to involve raising lysosomal pH and reducing Toll-like receptor signalling.
- Uses
- mild rheumatoid arthritis and SLE, particularly for skin and joint disease.
- Key adverse effect
- retinopathy, which is rare but irreversible.
- Screening
- annual eye review after 5 years of use, or from 1 year if extra risk factors are present.
- Risk factors
- a higher daily dose, longer duration, kidney disease and tamoxifen.
- Visual effects
- retinal toxicity can cause constant blurred vision, changes in colour vision or sensitivity to light.
Exam traps
- Reduced kidney function counts as a risk factor for hydroxychloroquine retinopathy, so it brings monitoring forward, but progressive renal failure is not the adverse effect that drives its long-term monitoring.
- Lung toxicity is a recognised problem with methotrexate, another conventional DMARD, and not the characteristic long-term harm of hydroxychloroquine, whose key adverse effect affects the eye.
- Bone marrow suppression (reduced blood cell production), checked with regular blood counts, is the classic monitored toxicity of drugs such as azathioprine, mycophenolate and sulfasalazine, not of hydroxychloroquine, where the irreversible risk is retinal.
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