Antimalarial Drugs and Lupus

Antimalarial drugs are medications that were originally used to treat malaria. But, research shows they are also highly effective at combatting lupus.

Antimalarials are used to treat malaria, a parasitic infection caused by the malaria parasite, Plasmodium falciparum. The parasite eats red blood cells, causing anemia, and produces toxic waste products that pollute and poison the bloodstream.

Malaria is a serious illness, including fevers and shaking chills, causing hundreds of millions of cases of serious disease and 0.5-2.5 million deaths per year. It is transmitted by mosquitos, and mostly found in the tropics and regions where mosquitos are common.  Many of the prevention methods involve killing or protecting people against mosquitos.

The original anti-malarial was quinine, which is derived from the bark of the cinchona plant. Quinine has been found to have health benefits beyond being an antimalarial including pain relief. It has been refined into synthetic compounds that are safer, easier to produce, and more effective against malaria.

What does this have to do with lupus? Several of these antimalarial drugs are used successfully to treat lupus and minimize flare risk. The side effects are rare and usually mild, mostly just upset stomachs and skin color changes. More serious side effects, like retina damage, can occur if high doses are taken over time. But, most lupus treatment teams consider this a small risk in contrast to the benefits provided.

What Antimalarial Drugs are Used for Lupus?

Hydroxychloroquine (Plaquenil), Chloroquine (Aralen) and Quinicrine (Atabrine) are all antimalarials used to treat lupus. Many antimalarials can also be used to treat rheumatoid arthritis, progressive systemic sclerosis, antiphospholipid syndrome, dermatomyositis, and sarcoidosis.

These medications work by modulating the immune system, possibly by preventing the activation of plasmacytoid dendritic cells, which produce interferon. They do not increase the risk of infection, and can be taken safely with other lupus medications, and are safe for use during pregnancy.

Hydroxychloroquine is one of the more well-known of these medications, and acts as a “disease-modifying anti-rheumatic drug” or DMARD.  It regulates the immune system – which is different than suppression. Regulation forces the immune system to work properly, protecting the body against disease and not attacking its own cells. Because of this, these medications do not increase the risk of infection — unlike immunosuppressants.

Lupus and Antimalarials

Antimalarials have been used to manage cutaneous and systemic lupus erythematosus since 1894. Lupus patients on antimalarials generally live longer and have fewer symptoms, and these medications can treat arthritis and Sjogren’s syndrome as well.

Antimalarial medications are very effective at treating a range of symptoms including:

• muscle pain
• joint pain
• rashes
• heart inflammation
• lung inflammation (pleuritis)
• fatigue
• fever

Additionally, they improve resistance to ultraviolet light and encourage skin lesions to heal, making them especially useful for CLE.

But, kidney disease, nervous system issues, and cardiovascular issues all require more than antimalarials. In these cases, immunosuppressive medications are used.

Notably, smoking cigarettes can make antimalarials less effective for people with lupus. There are many reasons not to smoke with lupus, which you can read about here – so add another one to the list!

How do Antimalarials Work?

Each antimalarial works differently to treat both malaria and lupus. But, they are all immunomodulatory in some way.

Chloroquine

Chloroquine interferes with the breakdown of proteins in a part of the cell called a lysosome. The lysosome breaks down and recycles used-up parts of the cell, as well as raw ingredients coming into the cell from the bloodstream. When the malaria parasite is treated with chloroquine, its lysosomes stop working properly and it cannot neutralize its own waste products.  Basically, it poisons them with their own poop!

Hydroxychloroquine

Hydroxychloroquine (HCQ or Plaquenil) is known to prevent some signaling particles from binding to toll-like receptors, which activate interferons – the alarm signal of the immune system.  Much like Chloroquine, HCQ also inhibits the ability of lysosomes to function.

The effect of antimalarials on the lysosomes might explain some of these medicine’s ability to treat lupus. In healthy cells, disrupting the lysosomes isn’t such an issue. However, in overactive cells – such as the immune system cells of a person with lupus – this forces the cell to slow down. For people with autoimmune disease, this can calm down their immune systems and prevent the organ damage associated with lupus.

Chloroquine also inhibits the processing and use of thymine, an important amino acid that is a building block of DNA and other proteins. When inhibited, it prevents hyperactive cells, such as immune system cells, from going out of control.

Other Benefits of Antimalarials

Part of what antimalarials do is protect against blood clotting, also known as thrombosis. Antimalarials also reduce lipid levels in the bloodstream effects.

Blood clots are a major problem for people with lupus, leading to a heightened stroke risk and contributing to brain fog and other symptoms. Some studies show that antimalarials reduce the clotting risk by about 68%, both in arteries and in veins. They may do this by affecting how and when platelets, the blood particles responsible for clotting, come together (or aggregate) into a clot. In particular, antimalarials effect how an antibody called “antiphospholipid–β2-glycoprotein I” binds to and communicates with the cells of the body.

Antiphospholipid antibodies are often found in lupus, so part of why antimalarials might help with lupus symptoms may have to do with their effects on this antiphospholipid-b2.

Side Effects of Antimalarials

Antimalarials can have several side effects, including:

• Dry skin
• Loss of appetite
• Bloating
• Stomach pain
• Retinal damage
• Headaches
• Muscle aches and weakness

And neurological effects such as:

• Nervousness
• Irritability
• Dizziness
• Confusion
• and Seizures

Notably, plaquenil makes psoriasis worse, and Quinacrine can cause a noticeable yellowing of the skin.

Use of these antimalarials can also damage the retina over time as the chemical ends up deposited in this area, though this is less common with hydroxychloroquine, also known as Plaquenil – only 1/5000 people who take Plaquenil for 5 years or more experience this symptom. They can also cause stomach upset, though this is mitigated by taking it with food.

However, lupus-related renal (kidney) damage, and related mortality rates, was reduced by about 9-10% when people were on antimalarials, and these side effects were rare.

As with all medications, speak with your lupus treatment team before starting or stopping and treatments — and always share any side effects that you do experience with your clinician.