How does Hydroxychloroquine work for Lupus (SLE)? [February 2025 Update]

Did you know that using hydroxychloroquine (HCQ) to help lupus patients was discovered by accident? Following that lucky discovery, we have learned a great deal about how hydroxychloroquine works for lupus patients. Furthermore, researchers discovered how it helps treat related autoimmune diseases, such as rheumatoid arthritis and Sjogren’s disease.

How exactly does a drug developed to treat infections help an autoimmune condition? In this article, we will explain how antimalarial drugs treat autoimmune diseases like lupus.

Click here to see the numerous benefits of taking HCQ for lupus.

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NOTE: Johns Hopkins University Press, publisher of The Lupus Encyclopedia, is a nonprofit publisher. If you purchase JHUP books, like The Lupus Encyclopedia, you support projects like Project MUSE.

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Antimalarial Drugs Helped WWII Lupus Soldiers

Dr. Francis Page was a British doctor who served during World War II. At that time, the military required soldiers to take quinacrine (mepacrine, atabrine) regularly to prevent malaria. This tropical infection initially devastated Allied forces in the Pacific theater. Interestingly, Dr. Page noticed a surprising trend. Many soldiers suffering from rheumatoid arthritis and lupus saw their symptoms improve dramatically while taking quinacrine.

Later, Dr. Page returned to England and joined the dermatology department at Middlesex Hospital in London. In June 1950, he met a 58-year-old man suffering from severe discoid lupus. For 20 years, this patient had failed all available therapies. Consequently, Dr. Page recalled his WWII experience and prescribed quinacrine. Within just eight weeks, the patient’s skin lesions vanished almost completely.

Afterward, Dr. Page and a colleague treated 17 more discoid lupus patients. All but one showed dramatic improvement. In addition, one systemic lupus patient and two inflammatory arthritis patients experienced significant relief.

Eventually, doctors switched to prescribing chloroquine because quinacrine caused yellow skin discoloration. However, chloroquine caused eye problems for some individuals. As a result, hydroxychloroquine became the preferred drug because it offers a much safer profile.

Hydroxychloroquine is “Life Insurance for Lupus”

Doctors have prescribed HCQ to treat lupus for over 60 years. Currently, it remains the safest lupus medication available. Most importantly, it is the only drug proven to prolong survival in patients. Despite its high safety profile, it delivers an incredible number of benefits. In fact, few medicines in modern healthcare offer as many advantages for lupus patients.

These remarkable benefits include:

• Reduces organ damage (is a true disease-modifying agent for lupus)
• Prolongs survival
• Decreases the need for steroids (steroid-sparing)
• Reduces infections
• Reduces cancer in lupus patients
• Reduces the risk of diabetes, and lowers sugar levels in diabetics
• Reduces bad cholesterol levels
• Prevents heart attacks, strokes, and blood clots (the top causes of death in SLE patients)
• Improves the chances for a successful pregnancy in SLE patients
• Lowers antiphospholipid antibody levels
• Increases the chances for remission in lupus nephritis
• Reduces lupus nephritis flares
• Is a disease-modifying agent for lupus nephritis (reduces kidney damage from lupus)
• Reduces systemic lupus flares

Top Tips on Taking Hydroxychloroquine

Medical experts recommend that all lupus patients take hydroxychloroquine (Plaquenil) or chloroquine. As listed above, these antimalarial drugs provide a ridiculous number of benefits. Furthermore, they remain the safest treatments we use today.

Fortunately, you can utilize numerous strategies to take hydroxychloroquine safely. Even if you experience side effects like a rash, itchy skin, or an upset stomach, you can manage them easily.

For more details, please see my other article on “Top Tips on Taking Hydroxychloroquine.”

 

“How do medicines used to treat malaria also work for autoimmune diseases like lupus?”

Antimalarial drugs, such as hydroxychloroquine (Plaquenil), chloroquine, and quinacrine, are very common treatments for autoimmune disorders. This is especially true for lupus (SLE) and Sjogren’s.

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Understanding the Immune System and Antigens

To understand how these medicines work, you first need to understand the human immune system. Specifically, we must look at a biological process called antigen presentation (figure 30.1A).

Antigens are specific foreign proteins. When the immune system detects them, it creates protective antibodies. For instance, imagine you catch the parvovirus. This virus can cause cold-like symptoms, rashes, and joint pain. First, your immune system “sees” the foreign parvovirus proteins. Next, it recognizes these invaders and launches a defensive war.

To fight back, your body makes antibodies that attach to the parvovirus antigens. Consequently, this action flags the virus as a threat. Finally, the antibodies alert specialized white blood cells to attack the virus. Your body now remembers this specific enemy. If you encounter parvovirus again, your white blood cells will destroy it before you feel sick.

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Hydroxychloroquine Changes the Acidity Inside Immune Cells

The Role of Macrophages in Lupus

Now, let us dive deeper into how your body makes these antibodies. We will focus on a concept called antigen processing (figure 30.1A). While this is a highly technical discussion, it perfectly explains how anti-malarial medicines work.

Macrophages are special white blood cells that identify foreign antigens. You can think of them as frontline soldiers. They make the first contact with invading viruses and bacteria. Immunologists often call macrophages “antigen-presenting cells.”

In lupus patients, the immune system mistakenly attacks healthy body parts. It wrongly assumes natural body proteins are foreign invaders. When macrophages spot these natural proteins, they swallow them into tiny bubbles called vacuoles (follow along in figure 30.1A). Inside these vacuoles, the cell digests the proteins into smaller pieces. Then, it reassembles them on the outside of the macrophage.

Afterward, the macrophage presents these proteins to T-cells. This presentation signals B-cells to create antibodies. In lupus, we call these misguided attackers “auto-antibodies.”

The Role of pH Levels in Lupus Inflammation

Let us look at a well-known example involving systemic lupus erythematosus (SLE). Ultraviolet (UV) light can damage human skin cells. Consequently, these damaged cells release their DNA into the bloodstream. The lupus immune system sees this natural DNA as a foreign attacker. As a result, it creates anti-DNA autoantibodies.

When these autoantibodies attach to the DNA, they form an “immune complex.” These complexes travel throughout the body and deposit in tissues like the kidneys. Ultimately, this causes severe inflammation, such as lupus nephritis. This sequence illustrates exactly how UV light exposure can cause a rash locally, while simultaneously damaging distant organs.

To prevent this, we must look at the macrophage vacuoles. These tiny bubbles need a highly acidic environment (low pH) to digest proteins. If the pH level rises, the digesting enzymes stop working completely.

Interrupting the Immune Response

This exact mechanism is where antimalarial medicines step in. Drugs like hydroxychloroquine enter the macrophages and gather inside the vacuoles (figure 30.1B). Because these medicines have a naturally high pH level, they make the vacuoles less acidic.

Consequently, the digestive enzymes fail to break down the proteins. Therefore, the T-cells cannot “see” the antigens. Because the T-cells stay blind to the proteins, they never signal the B-cells to make autoantibodies.

Ultimately, this process successfully calms down the overactive lupus immune system. Interestingly, it achieves this without causing overt immunosuppression. The rest of your immune system continues functioning normally, thereby protecting you from actual infections and cancers.

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Why Hydroxychloroquine Is Not a Cure for Autoimmune Diseases

After reading the explanation above, this medication might sound like a perfect cure. If it stops autoantibodies, it should completely control lupus, right?

Unfortunately, the human body operates in a much more complicated way. Antigen processing represents just one tiny part of the immune system. In SLE patients, many other immune processes also function abnormally. Furthermore, hydroxychloroquine does not completely stop antibody formation. It is actually a very mild medication.

Instead of shutting down the system, it simply “calms” the process. Honestly, we should be thankful it works this way! We still need our immune system to fight off real threats. Thanks to this balance, SLE patients taking HCQ actually experience fewer infections than those who skip the medication.

Moreover, antimalarials work on the immune system in other ways. For example, we believe that inhibiting part of the immune system called Toll-like receptors plays a massive role in treating lupus. However, delving deeper into that topic requires a completely different post. The purpose of this article was simply to explain one fascinating way an infection medication treats an autoimmune disease.

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​How Hydroxychloroquine Kills Malaria

Interestingly, a very similar chemical process happens when treating malaria. Single-celled parasites called Plasmodium cause malaria after a mosquito bite. First, these organisms invade red blood cells and consume iron-rich hemoglobin. Next, they digest this hemoglobin inside their own acidic vacuoles, just like our macrophages do.

Like human macrophages, the malaria parasites need an acidic environment to digest food and dispose of waste. The antimalarial medicine enters the parasite’s vacuoles and raises the pH level. Consequently, the organism cannot digest its food or clear out the toxic heme waste.

Ultimately, the trapped waste builds up, poisons the parasite, and stops it from reproducing. In summary, antimalarials increase the pH levels inside both malaria parasites and human macrophages. In the case of malaria, the organisms die. In the case of lupus, the immune system calms down, reducing bodily attacks.

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Hydroxychloroquine is the Safest Drug for SLE

Most side effects from HCQ fall into the “nuisance” category. Moreover, you can easily prevent most of these minor issues with simple interventions. For helpful advice, please read our guide on top tips on how to prevent side effects from HCQ.

The most significant potential side effect involves vision problems. In rare cases, the medication can deposit in the back of the eye. Fortunately, modern eye exams prevent this issue effectively. As long as you attend your annual checkups, it is rare to have any eye problems from HCQ.

Please get 2 yearly eye exams (SD-OCT and a VF 10-2) if you take Plaquenil or chloroquine.
Get 3 tests if you are Asian (add on a VF 24-2 or a VF 30-2)

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For more in-depth information on hydroxychloroquine and lupus:

Read chapters 29 and 30 of The Lupus Encyclopedia, edition 2

Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia.

If you enjoy the information from The Lupus Encyclopedia, please click the “SUPPORT” button at the top of the page to learn how you can help.

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What are your comments and opinions?

If you take hydroxychloroquine or chloroquine for lupus, what has your experience been? What do you recommend for other patients? Do you have any questions to ask Dr. Thomas?

Please click on “Leave a Comment” above to comment.

Please support “The Lupus Encyclopedia” blog post page

Click on “SUPPORT” at the top of the page to learn how you can support “The Lupus Encyclopedia.”

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The above excerpt and figure comes from “The Lupus Encyclopedia” by Johns Hopkins University Press. The language has been altered for better readability.

Source of electron microscope malaria parasite food vacuole: Jani D, et al. HDP-a novel heme detoxification protein from the malaria parasite. PLoS Pathog. 2008 Apr 25;4(4):e1000053. doi: 10.1371/journal.ppat.1000053. PMID: 18437218; PMCID: PMC2291572.

Author

Don Thomas, MD, author of “The Lupus Encyclopedia” and “The Lupus Secrets“

Other references:

Torigoe M, Sakata K, Ishii A, Iwata S, Nakayamada S, Tanaka Y. Hydroxychloroquine efficiently suppresses inflammatory responses of human class-switched memory B cells via Toll-like receptor 9 inhibition. Clin Immunol. 2018 Oct;195:1-7. doi: 10.1016/j.clim.2018.07.003. Epub 2018 Jul 4. PMID: 29981383.

Wang F, Muller S. Manipulating autophagic processes in autoimmune diseases: a special focus on modulating chaperone-mediated autophagy, an emerging therapeutic target. Front Immunol. 2015;6:252. Published 2015 May 19. doi:10.3389/fimmu.2015.00252

For more in-depth information on How does Hydroxychloroquine work for Lupus (SLE)? [February 2025 Update]:

Read more in The Lupus Encyclopedia, edition 2

Look up your symptoms, conditions, and medications in the Index of The Lupus Encyclopedia

If you enjoy the information from The Lupus Encyclopedia, please click the “SUPPORT” button at the top of the page to learn how you can help. 

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What are your comments and opinions?

If you have lupus, what has your experience been? What do you recommend for other patients?

Do you have any questions to ask Dr. Thomas?

Please click on “Leave a Comment” above to comment.

Please support “The Lupus Encyclopedia” blog post page

Click on “SUPPORT” at the top of the page to learn how you can support “The Lupus Encyclopedia“

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