What are the risks of in vitro fertilization for people with lupus?

IVF and lupus have a complicated relationship.

Hormonal changes in the body are notorious for causing problems for people with autoimmune diseases like systemic lupus (SLE.) This is why some people with lupus are careful about what contraceptives they use. Spikes in hormone levels from, say, a birth control pill may induce symptom flares. Thrombosis (life-threatening blood clots) has also been reported. You can read more about clot risks for people with lupus here.

IVF has been researched for the risk for causing disease flares because of its use of hormone therapy.

37 women with lupus (SLE) or antiphospholipid syndrome participated in a 2017 study published in the Journal of Rheumatology. 97 IVF procedures occurred during the study. The procedures resulted in 27 pregnancies. From those pregnancies, there were:

• 23 live births from 26 neonates (3 twin pregnancies)
• 2 miscarriages
• 2 terminations for trisomy 13 and 21

6 spontaneous pregnancies occurred during follow-up. In total, 26 of the 37 women delivered at least 1 healthy child.

 

Exploring the risks of IVF

The researchers noted that “complications occurred in or after 8 IVF cycles.” During the pregnancies, 4 people experienced lupus flares and 4 others experienced major thrombotic events. Also reported were 6 mild SLE and 1 deep-vein thrombosis. 

37% of the infants were pre-term (early) births, 15% had HELLP, and 7% had preeclampsia, a serious condition that can hurt both mother and child.

Rheumatology Advisor highlighted two challenges of this study:

• A relatively small sample size
• 15 procedures used Oocyte donation cycles. This type of procedure involved a milder stimulation protocol

A separate 2000 study found that neonatal lupus, a form of lupus that appears in newborns, was also sometimes reported.

IVF, pregnancy, & lupus

There is always a risk of complications with pregnancy, and lupus can add to those risks. Check out this article on pregnancy and lupus to learn more about those risks.

IVF success rates are good, but people with lupus have a slightly higher risk of complications according to the research. However, people with lupus can reduce this risk by sticking to their treatment plan.

In a study published in 2013, the researchers ruled that several symptom flares were not linked to IVF therapy at all. Failure to adhere to medication treatment plans and prescribed diets caused the symptom flares and thrombosis, according to the clinicians and researchers.

If you choose to undergo IVF, be sure to add all clinicians to your lupus and health treatment team. It will be important to continue consistently monitoring your health. You should also discuss any personal risks with your lupus treatment team.

Calcineurin is a hardworking molecule found in everything from plants to insects to humans. Calcineurin gets its name from the metal calcium (Ca on the periodic table) which is one of the materials that is used to build this molecule. Calcineurin inhibitors prevent calcineurin from doing its job and are used as immunosuppressant medications to treat lupus. Calcineurin inhibitors are under investigation for people with kidney focused lupus (lupus nephritis) that does not respond to other treatments. 

Is this a good idea? The answer is complicated.

What is Calcineurin?

Calcineurin is a phosphatase, a molecule that breaks apart and deactivates certain molecules that contain phosphate. In this case, it affects serine and threonine, which are involved in many different functions throughout the body. The nervous system is one area where calcineurin is involved, the kidneys are another. However, one of calcineurin’s other functions is activating T-cells, the immune system cells in the body produced in the thymus. 

T-cells are one of the immune system cells involved in autoimmune diseases such as lupus, which makes controlling calcineurin an important avenue for treating lupus. In many autoimmune diseases, some research indicates that calcineurin might not be doing its job properly. People with lupus might benefit from calcineurin being less active.

What is a Calcineurin Inhibitor?

Calcineurin inhibitors are used to treat autoimmune disorders such as lupus. Calcineurin inhibitors, also known as CNIs, include cyclosporine, tacrolimus, pimecrolimus, and voclosporin. 

Calcineurin inhibitors are highly fat soluble, which makes them able to easily reach organs that have a high fat content or insulation, such as the lymph nodes and kidneys. In general, calcineurin inhibitors work by taking up space on receptors on cells that would usually accept calcineurin, blocking the molecule from the receptor. Fewer calcineurin molecules are able to signal to the cells that they need to produce cytokines and activate t-cells. Tacrolimus and pimecrolimus work this way. Voclosprin, also known as “Lupkynis” does the same thing, but is actually more like Cyclosporin:  

Cyclosporin actually does the opposite – it attaches itself to cyclosporin, holding it back from attaching to receptors.

Most CNIs are taken orally (by mouth,) but some can be given topically (on the skin.) Either way, this reduces inflammation and the symptoms of autoimmune diseases such as lupus. 

Generally, tacrolimus and cyclosporine are used for lupus, and CNIs are taken alongside other treatments. Tacrolimus is a calcineurin inhibitor that doesn’t constrict the blood vessels as much as the others and doesn’t encourage scarring in injured organs which makes Tacrolimus a potential alternative for people who already have kidney damage. Other CNIs can also be used for lupus: Voclosporin seems to be especially beneficial for patients who are already on immunosuppressants. 

CNIs are not excreted in breast milk, so they are sometimes used to manage LN during that time. However, overall, CNIs are not usually recommended for use in pregnancy. A modified version of cyclosporin is approved for use in children. Lower doses might be needed for older kidney transplant patients because of the possibility that it can exacerbate kidney damage. 

Calcineurin and the Kidneys

Calcineurin is also involved in proper function of the membranes in the kidneys that filter the bloodstream. These membranes are on special cells called podocytes which act as the barrier between the bloodstream and the kidneys. When there is too much calcineurin, or when it isn’t functioning correctly in the body, then the podocytes can start to weaken and collapse. This may potentially be one of the main ways that the kidneys are damaged in lupus, both SLE and LN.

Calcineurin Inhibitor Side Effects

Patients on CNIs generally start with a higher dose (0.1mg/kg per day) and are gradually reduced to a lower chronic dose (dependent on patient.) This lower dose is generally tolerated well, but CNIs are stored in fat and will stay in the system for a significant amount of time.

On higher doses, CNIs can exacerbate kidney damage – this is the main reason why doctors are cautious before prescribing CNIs for lupus. However, there is some evidence that implies that the reduced kidney functionality might be from lupus damage instead. Doctors are still cautious, however, but do use CNIs when there is both a lower risk of kidney damage in the patient and a need for less immunosuppression for some reason.

Neurological and sensory symptoms can be exacerbated, and hypertension can be a potential side effect. Diabetes is also a side effect, mainly of tacrolimus. Gastrointestinal symptoms have also been reported. Tacrolimus doesn’t appear to have effects on fertility or pregnancy, though, fortunately.

Additionally, a 2024 study using the Lupus Registry of Nationwide Institutions (LUNA)  found that calcineurin inhibitors did not increase the risk of cancer in people with lupus.

The immune system works by sending specialized cells after targets that the body has marked with “flags” called antibodies. Every person has millions of different antibodies, each one unique and able to bind to different targets. In overall healthy people, antibodies that flag the body’s own cells for attack, called “autoantibodies” (“auto,” in this case, means “self”) are caught and destroyed by a sort of internal “quality control.”

However, in systemic lupus erythematosus (SLE) and other autoimmune diseases, the body doesn’t perform this quality control properly. As a result, healthy cells are misidentified and attacked throughout the body.

When the immune system attacks the body, it generates inflammation. Inflammation can cause pain, interfere with the proper function of organs, and can even cause lasting damage. In addition, it convinces the body that there is a threat to it, encouraging the production of more autoantibodies!

Because of this, Lupus Warriors may feel like their own immune system is the enemy. After all, the immune system is the root of their disease and the source of flares! Usually, lupus medications focus on regulating or almost turning it off completely (as in the case of immunosuppressants). But, what if the immune system could be used to fight the very lupus it causes? What if it could be manipulated in order to fix itself?

These are exactly the questions that a class of medications called monoclonal antibodies hope to answer.

What are Monoclonal Antibodies?

Monoclonal antibodies are molecules made in a laboratory to act like antibodies targeting specific substances in the body. Typically, they are administered intravenously (through the vein using an IV setup) in hospital or in an appropriately equipped home setting.

Essentially, monoclonal antibodies mark cells which causes the marked cells to be attacked by the immune system, destroying them. The targets, also known as antigens, can be anything. Specifically speaking, antigens that monoclonal antibodies target are engineered to target specific types of cells.

In their most prevalent use for treating cancer, monoclonal antibodies can be directed to mark:

• substances found on the surfaces of cancer cells
• proteins in the cell membranes of cancer cells
• signaling proteins involved in cell growth
• key proteins that control the development of blood vessels
• proteins that hold back immune system cells from attacking cancer cells

Once marked, these proteins are attacked by the immune system, slowing the growth of tumors or even destroying them.

Since monoclonal antibodies can be made to bind to targets only found on specific cells, they can also act as highly-specific delivery molecules. If something is attached to them, they can carry drugs, toxins, or radioactive substances directly to the cells of concern. This can increase the effectiveness of the treatment and reduce the impact on non-targeted cells. The fewer non-target cells that are affected by a treatment, the more precise the therapeutic delivery is.

While all of these features of monoclonal antibodies are of interest for lupus, the feature that most current monoclonal antibody treatments for lupus focus on is “mark-and-destroy.” Through these monoclonal antibodies, people with lupus and their treatment teams can potentially re-tune their immune systems.

 

B Cells and Monoclonal Antibodies

B-cells are very important targets for monoclonal antibodies. If they are disrupted or destroyed, B cells can no longer produce cytokines. (One role of cytokines is telling immune system cells to ramp up inflammation.)

Destroying B cells and preventing cytokines from being produced turns down the alarm level of the cells, and reduces lupus symptoms, making B-cells common targets for lupus. You can read more about B-cells and lupus here.

Monoclonal Antibodies (mABs) for Lupus

Today, there are limited pharmacologic options when it comes to treating lupus. mABs add more options and new strategies for development. This makes it a lot more likely that a lupus treatment team could tailor a medical strategy to that person.

Of the monoclonal antibodies, Rituximab is the most used monoclonal antibody or mAB for lupus. It acts on the membrane protein CD20, which is found on B lymphocytes. In studies, it improved symptoms. While it was not more effective than more conventional treatments, it was able to work in patients resistant or non-responsive to corticosteroids.

Belimumab, also known as Benlysta, targets a cytokine (BLyS) of the tumor-necrosis factor ligand and inhibits its activity. Epratuzumab and other mABs target other parts of the immune system.

Anifrolumab targets type-1 interferon (IFN,) which is continuously active in lupus and encourages inflammation. When IFN is blocked and turned off, inflammation is reduced. In trials, anifrolumab was able to reduce disease activity and symptoms even when the steroid dose was reduced.

A few other notable targets of monoclonal antibodies include:

• CD20
  • An antigen found on the membranes of all B cells, but not on other plasma cells, which makes it an ideal and relatively harmless target for monoclonal antibodies.
  • Several monoclonals, including veltuzumab and ocrelizumab target CD20.
• CD22
  • A receptor in the membranes of B-Cells that bind to sialic acid and act as inhibitors (limiters of B-cell activity). Targeting CD22 would target B cells too, but a delivery monoclonal antibody could deliver sialic acid right to it.
• BLyS, or the B-Lymphocyte Stimulator Protein
  • Controls whether B-cells self-destruct. If they are allowed to self-destruct, this can help reduce the immune response and SLE symptoms.

Also, the monoclonal antibody Eclulizumab targets C5, a protein that normally would bind two other proteins together. These two proteins combined create a compound, C5b-C9, that regulates inflammation in podocytes and glomeruli, the key cell types in the kidney. This makes Eclulizimab potentially very useful for the treatment of lupus nephritis.

Side Effects of Monoclonal Antibodies

For the most part, monoclonal antibodies have relatively mild side effects related to the activation of the immune system or the IV itself. This is a part of why monoclonal therapies are so promising as a treatment! However, these side effects can include:

• Allergic reactions, including hives or itching
• Irritation such as skin rashes
• Flu-like symptoms
• Nausea and Vomiting
• Lowered blood pressure
• Diarrhea

Subacute cutaneous lupus (SCLE) is a form of mild cutaneous lupus that might be caused by monoclonal antibodies. There are other side effects are specific to monoclonal antibodies for lupus, as well. Like all immune system suppressing drugs, some monoclonal antibodies can make people more vulnerable to infection.

In general, however, these symptoms are mild, and monoclonals are a viable medication for lupus.

Glucocorticoid medications are extremely powerful drugs for systemic lupus erythematosus (SLE) and other autoimmune diseases. One of the most common, Prednisone, is considered a gold standard for lupus treatment.

Unfortunately, the benefits of these medications also come with serious side effects. You can read more about glucocorticoid medications and their side effects here.

Despite the issues, stopping glucocorticoids is a complicated decision to make. Stopping glucorticoids can remove many burdensome side effects, including weight gain, from Lupus Warriors. Some research even suggests it can help people with lupus heal. However, the consequences of going off of the meds “cold turkey” can be serious. 

Doctors are also concerned that without the medication, the symptoms might flare. Because remission, defined as “a period of at least 5 years without active lupus symptoms,” is difficult to achieve in SLE without treatment, the goal is to have people with lupus take as low a dose as possible. The hope is this will minimize side effects and prevent symptoms.

However, if the side effects are particularly harsh, then a Lupus Warrior and their doctors might consider weaning off the medication – reducing the dose with the intent to carefully end the treatment. 

Doctor-Assisted Glucocorticoid Withdrawal

In a study published June 2019, 148 patients were selected from a group of people with lupus. Withdrawal from glucocorticoids was attempted in 91 patients (61.5%) and they were followed over the course of 6 years. They were weaned off of the medication with doctor assistance, and less than half of these patients were in complete (48.9%) or clinical (39.6%) remission. (Clinical remission is a less complete remission, but still has a reduction of symptoms.)

People with lupus who stopped glucocorticoids experienced significantly lower disease activity, and most (54.2%) were able to achieve complete remission. Some people still experienced flares.

However, this study concluded that glucocorticoid withdrawal is achievable. But, and the researchers stressed, it should be attempted only after long-term remission.

While steroid-free medical regimens are possible, they are still being investigated. 

Tapering or stopping glucocorticoids is a person-by-person decision. The main factor in such a decision should be your risk of relapse. For people at high risk, stopping prednisone, was associated with a four-fold risk of symptom onset.

If you are at high risk, low dose prednisone is less risky than stopping all together.

Avoiding Withdrawal from Glucorticoids

Stopping glucorticoids suddenly can cause a shift in body chemistry, leading to side effects known as “withdrawal symptoms.” These symptoms include fatigue, pain, and loss of appetite, and can make existing lupus symptoms worse. Tapering – the gradual reduction of glucorticoid dose – is a way to help keep the body from being shocked and prevent these symptoms from being too severe.

 

What does the Future Look Like?

Stopping medication is considered achievable after long-term remission,  but whether it is dangerous is not as clear. There is a clinical trial that hopes to clarify this:

It is not yet recruiting (though was entered in 2019,) but will be a 36-month randomized, double-blind, placebo-controlled, parallel group trial, investigating whether SLE can be kept in remission without low dose glucorticoids.

The need for new research

Two factors are increasing the study of non-medication-based treatments for pain:

1. Increased understanding of the prevalence, imposed physical limitations, and economic impact of chronic pain
   • 65% of people with lupus list chronic pain as the most difficult aspect of lupus
   • ⅔ people with chronic pain reported decreased ability to exercise, sleep, perform household chores, or drive a car
   • “The financial cost of chronic pain is roughly the same as cancer or cardiovascular disease.”
2. Overdose and death from opioids has become a major health crisis
   • “Every day, more than 130 people in the United States die after overdosing on opioids.”

New prescribing guidelines aiming to reduce opioid use disorder can also make it challenging for people with chronic pain to get treatments

Mindfulness-based stress reduction research

A January 2019 published meta-analysis in Evidence-Based Mental Health explored the effectiveness of alternative chronic pain treatments. The researchers analyzed 21 randomized controlled trials (12 of which met subsequent quality standards) on mindfulness-based stress reduction, cognitive behavioral therapy (CBT), and chronic pain.

Chronic pain as a result of lupus was not specifically studied. Chronic pain sources included musculoskeletal pain, fibromyalgia, chronic lower back pain, rheumatoid arthritis, and others. 

Mindfulness-based stress reduction and CBT showed “clinically important advantages relative to control” for physical functioning, pain intensity, depression. This is particularly fascinating as control participants in some study arms received standard-of-care pain management, including medications.

 

What is mindfulness-based stress reduction?

As the name suggests, mindfulness-based stress reductions are interventions that help reduce stress by cultivating an awareness of the current moment (mindfulness). Meditation, breathing exercises, and yoga are 3 examples of mindful exercises.

The goal of these exercises is to encourage a body awareness and bring the focus to the present. These strategies make it easier to recognize body sensations, emotions, and thoughts and then to let them go.

In the research paper discussed above, the mindfulness exercises were administered by certified MBSR teachers or other trained professionals.

4-7-8 Breathing

You can try these strategies out for yourself! A good one to start with is mindful breathing — also known as diaphragmatic breathing or abdominal breathing. The goal of this exercise is to pace your breaths and generate a calm feeling. 

 

Quick tips:

• Sit with your back straight
• Try to keep your tongue touching your gums just above your front teeth during the cycle. When you exhale with your mouth open, you will breathe around your tongue

 

Steps:

1. Exhale completely through your mouth — make a whoosh sound
2. Close your mouth and inhale through your nose. Count to 4 in your head
3. Hold your breath and count to 7
4. Exhale completely through your mouth, making a whoosh sound, and count to 8
5. Repeat until you complete the cycle 4 times

 

To start, try to complete the exercise twice per day. As you continue, you can add daily repetitions or increase the number of breaths that you take. 

Looking for other mindfulness exercises? Check out these 22 individual and group strategies

Chronic pain and medications

Medications will still continue to be an important part of the toolkit in the battle against chronic pain. It is not always possible to cure chronic pain. Work with your lupus treatment team to establish a safe and effective regimen. Even over-the-counter pain medications can be dangerous when taken at high doses or when taken in conjunction with other medications. Before starting any new medication, talk to your rheumatologist.

 

Prescription-strength medications, including opioids, are used in cases of severe pain. While opioids are strong pain relievers, they also come with a high risk of dependence and addiction. 

 

Opioid overdose risks are increased for people with reduced kidney or liver function. Be sure to check out these resources if you or a loved one is using an opioid for pain management:

• Safe Use, Storage, and Disposal of Opioid Drugs — by the American Academy of Family Physicians
• Opioid Overdose — by the U.S. National Library of Medicine

Over-the-counter (OTC) medications

OTC medications are available without a prescription, though they may still come in a variety of dosages. Be sure to read the labels to ensure you are taking a safe dose for your body weight. Always bring up new medications with your treatment team.

There are 2 main types of OTC pain relievers:

1. Acetaminophen
   1. Tylenol
2. Nonsteroidal anti-inflammatory drugs (NSAIDs)
   1. Aspirin
   2. Ibuprofen (Advil; Motrin)
   3. Naproxen (Aleve)

Virtual Reality and Mindfulness

Normal mindfulness practices have been well-documented and are beneficial to mental health. However, mindfulness practices can often be difficult to adopt. This can be due to environmental factors, personal distractors, or simply the inability to find the right avenue. Virtual reality may be the answer, by providing an immersive environment for practicing mindfulness techniques. It can also aid in orienting users to the present moment, without distractions, within a tailored virtual setting.

Research and understanding has been limited, making it difficult to draw assertive conclusions. A study in Australia studied a sample of 37 participants from the general population. They trialed a VR mindfulness app in a controlled laboratory setting. The VR app presented users with an omnidirectional video of a peaceful forest environment with a guided mindfulness voiceover that was delivered by a male narrator. Results showed that overall state of mindfulness significantly increased, and there were no notable changes in negative emotion.

Virtual reality may be a new way to achieve mindfulness, by providing guided meditation and an immersive environment. Stay updated for new research and studies into the VR and mindfulness field.

 

Updated on November 3, 2020.

Remission is a term used to describe the reduction, into nothing, of the symptoms of an autoimmune or chronic disease for three or more years. In lupus, remission includes the symptoms and the blood markers of inflammation as well, so the symptoms are not just being “masked” or “endured.” In an analysis of people with SLE over 32 years, 14.5% of the 532 people were able to achieve complete remission for 3 years. 

During remission, people with lupus may feel normal, aside from the side effects of medication. However, although medication can be tapered at this time, it shouldn’t be stopped without consultation with a doctor, because the lupus has not gone away – just dormant.

Flares and Remission

Medication can help make remission an achievable goal, but there are many factors involved and remission in lupus can be unpredictable making lupus treatment something of a puzzle. Every person with lupus is affected by their diet, environment, and genetics, and not all of these can be controlled. This is remission, too, not a cure: Remission can last as short a time as 3 months (not even meeting the definition of remission!) and flares can happen even after 10 years without symptoms, making long-term management and treatment of SLE important.

Flares are the sudden increase of symptoms in response to something that triggers the inflammatory response. Triggers are unique for each person, but a few common flare triggers are allergens, temperature, diet and stress. People with lupus often figure out their own triggers through trial and error, but not every trigger is completely avoidable.

How to Achieve Remission in Lupus

The current treatments for lupus focus on reducing symptoms and increasing quality of life. This includes protecting the organs from damage and reducing pain, but also reducing the inflammation responsible for the symptoms of lupus. This can sometimes lead to complete remission of symptoms. 

Lupus medications include antimalarials, glucorticoids, and corticosteroids. Medication is an important part of treatment, and one of the best ways to make your way to remission. You can read more about medications here. Diet can also be an important tool for achieving remission. 

However, even if complete remission isn’t possible, partial remission can leave you with more energy and ability, known in the community as “spoons,” to take care of yourself and do the things you enjoy. Treatment and a healthy lifestyle can also keep you out of the hospital, which can be costly in both time and money. This is why treatment usually focuses on finding a way to give people with lupus lighter symptoms, not complete remission. 

A Lupus Warriors Takeaway

Remission is very possible for people with lupus, but the goal should be to live your life with minimal pain and fatigue. Medication is an important part of this, but so is exercise, diet, and avoiding flare triggers.

Medication Interactions, OTCs, and Lupus

Overuse of OTC drugs can cause mood swings, memory issues, depression, anxiety, and can change one’s appetite and sleeping patterns to less healthy levels – all of which can be disrupted by lupus. OTCs can also interact with prescribed medications and interfere with treatment in inconvenient – or dangerous – ways: 

Some medicines interact via “Duplication,” where the OCT and prescribed medicine do the same things, so it causes an overdose. Most commonly, this occurs with NSAIDs like Ibuprofen and pain relievers like acetaminophen, two OTC medications often used by people with lupus. Too much of this type of medication can cause damage to the kidneys and liver as the body tries to filter it out of the bloodstream and gets overwhelmed. 

Some interact by “Opposition,” where the medicines have opposite effects. They tug-of-war with each other, and the effectiveness of one or both medications is reduced. Sometimes, the opposing effect isn’t even the main active ingredient or desired effect, but a side effect of the OTC. 

Some interact by “Alteration,” where one medicine changes the way that the other medicine operates in the body. It can affect the processing of the medication, the absorption of the medication, or even the transport of the medication. A well-known example is aspirin, which can cause a blood-thinning effect, and also changes how other blood thinners operate in the body.

NSAIDs, Pain Relievers and Lupus

NSAIDs are used to reduce swelling, stiffness, pain, headaches and fevers even at nonprescription strength. Acetaminophen is not an NSAID and is not anti-inflammatory, but some brands combine it with aspirin. Over the counter NSAIDs are generally made for short-term use and can cause damage over long periods of time. A basic rule of thumb is 3 days straight for fevers and 10 days for pain, unless a doctor says otherwise.  When they prescribe NSAIDs, doctors generally use the lowest effective dose for the shortest time possible. 

Non-Steroidal Anti-inflammatory drugs work by preventing a class of enzymes known as cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2) from producing signaling molecules associated with pain and inflammation. Many NSAIDs block both COX-1 and COX-2, which reduces inflammation but also reduces protection to the stomach lining and kidneys. Celebrex is formulated to only block COX-2. As a selective NSAID, it might be less likely to cause stomach problems associated with blocking COX-2. Antacids or taking the NSAID with food can reduce the effects of NSAIDs on the stomach. 

NSAIDs can cause gastrointestinal issues that include bleeding, poor absorption or processing of nutrients.

NSAIDS can conflict with ACE inhibitors, beta blockers, or diuretics (medicines that encourage urination to remove excess fluids,) and prevent them from properly working to prevent heart failure and high blood pressure. This can also overload the kidneys, which exacerbates kidney damage and certain other lupus symptoms. Kidney damage from overuse of NSAIDs or interactions with NSAIDs can be a major issue, especially if there are symptoms of lupus nephritis or other kidney damage. For people with lupus who may be more vulnerable to gastrointestinal, kidney, and nutritional issues, this can be additionally dangerous. You can read more about kidney damage and lupus here. 

Most NSAIDs, aside from aspirin, can cause higher blood pressure and increase the risks of heart attack and stroke. People with lupus are at increased risk of cardiovascular disease and stroke already, so this is something to consider. Aspirin is an anticoagulant, so it thins the blood and is considered to reduce the risks of stroke (ischemic stroke, not intra-cerebral bleeds,) and cardiovascular events. However, that can also be an issue for people taking blood thinners, because NSAIDs interact with blood thinners to increase the risk of bleeding.

Some people with lupus also use methotrexate (or rheumatrex,) a chemotherapy drug that is used as an immunosuppressant. This drug interacts with NSAIDs and increases the risks of liver toxicity and damage. 

Most of the time, taking over the counter NSAIDs is not too much of an issue for people with lupus. They just should be taken with care, under a doctor’s guidance, and not overused.

Antihistamines, Allergy Medications, and Lupus

Antihistamines are used to treat the symptoms of allergies. Usually, they are used to treat seasonal allergies like pollen but also help with allergies to other, usually external, triggers, such as food, dust, mold, and insect bites. Antihistamines can also help treat allergies to certain medications and drugs, stomach problems, colds, and even anxiety. Antihistamines can safely be taken daily, and do not have medical interactions. However, the side effects might make other lupus symptoms worse. 

In particular, antihistamines can interact with sleeping medications, pain medications, antidepressants, and seizure medications, and can make existing drowsiness worse. Newer antihistamines are less likely to cause drowsiness and other side effects. 

Additionally important for people with lupus, many anti-allergy medications contain corticosteroids, which are also often prescribed for lupus. People prescribed corticosteroid medications or creams should use those to treat their lupus symptoms and not also purchase. 

Mouthwash, Oral Products, and Lupus

People with lupus have to take special care of their extra-vulnerable mouths, but even certain oral health supplies, such as toothpastes and mouthwashes can cause interactions. 

50% of people with lupus endure painful sores in their mouth, also known as mouth ulcers or “canker sores.” These sores can form after an injury to the mouth or can come and go with hormone cycles and as a part of a lupus flare. Mouth ulcers can make eating and drinking difficult and also act as a way for bacteria to enter the body. Many people with lupus also experience xerostomia or dry mouth, a condition where not enough saliva is produced in the mouth.

Both can be treated with regular and gentle toothbrushing, flossing, mouthwashes. However, mouthwash containing alcohol can actually make dry mouth worse, and some mouthwashes can irritate the inside of the mouth and make it more vulnerable to being damaged. Sodium lauryl sulfate, found in mouth rinses and toothpastes can sometimes even spread the sores, though this is less common.

The American Dental Association recommends buying mouthwash with fluoride instead. Mouthwashing can also disrupt the natural microbiome of the mouth, which also makes infections more likely. Using gentler formulas can help preserve the microbiome and, potentially, reduce the tingling or burning sensation that many mouthwashes leave behind. 

An alternative, especially for other types of injuries inside the mouth, is to rinse with salt water. This kills the bacteria and is less likely to cause drying. 

Other OTC Medications and Lupus

Some medications, especially cold medicine, can cause a high and hallucinations, as well as a wide range of neurological symptoms if overused. This is because of the active ingredients dextromethorphan  – which numbs the discomfort that leads to coughing –  and pseudoephedrine  – which is a stimulant that relieves sinus congestion and narrows blood vessels in the nasal passages. Because these work directly on the nervous system, overuse of cough medications to treat persistent coughs or colds can make already existing neurological symptoms worse. For people with lupus who are also treating depression, anxiety, or other mental health symptoms, these chemicals can affect how other neurological medications work in their body. 

Motion sickness medications like Dramamine contain dimenhydrinate, which acts as both an antihistamine and inhibits the neurotransmitter acetylcholine. This blocks the feeling of disorientation and nausea, and in normal doses, this drug can be very helpful. In high doses, it can cause a ‘high’ with psychedelic affects and can cause issues throughout the brain and nervous system, including hallucinations, ringing in the ears, heart palpitations, seizures, and can even lead to coma and death. Fortunately, most of these symptoms occur at very high doses, but people with lupus who are taking medications for similar issues should check with their doctor to make sure that their medications will still be effective.

People with lupus frequently have to deal with gas, heartburn, indigestion, and acid reflux, among other gastrointestinal woes. There are many over the counter remedies for these. However, some of the most common medications have drug interactions; Antacidsv can affect how medicines are absorbed into the body. Corticosteroids can interact with laxatives and diuretics. 

Antidiarrheals and anti-gas OTC medications also often contain loperamide, which is sometimes used by people experiencing opioid withdrawal to relieve their symptoms. Overuse – or use with narcotic opioid-based painkillers – can cause abnormal heart rhythms, including cardiac arrest and a rapid heart rate, potentially leading to unconsciousness. 

Proton pump inhibitors such as omeprazole are used to treat gastrointestinal issues and heartburn. This reduces the amount of acid produced by the stomach, protecting the stomach lining. However, lower levels of acid can also cause infections as more bacteria survive the stomach acid.

On the skin side of things, lotions and creams, both medicated (usually with corticosteroids,) and not, can be a boon for the skin of people with lupus. However, medicated creams might accidentally dose you with too much of that anti-inflammatory, and other lotions might have ingredients that could trigger an allergy or a flare. Always check the ingredients list and make sure you aren’t allergic before using. 

Allergies to OTCs can affect lupus symptoms, too – be careful out there!

A Lupus Warrior’s Takeaway

NSAIDs and other over the counter medications are powerful tools for lupuswarriors hoping to manage their symptoms. This is not a warning not to take OTC medications, but to take them carefully. For the most part, if the dose and frequency of OTCs is low, then it’s not usually a problem. However, people with lupus often find themselves needing to take OTCs often, so if there is one that you take particularly frequently, such as ibuprofen or cough medicine, then it might be time to take a look at your prescriptions again and adjust things.

This article doesn’t deal with herbal supplements, but they have important interactions with common lupus and lupus-adjacent medications like warfarin, blood thinners, and blood pressure medicine.  OTC drugs can be abused or overused as well and have the potential for serious side effects. You can read more about them here. 

There are many dangerous interactions that over the counter drugs and supplements can have with each other – Men’s Health has a very extensive article here. 

Always inform your treatment team about the medicines that you typically use, even vitamins, herbal supplements, and even your general diet. However, pharmacists can help act as a first line of defense, as they know about the OTC drugs and their interactions, so if you have access to a pharmacist, you can ask them at the point of sale.  

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that affects organ systems throughout the body, including the joints, internal organs, nervous system, and skin. 1.5 million Americans have lupus, about 1 in 200 people, 90% of whom are women and African Americans, Hispanics/Latinos, Native Americans, Asians, Alaska Natives, Native Hawaiians and other Pacific Islanders are hugely overrepresented among people with lupus.  Each person with lupus can have a wide range of symptoms, so management is unique to every patient and can be a complicated mixture of medications and therapies.

Sticking to medications can be difficult for many reasons. People with lupus often have trouble with this, also known as medication adherence. According to the CDC, approximately 50% of prescriptions are taken incorrectly. This is particularly true for people with lupus who are also minorities, and they suffer the consequences in the form of more intense symptoms and more frequent flares. Unfortunately, treatment teams and researchers have a major obstacle for solving this problem: there can be many reasons for not regularly taking medications, so it can be difficult to find a solution. 

What happens if someone is noncompliant with their medications? Simply put, the medications or therapies cannot do their jobs if they are not done. The symptoms of the disease remain or get worse – in the case of lupus this can involve joint pain, the manifestation of new symptoms and a higher frequency of flares. It benefits both patients and medical professionals to take medications regularly, but it’s not as simple as telling a patient “just take your meds!”

Why do People Not Stick to Their Meds?

In a study published in Arthritis Care and Research in October 2022, researchers followed 77 patients to see if they could figure out why people are medically noncompliant. The study found that communication was a major issue for people with lupus. Doctors spoke too quickly, used words that were not at the patient’s level, and did not adequately explain the medication. The patients were left to manage their medications on their own with a lower than optimal amount of information, and they suffered for it. 

This is, however, only a part of the reason why someone might not be compliant with their medications. A 2019 survey noted that the medication or therapy itself can be the issue, with side effects or methods of administration that the person with lupus might not be able to handle regularly. The disease might make it difficult to take the medication to treat it, such as causing intense joint pain and preventing physical therapy or causing fatigue or nausea and making pills more difficult to take. Staying “compliant” can be a major task – or multiple tasks – that overwhelms the patient. They find themselves unable to keep up with medication and life without overextending themselves. 

Healthcare Accessibility and Medication Compliance

The accessibility of healthcare is also an issue that people with lupus struggle with. If it’s difficult to access health care, or even just to access the same trusted people, it becomes more difficult to keep up with treatment.

Barriers to effective management of lupus include a chaotic home environment, a stressful or dangerous work environment, an unsafe neighborhood, being unable to access appropriate care due to monetary or other restraints, and even taking care of other members of the family with lupus. Read more here about the many complications that lupuswarriors face when trying to manage their lupus. You can read more about the social determinants of health – the health cost of racism and income – here. 

However, communication between patient and physician, health literacy derived from that communication, and the degree of trust that the patient has in their physician were noted to be the most important factors. 

How Do You Overcome Noncompliance

Self-efficacy, or the active participation of the patient in their medical care, both makes patients more confident and also improves outcomes, so it’s good to have! So, how do you do it?

If you have trouble keeping up with your meds, telling you to “just take them” isn’t going to cut it. People with lupus already have a lot of responsibilities they are juggling, and not enough energy to get to it all. Sometimes medication and self-care fall by the wayside. You can read more about chronic illness and managing energy here. 

The patient and medical professionals alike will have to do more investigating to find out why a person with lupus isn’t taking the medication or keeping up with the latest health recommendation. Figuring out what’s holding back a person with lupus will allow patients and medical professionals alike to tailor the therapy. Hopefully, they can make the therapy something that the patient can stick to and provide the most benefits. The benefits can be huge, but most would say that finding the root cause and tailoring a solution can be a big ask. 

Explanation, Education, and Compliance

When medical professionals explained the medication, its purpose, its side effects, and how to take it clearly, taking medication was made easier on the patient end as well.  The better the relationship is between patient and provider, the more likely it is for patients to keep up their treatments. However, communication and trust are real issues, and this extends to the patient’s outer world, too. Family and friends sometimes just do not get the struggles of people with lupus and aren’t able to provide the support network that patients need to thrive. Better communication between medical providers, people with lupus, and their support networks need to be done all together, will help overall health (let alone outcomes!)

Better communication and trust can be built up by having good, old-fashioned conversations during appointments. Though these can be difficult to have in the time crunch of modern medicine, the benefits for patients and medical professionals are well worth it. These conversations also have the effect of dispelling medical misinformation, a common cause of noncompliance.

Keeping it SIMPLE

Medical professionals are advised to “keep it SIMPLE.” 

• Simplify the treatment regimen to make it easier to get through
• Impart knowledge about the treatment and disease to allow the patient to make more informed decisions about their illness and treatment.
• Modify beliefs, both of the medical professional and the patient. Both parties can sometimes have belief structures that they hold onto tightly that can influence patient care. Keeping an open mind and being willing to change belief in response to facts can help treatment and compliance immensely!
• Patient and family communication is important, since the family is often a support system and they also need to know how treatment works in order to assist.
• Leave bias behind – finding one’s biases is the first step to recognizing where they might be interfering in care, on either end. This doesn’t just mean race: people make assumptions about other people due to education, word choice, neighborhood, and a number of other factors. It is important to recognize when stereotypes are influencing the patient-provider relationship and to work around them.
• Evaluating compliance regularly will be key to finding the right treatment solution. Keep checking in to see what changes are working and what changes are not, and then tweak the regimen to match. 

The SIMPLE strategy addresses many of the issues that cause noncompliance, so it is very advisable to use it. To a degree, this same lack of trust and dialog is also part of what causes lupus misdiagnosis. 

Diversity, Communication, and Lupus

It is well known that, in addition to being more likely to develop lupus, minority groups also have worse medical outcomes. This is due to many factors, including racial inequity in the medical field both on the patient and provider ends.  It is now commonly understood that this has less to do with genetic differences and more to do with socioeconomic differences brought on by racism. One of the causes of these poorer outcomes is due to low medication compliance in these groups, which in turn is due to a lack of trust and education in these communities.

As diversity improves within the medical profession, trust between patient and provider might get less thorny and compliance will improve. It’s easier to trust someone who looks like you or is from the same or similar background: you feel that they are on your side and may be more sympathetic to you. Matching the ethnicity of the doctor with that of the patient can help with trust, and this has been known to actually translate into better medical practices and outcomes for people with lupus, so it’s something to keep an eye on.  However, until there is more diversity in medicine, this remains challenging.

Patients want to feel like they are being listened to, like their doctors care about them and are paying attention. If they don’t feel that way, they aren’t as likely to trust advice from a medical professional. Unfortunately, you – the patient – sometimes must be the one push for a discussion.

Tips and Tricks for Improving Your Compliance

Noncompliance happens on the patient end, but people with lupus: It’s not entirely your fault! You have real lives and many burdens. Unfortunately, Doctors are often rushed and it can be hard for them to start the conversations that lupus warriors need. Taking an active role in one’s health, perhaps by using internet resources, and having discussions with providers can also help improve compliance. Knowing some questions to ask can get the discussion started. When you know what’s supposed to be happening, you not only advocate for your health more, but you are more likely to follow appropriate instructions.

Here are some things that you can do to make medication and therapy easier on you:

• Forgive yourself. You are doing your best with a very frustrating disease and navigating healthcare and life are both difficult roads. You are only human. Slipping up is okay – you can find ways to do better.
• Find out what is going on in your life that’s causing the issues. Is it the side effects? Are you just not remembering to take a battery of pills every day? Does your life and lifestyle make pills or exercise difficult? Is it simply too chaotic to take care of yourself properly in the mornings? There can be many causes, but the first step is to find them all.

• Start a conversation with your doctor when you can get a visit. Working together with your treatment team will be key to tailoring your plan to fit your needs and life.
• Recordkeeping and research can help you find the questions you need to ask in order to start the discussion about lupus and treatment. Read more about recordkeeping and lupus here.v 
• Figure out, with your treatment team, which aspects of your treatment are the most important and which ones you can slip up on without issue. Prioritizing can help with compliance as well as feelings of guilt.
• If the treatment team is not responding, try changing your routine, putting the medications or medical equipment in a different location, or bringing medication with you. Depending on your troubles, a small change can make all of the difference.  
• What happens at home is important too – build a support network and figure out a support ‘treatment’ to help you. 

Blood clots are a major issue for people with lupus. People with systemic lupus erythematosus (SLE) are at higher risks of strokes, heart attacks, embolisms, and are more likely to have poor outcomes both physically and mentally. These can be very severe, and even the eyes can be affected. 

Why are Lupus Warriors more susceptible to blood clots? The answer lies both in the inflammation caused by lupus and certain lupus medications. Both make cells in blood vessels and arteries more likely to be damaged, which can cause platelets and other particles in the bloodstream to build up and clots to form. Lupus also interferes with clotting directly and may be associated with certain clotting antibodies that clot more quickly and easily.

3.1% of people with lupus experienced some time of stroke according to studies, and heart attacks and stroke account for 20-30% of deaths in SLE.  This makes anti-clotting medications an important addition to the medication regimen of many Lupus Warriors.

What are Anticoagulants?

Anticoagulants, also known as “blood thinners” are medications that help prevent blood clots. Blood clots are the body’s way to stop bleeding, plugging up wounds as a sort of natural band-aid so that the body can heal. However, when they form in the wrong place, they can prevent blood from flowing to vital organs, starving them of oxygen. When blood clots block off blood vessels leading to the brain, heart, and lungs, they cause heart attacks, strokes, and pulmonary embolisms respectively. Anticoagulants interrupt the clotting process midway, preventing the clot from forming. Generally, these are prescribed when a person’s blood makes clots too often or is at a high risk of doing so.

Types of Anticoagulants

There are many types of anticoagulants available for people with lupus. According to Johns Hopkins, Warfarin, Heparin, Dalteparin, Danaparoid, Enoxaparin, Tinzaparin, and Fondaparinux are the ones most commonly used for lupus.

 Vitamin K Antagonists

Vitamin K antagonists prevent the body from processing vitamin K, a nutrient found mainly in green leafy vegetables and produced to a limited extent in the body. It’s easy to get enough vitamin k through a balanced, healthy diet.  Vitamin K is broken down or otherwise used by the body to build blood clotting and bone-building materials in the body. 

Antagonists prevent the body from breaking down vitamin K and turning them into clotting factors. This leads to the body not being able to produce as much clotting factors. 

Vitamin K antagonists can be reversed in an emergency with an injection of vitamin k (in fact, this is often given to newborn infants to help them properly make live-saving clots!) However, they also require you to keep your diet consistent because the correct dose depends on how much vitamin k you are taking in.

Warfarin is a vitamin K antagonist that is taken orally.

Direct Oral Anticoagulants (DOACs)

Other anticoagulants interfere more directly. Blood clots are formed when a series of enzyme interactions occur in the bloodstream to create a mesh that catches and holds back blood cells. This process has many steps. Direct Oral Anticoagulants target the clotting process itself, preventing the next step from occuring and stopping the clot mid-formation. 

Dabigatran, apixaban, edoxaban, and betrixaban are all DOACs.

What is Lupus Anticoagulant?

People with lupus often take anticoagulant medications, but when you look for information, it can get confusing because of the presence of ‘lupus anticoagulants.’ Although both anticoagulant medications and lupus anticoagulants are involved with how and when blood clots form, they are not the same.

Lupus anticoagulants are antibodies in the blood that are associated with blood clotting disorders. Antiphospholipid antibody tests are how doctors test for them. 50% of people with lupus have these antibodies in their bloodstream and are at higher risk of clotting disorders. Clotting disorders related to these antibodies can happen even when the symptoms of lupus are otherwise well controlled or in remission so it is important to also treat the clotting as well.  

Knowing whether you have these antibodies can help your treatment team better prepare and medicate for clotting problems, but can also be a part of diagnosing lupus. 

Things to Keep in Mind with Anticoagulants

Anticoagulants prevent blood from clotting in the wrong places or at the wrong times. Unfortunately, this also means that blood also becomes less likely to clot in the right places or times, which can lead to bleeding and poor wound healing. Usually, if you are being prescribed anticoagulants, it is because your treatment team has weighed the risks of bleeding versus the benefits of lower risks of stroke and heart attack. However, it is a notable side effect that you should definitely keep an eye out for.

This bleeding can be external, such as an injury that breaks the skin or even a bruise, or internal. Anticoagulants also effect periods, leading to heavier periods. You can read more about lupus and menstruation here. These side effects be dangerous if the bleeding goes on too long or the damage is not healed by the body. 

For this reason, doctors and surgeons often advice people to stop taking anticoagulants for a short period of time before the surgery to protect against bleeding. Anticoagulants are also not good for pregnant women. 

As always, consult with your treatment team before stopping use, but let them know if you are about to have surgery or are about to be pregnant. 

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.