When I mention lupus to my patients, sometimes I get a confused look because it’s not a well-understood condition. People wonder why the body would attack itself, as is the case with lupus and other autoimmune diseases.
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Here are five surprising facts that many people don’t know about lupus:
- 1. Lupus affects nine times more women than men, and more women of color than white women.
- 2. Lupus symptoms can differ greatly from person to person.
- 3. Lupus is a disease of flares and remissions.
- 4. Diagnosis begins with a simple blood test.
- 5. Treatment depends on the type of flare-ups you have.
- A Closer Look at Lupus Treatments
- Lupus, Emotional Stress, and Depression
- Why Is a Lupus Diagnosis Such an Emotional Challenge?
- When Does Lupus Depression Need To Be Treated?
- How to Stay Emotionally Healthy With Lupus
- The Effects of Lupus and Lupus Medications on Mood
- The Impact of SLE Symptoms
- Direct Complications of SLE
- Biology of Neuropsychiatric Symptoms
- The Psychological Impact of SLE
- Ways to Improve the Negative Effects of SLE
- List of Common Lupus Medications
1. Lupus affects nine times more women than men, and more women of color than white women.
I’ve diagnosed men, senior citizens and toddlers with lupus. But women of childbearing age — 13 to 49 — are far more likely to be affected.
Genetics also plays a role. If you’re a woman with no family history of lupus, your chances of getting lupus are about one in 400. If your parents or a sibling has lupus, your chances jump to one in 25.
African-American and Latina women with no family history of lupus have about a one in 250 chance of developing the disease.
2. Lupus symptoms can differ greatly from person to person.
Some symptoms are common to other conditions, too, which can make diagnosis difficult. Common lupus symptoms include:
- Constant fatigue
- Achy joints
- A butterfly-shaped rash around the cheeks and nose
- Hair loss
- Blood clots
- Sensitivity to light
- Chest pain when breathing
- Mouth sores
- Swelling in the extremities or around the eyes
3. Lupus is a disease of flares and remissions.
Lupus flare-ups can be mild, or they can be severe. At least 75 percent of people with lupus have arthritis and skin rashes. Half have kidney problems. Lupus patients are also more vulnerable to infection than most people.
4. Diagnosis begins with a simple blood test.
When I suspect lupus, I will order an antinuclear antibody (ANA) blood test. A negative ANA test result usually rules out lupus.
We know that ANA test results will come back positive in virtually everyone with lupus. However, some people will have a positive result even though they do not have lupus. When the test comes back positive, other criteria has have to be examined.
In those cases, I compare the patient’s symptoms with a list of 11 criteria for lupus. If they meet four or more of the criteria, they are usually diagnosed with lupus.
5. Treatment depends on the type of flare-ups you have.
Mild swelling and joint pain may be treated with acetaminophen or a non-steroidal anti-inflammatory drug like naproxen, or ibuprofen.
Plaquenil, an anti-malarial drug, treats skin rashes, arthritis, and sometimes fatigue.
Rashes may be treated with topical steroid creams. And corticosteroids like prednisone and immunosuppressants treat serious kidney problems.
It’s good to remember that diagnosis and treatment of lupus keeps getting better. Ninety-five percent of lupus patients have a five-year survival rate today, compared to 5 percent in the 1950s.
And many people with lupus have a mild form. I tell my patients that proper medication can even help people with severe lupus control their flare-ups and live productive lives.
By: Howard Smith, MD
A new discovery from scientists at OMRF could be used by physicians to predict and prevent lupus flares.
Lupus is a multifaceted autoimmune disease in which the body’s immune system is unbalanced, which can lead to disease “flares” of inflammation, damaging tissue and organs. The Lupus Foundation of America estimates 1.5 million Americans have the disease, which predominantly strikes women.
Patients are often not aware when a disease flare is about to occur. This delays treatment and allows inflammation to persist, putting patients at risk for organ damage.
“We’re often reacting to a bad situation in the clinic, rather than preventing the next one,” said Judith James, M.D., Ph.D., head of OMRF’s Arthritis and Clinical Immunology Research Program. “With this research, we hope we can identify the patients at the highest risk of flare and intervene earlier.”
In a new paper which will be published in the July issue of the journal Arthritis & Rheumatology, James and OMRF scientist Melissa Munroe, M.D., Ph.D., describe how a study of patients receiving an influenza vaccine led to a method that might predict flares in a clinical setting.
Lupus patients were evaluated just before receiving an influenza vaccine, and then tracked at 2, 6 and 12 weeks after receiving the shot.
“The initial study was to determine if the immune system of lupus patients could create antibodies to the influenza vaccine,” said Munroe. “Fortunately, the study design and the generosity of the patients allowed us to also gather this important information about lupus and what makes it flare.”
Researchers also monitored if the patients had a flare in the weeks after receiving the vaccine and looked at blood samples leading up to the attack.
“We were able to compare their immune system numbers to a baseline to identify potential indicators for inflammation,” said James, who holds the Lou C. Kerr Endowed Chair in Biomedical Research at OMRF.
For those with lupus, the immune system is like a teeter-totter, said Munroe. It’s almost always out of balance, with inflammation winning over regulation.
The study evaluated 52 mediators—molecules that increase or decrease the chance of a lupus flare by driving or suppressing inflammation, she said. These can be used to “score” patients to predict who might need a pre-flare intervention as many as three months in advance.
They have filed for a provisional patent for the system.
“Even if they aren’t feeling too bad, patients’ immune systems are warning us that a flare is coming,” James said. “If we know they’re not going to flare, we can avoid giving them a lot of unnecessary and potentially toxic drugs.”
The discovery will help physicians move closer to tailored therapies for patients, but it could also have a potential benefit for clinical trials, she said. One challenge in testing new medications for lupus is discerning if a lack of disease activity is due to a drug’s effects or other factors.
In the next step, researchers will seek to use the data to group patients into smaller sets in order to better treat their specific disease, James said.
“I’ve had two lupus patients sitting together discussing their symptoms, and they don’t realize they have the same disease,” she said. “This could allow doctors to define patients from a molecular standpoint and really get at precisely what’s happening in their disease process.”
This study was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases with co-funding by the Office of Research on Women’s Health, and the National Institute of General Medicinal Sciences of the National Institutes of Health under award numbers P30AR053483, U19AI082714, U01AI101934, P30GM103510, S10RR026735, and HHSN266200500026C. The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
A Closer Look at Lupus Treatments
Medications to treat symptoms and suppress your immune system, along with some alternative therapies.
Reviewed By Don L. Goldenberg, MD
Since lupus presents differently in each person, treatment will be personalized for your specific needs. As your needs change, according to different stages in your life and in your lupus experience, your treatments may need to be modified. This typically will depend on the severity of symptoms, as well as on the systems and organs the lupus is affecting. In mild lupus cases, symptoms can often be managed with one or two uncomplicated medications. However, if you have moderate or severe lupus, your doctor will prescribe more aggressive treatments. And even with mild lupus, if you experience a flare-up of symptoms, you will also benefit from more aggressive treatments for a few weeks. Getting enough sleep and exercising will reduce your fatigue, and that may also alleviate some of your joint pain.
Doctors frequently discontinue a medication after the disease enters a period of remission. So, it is important to see your doctor frequently, allowing him or her to adjust your treatments according to your symptoms.
Hydroxychloroquine is an antimalarial drug that is commonly used to treat lupus. It reduces joint pain and helps prevent lupus flare-ups. It also reduces inflammation in the linings that protect your heart and lungs, and it relieves lupus-related fatigue and fever. Some people experience an upset stomach from this medication and in rare cases, it can damage the retina of the eye, so it’s important to get regular eye exams while taking this medication.
Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, celecoxib, diflunisal, and naproxen are very effective at treating pain, fevers, and inflammation from lupus. However, because of their side effects, some doctors encourage their patients to use NSAIDs mainly for lupus flares. Using NSAIDs over a long period of time can damage your digestive system and kidneys.
NSAIDs can also cause headaches, skin rashes, and other symptoms that mimic lupus flares. This makes it harder for your doctor to know if you need more aggressive lupus treatment—or if you are just experiencing NSAID side effects. If you have a flare-up, and hydroxychloroquine and NSAIDs are not providing enough relief, your doctor may choose to treat you with a corticosteroid (often referred to as a steroid), which is an anti-inflammatory treatment to help fight the infection.
Prednisone pills are the most common administration of a steroid. However, steroid injections and IVs can also be extremely effective. When taking a steroid, you could experience weight gain, bruising, osteoporosis, diabetes, high blood pressure, and be more likely to get an infection.
Suppressing Your Immune System
When lupus threatens organs, doctors move aggressively to suppress your malfunctioning immune system with a class of medications that includes azathioprine, mycophenolate mofetil, and methotrexate.
While such drugs may dramatically reduce your lupus symptoms, they also carry some risks you’ll need to consider, including the possibility of liver damage, lowered fertility, and increased risk of cancer. Suppressing your immune system with these medications also increases your risk of infection. Therefore, you will need to safeguard your personal hygiene and avoid sick people.
These medications also interact with many other pharmaceuticals. If you live with other health conditions, you may have tough decisions to make about the tradeoff between treating lupus and the effect that the immune suppressors may have on your other conditions. Your doctor will help you make that decision.
There are also a few newer forms of treatments being tried for lupus with some success. For instance, belimumab (brand name: Benlysta) is the first biologic (a medication made from live organisms) approved for lupus. It can be self-injected by patients, which offers important convenience. Some people experience mild side effects from this drug, including nausea, diarrhea and an increased risk of infections.
A recent study also explored the benefits of using rituximab (brand name: Rituxan) for people with resistant lupus. This can reduce reliance on steroids, and minimize related side effects. However, rituximab can increase the risk of infections in users.
Looking to the Future
“We are still awaiting a ‘home-run’ immune therapy for lupus, similar to the many breakthrough therapies for rheumatoid arthritis. Until then, the best option is early diagnosis and case-by-case treatment by a rheumatologist,” says Don Goldenberg, MD, rheumatologist and emeritus professor of medicine at the Tufts University School of Medicine in Boston, MA. He currently serves as adjunct faculty in the Department of Medicine and Nursing at Oregon Health & Science University in Portland, OR. He adds that the vast majority of lupus patients will have good outcomes, although ongoing treatment may be needed over the long-term.
Lifestyle Choices and Alternative Treatments
Making smart lifestyle choices—including eating a balanced diet, getting enough sleep, and engaging in regular exercise—can help you manage lupus. Some people with lupus also find complementary and alternative treatments to be helpful in controlling symptoms. Just be sure to talk to your doctor before trying anything new. There is always the risk that it can interfere with your medications.
Watching for Flare-ups
You can prevent, or reduce the intensity of, a lupus emergency by learning to sense the onset of a lupus flare. If you sense a flare-up, you’ll need to start preventative treatment with your doctor. Some common warning signs are:
- stomach aches;
- and aching muscles.
Working with a Rheumatologist
Lupus treatment is complex, and you need to have a doctor who is experienced in managing the symptoms. Early in the course of your illness, your primary care provider may be qualified to treat mild lupus. However, if you develop moderate or severe lupus symptoms, you will benefit from the additional experience and focus of a rheumatologist who specializes in the condition.
-Additional reporting by Lisa Ellis, October 2018
Updated on: 10/19/18 View Sources
Carlson KJ, Eisenstat SA, Ziporyn TD. The new Harvard guide to women’s health. Harvard University Press; 2004.
Gracia-Tello B, Ezeonyeji A, Isenberg D. The use of rituximab in newly diagnosed patients with systemic lupus erythematosus: long-term steroid saving capacity and clinical effectiveness. Lupus Sci Med. 2017;4(1):e000182.
Continue Reading: Lupus Causes
Lupus, Emotional Stress, and Depression
Systemic lupus is an autoimmune disease that usually strikes in the prime of patients’ lives.
The average person with a lupus diagnosis is a young woman in her reproductive years. Because lupus is an unpredictable disease that you may have to deal with for most of your life, it can cause more emotional stress than other common chronic diseases.
“Think of your immune system as a police force,” says Charles Raison, MD, a psychiatrist and clinical director of the Mind-Body Program at the Emory University Department of Psychiatry and Behavioral Sciences in Atlanta. “Its job is to shoot foreign invaders like viruses and bacteria, but in an autoimmune disease like lupus the police have gone rogue and start shooting the civilians.”
Why Is a Lupus Diagnosis Such an Emotional Challenge?
Dealing with any chronic disease is stressful. Up to 60 percent of people with a chronic disease may suffer from periods of depression. If you’ve received a lupus diagnosis, there is also the chance that some of the medications you take, especially steroids, can make you more emotional and more prone to depression. Lupus can directly involve your nervous system and cause symptoms such as memory problems, difficulty concentrating, mood swings, and confusion. These symptoms are sometimes referred to as “lupus fog.”
“A chronic disease like lupus, with symptoms of being tired and feeling ill, causes stress that signals your immune system to activate and causes inflammation. Psychological stress and illness travel the same brain pathways. This can become a vicious cycle in autoimmune disease. Sickness causes stress which causes more sickness,” notes Dr. Raison.
RELATED: The United States of Stress
When Does Lupus Depression Need To Be Treated?
If you have lupus, you can expect to have times when you won’t feel well emotionally. Sometimes, lupus can prevent you from going out and doing the things you want to do. Maybe your lupus rash has flared up and you don’t look the way you’d like — it’s only natural that this can lead to feelings of sadness and stress in a young woman.
When such feelings lead to depression, it’s known as reactive depression. Once patients start feeling better with their lupus, most recover from the subsequent reactive depression. The other, more commonly recognized form of depression is called chemical depression, (sometimes referred to as clinical depression), and it can go on for longer and be much harder to come out of.
This type of depression, which is caused by a chemical imbalance in the brain, can make your lupus symptoms feel worse, and it needs to be treated. Some warning signs of clinical depression are:
- Feeling empty, hopeless, or helpless and like you can’t work your way through these emotions on your own.
- Losing interest in the things you used to enjoy or feeling like nothing seems to bring you joy anymore.
- Feeling like you can’t go on anymore.
- Feeling like a failure and that nobody cares about you.
These kinds of moods and dark thoughts may be a sign that you need professional evaluation and treatment. If you think you might be depressed, talk to your doctor, because depression should be treated as aggressively as you would treat a lupus flare. The good news is that treatments such as antidepressants and psychotherapy work well in treating the symptoms of depression.
How to Stay Emotionally Healthy With Lupus
The following factors can help you maintain your emotional well-being:
- Exercise regularly and eat a healthy diet.
- Know your limits emotionally and physically
- Make sure to get enough rest.
- Join a lupus support group.
- Be good to yourself. Have fun. Do something that makes you laugh.
- Try mind/body exercises that can help you relax, like meditation. Several recent studies have shown that meditation can reduce stress and stress-induced immune responses.
If you have a chronic and unpredictable disease like lupus, you are going to have stress and there will be emotional ups and downs. It may be hard at times to know if depression is related to lupus fog or something more serious. If you are struggling with emotional issues you need to let people know.
Emotional stress can make lupus worse and depression can be treated successfully. Make sure you know the warning signs of depression, and don’t hesitate to ask for help when you need it.
The Effects of Lupus and Lupus Medications on Mood
Lupus can have a profound effect on one’s mood and outlook on life. Whether triggered by the physical symptoms of the condition itself, or as a result of side effects of medications commonly administered to lupus patients, the effects of lupus can have a marked psychological impact on those who live with it.
Lupus is a very complicated illness, and the various forms of the disease can affect people in different ways. Occasionally, this unpredictability leads to confusion, distrust, and stress.
Lupus is caused by an overactive immune system. Treatment is aimed at resetting the thermostat of the immune system so it’s not overreacting without causing major side effects; in short, the goal is to try to return the immune system to being normal. Occasionally, however, there will be unpredictable effects of a medication.
This presentation aims to explain the differences between the psychological effects of the condition and the medications used to treat it.
The Impact of SLE Symptoms
Lupus presents in so many different ways that it is known as “the great imitator.” The broad range of symptoms can confuse both patients and their primary physicians, and so an initial diagnosis is often very difficult to make.
Further, even when the diagnosis is made, it isn’t possible to precisely anticipate the course of the illness. Delays in diagnosis and the unpredictability of symptoms tend to frustrate patients and can reduce their confidence in their medical teams.
An additional frustration relates to the fact that many of the symptoms of lupus are the sorts of aches, pains, and fatigue that are common among people who don’t have lupus. People with lupus are, therefore, faced with further uncertainty: Is their symptom related to lupus, or can it be chalked up to aging or a completely unconnected ailment?
This uncertainty can lead people with lupus to worry that every symptom is a sign of SLE and to have problems believing their medical team when they say not to be concerned. Such uncertainty can also lead to vague, chronic worry about health and can interfere with the ability to make plans for the future.
Is lupus caused by stress? The short answer is “no.”
While stress may appear to set off lupus flares, there hasn’t yet been evidence to indicate that stress, in itself, is enough to cause lupus or a lupus flare.
This clinical evidence is important in that some people might blame themselves for their lupus, believing that their stress might have caused the lupus. Such a rationalization is very human and understandable, but the reality is that our understanding of the cause of lupus is incomplete but that it does appear that lupus is not caused by psychological factors.
There is some biological evidence of links between stress and lupus flares. Such research focuses on B and T suppressor cells, cytokines, and various types of antibodies. It should be noted, however, that these research findings are interesting but have not yet been shown to have clinical, practical relevance.
While stress does not seem to be a primary cause for lupus, it is clear that lupus causes people stress through its physical effects, its related uncertainty, and the resulting worries about physical problems.
Direct Complications of SLE
Lupus can directly affect thinking, mood, and personality. When it has these effects, it is called neuropsychiatric lupus. Symptoms of neuropsychiatric lupus include:
- Cognitive dysfunction: Refers to a variety of related experiences, including forgetfulness, worry, mistrust, and a general difficulty in thinking. Some people with lupus describe feeling “fuzzy-headed” or being in a “lupus fog.” Often mild and reversible, cognitive dysfunction is commonly seen during lupus flares. These feelings are experienced by those without lupus as well, of course, and are perfect examples of the difficulty physicians face in diagnosing lupus.
- Depression and anxiety: May occur as direct effect of the lupus, as a psychological reaction to the illness, or as a reaction to medications used to treat lupus. Mood symptoms also occur commonly in people without lupus, and so it is generally difficult to be certain about what causes depression and anxiety in people with lupus.
- A personality change: This can refer to feelings of anger, irritability, and lability (the sensation of not feeling or acting like yourself). The unpredictability of these changes makes it hard for some people with lupus to connect with those around them. They may even wonder if their communication problems are the result of their friends and loved ones reacting poorly to their condition
Steroids are often central to the treatment of lupus, but steroids such as prednisone can cause all of the symptoms of neuropsychiatric lupus. Because neuropsychiatric symptoms are common in SLE, terms have sprung up that are widely used but are also often inaccurate.
“Steroid psychosis” is a term that some use for the emotional effects of steroids. It should be emphasized, however, that steroids don’t commonly cause psychosis, but more often cause milder emotional changes, such as anxiety or depression. The term “lupus cerebritis” is used to specifically refer to the effects of lupus itself on the brain.
In trying to distinguish the cause of neuropsychiatric symptoms, it is useful to recall that lupus is more likely to be the cause than steroids when:
- It has been more than two weeks after an increase in prednisone
- The prednisone dose was less than 40 milligrams per day
- The emotional symptoms improve with additional steroids.
Biology of Neuropsychiatric Symptoms
Those with lupus may wonder how their condition can directly and biologically cause problems with thinking and mood.
Often, there is a direct neurological involvement in lupus related to the autoimmune system. There remains controversy about how lupus affects the brain. Antineuronal antibodies (antibodies against nerve tissue) have been demonstrated, but it is not yet clear whether it these antibodies cause direct damage to the nerves. We know that patients with lupus, on no steroids, can have depression, delirium, confusion, mistrust, and even psychosis.
Anti-phospholipid antibodies are also present in some patients with lupus. Anti-phospholipid antibodies don’t seem to cause inflammation, but rather are involved with increased clotting risk, and can be associated with stroke and cognitive problems.
Many of these neuropsychiatric effects are reversible, and there is a much lower risk of developing these problems if a patient with lupus only has joint and skin involvement, if the patient is ANA-negative or if the illness is a the result of a medication, which can be withdrawn.
The Psychological Impact of SLE
People react to having lupus in different ways, and these reactions can change with time. Some of these reactions may include:
- Regression and reduced independence (due to physical limitations, etc.)
- Isolation and social withdrawal (due to unpredictable moods, a prominent rash, etc.)
- Fears of worsening disease and disability
- Fears of cognitive problems, stroke, kidney failure, becoming a burden, etc.
It is important to note, however, that along with these “negative” reactions, those in the lupus community have rallied around each other to promote the positive effects of taking part in their shared experience. Feelings of pride, endurance, connection, appreciation, and maturity have also been commonly seen in people with lupus.
Ways to Improve the Negative Effects of SLE
After opening the topic up for discussion in the workshop, it became immediately clear that everyone in the room had a different way to cope with – and improve – their own relationship with lupus.
Advice from workshop members ranged from treating yourself (to additional sleep, to your favorite food item, to a vacation, or a book, or a movie, or TV, or a visit to a favorite place) to communicating with those who understand, or at least can empathize with – your struggle.
While it’s important to try to focus on the positive, it’s equally important to accept that certain days will be difficult and that merely trying to remain positive may not be enough. As one member put it, “you can live with it for years and years, and some times are better than others.”
“Be honest with yourself,” added another member. “Sometimes, it’s too much to ask to put on a front.”
“Sometimes I find myself spinning my own wheels, staying angry,” another member explained, “spending too much time on the Internet overdiagnosing myself, driving myself crazy. I had to tell myself not to obsess on the computer. Sit back. Get a different perspective.”
One way to get a new perspective is to reach out for help and accept that it’s okay to do so. Talk to those going through what you’re going through. Isolation can set in, and it’s important to realize that you’re not alone.
A major benefit of talking with others who share your experiences is to understand which tools they use in their “toolbox.” Each person has his or her own way of making their situation better, whether it’s a technique such as muscle relaxation, yoga, TV watching, or reading. You may have your own tools, but you may find that the tools other people are using can help you as well.
Learn more about the HSS SLE Workshop, a free support and education group held monthly for people with lupus and their families and friends.
Summary by Mike Elvin
John Barnhill, MD
Chief of Psychiatry, Hospital for Special Surgery
Professor of Clinical Psychiatry, Weill Cornell Medical College
List of Common Lupus Medications
OTC drugs such as acetaminophen (Tylenol) can offer some relief from your lupus symptoms. These drugs can control pain and reduce fever. In general, acetaminophen may cause fewer intestinal side effects than prescription drugs. But it may also cause kidney and liver problems. Ask your doctor what the right dosage is for you. Taking the correct dosage extra important if you have kidney disease from lupus. You may be more sensitive to the side effects from acetaminophen.
If NSAIDs or acetaminophen don’t relieve your pain, your doctor may give you an opioid. These drugs are prescription pain medications. They’re powerful and can be habit-forming. In fact, these drugs aren’t normally a first-line treatment for lupus because of the risk of addiction. Opioids can also make you very sleepy. You should never take these drugs with alcohol.
These drugs include:
Learn more: Understanding hydrocodone addiction “
Tramadol (Ultram) is a prescription pain drug. It acts like both an opioid pain reliever and an antidepressant. It can help ease short-term pain from lupus. Like opioids, this drug is habit-forming and can make you sleepy. You shouldn’t take it with alcohol.
Disease-modifying anti-rheumatic drugs (DMARDs)
These drugs are used to treat certain autoimmune diseases. They work by suppressing an overactive immune system. This reduces inflammation caused by lupus, which can help relieve symptoms. DMARDS often are used with NSAIDs.
These drugs include:
- hydroxychloroquine (Plaquenil)
- cyclosporine (Gengraf, Neoral, Sandimmune)
- azathioprine (Azasan, Imuran)
These drugs were first approved to treat malaria. They decrease autoantibody production in your body. This effect reduces the damage lupus can do to your organs. These drugs also help ease lupus symptoms.
These medications can take several months to be effective, so they’re only given after other drugs don’t work. Side effects are usually mild. However, these drugs can cause vision changes in some people. If you take any of these drugs, you need to have your vision checked as often as your doctor suggests.
Antimalarials for lupus include:
- chloroquine (Aralen), used off-label
- hydroxychloroquine (Plaquenil)
BLyS-specific inhibitors or monoclonal antibodies (MAbS)
Belimumab (Benlysta) works by suppressing autoantibodies in people with lupus. This helps to improve lupus symptoms. This drug was approved in 2011. It was the first drug created specifically for lupus in 50 years. This type of drug has shown to be helpful, but more research is needed to know how well it works long-term.
Immunosuppressive agents and immune modulators
In advanced cases of lupus, these drugs might be used to suppress the overactive immune system. These drugs include:
- azathioprine (Imuran)
- methotrexate (Rheumatrex)
- mycophenolate mofetil
- cyclophosphamide (Cytoxan)
Your doctor may prescribe these drugs when other medications haven’t worked to control your symptoms. These drugs aren’t a first-line treatment for lupus because they have potentially severe side effects. Your doctor will monitor you closely for side effects during treatment if you take any of these drugs. These effects can include:
- liver damage
- certain types of cancer
- infertility in men and women
- sun sensitivity
- hair loss
People with lupus have a higher risk of blood clots. If your doctor decides you need preventive treatment, they may give you a drug to thin your blood. Anticoagulants do not treat lupus specifically but may be a part of your lupus care. If your doctor gives you one of these drugs, they will watch you closely to make sure your blood doesn’t become too thin.
These drugs include:
Ten percent of individuals worldwide are affected by autoimmune diseases, with systemic lupus erythematosus (SLE) being one of the most common.1 Drug-induced lupus erythematosus (DILE) was first recognized in 1945 with sulfadiazine as the offending agent.2 Since then, more than 90 medications from more than 10 drug classes have been implicated in causing lupus.1,3 DILE is estimated to affect 15,000 to 20,000 individuals each year and accounts for 10% of SLE cases.1,2 Risk factors for DILE include being a slow acetylator, having certain serologic features (eg, HLA-DR4 and HLADR0301), having complement C4 null allele, and being female.2
Drug-Induced Lupus Erythematosus
DILE is similar to idiopathic SLE. However, the prognosis of DILE is promising compared with that of SLE. DILE presents itself after exposure to the offending medication and the symptoms usually resolve within weeks of discontinuing the offending agent.2 Refer to Table 13 for a comparison of DILE and idiopathic SLE.
Patients presenting with DILE may experience fever, arthralgia, arthritis, myalgia, or serositis. In fact, 90% of affected patients present with arthralgia and 50% present with myalgia.2 After initiation of an offending medication, DILE can develop from 1 month to more than a decade after exposure to it.2
DILE can be defined by the following, according to Dipiro and colleagues4:
- Exposure to a suspected medication
- No history of idiopathic SLE prior to exposure to an offending medication
- Positive antinuclear antibody (ANA) test result; usually antihistone antibodies
- At least one clinical feature of SLE
- Rapid improvement of symptoms after offending drug is discontinued
- Gradual decline in ANAs after offending drug is discontinued
Medications reported to have a definite relationship to DILE, based on controlled studies, include the following2:
Procainamide and hydralazine are associated with the highest risk for developing DILE. Procainamide carries a 15% to 20% risk and hydralazine carries a 7% to 13% risk.3 Quinidine has been classified as having a moderate risk.1 Refer to Online Table 22,3 for a list of medications and their likelihood of causing DILE.
Table 2: Drugs Implicated in the Development of Drug-Induced Lupus Erythematosus
|Definite||Probable||Possible||Recent case reports|
Adapted from references 2 and 3.
Recently, DILE has also been associated with newer medications on the market, which include tumor necrosis factor (TNF) blockers and interferons. There have been several cases of TNF-alpha antagonist–induced lupus syndrome, which is otherwise known as TAILS.3
TNF blockers include the following:
- Remicade (infliximab)
- Enbrel (etanercept)
- Humira (adalimumab)
- Cimzia (certolizumab pegol)
- Simponi (golimumab)
According to an article published in Lupus, “Most cases of TAILS have been … due to infliximab because it is the most immunogenic based on its chimeric structure and its ability to reach high tissue concentrations, followed by etanercept and adalimumab, which is a humanized monoclonal antibody. Only one case has been described with certolizumab pegol, and we are unaware of any cases being reported following golimumab therapy.”3
The interferons that are implicated in DILE include interferons alpha and beta. However, interferon alpha carries the highest incidence of DILE.1,3 Other medications that may be linked to DILE include ticlopidine, various statins, and lisinopril.2,3
Medications that are thought to cause lupus include the following:3
- Estrogens, oral contraceptives
- Calcium channel blockers
Drug-Induced Subacute Cutaneous Lupus Erythematosus
There have also been reports of drugs inducing subacute cutaneous lupus erythematosus (SCLE). Medications that have been implicated in SCLE include antihypertensives (calcium channel blockers, angiotensin-converting enzyme inhibitors, beta-blockers), terbinafine, ticlopidine, and statins.1 Refer to Online Table 31 for a list of medications implicated in SCLE.1
Table 3: Drugs Associated with Subacute Cutaneous Lupus Erythematosus1
|Calcium channel blockers||Diltiazem, verapamil, nifedipine|
|Angiotensin-converting enzyme inhibitors|
|HMG-CoA reductase inhibitors (statins)|
|Interferon alpha and beta|
|Nonsteroidal anti-inflammatory drugs||Piroxicam, naproxen|
|Others||Lansoprazole, tamoxifen, leflunomide, docetaxel|
|Biologicals||Efalizumab, etanercept, infliximab, interferon-beta|
Adapted from reference 1.
Because there are no set criteria for diagnosing DILE, diagnosis presents a challenge. When making a diagnosis, a clinician must be aware of the differential diagnosis, which includes drug hypersensitivity, eosinophilia- myalgia syndrome, serum sickness, toxic oil syndrome, hemolytic anemia, and other environment factors.1
In The Annals of the New York Academy of Sciences, Borchers et al suggested criteria for diagnosing DILE that included no previous SLE or autoimmune disease.5 This poses a challenge when diagnosing DILE in the case of TNF blockers or other biologic agents, as affected patients already have an autoimmune disease. In these cases, health care providers need to rule out an exacerbation of preexisting lupus and the possibility of unmasking a second autoimmune disease.1
Once DILE is confirmed, stopping the offending agent is the first step in treatment. When treating musculoskeletal symptoms, nonsteroidal anti-inflammatory drugs can be prescribed.4 If symptoms are serious, more aggressive therapy can be prescribed. In these cases, corticosteroids are considered first-line treatment.3
Other Drug-Induced Autoimmune Diseases
In a review article published in Drug Safety, Chang and Gershwin reported, “Drugs have also been implicated in other autoimmune diseases, including rheumatoid arthritis, polymyositis, dermatomyositis, myasthenia gravis, pemphigus, pemphigoid, membranous glomerulonephritis, autoimmune hepatitis, autoimmune thyroiditis, autoimmune haemolytic anaemia, Sjögren’s syndrome, and scleroderma.”1
Although DILE has a more favorable prognosis than SLE, prompt diagnosis and discontinuation of the offending agent are critical. Once mainly associated with cardiovascular drugs, DILE is now associated with more drug classes, including TNF blockers and interferons. Because these agents are used to manage autoimmune disorders, diagnosing DILE can be challenging. The challenge is being able to differentiate a true drug-induced lupus from an exacerbation of preexisting lupus or the unmasking of a second autoimmune disease.1
As we gain a better understanding of pharmacogenetics, it is important that we use the available tools to identify patients who are at higher risk of developing DILE. In addition, research efforts need to focus on identifying susceptible genes to stand as biomarkers to help identify patients at risk for developing DILE.
Dr. Garza received her doctor of pharmacy degree from the University of Texas at Austin. She is currently working as the director of the Life Sciences Library at RxWiki, where she continues to build her practice on the fundamental belief that providing patients with medication information and medical knowledge contributes significantly to the quality of care they receive and improves quality of life and health outcomes. Her work focuses on educating patients and providing them with the resources needed to navigate the overwhelming and complex health system. Before RxWiki, she was director of pharmacy for a Central Texas Department of Aging and Disability facility.