Search Results for: skin lupus

Systemic Lupus Erythematosus (“SLE”)

When people use the term “lupus,” they usually refer to systemic lupus erythematosus, or “SLE.” Throughout this website, the term “lupus” is used to signal systemic lupus, since SLE constitutes the most common form of the disease. Systemic lupus is so-named because it affects many different organ systems in the body. It is marked by chronic inflammation, especially of the kidneys, joints, and skin. The cardiovascular and nervous systems can also be affected. Please explore the site for information on the manner in which SLE acts upon the various systems of the body.

Lupus Limited to the Skin

The term “chronic cutaneous lupus erythematosus” refers to a specific form of lupus that is limited to the skin. This form of lupus can exist in people who do not have systemic lupus. However, five percent or more of the people with this form of lupus may develop SLE later in life. Three types of skin lupus exist: chronic cutaneous lupus erythematosus (CCLE) (also known as Discoid Lupus Erythematosus [DLE]), subacute cutaneous lupus erythematosus (SCLE), and tumid lupus. A skin biopsy is usually obtained to diagnose skin lupus, and each form possesses its own characteristic lesions and pattern. For more information on the way that lupus affects the skin, please see the “Skin Lupus” article on this site.

Drug-Induced Lupus Erythematosus

Certain drugs can actually cause lupus-like symptoms in people who do not have SLE. However, this form of lupus is temporary and usually subsides within months of the time that the medication is stopped. In addition, many drugs that cause this form of lupus are actually losing favor among physicians. Medications known to induce lupus-like symptoms in some individuals include the blood pressure medications hydralazine and methyldopa, a heart medication called procainamide, and a drug called D-penicillamine, which is used in cases of metal poisoning. Other causes of drug-induced lupus include minocycline (used to treat acne) and anti-TNF (used to treat rheumatoid arthritis).

Neonatal Lupus Erythematosus

A certain form of lupus known as neonatal lupus may affect the babies of women with certain autoantibodies, namely anti-Ro, anti-La, and anti-RNP. About 1 in 1000 perfectly healthy women possesses either anti-Ro or anti-La, and a mother who gives birth to a child with neonatal lupus may not have lupus herself. In fact, only about 40% of women bearing children with neonatal lupus actually have lupus, but lupus or Sjogren’s (dry eye) syndrome may occur later in life. Usually neonatal lupus involves only the baby’s skin and subsides on its own, even without treatment. However, 1-2% of infants with neonatal lupus experience congenital heart block. This can be treated by the implantation of a pacemaker, and generally these children go on to lead healthy lives. Yet, rare deaths can occur from congenital heartblock, especially if major heart damage occurs in utero.

Childhood Lupus

The lupus that occurs in children affects the body in the same manner as adult lupus. However, boys are more likely to get childhood lupus than men are to get adult lupus, and usually childhood lupus affects certain organs, such as the kidneys, to a greater degree. The incidence of kidney disease in childhood lupus is about 2-times greater than that of adult lupus. Childhood lupus generally requires more aggressive therapy than adult lupus, yet physicians must keep in mind the risks of the long-term use of certain medications (e.g., prednisone).

Sources

• “Forms of Lupus.” Lupus Foundation of America. 1 July 2009.
• Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995. 47-51, 65-73. 159-63.

Most people with lupus experience some sort of skin involvement during the course of their disease. In fact, skin conditions comprise 4 of the 11 criteria used by the American College of Rheumatology for classifying lupus. There are three major types of skin disease specific to lupus and various other non-specific skin manifestautions associated with the disease.

Lupus-Specific Skin Disease

Three forms of specific skin disease occur in people with lupus, and it is possible to have lesions of multiple types. In addition, a person can also have one of the three forms outlined below without actually having full-blown systemic lupus erythematosus (SLE), but the presence of one of these disease forms may increase a person’s risk of developing SLE later in life. Usually, a skin biopsy is used to diagnose forms of cutaneous lupus, and various medications are available for treatment, including steroid ointments, corticosteroids (e.g., prednisone), and antimalarials (e.g., Plaquenil).

Chronic Cutaneous Lupus Erythematosus (CCLE) / Discoid Lupus Erythematosus (DLE)

Chronic cutaneous (discoid) lupus erythematosus is usually diagnosed when someone exhibits signs of lupus in the skin. People with SLE can also have discoid lesions, and about 5% of all people with DLE will develop SLE later in life. A skin biopsy is used to diagnose this condition, and the lesions have a characteristic pattern known to clinicians: they are thick and scaly, plug the hair follicles, appear usually on surfaces of the skin exposed to sun (but can occur in non-exposed areas), tend to scar, and usually do not itch.

If you are diagnosed with discoid lupus, you should try to avoid sun exposure when possible and wear sunscreen with Helioplex and an SPF of 70 or higher. In addition, you doctor may prescribe medications to help prevent and curb inflammation, including steroid ointments, pills, or injections , antimalarial medications such as Plaquenil, and/or immunosuppressive medications.

Subacute Cutaneous Lupus Erythematosus (SCLE)

About 10% of lupus patients have SCLE. The lesions characteristic of this condition usually do not scar, do not appear thick and scaly, and usually do not itch. About half of all people with SCLE will also fulfill the criteria for systemic lupus. Treatment can be tricky because SCLE lesions often resist treatments with steroid creams and antimalarials. People with SCLE should be sure to put on sunscreen and protective clothing when going outdoors in order to avoid sun exposure, which may trigger the development of more lesions.

Acute Cutaneous Lupus Erythematosus (ACLE)

Most people with ACLE have active SLE with skin inflammation, and ACLE lesions are found in about half of all people with SLE at some point during the course of the disease. The lesions characteristic of ACLE usually occur in areas exposed to the sun and can be triggered by sun exposure. Therefore, it is very important that people with ACLE wear sunscreen and protective clothing when going outdoors.

Common Lupus  Skin Problems

Malar Rash

About half of all lupus patients experience a characteristic rash called the malar or “butterfly” rash that may occur spontaneously or after exposure to the sun. This rash is so-named because it resembles a butterfly, spanning the width of the face and covering both cheeks and the bridge of the nose. The malar rash appears red, elevated, and sometimes scaly and can be distinguished from other rashes because it spares the nasal folds (the spaces just under each side of your nose). The butterfly rash may appear on its own, but some people observe that the appearance of the malar rash indicates an oncoming disease flare. Whatever the case, it is important to pay attention to your body’s signals and notify your physician of anything unusual.

Photosensitivity

50% of all people with lupus experience sensitivity to sunlight and other sources of UV radiation, including artificial lighting. For many people, sun exposure causes exaggerated sunburn-like reactions and skin rashes, yet sunlight can precipitate lupus flares involving other parts of the body. For this reason, sun protection is very important for people with lupus. Since both UV-A and UV-B rays are known to cause activation of lupus, patients should wear sunscreen containing Helioplex and an SPF of 70 or higher. Sunscreen should be applied everywhere, including areas of your skin covered by clothing, since most clothing items contain an SPF of only about 5. Be sure to reapply as directed on the bottle, since sweat and prolonged exposure can cause coverage to dissipate.

Livedo reticularis

People with lupus may experience a lacy pattern under the skin called livedo reticularis. This pattern may range anywhere from a violet web just under the surface of the skin to something that looks like a reddish stain. Livedo can also be seen in babies and young women, is more prominent on the extremities, and is often accentuated by cold exposure. The presence of livedo is usually not a cause for alarm, but it can be associated with antiphospholipid antibodies.

Alopecia

About 70% of people with lupus will experience hair loss (alopecia) at some point during the course of the disease. Hair loss in lupus is usually characterized by dry, brittle hair that breaks, and hair loss is more common around the top of the forehead. Physical and mental stress can also cause hair loss, as can certain medications, including corticosteroids such as prednisone. In many cases the hair will grow back, but hair loss due to scarring from discoid skin lesions may be permanent. There is no cure-all for hair loss, but treatments such as topical steroids and Rogaine may be prescribed. Sometimes dealing with the cosmetic side effects of lupus can be difficult, but some people find using hairpieces and wigs to be an effective means of disguising hair loss.

Oral and Nasal Ulcers

About 25% of people with lupus experience lesions that affect the mouth, nose, and sometimes even the eyes. These lesions may feel like small ulcers or “canker sores.” Such sores are not dangerous but can be uncomfortable if not treated. If you experience these types of lesions, your doctor may give you special mouthwash or Kenalog in Orabase (triamcinolone dental paste) to help expedite the healing process.

Raynaud’s Phenomenon

Approximately one-third of all people with lupus experience a condition called Raynaud’s phenomenon in which the blood vessels supplying the fingers and toes constrict. The digits of people with Raynaud’s are especially susceptible to cold temperatures. Often people with the condition will experience a blanching (loss of color) in the digits, followed by blue, then red discoloration in temperatures that would only be mildly uncomfortable to other people (such as a highly air-conditioned room). It is very important that people with Raynaud’s wear gloves and socks when in air-conditioned spaces or outside in cool weather. Hand warmers used for winter sports (e.g., Hot Hands) can also be purchased and kept in your pockets to keep your hands warm. These measures are very important, since Raynaud’s phenomenon can cause ulceration and even tissue death of the fingers and toes if precautions are not taken. People have even lost the ends of their fingers and toes due to the poor circulation involved in Raynaud’s phenomenon. Cigarettes and caffeine can exacerbate the effects of Raynaud’s, so be sure to avoid these substances. If needed, your doctor may also recommend a calcium channel blocker medication such as nifedipine or amlodipine to help dilate your blood vessels.

Hives (Urticaria)

About 10% of all people with lupus will experience hives (urticaria). These lesions usually itch, and even though people often experience hives due to allergic reactions, hives lasting more than 24 hours are likely due to lupus. If you experience this condition, be sure to speak with your doctor, since s/he will want to be sure that the lesions are not caused by some other underlying condition, such as vasculitis or a reaction to medication. Your doctor will probably distinguish these lesions from those caused by vasculitis by touching them to see if they blanch (turn white).

Purpura

Approximately 15% of people with lupus will experience purpura (small red or purple discolorations caused by leaking of blood vessels just underneath the skin) during the course of the disease. Small purpura spots are called petechiae, and larger spots are called eccymoses. Purpura may indicate insufficient blood platelet levels, effects of medications, and other conditions.

Cutaneous Vasculitis

Some people with lupus may develop a condition known as cutaneous vasculitis, in which the blood vessels near the skin experience inflammation that ultimately restricts blood flow. This condition can cause hive-like lesions on the skin that may itch and do not turn white when depressed. Other skin abnormalities may also be present, including actual gangrene of the digits. If left untreated, vasculitic lesions may cause ulceration and necrosis (cell death), and dead tissue must be surgically removed. Rarely, fingers or toes with aggressive ulceration and gangrene may require amputation. Therefore, it is very important that you notify your doctor of any skin abnormalities.

• Azathioprine (Imuran)
• Mycophenolate mofetil (Cellcept)
• Cyclosporine (Neoral, Sandimmune, Gengraf)
• Methotrexate (Rheumatrex)
• Leflunomide (Arava)
• Cyclophosphamide (Cytoxan)
• Chlorambucil (Leukeran)
• Nitrogen mustard (Mustargen)

What are immunosuppressive medications?

Immunosuppressives are medications that help suppress the immune system. Many were originally used in patients who received organ transplants to help prevent their bodies from rejecting the transplanted organ. However, these drugs are now also used for the treatment of certain autoimmune diseases, such as lupus and rheumatoid arthritis. In people with lupus, the immune system mistakenly attacks the body’s own tissues. Most immunosuppressives work to downregulate (suppress) this attack by interfering with the synthesis of DNA, the material in your cells that contains the blueprints for all of your genetic information. In doing this, these medications prevent the cells of your immune system from dividing. When cells cannot divide correctly, they will eventually die. The immunosuppressives prescribed most commonly for the treatment of lupus are azathioprine (Imuran), mycophenolate (Cellcept), and cyclosporine (Neoral, Sandimmune, Gengraf).

Immunosuppressive medications are used to control more serious lupus activity that affects major organs, including the kidney, brain, cardiovascular system, and lungs. Before prescribing an immunosuppressive medication, your doctor may perform a biopsy of the kidney or affected organ system to evaluate the most effective course of treatment. Sometimes immunosuppressive medications are given in addition to or instead of steroid therapy to lower the dose of steroids needed and thus spare some of the undesirable side effects of steroid therapy. For this reason, these drugs are sometimes called “steroid-sparing” medications or “adjuvant” (helping) drugs. Steroid-sparing drugs usually have a two-fold benefit, since they often reduce or eliminate the need for steroids while also improving lupus symptoms.

Because immunosuppressive drugs put down the immune system, people taking them are at an increased risk for infection. Try to stay away from people who have colds or other illnesses, and make sure to wash your hands regularly and maintain good personal hygiene. If you are also taking steroid medications, you may not realize that you are ill because the steroid may suppress your fever symptoms. Contact your doctor immediately at the first sign of any infection or illness.

In addition, immunosuppressive medications are known to increase the risk of cancer development later in life. However, lupus itself is also known to increase the risk of cancer, so by controlling your lupus now and preventing it from doing further damage to your body, immunosuppressive therapy may actually decrease your risk of developing cancer. Either way, it is very important to control your lupus activity now to prevent other potentially life-threatening complications.

Types of Immunosuppressive Medications

Azathioprine (Imuran)

Imuran is an anti-inflammatory immunosuppressive that can decrease joint damage and disability in people with lupus, rheumatoid arthritis, and other conditions. In addition, Imuran has proven to clearly improve lupus affecting the liver and kidneys. Imuran is “steroid-sparing,” which means that it may allow for a reduction of the amount of steroid being taken. Since the side effects of steroids generally increase with the dosage, this medication generally promotes a reduction in steroid side effects as well.

People with lupus have overactive immune systems. Imuran works by preventing some of the cells involved in this immune response (specifically, white blood cells [WBCs], or leukocytes) from spreading. Imuran is a “slow onset” drug, which means it may take 6-12 weeks for you to notice its effects. It usually comes in pill form and has fewer side effects than many other immunosuppressive medications. The most common and serious side effects involve the stomach and blood cells. Nausea and vomiting can occur, sometimes with stomach pain and diarrhea. Taking the medication with food may help to reduce these symptoms. Imuran can also decrease the number of certain cells in your blood. For this reason, blood tests should be done regularly to determine your white blood cell, platelet, and red blood cell count.

Less common side effects include liver test abnormalities, hepatitis (inflammation of the liver), pancreatitis (inflammation of the pancreas, a gland behind the stomach, that can cause abdominal pain), or an allergic reaction that can seem like the flu. During treatment, your doctor may perform tests for breakdown products (metabolites) of Imuran that can help monitor how your body is reacting to the drug.

Even though Imuran is effective in treating serious lupus symptoms, long term use of this medication does increase the risk of developing cancer. Your doctor can speak with you about this risk and any other concerns you may have. She/he will work with you to minimize the side effects of your medications while also maximizing the benefits.

In addition to having regular blood tests (CBCs), you should notify your doctor if you experience any of the following symptoms while taking Imuran: fever, a new rash, easy bruising or bleeding, or signs of infection. Be sure to speak with your doctor before taking getting any vaccines or having surgery. In addition, consult your doctor if you are pregnant, may become pregnant, or are breastfeeding, since Imuran can be harmful to your child.

Certain medications may interfere with Imuran, so be sure to notify your doctor of any other drugs you are taking. Medications that can interfere with Imuran include the gout medication allopurinol (Aloprim, Zyloprim), warfarin (Coumadin), some blood pressure medications including some ACE inhibitors (Accupril or Vasotec), olsalazine (Dipentum), mesalamine (Asacol, Pentasa), and sulfasalazine* (Azulfidine).

Mycophenolate mofetil (Cellcept)

Cellcept is an immunosuppressant used especially for lupus patients with signs of kidney disease. It works by targeting an enzyme in the body—a protein responsible for certain chemical reactions—that is important in the formation of DNA in your cells. In doing so, Cellcept impairs your immune system function as well. Usually Cellcept is given twice a day for a total dose of about 2000-3000 milligrams (mg) per day, but this dosage may be reduced. Like Imuran, Cellcept is steroid-sparing, so it may allow you and your doctor to reduce your dosage of steroid medications and thus also reduce their side effects.

Cellcept may cause some side effects. The most common effects include stomachache, nausea, vomiting, and/or diarrhea. Headache, dizziness, sleeplessness, and tremors (involuntary muscle movements) may also occur. Skin rashes can arise but are less common. Since lupus can also cause skin rashes, it may be difficult to determine whether a rash is from your medication or your lupus. You should speak with your doctor upon detecting any new rashes or symptoms.

Cellcept may also cause a reduction in the number of certain cells in your blood. A reduction in your white blood cell count could increase your chance of infection. As with other immunosuppressive medications, it is important that you try to avoid infection and notify your doctor at the first sign of illness. In addition, a reduction in red blood cells caused by Cellcept may lead to anemia, which could make you tired or lead to easy bruising. Cellcept can also reduce the number of platelets in your blood, which may also cause easy bruising or gastrointestinal bleeding (bleeding anywhere along the pathway that food travels in the body). Obtaining periodic blood tests while taking Cellcept can help you and your doctor to detect and correct these problems. Blood tests should be performed frequently during the first several months of taking this medication and less often as more time passes.

People over 65 and those that have experienced ulcers or other gastrointestinal disorders should speak to their doctors before taking Cellcept. People in these groups may experience an increased risk of side effects. In addition, there may be an increased risk of developing cancer such as lymphoma and skin cancer when taking immunosuppressives such as Cellcept. You should discuss this with your doctor before beginning this medication. It is important to realize, however, that Cellcept may be the best way to control the kidney disease associated with lupus, and that lupus too can cause cancer. Thus, prescribing Cellcept for your kidney involvement is not meant to introduce new risk factors, but rather to treat the seriousness of your condition at this moment in time.

In addition, be sure to wear sunscreen when going outside and avoid prolonged sun exposure—even if you are not taking immunosuppressive medications—since sunlight can also aggravate your lupus symptoms.

If you are pregnant, may become pregnant, or are breast-feeding, your doctor will strongly recommend that you stop taking Cellcept due to the risk of birth defects. In addition, even though it is not known whether Cellcept decreases the effectiveness of oral contraceptives, it may be able to reduce their concentration in the blood, so other forms of birth control are advised. Antacids can also interfere with your body’s absorption of Cellcept. If you need to take an antacid, do so at least one hour before or at least two hours after taking Cellcept. As with other immunosuppressive medications, you should speak to your doctor before getting any vaccines or having any sort of surgery.

Certain drugs may interact or interfere with the effectiveness of Cellcept. These medications include: cholestercholestyramine (Questran), acyclovir (Zovirax), gancyclovir (Cytovene), azathioprine (Imuran), antacids containing magnesium or aluminum hydroxide (such as Maalox, Rolaids, or Mylanta), oral contraceptives, trimethoprim/sulfamethoxazole (Bactrim),* theophylline (Theo-Dur), phenytoin (Dilantin), probenecid (Benemid), or aspirin and other salicylates.

Be sure to notify your doctor immediately if you experience easy bruising or bleeding, persistent or bloody diarrhea, trouble breathing, fever, or any sign of infection.

Recently, the FDA issued an alert regarding a possible relationship between Cellcept and a serious neurological disease called multifocal leukoencephalopathy (PML). A similar warning was issued regarding the drug rituximab (Rituxan) in late 2006. PML is an extremely rare but fatal disease, but it is important to understand that Cellcept and rituximab are not unique in their linkage to PML. PML is associated with conditions of severe immune deficiency, such as AIDS, cancer, lupus, and the immunosuppression that can be involved in the treatment of those conditions. Although immunosuppressive medications are effective in the treatment of lupus, your doctor can discuss with you the risk of this possible relationship and the use of the immunosuppressive medications involved in your advised treatment.

Cyclosporine (Neoral, Sandimmune, Gengraf)

Cyclosporine is a more potent immunosuppressive medication that works by blocking the function of cells in your immune system called T-lymphocytes, or “T-cells.” Like other immunosuppressives, it was originally used to prevent the immune systems of patients with transplanted kidneys from rejecting the transplanted organs. It is now also prescribed for people who suffer from inflammation of the kidney caused by lupus, otherwise known as lupus nephritis. However, cyclosporine can be toxic to the kidneys, so use of this medication is usually reserved for cases in which a person’s lupus does not respond to other immunosuppressive medications like Cellcept. Cyclosporine is also prescribed for people with severe psoriasis, a skin condition that can also cause pain and swelling of the joints, and it can be helpful in reducing some of the pain, swelling, and stiffness associated with lupus arthritis.

The starting dose of cyclosporine depends on your body weight (usually 2.5 milligrams [mg] per kilogram [kg] per day). The dose is then increased depending on how well the medication works for you and how well your body tolerates the drug. Cyclosporine comes in 25 and 100 mg tablets, and patients usually end up taking 75 or 100 mg per day. You may notice some reduction in pain and swelling after about a week of taking the medication, but its full effects are usually not felt for about 3 months.

Cyclosporine can cause some side effects. About 25% of people taking cyclosporine develop high blood pressure (hypertension). In addition, because cyclosporine can be tough on the kidneys, it can cause a substance called uric acid to build up in the blood (a state known as hyperuricemia). Sometimes this buildup of uric acid can cause gout, a condition that causes intense swelling in one of the joints, often the the big toe. If you already have gout, your condition may worsen while taking cyclosporine. Fortunately, many of these side effects go away as treatment with cyclosporine is reduced or stopped, so your doctor can work with you to adjust your dosage if you begin to experience these problems.

Other common side effects include headaches, stomach pain (including dyspepsia, a gnawing or burning pain in the pit of your stomach accompanied by bloating), vomiting, diarrhea, and swelling in your hands or feet. Less common side effects include tremors (unintentional muscle movements), increased hair growth, muscle cramps, and numbness or tingling in your hands and feet (a condition known as neuropathy). Some people may also experience swelling of the gums while taking cyclosporine. Be sure to brush and floss regularly; this routine may alleviate some of this swelling.

Cyclosporine may increase your risk of developing certain types of cancer, including skin cancer. For this reason, you should coordinate regular skin exams with your doctor. In addition, try to stay out of the sun and make sure to wear sunscreen when you do go outside.

Do not eat grapefruit or drink grapefruit juice while taking cyclosporine. Grapefruit increases the amount of cyclosporine that is absorbed by your body.

Like other immunosuppressive medications, cyclosporine increases your risk of infection, so make sure to wash your hands and stay away from people who may be sick. Notify your doctor at the first sign of any illness. In addition, tell your doctor if you plan to have any vaccines or surgeries, since both can pose risks for people taking immunosuppressive medications.

Cyclosporine can cause serious complications during pregnancy such premature labor and high blood pressure and fluid retention in your baby, so you should not take cyclosporine if you are pregnant or may become pregnant. Also, do not take cyclosporine while breast-feeding, since it can be passed to your baby through breast milk.

Cyclosporine interacts with certain drugs, so be sure to notify your doctor of any medications you may be taking, including prescription and over-the-counter drugs, supplements, and vitamins. Drugs that may interfere or interact with cyclosporine include:

• Heart and blood pressure medications: diltiazem (Cardizem, Tiazac), nicardipine (Cardene), verapamil (Calan, Covera-HS, Isoptin, Verelan), “potassium sparing diuretics” amiloride (Midamor), spironolactone (Aldactone) and triamterene (Dyrenium)
• Cholesterol lowering medications: lovastatin (Mevacor) and simvastatin (Zocor)
• Antibiotics and antifungals: clarithromycin (Biaxin), erythromycin, naficillin, fluconazole (Diflucan), intraconazole (Sporanox), ketoconazole (Nizoral), and rifampin (Rifadin, Rimactane)
• Anti-seizure (anti-epileptic) medications: carbamazepine (Tegretol), phenobarbital (Solfoton), and phenytoin (Dilantin)
• Antidepressants: nefazadone (Serzone) and the selective serotonin reuptake inhibitors (SSRIs) such as paroxitine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft)
• Human immunodeficiency virus (HIV) protease inhibitors: indinivir (Crixivan), saquinavir (Fortovase, Invirase), ritonavir (Norvir), and nelfinavir (Viracept)
• Others: allopurinol (Lopurin, Zyloprim), bromocryptine (Parlodel), androgens (male hormones), estrogens (female hormones), danazol (Danocrine), metoclopramide (Reglan), methylprednisolone, octreotide, ticlopidine (Ticlid), cimetidine (Tagamet), methoxsalen (Oxsoralen), coal tar (Balnetar, Zetar), trioxsalen (Trisoralen)

Be sure to tell your doctor if you are taking any of these medications.

Disease-Modifying Antirheumatic Drugs (DMARDs)

Methotrexate (Rheumatrex)
Leflunomide (Arava)

Disease-modifying antirheumatic drugs, better known as “DMARDs,” are immunosuppressive medications that are used to treat the pain and swelling of the arthritis that can accompany lupus. DMARDs not only reduce this pain and swelling, but they may also be able to decrease long term damage to your joints.

Methotrexate (Rheumatrex)

Methotrexate is one of the most commonly used drugs for the treatment of rheumatoid arthritis, and it is used in lupus patients to alleviate the joint pain and swelling of polyarthritis (arthritis involving multiple joints). It is only mildly effective for more severe lupus symptoms involving the kidneys and other organs and should be used carefully in people with these conditions. Historically, methotrexate has been used to treat cancer and psoriasis, a skin condition that can also affect the joints. However, in the late 1980s, the medication was approved by the FDA for the treatment of arthritis and has been used commonly for this ever since. Methotrexate works by interfering with the production of folic acid, which is a building block for growing cells in your body. As a result, methotrexate hinders the growth of certain cells, including those of the immune system. This medication is also steroid-sparing, meaning it can be used in conjunction with steroids to lower the dose of steroid therapy and thus also lower the associated side effects.

The medication is usually taken as a tablet in doses of 7.5 to 25 milligrams (mg) per week, but it can also be given as an injection. People taking methotrexate usually feel improvements in 3-6 weeks, but it can take up to 3 months to feel the full benefit of the drug. Be sure to take this medication as directed. If you miss a dose, you can usually take the medication up to 4 or 5 days after. However, if you miss this window, contact your doctor regarding how you should proceed.

Most people taking methotrexate do not experience side effects and many of the more minor side effects will decrease with time. However, the likelihood of these side effects does increase as your dosage goes up. Many of the side effects of methotrexate involve the fact that the medication works by interfering with the production of folic acid in your body. Therefore, your doctor will most likely recommend that you take folate supplements, which will prevent many of these side effects, including mouth sores (stomatitis). Other side effects may include nausea, vomiting, and an increased risk for abnormal liver function tests. Because of the danger to your liver, you should not drink alcohol while taking methotrexate; drinking while on this medication can cause irreversible damage to your liver. In addition, it is important that people taking methotrexate have normal liver function tests. Be sure to tell your doctor if you have a history of liver disease. In addition, lung problems, such as a continuing cough or shortness of breath, can occur while taking this medication but are more common in people with preexisting lung conditions. Talk to you doctor if you experience these symptoms.

Some patients experience gradual hair loss (alopecia), but hair usually grows back once you stop taking methotrexate. In addition, methotrexate can increase your sensitivity to sunlight. Since many lupus patients already experience sun sensitivity, try to limit sun exposure and be sure to wear sunscreen when going outdoors.

It is important to remember that sometimes the side effects of this medication can go unnoticed; sometimes people may have abnormal blood tests while feeling no side effects at all, so it is important to have blood tests (complete blood counts, or “CBCs”) performed every 2-3 months while taking methotrexate.

If you are pregnant, may become pregnant, or are breastfeeding, you should not take this medication because it can cause serious birth defects and complications during pregnancy. Women taking this medication should use an effective method of birth control. Speak to your doctor about any pregnancy plans or concerns.

As with other drugs that may suppress your immune system, talk to your doctor about any vaccines or surgeries you may have. In addition, be sure to notify him/her of any other medications, both prescription and over-the-counter, that you may be taking. Methotrexate can interact with certain drugs, including the antibiotic trimethoprim (Bactrim)* and NSAIDs such as ibuprofen (Advil, Motrin) and celecoxib (Celebrex). Do remember, though, that sometimes methotrexate may be used in combination with certain NSAIDs to treat lupus. Your doctor will work with you to determine which treatments will work best to treat your lupus symptoms with the fewest side effects.

Leflunomide (Arava)

Leflunomide is another DMARD used to treat the swelling, pain, and stiffness that many lupus patients feel due to arthritis. It can either be prescribed alone or in combination with other treatments, such as methotrexate; often leflunomide is prescribed for patients who do not respond well to methotrexate. Leflunomide works by blocking the formation of DNA in the cells of your body, including those of the immune system. In hindering the formation of DNA, leflunomide stops the body from producing the overactive immune cells that are responsible for the swelling, stiffness, and pain in your joints.

Leflunomide is usually taken in tablets of 10 or 20 milligrams (mg) once a day. 6-12 weeks may pass before you feel the full benefits of this medication, although your joint pain and stiffness will probably start to improve after just a few weeks. It takes some time for the medication to build up in your body, so some doctors may prescribe something called a “loading dose” when you first begin to take leflunomide. A loading dose is a large dose—about 100 mg—usually given once a week for three weeks in addition to your regular dose. Alternatively, some doctors may give this loading dose over the first three days. This technique, however, usually increases the chance that the person will develop side effects, including diarrhea. The good news is that the diarrhea usually goes away once the loading dose is stopped.

Leflunomide does have several side effects. The most common side effect is diarrhea, which affects about 1 in 5 people, but this symptom usually goes away with time. In addition, your doctor can talk with you about taking an anti-diarrheal medication to curb some of this discomfort. If the diarrhea persists, she/he may lower your dosage.

Other side effects include nausea, indigestion, rash, or hair loss (alopecia), but these effects are less common. In addition, about 1 in 10 patients taking leflunomide have abnormal liver function tests or decreased blood cell counts, so individuals taking this medication should have liver enzyme and blood count tests done regularly every 3-4 months. Because of this risk to your liver, you should not drink alcohol while taking leflunomide, and you should tell your doctor if you have had liver problems in the past.

Women who are pregnant, may become pregnant, or are breastfeeding should speak with their doctor before taking leflunomide, since this medication can cause serious birth defects and complications. In addition, women should use an effective method of birth control while taking leflunomide and continue to do so until two years after leflunomide is stopped, since the medication is known to remain in your body well after you actually stop taking it. Men who want to have children should also talk to their doctor about stopping the medication. Anyone who is on the medication and would like to have children should speak to their doctor about a medication called cholestyramine (Questran), which can help eliminate leflunomide from your body.

As with other drugs that suppress your immune system, speak with your doctor about any vaccinations or surgeries you plan to have and any other medications you may be taking, including prescription drugs, over-the-counter medications, vitamins, and supplements. Medications that can interact with leflunomide include cholestyramine (Questran), tolbutamide (Orinase), and rifampin (Rifadin, Rimactane), so be sure to tell your doctor if you are on these medications.

Cytotoxic Drugs

Cyclophosphamide (Cytoxan)
Chlorambucil (Leukeran)
Nitrogen mustard (Mustargen)

Cytotoxic medications are a class of immunosuppressives that were originally developed (and are still used) to treat certain types of cancer. The cytotoxic drugs usually prescribed to treat lupus symptoms are classified as alkylating agents and are reserved for patients with more serious forms of lupus that involve organs such as the kidneys, central nervous system, lungs, and blood vessels. Cytotoxic medications work against the cells of your immune system that make antibodies (immunoglobulins). Usually, these molecules help the body to ward of infections and other invaders. However, with lupus, these antibodies actually work against your own body and are produced at a rapid rate. Cytoxic drugs fight the rapidly dividing cells of the immune system, but in doing so, they also work against other rapidly dividing cells in your body, including blood cells, hair cells, and sex cells. As a result, cytotoxic medications can have serious long term side effects. Even though cytotoxics have proven to improve the symptoms of kidney, nervous system, lung, and blood vessel disease in lupus patients, it is important for you and your doctor to evaluate the costs and benefits of cytotoxic therapy before beginning this treatment.

Cytoxan (cyclophosphamide)

Cytoxan is a cytotoxic medication usually reserved for lupus patients with serious kidney problems who have not responded to other medications. The dosage of Cytoxan varies from person to person. It can be taken in tablet form, but more often it is given intravenously (IV) at the doctor’s office. The IV procedure usually take about 15 to 60 minutes, and a medication may be given before to reduce any nausea you may feel. Doctors usually give Cytoxan once a month for 6 months and then every 2 to 3 months for two years. It may take a few weeks or months for Cytoxan to improve your lupus symptoms.

The side effects of Cytoxan range from mild to severe and may be worse when the medication is taken in tablet form. Side effects include nausea and vomiting, which can sometimes be prevented with an anti-nausea medication such as ondansetron (Zofran). Hair loss (alopecia) can occur, but hair usually grows back when the medication is stopped. Skin rashes can also occur and be difficult to differentiate from lupus symptoms. Like other medications that suppress your immune system, Cytoxan can increase your risk of infections, especially shingles and certain “opportunistic infections,” infections that do not usually cause disease in healthy individuals. Therefore, it is important that you wash your hands regularly, maintain good personal hygiene, and notify your doctor at the first sign of any infection or fever. Also tell your doctor if you are to have any vaccines or surgeries, since your immune system will be suppressed by Cytoxan.

More serious side effects include a reduction in white blood cell count, which usually occurs about 8-12 days after starting treatment. Your doctor should perform blood tests at this time to determine whether your dosage should be altered. In addition, Cytoxan can cause infertility in both men and women when taken for long periods of time. However, an injection called leuprolide (Lupron) can be given to help protect your body against this sterility; you may want to discuss this issue with your doctor before starting the medication. In addition, women can stop having periods when on Cytoxan. However, you can still become pregnant, so it is recommended that you use a method of birth control, since taking this drug can cause serious harm to the fetus. Be sure to talk to your doctor before taking Cytoxan if you are pregnant, could become pregnant, or are breastfeeding.

Cytoxan can also cause certain bladder problems. In order to use this drug, your body must break it down into several byproducts, one of which can irritate your bladder and cause scarring or blood in your urine. This side effect is common, so you should drink plenty of fluids—at least 8 glasses of water—per day. If you are taking Cytoxan intravenously, you may be given mesna (Mesnex) to prevent these bladder issues.

Because Cytoxan targets normal cells within your body in addition to those of the immune system, it increases your risk of cancer. The more Cytoxan you take and the longer you take it, the greater your risk of developing cancer, even later in life. Leukemia and bladder cancer are the most common form of cancer developed in patients taking Cytoxan, so your doctor should perform urine tests regularly.
Cytoxan can interact with certain drugs, so be sure to tell your doctor about any medications you are taking, either prescription or over-the-counter. Also tell him/her about any dietary supplements (including herbal supplements) and/or vitamins that you may be taking. The following drugs can interact with Cytoxan: the gout medication allopurinol (Aloprim, Zyloprim), phenobarbital (Solfoton), warfarin (Coumadin), thiazide diuretics, such as hydrochlorothiazide, and some psychiatric medications. Be sure to notify your doctor if you are taking any of these medications.

Chlorambucil (Leukeran) and nitrogen mustard (Mustargen)

Chlorambucil (Leukeran) and nitrogen mustard (Mustargen) are cytotoxic medications similar to Cytoxan. They have been used in the past to treat lupus symptoms but are not used as commonly as Cytoxan at present. Leukeran is usually taken by mouth and is commonly used in Europe and developing countries. In the U.S., it is usually given to people who cannot tolerate Cytoxan or who have an allergy to the medication. The medication is usually tolerated better than Cytoxan tablets. However, it is more dangerous than IV Cytoxan because it must be taken for a longer period of time, which increases the risk of developing cancer. Therefore, if you take Leukeran tablets, you should do so only for a maximum of two years.

Nitrogen mustard was actually the first cytotoxic medication found to be effective in the treatment of lupus. However, it is seldom used today because it is trickier to administer and it must be given intravenously in the hospital. Your doctor will speak to you in more detail if this medication becomes involved in your treatment.

∗ People with lupus should not take Bactrim, sulfa antibiotics (e.g., Gantrisin, Septra), or sulfa diuretics (e.g., Aldactone), since these medications can cause lupus flares by increasing sun sensitivity and occasionally lowering blood counts. If you are prescribed one of these medications, talk to your doctor about possible alternatives.

Blood Tests Used in the Diagnosis of Lupus

Antibodies form in the body as a response to infection. When an invader (antigen) enters the body, white blood cells known as B lymphocytes react by making special types of proteins called antibodies. Antibodies are your body’s way of remembering an antigen; if it enters the body again, the antibodies will recognize it, combine with it, and neutralize it to prevent you from becoming infected. However, with autoimmune diseases such as lupus, the immune system can produce antibodies (auto-antibodies) that attack your body’s cells as though they were invaders, causing inflammation, damage, and even destruction. Several blood tests can be performed to detect specific auto-antibodies and help make the diagnosis of lupus. These blood tests are not conclusive by themselves, but combining the tests with certain physical findings can help to corroborate a diagnosis.

Anti-Nuclear Antibody (ANA) Test

Anti-nuclear antibodies (ANA) are autoantibodies to the nuclei of your cells. 98% of all people with systemic lupus have a positive ANA test, making it the most sensitive diagnostic test for confirming diagnosis of the disease. The test for anti-nuclear antibodies is called the immunofluorescent antinuclear antibody test. In this test, a blood sample is drawn and sent to a laboratory. Serum from the blood sample is then added to a microscopic slide prepared with specific cells (usually sections of rodent liver/kidney or human tissue culture cell lines) on the slide surface. If the patient has antinuclear antibodies, their serum will bind to the cells on the slide. Then, a second antibody tagged with a fluorescent dye is added so that it attaches to the serum antibodies and cells that have bound together. Lastly, the slide is viewed using a fluorescence microscope, and the intensity of staining and pattern of binding are scored at various dilutions. The test is read as positive if fluorescent cells are observed.

Usually, the results of the ANA test are reported in titers and patterns. The titer gives information about how many times the lab technician diluted the blood plasma to get a sample of ANAs. Each titer involves doubling the amount of test fluid, so that the difference between a titer of 1:640 and 1:320 is one dilution. A titer above a certain level then qualifies as a positive test result. ANA titers may increase and decrease over the course of the disease; these fluctuations do not necessarily correlate with disease activity. Thus, it is not useful to follow the ANA test in someone already diagnosed with lupus.

The pattern of the ANA test can give information about the type of autoimmune disease present and the appropriate treatment program. A homogenous (diffuse) pattern appears as total nuclear fluorescence and is common in people with systemic lupus. A peripheral pattern indicates that fluorescence occurs at the edges of the nucleus in a shaggy appearance; this pattern is almost exclusive to systemic lupus. A speckled pattern is also found in lupus. Another pattern, known as a nucleolar pattern, is common in people with scleroderma.

It is important to realize that even though 98% of people with lupus will have a positive ANA, ANAs are also present in healthy individuals (5-10%) and people with other connective tissue diseases, such as scleroderma and rheumatoid arthritis. Moreover, about 20% of healthy women will have a weakly positive ANA, and the majority of these people will never develop any signs of lupus. One source cites that some ten million Americans have a positive ANA, but fewer than 1 million of them have lupus. Therefore, a positive ANA test alone is never enough to diagnosis systemic lupus. Rather, a physician will order an ANA test if the patient first exhibits other signs of lupus. This is because by itself, the test has low diagnostic specificity for systemic lupus, but its value increases as a patient meets other clinical criteria. It is possible for people with lupus to have a negative ANA, but these instances are rare. In fact, only 2% of people with lupus will have a negative ANA. People with lupus who have a negative ANA test may have anti-Ro/SSA or antiphospholipid antibodies.

Other Diagnostic Tests

In people with a positive ANA, more tests are usually performed to check for other antibodies that can help to confirm the diagnosis. Certain autoantibodies and substances in the blood can give information about which autoimmune disease, if any, is present. To check for these antibodies, doctors usually order what is called an ANA panel, which checks for the following antibodies: anti-double-stranded DNA, anti-Smith, anti-U1RNP, anti-Ro/SSA, and anti-La/SSB. Some laboratories also include other antibodies in their panel, including antinucleoprotein, anticentromere, or antihistone.

Anti-dsDNA Antibody

The anti-double-stranded DNA antibody (anti-dsDNA) is a specific type of ANA antibody found in about 30% of people with systemic lupus. Less than 1% of healthy individuals have this antibody, making it helpful in confirming a diagnosis of systemic lupus. [The absence of anti-dsDNA, however, does not exclude a diagnosis of lupus.] The presence of anti-dsDNA antibodies often suggests more serious lupus, such as lupus nephritis (kidney lupus). When the disease is active, especially in the kidneys, high amounts of anti-DNA antibodies are usually present. However, the anti-dsDNA test cannot be used to monitor lupus activity, because anti-dsDNA can be present without any clinical activity. Three tests are currently used to detect anti-dsDNA antibodies, namely enzyme-linked immunosorbent assay (ELISA), the Crithidia luciliae immunofluorescence test, and a test called radioimmunoassay.

Anti-Smith Antibody

An antibody to Sm, a ribonucleoprotein found in the nucleus of a cell, is found almost exclusively in people with lupus. It is present in 20% of people with the disease (although the incidence varies among different ethnic groups), but it is rarely found in people with other rheumatic diseases and its incidence in healthy individuals is less than 1%. Therefore, it can also be helpful in confirming a diagnosis of systemic lupus. Unlike anti-dsDNA, anti-Sm does not correlate with the presence of kidney lupus. Prospective studies have been performed as to whether anti-Sm correlates with lupus flares and disease activity, although evidence seems to suggests that it does not. The anti-Sm antibody is usually measured by one of four methods: ELISA, counterimmunoelectrophoreses (CIE), immunodiffusion, or hemagglutination.

Anti-U1RNP Antibody

Anti-U1RNP antibodies are commonly found along with anti-Sm antibodies in people with SLE. The incidence of anti-U1RNP antibodies in people with lupus is approximately 25%, while less than 1% of healthy individuals possess this antibody. However, unlike anti-dsDNA and anti-Sm antibodies, anti-U1RNP antibodies are not specific to lupus; they can be found in other rheumatic conditions, including rheumatoid arthritis, systemic sclerosis, Sjogren’s syndrome, and polymyositis.
Anti-U1RNP has shown to be associated with features of scleroderma, including Raynaud’s phenomenon; it has also been linked to other conditions, such as Jaccoud’s arthropathy, a deformity of the hand caused by arthritis. Levels of anti-U1RNP may fluctuate in individuals over time, but this fluctuation has not proven to be a significant indicator of disease activity.

Anti-Ro/SSA and Anti-La/SSB Antibodies

Anti-Ro/SSA and Anti-La/SSB are antibodies found mostly in people with systemic lupus (30-40%) and primary Sjogren’s syndrome. They are also commonly found in people with lupus who have tested negative for anti-nuclear antibodies. Anti-Ro and anti-La can also be found in other rheumatic diseases, such as systemic sclerosis, rheumatoid arthritis, and polymyositis, and are present in low titers in about 15% of healthy individuals. These antibodies are not highly specific for systemic lupus, but they are associated with certain conditions, including extreme sun sensitivity, a clinical subset of lupus called subacute cutaneous lupus erythematosus (SCLE), and a lupus-like syndrome associated with a genetic deficiency of a substance called complement (a system of proteins that helps mediate your body’s immune response). In addition, babies of mothers with anti-Ro and anti-La antibodies are at an increased risk of neonatal lupus, an uncommon condition that produces a temporary rash and can lead to congenital heart block. Therefore, women with lupus who wish to become pregnant should be tested for these antibodies.

Anti-Histone Antibodies

Antibodies to histones, proteins that help to lend structure to DNA, are usually found in people with drug-induced lupus (DIL), but they can also be found in people with systemic lupus. However, they are not specific enough to systemic lupus to be used to make a concrete diagnosis.

Serum (blood) Complement Test

A serum complement test measures the levels of proteins consumed during the inflammatory process. Thus, low complement levels reflect that inflammation is taking place within the body. Variations in complement levels exist in different individuals simply due to genetic factors.

Sources

• “ANA.” 8 April 2009. Lab Tests Online. 8 April 2009. American Association for Clinical Chemistry. 6 July 2009. – Link
• “Blood Tests.” The Lupus Site. 6 July 2009. – Link
• “Laboratory Tests.” Lupus Foundation of America. 6 July 2009. – Link
• Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995.
• Wallace, Daniel J., and Bevra Hannahs Hahn, eds. Dubois’ Lupus Erythematosus. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007.

Systemic lupus erythematosus (“lupus” or “SLE”) and other autoimmune diseases are linked to an increased risk of certain types of cancer. Specifically, lupus patients may experience an elevated risk of lymphoma and other cancers, such as cancer of the cervix. Researchers have elucidated certain connections between lupus and cancer. For example, it is widely accepted that immunosuppressive medications, such as azathioprine (Imuran) and mycophenolate mofetil (Cellcept) contribute to elevated cancer risk. However, one of the largest studies to investigate this connection suggests that the risk of cancer is actually greatest during the earlier stages of lupus, indicating that exposure to immunosuppressive therapy is not the only link between lupus and cancer. Physicians do not yet understand the precise relationship between lupus and cancer.

Lupus and lymphoma

Studies show an increased risk of both Hodgkin’s and non-Hodgkin lymphoma in lupus patients. It is believed that the elevated risk of lymphoma results from the disease process of lupus—specifically the overstimulation of B-cells coupled with defects in the immune system’s surveillance system—and not just from medications or other associated risk factors. Some suggest that immunosuppressive medications also increase the risk of lymphoma and other blood cancers, especially 5 or more years after taking the drug. In addition, people with Sjogren’s syndrome, which is relatively common in lupus, experience an even greater elevation of lymphoma risk, suggesting that lymphoma in lupus patients may also be linked to this condition.

Lupus and breast cancer

Some data indicate that women with lupus experience an increased risk of breast cancer. Increased estrogen levels might contribute to a higher risk of breast cancer in women with lupus.

Lupus and lung cancer

Lung cancer is about 1.4 times more common in people with lupus than in the general population. Interestingly, people with lupus and lung cancer are more likely to experience rare types of lung cancer. However, like the general population, many of the people with lupus who develop lung cancer are smokers. In fact, 85% of lung cancer is caused by tobacco. It is very important that people with lupus do not smoke. Smoking not only increases the chance of developing lung cancer, it also ups the risk for cardiovascular disease (which is also markedly increased in people with lupus), and prevents lupus drugs like Plaquenil from working properly. If you need help quitting, talk to your doctor. S/he can help you find the most effective strategy to curb your smoking habit.

Lupus and cervical cancer

Certain studies have shown an elevated risk of cervical cancer and abnormal PAP tests in women with lupus. One study linked the increased incidence of abnormal PAP tests with histories of sexually transmitted disease, contraceptive use, and immunosuppressive medications. Some physicians suggest that either the use of immunosuppressives or flawed inherent immunity lead to a decrease in the ability of lupus patients to fight off human papilloma virus (HPV), a virus associated with cervical cancer. [Gardasil (the HPV vaccine)  is recommended for young women with lupus to reduce the risk of later cervical cancer.] However, like much of our knowledge of cancer in lupus, these connections are not fully known or understood.

Lupus and endometrial cancer

New evidence suggests that lupus patients also experience an elevated incidence of endometrial cancer, although the cause for this risk is unknown.

NSAIDs and cancer

It has been found that people with Rheumatoid Arthritis, another autoimmune disease, experience a lower incidence of colorectal cancer than the general population. Although the precise cause of this phenomenon is unknown, it has been attributed to the long-term (10 years or more) use of non-steroidal anti-inflammatory drugs (NSAIDS) and aspirin. Evidence has also been found that long-term aspirin and NSAID use may also reduce the risk of colorectal, breast, and prostate cancer in the general population. It is likely that this benefit also holds for people with lupus, but that does not mean that one should begin taking aspirin and NSAIDs for this reason. In fact, long term NSAID use can increase cardiovascular disease. Therefore, you should only take medications as directed by your physician.

The importance of regular cancer screenings

Despite the increased risk of cancer in people with lupus, studies show that lupus patients are actually equally or even less likely than the general population to undergo cancer screenings. Thus, it is very important that you speak with your doctor about lupus and cancer to ensure that you see the appropriate physicians for cancer screenings as often as recommended.

Healthy habits

Certain risk factors, such as smoking, obesity, hormone replacement therapy, and exposure to immunosuppressive medications, increase the chance that an individual will develop cancer. Therefore, it is also important that you practice healthy lifestyle habits. Obesity also increases the risk of certain cancers, so try to eat foods that help you maintain a healthy weight.

Sunlight causes lupus flares and also increases the risk of skin cancer. People with lupus should avoid the sun whenever possible. If you need to be outdoors, wear sunscreen with an SPF of 85 or greater and be sure that your sunscreen contains Helioplex to protect you from both UV-A and UV-B rays.

Sources

• Gayed M, Bernatsky S, Ramsey-Goldman R, Clarke A, Gordon C. Lupus and cancer. Lupus. 209; 18(6); 479-85.
• Research Update: Cancer in Lupus. (Based on presentation by Dr. Sasha Bernatsky at BC Lupus Society Symposium.) 22 Oct. 2005. Available at <http://www.bclupus.org/resources.html>.

Antiphospholipid antibodies are antibodies directed against phosphorus-fat components of your cell membranes called phospholipids, certain blood proteins that bind with phospholipids, and the complexes formed when proteins and phospholipids bind. Approximately 50% of people with lupus possesses these antibodies, and over a twenty-year period of time, one half of lupus patients with one of these antibodies—the lupus anticoagulant—will experience a blood clot. People without lupus can also have antiphospholipid antibodies.

The most commonly discussed antiphospholipid antibodies are the lupus anticoagulant (LA) and anticardiolipin antibody (aCL). These two antibodies are often found together, but can also be detected alone in an individual. Other antiphospholipid antibodies include anti-beta 2 glycoprotein 1 (anti-ß2 GPI), anti-prothrombin, and the “false-positive” test for syphilis. Like other antibodies involved in lupus that are directed against self (auto-antibodies), antiphospholipid antibodies can come and go or increase and decrease.

The presence of an antiphospholipid antibody such as the lupus anticoagulant and anticardiolipin antibody in an individual is associated with a predisposition for blood clots. Blood clots can form anywhere in the body and can lead to stroke, gangrene, heart attack, and other serious complications. In people with lupus, the risk of clotting does not necessarily correlate with disease activity, so the presence of these antibodies can cause problems even when a person’s lupus is in control. Complications of antiphospolipid antibodies in lupus include fetal loss and/or miscarriages, blood clots of the veins or arteries (thromboses), low platelet counts (autoimmune thrombocytopenia), strokes, transient ischemic attacks (stroke warnings), Libman-Sacks endocarditis (formation of a clot on a specific heart valve), pulmonary emboli, and pulmonary hypertension.

Many people with antiphospholipid antibodies have a purple or reddish lacy pattern just under their skin known as livedo. This pattern is especially apparent on the extremities (i.e., the arms and legs). It is important to realize, however, that having livedo does not necessarily mean one has antiphospholipid antibodies; rather, doctors acknowledge a correlation between the two conditions. Livedo can be associated with other diseases of the blood vessels, but in fact, many perfectly healthy women also experience the condition.

Antiphospholipid Antibody Syndrome (APS)

Individuals who experience complications from antiphospholipid antibodies are diagnosed with Antiphospholipid Antibody Syndrome (APS). This condition can occur both in people with lupus and those without lupus. Fifty percent of people with lupus have APS. The presence of one or more clinical episodes of thromboses (blood clots) and/or complications during pregnancy, such as miscarriage or premature birth, in conjunction with a significant level of anticardiolipin antibodies, antiphospholipid antibodies, and/or anti-ß2 GPI anti- antibodies usually indicates the presence of APS. When APS is the sole diagnosis, and no other connective tissue diseases are present, APS is often said to be the primary diagnosis; when APS is present in association with lupus or another connective tissue disease, APS is said to be “secondary.” This classification is controversial, however, because some people with primary APS (about 8%) later develop lupus, suggesting a connection between the two conditions.

Types of Antiphospholipid Antibodies

False-Positive Test for Syphilis

In the 1940s, when it was common for people to have premarital exams, doctors realized that some women with lupus tested positive for syphilis. Further studies indicated that 1 in 5 people with lupus had a false-positive syphilis test. The syphilis test of those days—the Wasserman test—was dependant on an antibody found in syphilis patients called reagin. The substance to which this antibody reacts is cardiolipin, so the individuals with a false-positive syphilis test actually had a form of anticardiolipin antibodies. The false-positive syphilis test was the first recognized test for antiphospholipid antibodies, but it is now known that people can have antiphospholipid antibodies without having a false-positive syphilis test and vice versa. The false-positive test is not associated with an increased risk of blood clots in all medical studies performed in the past, but certain studies, including the Johns Hopkins Lupus Cohort, suggest that there is a connection.

The false-positive syphilis test was one of the first three recognized indications of antiphospholipid antibodies. The other two were the lupus anticoagulant and anticardiolipin antibody.

Lupus Anticoagulant

In the late 1940s, it was found that an antibody present in some lupus patients prolonged a clotting test dependent on phospholipids. For this reason, it was thought that this antibody increased the tendency to bleed, and thus it was deemed the lupus anticoagulant. However, this name is now recognized as a misnomer for two reasons. First, the term “anticoagulant” is a false label, since lupus anticoagulant actually increases the ability of the blood to clot. Second, the term “lupus” in the name of the antibody is misleading, since more than half of all people who possess this antibody do not have lupus.

Tests called coagulation tests are used to detect the lupus anticoagulant (LA). Remember that even though the lupus anticoagulant causes the blood to clot more easily in vivo (i.e., in a person’s body), they actually cause prolonged clotting times in vitro (i.e., in a test tube). Therefore, if it takes more time than normal for the blood to clot, the lupus anticoagulant is usually suspected. The activated partial thromboplastin time (aPTT) is often used to test for LA. If this test is normal, more sensitive coagulation tests are performed, including the modified Russell viper venom time (RVVT), platelet neutralization procedure (PNP), and kaolin clotting time (KCT). Normally, two of these tests (the apt and the RVVT) are performed to detect whether lupus anticoagulant is present.

Anticardiolipin Antibody

Even though the false-positive syphilis test and the lupus anticoagulant were identified in the 1940s, the link between these entities was not investigated until the 1980s, when a researcher at the Graham Hughes laboratory in Britain named Nigel Harris began looking at antibodies to the phospholipid antigens. Harris realized that cardiolipin was a major element of the false-positive syphilis test, and he developed a more specific test for the antibody. He also determined that the presence of these anticardiolipin antibodies was associated with recurrent thromboses (blood clots) and pregnancy losses. Others in Hughes’ laboratory began to publish studies showing the link between anticardiolipin antibodies and stroke, deep vein thrombosis (DVT), recurrent pregnancy loss, livedo, seizures, and other conditions. In fact, what we now know as antiphospholipid syndrome was known as the anticardiolipin syndrome even though other antiphospholipids, namely the lupus anticoagulant, were known to produce similar effects.

There are different classes (isotypes) of anticardiolipin antibody, namely IgG, IgM, and IgA. IgG is the anticardiolipin antibody type most associated with complications. An enzyme-linked immunosorbent assay (ELISA) is used to test for anticardiolipin antibodies. One can test for all isotypes at once, or they can be detected separately. High levels of the IgM isotype are associated with autoimmune hemolytic anemia, a condition in which an individual’s immune system attacks their red blood cells.

Anti-beta2 glycoprotein 1

Beta2 glycoprotein 1 is the protein in the body to which anticardiolipin antibodies bind, and it is also possible to measure antibodies to beta2 glycoprotein 1. An individual can be positive for anticardiolipin antibodies and negative for anti-ß2 GPI and vice versa, and detection of anti-ß2 GPI is not yet part of routine testing done for patients with an increased likelihood of blood clots.

Sources

• “Antiphospholipid Antibodies.” Lab Tests Online. 3 June 2009.  American Association for Clinical Chemistry. 6 July 2009 <http://labtestsonline.org/understanding/analytes/antiphospholipids/test.html>.
• “Blood Tests.” The Lupus Site. 6 July 2009 <http://www.uklupus.co.uk/tests.html>.
• “Cardiolipin Antibodies.” Lab Tests Online. 3 June 2009.  American Association for Clinical Chemistry. 6 July 2009 <http://labtestsonline.org/understanding/analytes/cardiolipin/test.html>.

• “Laboratory Tests.” Lupus Foundation of America. 6 July 2009 <http://www.lupus.org/webmodules/webarticlesnet/templates/new_aboutdiagnosis.aspx?articleid=364&zoneid=15>.
• Laboratory Tests for Lupus.” Lupus Foundation of America. 12 July 2009 <http://www.lupus.org/webmodules/webarticlesnet/templates/new_learndiagnosing.aspx?articleid=2242&zoneid=524>.
• “Lupus Anticoagulant.” Lab Tests Online. 3 June 2009.  American Association for Clinical Chemistry. 6 July 2009 <http://labtestsonline.org/understanding/analytes/lupus_anticoagulant/test.html>.
• Wallace, Daniel J. The Lupus Book: A Guide for Patients and Their Families. 1st ed. New York: Oxford University Press, 1995.
• Wallace, Daniel J., and Bevra Hannahs Hahn, eds. Dubois’ Lupus Erythematosus. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2007.