Causes and Risk Factors of Lupus

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lupus causes
Illustration by Joshua Seong. © Verywell, 2018. 

Lupus is one of those mysterious diseases that doctors haven't quite pinned down. No one knows for sure how or why it occurs. However, most experts believe lupus is caused by a combination of genetic and environmental factors—that is, things you can and cannot control. 

It won't be until the science catches up with the disease that we will truly understand its roots. In the meantime, we can look at contributors believed to factor into lupus as scientists understand them now.

Common Risk Factors

Lupus is an autoimmune disease in which your immune system malfunctions, prompting your body to attack its own tissues. These factors are considered common potential culprits:

Hormones

Research suggests that hormonal factors are linked to autoimmune disease, though research is still in its infancy and the link between the two is still nebulous. Considering that 90 percent of people with lupus are female, the hormonal factor seems like an important one. However, female hormones like estrogen do not appear to cause lupus. Rather, they appear to increase risk in those who are already susceptible to developing the disease. 

Infection

Viruses and bacteria may play a part in the development of lupus, but a direct causal link has not been established. However, infection is cited as one of the most common potential triggers for developing lupus. The Epstein-Barr virus (EBV) in children is linked to childhood lupus, as well as lupus in adults.

Viruses and bacteria may also cause lupus flares.

Medications

It has been established that some medications are triggers of lupus and lupus flares. In fact, a subset of the disease, drug-induced lupus, is based on this premise. This type of lupus is usually brought on by long-term use of certain medications such as anticonvulsants, antibiotics, and blood pressure medications and symptoms nearly always go away when the drug is discontinued.

Additionally, allergies to medications are seen more often in people with lupus that has just been diagnosed than in those without lupus.

Environment

Environmental factors, though not specifically proven, are believed to potentially trigger lupus and/or lupus flares and may include:

  • Exposure to ultraviolet light (photosensitivity) from light bulbs or the sun
  • Exposure to silica dust, which is found in soil, cigarette smoke, pottery, and cleaning powders
  • Exposure to smoking

Certain hair dyes, pesticides, topicals, and even alcohol were once believed to be lupus triggers, but that has been disproved.

Lifestyle

Certain choices you make for yourself, as well as how you weather challenges both physically and mentally, can also play a role in the development of lupus. These three factors are commonly considered:

  • Stress, whether emotional or physical
  • Exhaustion
  • Smoking

Demographic Risk Factors

Ancestry, age, and gender all influence risk of developing lupus (SLE):

  • Race: In the U.S. and Europe, the highest rates of lupus (SLE) are seen among people of Hispanic, Asian, and African ancestry; the lowest rates are seen in people of European ancestry. 
  • Age: Most people are diagnosed with lupus between the ages of 15 and 45, although it can occur at any time.
  • Sex: Nine out of 10 people diagnosed with lupus are female.

Genetics

If there's lupus in your immediate family, you may be predisposed to lupus and the related impact of the above factors. Most researchers agree that genetics or heredity is at least one factor in determining your propensity for developing lupus; however, by itself, this factor is usually not enough to cause lupus.

Remember, though, a family history of lupus does not mean you will get lupus, only that you're more susceptible. To date, there are more than 50 genes that scientists have linked to lupus, though it hasn't been proven that they cause lupus, just that they may contribute.

 

The Role of Antigens

An antigen is a substance that enters the body and stimulates an immune response, particularly the production of antibodies, which fight what the body perceives as an invader. Antigens can derive from toxins, bacteria, foreign blood cells, and the cells of transplanted organs. In patients with lupus, particularly SLE, the immune system attacks antigens in healthy tissues—so-called auto-antigens or self-antigens. 

In other words, normal tolerance of these autoantigens has been lost in lupus patients, mainly due to genetic and environmental factors. In people with lupus, antibodies directed against auto-antigens like double-stranded DNA and the Smith (Sm) antigen are helpful in diagnosis. These antibodies directed against auto-antigens are called auto-antibodies. 

Lupus is a systemic, or whole-body, an autoimmune disease that affects a number of different organs such as the kidneys, joints, skin, nervous system, blood cells, and blood vessels. When one of these organs is being attacked by your immune system, signs, and symptoms related to that organ are manifested. For instance, if your immune system is producing antibodies that are attacking your kidneys, symptoms like protein in your urine (which can produce foamy urine), high blood pressure, and/or a rise in your blood creatinine level often occur.

The launch of an organ attack starts with the immune system thinking that a self-antigen (like a normal protein in the body) is something foreign and bad. The recognition of the antigen as bad by your body requires a combination of events, like a genetic predisposition and one or more triggers, such as an infection.

In other words, it takes a number of coincidental, unfortunate events—a perfect storm, so to speak.

Sources:

Fattal I, Shental N, Mevorach D, et al. An Antibody Profile of Systemic Lupus Erythematosus Detected by Antigen Microarray. Immunology. 2010;130(3):337-343. doi:10.1111/j.1365-2567.2010.03245.x.

Lee AY, Ang EB. A Clinical Overview of Autoantibodies in General Practice Rheumatology. The British Journal of General Practice. 2014;64(626):e599-e601. doi:10.3399/bjgp14X681601.

Lupus Foundation of America. What Causes Lupus? Updated November 28, 2016.

Mayo Clinic Staff. Lupus. Mayo Clinic Staff. Updated October 25, 2017.

Schur PH, Hahn BH. Epidemiology and Pathogenesis of Systemic Lupus Erythematosus. UpToDate. Updated April 26, 2017.