Why lupus develops “is yet to be discovered,” says Roberto Caricchio, MD, the chief of rheumatology at the University of Massachusetts Chan Medical School in Worcester, Massachusetts. But the cause of “the condition appears to be multifactorial,” he adds. Some contributors to the most common form of the disease, systemic lupus erythematosus, appear to be genetics, environmental factors, and hormones, according to Dr. Caricchio. In some families specific autoimmune diseases, such as lupus, may cluster, says Stacy Ardoin, MD, a rheumatologist at the Ohio State University Wexner Medical Center in Columbus. Additionally, minorities, including African Americans, Asian Americans, Native Americans, and Hispanics are also at higher risk, she says — “which may have to do with genetics, but this disparity is still largely unexplained.” Research has shown that specific genetic abnormalities are linked to a higher likelihood of lupus, while other genetic abnormalities appear to reduce risk, says Dr. Ardoin. However, there is no single gene that has been found to cause the disease and no genetic test to predict the risk of lupus or to confirm a diagnosis. “Researchers don’t yet understand how genetic abnormalities work together to increase risk, while other genetic changes reduce risk,” Ardoin says. About 100 variations in our DNA’s genetic code have been linked to lupus, according to the Lupus Foundation of America. (1) And many of these genes are ones that affect immune system function. (2) For example, certain variations in the gene TNFAIP3 appear to code for certain proteins which cause inflammation. And a 2016 data review found that TNFAIP3 was associated with systemic lupus erythematosus in Asians and Europeans. (3) Additionally, some genes have been associated with subsets of systemic lupus erythematosus — more specifically, those gene variants are linked with patients who develop nephritis or experience stroke, notes Dr. Kaplan. Certain infections, including those due to the Epstein-Barr virus, may contribute to the development of lupus, according to a study. (4) However, research has yet to prove this link, Kaplan says. Another environmental factor, sun exposure, can cause a lupus rash and some systemic lupus activity, says Ardoin. Ultraviolet light can damage the skin, which may cause skin cells to release their contents into the bloodstream, possibly irritating the immune system, she explains. Other potential environmental triggers include:
Medication That Makes People More Sensitive to Sunlight These include the antibiotics trimethoprim-sulfamethoxazole, sulfisoxazole, and minocycline, among others. Sometimes, drug-induced lupus develops; this form of lupus is temporary. (5)Emotional Stress and Physical Stress, Such as Surgery A 2017 study concluded that trauma and post-traumatic stress disorder may contribute to the development of lupus in women. (6)Exposure to Silica Dust From Construction and Manufacturing
Because lupus affects more women than men, scientists have made an assumption that hormones may play a role in disease development, says Ardoin. “It’s also very common to be diagnosed during or immediately after a pregnancy,” she says. “And it’s not uncommon to have a flare during pregnancy or during the postpartum period.” Scientists have some clues that estrogen may affect immune cell function, but none are definitive at this point, adds Ardoin. For example, one study found a link between hormone replacement therapy and an increased risk of lupus and flares. (8) “However, this finding needs to be taken with a grain of salt because other factors could be contributing to disease development,” she says. Once patients are diagnosed with lupus, they can work with their doctors to manage and prevent lupus flares by using medication and by avoiding possible flare triggers, says Neil Kramer, MD, the co-medical director at the Institute for Rheumatic and Autoimmune Diseases at Overlook Medical Center in Summit, New Jersey. “Recognized causes of lupus flares include sun exposure, infections, and very importantly, noncompliance with prescribed medication,” says Dr. Kramer. Additionally, emotional or physical stress may play a role, “although it is difficult to quantify what this effect may be. In most cases we just do not really know what causes lupus to flare.” Patients can work with their rheumatologists to prevent flares by taking their prescribed medication, protecting themselves from sun exposure, and adopting lifestyle practices that decrease stress, such as regular low-impact aerobic exercise, meditation, and tai chi, says Kramer. Because smoking can aggravate cardiovascular complications of lupus, smoking cessation is also important, he adds.
