A rheumatologist explains how a variety of genetic, hormonal, and environmental factors may cause lupus.
It’s difficult to believe that a disease can affect any part of your body and still be mostly hidden to the naked eye. But that’s the reality for the nearly 1.5 million Americans who live with some form of lupus.
Lupus is an autoimmune disease, meaning a person’s immune system starts to attack healthy cells and tissues. Nearly 70 percent of all causes of lupus are classified as systemic lupus, affecting a major organ or tissue, like the heart, lungs, kidneys, or brain, according to the Lupus Foundation of America.
“The immune system is unable to recognize what is part of the body and what is not,” explains rheumatologist George Stojan, MD, an assistant professor of medicine at Johns Hopkins University School of Medicine and co-director of the Hopkins Lupus Center.
Lupus presents a wide variety of symptoms that range from benign to life-threatening, including joint stiffness and swelling, facial rashes (most notably a butterfly-shaped rash across the cheeks and nose), mouth sores, seizures, chest pain due to fluid around the heart or lungs, fevers, swollen glands, and low blood counts, says Dr. Stojan. The buildup of these symptoms can take their toll: 65 percent of lupus patients say chronic pain is the most difficult thing about living with the disease.
But the most mysterious thing about lupus? There are no known concrete causes or cures. “There’s this entire range of things that have been associated with lupus, but association alone doesn’t mean causation,” says Dr. Stojan.
Researchers have linked genetics, hormones, and environmental changes to the development of lupus, but it’s difficult to say which factor plays the biggest role. “It’s probably a perfect storm that occurs and leads to the occurrence of the disease,” says Dr. Stojan.
So, what exactly do we know about the triggers of the autoimmune condition? Here, the possible causes of lupus that researchers are digging into—and what treatment looks like once someone is diagnosed.Genetics
Lupus tends to cluster in families. In fact, a person has a 20 times higher risk of developing lupus if they have a sibling with the disease. A handful of gene variations have been linked to the development of lupus, and most are thought to be involved in immune system function, according to the U.S. National Library of Medicine.
Certain gene mutations have also presented a link, such as TREX1, but they’re quite rare and not all patients have them, says Dr. Stojan. “It’s thought that there is this combination of susceptibility genes and an absence of protective genes that allow the development of the disease in people who have certain environmental exposures or certain infectious agent exposures,” he adds.Race
Lupus disproportionately impacts certain ethnic groups. In fact, the disease is two to three times more prevalent in women of color, including African Americans, Hispanics and Latinos, Asians, Native Americans, Pacific Islanders, and more. One 2014 study determined that the prevalence of lupus reached 1 in 537 black women.
Studies have also shown that women of color develop lupus earlier, suffer from more serious complications, and experience higher mortality rates. Why? Genetics, once again, could increase the risk here, but other factors, like healthcare coverage and access, language barriers, and income levels could also play a role, researchers speculate.Hormones
Women in general are much more likely to have lupus than men, says Dr. Stojan. Nineout of 10 people diagnosed with it are women between 15 and 44 years old. One big reason for the discrepancy? Hormones like estrogen and prolactin, which are much higher in women, may throw a certain inflammatory pathway (known as type 1 interferon) off balance, says Dr. Stojan, driving lupus in the process.
Landmark research also found that “women who were treated with estrogen-containing regimens, like oral contraceptives or hormonal replacement therapy, had a significantly increased risk of developing lupus.” Estrogen also releases interleukin-1, a group of inflammatory responses that have been linked to lupus flares, he says.ADVERTISEMENT – CONTINUE READING BELOW
Ultraviolet light can damage any person’s cells, but people with lupus are much sensitive to it. It has not been identified as a direct cause of the disease, but UV light can modify skin cells in a way that is recognized as a threat by the immune system in people with lupus, activating or worsening symptoms, says Dr. Stojan.
“The ultraviolet light can both induce mutations in certain genes that then become unrecognized by the immune system and become targets, leading to lupus rashes,” he explains. “But it also can directly stimulate keratin inside the cells of the skin to create more inflammatory mediators.”Toxic exposures
“We know that silica dust that’s present in some cleaning powders and cigarette smoke can increase the risk of developing lupus,” says Dr. Stojan, but researchers aren’t entirely sure why.
However, the connection is strong and well-studied: People who are exposed to silica at work (say, in mining or glass production) have a two to five times higher risk of lupus. Researchers have also linked mercury, pesticides, and smoking tobacco to the development of lupus.Infections
Various viral infections have been linked to lupus flares, including human parvovirus, herpes simplex virus, and hepatitis A. Epstein-Barr, the virus that causes mononucleosis, has been studied closely in particular, and scientists believe that antibodies produced post-exposure may cause an unusual immune system response. However, Dr. Stojan emphasizes that exposure to Epstein-Barr does not guarantee the development of lupus.
“After age 20, approximately 90 percent of Americans are exposed to Epstein-Barr, so it’s almost impossible to say whether that exposure in any way affected someone’s risk, simply because everybody gets exposed,” he explains. “It’s certainly possible but having these antibodies alone doesn’t mean somebody will develop lupus in the future.”ADVERTISEMENT – CONTINUE READING BELOW
Changes in pollution, wind patterns, barometric pressure, humidity, and temperature are strongly associated with specific forms of organ flares in lupus, preliminary research by Dr. Stojan has found. However, not one variable is associated with all flares, he explains. For example, fine particulate matter pollution has been linked to lung flares, and temperature changes may impact neurologic flares and rashes, while humidity is associated with joint flares. “You can technically predict it based on these changes in atmospheric factors 10 days prior to the time the patient shows up for their clinic visit,” he says.Stress
“I’m not aware of any human epidemiological model that showed how stress affects lupus, but I can tell you that every patient does say that it affects them,” says Dr. Stojan. Anecdotally, lupus patients say that emotional stress (say, a death in the family or divorce) as well as physical stress like surgery or injury may trigger lupus symptoms.How is lupus treated?
Once you’ve been diagnosed with lupus, your treatment will largely depend on the severity of the disease, says Dr. Stojan. If you have mild to moderate symptoms, your doctor will likely start you on antimalarial drugs, like hydroxychloroquine, to reduce pain, skin rashes, and other symptoms in an effort to protect organs and prevent damage to the body.
These medications have been shown to prevent flares by 50 percent and ultimately help patients live longer, says Dr. Stojan. “It’s something that we keep all lupus patients on as long as they can tolerate it,” he adds.
Another option is corticosteroids, which are typically administered to help patients work through a flare, since the drug works quickly. However, doctors generally try to avoid them in the long-run to avoid potential side effects, says Dr. Stojan.
In general, lupus can be tricky to treat because there is no established cure, but working closely with your doctor to create a plan can help you reach the ultimate goal of remission, says Dr. Stojan.