The symptoms started with body aches, a fever, nausea. Cynthia Wooldridge thought maybe she had caught a bug from a patient at the medical clinic where she worked.
But a few days later, when the 43-year-old’s eyes turned yellow, a telltale sign of liver damage, her husband rushed her to the emergency room nearest to their Madras home. She was discharged after a few days.
That’s when things got really bad. She became disoriented, confused. Her husband brought her back to the hospital on Jan. 6. This time, the staff put the mother of two in a helicopter to Portland, where she would spend the next two weeks hospitalized.
“Honestly I can’t tell you in words how rapidly everything happened,” her husband, Jay Wooldridge, explained, tearfully recounting the family’s ordeal.
The doctors worked tirelessly to save Cynthia, but eventually her liver stopped working. Then her lungs. Then her kidneys. Lastly, on Jan. 20, her heart stopped beating.
Doctors told Jay they believed his wife had lupus, a chronic condition that causes the body’s immune system to attack healthy tissue, such as specific organs, the skin or joints. In this case, the liver. She also had autoimmune hepatitis, a condition that attacks the liver and commonly accompanies lupus.
Lupus presents differently in every person it strikes. In some, the symptoms are mild. In others, the condition can surface as organ failure. Some research has found that women of color, including American Indian women like Wooldridge, are not only more likely to get lupus, but also more likely to experience life-threatening manifestations. “Lupus can present with serious organ involvement as the initial manifestation,” said Dr. Atul Deodhar, a rheumatologist and professor of medicine at Oregon Health & Science University. “It doesn’t have to be someone has to have lupus for years before they have major organ complication.”
Doctors who’ve worked with patients on Central Oregon’s Warm Springs Indian Reservation, however, said lupus is still very rare among tribal members there.
Like other autoimmune disorders, lupus is caused by a mixture of both genetic factors and environmental triggers, although doctors haven’t pinpointed what in someone’s environment triggers the condition’s onset. There’s also disagreement within the medical community over whether the condition is underdiagnosed or overdiagnosed.
Difficult to study
More than 90 percent of lupus patients are women ages 15 to 45. Since lupus isn’t among the conditions doctors are required to report to the federal government when they diagnose patients, it’s not clear exactly how many people have it. According to the Lupus Foundation of America, that number is estimated to be about 1.5 million Americans.
It’s especially unclear what proportion of American Indians have lupus, as it’s a population that’s difficult to study. A landmark 2014 study that finally gained access to three American Indian regions speculated they may have the highest prevalence of any racial group. The study didn’t break down its data by tribe, though, and experts say there is still a lot of variation in prevalence from tribe to tribe.
American Indian groups are concerned about the potential for research findings to stigmatize the population, and have offered limited windows into their health data, such as the 2014 study. But the more doctors learn, the more they recognize it’s an important group to focus on when it comes to lupus awareness. The American College of Rheumatology recently hosted a series of educational events in Central Oregon to help medical providers recognize the different ways lupus presents in women of color.
Dr. S. Sam Lim, a medicine and epidemiology professor in Emory University’s School of Medicine and chair of an ACR education program on lupus, said doctors are always told: When you hear hoofbeats, think of horses, not zebras. In other words, it’s probably something simple and common, not some rare disorder like lupus.
But Lim wants to encourage doctors to consider lupus if they’re faced with young American Indian/Alaska Native or African-American women who show the telltale signs: joint swelling, extreme fatigue, pain, hair loss and rashes.
“Then lupus is not as uncommon as you’d think,” he said. “That’s what we’re really trying to get out.”
Understanding the disease
When Lim set out to study lupus among American Indians, information on the subject was sparse. But what little information did exist suggested something big was happening.
If, in fact, the prevalence of lupus was found to be as high among American Indian women as it is among black women — a group that sees more than three times that of Caucasian women — that could help doctors diagnose and treat the condition among American Indian women, Lim said.
“The fact that there are these amazing racial and gender disparities, that tells us something that will ultimately benefit everybody with lupus,” said Lim, who also serves as chief of rheumatology at Grady Health System in Atlanta. “There is a reason why there is such a big difference in these groups. If you work backwards from that, it will help us understand the disease better.”
— Dr. S. Sam Lim
Lim’s research team gained access to valuable data, the scope of which no previous researchers had access to: medical records from the Indian Health Service that spanned three regions of the U.S. The IHS, a division within the Department of Health and Human Services that provides health services to American Indians and Alaska Natives, is tightly protective of its data, an attitude Lim came to experience firsthand.
Until that point, smaller studies on limited groups of people had hinted that lupus was more common among American Indians, but they were far from definitive. A 2000 study in the Journal of Rheumatology, for example, found the prevalence of lupus among North American Indians was double that of the non-Indian population, and the patients were younger, their cases more advanced upon diagnosis and were more likely to have kidney damage. That study, however, examined only 257 cases and did not use Indian Health Service data. A few other studies that also relied on small patient samples arrived at similar findings.
Lim’s findings, published in a 2014 issue of the journal Arthritis & Rheumatology, were groundbreaking: The estimated prevalence of lupus among American Indian women — 271 cases per 100,000 people — is at least equal to, if not more, than that of black women, which has been shown to be between 186 and 196 per 100,000 people.
“To see them relative to African-Americans to be at least equivalent and suggestively more is definitely remarkable,” he said.
Dr. Miles Rudd, chief medical officer of the Portland area IHS, said each tribe is different with respect to the prevalence of certain diseases. In Warm Springs, for example, lupus is still uncommon.
‘Control over their’ own ‘destiny’
The Indian Health Service, Lim learned, is sensitive about the potential for research findings to stigmatize the American Indian population. That’s what happened with early research on alcoholism. Although not the primary aim of such research, some felt the media coverage that ensued cast tribes in a poor light.
“That really created a lot of the tribes to clamp down,” he said, “and so they sort of want control over their destiny in that regard.”
When it came to Lim’s research, each individual tribe whose information was used had to approve the study protocol, which created logistical issues.
The team’s registry included data by tribe, but the researchers were not permitted to analyze the data at that level and, when the study was complete, the Indian Health Service made the team destroy the tribal-level data, Lim said.
“It’s unfortunate,” he said, “after all of this, we lose that opportunity. I have to respect that.”
But not having Indian Health Service data also limits researchers’ ability to study a key population when it comes to lupus, a condition that’s heavily rooted in genetics. Many tribal populations are more homogeneous than non-Native populations in the U.S. because they’re more likely to have stayed within the local area for generations, Lim said.
“Rarely do we have in human populations such homogeneous genetic groups with a limited mixture of environment and travel,” he said.
Rudd, of the Indian Health Service in Portland, said even though there’s no publicly available data by tribe, medical providers in each area know how common certain diseases are and use that knowledge when they’re assessing patients’ symptoms.
Dr. Lisa Sumner, a rheumatologist with the Phoenix Indian Medical Center, treats patients in 11 different tribal communities and has learned from her experience in each area which ones have higher rates of lupus, rheumatoid arthritis and other conditions. Having broader prevalence data outside of specific clinic populations would be helpful, she said, but ultimately getting the permission from each tribe would be too time consuming.
Dr. Christine Peschken, an associate professor of medicine and community health sciences at the University of Manitoba, has found a higher prevalence of lupus among her region’s North American Indian population. But she, too, has struggled with research barriers.
“It’s partially because of, frankly, abuses where research has been done,” she said.
Much like the U.S., Canada has an ugly history with respect to its treatment of native tribes. The government colonized their land, forced them to move and forced children into residential schools.
In fact, Peschken said she believes some of the lupus the population sees today may be rooted in the stress from that time.
Eventually, though, as technology increasingly allows the use of personalized medicine, which involves using patients’ genetic information to inform their treatment, it will become more important to understand North American Indians’ genetic backgrounds, Peschken said.
Right now, for example, doctors know that a medicine that used to be the standard treatment for lupus patients with kidney involvement does not work as well in African-Americans, she said. So they use something else.
“How do we know if that’s the right molecule in one person versus another?” Peschken said. “That’s all information we would like to be able to have.”
The long road to diagnosis
At first, Denise Tripolone shrugged off her symptoms, strange as they were. Her knees and ankles would swell — sometimes to three times their size — then go back to normal.
“It was just like, ‘Oh, I’m working out too hard,’ or I would just blame it on something else,” said the now-31-year-old Bend resident. She was living in Denver at the time.
That was in spring 2013. As her wedding approached that May, it got much worse. Rashes appeared on her legs. Suddenly, she had terrible gastrointestinal issues. She was throwing up and had to be hospitalized.
“I blew all the blood vessels in both of my eyes right before my wedding,” she said. “It was really traumatic.”
Despite all that, the wedding proceeded. Her symptoms improved and she and her husband went on their honeymoon. When they returned, the symptoms came back with a vengeance. She was hospitalized again. This time, doctors said she had fluid around her lungs. She had gained about 20 pounds, most of it from fluid collecting in her body.
Doctors were stumped.
Then, as quickly as they had presented, her symptoms mysteriously went away again — for a time. They returned when Tripolone and her husband moved from Denver to Austin. This time, it was joint swelling, severe rashes and she felt drained of energy.
A doctor in Austin told her he suspected lupus, but it took several months and specialized tests before that diagnosis was confirmed in 2015. She was 29 years old.
“It’s complicated,” said Tripolone, who moved to Bend, where her father lives, in 2015. “There are so many different things that it can resemble. It’s pretty tough to diagnose.”
Lupus is often called the “great masquerader” because its symptoms can be vague and tend to mimic other conditions, said Dr. Heather Hansen, a rheumatologist who works for St. Charles Health System.
“There are so many other, more common explanations for what somebody might have than lupus, which is more rare,” Hansen said.
It takes lupus patients on average nearly 6 years between the first appearance of symptoms and a diagnosis, according to a 2015 article in the Annals of the Rheumatic Diseases. They go through an average of three providers in that time.
There isn’t a definitive test for diagnosing lupus. If doctors suspect the condition, they’ll perform what’s called an antinuclear antibody, or ANA, test, which detects signs that the immune system is reacting to the body’s own cells. Approximately 13 percent of women in the general population will test positive on an ANA test, Hansen said. Doctors can then perform more specific tests on ANA subsets.
When patients complain about feeling tired or achy, many providers brush off their symptoms or treat them as psychological in nature rather than suspecting lupus, Hansen said.
— Dr. Heather Hansen
“I think a lot of the early symptoms of lupus can very easily be mistaken for that,” she said. “‘She’s just depressed’ or ‘She’s stressed.’”
Potential for overdiagnosis
Deodhar, who also directs OHSU’s rheumatology clinics, including one in Warm Springs, sees things very differently. He thinks the bigger problem is that primary care doctors are too quick to jump to lupus when patients actually have something different. He believes this is the case with most lupus diagnoses.
Deodhar recently treated a pregnant patient who had been treated for lupus for 10 years. He realized she did not have lupus, nor had she ever had the condition. Luckily, the medication she had been taking was benign.
“I certainly see these cases all the time,” he said.
A misdiagnosis can be especially harmful if the patient is prescribed a steroid called prednisone, which is commonly given to lupus patients, Deodhar said.
There are 11 symptoms of lupus, including certain rashes, inflammation, kidney problems, arthritis and sensitivity to sunlight. The American College of Rheumatology urges doctors to consider lupus if patients display at least four.
A common form of lupus is called lupus nephritis, meaning the condition attacks the kidneys. That’s what Tripolone has, which explains the protein that showed up in her urine early on.
Lupus can cause fluid to accumulate around the heart or, as happened to Tripolone, the lungs. It can cause inflammation around the brain and spinal cord. It can cause blood clots in arteries and low red or white blood cell counts, as well as low platelet counts. Lupus can also affect the brain, prompting seizures or bouts of psychosis, said Dr. Michael Liebling, an assistant professor of arthritis and rheumatic disease with Oregon Health & Science University.
“I can remember when I first saw (the neurologic symptoms), I commented, ‘Maybe it would be easier to say what they can’t get neurologically,’” he said.
Some of the symptoms associated with lupus can be so vague at the outset, it’s no wonder people miss them or attribute them to something like allergies or the flu, Lim said. Many of the patients — young women — don’t even need to go to the doctor for regular checkups, he said.
“They’re at the prime of their life in the sense that they’re just starting their careers, their families, maybe advanced education,” Lim said. “It’s not a group that is even thinking about a chronic disease.”
‘Extraordinarily sick patients’
Lim’s research on American Indian populations didn’t just find a higher prevalence of lupus; his team learned they were more likely to develop a severe complication: kidney disease.
Of the diagnosed cases in the study registry, nearly 40 percent had kidney disease, which can lead to kidney failure, requiring dialysis or a transplant. Of those, 5.6 percent were already at the point of kidney failure. That’s on par with the rate of kidney disease previous research had found among black lupus patients.
“It’s not too much of a stretch to say that if they get lupus easier, they probably get severe forms a lot easier, too,” Lim said. “They just have a lot more predisposing factors that not only allow you to cross that threshold to get the diagnosis but just to keep going further and further and developing more severe disease.”
OHSU’s Deodhar has led a rheumatology clinic in Warm Springs for the past decade. He and two resident physicians visit the medical clinic there four times a year to see patients, many of whom have conditions like arthritis.
Lupus is still rare. Deodhar estimates in his entire time there, he’s only seen a handful of patients with the condition.
The problem is, some people are extremely sick once they’re diagnosed. Their conditions can progress so rapidly that they show up at the clinic in kidney failure. It may have started with swelling in the legs and shortness of breath that went ignored.
It doesn’t always have to be kidney failure, either. Lupus can attack the heart, lungs, liver or brain, the latter of which might present with unexplained seizures, Deodhar said.
Hansen, with St. Charles, is leading a series of seminars that are in part meant to help doctors recognize how lupus presents differently in women of color.
Research has found that Caucasian lupus patients, for example, are more likely to get a telltale butterfly-shaped rash across the bridge of their nose and onto their cheeks. Hispanic lupus patients are more likely to develop rashes when exposed to sunlight. Black and some Hispanic lupus patients are more prone to both arthritis and kidney disease.
Crossing the imaginary bar
When asked why some people get lupus and others don’t, Lim tells people to picture an imaginary bar. When that bar is crossed, it means a person is diagnosed with lupus.
Having a genetic predisposition to lupus — such as being African-American or American Indian — automatically puts people much closer to that bar, he said.
In 2008, an international team of researchers working with the Oklahoma Medical Research Foundation identified 13 genes linked to lupus.
Lupus research on identical twins has determined that if one has lupus, the other has a 30 percent chance of getting the condition, Peschken said. “That’s considered evidence actually of a strong genetic burden but it also gives you the information that there’s a lot more needed than that,” she said, “because these twins would have presumably had identical genetics but also similar backgrounds growing up.”
Hormones seem to play an important role, which is why women of childbearing age comprise the majority of cases. High-dose estrogen-containing contraceptives have been studied as a potential culprit, Liebling said, so doctors tend to steer lupus patients toward alternative contraceptive methods.
A person’s environment plays a role, although that component is not well understood. Some research has suggested sun exposure and tobacco use increase one’s risk. One study found exposure to silica dust in soil increases a person’s risk.
Diet could be a factor. Tripolone said she believes diet and stress have big effects on her symptoms, as evidenced by the fact that she had major attacks before her wedding and after she moved to a new city. She’s cut out all processed foods, dairy, grains and soy from her diet and eats only meats, fish, fruits and vegetables.
Exercise, including cardio and weight training, has always been a big part of her life. For the past four months, she’s been doing CrossFit five days per week. “I just wanted to start doing something more intense,” she said. “I love it.”
For his part, Lim said he believes psychological stress may play a role. “Could that be one of the themes in these groups that isn’t the only cause, but in the mix of everything else is just a strong signal that just puts them over that magic bar?” •