Systemic lupus erythematosus (SLE) is one of the most enigmatic diseases a health care professional might come across. A life-threatening autoimmune disorder, SLE presents in such a diverse fashion that physicians often confuse it with other conditions, and that can mean years before a diagnosis. One reason that SLE—often called simply lupus, though it is not the only form of the disease—remains so mysterious is that it is relatively rare; estimates of its prevalence range from 20 to 150 per 100,000 people, with women—and particularly women of color—most likely to be affected.1-2 Approximately 16,000 new cases are diagnosed yearly, mostly in patients 15 to 44 years old.2 In a minority of cases, lupus can be deadly: estimates figure that 10 to 15 percent of people with lupus die prematurely due to complications from the disease.2

Like other autoimmune disorders, lupus occurs when a patient’s immune system treats the body’s tissues as foreign invaders, creating antibodies that then attack the organs—potentially including the skin, kidneys, lungs, and heart. What launches that process, known as autoimmunity,3 is not yet known, although research has found more than 50 genes that appear to contribute to the disease.4 The current consensus is that both genetics and environment play a role; among the most likely environmental triggers are ultraviolet light or infections, including effects of the Epstein-Barr virus.4 Women account for around 90 percent of all diagnosed lupus cases, and because many patients report increased disease activity before their period or during pregnancy, hormones are also a potential contributing factor.4

Adding to the confusion surrounding lupus is that patients tend to exhibit highly individualized sets of symptoms, with many of the disease manifestations mimicking those of other, more common conditions. “The perfect word for lupus is kaleidoscopic,” says Irene Blanco, MD, MS, associate professor of medicine and director of the rheumatology fellowship program at Albert Einstein College of Medicine in the Bronx, New York. “It can present with so many different variations of so many symptoms and with so many different organs being involved.”

Aliases and accomplices

While the features of an individual patient’s disease can vary wildly, the American College of Rheumatology cites the following as some of the most common symptoms of lupus3:

  • Rashes, such as malar rash (butterfly-shaped rash over the cheeks), discoid rash (red rash with raised round or oval patches), or rash on skin exposed to the sun
  • Sores in the mouth or nose that last from a few days to longer than a month
  • Arthritis lasting for several weeks in two or more joints
  • Lung or heart inflammation, which can cause chest pain when breathing deeply
  • Kidney problems, such as blood or protein in the urine
  • Neurological problems, including seizures, strokes, and psychosis
  • Low blood cell counts, including anemia, low white blood cells, and low platelets
  • Positive result from an antinuclear antibodies (ANA) test
  • Abnormal antibodies, such as anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), and antiphospholipid antibodies

Experts say that patients who exhibit several of these symptoms should be assessed for lupus. “Certain things that make me think about [lupus] are people who get rashes, specifically a butterfly-looking rash on their face from the sun, or who feel sick from the sun,” says Candace Feldman, MD, ScD, associate physician at Brigham and Women’s Hospital and assistant professor of medicine at Harvard Medical School in Boston.

In addition, patients who have recurring symptoms from this list but show no signs of infection could also have the disorder. “If they keep coming back for the same thing over and over, you’ve got to think, ‘We need to go a little bit further into this and look at these less-prevalent diseases,’” says Kristie Wintz, CMA (AAMA), a medical assistant at Avera Medical Group Spirit Lake Medical Center, in Spirit Lake, Iowa.

Mistaken identities

Because of the high variability of lupus symptoms, diagnosis is often a matter of weeding out other possible conditions. One standard screening test is the ANA, but that by itself is not sufficient to make a diagnosis. “You can see a positive result in patients with other autoimmune diseases that are not lupus,” says Dr. Blanco. Some might display no disease activity at all. “You have to take the ANA with all of the things the patient’s presenting with in order to diagnose lupus.”

Once a diagnosis has been made, treatment must deal with the patient’s particular constellation of symptoms. That can prove challenging. Only a few drugs have received Food and Drug Administration approval for lupus specifically; the most recent, belimumab (Benlysta), was authorized in 2011 as an intravenous infusion and was the first such drug approved in more than 50 years. Nonetheless, physicians have a host of other drugs in their arsenal, many prescribed off-label. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often successful in treating inflammation, arthritis, pain, and fever. The antimalarial hydroxychloroquine (Plaquenil) has been found effective at reducing lupus symptoms, while corticosteroids and immunosuppressants are used to treat severe cases.3

For now, though, lupus treatment requires a fair amount of trial and error. “One thing that everybody is looking for with the move to precision medicine is to understand whether we can target the drug to the specific mechanism of action that’s active in a person’s disease,” says Dr. Feldman. “I think we’re not quite there yet with lupus, so we use these sorts of sledgehammer approaches to the immune system to attempt to suppress inflammation broadly, because we don’t fully understand the mechanisms.”

Like any mystery, lupus cannot be solved without clues. And the lack of a treatment solution does not mean a lack of progress. As more treatment possibilities are investigated and approved, as the medical community’s knowledge grows, so too does the ability to tailor approaches to individual patients.