Early signs of lupus, even before a diagnosis can be made?
- Clinical criteria for systemic lupus erythematosus precede diagnosis and associated autoantibodies are present before clinical symptoms
- Arthritis & Rheumatism, Volume 56, Issue 7, July 2007, pp. 2344-2351
What is the topic?
Diagnosing lupus is can sometimes be difficult. Because lupus symptoms may come and go and resemble other illnesses, it may take months or even years before a doctor can sort out what is going on. During this run-up period, most doctors agree, lupus disease activity is probably taking place, and lupus-related antibodies may be present even before symptoms occur.
What did the researchers hope to learn?
The researchers wanted to find out which symptoms tended to appear early on in most lupus patients and what antibodies might be present before certain clinical symptoms appear. They hoped this kind of analysis might provide clues about lupus disease activity and what course the disease might take even before symptoms are apparent.
Who was studied?
The researchers selected 130 patients who were diagnosed with lupus while they were in the United States military. Whenever someone joins the military, he or she has a baseline medical examination that includes an in-depth physical examination, medical history, and blood tests. The researchers would be able to use that information to look for signs of lupus and run tests for antibodies that were present before the diagnosis was made.
How was the study conducted?
Medical records for each of the 130 patients in the study were reviewed, and the researchers collected information about various features of lupus if and when they occurred, and if they appeared before the lupus diagnosis was made, how many months/years before. They also ran antibody tests on the blood samples to see what antibodies might have been present before clinical symptoms appeared. The researchers compared all of this information for patients based on their ethnic background, age when they were diagnosed with lupus, and the time frame separating symptoms’ appearance and diagnosis.
What did the researchers find?
Of the 130 patients studied, 104 had at least one clinical feature present before the diagnosis was made. Most of these patients (74) had only a single feature. The initial feature varied widely from patient to patient, but the most common early symptom was arthritis. In terms of time, discoid rash and seizures tended to be the earliest findings, occurring nearly two years before the diagnosis was made; interestingly, central nervous system involvement, which was one of the earliest problems to appear in patients in the study, did not commonly appear after the diagnosis.
There were also interesting differences across populations. Men were more likely than women to have kidney disease as a first symptom, and Caucasians more likely than African Americans to have early rash on the cheeks and rashes that were made worse in the sun.
Of the 104 patients who had clinical symptoms before their diagnosis, antibodies were often detectable before these symptoms. Antinuclear antibodies (ANA) showed up in 81 before the initial symptom. Seventeen patients had rheumatoid factor present when their blood was tested; arthritis developed later in 16 of them. As for anti-dsDNA and anti-C1q antibodies, which have been associated with kidney disease in lupus, 80 patients were positive for anti-dsDNA, and 38 of these patients had kidney disease; in 92 percent of these cases, the anti-dsDNA antibodies were detected prior to or at the same time as the diagnosis of kidney disease. About half of the patients who had anti-C1q antibodies developed kidney disease, but half did not; however, among the 18 anti-C1q patients who did have kidney disease, in 13 cases the antibodies showed up before the kidney disease was diagnosed, on average nearly one and a half years beforehand.
What were the limitations of the study?
The study was limited by the fact that the researchers had to rely on previously collected data, which had been provided for other purposes rather than specifically to look at lupus symptoms and lupus disease. Therefore, some lupus symptoms (like mouth sores) might not have been recorded because they weren’t really being looked for and they weren’t considered important in the overall health record of the patient at the time. Since the doctors following these patients before they were known to have lupus would not usually have been rheumatologists, there might have been many features of lupus that were simply missed. Also, though the researchers had at least one pre-diagnosis blood sample for each patient in the study, for some that was all they had, and the time intervals between that blood test and the lupus diagnosis varied greatly. For some patients there may have been changes in the antibody profile during that interval that the researchers wouldn’t have known about.
What do the results mean for you?
This study reinforces the notion that a lot of lupus disease activity may be taking place without patients’ or their doctors’ knowing it, in many cases long before the patient is diagnosed with lupus. However, the presence of certain antibodies may be a sign that later clinical symptoms are likely to appear, and so finding these antibodies early on when a patient has only one or a couple of symptoms may help doctors decide how they manage different patients, both before and after they have enough clinical criteria to determine a patient has lupus. On the other hand, it is also known that many family members of patients with lupus have lupus-related antibodies for many years without ever developing lupus. Some people can have these antibodies detectable temporarily during a viral illness or for unknown reasons, and then they go away. And as people age, they sometimes develop lupus-like antibodies as well, without becoming ill. The development of certain autoantibodies is probably one of several events that have to occur before a person develops lupus.