“I have often stated that the single most interesting clinical clue to lupus is the 9:1 sex ratio,” says Dr. Lockshin. “Understanding why that happens is going to be infinitely more important to finding the cause and treatment than any of the other science currently ongoing. It can’t be just a coincidence. There has to be a reason behind it, and the reason has to be critical to causation of illness.”
Other research tidbits are coming to the forefront that, while not proving a genetic link, at least give researchers a reason to continue looking for one.
“Although systemic lupus erythematosus (SLE) is much more common in women, men with lupus sometimes have unusual genetic backgrounds,” says David Felson, MD, professor of medicine at Boston University. This can give them characteristics more commonly found in women. “This unusual background may predispose them to the disease,” he says.
Same Disease, Different Presentation?
Some of the differences in incidence in at least some of the diseases may be related to differences in presentation. In AS it is well documented that men tend to present with spinal arthritis and other symptoms that march up the spine. Women, on the other hand, are more likely to see a doctor initially for complaints related to the neck or peripheral joints, but not the lower back.
There may also be differences in the environments of the two genders that affect the incidence and possibly the susceptibility of an individual. While scleroderma appears spontaneously in women, men with the disease tend to be over-represented in the gold- and coal-mining industries.
The environmental differences may also show up only after long lead times. Dr. Lockshin points to research done in Army recruits that shows positive blood tests for SLE and RA up to 10 years prior to diagnosis. Are there things that little girls are exposed to in greater amounts that manifest themselves only 10 to 20 years later?
Perceptions Another Variable
Perceived differences in severity appear to be a fertile area for behavioral differences to be important.
“It is known that pain perception is different in women than in men, females having a somewhat lower threshold at which a stimulus is perceived as pain,” says Ronald van Vollenhoven, MD, associate professor of rheumatology at the Karolinska Institute in Sweden. “This could imply that pain symptoms are experienced more severely by female patients, which could contribute to the slightly worse long-term prognosis for female patients with inflammatory disease of the joints, such as RA. Our recent studies have suggested that this, indeed, might be the case, and that treatment decisions may not sufficiently reflect these differences.”
