Striking Gender Differences Found in Rheumatoid Arthritis

Rosalind Russell Center donors play important role in supporting study on who is at greatest risk for severe rheumatoid arthritis

Pioneering research supported by the Rosalind Russell Medical Research Center for Arthritis has shown that, although women are three times more likely than men to be diagnosed with rheumatoid arthritis (RA), men who get the disease are at higher risk to experience a severe, destructive and progressive form of the disease.

The investigators also found that women who are afflicted with severe RA are more likely than other female patients to come from families in which males also have been affected by the disease.

"As evidenced by their lower incidence of RA, males appear to be naturally protected from the disease," according to study leader and internationally recognized genetic epidemiologist Dr. Lindsey Criswell, Professor in the UCSF Division of Rheumatology. "Our hypothesis is that there is a heavier genetic load toward RA in families in which males get the disease." Results of the study were published in the prestigious journal, Arthritis & Rheumatism.

"The take-home message to patients and physicians is that family history matters," says Dr. Criswell. "There are strong implications about the course of your disease if you are a male with RA or if you are a female RA patient with an affected male sibling."

Rheumatoid arthritis is a chronic "autoimmune" disease, meaning it occurs when a person's immune system goes awry and attacks the body's own cells and tissues. RA—which is less often crippling today due to major treatment advances in the last decade —afflicts two million Americans and is the second most common form of arthritis, after osteoarthritis.

Each of the study's 1,004 patient volunteers was interviewed to collect relevant personal details, including age at onset of RA symptoms, age at diagnosis, medication history and smoking history. Each patient volunteer was also examined for joint tenderness and underwent radiographs of the hands and wrists to evaluate bone erosions. In addition, each was tested for two auto-antibodies closely associated with the disease: RF (rheumatoid factor) and anti-CCP (anti-cyclic citrullinated peptides).

"We documented substantially higher concentrations of these auto-antibodies in male patients compared to female patients," says Dr. Criswell. "This and other differences between the male and female patients support the conclusion that, when RA develops, males are more likely to have severe disease compared to the average female patient."

"Then we wanted to determine if these differences reflect something inherent to males or if they reflect something about the families in which males get the disease. To do that, we compared women with sisters with the disease to women with brothers with the disease. By comparing women to women, we ruled out any factors that are due to being male-what we find is due to something about the families that have affected males."

"In that analysis, we found that it's not necessarily something about being male per se that results in more severe disease-it's something about those families."

"In modern medicine, there is a real tendency for doctors to see patients very quickly and to forget about things like family history," says Dr. Criswell. "These findings remind all of us how important family history is in rheumatoid arthritis."

(Published June 2007 in Arthritis Progress Report, the newsletter of the Rosalind Russell Medical Research Center for Arthritis. To be added to our mailing list, please send us a note with your name and address to Your information will not be shared with any other organizations.)

"There are strong implications about the course of your disease if you are a male with RA or if you are a female RA patient with an affected male sibling."

--Dr. Criswell

Top of page