Women may be far more likely than men to be diagnosed with systemic lupus erythematosus, but new research suggests that at the time of diagnosis, men with the disease may be worse off.
The research, published online ahead of print in the journal Lupus, finds that men had more disease activity at diagnosis than women, though the disease course appeared similar between the sexes — a finding that contradicts earlier studies that suggest that men with systemic lupus erythematosus have more renal involvement and hematological manifestations than women, study researcher Jorge Acosta-Reyes of the department of public health at Colombia's Universidad del Norte and his colleagues wrote. Earlier studies have found, for example, that men are more likely to have end organ damage and to die of their disease than women; one 2012 study in the Journal of Rheumatology found that most odds ratios for organ damage in men versus women were greater than two, revealing a major gender gap. Hypotheses for the gender differences have included the possibility that men are less likely to seek medical care as well as the possible influences of sex hormones and sex chromosomes.
The new study drew from rheumatology patients at the Hospital Universitario de San Vicente Fundación in Colombia who had been diagnosed with lupus between 2001 and 2011 and how had at least three months of follow-up. Forty males were included, and each was matched by age and race and ethnicity with three female patients, for a total of 160 patients in the study. Disease activity was assessed with the SLEDAI-2K, and additional laboratory measures were taken six months after diagnosis.
The researchers found no significant differences in the clinical manifestations of the disease beyond more alopecia in women (52.5 percent versus 17.5 percent; p<0.001). Renal involvement was similar at diagnoses, but men underwent more renal biopsies. Among the laboratory results, only anti-Ro antibody positivity was significantly different between men and women, with women showing a higher frequency (53.6 percent versus 33.3 percent; p=0.034).
But men did more frequently show high disease activity at diagnosis than women, as defined by SLEDAI scores greater than 12, the researchers reported. To discuss these findings, Rheumatology Network talked with Acosta-Reyes about how gender might matter in systemic lupus erythematosus.
RN: Why were you interested in looking at sex differences in lupus? What questions had previous research left unanswered?
The interest for the investigation began with two important facts. The first was that in clinical practice SLE is more common in women than in men. Several investigations have found that SLE is eight to 15 times more common in women of reproductive age than men of the same age. The result is that most investigations have focused on women. The second fact is given by the findings of some studies that suggest a different clinical behavior of SLE in men, apparently showing more severe SLE manifestations in men and probably a worse prognosis regarding further damage.
RN: What were your most important findings?
I think that the most important finding was that male sex was associated with a more active disease (as determined by an SLEDAI-2K 12) at the time of diagnosis, independent of age and race/ethnicity. It is important because it invites us to take more interest in SLE in men, which may include more aggressive treatment and closer following of patients. This could enable to change the prognosis of men SLE.
RN: Why might men have higher levels of disease activity at diagnosis?
Well, the first thing that we consider is that definitively the men had worse damage. We can think of some hypotheses, for example, that doctors don´t think of SLE in men as a first diagnosis, and when the diagnosis of SLE is made the activity is greater. Another is that the men look for a medical consult in more advanced moments of the disease. Finally, and I think the most important, is that SLE is more aggressive in men than woman in the beginning of the disease.
RN: How surprising was it that the disease course was otherwise similar?
That was very surprising, because we found that the most manifestations were similar between men and women. The only clinical manifestation different was alopecia.
But this finding is important in two ways: first, the clinical aspects of patients (men and women) are not useful to determine the difference in severity and it is necessary use another aid like SLEDAI or other validated scales; and second, physicians need consider all aspects the patients for improving diagnostic accuracy and offering a better treatment of the disease.
RN: Why do you think this finding differed from the findings of earlier studies?
I think that one reason was that we used clinical categories of SLEDAI (higher, moderate and mild), and other authors used the mean. When categories of the SLEDAI scores are used, that allows for the observation of real differences. Other explanations are related to the population, i.e., in our study the patients were referred through the university referral center, a tertiary care facility, or differences in ethnic backgrounds of patients.
RN: Why might you see more men getting kidney biopsies despite similar kidney involvement?
I believe that it is explained in part because some studies have found that men have more renal compromise than women and a higher rate of renal manifestations. So in the clinical practice the physicians look for these findings. And our findings show that the renal compromise is similar.
RN: Given your findings, what should physicians consider when diagnosing or treating men with lupus?
The most important is thinking that they are fighting with a more aggressive disease than in women, so they should use more aggressive treatment and be more consistent in the follow-up with patients. The main objective is improving the prognosis of these patients.
RN: Do you have plans for further work on these issues of gender and systemic lupus erythematosus?
In clinical research, with each study completed more questions appear. That is the most interesting aspect in our work. It's a work that doesn't have a real or definite finale. But each answer allows us to find a new light for application in our patients. After this research, we hope to focus our attention on explaining the reasons for the difference in the diagnosis, not only in speculative form. We need formal research in this field. Of course, similar to others researchers in the world, we want follow men with SLE to recognize the differences between sex in the prognosis.
Munoz-Grajales C, Gonzalez LA, Alarcon GS, Acosta-Reyes J. "Gender differences in disease activity and clinical features in newly diagnosed systemic lupus erythematosus patients." Lupus 2016. pii: 0961203316635286.
Tan TC, Fang H, Magder LS, Petri MA. "Differences between male and female systemic lupus erythematosus in a multiethnic population." J Rheumatol 2012; 39: 759–769. doi: 10.3899/jrheum.111061.
Lu L-J, Wallace DJ, Ishimori ML, Scofield RH, Weisman MH. "Male systemic lupus erthematosus: A review of sex disparities in this disease." Lupus. 2010;19:119–129. doi: 10.1177/0961203309350755