Another Look at Lupus in Men
A Review of the Veterans Administration Healthcare Population
By Pamela Elaine Prete, M.D., F.A.C.P., Professor of Medicine, In Residence University of California Irvine, Chief of Rheumatology VAMC, Long Beach, CA
Systemic lupus erythematosus, a connective tissue disease of unknown etiology, is generally considered to be uncommon among men. It is so prevalent among young women that some have considered that it may be a separate disease when it occurs in men. Previous studies have reported differences in lupus disease manifestations between men and women in such things as age at onset, kidney or skin involvement, and even in overall survival. The majority of this information is gathered from the previously reported studies, which would only contain small numbers of men with lupus compared to the large number of women in the study. With so few male patients at each study location, the results were often confusing so that very little is established about the disease course in men.
Some studies have noted that the age of onset of lupus in men is much later than that in women. One study suggested men with lupus were an average of 10 years older than women at the time of first diagnosis. One research group from Canada reported that a quarter of his male lupus patients were over 50 years of age at diagnosis and several other investigators have suggested that only men get older age lupus. Others have reported little difference in the age of onset between men and women. Although some studies report conflicting data, one of the most recurrent theories in the previous studies that analyzed gender differences in lupus was the demonstration of a higher prevalence of kidney disease in male patients with lupus, in both the adult and pediatric population. It would also seem that overall survival in men with lupus also tends to be significantly lower than that reported for females.
A Russian study analyzed the survival pattern in 120 Russian male patients with lupus and found that 22.5% of the patients died during the follow-up period, with end-stage kidney disease being the most common cause of death. It has been suggested that the survival at 5, 10, and 15 years was lower in the male lupus group compared to female lupus patients. Indeed, an American group also found that males with lupus had a higher total mortality rate than females with lupus, but the causes of death did not seem to be directly related to lupus.
Our group of researchers at the VA Long Beach Healthcare System, decided that very useful information about the disease course in men with lupus could be obtained from all the hospitals in the Department of Veterans Affairs system. We reasoned that this healthcare system offered a unique opportunity to study a large population that is so predominately male, that the case histories of large numbers of male patients with lupus could be examined. Data for our study were retrieved from the National Patient Treatment Files (PTF) maintained by the central Department of Veterans Affairs computerized record system that was established in 1987. This vast system includes data from the computerized healthcare records of Veteran patient hospitalizations in all of the VA hospitals in the United States, Puerto Rico, Philippines, and Guam. 
All lupus patients were identified from the hospitalization discharge diagnostic records by the appearance of the code for lupus in any of the first five positions. Discoid lupus and drug induced lupus codes were specifically excluded from study. We found that from 1987 to 1996, there were 2,614 lupus patients in the system. Two thousand one hundred and eight patients were males and 426 were females with male to female ratio to 5 to 1. We found the average age of lupus onset is nearly a decade later at 55.6 years for men, compared to 42.6 years for females with lupus. With so many lupus patients in our study, our data confirmed that, for the majority of men with lupus, the disease comes on at middle age or older. 
In our study, men with lupus had more hospitalizations and longer hospital stays (13 days compared to 9.3 days for women with lupus), suggesting that men with lupus were sicker and had more complications, suggesting a higher morbidity for men with lupus. We also found overall cancers and heart attacks were more frequent among men with lupus, while thyroid disease was more common in the women with lupus. Kidney disease affected 15% of VA men with lupus and 13.1% of women with lupus during this ten-year study period, but this was not a statistically significant difference. Kidney disease was more broadly defined in our study, yet there was no apparent difference between the sexes for kidney disease. There is no ready explanation for these results in our study except that the relationship of lupus, sex, and kidney disease may merit further study. The men with lupus in the study had three times the acute heart attack or myocardial infarction rate than that of the women with lupus. Which suggested to us that cardiovascular disease contributes significantly to mortality of men with lupus.
Whether or not the cardiovascular disease is caused by the lupus or merely associated with the more advanced age of men with lupus in the study could not be discerned. What was a little surprising was that we also demonstrated that there were wide regional variations in many of our results in the morality statistics in our large nationwide study. Regional variations in data results, such as the ones we found in our study have not been mentioned or discussed in prior studies. This suggested to us that in order to reflect an accurate picture of lupus and its disease parameters, future lupus studies will need to include data from multiple geographic areas. The results of our study confirmed the previous observations in noting a decreased survival in men with lupus.
The late age at onset and mortality rates in our large study closely resemble other smaller studies and add support to the generally poor prognosis that is reported in certain groups of men with lupus. These findings suggest that men with lupus have a more complex clinical course than women, although the data did not illuminate whether the other diseases that occur are due to or coincident with lupus. Based on our findings, not only rheumatologists, but general practitioners may need to consider lupus in the differential diagnosis for older men, and be more attentive to the concomitant presence of heart disease and cancer in men with lupus.