Stanley L. Lee

The epidemiology of systemic lupus erythematosus

Abstract The present review has focused on the methods and results of epidemiological studies of SLE for clues to its etiology based on reports of the occurrence of SLE in the general population and on the conditions under which it is likely to occur. The review covers the period from 1950 to 1972, and is limited to idiopathic SLE. Reports of population studies on SLE were published from four widely scattered regions, namely, New York City; Jefferson County, Alabama; Rochester, Minnesota; and Malmo, Sweden. Geographic variations in the prevalence of the disorder were observed, which were largely attributed to regional differences in completeness of case finding. The reported crude rates were highest in Rochester, lowest in Jefferson County, and at an intermediate level in Malmo and New York City where the findings were similar. In New York City, the annual incidence of newly occurring cases of idiopathic SLE from 1956 to 1965 appeared to be stabilized at a level of about 2.5/100,000 general population, while the prevalence of existing cases rose progressively from 4.1 to 15.5 per 100,000 during the same 10-yr period. The even level in incidence trend indicated that the occurrence of SLE was not appreciably influenced by changes in host or environmental conditions during the study period. The steady increase in prevalence was attributed to earlier recognition of the disease and to longer survival because of improved therapy. The annual mortality was roughly half the incidence in the decade 1956–1965. The specific incidence of the disease by age and sex was usually highest at 15–44 yr of age, while its prevalence was maximal at 45–64 yr. The respective incidence and prevalence rates at these ages were 14.0 and 90.9/100,000 for black females and 3.8 and 27.6 for white females in New York City. The rates among Puerto Ricans appeared to be intermediate between those for blacks and whites. However, some of the evidence on age and SLE pointed to an earlier age-distribution of cases among Puerto Ricans than among blacks or whites. The risk of SLE was higher for black females than whites in both New York City and Jefferson County, Alabama, according to cooperative studies there. In males, however, the comparative results on ethnic differences in the occurrence of SLE were conflicting and inconclusive because of the small number of cases in each area. The higher rates of SLE for blacks and Puerto Ricans could not be related to more complete case finding or to unfavorable environmental conditions in low socioeconomic groups. On the other hand, the results appeared to be related to underlying ethnic differences in immune mechanism, according to studies on serum gamma globulin level and Mantoux reaction to BCG in normal subjects. Familial studies revealed some evidence of an increase in serum gamma globulin, and possibly in antinuclear factor and other SLE-related immunological and clinical abnormalities among first-degree relatives of SLE cases. The findings were indicative of a demonstrable familial or a genetic influence in the occurrence of the disorder. The abnormalities were mainly concentrated in selected families, and environmental factors could not be excluded. However, the occurrence of the disease was found to be independent of birth order, an indication that it represents a random event consistent with genetic factors and unrelated to change with time in parity, parental age, and related environmental influences. More direct evidence for genetically determined host factors in the predisposition to SLE has been sought in studies on the relationship of the disorder to the histocompatibility (HL-A) antigens which may be closely linked to the activity of the immune mechanism. Thus far, different specific HL-A antigens, viz., A5, A7, A8, A13, W5, W15, and an X type, were observed by various investigators in association with SLE and the risk of developing the disease. Whether these diverse findings have biological significance or are artifacts attributable to chance and other factors unrelated to SLE is still not known. In the predisposed subject, each of the three broad groups of environmental agents, namely, physical, chemical, and biologic, has been associated with SLE. The relationship of the disorder to physical agents such as ultraviolet radiation and trauma has been well documented in past clinical experiences. The association of SLE and chemical agents described in early clinical reports on inducing factors has been strengthened by many studies on procainamide, hydralazine, and other drugs responsible for an increased frequency of drug-induced SLE. Interest in the role of biological agents has been renewed by reports on increased antibody levels for paramyxovirus and other viral antigens in affected patients, and the detection of cellular inclusions resembling paramyxoviruses in cases of SLE and other disorders. Whether these widespread findings in man are coincidental manifestations of SLE or evidence of persistent virus infections that may be responsible for the disease has not yet been ascertained. In animals, however, support for the role of viral and genetic factors in the pathogenesis of SLE has been well documented in the susceptibility of inbred NZB/NZW mice to SLE-like disorders, and the identification of a virus-like agent in the affected NZB mice. In susceptible dogs, also, SLE-like manifestations appear to be due to genetic and nongenetic factors, presumably of viral origin.

Occurrence of acute leukemia in females in a genetically isolated population

Acute lymphoblastic leukemia was found in six young females in a genetically isolated Syrian Jewish Community in Brooklyn, N.Y. over a 15‐year period. This represents a frequency 30 times greater than the expected rate. In this community the frequency of first cousin marriages is estimated to be seven percent. Three cases were related on their maternal side, the parents of a fourth case were themselves related as were both sets of grandparents of a fifth case. In two families a history of infertility was present. On average, fathers of the cases were 5.5 years older at birth of the cases than a matched sample of community controls and 7.2 years older than a matched sample of non‐community controls. The high frequency of consanguinity and the older age of the fathers may increase risk to acute leukemia for young girls in this community.

A study of adult T‐cell leukemia/lymphoma incidence in central Brooklyn

Adult T7hyphen;cell leukemia/lymphoma (ATL), a rare outcome of infection with human T‐lymphotropic virus (HTLV‐I), is endemic in central Brooklyn, which has a large Caribbean migrant population. Previous studies have suggested that HTLV‐I prevalence in central Brooklyn may be similar to that recorded in the Caribbean islands. We established a pilot 1‐year surveillance program to identify cases of ATL in 7 of 10 hospitals serving the residents of 18 zip codes of central Brooklyn with a combined population of 1,184,670. Of the 6,198 in‐patient beds in the catchment area, approximately 83% were covered. Twelve incident cases of ATL were ascertained, all among persons of Afro‐Caribbean descent, indicating an annual incidence in African‐Americans in this community of approximately 3.2/100,000 person‐years. Unexplained hypercalcemia was the most useful screening method, identifying 3 of 5 patients not referred for possible ATL by a local hematologist. The female:male ratio was 3:1. The age pattern was different from that reported in the Caribbean Basin and closer to the pattern seen in Japan. Our study supports evidence that HTLV‐I infection and ATL are endemic in central Brooklyn and suggests that a more intensive surveillance program for this disease coupled with intervention efforts to reduce HTLV‐I transmission are warranted. Int. J. Cancer 80:662–666, 1999. Published 1999 Wiley‐Liss, Inc.