Health Services Research and Systemic Lupus Erythematosus: A Reciprocal Relationship

HEALTH SERVICES RESEARCH AND SYSTEMIC LUPUS ERYTHEMATOSUS: A RECIPROCAL RELATIONSHIP DANIEL A. ALBERT* Introduction Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease. Predominantly attacking young women, it causes damage in many organ systems resulting in pleomorphic symptoms. Common features include a photosensitive skin rash, fever, and polyarthritis. Visceral organ involvement is often widespread and is particularly devastating when it includes the central nervous system or renal disease. The disorder has a wide spectrum of manifestations and severity, making the course of the illness difficult to predict. Consequently, counseling patients, making medication decisions , and determining the effect of therapies are difficult. Furthermore, the disease has undergone a significant evolution in terms of diagnosis, prognosis, and disease manifestations since it was initially described in the 19th century. Then it was thought to be invariably fatal. Many of the protean manifestations were recognized and described by Osier, although pathological studies by Libman and Sacks and others greatly enhanced understanding of the disease [I]. Discovery of the LE cell phenomenon in 1948 by Hargraves and the recognition that it is a manifestation of antinuclear antibodies revolutionized our understanding of the disease. Indirectly, it led to a profound alteration in clinical management. The antinuclear antibody test increased the number of patients identified as having SLE and enlarged the description of the clinical manifestations. From the outset this disease has provoked interest far in excess of what its prevalence would dictate. Many factors have played a role in this focus, including: its reputation as a lethal disease with poor response to therapy; *Department of Medicine, Rheumatology Department, 3400 Spruce Street, Philadelphia, PA 19104. Supported by a grant (AR43584) from the National Institutes of Health (ARAMIS) .© 1998 by The University of Chicago. AU rights reserved. 0031-5982/98/4003-1042$01 .00 Perspectives in Biology and Medicine, 41, 3 ¦ Spring 1998 327 the discovery of the autoimmune pathogenesis of the disease; its unpredictable exacerbations and remissions; and its protean manifestations. As our understanding of the disease has enlarged with clinical and laboratory investigations our whole conception of the disease changed. Originally it was thought to be rare. Now studies suggest a prevalence of up to 1:1000 women. This increased frequency is a consequence of better diagnostic screening, which in turn is due to better laboratory testing. Better diagnostic testing enlarges the patient pool by increasing the number of less severely ill patients. Better diagnostic testing also increases the range of clinical manifestations and improves the prognosis by including less ill patients into the pool. Studies of systemic lupus have used clinical, laboratory, and epidemiologic approaches, and in many of these areas the disease has provoked lines of investigation that stimulated the development of experimented techniques . An example of this interaction is the development of immunofluorescent techniques to explore the phenomenon of autoantibodies. The biology of the serum protein system known as complement is another example. Much of the biochemistry of complement was elucidated in reference to SLE. In the clinical arena the autoimmune pathogenesis of many syndromes, such as idiopathic thrombocytopenic purpura (ITP), autoimmune hemolytic anemia, and some forms of recurrent miscarriage, were developed as a consequence of their presence as manifestations of SLE. Eventually each of these syndromes were shown to be a consequence of autoantibodies. This kind of close interaction between the basic science of lupus and the evolution of clinical knowledge and understanding of the disease was not limited to laboratory studies. The thesis I will develop in this paper is that there has been a close interaction between the study of the disease systemic lupus erythematosus and the development of novel techniques in clinical epidemiology and health services research. Four areas of significant synergy are: life table analysis; meta-analysis; decision analysis; and Markov analysis. In each of these cases, questions arising out of the study of patients with SLE led to the introduction of specific techniques to answer these questions and contributed to general clinical epidemiologic progress. Although the roots of epidemiology can be traced thousands of years to observations and conjectures on plagues and epidemics, most people date modern epidemiology from John Snow's historic treatise on the origin of cholera in London [2]. In this study he was...