A Case-Control Etiologic Study of Sarcoidosis (ACCESS)

Objectives:

To determine the etiology of sarcoidosis by establishig a case control, multi-center study. In addition to etiology, this study also sought to examine socioeconomic variables and the clinical course of patients with sarcoidosis, including quality of life.

Background:

Sarcoidosis is a chronic granulomatous disorder of unkonwn cause that is characterized by activation of T-lymphocytes and macrophages. For many years sarcoidosis was presumed to be an atypical manifestation of tuberculosis because of the similarity between the inflammatory responses of the two diseases. However, as culture techniques became more widely employed to diagnose tuberculosis and it became less common, it became clear that sarcoidosis was not simply a variation of tuberculosis. Data on the etiology of sarcoidosis have come from diverse sources: in clinical investigations, alveolitis has been found to precede granulomatous inflammation; in case control studies, familial aggregation has been identified; and in case reports, recurrence of granulomatous inflammation has been observed after lung transplantation. The cause may not prove to be a single, known exposure. Interactions of exposures with genetic dispositions could have important implications for our understanding of immune responses as well as the pathogenesis of sarcoidosis.

Subjects:

736 patients with sarcoidosis enrolled within 6 months of diagnosis from 10 clinical centers in the U.S. Using the ACCESS sarcoidosis assessment system, organ involvement was determined for the whole group and for subgroups differentiated by sex, race, and age (<40 or 40 and older). Cases were matched with a control, and there was a two-year follow-up on cases. The ACCESS group proposed an instrument fo defining organ involvement in sarcoidosis. Biological specimens included DNA, plasma, and bronchoalveolar lavage samples were obtained. The Limited Access Data set includes 718 cases, 686 controls, and two-year follow-up data on 210 cases.

Conclusions:

The initial presentation of sarcoidosis is related to sex, race and age, and it tends to remain stable over two years in the majority of patients. The etiology is probably multifactoral with both genetic and environmental factors contributing.

Publications (as of June 9, 2004):

1. Judson M. et al. Defining Organ Involvement in Sarcoidosis: The ACCESS Proposed Instrument. Sarcoidosis, Vasculitis and Diffuse Lung Diseases. 1999; 16:75-86.
2. ACCESS Research Group. Design of a Case Control Etiologic Study of Sarcoidosis (ACCESS). Journal of Clinical Epidemiology. 1999; 52:1173-1186.
3. Baughman R, et al. Clinical Characteristics of Patients in a Case Control Etiologic Study of Sarcoidosis. American Journal of Respiratory and Critical Care Medicine, 2001; 164:1885-1889.
4. Rybicki B, et al. Familial Aggregation of Sarcoidosis: A Case Control Etiologic Study of Sarcoidosis (ACCESS). American Journal of Respiratory and Critical Care Medicine, 2001; 164:2085-2091.
5. Pandey JP, et al. TNF-a, IL1-ß, and Immunoglobulin (GM and KM) Gene Polymorphisms in Sarcoidosis. Human Immunology 2002; 63:485-91.
6. Judson M, et al. The Diagnostic Pathway to Sarcoidosis. Chest 2003;' 123:406-12.
7. Brown ST, et al. Recovery of Cell Wall-Deficient Organisms from Blood Does Not Distinguish between Patients with Sarcoidosis and Control Subjects. Chest 2003; 123: 413-17.
8. Judson, MA, et al. Two-year Prognosis of Sarcoidosis. The ACCESS experience. Sarcoidosis, Vasculitis and Diffuse Lung Disease 2003; 20:204-11.
9. Rossman MD et al. HLA-DRB1* 1101: A significant risk factor for sarcoidosis in blacks and whites. Am J Hum Genet 2003; 73(4): 720-34.