CINCINNATI—Two recent analyses have yielded some of the most authoritative data ever published on the epidemiology of sarcoidosis.

One analysis has proved what previous anecdotal reports only hinted at—that sarcoidosis aggregates in families.[1] It found that the risk for sarcoidosis was increased 4.5-fold in parents and siblings of patients with the disease, lead investigator Benjamin A. Rybicki, PhD, told PULMONARY REVIEWS. Familial aggregation was much more prominent in whites than in African-Americans, but an important risk factor in both races, added Dr. Rybicki, Senior Research Epidemiologist with the Henry Ford Health System in Detroit.

The second analysis revealed that the initial presentation of sarcoidosis varies by age, sex, and race.[2] This finding challenges the widely held stereotype that the patients most often affected are African-Americans and young adults, said lead investigator Robert P. Baughman, MD, Professor of Medicine at the University of Cincinnati.

FAMILIAL AGGREGATION

Both analyses used data derived from A Case Control Etiologic Study of Sarcoidosis (ACCESS), which is unique among sarcoidosis studies in that it had a standardized system for reporting organ involvement. ACCESS included 736 sarcoidosis patients and an equal number of matched controls from 10 centers in the United States; the case patients were enrolled within six months of receiving a positive biopsy result indicating sarcoidosis.

Dr. Rybicki’s familial aggregation analysis included 10,862 first-degree and 17,047 second-degree relatives identified by 706 of the case-control pairs. First-degree relatives included parents, siblings, and children, whereas grandparents, uncles, and aunts were considered second-degree relatives. Complete information on the presence of sarcoidosis in these relatives was obtained from 646 case-control pairs.

The crude odds ratio (OR) for sarcoidosis among first-degree relatives of case patients was 3.8; it was 5.2 among second-degree relatives. Siblings of case patients had the highest crude OR (5.8), followed by uncles and aunts (5.7), grandparents (5.2), parents (3.8), and children (3.3). In addition, case patients were three times more likely than were controls to report that some other blood relative had sarcoidosis.

To investigate the impact of confounding variables on the likelihood of sarcoidosis, the authors conducted a multivariate analysis, but it was limited to adult first-degree relatives. (None of the second-degree relatives had been asked to provide detailed information, and most of the children were too young to have been affected by the disease.) In this analysis, confounding variables had no significant effect on the overall ORs for sarcoidosis.

Race, however, seemed to have a large influence on risk. Among the adult first-degree relatives of white case patients, the OR for sarcoidosis was 16.6; it was only 3.1 among the adult first-degree relatives of African-American case patients. Although this difference did not reach significance, it does suggest that familial factors contribute more to sarcoidosis susceptibility in whites than in African-Americans, said Dr. Rybicki.

He and his colleagues admit that bias in participants’ recall of their relatives’ health status was a possible limitation of the analysis. In fact, sarcoidosis rates reported among the parents and siblings of controls were much lower than expected based on recent incidence estimates, suggesting that recall bias did affect the findings. Bias in sarcoidosis detection may have influenced the results as well, the investigators added. Nevertheless, their study is the largest effort that has been conducted to date to assess familial aggregation of this disease, and their methodology made it unlikely that there was a high false-positive rate among the relatives of either cases or controls.

Despite the comparatively large increase in risk among first-degree and second-degree relatives of patients with sarcoidosis, Dr. Rybicki noted that the absolute risk of the disease was extremely low (1%). “It is, therefore, probably not necessary to screen for the disease in relatives of patients with sarcoidosis,” he concluded. However, family history should not be disregarded as an etiologic factor, he stressed.

PRESENTATION BY AGE, SEX, AND RACE

All 736 of the patients with sarcoidosis from ACCESS were included in Dr. Baughman’s analysis of the effects of age, sex, and race on disease presentation. Perhaps the first surprise he and his coworkers found was that 53.4% of the patients were white and only 44.2% were African-American, showing that sarcoidosis is not primarily a disease of the latter group, as had been previously thought. The stereotype that severe sarcoidosis occurs almost exclusively in African-Americans did not hold up, either. “We had a substantial number of white patients with severe disease,” Dr. Baughman related.

However, race does appear to be the major determinant of organ involvement in sarcoidosis. Overall, the disease affected one organ in 50% of the patients and two organs in 30%; the remaining patients had three or more organs involved. The lungs were by far the most common organ affected; pulmonary involvement was found in 95% of patients. The skin was affected in 16% of patients; the lymph nodes, in 15%; and the eyes and liver, in 12% each.

African-Americans were much more likely than were whites to have involvement of the eyes, liver, bone marrow, extrathoracic lymph nodes, or skin. In contrast, abnormalities of calcium metabolism were more common in whites; these abnormalities were also more common in men than in women. However, women were more likely to have eye involvement, neurologic dysfunction, or erythema nodosum. Younger patients (those in whom the disease developed before age 40) had a greater likelihood of extrathoracic lymph node involvement, whereas older patients more often had calcium metabolism abnormalities.

The analysis also found that sarcoidosis does not primarily affect young adults. Half of the patients were older than 40 years at the time of diagnosis, Dr. Baughman pointed out, and some patients were in their 60s and 70s.

Dr. Baughman acknowledged that his study, like Dr. Rybicki’s, has limitations. Although the patients enrolled in ACCESS appeared to be characteristic of patients with sarcoidosis in the United States, those with pulmonary disease may have been overrepresented, given that the primary investigator at each center was a pulmonologist. It is also possible that African-Americans with sarcoidosis were underrepresented. Nevertheless, he concluded that variability in presentation by age, sex, and race should be considered in all etiologic and therapeutic studies of sarcoidosis

—Timothy Begany

References

1. Rybicki BA, Iannuzzi MC, Frederick MM, et al. Familial aggregation of sarcoidosis: A Case-Control Etiologic Study of Sarcoidosis (ACCESS). Am J Respir Crit Care Med. 2001;164:2085-2091.
2. Baughman RP, Teirstein AS, Judson MA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med. 2001;164:1885-1889.

Return to table of contents