Category Archives: Sarcoidosis

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Comment

Because siblings share both a portion of their genome and some environmental exposures, it is logical to test the hypothesis that phenotypic expression of sarcoidosis between affected siblings should be more similar than between cases selected at random. The concordance of liver and ocular sarcoidosis between affected siblings supports, albeit weakly, this hypothesis, whereas the other organ systems and phenotypic parameters of sarcoidosis we examined failed to show concordance between siblings.
In addition, if sarcoidosis is a multigenetic disease associated with environmental exposure, then our inability to find close phenotypic similarities between siblings would not necessarily disprove a genetic basis for the disease. It may be that a specific combination of genes determines sarcoid phenotypes. In addition, it is possible that the genes responsible for the development of sarcoidosis are distinct from those that determine the phenotypic expression of the disease. Thus, while affected siblings may share disease predisposing genes, differences in genes and/or exposures important in the determination of sarcoidosis phenotypes may still exist between sibling pairs. The concept of multiple sarcoidosis susceptibility genes is supported by two studies’ that identified multiple linkage sites associated with sarcoidosis. It is also possible that few phenotypic similarities were seen in sibling pairs because environmental influences were different enough to override the genetic similarities. Because a genetic analysis of affected sibling pairs that included environmental histories was not performed in this study, these issues remain unresolved.
Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Conclusion

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: ConclusionIn terms of degree of pulmonary involvement and clinical course of disease, almost no phenotypic similarities between the siblings were detected regardless whether the full-sibling and half-sibling pairs were analyzed together or only the full-sibling pairs were examined. Sibling pairs were not significantly concordant in baseline radiographic stage, changes in spirometry, number of organ systems involved, chest radiograph, or overall clinical assessment over time. The only statistically significant concordance found concerned the need for treatment. Although this concordance was detected in both the full-sibling and half-sibling pair and the full sibling pair groups, the level of agreement was poor (к = 0.14 and к = 0.15, respectively). starlix medication
Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Discussion

The strongest correlations found were that the second sibling with sarcoidosis was three times more likely to have ocular or liver involvement if the first sibling had involvement of these organs. However, the concordance of these phenotypes was relatively weak. In addition, there was virtually no concordance between the members of sibling pairs in terms of clinical course.
Our approach in analyzing phenotypic expression of a disease in sibling pairs was not unique. A similar approach as been used to examine disease similarity in sibling pairs with multiple sclerosis and rheumatoid arthritis. Trojano and colleagues found that sibling pairs with multiple sclerosis were more likely than unrelated patients to have a similar age of onset, progression of disease, and sensory symptoms. However these investigators could not identify a genetic explanation for these phenotypic differences. Silman et al failed to find a greater concordance of rheumatoid arthritis phenotypes within families than between them.
Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Research

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: ResearchTable 2 shows the sibling concordance by organ system. Overall к values were low, ranging from -0.04 to 0.18, demonstrating poor concordance for these phenotypes. There was significant but weak sibling concordance for ocular (к = 0.16; p < 0.05) and liver involvement (к = 0.16; p < 0.05). Concordance was also statistically significant, but weak, for ocular involvement when only full siblings were considered (к = 0.18; p < 0.05).
Table 3 shows the sibling concordance for other clinical outcomes of interest. For the full-sibling pairs and the full-sibling and half-sibling pairs, only receiving treatment showed a significant concordance between sibling pairs (p < 0.05), but the level of agreement was weak (к = 0.14 for full-sibling and half-sibling pairs, к = 0.15 for full-sibling pairs alone). Seventy-six percent of the sibling pairs were concordant with respect to ever being treated. whitening gel
Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Results

The final study sample consisted of 231 families containing > 2 affected siblings with sarcoidosis comprising a total of 509 affected siblings. Women represented the majority of the affected siblings in the sample (75.1%). Approximately 15% of the enrolled families were comprised of three or more affected siblings, in which all possible sibling pair combinations were counted; there were 197 pairs, 23 trios, 9 quartets, and 2 quintets of affected siblings with sarcoidosis representing a total of 340 affected sibling pairs. Of these, 25% were half-sibling pairs. natural breast enhancement pill
Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Analysis

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: AnalysisTo determine the degree that concordance occurred for a particular organ or for other clinical outcomes, we computed к statistics for affected sibling pairs using a technique developed by Fleiss. While this technique was initially developed for measuring agreement between raters, it has also been applied to sibling analysis in multiple sclerosis and rheumatoid arthritis. Each variable tested for concordance was dichotomized by the presence or absence of the condition. Proportions of siblings with the condition present were computed to determine if the concordance differed from what would be expected by chance. The resulting к statistic ranged from + 1 (indicating perfect concordance) to – 1 (indicating perfect discordance). A separate analysis was performed for full siblings only.
Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings: Enrollment and Data Collection

Patients from 11 clinical centers were enrolled in this study. All clinical centers had this study approved by their institutional review boards. Subjects were required to sign an informed consent statement for participation. Subjects could be enrolled only if they self-designated their race as “black or African American.” Only African Americans were selected for the SAGA study because they have a higher occurrence of first-degree relatives affected with sarcoidosis than whites. Study subjects were enrolled as families with the minimal family configuration consisting of an initial case (proband) and at least one sibling with a diagnosis of sarcoidosis. Full siblings were defined as siblings who had the same two parents. Half siblings were defined as sharing one of their two parents.

Continue reading

Comparison of Sarcoidosis Phenotypes Among Affected African-American Siblings

Comparison of Sarcoidosis Phenotypes Among Affected African-American SiblingsSarcoidosis is a multisystem granulomatous disease  of unknown cause. Although the lung is most commonly affected, sarcoidosis may occur in any organ. The severity of pulmonary sarcoidosis may range from an abnormal screening chest radiograph finding in a patient free of symptoms, to end-stage lung disease with respiratory failure. Some patients have clinical disease that is most prominent in extrapulmonary organs. The prognosis of sarcoidosis is highly variable with a tendency to wax and wane, and may resolve either spontaneously or in response to therapy. The clinical course is chronic or progressive in 10 to 30% of patients.
Continue reading