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.
Table 1 gives the criteria for the diagnosis of sarcoidosis of each member of the sibling pair. For the purposes of this study, an affected sibling pair was defined as two siblings having “definite” or “highly probable” sarcoidosis on the basis of Table 1. In addition, unaffected siblings for each sibling pair were recruited for enrollment, as were parents. The strategies for enrollment varied at the different clinical centers and included enrollment directly from clinics, contact from local physicians practicing outside the clinical centers, and various forms of advertising. Details about the study design and enrollment experience have been published elsewhere.
An organ was considered involved with sarcoidosis if a biopsy of the organ showed granulomatous inflammation with no known cause, or if the criteria listed in Appendix 2 were met. Spleen, upper respiratory tract, and nonthoracic lymph node are not listed in Appendix 2 because only a biopsy sample showing granulomatous inflammation was accepted as organ involvement.
An attempt was made to obtain two sets of chest radiographs and spirometry, one at or close to date of diagnosis, and one close to time of enrollment. The chest radiographs were categorized by Scadding stage (stages 0 to 4), and improvement or worsening was determined by a change of > 1 Scadding stage. FVC and FEV1 were considered to have improved or worsened if they increased or decreased by > 10% over time. Percentage of predicted FVC and FEV1 were computed for men and women from age and height according to the methods of Hankinson et al. The principal investigator (PI) at each clinical center was also asked to make a subjective assessment whether sarcoidosis had gotten better, worse, or stayed the same.
Table 1—Criteria for Diagnosis of Sarcoidosis
|Definite is defined as at least one in item 1 and at least one in item 2|
|1. Histologic confirmation|
|A. Noncaseating granulomas on pathology review|
|B. Positive Kveim test|
|2. Organ involvement definite (as defined in Appendix 2)|
|B. Two or more nonthoracic organ systems|
|Highly probable is defined as at least one of items 1 through 4.|
|1. Both (A) and (B)|
|A. Erythema nodosum (present or by acceptable history)|
|B. Typical chest radiograph finding (usually bilateral hilar adenopathy with or without parenchymal infiltrates)|
|2. Typical chest radiograph finding (Scadding stage I though IV) with 2 yr of observation during which no other disease is found to explain radiographic abnormalities|
|3. At least two of (A) through (F)|
|A. Typical skin involvement (lupus pernio, annular lesions, macular papular lesions, nodules, or plaques anywhere on body)|
|B. Typical chest radiograph (Scadding stage I through IV)|
|C. Granulomatous uveitis|
|E. Ga scan with thoracic lambda (lacrimal) or panda (parietal) pattern|
|F. Patient verbal report (unconfirmed) of biopsy consistent with sarcoidosis|
|4. Other criteria referred to the SAGA Operations Committee for resolution that was deemed to be clinically consistent with the diagnosis of sarcoidosis|