Sarcoidosis is a granulomatous disorder associated with an accumulation of CD4+ T cells and a Th1 immune response. In childhood, 2 distinct types of sarcoidosis have been described (Shetty and Gedalia, 1998). Usually the disease is detected in ... Sarcoidosis is a granulomatous disorder associated with an accumulation of CD4+ T cells and a Th1 immune response. In childhood, 2 distinct types of sarcoidosis have been described (Shetty and Gedalia, 1998). Usually the disease is detected in older children by chest radiography, and the clinical manifestations are characterized by a classic triad of lung, lymph node, and eye involvement, similar to those in adults. In contrast, early-onset sarcoidosis (EOS; 609464), which usually appears in those younger than 4 years of age, is rare and has a distinct triad of skin, joint, and eye disorders, without apparent pulmonary involvement. Compared with an asymptomatic and sometimes naturally disappearing course of the disease in older children, EOS is progressive and in many cases causes severe complications, such as blindness, joint destruction, and visceral involvement.
Willoughby et al. (1971) described 3 sibs of whom 2 had sarcoidosis and 1 had Crohn disease. Gronhagen-Riska et al. (1983) commented on the occurrence of sarcoidosis and regional enteritis in the same family.
Nowack and ... Willoughby et al. (1971) described 3 sibs of whom 2 had sarcoidosis and 1 had Crohn disease. Gronhagen-Riska et al. (1983) commented on the occurrence of sarcoidosis and regional enteritis in the same family. Nowack and Goebel (1987) found an unusually high frequency of HLA-DR5 (relative risk, 6.6) in patients with sarcoidosis. Their study was done in Marburg, West Germany, where, during the previous 18 years, 440 patients with sarcoidosis had 'regularly attended the University Hospital of Marburg or neighboring clinics.' Kronauer et al. (1988) described sarcoidosis in a father and son of 1 family and in 2 sisters of a second family. Among 76 patients with ocular sarcoidosis, Khalatbari et al. (2004) compared the frequency of posterior segment involvement (PSI), the prevalence of specific posterior segment signs, and visual acuity by race, sex, and age. Sixty-eight percent of the patients were black (34 females and 18 males) and 32% were white (18 females and 6 males). Sixty-eight patients (89%) had PSI: 85% of black patients and 100% of white patients. The most common findings of PSI were vitritis (69%); choroidal 'punched-out' lesions (56%); 'snowball' lesions (46%); cystoid macular edema (31%); and periphlebitis, vitreous opacity, and posterior vitreous detachment (29% each).
Rossman et al. (2003) performed high-resolution typing for HLA-DPB1 (142858), HLA-DQB1 (604305), HLA-DRB1 (142857), and HLA-DRB3 (612735) loci and the presence of the DRB4 or DRB5 locus, to define HLA class II associations with sarcoidosis. A case-control etiologic ... Rossman et al. (2003) performed high-resolution typing for HLA-DPB1 (142858), HLA-DQB1 (604305), HLA-DRB1 (142857), and HLA-DRB3 (612735) loci and the presence of the DRB4 or DRB5 locus, to define HLA class II associations with sarcoidosis. A case-control etiologic study of sarcoidosis (ACCESS) enrolled 736 biopsy-confirmed cases from 10 centers in the United States; 706 controls were case-matched for age, race, sex, and geographic area (ACCESS Research Group, 1999). In the first 474 patients and case-matched controls, the HLA-DRB1 alleles were differentially distributed between cases and controls (P less than 0.0001). The HLA-DRB1*1101 allele was associated (p less than 0.01) with sarcoidosis in blacks and whites and had a population-attributable risk of 16% in blacks and 9% in whites. Phenylalanine-47 was the amino acid residue of HLA-DRB1 most associated with sarcoidosis and independently associated with sarcoidosis in whites. The HLA-DPB1 locus also contributed to susceptibility to sarcoidosis and, in contrast to chronic beryllium disease, a non-glu69-containing allele, HLA-DPB1*0101, conveyed most of the risk (see 142858.0001). Although significant differences were observed in the distribution of HLA class II alleles between blacks and whites, only HLA-DRB1*1501 was differentially associated with sarcoidosis (p less than 0.003). In addition to being susceptibility markers, HLA class II alleles may be markers for different phenotypes of sarcoidosis: DRB1*0401 for ocular involvement in blacks and whites, DRB3 for bone marrow involvement in blacks, and DPB1*0101 for hypercalcemia in whites. These studies confirmed a genetic predisposition to sarcoidosis and presented evidence for the allelic variation at the HLA-DRB1 locus as a major contributor.