TY - CHAP M1 - Book, Section TI - Sarcoidosis A1 - Sah, Birendra P. A1 - Iannuzzi, Michael A2 - Murray, Michael F. A2 - Babyatsky, Mark W. A2 - Giovanni, Monica A. A2 - Alkuraya, Fowzan S. A2 - Stewart, Douglas R. PY - 2014 T2 - Clinical Genomics: Practical Applications in Adult Patient Care AB - Disease summary:Sarcoidosis is a multisystemic disease of unknown etiology that is characterized by granulomatous inflammation. It is presumed to be triggered by a complex interaction between environmental and genetic factors.The incidence of sarcoidosis varies widely throughout the world depending on ethnicity and geographic region. The annual incidence ranges from 1 to 64 cases per 100,000 persons.Although sarcoidosis affects people of all racial and ethnic groups and occurs at all ages, it usually develops before the age of 50 years and it is three times more common among blacks than whites. Blacks also develop more severe and chronic disease.Sarcoidosis can involve any organ system, with the respiratory system most commonly involved. About 50% of cases are detected in asymptomatic individuals due to incidental radiographic abnormalities of bilateral hilar lymphadenopathy with or without pulmonary infiltrates. When symptomatic the most common complaints are cough, dyspnea, chest pain, eye lesions, and/or skin lesions.Differential diagnosis:Mycobaterial and fungal infections (histoplasmosis, coccidiodomycosis), chronic berylliosis, talcosis, hypersensitivity pneumonitis, autoimmune disorders (Wegener granulomatosis, primary biliary cirrhosis, Crohn disease), lymphoma, and tumor-related granulomatous disease.Monogenic forms:Blau syndrome (early-onset sarcoidosis), an autosomal dominant disorder, results from mutations in the NACHT domain of CARD15 (also known as NOD2) located on chromosome 16q12.1-13. Blau syndrome usually presents before the age of 4 years and mainly involves skin, joints, and eyes. Lung involvement is notably absent.Family history:From 3.6% to 9.6% of patients report that their first- or second-degree relatives also have sarcoidosis. Siblings of the affected patient have a fivefold increase in the relative risk of developing sarcoidosis.Twin studies:A registry-based twin study showed about a 10-fold increased risk for concordant disease in monozygotic twins compared to dizygotic twins.Environmental factors:Exposures associated with increased risk for sarcoidosis include agricultural employment, mold or mildew, musty odors at work, and pesticide-using industries. Tobacco use is negatively associated with sarcoidosis. In the United States, occupational clustering of sarcoidosis has been reported in ship workers, firefighters, and rescue workers who responded to the attacks on the World Trade Center.Genome-wide associations:Genome-wide association studies (GWASs) have identified several human leukocyte antigen (HLA) and non-HLA candidate disease genes for sarcoidosis (Tables 117-1 and 117-2).Pharmacogenomics:Pharmacogenetic studies are indicated for some of the medications used in sarcoidosis treatment (Table 117-3). SN - PB - McGraw-Hill Education CY - New York, NY Y2 - 2024/03/28 UR - accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102704610 ER -