RT Book, Section A1 Rullo, Ornella J. A1 Deng, Yun A1 Rullo, Ornella J. A2 Murray, Michael F. A2 Babyatsky, Mark W. A2 Giovanni, Monica A. A2 Alkuraya, Fowzan S. A2 Stewart, Douglas R. SR Print(0) ID 1102705921 T1 Systemic Lupus Erythematosus T2 Clinical Genomics: Practical Applications in Adult Patient Care YR 2014 FD 2014 PB McGraw-Hill Education PP New York, NY SN 9780071622448 LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102705921 RD 2024/03/29 AB Disease summary:Systemic lupus erythematosus (SLE) is a complex, autoimmune disease characterized by the presence of antibodies to nuclear components. An interplay of genetic and environmental factors contribute to the immunologic manifestations and disease pathogenesis, which can involve the skin, kidneys, hematologic system, nervous system, joints, mucosal and serosal membranes, and/or other organs.Clinically, the disease spectrum is varied and affected individuals can experience periods of disease activity and remission.Women are affected more frequently than men, with a reported ratio of up to 9:1, and diagnosis most often occurring in the third through fifth decades of life.The diagnosis of SLE is clinical, and a typical presentation is often a young woman with constitutional, skin, and musculoskeletal complaints.Organ involvement, such as kidney, central nervous system, or cardiopulmonary, can occur early in the disease course or at diagnosis, and can be severe and dominate the patient’s disease course.Differential diagnosis:Some important general considerations when evaluating an individual with potential SLE include drug-induced lupus, infection, malignancy, and other autoimmune conditions. Due to the number of possible clinical manifestations of SLE, it is beyond the scope of this review to fully summarize the differential diagnosis. However, if one organ manifestation dominates, then the differential will include related conditions. For example, in a patient presenting with seizures, considerations for diagnosis include new-onset epilepsy, metabolic abnormalities, drug toxicity or withdrawal, and hypoxia, among others.Monogenic forms:Several rare mutations that lead to either a deficiency of classical complement components, or impaired DNA degradation, clearance, and/or antigen signaling have been identified in small numbers of patients with SLE or lupus-like manifestations. The genes include C1Q (1p36), C1R/C1S (12p13), C4A&B (6p21.3), C2 (6p21.3), TREX1 (3p21.31), DNASE1 (16p13.3), ACP5 (19p13), SIAE (11q24), and DNASE1L3 (3p14.3).Family history:Most individuals with SLE do not have an affected family member. However, a familial prevalence of up to 12% has been reported. In families with clusters of members with SLE, the inheritance pattern does not follow a classic single-gene Mendelian pattern.Twin studies:The disease concordance rate is 2% to 5% for dizygotic twins and 24% to 58% for monozygotic twins. The rate of concordance in monozygotic twins supports the possibility that development of disease is multifactorial, which may include multiple genes, as well as environmental and hormonal factors.Environmental factors:Several infections have been associated with the development of SLE, with the strongest evidence linked to Epstein-Barr virus; the correlation of disease flares in patients with SLE who develop viral infections supports this possibility. Environmental exposures or contaminants, such as trichloroethylene (an industrial solvent) and various pesticides have all been suggested in epidemiologic studies as possible triggers of SLE in susceptible individuals, but further study in this area is necessary. Plausible biologic evidence links SLE and other autoimmune diseases to silica exposure, which can occur due to diverse occupations such as farming, construction, mining, and manufacturing. High silica exposure has been associated with the development of SLE (odds ratio [OR] 4.6, 1.4-15.4). Additionally, a number of medications have been implicated in precipitating SLE, including hydrochlorothiazide, antihistamines, calcium channel blockers, terbinafine, and naproxen. Antitumor necrosis ...