rate of sle. however, a 2010 review of studies that correlate race and sle identified several sources of systematic and methodological error, indicating that the connection between race and sle may be spurious. for example, studies show that social support is a modulating factor which buffers against sle-related damage and maintains physiological functionality. studies have not been conducted to determine whether people of different racial backgrounds receive differing levels of social support. if there is a difference, this could act as a confounding variable in studies correlating race and sle. another caveat to note when examining studies about sle is that symptoms are often self-reported. this process introduces additional sources of methodological error. studies have shown that self-reported data is affected by more than just the patient's experience with the disease- social support, the level of helplessness, and abnormal illness-related behaviors also factor into a self-assessment. additionally, other factors like the degree of social support that a person receives, socioeconomic status, health insurance, and access to care can contribute to an individual's disease progression. racial differences in lupus progression have not been found in studies that control for the socioeconomic status of participants. studies that control for the ses of its participants have found that non-white people have more abrupt disease onset compared to white people and that their disease progresses more quickly. non-white patients often report more hematological, serosal, neurological, and renal symptoms. however, the severity of symptoms and mortality are both similar in white and non-white patients. studies that report different rates of disease progression in late-stage sle are most likely reflecting differences in socioeconomic status and the corresponding access to care. the people who receive medical care have often accrued less disease-related damage and are less likely to be below the poverty line. additional studies have found that education, marital status, occupation, and income create a social context that affects disease progression. sex sle, like many autoimmune diseases, affects females more frequently than males, at a rate of about 9 to 1. the x chromosome carries immunological related genes, which can mutate and contribute to the onset of sle. the y chromosome has no identified mutations associated with autoimmune disease. hormonal mechanisms could explain the increased incidence of sle in females. the onset of sle could be attributed to the elevated hydroxylation of estrogen and the abnormally decreased levels of androgens in females. in addition, differences in gnrh signalling have also been shown to contribute to the onset of sle. while females are more likely to relapse than males, the intensity of these relapses is the same for both sexes. in addition to hormonal mechanisms, specific genetic influences found on the x chromosome may also contribute to the development of sle. studies indicate that the x chromosome can determine the levels of sex hormones. a study has shown an association between klinefelter syndrome and sle. xxy males with sle have an abnormal x–y translocation resulting in the partial triplication of the par1 gene region. changing rate of disease the rate of sle in the united states increased from 1.0 in 1955 to 7.6 in 1974. whether the increase is due to better diagnosis or an increased frequency of the disease is unknown. history a historical drawing of lupus erythematosus as it was once considered as a non-fatal disfiguring skin disease. the history of sle can be divided into three periods: classical, neoclassical, and modern. in each period, research and documentation advanced the understanding and diagnosis of sle, leading to its classification as an autoimmune disease in 1851, and to the various diagnostic options and treatments now available to people with sle. the advances made by medical science in the diagnosis and treatment of sle have dramatically improved the life expectancy of a person diagnosed with sle. etymology there are several explanations ventured for the term lupus erythematosus. lupus is latin for "wolf", and in medieval latin was also used to refer to a disease of the skin, and "erythematosus" is derived from ἐρύθημα, ancient greek for "redness of the skin". all explanations originate with the reddish, butterfly-shaped malar rash that the disease classically exhibits across the nose and cheeks. the reason the term lupus was used to describe this disease comes from the mid-19th century. many diseases that caused ulceration or necrosis were given the term "lupus" due to the wound being reminiscent of a wolf's bite. this is similar to the naming of lupus vulgaris or chronic facial tuberculosis, where the lesions are ragged and punched out and are said to resemble the bite of a wolf. classical period the classical period began when the disease was first recognized in the middle ages. the term lupus is attributed to 12th-century italian physician rogerius frugard, who used it to describe ulcerating sores on the legs of people. no formal treatment for the disease existed and the resources available to physicians to help people were limited. neoclassical period the neoclassical period began in 1851 when the skin disease which is now known as discoid lupus was documented by the french physician, pierre cazenave. cazenave termed the illness lupus and added the word erythematosus to distinguish this disease from other illnesses that affected the skin except they were infectious. cazenave observed the disease in several people and made very detailed notes to assist others in its diagnosis. he was one of the first to document that lupus affected adults from adolescence into the early thirties and that facial rash is its most distinguishing feature. research and documentation of the disease continued in the neoclassical period with the work of ferdinand von hebra and his son-in-law, moritz kaposi. they documented the physical effects of lupus as well as some insights into the possibility that the disease caused internal trauma. von hebra observed that lupus symptoms could last many years and that the disease could go "dormant" after years of aggressive activity and then re-appear with symptoms following the same general pattern. these observations led hebra to term lupus a chronic disease in 1872. kaposi observed that lupus assumed two forms: the skin lesions (now known as discoid lupus) and a more aggravated form that affected not only the skin but also caused fever, arthritis, and other systemic disorders in people. the latter also presented a rash confined to the face, appearing on the cheeks and across the bridge of the nose; he called this the "butterfly rash". kaposi also observed those patients who developed the butterfly rash were often afflicted with another disease such as tuberculosis, anemia, or chlorisis which often caused death. kaposi was one of the first people to recognize what is now termed systemic lupus erythematosus in his documentation of the remitting and relapsing nature of the disease and the relationship of skin and systemic manifestations during disease activity. the 19th century's research into lupus continued with the work of sir william osler who, in 1895, published the first of his three papers about the internal complications of erythema exudativum multiforme. not all the patient cases in his paper had sle but osler's work expanded the knowledge of systemic diseases and documented extensive and critical visceral complications for several diseases including lupus. noting that many people with lupus had a disease that not only affected the skin but many other organs in the body as well, osler added the word "systemic" to the term lupus erythematosus to distinguish this type of disease from discoid lupus erythematosus. osler's second paper noted that reoccurrence is a special feature of the disease and that attacks can be sustained for months or even years. further study of the disease led to a third paper, published in 1903, documenting afflictions such as arthritis, pneumonia, the inability to form coherent ideas, delirium, and central nervous system damage as all affecting patients diagnosed with sle. modern period the modern period, beginning in 1920, saw major developments in research into the cause and treatment of discoid and systemic lupus. research conducted in the 1920s and 1930s led to the first detailed pathologic descriptions of lupus and demonstrated how the disease affected the kidney, heart, and lung tissue. a breakthrough was made in 1948 with the discovery of the le cell (the lupus erythematosus cell—a misnomer, as it occurs with other diseases as well). discovered by a team of researchers at the mayo clinic, they discovered that the white blood cells contained the nucleus of another cell that was pushing against the white's cell proper nucleus. noting that the invading nucleus was coated with antibody that allowed it to be ingested by a phagocytic or scavenger cell, they named the antibody that causes one cell to ingest another the le factor and the two nuclei cell result in the le cell. the le cell, it was determined, was a part of an anti-nuclear antibody (ana) reaction; the body produces antibodies against its own tissue. this discovery led to one of the first definitive tests for lupus since le cells are found in approximately 60% of all people diagnosed with lupus. the le cell test is rarely performed as a definitive lupus test today as le cells do not always occur in people with sle and can occur in individuals with other autoimmune diseases. their presence can help establish a diagnosis but no longer indicates a definitive sle diagnosis. the discovery of the le cell led to further research and this resulted in more definitive tests for lupus. building on the knowledge that those with sle had auto-antibodies that would attach themselves to the nuclei of normal cells, causing the immune system to send white blood cells to fight off these "invaders", a test was developed to look for the anti-nuclear antibody (ana) rather than the le cell specifically. this ana test was easier to perform and led not only to a definitive diagnosis of lupus but also many other related diseases. this discovery led to the understanding of what is now known as autoimmune diseases. to ensure that the person has lupus and not another autoimmune disease, the american college of rheumatology (acr) established a list of clinical and immunologic criteria that, in any combination, point to sle. the criteria include symptoms that the person can identify (e.g. pain) and things that a physician can detect in a physical examination and through laboratory test results. the list was originally compiled in 1971, initially revised in 1982, and further revised and improved in 2009. medical historians have theorized that people with porphyria (a disease that shares many symptoms with sle) generated folklore stories of vampires and werewolves, due to the photosensitivity, scarring, hair growth, and porphyrin brownish-red stained teeth in severe recessive forms of porphyria (or combinations of the disorder, known as dual, homozygous, or compound heterozygous porphyrias). useful medication for the disease was first found in 1894 when quinine was first reported as an effective therapy. four years later, the use of salicylates in conjunction with quinine was noted to be of still greater benefit. this was the best available treatment until the middle of the twentieth century when hench discovered the efficacy of corticosteroids in the treatment of sle. research a study called bliss-76 tested the drug belimumab, a fully human monoclonal anti-baff (or anti-blys) antibody. baff stimulates and extends the life of b lymphocytes, which produce antibodies against foreign and self-protein. it was approved by the fda in march 2011. genetically engineered immune cells are also being studied in animal models of the disease as of 2019. in september 2022, researchers at the university of erlangen-nuremberg published promising results using genetically altered immune cells to treat severely ill patients. four women and one man received transfusions of car t cells modified to attack their b cells, eliminating the aberrant ones. the therapy drove the disease into remission in all five patients, who have been off lupus medication for several months after the treatment ended. famous cases shannon boxx, u.s olympic soccer player. nick cannon, television mogul. pumpuang duangjan, thai luk thung singer. selena gomez, singer, actress, producer, and businesswoman. sally hawkins, actress. flannery o'connor, southern gothic novelist and short-story author.