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Dr. Obar: This paper is focused on revising and rewriting the section on the history and culture for Systemic Lupus Erythematosus (SLE). The link to the original article can be found here: Systemic Lupus Erythematosus

HISTORY OF SLE
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 SLE patients. The advances made by medical science in the diagnosis and treatment of SLE has dramatically improved the life expectancy of a person diagnosed with SLE.

Classical Period
The classical period began when the disease was first recognized in the Middle Ages. The term lupus is attributed to 12th-centry Italian physician Rogerius Frugard, who used it describe ulcerating sores on the legs of patients. No formal treatment for the disease existed and the resources available to physicians to relieve the suffering of their patients was limited.

Neoclassical Period
The neoclassical period began in 1851 when the skin disease now known as discoid lupus was documented by 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 but were also infectious. Cazenave observed the disease in several patients and made very detailed notes to assist others in itsdiagnosis. He was one of the first to document that lupus affected adults from adolescence into the early thirties and that the 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 patients. 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" (or malar rash) often were afflicted with another disease such as tuberculosis, anemia, or chlorisis which often caused death. Kaposi was one of the first persons 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 suffered from 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 patients 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 major 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 anti-body 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 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 for LE cells are found in approximately 60% of all people diagnosed with lupus. (Note: The LE cell test is rarely performed as a definitive lupus test today as LE cells do not always occur in lupus patients and can occur in individuals with other autoimmune diseases.  Their presence, however, can be helpful in establishing a diagnosis but is 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 for lupus but also many other related diseases. This discovery led to the development of what are now known as autoimmune diseases.

To ensure that the patient 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 patient 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.