The History of Lupus

The term Lupus means “wolf” in Latin (in German “wolf »). In consulting medical writing of the ancients is noted that this term used to characterize various affection of skin that the lesion are reminiscent of wolf bite. It appears for the first time in medical literature in 916 AD about the illness of the Bishop of Liege, Eraclius, Lupus, which he was miraculously cured during a pilgrimage to the grave of St. Martin in Tours. This type of skin condition has not gone unnoticed by the doctors of Antiquity. Frescoes of Ancient Egypt give a reflection fairly exact of skin condition of the inhabitants of the Nile Valley. The Study of medical papyrus, dating from 1000-1700 AD, permit to identify semiologic descriptions of many skin diseases. Hippocrates lived on Kos Island between 460-375 BC described ulcerative skin lesions call Herpes Esthiomenos (Herpes which extends over the skin, Esthiomenos which gnaws). Claudius Galen, Greek physician practicing in Rome between 131-201 AD is used the name Herpes in a less indeterminate sense to refer to superficial ulcerations of the skin. Persian physician as Raazes and Avicenna describe the condition known as « formica corrosiva » which will be retained by Paul Aegina, a Greek physician of the island of Aegina, and Galen. In the writings of the famous medical school of Salerno in the Middle Ages we find the writing of Rogerius Frugarti describes lupus characterized by blistering of the extremities.Rolandus devotes appellation of “Noli Me Tangere” (do not touch me) for skin diseases. Bernard de Gordon, physician of Montpellier School (1305) also mentions the ulcerous form of herpes who calls Lupus. In 1500, Paracelse submit the term of « consolida lupi » for describe a disease different of esthiomenos, fistula or cancer. He uses the term of « lupus vorax ». Girolamo Mercurialis gives an description of lupus in his treatise “Morbei-Cutanei” of 1572, the first book of dermatology published in Europe.

                           In 1950, the name of Lupus appears for the first time in an American medical book “A method of Physick” of Philips Barrough. The used of the word Lupus will be reserve for red rash of the face, by Hans van Gersdorf of Strasbourg in 1577 and used again by Jean Dolaeus in 1684. In 1790, the British Robert Willan established an initial classification of skin diseases in which there is the description of Lupus that he clearly separates of “Noli Me Tangere” and of herpes. Willan writes the first atlas of dermatology “Manual on Skin Diseases” which it includes many colour illustrations entirely hand-drawn by hand, which will relay its release. In 1808, a new edition is published in which Willan reserve the denomination of Lupus to nodular rash which is complicated by ulcerations. Two type of Lupus are described,  LupusTuberculosis and Lupus Vulgaris . After the untimely death of Willan, his student Thomas Bateman actively continues his work. A new atlas of skin diseases will emerge in 1810 that will influence the history of dermatology. In France, St Louis Hospital of Paris, develops a dermatology department in 1801 which is entrusted the management to Jean-Louis Alibert. This one published, in 1832, a book entitled “Descriptions of Skin Diseases observed in Hospital St Louis” with 50 coloured engravings. He makes the description of “the scabs” in which he isolates the red patches corresponding to affection described by his predecessor as Lupus.Alibert precise that Esthiomenos corresponding to Vorax Lupus of Paracelse and Lupus of Willan which are associated to Tuberculosis. In 1815, Alibert leaves the service at St Louis to Lawrence Theodore Biett, a Swiss-born physician, which has studied the dermatology with Bateman in London and he will apply the classification of dermatitis according to his English masters. His collaborators, Alphée Cazenave and Henri-Edouard Schedel publish in 1833 the first edition of « Abbreviated pratices of skin diseases » in which the authors divide different forms of Lupus : Lupus destroyed in depth and Lupus with hypertrophy. They demonstrate that « Noli Me Tangere » is cancerous origin and seperate thus clearly  this affection of Lupus. In the second edition of 1833, the chapter devoted to Lupus is completed by an particular form which is described under the name « Erythema Centrifugum ».

                          In 1851, Cazenave extends the description of Erythema Centrifugum noting the skin lesions with atrophy, telangiectasias, erythema fixed and he changes the appellation  » Lupus Erythematosus ». The works on Lupus will then continue to Vienna, top-place of the Austro-Hungarian medicine. Ferdinand von Hebra is responsible in 1841 of the Dermatology Clinic of this city. He describes in 1846 an affection that affects the face which calls “seborrhea congestiva”. He describes the particular aspect of malar rash in “butterfly wing”. In 1866, Von Hebra will specify that affection is identical to that Cazenave described under the name of « Lupus Erythematosus”.Thus he supported the thesis of Cazenave and accepts definitively this term which will be universally retained. The first illustration of Lupus Erythematosus appears in 1856 in atlas of Skin Diseases of Von Hebra which includes many hand-painted illustrations by his collaborator, the Swiss Anton Elfinger. In 1866, a young Hungarian physician, Moriz Kohn, joined the Skin Service of Von Hebra. Brilliant physician, polyglot, talented speaker, Kohn will improve the teaching of his master Von Hebra. He published, in 1869, the first article on Lupus Erythematosus. In 1871, Moritz Kohn gets approval to change its surname in KAPOSI and it’s under this identity that he will continue to publish numerous works. In 1872, in a detailed treaty, he described the existence of two types of Lupus : discoid Lupus, exclusively cutaneous, and a disseminate form associating of visceral systemic complications such as nodules subcutaneous, arthralgia, lymphadenopathy, fever, weight loss, anemia.He calls this form : Lupus Erythematosus disseminated and aggregated. A confusion will arise about the adjective disseminated which is in connection with the evolution of cutaneous rash and not to the multi-organ nature (systemic) of affection.In 1902, Sequira and Balean in London will publish a review of 71 case of Lupus whose 60 discoid and 11 disseminate.They report the existence in the latter group with a frequency of acroasphyxia (which will be later better known as Raynaud’s phenomenon), a renal impairment and pleurisy / pericarditis. Jadassohn, German dermatologist practicing in Berne in Switzerland, in 1904 contributes to the substitution of the term of “Lupus Erythematosus disseminated” by “Lupus Erythematosus Systemic” or better “Lupus disease”. Sir Williams Osler will confirm the concept of Lupus Systemic thanks to many publications between 1895 and 1904. In 1936, CK Friedberg described the existence of lupus disease without cutaneous manifestations. Lupus Systemic seems to have existed since antiquity. Indeed, a group of researchers under the direction of Marvin Alison and Alejandro Pezza of Incas Museum of Peru were able to examine carefully a mummy of a 14 years old girl, dating from 890 BC, whose examination revealed alopecia, pericarditis, glomerulonephritis compatible with a Lupus Systemic.

                     We also find reproductions of Lupus disease in the paintings of the great masters.So, in 1634 Rembrandt painted the portrait of Maria Bockenolle, the wife of Pastor Elison, in which we can notice a red rash on the face and joint deformity of the hand. At the Louvre Museum, we can admire the picture of French painter Simeon Chardin of 1746 and which a copy of 1746 is at Hermitage Museum of St Petersburg, the « grace » in which we can observe the facial erythema of the little girl.The twentieth century opens the era of the biology of lupus. In 1910, Hanck indicates the positivity of the reaction of complement’s fixation of Wasserman with the serum of lupus patient. In 1948, Hargraves discovered, in the sternal marrow of lupus, the presence of particular cells formed of polymorphonuclear neutrophils that phagocytosed the nucleus of another cell who were called LE cells.The following year, Haserick shows that the serum of lupus patient was able of causing the formation of LE cells with cells of marrow of normal subjects. In 1954, Peter Miescher, a Swiss immunologist, managed to absorb the LE serum factor with thymus nuclei showing that the factor was antibodies anti-nuclear.In 1957, it could be shown that these antibodies reacted with nucleoprotein, that is to say the constitutional subunit of chromatin. The same year, Maxime Seligman in Paris, showed that the serum of Lupus disease causes a precipitate with DNA. This was confirmed by the German Deischer in the laboratory of Henry Kunkel and by the Italian Ceppelini. Thus the anti-DNA became the specific serological markers of Lupus. An important discovery will revolutionize the practice of immunology. It is an important discovery, in 1953, it’s the development of the immunofluorescence technique realized by Coons. Friou applied it, in 1957, in search of antinuclear antibodies but it becomes widespread until 1968 when the first microscopes equipped with a UV light will spread in laboratories. From 1975, the research of antinuclear antibodies will be on cultures of Hep-2 cells. substrate still used today.

                          In 1961, Anderson in Glasgow, will show that the antibodies present in the serum of lupus disease precipitated soluble extracts thymus nuclei. It is the starting of work on anti-ENA “Extractable Nuclear Antigens” antibodies that is to say soluble antigens of nuclei. In 1966, Tan identifies in a Lupus patient, Mrs. Smith, a first anti-ENA which was called anti-Sm. Other specifics will be identified in subsequent years. The sophistication and standardization of detection techniques of antinuclear antibodies will bring genuine diagnostic advances in lupus. Dermatological Lupus has been the subject of treatment attempts since antiquity. At the beginning of fifteenth century, the German physician Johan Tollat Von Vorchenberg wrote “For Lupus (“Wolf” in German) caprifolin”, that is to say honeysuckle. The medicine at the time used a rich pharmacopoeia borrowed from vegetable and mineral kingdoms. Jonathan Hutchinson, 1880, proposes cod liver oil, arsenic, zinc chloride and mercury nitrate. Anderson proposes the application of iodine. Gold salts were introduced in 1913 for the treatment of discoid lupus. For the treatment of Lupus Systemic the quinidine is introduced by JF Paynes in 1894, aspirin is used in 1899 by Radcliffe-Crocker and the quinine by Mac Lead in 1908. In 1956, it is the introduction of Plaquenil is widely used today. In 1935 Edward Kendall isolates the cortisone which will be used for the treatment for Lupus by Hensch. From 1952, we use immunomodulators such as cyclophosphamide, mycophenolate, azathioprine, then monoclonal as rituximab. Other therapies are being developed. The first descriptions of Lupus relate to dermatological manifestations. Different varieties of cutaneous lupus have been described by dermatologists. At the end of nineteenth century we see that some Lupus could be complicated by diffuse visceral manifestations and the term Lupus Erythematosus Systemic will be substituted to Lupus Erythematosus Disseminate.Thanks to the development of our knowledge in immunology, we will demonstrate at the end of twentieth century that the Lupus disease is an autoimmune disease. Immunologic tests have been developed which allow a precise diagnosis of Lupus Systemic. And the other hands, the knowledge of the etiology of the disease will allow the implementation of targeted therapies more and more effective.