Story of Lupus In Man History

 The term lupus means "wolf" in Latin (in German "wolf"). In consulting the medical writings of the ancients, it was noted that this term was used to characterize various skin conditions whose marks are reminiscent of wolf bites. It appears for the first time in medical literature in 916 AD concerning the illness of the Bishop of Liège, Eraclius, lupus, from which he was miraculously cured on the occasion of a pilgrimage to the tomb of St Martin in Tours.

Story of Lupus In Man History

History of Lupus

The observation is reported by Herbert of Tours: "He Eraclius, whom he calls Hildricus, suffered from an ulcerous disease, lupus, which manifested itself by a red line on the forehead." This type of skin condition certainly did not go unnoticed by ancient physicians. The frescoes of ancient Egypt give a fairly accurate reflection of the skin condition of the inhabitants of the Nile Valley. The study of medical papyri, dating from 1000-1700 BC, has made it possible to identify the semiological descriptions of many skin diseases.

Hippocrates, who lived on the island of Kos between 460-375 BC, described ulcerative lesions of the skin that he called Herpes Esthiomenos (Herpes spreading on the skin, Esthiomenos gnawing). Claudius Galen, a Greek physician practicing in Rome between 131-201 AD, used the name Herpes in a less vague sense to designate superficial ulcerations of the skin.

Persian physicians such as Raazes (900 AD) and Avicenna (1000 AD) described the condition under the name "formica corrosiva" which was retained by Paul Aegina, a Greek physician from the island of Aegina, and by Galen. In the writings of the famous School of Medicine of Salerno of the Middle Ages, we find the writings of Rogerius Frugarti who describes lupus characterized by swellings of the extremities. Rolandus devotes the term "noli me tangere" (do not touch me) for diseases affecting the face.

Bernard of Gordon, physician of the School of Montpellier (1305) also mentions the ulcerative form of herpes which he calls lupus. In 1500, Paracelsus introduces the term consolida lupi to describe a disease different from estthiomenos, fistula and cancer. He thus uses the term lupus vorax. Girolamo Mercurialis gives a description of lupus in his treatise "de Morbei-Cutanei" of 1572, the first work of dermatology published in Europe.

In 1750, the name lupus appeared for the first time in an American medical work "A method of Physics" by Philips Barrough. The use of the word lupus will be reserved for red eruptions of the face by Hans van Gersdorf of Strasbourg in 1577 and taken up by Jean Dolaeus in 1684.

In 1790, the British Robert Willan established a first classification of skin diseases in which we find the description of lupus which he clearly separates from "noli me tangere" and herpes. Willan wrote the first atlas of dermatology "Manual on Skin Diseases" which includes many color illustrations entirely drawn by hand, which will greatly delay its publication.

In 1808, a new edition was published in which Willan reserved the name lupus for a nodular eruption of the face that was complicated by ulcers. Two types of lupus were described, tuberculous lupus and lupus vulgaris. After Willan's premature death, his student Thomas Bateman continued his work. A new atlas of skin diseases was published in 1810 that would influence the history of dermatology. In France, the St Louis hospital in Paris developed a dermatology department in 1801, the direction of which was entrusted to Jean-Louis Alibert.

In 1832, he published a work entitled "Descriptions of Skin Diseases observed at St Louis Hospital" with 50 color engravings. In it, he describes "tartars" within which he isolates the reddening scab corresponding to the condition described by his predecessors under the name of lupus. Alibert specifies that esthiomene corresponds to Paracelsus' lupus vorax and Willan's lupus which are associated with tuberculosis.

In 1815, Alibert left the service of the St Louis hospital to Laurent Théodore Biett, a doctor of Swiss origin, who had studied dermatology with Bateman in London and who would therefore apply the classification of dermatoses according to his English masters. His collaborators, Alphée Cazenave and Henri-Edouard Schedel published in 1828 the first edition of the "Practical Abbreviations of Skin Diseases" in which the authors separated different forms of lupus: lupus which destroys on the surface, which destroys in depth and lupus with hypertrophy. They demonstrated that "noli me tangere" is of cancerous origin and therefore clearly separates this condition from lupus.

In the second edition of 1833, the chapter devoted to lupus is supplemented by a particular form which is described under the name of "Erythema centrifugum".

In 1851, Cazenave extended the description of centrifugal erythema by noting skin lesions with atrophy, telangiectasia, fixed erythema and he modified the name to "Lupus Erythematosus". Work on lupus then continued in Vienna, a center of Austro-Hungarian medicine. Ferdinand von Hebra was put in charge of the Dermatology clinic in this city in 1841.

In 1846 he described a condition affecting the face that he called "seborrhea congestiva". He described the very particular appearance of the malar rash as a "butterfly wing".

In 1866, Von Hebra would specify that the condition was identical to that which Cazenave had described under the name of Lupus erythematosus. He therefore rallied to Cazenave's thesis and definitively accepted this term which would be universally retained. The first illustration of lupus erythematosus appeared in 1856 in Von Hebra's Atlas of Skin Diseases which included numerous hand-painted illustrations by his collaborator, the Swiss Anton Elfinger.

In 1866, a young Hungarian doctor, Moriz Kohn, joined Von Hebra's service. A brilliant doctor, polyglot, talented orator, Kohn would perfect the teaching of his master Von Hebra.

In 1869, he published his first article on lupus erythematosus.

In 1871, Moriz Kohn obtained permission to change his surname to KAPOSI and it was under this identity that he continued to publish numerous works.

In 1872, in a detailed treatise, he described the existence of two types of lupus: discoid lupus, exclusively cutaneous, and a disseminated form associating systemic visceral complications including subcutaneous nodules, arthralgia, lymphadenopathy, fever, weight loss, anemia. He called this form "disseminated and aggregated lupus erythematosus". Confusion arose about the adjective disseminated which is related to the cutaneous evolution and not to the multivisceral (systemic) character of the condition.

In 1902, Sequira and Baleau in London published a review of 71 cases of lupus, including 60 discoid and 11 disseminated. They noted the existence in this latter group of a frequency of acroasphyxia (which would later be better known as Raynaud's phenomenon), renal damage as well as pleurisy (pericarditis. Jadasshon, a German dermatologist practicing in Berne, Switzerland, contributed in 1904 to the replacement of the term "disseminated lupus erythematosus" by that of "systemic lupus erythematosus" or better "lupus disease". Sir Williams Osler would confirm the concept of systemic lupus thanks to numerous publications between 1895 and 1904. In 1936, CK Friedberg described the existence of lupus disease without cutaneous manifestations.

Systemic lupus seems to have existed since ancient times. Indeed, a group of researchers under the direction of Marvin Alison and Alejandro Pezza from the Inca Museum in Peru were able to carefully examine a mummy of a 14-year-old girl, dating from 890 BC, whose examination revealed alopecia, pleurisy and pericarditis, glomerulonephritis compatible with systemic lupus. Reproductions of lupus disease are also found in paintings by old masters.

Thus, Rembrandt in 1634 painted the portrait of Maria Bockenolle, the wife of Pastor Elison, in which one can notice the red rash on the face and the joint deformation of the hand.

At the Louvre Museum, one can admire the painting by the French painter Simeon Chardin from 1740, a copy of which from 1746 is in the Hermitage Museum in St. Petersburg, the "Benedicité" on which one can observe the erythema of the little girl's face.

The 20th century opened the era of lupus biology. In 1910, Hank reported the positivity of the Wasserman complement fixation reaction with the serum of lupus patients. In 1846, Hargraves discovered, in the sternal marrow of lupus patients, the presence of particular cells consisting of neutrophil polymorphonuclear cells having phagocytosed the nucleus of another cell which were called LE cells. The following year, Haserick showed that the serum of lupus patients was capable of causing the formation of LE cells with cells from the marrow of normal subjects.

In 1954, Peter Miescher, a Swiss immunologist, succeeded in absorbing serum factor LE with thymus cell nuclei, thus demonstrating that the factor was an anti-nuclear antibody.

In 1957, it was shown that these antibodies reacted with nucleoproteins, that is, the constitutional subunit of chromatin. The same year, Maxime Seligman in Paris showed that the serum of lupus patients causes a precipitate with DNA. This was confirmed by the German Deicher in Henri Kunkel's laboratory and by the Italian Ceppelini. Thus anti-DNA became the specific serological markers of lupus. An important discovery was to revolutionize the practice of immunology.

This is the development by Coons in 1953 of the immunofluorescence technique.

Friou applied it in 1957 to the search for anti-nuclear antibodies but it would not become widespread until 1968 when the first microscopes equipped with UV lighting became widespread in laboratories. From 1975 onwards, the search for anti-nuclear antibodies was carried out on Hep-2 cells, a substrate still used today.

In 1961, Anderson in Glasgow, will show that the antibodies present in the serum of lupus patients precipitated soluble extracts of thymus nuclei. This is the start of work on anti-ENA antibodies for "Extractable Nuclear Antigens", i.e. soluble antigens of the nucleus. In 1966, Tan identified in a lupus patient, Mrs Smith, a first anti-ENA, which was called anti-Sm. Other specificities will be identified in the following years. The sophistication and standardization of anti-nuclear antibody detection techniques will lead to genuine diagnostic progress in lupus disease.

Dermatological lupus has been the subject of treatment attempts since antiquity. At the beginning of the 15th century, the German physician Johan Tollat ​​von Vorchenberg wrote "for lupus caprifolin", that is to say honeysuckle. Medicine at the time used a very rich pharmacopoeia borrowed from the plant and mineral kingdoms. Jonathan Hutchinson, 1880, proposed cod liver oil, arsenic, zinc chloride and mercury nitrate. Anderson added the application of iodine. Gold salts were introduced in 1913 for the treatment of discoid lupus. For that of systemic lupus, quinidine was introduced by JF Payne in 1894, aspirin was used in 1899 by Radcliffe-Crocker and quinine by Mac Lead in 1908.

In 1956, plaquenil was introduced, which is still widely used today.

In 1935, Edward Kendall isolated cortisone, which was used to treat lupus by Hensch. From 1952, immunomodulators such as cyclophosphamide, mycophenolate, azathioprine, and then monoclonals such as rituximab were used. Other therapies are under development.

The first descriptions of lupus focused on dermatological manifestations. Various varieties of cutaneous lupus have been described by dermatologists.

At the end of the 19th century, it was realized that some lupus could be complicated by diffuse visceral manifestations and the dermis of systemic lupus erythematosus replaced that of disseminated lupus erythematosus. Thanks to the development of our knowledge in immunology, it was demonstrated at the end of the 20th century that lupus disease is an autoimmune disease. Immunological tests were developed that allow a precise diagnosis of systemic lupus. On the other hand, the knowledge acquired about the etiology of the disease will allow the implementation of increasingly effective targeted therapies.

Prof. René-Louis HUMBEL

Laboratory of Immunopathology, Luxembourg


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