ESHDV Special Annual Lecture, Geneva, October 11th, 2000

The History of Urticaria and Angioedema

Professor Lennart Juhlin,
Department of Dermatology, University Hospital, Uppsala, Sweden

Probably the most early description of the disease we today call urticaria is found in "The Yellow Emperor's Inner Classic", Huang Di Nei Jing, which was written sometimes between 1000-200 years before Christ (1, 2). In chapter 64 of Basic questions (Sin Wen) urticaria is called "Feng Yin Zheng" which means wind-type concealed rash. This is still the Chinese word for urticaria which was thought to be due to excess in lesser Yin which causes obstruction of fluid in the skin.

Hippokrates who lived 460-377 BC described elevated itching lesions caused by nettles and mosquitoes which he called knidosis after the Greek word for nettle (knido). He also mentions that the weals can occur in patients with gastrointestinal disorders but then often with less itching. The same name was again introduced by Jean-Louis Alibert in Paris in his book on skin diseases published in 1833 (3). Hebra used the term knidosis for the chronic type of nettle rash whereas in Andrew's and Domonko's textbook from 1963 it is used synonymously with urticaria.

Plinius (32-79 AD) introduced the name uredo which means burning. The term was used by Latin speaking doctors such as Carl von Linné for "red, evanescent itching eruptions".

In the 10th century Ali Ibu Al-Abba called it essera which in the Persian language means elevation. With the decline of the Roman empire this term was used for centuries in both the Arabic and the European world.

Thomas More in his book "King Richard III" gives an excellent description of the condition without giving it a name (4). However, it is of interest since it is the first case of urticaria reported to cause death. In 1480 before the coronation of King Richard the lords wanted to please him by serving him a cup of strawberries. A few hours later he suddenly assembled the lords, opened his shirt and showed his chest which was covered with red elevated and itching spots. He accused one of the lords for trying to poison him and had him assassinated on the spot.

Zedler in his "Grosses vollständige Universallexikon" from 1734-1740 changed uredo to urticatio (5). The word urticaria was first introduced in 1769 by William Cullen in his book "Synopsia Nosalogiae Methodica" (6). It also appeared in the first edition of Encyclopaedia Britannica (1771) written by a pseudonym "A society of Gentlemen in Scotland". The term urticaria was later accepted by Peter Frank in Vienna and other centres. Cullen was Professor of Medicine in Edinburgh and had started to classify the skin disorders as Linné had done for the plants. He was a Quaker as were several of the doctors from the University of Pennsylvania who came to visit him (7). Philadelphia is still called the Quaker City, and here the first medical school in North America was founded in 1765. The first professors were all trained in Edinburgh.

Robert Wilan from England was also a Quaker and could therefore not be allowed to study in Oxford or Cambridge. He started his medical education 1777 in Edinburgh and become influenced by the ideas of Cullen on classification of skin disorders. In 1783 Willan returned to London where he soon was appointed physician to a newly established Public Dispensory in Carey Street. Here he saw a lot of poor people and also visited their home. Willan was kind to his patients, a sincere and reserved man, a good teacher and had an intense dislike for alcohol which was a common cause of premature death among his patients. He was especially interested in skin disorders and perfected the classification of cutaneous diseases based on the morphology of the lesions. He had read a book by Josef Plenck on the subject published in 1776 but since it was a mixture of lesion type, location and etiology he did not cite it (8). Willan's findings started order in the existing classification and were published in parts between 1798 and 1808 (9).

In 1801 he met Thomas Bateman who had just finished his medical studies in Edinburgh. He joined him in the dispensory. Bateman was very religious and fond of music. He was said never to waste a minute and his pen was always in his hand. Bateman grasped Willan's approach to skin problems and soon become his trusted assistant, friend and finally successor. Willan was stricken by a heart problem at the height of his fame. In 1811 he retired and sailed for Madeira to get cured, but died there at the age of 55. His work was completed by Bateman in an influential masterwork "A Practical Synopsis of Cutaneous Diseases" published 1813 and translated into many languages (10). Here different types of urticaria were described: 1. Urticaria febrilis, where the patient has fever and abdominal pain for some days before the skin lesions appear. This urticaria usually last for a week; 2. Urticaria evanida where new lesions can continue to appear for many months or years and mainly itching at night. It thus corresponds to chronic urticaria; 3. Urticaria perstans where the single central weal remains for some days and feels hard. The initial reddening around the weal disappears early. The description corresponds to urticarial vasculitis. Bateman also described lichen urticatus or papular urticaria in children, which he differentiated from the urticarias.

However, not everyone accepted their system. One was Jean Louis Alibert who was the leading dermatologist in Paris at this time. As mentioned before he preferred the Greek word knidosis for urticaria and wanted a new classification since Willan's study was based on outpatients without a follow-up of possible etiology. Alibert was an excellent teacher and observer who attracted doctors from all over Europe to Hopital Saint-Louis. When the lecture room become too small, he lectured in the hospital garden under the trees. Alibert stood on a wooden platform and called up the patients by name of the disease (11, 12). A book on skin diseases by Alibert was admired by King Ludvig XVIII and he was appointed the King's personal physician, which meant an important social position. After the death of King Ludvig, King Charles X kept him as physician and he was rewarded by the title Baron. He therefore left his department for many years. Laurent Biett, his best pupil, took over. He visited Bateman in 1816 and reintroduced the Willan-Bateman method in Paris. When Baron Alibert returned to St Louis in 1829 he tried to introduce his construction of a tree with dermatosis on the branches, but failed since it was too complicated and useless (33).

Several physical urticarias were early mentioned: Solar urticaria was described by Borsch in 1799 but it was not until 1887 that Veiel showed that it was only solar rays and not heat from a stove or candle that was responsible (13, 14). Factitial urticaria was first documented in the middle-ages since people with this condition were beheaded or burnt alive because they were assumed to be related to the devil (15). In the medical literature it was described by Heberden in 1767 and Gull coined the name factitious urticaria in 1859 (16, 17). Cold urticaria was described by Frank in 1792 (18). Urticaria caused by heat and mental or physical exertion was published in 1924 in JAMA by Duke (19). Pressure urticaria was described by Urbach and Fasal in 1929 (20). Aquagenic urticaria was reported by Shelley and Rawnsley in 1964 and adrenergic urticaria by Shelley & Shelley in 1985 (21, 22).

Urticaria pigmentosa was described by Edward Nettleship early in this career (1869) before he specialized in ophthalmology (23). He called it chronic urticaria leaving brown stains. Sangster named it urticaria pigmentosa and Unna discovered the mast cells in the lesions (24, 25).

Angio-oedema was described 1586 by Marcello Donati in a young count who was sensitive to egg (26). Hereditary angio-oedema was reported by Osler in 1885 (27). It was a fatal case due to suffocation which in the family was a common cause of death. In Sweden the cause of death has been registered by the church. Therefore, Arnoldsson et al in 1966, could trace a family back to the 17th century (28). Donaldson and Evans in 1963 found that these patients could have low levels of the inhibitor to C1 esterase which caused the swelling (29).

How about Heinrich Iraneus Quinke? He became Professor in Kiel in 1878 where he remained for 30 years. He made significant contributions on various internal disorders and introduced lumbar puncture as a diagnostic and therapeutic aid. Quincke also introduced new apparatuses into medicine. One of his doctoral students Eugen Dinkellacker published a thesis in 1882 on acute oedema with 12 references to previous reports. Quincke wrote the same year a summary of it (30). It appeared as an original report but had no references to the previous reports although he was well aware of their existence. To honour Quinke, Dr F Mendel in 1902 published a paper in Berliner Woshensschrift on circumscribed oedema and proposed the name Quinke oedema. Within the same year this name was used all over the world which means that it is possible to get your name attached to a disease if you are just clever enough.

I would also shortly like to mention some important findings on the pathophysiology of urticaria. Jean Astruc (1684-1766) founder of modern dermatology and histology, showed that the weal was due to a local obstruction of oedema. The French author EJ Marey sent Lister a paper where he in 1858 described the triple response but he did not mention where it had been published (32). Imidizolethylamine was synthetized by Windaus and Vogt (33). Dale and Laidlow showed that the tissue contained an amine which affected smooth muscles and vessels. They called it histamine (34). The first antihistaminic compound was discovered by Bovet and Staub (35). Recent advances in diagnosis and treatment have been the use of the RAST, the corticosteroids and the non or less sedating antihistamines.




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