Description

Behçet disease is a chronic and multisystemic inflammatory condition involving small and large vessels of unknown aetiology. It is characterised by the classical triad originally described by Hulusi Behçet (1937) of recurrent oral aphthous ulcers, genital ulcers, and ocular lesions – iridocyclitis with or without hypopyon – which may not always be present.

Other clinical findings may include erythema nodosum, thrombophlebitis, arthralgia, neurological abnormalitis, and gastrointestinal features.

The diagnostic criteria by the International Working Group for Behçet Disease includes ‘oral ulceration plus any two of genital ulceration, typical defined eye lesions, typical defined skin lesions, or a positive pathergy test’.


History

~5th century B.C. Hippocrates of Kos (460-377 B.C.) described an endemic disease with the triad of symptoms associated with Behçet disease in his book ‘Epidemics III’ (case 7), which was likely the first reported description of the disease.

But there were also other fevers, as it will be described. Many had their mouths affected with aphthous ulcerations. There were also many defluxions about the genital parts, and ulcerations, boils (phymata), externally and internally about the groins. Watery ophthalmies of a chronic character, with pains; fungous excrescences of the eyelids, externally and internally, called fici, which destroyed the sight of many persons…

Several case reports described similar features to the classical triad of Behçet disease, but all attributing the clinical findings to tuberculosis, syphilis, septic metastases, other infection, allergy or coincidence, rather than a separate disease entity.

Published reports pre-Behçet [1772-1937]
  • 1772 – Janin observed a male patient with recurrent hypopyon and iritis in France
  • 1895 – Christlieb observed one female patient with recurrent orogenital aphthous ulceration in Germany.
  • 1895 – Neumann reported 11 female patients in Austria with recurrent oral aphthous and genital ulcers.
  • 1906 – Reis in Germany reported a male patient with recurrent ocular inflammation, erythema nodosum, and monoarthritis.
  • 1908 – Blüthe reported four patients (three male and one female) with recurrent hypopyon and iridocyclitis, mucocutaneous lesions, orchitis, arthritis, and uveitis with optic nerve atrophy on histology.
  • 1920 – Gilbert suggested staphylococcus infection, iridocyclitis septica, or opthalmia lenta as causes of recurrent uveitis, cutaneous lesions, arthritis, and middle ear infections in three male patients from Germany. Further reports in 1921 and 1923
  • 1922 – Planner and Remenowsky reported iritis, and genital lesions in one female patient from Austria, describing the disease as ‘apthosis
  • 1923 – Weve suggested a staphylococcal infection in a female patient from the Netherlands with recurrent hypopyon-iridocyclitis, mucocutaneous lesions, periodontitis, maxillary sinus empyema, and neurological signs.
  • 1924 – Shigeta described a male patient from Japan with hypopyon-iridocyclitis, histological uveitis and optic nerve atrophy, and recurrent mucocutaneous lesions.
  • 1925 – Pils published one female patient from Vienna with mucocutaneous lesions, thrombophlebitis, and arthralgia correlated with menstruation.
  • 1926 – Grütz reported one female patient with four normal births, presenting with recurrent genital ulcers, depression, and deterioration pre-delivery.
  • 1928 – Carol and Puys described a female patient from the Netherlands with recurrent genital lesions and arthralgia.
  • 1929 – Samek and Fisher pioneered the use of the pathergy test (ulcerations with minimal skin trauma) in a female patient from Prague with recurrent mucocutaneous lesions and erythema nodosum.
  • 1930 – Walter and Roman, along with Kumer separately identified histological evidence of leukocytoclastic vasculitis in genital ulcers and skin lesions from two and one female patients with recurrent mucocutaneous lesions from Poland and Austria, respectively.
  • 1932 – Dascalopoulos suggested that uveitis recidivans aphthosa as the cause of two male patients in Greece with recurrent hypopyon-iridocyclitis, orogenital ulcers, and haemoptysis.
  • 1934 – Whitwell reported two female and one male from London with mucocutaneous lesions and iritis.
  • 1936 – Nishimura reported a Japanese female patient with orogenital aphthous ulcers and iritis.
  • 1937 – Blobner, in Prague, identified a male patient with recurrent hypopyon-iritis, erythema nodosum, arthralgia, headaches, and a positive pathergy test.

1931 – Benediktos Adamantiades (1875–1962), a Greek ophthalmologist, presented a 20 year-old male patient at a medical conference in Athens who developed oedema and ulceration of the left leg (diagnosed as thrombophlebitis), which then progressed to recurrent episodes of scrotal ulcers, mouth aphthous ulcers, sterile arthritis of knees, and iritis with hypopyon bilaterally, eventually leading to optic nerve atrophy and blindness. Adamantiades thought that the recurrent ocular inflammation was part of a new clinical entity.

1937Hulusi Behçet (1889 – 1948) published two cases with the clinical triad of lesions in the mouth, genitalia, conjunctivae, and inflammation of the iris, which were either simultaneous or periodic, and relapsed several times a year. He postulated a new systemic disease of viral aetiology after investigation for numerous differential diagnoses, such as tuberculosis, syphilis, diphtheria, simple ulcers, Nicolas-Favre syndrome, and several other dermatological conditions, were negative.

  • Behçet Case 1: Otherwise healthy 40 year-old man with ulceration of his mouth, scrotum and cornea (traumatic); and perikeratitis and iritis over the preceding 20 years. Other physicians who consulted the patient prior thought the manifestations were of tuberculosis, syphilis, or parasites, and treatment with gold and arsenic seemed to reduce relapses initially. The patient underwent several iridectomies, but eventually became blind.
  • Behçet Case 2: 34 year-old woman, otherwise well with healthy children, who had a seven year history of relapsing painful lesions starting on the tongue then spreading throughout the mouth, and eventually involving the genitalia (vulva). Corneal erosions and episcleritis were also observed. Each relapse lasted up to one month. Biopsies of the orogenital ulcers on microscopy showed chronic inflammation, vessel wall thickening and elementary viral particles that was negative on subsequent biopsies.

The cases which are considered here exhibit the following clinical picture: lesions in the mouth, on the genitalia, and of the eyes…the lesions of the relapses which occurred several times a year appeared either simultaneously or successively in the mouth, on the genitalia, on the conjunctiva, and even as an inflammation of the iris

Behçet 1937

1938 – Behçet published another case of a male patient with oral pemphigus-like lesions, scrotal ulcers, eye irritation, acneiform lesions on the back, fevers, abdominal pain, and a dental cyst.

  • Behçet H. Considerations sur les lesions aphtheuses de la bouche et des parties genitals, ainsi que sur les manifestations oculaires d’origine probablement virutique et observations concernant leur foyer d’infection. Bull Soc Fr Dermatol Syphiligr. 1938;45:420–433.

1938-40 – Behçet published four additional cases separately in German, French and English with what he named the ‘triple symptom complex’. He observed additional characteristics of acneiform skin lesions, erythema nodosum, periodontitis, and arthralgia as part of what he argued was a new disease of potential viral aetiology. In his 1940 English publication, Behçet referred to the cases reported by Adamantiades (1931), Wewe (1923), and Blobner (1937) whom he stated considered the ocular inflammation separately and not as another manifestation along with skin and mucocutaneous symptoms.

1941 – Jensen observed a case with the triple symptom complex and ulcerous hemorrhagic colitis. He used the term ‘Behçet’s syndrome’’ to describe the disease for the first time, and also established the pathergy test as a diagnostic criterion.

1944-47 – Multiple authors around the world published case reports with the ‘triple symptom complex’ and referred to the disease using Behçet’s name.

1947 – At the International Dermatology Congress in Switzerland, Professor Guido Mischner (Director of Dermatology, Zürich Medicine Faculty) suggested the disease to be named ‘Morbus Behçet’.

1990 – The International Study Group for Behçet disease proposed a diagnostic criteria including major and minor features for the condition.


Associated Persons

Alternative names
  • Behçet syndrome
  • Morbus Behçet (1947)
  • Adamantiades-Behçet disease
  • Silk Road disease
  • Gilbert-Behçet disease

Controversies

The naming of Behçet disease has been debated due to several case reports prior to Dr Hulusi Behçet’s publication in 1937 describing patients with the disease. However, Dr Behçet was the first to identify the ‘triple symptom complex’ as a separate new entity.

Several authors refer to Behçet disease as Adamantiades-Behçet disease to acknowledge Adamantiades’ proposed idea that the recurrent iridocyclitis observed was part of a new disease. However, this does not encompass the clinical triad of Behçet disease, and Adamantiades (1875-1962) himself referred to the disease as Behcet syndrome in a later publication (1949) on the ocular manifestations.


References
References: pre-Behçet [1772-1937]
  • Janin J. Memoires et Observations anatomiques, physiologiques et physiques sur l’oeil, et sur les maladies qui affectent cet organe. 1772: 412–414.
  • Christlieb O. Über Stomatitis und Vulvitis aphthosa. Inaugural-Dissertation. Würzburg, 1895
  • Neumann I. Die Aphthen am weiblichen Genitale. Wien Klin Rundsch. 1895; 9: 289-307.
  • Reis W. Augenerkrankung und Erythema nodosum. Klin Monatsbl Augenheilkd 1906; 44: 203–206.
  • Blüthe L. Zur Kenntnis des rezidivierenden Hypopyons. Thesis, D Strauss, Heidelberg. 1908
  • Gilbert W. Über die rezidivierende eitrige Iridozyklitis (I. septica) und ihre Beziehungen zur septischen Allgemeinerkrankung. Arch Augenheilkd. 1920; 86: 29–49.
  • Gilbert W. Über den pathologisch-anatomischen Befund bei Iridocyclitis septica (Iritis mit rezidivierendem Hypopyon). Arch Augenheilkd. 1921;87:27–34.
  • Gilbert W. Zur Frage der Iridozyklitis mit rezidivierendem Hypopyon (‘‘Iritis septica’’). Klin Monatsbl Augenheilkd. 1923; 71: 409–414.
  • Planner H, Remenowsky F. Beiträge zur Kenntnis der Ulcerationen am außeren weiblichen Genitale. Arch Dermatol Syphil (Berlin) 1922; 140: 162–188.
  • Weve H. Uber rezidivierende allergische. Staphylokokkenuveitis. Arch Augenheilkd 1923; 93: 14–39.
  • Shigeta T. Recurrent iritis with hypopyon and its pathological findings. Acta Soc Ophthalmol Jpn 1924; 28: 516–522.
  • Pils H. Ein Beitrag zur Aphthosis. Arch Dermatol Syph (Berlin). 1925; 149: 4-8.
  • Grütz O. Stomatitis et vulvitis aphthosa chronica rezidivans (blastomycetica)? Zbl Haut. 1926; 20: 415-416.
  • Carol WLL, Ruys SC. Over aphthosis en ulcus vulvae acutum. Ned Tschr Genek I. 1928: 396-406.
  • Samek J, Fischer E. Erythema nodosum als bakterielle Metastase eines Ulcus vulvae acutum. Arch Dermatol Syph (Berlin). 1929; 158: 729-733.
  • Kumer L. Über Haut- und Mundschleimhauterscheinungen beim Ulcus vulvae acutum. Dermatol Z. 1930; 57: 401-411.
  • Walter F, Roman I. Beitrag zur Kenntnis der haÈmatogenen Hautmetastasen bei Ulcus vulvae acutum. Dermatol Wochenschr. 1930; 90: 705-709.
  • Adamantiades B. A case of relapsing iritis with hypopyon (in Greek). Archia Iatrikis Etairias, (Proceedings of the Medical Society of Athens). Athens 1930; 586–593.
  • Adamantiades B. Sur un cas d’iritis à hypopyon récidivant. Annales d’oculistique, 1931; 168: 271-78
  • Dascalopoulos N. Sur deux cas d’uv´eite r´ecidivante. Ann Ocul (Paris) 1932; 169: 387–389.
  • Whitwell GP. Recurrent buccal and vulvar ulcers with associated embolic phenomenon in skin and eye. Br J Dermatol 1934; 46: 414–419.
  • Nishimura M. A case of ulcus vulvae acutum with aphthae-like lesions in the mucous membranes of the mouth associated with acute iritis. Arch Dermatol Syphil (Chicago) 1936; 34: 900.
  • Blobner F. Zur rezidivierenden Hypopyoniritis. Z Augenheilkd. 1937;91:129–139.
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Doctor in Australia. Keen interest in internal medicine, medical education, and medical history.

Emergency physician MA (Oxon) MBChB (Edin) FACEM FFSEM with a passion for rugby; medical history; medical education; and asynchronous learning #FOAMed evangelist. Co-founder and CTO of Life in the Fast lane | Eponyms | Books |

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