Behçet Disease

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.

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.

• Adamantiades B. Sur un cas d’iritis à hypopyon récidivant. Annales d’oculistique, 1931; 168: 271-78

1937 – Hulusi 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

• Behçet H. Über rezidivierende, aphtöse, durch ein Virus verursachte Geschwüre am Mund, am Auge und an den Genitalien [On relapsing, aphthous ulcers of the mouth, eye and genitalia caused by a virus]. Dermatologische Wochenschrift. 1937;105:1152–63.

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.

• Behçet H. Kurze Mitteilung über Fokalsepsis mit aphthoÈsen Erscheinungen an Mund, Genitalien und VeraÈnderungen an den Augen, als wahrscheinliche Folge einer durch Virus bedingten Allgemeininfektion. Dermatol Wochenschr. 1938;107:1037-40.
• Behçet H. A propos d’une entité morbide due probablement à un virus spécial donnant lieu à une affection géné ralisée se manifestant par poussées récidivantes en trois régions principales et occasionnant en particulier des iritis répétés. Bull Soc Fr Dermatol Syph. 1939;46:674-687.
• Behçet H. Einige Bemerkungen zu meinen Beobachtungen über den Tri Symptomen komplex. Med Welt. 1939;13:1222-27.
• Behçet H. Some observations on the clinical picture of the so-called triple symptom complex. Dermatologica. 1940;81:73–78.

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.

• Jensen T. Sur les ulcerations aphteuses de la muqueuse de la bouche et de la peau genitale combinees avec les symptomes oculaires (Syndrome Behçet). Acta Dermatol Venereol. 1941;22:64–79.

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

• 1944 – Chaim Berlin titled his case report ‘Behçet’s syndrome’ to describe a patient from Tel Aviv with oral, genital and eye lesions.
  • Berlin C. Behçet’s syndrome with involvement of central nervous system. Report of a case, with necropsy, of lesions of the mouth, genitalia and eyes; review of the literature. Arch Dermatol Syph (Chicago). 1944;49(3):227-233.
• 1944 – Ephraim similarly titled an autopsy case from Haifa (Israel) with the clinical triad as ‘the triple symptom complex of Behçet.
  • Ephraim H. Triple symptom complex of Behçet. Arch Dermatol Syph (Chicago). 1944;50(1):37-38.
• 1946 – Helene Ollendorff Curth (1899 – 1982) observed two patients from the USA with the triple symptom complex, which she referred to as ‘Behçet’s syndrome’ in her publications.
  • Ollendorff Curth H. Recurrent genito-oral aphthosis and uveitis with hypopyon (Behçet’s syndrome). Arch Dermatol Syph (Chicago). 1946;54(2):179-196.
  • Ollendorff Curth H. Behçet’s syndrome, abortive form (?) (recurrent genital ulcerations). Arch Dermatol Syph (Chicago). 1946;54(4):481-483.
• 1946 – Feigenbaum and Kornblueth used the eponym ‘Behçet’s disease’ in their case report of four patients from Jerusalem with the triple symptom complex.
  • Feigenbaum A, Kornblueth W. Behçet’s disease as manifestation of a chronic septic condition connected with a constitutional disorder. With a report of 4 cases. Acta Medica Orientalia. 1946;5:139-151.

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.

• Criteria for diagnosis of Behçet’s disease. International Study Group for Behçet’s Disease. Lancet. 1990 May 5;335(8697):1078-80

Associated Persons

• Hulusi Behçet (1889 – 1948)

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

Further Reading

• Adamantiades B, Lorendo N. Sur le syndrome complex de uveite recidivante ou soi-diatant syndrome de Behçet. Presse Médicale. 1949:57;101.
• Dimitrakakis G, Dimitrakaki IA. eComment. Behcet’s disease or Adamantiades-Behcet’s disease?. Interact Cardiovasc Thorac Surg. 2012;14(3):373–374.
• Evereklioglu C. The migration pattern, patient selection with diagnostic methodological flaw and confusing naming dilemma in Behçet disease. Eur J Echocardiogr. 2007;8(3):167-73; author reply 174.
• Evereklioglu C. Behçet’s disease or Adamantiades-Behçet disease? An evidence-based historical survey. Med Sci Monit. 2010; 16(6): RA136-42
• Zouboulis CC, Keitel W. A historical review of early descriptions of Adamantiades-Behcet’s disease. J Invest Dermatol 2002;119:201–205