Behçet's disease

Behçet disease (Behçet's syndrome, Morbus Behçet, silk road disease) (pronounced /bɛˈtʃɛt/) is a form of vasculitis^[1] that can lead to ulceration and other lesions. It can be interpreted as a chronic disturbance in the body’s immune system. This system, which normally protects the body against infections through controlled inflammation, becomes overactive and produces unpredictable outbreaks of exaggerated inflammation. This extra inflammation affects blood vessels, usually the small ones. As a result, symptoms occur wherever there is a patch of inflammation, and can be anywhere where there is a blood supply.

The etiology is not well-defined, but it is characterized by inflammation of the blood vessels. Although sometimes erroneously referred to as a "diagnosis of exclusion," the diagnosis can be reached by pathologic examination of the affected areas.^[2]

History

Behçet disease is named after Hulusi Behçet (1889–1948), the Turkish dermatologist and scientist who first recognized the syndrome in one of his patients in 1924 and reported his research on the disease in Journal of Skin and Venereal Diseases in 1936.^[3][4] The name (Morbus Behçet) was formally adopted at the International Congress of Dermatology in Geneva in September 1947.

Symptoms of this disease may have been described by Hippocrates in the 5th century BC, in his 3rd Epidemion-book.^[5] Its first modern formal description was published in 1922.^[3]

Some sources use the term "Adamantiades’ syndrome" or "Adamandiades-Behçet syndrome", for the work done by Benediktos Adamantiades.^[6] However, the current World Health Organization/ICD-10 standard is "Behçet's disease".

In 1991, Saudi Arabian medical researchers described "neuro-Behçet's disease",^[7] a neurological involvement in Behçet's disease, considered one of the most devastating manifestations of the disease as investigated by an Egyptian researcher Sahar Saleem.^[8] The mechanism can be immune-mediated, or thrombotic.^[9] The term dates back to at least 1990.^[10]

Diagnosis

There is no specific pathological test for Behçet disease at present. It is diagnosed clinically by specific patterns of symptoms and repeated outbreaks. Other causes for these symptoms have to be ruled out before making the diagnosis. The symptoms do not have to occur together, but can have happened at any time.

There are three levels of certainty for diagnosis:

1. International Study Group diagnostic guidelines^[11] (very strict for research purposes)
2. Practical clinical diagnosis (generally agreed pattern but not as strict)
3. 'Suspected' or 'Possible' diagnosis (incomplete pattern of symptoms)

International Study Group diagnostic guidelines

According to the Internation Study Group for Behçet's disease,^[11] to be diagnosed with this condition a person must have

• oral (aphthous) ulcers (any shape, size or number at least 3 times in any 12 months),

along with 2 out of the next 4 "hallmark" symptoms:

• genital ulcers (including anal ulcers and spots in the genital region and swollen testicles or epididymitis in men),
• skin lesions (papulo-pustules, folliculitis, erythema nodosum, acne in post-adolescents not on corticosteroids),
• eye inflammation (iritis, uveitis, retinal vasculitis, cells in the vitreous),
• pathergy reaction (papule >2 mm dia. 24-48 hrs or more after needle-prick).

Practical clinical diagnosis

Magnetic resonance venogram demonstrating occlusion of the left sigmoid and transverse sinuses.

Must have

• mouth ulcers,

along with 1 of the 4 hallmark symptoms above and with 2 of the symptoms below:

• arthritis/arthralgia;
• nervous system symptoms;
• stomach and/or bowel inflammation;
• deep vein thrombosis;
• superficial thrombophlebitis;
• cardio-vascular problems of inflammatory origin;
• inflammatory problems in chest and lungs;
• problems with hearing and/or balance;
• extreme exhaustion;
• changes of personality, psychoses;
• any other members of the family with a diagnosis of Behçet disease.

'Suspected' or 'Possible' diagnosis

Usually given when someone does not have mouth ulcers or has mouth ulcers but does not have 1 of the 4 hallmark symptoms but has other symptoms and signs of inflammation and other causes for these have been ruled out.

Causes

No one knows why the immune system starts to behave this way in Behçet disease. First degree relatives are affected in more than expected proportion of patients.

It is rare in the United States, but is common in the Middle East and Asia, suggesting a cause endemic to the tropical areas.^[12]

It is not associated with cancer, and links with tissue-types (which are under investigation) are not certain. It does not follow the usual pattern for autoimmune diseases. However, one study has revealed a possible connection to food allergies, particularly to dairy products.^[13]

Treatment

Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. Corticosteroid therapy (1 mg/kg/d oral prednisone) is indicated for severe disease manifestations^[14]. Anti-TNF therapy such as infliximab has shown promise in treating the uveitis associated with the disease.^[15][16] Another Anti-TNF agent, Etanercept, may be useful in patients with mainly skin and mucosal symptoms.^[17]

Interferon alfa-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers^[18] as well as ocular lesions.^[19] Azathioprine, when used in combination with interferon alfa-2b also shows promise,^[20] and Colchicine can be useful for treating some genital ulcers, erythema nodosum, and arthritis.^[21]

Thalidomide has also been used due to its immune-modifying effect.^[22] Dapsone and rebamipide have been shown, in small studies, to have beneficial results for mucocutaneous lesions.^[23][24]

Pathophysiology

Behçet disease is considered more prevalent in the areas surrounding the old silk trading routes in the Middle East and in Central Asia. Thus, it is sometimes known as Silk Road Disease. However, this disease is not restricted to people from these regions. A large number of serological studies show a linkage between the disease and HLA-B51.^[26] HLA-B51 is more frequently found from the Middle East to South Eastern Siberia, but the incidence of B51 in some studies was 3 fold higher than the normal population. However, B51 tends not to be found in disease when a certain SUMO4 gene variant is involved,^[27] and symptoms appear to be milder when HLA-B27 is present.^[28] At the current time, a similar infectious origin has not yet been confirmed that leads to Behçet's disease, but certain strains of Streptococcus sanguinis has been found to have a homologous antigenicity.^[29]

Epidemiology

An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 1 case for every 100,000 people.^[30] Globally, males are affected more frequently than females.^[31] In the United States, more females are affected than males.

Pronunciation

Because Hulusi Behçet was Turkish, the correct pronunciation is with a hard "ch", as in "choice", with "e" (both first and second e letters) as in "end" and with the terminal "t" sounded: "Beh-chet". Because it contains a cedilla, "Behçet" is frequently wrongly assumed to be French in origin and pronounced with a sibilant "s" sound (as in "satsuma") or soft "ch" (as in "shoe"), with the "e" incorrectly like "i" (as in see), with the "t" incorrectly silenced: "Beshay".

See also

• Behcet's Disease of the Optic Nerve
• List of cutaneous conditions

References

External links

• Behçet's disease at the Open Directory Project