Behçet's disease

Behçet disease (Behçet's syndrome, Morbus Behçet, silk road disease) is a chronic condition due to disturbances 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.

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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.^[1][2] The name (Morbus Behçet) was formally adopted at the International Congress of Dermatology in Geneva in September 1947.

The disease was probably first described by Hippocrates in the 5th century BC, in his 3rd Epidemion-book.^[3] Its first modern formal description was published in 1922.^[1]

Some sources use the term "Adamantiades’ syndrome" or "Adamandiades-Behçet syndrome", for the work done by Benedikt Adamandiades.^[4] However, the current World Health Organization/ICD-10 standard is "Behçet's disease".

Pathology

The symptoms of Behçet disease are believed to be caused by an over-active immune system which, without any apparent infections, produces recurrent outbreaks of inflammation in small blood vessels. Common symptoms include mouth ulcers, sore genitals and eye inflammation, and arthritis in older patients, mostly painful but not life-threatening conditions. However, some patients may be unable to work because of the pain and the impaired vision and mobility. In some severe cases, uncontrolled inflammation may lead to blindness, intestinal complications, stroke, and even meningitis, which can be fatal.

This disease usually first strikes patients in their 20s and 30s. It then becomes a fluctuating lifelong disorder with a series of remissions and exacerbations which can be from days to months. Complete remission is rare.

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 (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

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

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 Behcet 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. It is not because of any known infections, it is not hereditary, it does not have to do with ethnic origin, gender, life-style, or age, where someone has lived or where they have been on holiday. 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.

Treatment

Current treatment is aimed at easing the symptoms, reducing inflammation, and controlling the immune system. Anti-TNF therapy such as infliximab has shown promise in treating the uveitis associated with the disease.^[5][6] Another Anti-TNF agent, Etanercept, may be useful in patients with mainly skin and mucosal symptoms.^[7]

Interferon alfa-2a may also be an effective alternative treatment, particularly for the genital and oral ulcers^[8] as well as ocular lesions.^[9] Azathioprine, when used in combination with interferon alfa-2b also shows promise,^[10] and Colchicine can be useful for treating some genital ulcers, erythema nodosum, and arthritis in women, and arthritis in men.^[11]

Thalidomide has also been used due to its immune-modifying effect.^[12] Dapsone and rebamipide have been shown, in small studies, to have beneficial results for mucocutaneous lesions.^[13][14]

A different orientation could be explored in Behçet Disease, especially with genetic linkage to HLA-B51 antigen, just like the prevalence of HLA-B27 in ankylosing spondylitis. Ankylosing spondylitis is not due to an 'oveactive' immune system; instead it is a true autoimmune disease caused by molecular mimicry of the Osp (outer surface protein) with the Klebsiella pneumoniae germ (2 enzymes produced by this normally non-virulent pathogen), which is always present as a sub-clinical infection, typically at the ileocecal junction. The combination of antibiotics targeted to this specific germ, and dietary controls (elimination or severe restriction of all starches) could therefore potentially provide the most effective treatments, but such treatments have not yet been proven or generally approved. At the current time, a similar infectious origin has not yet been confirmed that leads to Behçet disease, but certain strains of Streptococcus sanguis has been found to have a homologous antigenicity.

Epidemiology

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.

An estimated 15,000 to 20,000 Americans have been diagnosed with this disease. In the UK, it is estimated to have about 2 cases for every 100,000 people.

Globally, males are affected more frequently than females. In the United States, more females are affected than males.

Pronunciation note

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 "t" incorrectly silenced: "Beshay". Because Hulusi Behçet was Turkish, the correct pronunciation is with a hard "ch", as in "choice", and with the terminal "t" sounded: "Beh-chet".

References