What is Behçet disease?
Behçet disease (BD) is a rare, multi-system condition characterised byrecurrentpainful oral andgenitalulcers, a variety of skinlesions, and eye problems.
Many other organs such as the gut, nervous system, lungs, andarteriesmay also be affected. It is a form ofvasculitiswhich primarily targets small arteries, but can affect both arteries and veins of all sizes.
It is also known as Adamantiades-Behçet disease, Behçetsyndrome, andmalignant口疮病.
Who gets Behçet disease?
Behçet disease is most common in individuals originating from eastern and central Asia as well as the eastern Mediterranean. It is mostprevalentin Turkey (80–370 cases per 100,000), followed by Iran, and Japan. It is much rarer in those of northern European, African, and Latin American descent.
Onset is usually between 30 and 40 years of age. It rarely occurs in children. It was previously thought that BD was more common in males compared with females, but more recent data suggests thatincidenceis similar, although this varies between different ethnic and geographic groups.
What causes Behçet disease?
Behçet disease is of unknown cause, but it is thought to have anautoimmunebasis. It is associated with severalgeneticfactors, particularlyHLA-B51. Severalinfectionshave also been implicated as potential triggers includingStreptococcus sanguis,herpessimplexvirus,hepatitisviruses, andparvovirus B19.
What are the clinical features of Behçet disease?
Oral ulcers— anywhere in the mouth,pharynx, and tonsils.
- Typically multiple in number and measure 1–3 cm in size, although they can be larger.
- Usually sharp defined margin with afibrin-coated base, surroundingerythema, and yellow pseudomembrane.
- Multiple shallow pinpoint ulcers 1–2 mm in diameter, occurring in clusters (herpetiformulcers).
Genital ulcers— painful, recurrent ulcers on thevulva,vagina,perineumandinguinalareas, scrotum, and penis.
- Genital sores are less common than oral lesions and may heal with scars.
Pathergyis a commonly observed feature in Behçet disease, and refers to theeruptionofpapulopustulesat the site of a needle injury within 24–48 hours. Pathergy is not specific to BD, and can also occur inpyodermagangrenosumandSweet syndrome.
Other skin lesions include:
- Erythema nodosum
- Acutefebrileneutrophilicdermatosis(Sweet syndrome).
For more images, see theBehçet disease imagepage.
Ophthalmic lesions — seen in 70% of patients, and include:
- Retinal vasculitis
- Thrombosisof the retinalarteryand vein
- Optic neuritis.
- A mono- oroligoarthritisof the medium and large joints
Vascularinvolvement is present in 25% of patients, resulting in:
- Superficial thrombophlebitis and deep vein thrombosis
- Thrombosis of the vena cava, duralsinus, and Budd-Chiari syndrome
- Arterialmanifestationsresulting instenosis, thrombosis, andaneurysmformation.
Involvement of the aorta andpulmonaryartery can cause life-threateningocclusionorhaemorrhagefrom aneurysm formation.
Other organ systems which can be affected less commonly include neurological, pulmonary,renal, and cardiac.
How do clinical features vary in differing types of skin?
The features are similar, although Behçet disease is less common in those with skin of colour.
What are the complications of Behçet disease?
Given the multi-system nature of Behçet disease, there are many potential complications.
- Vascular complications, particularly when the aorta and pulmonary arteries are affected — this can be life-threatening
- CNSinvolvement leading to permanentneurologicaldeficits
- Bowelperforationand peritonitis.
How is Behçet disease diagnosed?
BD can be challenging to diagnose, and several years may elapse before a confident diagnosis can be made, and strict diagnostic criteria fulfilled. It is sometimes useful to classify sufferers as having possible, probable, or definite Behçet disease as new symptoms evolve. There are no definitive confirmatory diagnostic tests.
The International Study Group Criteria are widely used in diagnosis, and criteria include:
- At least three episodes of minor aphthous, major aphthous, or herpetiform oralulcerationover a 12-month period (observed by a doctor or patient) plus at least two of the following:
- Recurrent genital ulceration — aphthous ulceration or scarring observed by a doctor or patient
- Ophthalmic involvement — anterior uveitis, posterior uveitis or cells in vitreous on slit examination or retinal vasculitis observed by anophthalmologist
- Cutaneouslesions — erythema nodosum observed by a doctor or patient, pseudofolliculitis or papulopustular lesions, oracneiformnodulesobserved by a doctor
- Positive pathergy test — observed at 24–48 hours.
Common investigations include:
- Full blood count
- Urea and electrolytes
- Antinuclear factor
- Serumiron, folate, zinc and vitamin B12
- Culture/PCRfrom oral or genital ulcers to exclude HSVinfection
Other investigations may be required and depend on the organ system affected.
What is thedifferential diagnosisfor Behçet disease?
This depends on the clinical presentation but other common conditions which cause orogenital aphthous ulcers should be considered.
- Herpesvirus infections
- Primaryand secondarysyphilis
- Vitamin B12 deficiency
- Complex aphthosis (recurrent oral and genital ulcers in the absence of other features)
- Inflammatorybowel disease
- Erythema multiforme
- PFAPAsyndrome (periodicfever, aphthosis,pharyngitis, adenitis)
- Acute febrile neutrophilic dermatosis
- MAGIC syndrome (mouth and genital ulcers with inflamed cartilage).
What is the treatment for Behçet disease?
Behçet disease treatment should be tailored to each individual patient based on clinical manifestations and extent of disease — an MDT approach is required. Behçet disease typically has a relapsing-remitting course, and treatments should aim to suppress any inflammatoryexacerbationsand prevent irreversible organ damage, particularly in the initial phase of disease.
Ocular, vascular, and neurological manifestations are often more serious and require more aggressive treatment.
- Corticosteroidsapplied ascreams, gels, or mouth rinses
- Pimecrolimus— as an alternative to topical steroids
- Antibioticssuch astetracyclines
- Antiseptics — chlorhexidine mouthwash
- Hydroxypropyl cellulose
Systemic treatments for mucosal disease include:
- Interferon alpha-21 and interferon alpha-2b
Treatment of skin manifestations
Erythema nodosum in Behçet disease:
- Raises the possibility of underlyingdermalvasculitis
- 秋水仙碱通常使用一线,但如果this fails, systemic glucocorticoids combined with anotherimmunosuppressiveagent may be used.
Evidence of ulceration or detection of medium-vessel vasculitis on skin biopsy is an indication for systemic glucocorticoids with another immunosuppressive agent (typically azathioprine).
脓皮病遗传算法ngrenosum in BD should be managed as in other causes of this disease.
Treatment of multi-system Behçet disease
The key management points are:
- Oral corticosteroids: recommended treatment for patients with moderate to severe disease with ocular, vascular, gastrointestinal, orneurologicinvolvement.
- Azathioprine: as a steroid-sparing agent
- TNF-alphainhibitors, particularly infliximab forrefractoryocular BD
- Cyclophosphamide— reserved for life-threatening complications of BD mainly when there is major vessel or CNS involvement
- Majorblood vesseldisease, including thrombosis is treated withimmunosuppressionand not anticoagulation
- CNS involvement is typically more refractory to treatment
- Other agents that can be used includeinterleukin-1receptorantagonists (e.g.anakinra), alemtuzumab, tocilizumab,rituximab, and stem celltransplantation.
What is the outcome for Behçet disease?
Behçet disease typically runs a relapsing-remitting course and theprognosisvaries depending on the organ systems affected.
Mortalityis low but is increased in patients with neurological, vascular, and gastrointestinal involvement. Ophthalmic involvement is a major cause ofmorbidity.
The prognosis is worse in males.