Behçet Disease

Behçet disease is a chronic relapsing remitting multisystem inflammatory disorder, classified as a variable vessel vasculitis. It can affect vessels of any size in both the arterial and venous circulation.

It is characterised by recurrent oral and genital ulceration, uveitis, and a wide range of mucocutaneous, vascular, articular, gastrointestinal and neurological manifestations. It has a distinctive geographical distribution along the historic Silk Road, from East Asia through the Middle East to the Mediterranean.

Pathophysiology

An interplay of genetic susceptibility (a strong association with HLA B51), environmental triggers and dysregulated innate and adaptive immune responses drives inflammation targeting vessels of all sizes in both arterial and venous circulations.

This distinguishes Behçet disease from most other vasculitides and underlies its unusually diverse clinical manifestations.

These include a propensity for venous thrombosis, which is thought to reflect vessel wall inflammation rather than a primary hypercoagulable state.

• Recurrent, painful oral ulceration, typically occurring three or more times within a twelve month period, is the most consistent and usually the earliest feature. The ulcers resemble aphthous ulcers but recur with greater frequency and severity.

• Genital ulceration, typically scrotal in men and on the vulva in women, is characteristic. Unlike oral ulcers, it frequently heals with scarring.

• Ocular involvement, particularly posterior or panuveitis, is a major cause of morbidity and a leading cause of blindness if inadequately treated. It requires urgent ophthalmological assessment whenever visual symptoms occur.

• Cutaneous manifestations include erythema nodosum, pseudofolliculitis and acneiform lesions.

• Pathergy is an exaggerated skin inflammatory response to minor trauma such as a needle prick. It is a characteristic though insensitive diagnostic sign.

• Vascular involvement is distinctive. Venous thrombosis is more common than in most vasculitides, including superficial and deep venous thrombosis and, notably, vena caval and cerebral venous sinus thrombosis.

• Arterial aneurysm formation also occurs, particularly of the pulmonary arteries, and carries a high mortality risk if it ruptures.

• Arthritis is typically non erosive and affects large joints.

• Gastrointestinal involvement causes ulceration that can mimic inflammatory bowel disease, with risk of perforation.

• Neurological involvement is either parenchymal central nervous system disease or cerebral venous sinus thrombosis.

Diagnosis is clinical, based on established criteria requiring recurrent oral ulceration together with at least two of recurrent genital ulceration, eye lesions, skin lesions or a positive pathergy test, since no specific diagnostic laboratory test exists for this condition.

• HLA B51 testing supports the diagnosis in the appropriate clinical and geographical context but is neither sensitive nor specific enough to be diagnostic in isolation.

• Inflammatory markers are typically elevated during active disease but are non specific.

• Ophthalmological assessment with slit lamp examination and fundoscopy is essential in every patient given the significant risk of sight threatening uveitis, which may be present even without overt visual symptoms.

• Imaging (magnetic resonance venography for suspected cerebral venous sinus thrombosis, computed tomography angiography for suspected pulmonary or other arterial aneurysm) is directed by the specific pattern of organ involvement suspected clinically.

• Exclusion of other causes of recurrent oral and genital ulceration (herpes simplex virus, inflammatory bowel disease, other autoimmune causes) is an important part of the diagnostic process, particularly in atypical presentations.

• Mucocutaneous disease is managed with topical corticosteroids for oral and genital ulcers.

• Colchicine is used for recurrent mucocutaneous and articular symptoms. It is particularly effective for erythema nodosum and arthritis.

• Azathioprine is commonly used as a steroid sparing agent for moderate disease and for prevention of ocular complications.

• Sight threatening uveitis requires urgent, aggressive treatment with high dose corticosteroids. Given the risk of relapse and visual loss, introduce a steroid sparing immunosuppressant early.

• Tumour necrosis factor inhibitors (particularly infliximab and adalimumab) are increasingly used as first line or early treatment for severe ocular disease, given their rapid and sustained efficacy.

• Vascular involvement is managed with immunosuppression (corticosteroids and azathioprine or cyclophosphamide for arterial disease) rather than anticoagulation alone.

• This is particularly important for pulmonary artery aneurysm. Anticoagulation without immunosuppressive control of the underlying vasculitis can be hazardous because of the coexisting bleeding risk from the aneurysm itself.

• This is an important and counterintuitive distinction from typical venous thromboembolism management.

• Neurological involvement requires high dose corticosteroids and immunosuppression. Interferon alfa or tumour necrosis factor inhibitors are used for severe or refractory neurological or ocular disease.

• Gastrointestinal involvement is managed with corticosteroids and immunosuppression, following principles similar to inflammatory bowel disease. Surgery is reserved for perforation or severe refractory disease.

Long term multidisciplinary follow up (rheumatology, ophthalmology, and as needed dermatology, gastroenterology and neurology) is essential, given the chronic relapsing course and the potential for serious, sight or life threatening complications.

Disease activity and treatment intensity generally decrease over years in many patients. A subset experience persistent severe disease requiring sustained treatment.