Behcet’s disease, also known as an oculo-orogenital syndrome, is a chronic remitting and relapsing inflammatory disorder characterized by recurrent oral aphthous ulcers, genital ulcerations, ocular manifestations (e.g., uveitis, conjunctivitis) and other systemic involvement. It is also known as Behcet syndrome and Malignant aphthosis.
The exact etiological basis of Behcet’s disease is unknown. It is considered to be an autoimmune disease triggered by infections like herpes simplex virus (HSV), Streptococcus, and Staphylococcus in genetically predisposed individuals. Genetic predisposition to develop this syndrome has been found in HLA-B51 carriers.
The incidence and prevalence of this disease are high amongst the Far Eastern and Mediterranean ancestries. Turkey has the highest prevalence affecting 420 people per 100,000 population.
It affects patients in their twenties and thirties; however early and late onsets have been reported. Both genders are equally affected by the disease; a male predominance is observed in Arab populations while female predominance is evident in Korea, China, United States, and some northern European countries.
Behcet’s disease is characterized by vasculitis of all sized vessels that involves both arterial and venous sides of the circulation. Cell-mediated immunity plays a major role in the pathogenesis of this disease. Helper T- cells type-1 activation leads to increased circulating levels of CD-4 positive and cytotoxic (CD8 positive) lymphocytes in the peripheral blood which target the oral mucosa, skin and other systems of the body. There are a number of immunological findings in Behcet's disease;
However, the common pathogenic denominator is leukocytoclastic vasculitis which is considered to be pathognomonic for the disease. Due to the involvement of immune complexes, the disease shares a number of common features to other diseases (e.g., SLE) which have similar pathogenesis. An example of this is erythema nodosum commonly manifested in these diseases.
Histopathological features of the disease are vasculitis and thrombosis. Mucocutaneous lesions biopsies show a neutrophil-predominant reaction with endothelial swelling, extravasation of RBCs and leukocytoclastic vasculitis (suggestive sign of the disease) with fibrinoid necrosis of the blood vessel walls. Some older lesions show lymphocytic perivasculitis. However, a neutrophilic vascular reaction is considered to be the most predominant reaction in Behcet's disease. Involvement of vasa vasorum (vasculitis) may result in the formation of aneurysms in the large arteries.
Typically patients have a history of recurrent painful oral lesions (aphthous ulcers) with odynophagia, foul-smelling breath, photophobia, vision loss, joint pains, and painful genital lesions.
Multiple aphthous ulcers in the oral cavity involving the soft palate, hard palate, buccal mucosa, and tonsils, having a sharp regular border with a grayish base and surrounding bright red halo. Genital lesions may occur on the scrotum in males and vulva and vagina in females.
Ocular manifestations may include conjunctivitis, uveitis, and hypopyon. Retinal vasculitis or posterior uveitis is the most classic ocular sign and an important cause of blindness in these patients. Other secondary ocular complications are cataract, glaucoma and neovascular lesions. Retinal inflammation can lead to vascular occlusion and ultimately results in tractional retinal detachment. Recurrent vasculitic changes can ultimately result in ischemic optic nerve atrophy and can cause blindness.
Non-deforming arthritis of medium and large joints is seen in many patients. The characteristic arthritis is non-erosive, asymmetrical, sterile and seronegative; however symmetrical polyarticular involvement is comm in Behcet's disease. Joint manifestations frequently occur in one knee or ankle and then other as a migratory monoarthritis, then in both joints simultaneously and finally affecting nearly all joints of the body. An important differential to be excluded is an HLA-B27-positive erosive sacroiliitis.
Neurological and gastrointestinal manifestations may also be seen. Neurological manifestations include meningoencephalitis, cerebral venous thrombosis, benign intracranial hypertension, cranial nerve palsies and various pyramidal and extrapyramidal lesions.
Behcet’s disease is characterized by both arterial and venous thrombosis; however arterial involvement is rare. A swollen tender calf (due to deep venous thrombosis) in a patient with orogenital ulcers and eye involvement is highly suggestive of Behcet’s disease.
Diagnosis is mainly clinical, and the diagnostic criteria consist of recurrent oral aphthous stomatitis with two or more of the following clinical findings in the absence of other systemic diseases:
Differential diagnoses include:
Treatment is aimed at preventing the recurrence of the disease. Treatment strategy depends on the site and severity of the disease. Following order shows the treatment plan according to involvement sites and severity:
In pregnancy, prednisolone is the systemic drug of choice without potential side effects related to pregnancy.
For refractory cases, the following drugs are being used as second and third line therapies:
Ophthalmic and neurological complications are the leading causes of morbidity in these patients. Others are severe vascular and extensive gastrointestinal involvement.
Severe or progressive recurrent aphthous stomatitis in patients should raise suspicion of the disease, and they should be followed for up to years as potential candidates for Behcet's disease. Especially those with a strong family history.
Patients who are suspected to have this disease should be referred for specialty consultation.
Patients (especially males) who present with systemic involvement as a presenting sign should be treated with systemic drugs.
Patients who have early onset of the disease have a poor prognosis.
Because of the diverse presentation of Behcet disease, it is best managed by a multidisciplinary team that consists of an ophthalmologist, rheumatologist, internist, cardiologist, neurologist, dermatologist, vascular surgeon, and a gastroenterologist. There is no cure for the disease and all treatments are aimed at preventing recurrence. Besides corticosteroids, the patients are treated with newer biological therapies. Surgery is sometimes required when the peripheral vessels are involved. The disease is progressive and patients need life long monitoring. Family members have to be screened early on to prevent the high morbidity. Overall, the prognosis for most patients with Behcet disease is poor. (Level V)
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