Behcet’s syndrome or Behcet’s disease is a multisystem inflammatory disease characterized by oral aphthous ulcers and a myriad potential systemic manifestations.
Behcet’s syndrome is confirmed in the presence of any two of the following criteria:
One of the first symptoms to appear in the case of Behcet’s syndrome is aphthous or herpetiform oral lesions. These lesions have a high recurrence rate and may be found as multiple lesions. Skin lesions are also present in the genital regions. Lesions may be found in scrotum or on the penile shaft. In females lesions develop in the labia, vagina or perineum. These lesions heal with scarring. Tender, erythematosus nodules may develop in the lower extremities and resolve within a few weeks. These nodules are common in females and have a high recurrence rate. In males, acneiform nodules may arise on the trunk and extremities. Ulcerations may occur in axillae, neck, breast and interdigital skin .
Oral ulcerations are often followed by ocular manifestations including anterior and posterior uveitis, hypopyon, retinal vasculitis and cystoid macular degeneration. Patients with ocular manifestations may present with blurred vision, photophobia, increased lacrimation and periorbital pain. Ocular symptoms are found to be severe in Iranian and Japanese population. Posterior uveitis may lead to blindness.
As the disease progresses, neurologic manifestations develop. These symptoms often develop 7 to 8 years after the onset of the disease. Most of the neurologic symptoms arise due to the involvement of brain stem. Memory loss is the most common manifestation. Other common neurologic signs include seizures, difficulty in speech, deafness, and clonus.
Pulmonary artery aneurysm may lead to hemoptysis, cough, chest pain and dyspnea . Many small and large blood vessels develop vasculitis and manifestations depend on location of the lesions. Superficial thrombophlebitis with erythema is associated with venous involvement. Deep vein thrombosis is seen in some patients. About 60% of the patients may have arthritis and arthralgia, particularly in knees, ankles, wrists and elbows. Cardiac involvement in the form of coronary vasculitis, pericarditis, myocarditis, endocarditis and diastolic anomalies is also observed in some.
Imaging techniques like MRI, CT scan, and radiography are useful in identifying tissue swelling, effusions and areas of ischemia. Brain MRI is necessary when there is an involvement of CNS. MRI helps in locating focal lesions of cerebral vasculopathy. Aneurysms can be detected using angiograms. Echocardiography is an imaging method useful in diagnosing ventricular thrombi.
There are no specific laboratory tests for the diagnosis of Behcet’s syndrome. Patients often have normal levels of serum components. Some of the complements may show a change when ocular or skin manifestations arise. Few patients may show increased ESR and C-reactive protein levels. Anticardiolipin antibodies are reported in some patients.
Gastrointestinal lesions are diagnosed using endoscopy. Eye examination is essential when ocular manifestations are obvious. Retinal vessels are evaluated using fluorescein angiography. Positive pathergy test is indicative of Behcet’s disese as skin prick may trigger nodule or pustule formation within 2 days. Perivascular infiltration and vasculitis can be identified using sample biopsy.
Treatment modality depends on the organ involved and severity of the symptoms. Topical steroids and sucralfate solution are recommended in mild cases of oral and genital ulcerations. Colchicine is used to prevent relapse of mucocutaneous lesions . Severe lesions are treated with systemic corticosteroids, azathioprine, dapsone and interferon-alpha. Mild ocular manifestations are treated with azathioprine. In severe cases of ocular symptoms, cyclosporine A or infliximab is used in combination with corticosteroids. Interferon-alpha is also recommended in severe cases of ocular manifestations. Systemic corticosteroids and azathioprine are suggested for gastrointestinal ulcerations. For cutaneous manifestations, colchicine and dapsone are used. Thrombi in vessels are treated with systemic anticoagulants with corticosteroids or azathioprine. Aneurysms in pulmonary vessels need cyclophosphamide with corticosteroids.
Those presenting with intestinal stenosis, severe bleeding, perforations and fistula, may need surgery. Resection is suggested for ischemic damage with vasculitis. Surgery is also recommended in coronary thrombosis, endocardial fibrosis or ventricular aneurysms. Some ocular manifestations like glaucoma, cataract and retinal detachment may require surgical intervention. Clots and aneurysms in the CNS are also improved with surgery.
In general, prognosis depend on the clinical manifestations of the disease. Treatment, rest and exercise are the best steps to improve the symptoms of the condition. Effective treatment helps to prevent exacerbations. Patients may enter a period of remission in most of the cases, while serious complications may arise in some. Those who develop retinal vasculitis, vascular aneurysms, and neurological manifestations may not have a good prognosis. Retinal vasculitis may lead to blindness while aneurysms in the blood vessels may rupture.
Etiology of the disease is not defined. Viral etiology, though accepted earlier, was disproved over the years. New theories propose various other factors as the causative feature including bacterial infection, exposure to chemicals and, most recent, autoimmune reaction. Clinical manifestations are caused by immune responses that lead to vasculitis of small and medium sized blood vessels. The reaction is also thought to initiate inflammation of epithelium mediated by hyperactive T lymphocytes and plasma cells. Increased function of neutrophils noted in patients is also implicated in the development of clinical manifestations.
A genetic component, particularly HLA-B51, has an association with this syndrome. Interleukin 10 (IL-10) and IL-23 are also reported to have strong influences in the development of Behcet’s disease . Patients with active form of Becet’s syndrome have elevated levels of IL-6, while IL-10 remains lower than normal .
This syndrome exists worldwide, but with distinct differences in the regions. Worldwide prevalence studies show the estimate to be 1:10,000. Behcet’s disease is a more prevalent condition in the Far East, Middle East and Mediterranean countries like Iran, Turkey and Israel. In Turkey the estimate is in the range of 80-370 in a population of 100,000. Western countries show a prevalence ranging from 5 to 6.4 per 100,000 population . Incidence was found to be higher among males in the Mediterranean region, and this is particularly true for men in the age group of 30-40 years. In Eastern countries the male to female ratio was found to be 1:1, while in Japan and Korea females are more commonly affected. Although there is a variation in the sex ratios from different regions, the course of the disease is more severe among males. Average onset age (25-35 years) was similar in men and women, some cases have been reported in childhood as well. It is rare for the disease to occur before school age. In Turkey the mean age for the onset of Behcet’s disease is 11.7 years.
A number of theories have been put forward to explain pathogenesis of this disease. The latest and most accepted one is the autoimmune pathogenesis of Behcet’s syndrome. Infectious agents like Streptococcus, Staphylococcus species, and herpes simplex virus (HSV) may trigger an immune reaction. Heat shock proteins (HSP) are also suspected as triggers of cross-reactive immune reaction that lead to Behcet’s disease. In high-risk populations, including Turkey and Japan, HSPs bring out an enhanced activation of lymphocytes resulting in a proliferative response, characteristic of the disease . Different ethnic populations show increased T- and B-cell responses to these proteins and hence HSPs may be pathophysiologically related to the development of Behcet’s syndrome.
T-cells and neutrophils undergo inflammatory tissue infiltration resulting in vasculitic and vasculopathic lesions that are common manifestations in the disease . The specific roles of the neutrophils in the disease is not fully characterized. Chemotaxis, active oxygen production, phagocytosis, and infiltration are all implicated in the course of this syndrome . Many recent evidences suggest a critical role for nitric oxide, a free oxygen radical released by endothelial cells upon stimulation by cytokines, in the development and progression of Behcet’s disease. Increased production of nitrogen oxide is associated with increased susceptibility to the syndrome .
Behcet’s disease may be seen in a family, which suggests genetic pathophysiology of the disease. Presence of HLA-B51/HLA-B5 genetic structure is associated with increased risk of this syndrome . But these genes are not shown to have any effect on the severity of the disease.
No known preventive measures exist for Behcet’s syndrome.
Behcet’s syndrome or Behcet’s disease is a multisystemic inflammatory disease first described by Turkish dermatologist Hulusi Behçet in 1937. It was initially described as a ‘triple symptoms complex’ with characteristic symptoms – aphthous ulceration, genital ulceration and inflammatory eye disease . The condition may cause heterogeneous clinical manifestations including ocular, mucocutaneous, neurologic, cardiovascular, pulmonary, renal and gastrointestinal symptoms. Symptoms often cluster together, but the manifestations may vary from region to region.
The precise etiology of the disease is not yet known. Highest incidence of Behcet’s syndrome is reported from the Middle East, Mediterranean and the Far East. It is a rare syndrome and young adult men are more commonly affected by the condition. Family aggregation of the syndrome, affecting three brothers in a family, is also reported. A number of etiologic factors are thought to be associated with the development of Behcet’s syndrome, the latest and most accepted one being autoimmune reaction. Treatment is based on clinical manifestations of the condition.
Behcet’s syndrome or Behcet’s disease is an autoimmune disease characterized by triad of symptoms – oral ulcers, sores in the genital area and inflammation in parts of the eye. Many tissues and blood vessels may become inflamed, resulting in the different symptoms of the disease. Symptoms may vary from person to person depending on the location of inflammation and the organ involved. Some of the areas that are commonly affected by the disease include mouth, skin, genitals, eyes, blood vessels, digestive system, brain, and joints.
The actual cause of the disease is not fully characterized. A combination of environmental and genetic factors are thought to play an important role in the development of this condition. This syndrome is more common among men and women in the age group of 30 to 40 years. People from Far East, Mediterranean, and Middle East have an increased risk of developing this syndrome. Certain genes are also known to be associated with the disease. Behcet’s syndrome is seen in both men and women, but is more severe in men.
Confirmatory diagnosis depends on the presence of any of the two symptoms given below:
Complete cure for the disease is not available. Treatment often depends on the severity of the symptoms and the organ involved. Topical creams are used for sores in the skin and genital area. Eye drops containing corticosteroids are useful in improving the symptoms of the eye. When topical medications are not effective, oral medications are recommended. Medications are used to suppress the immune system and also to control inflammation. In some cases medications are suggested to regulate the response of the immune system. Prompt treatment, adequate rest, good diet and exercise go a long way in controlling the symptoms of Behcet’s syndrome.