Behcets Disease

Andrea Honeycutt AM Report

Behcets: Epidemiology

Disease prevalence and expression vary geographically and it affects people of Middle Eastern or Far Eastern ancestry more often than those from other regions. Turkey has the highest prevalence: 80 to 370 cases per 100,000 population.

Behcets: Epidemiology

Prevalence in Japan, Korea, China, Iran, and Saudi Arabia ranges from 13.5 to 20 cases per 100,000 The prevalence is much lower in Western countries. Prevalence of 0.33 per 100,000 in the United States.

Behcets: Pathophysiology

The underlying cause of Behcet's disease is unknown. As with other autoimmune diseases, the disorder may represent aberrant immune activity triggered by exposure to an agent, perhaps infectious, in patients with a genetic predisposition to develop the disease.

Behcets: Pathophysiology

The prevalence of the HLA-B51 allele is high among patients with Behet's disease who are of Middle Eastern or Far Eastern ancestry (up to 81 percent of Asian patients have the allele) but not among white patients who live in Western countries (13 percent). Studies suggest a possible pathogenic role of certain bacterial/viral antigens that have crossreactivity with human peptides.

Behcets: Pathophysiology

Endothelial activation in affected blood vessels has been proposed as a mediator of vascular inflammation as well as thrombosis in Behcet's. Hyperfunction of neutrophils noted within active lesions

Clinical Manifestations: Oral Lesions

Oral ulceration is usually an initial symptom and is seen in all patients at some time in the clinical course, sometimes precedes other manifestations by a number of years. Oral aphthae which are grossly and histologically similar to common oral ulcers, but tend to be more extensive and often multiple Lesions heal within about 10 days without scarring.

Clinical Manifestations: Uro-genital Lesions

Genital ulceration occur in 75 percent or more of patients with Behcet's disease. The ulcers are similar in appearance to the oral aphthae. Genital ulcers are most commonly found on the scrotum in men and the vulva in women Recurrence is typically less frequent than with oral ulcerations.

Clinical Manifestations: Cutaneous Lesions

Cutaneous lesions also occur in over 75 percent of patients with Behcet's disease. May include acneiform lesions, erythema nodosum, pyoderma gangrenosum-type lesions, and palpable purpura.

Clinical Manifestations: Cutaneous Lesions

Pathergy refers to an erythematous papular or pustular response to local skin injury. Defined as a greater than 5 mm lesion that appears 24 to 48 hours after skin prick by a needle. Less common in European decent patients with Behcet's disease (10 to 20 percent), than in Eastern patients (50 to 75 percent). The pathergy test can also be positive in Sweet's syndrome and pyoderma gangrenosum.

Clinical Manifestations: Arthritis

Nonerosive, asymmetric, usually nondeforming arthritis occurs in about one-half of patients with Behcet's disease, particularly during exacerbations. Most commonly affects the medium and large joints, including the knee, ankle, and wrist.

Clinical Manifestations: Ocular

Ocular disease occurs in 25 to 75 percent of patients with Behcet's disease, and may progress to blindness. Symptoms, including blurred vision, eye pain, photophobia, lacrimation, floaters Uveitis is often the dominant feature of Behcet's disease. It is typically bilateral and episodic.

Clinical Manifestations: Ocular

Hypopyon, a visible layer of pus in the anterior ocular chamber, is characteristic of Behet's disease The most serious ocular problem in patients with Behet's disease is retinal disease, as a result of vaso-occlusive lesions.

Clinical Manifestations: Gastrointestinal

Symptoms include abdominal pain, diarrhea, melena, and sometimes perforation. Gastrointestinal ulcerations occur most often in the terminal ileum, cecum, and ascending colon. Histologically, the intestinal ulcers of Behet's disease are indistinguishable from those of ulcerative colitis. It is often difficult to distinguish between Behet's disease and inflammatory bowel diseases, because of the similarity in extraintestinal symptoms

Clinical Manifestations: Gastrointestinal

The other parts of the gastrointestinal system and liver (except in Budd-Chiari syndrome), pancreas, and spleen are rarely involved. A large Japanese autopsy registry of subjects with Behcets, reported 5 cases of histologic pancreatitis in a total 170 cases.

Clinical Manifestations: Neurologic

Neurologic disease occurs in fewer than one-fifth of patients with Behcet's disease, more frequently in men than women. Classically, meningitis or meningoencephalitis, neurologic deficits such as motor disturbances and brain-stem symptoms, and psychiatric symptoms including personality changes develop more than five years after Behet's disease is diagnosed.

Clinical Manifestations: Neurologic

Symptoms have exacerbations and remissions and gradually cause irreversible disability. In the terminal stage, dementia becomes evident in about 30 percent of affected patients

Clinical Manifestations: Vascular

Small-vessel vasculitis is common and accounts for much of the pathologic process in Behet's disease. Large vessel vascular involvement occurs in approximately one-third of patients with Behcet's disease. Superficial and deep venous thrombosis are common.

Clinical Manifestations: Vascular

This may lead to stenosis or aneurysm formation. Rupture of such aneurysms may be fatal. Vascular lesions in the lung, including thrombosis, aneurysm, and arteriobronchial fistula, cause recurrent episodes of dyspnea, cough, chest pain, and hemoptysis.

Vascular disease in 728 patients with Behcet's disease

Number of patients Venous disease Deep venous thrombosis Subcutaneous thrombophlebitis SVC occlusion 221 205 122

IVC occlusion
Cerebral sinus thrombosis Budd-Chiari syndrome Other venous occlusion* Arterial disease

93
30 17 24

Pulmonary artery occlusion or aneurysm 36 Aortic aneurysm 17 Extremity arterial occlusion or aneurysm 45

Other arterial occlusion or aneurysm

Right ventricular thrombus

42
2

Behcets Disease: Diagnosis

There are no pathognomonic symptoms or laboratory findings, the diagnosis is made on the basis of clinical findings New international criteria were published in 1990

Behcets Disease: Treatment

The choice of the treatment depends on the patient's clinical manifestations. Significant ocular, neurologic, gastrointestinal, vascular, or other serious end organ manifestations typically require treatment with steroids and other immunosuppressive agents.

Behcets Disease (Systemic): Treatment

High dose steroids and

Azathioprine Methotrexate Cyclophosphamide Cyclosporine

There is no consensus as to which immunosuppressive agent to use with steroids. The choice depends upon the severity of disease, type of organ involvement, and clinician experience with available agents.

Behcets Disease (Mucocutaneous): Treatment

Treated with topical anesthetics, high potency glucocorticoids, intralesional steroids, colchicine. Ulcers that are refractory to these treatments, require systemic steroids, thalidomide, or the immunosuppressive agents.

Behcets Disease (Ocular): Treatment

Ocular lesions are treated with topical mydriatics, glucocorticoids. Relapses and/or progressive disease may occur with steroid treatment alone. Combination therapy, as for systemic disease, is often necessary. There is evidence of benefit from cyclosporine and azathioprine. No efficacy for cyclophosphamide or colchicine.

Behcets Disease (Neurologic): Treatment

Aseptic acute meningitis or meningoencephalitis in the early phase of the disease responds well to treatment with corticosteroids. In contrast, chronic progressive central nervous system disease is resistant to all the currently available therapies.

Behcets Disease (Arterial): Treatment

Arterial lesions are generally treated with steroids and another systemic immunosuppressive agent and may require surgical repair. Although surgery is ideally performed when the patient's disease is quiescent, it is often necessary to operate urgently or emergently due to enlarging or ruptured true or pseudoaneurysms or limb or viscera-threatening ischeia

Behcets Disease (Venous): Treatment

Low dose aspirin is probably reasonable in patients with Behcet's associated superficial thrombophlebitis. Systemic anticoagulation is often used in patients with deep venous thrombosis. Anticoagulant drugs should be given carefully in patients with pulmonary-vessel disease because of the risk of potentially fatal hemoptysis.

Behcets Disease: Prognosis

Behcet's disease has an undulating course of exacerbations and remissions, and may become less severe after approximately 20 years. The disease appears to be more severe in young, male, and Middle Eastern or Far Eastern patients.

Behcets Disease: Prognosis

Mucocutaneous, articular and ocular disease are often at their worst in the early years of disease. Central nervous system and large vessel disease, if they develop, typically do so later in the disease course.

Behcets Disease: Prognosis

In one study, 20 percent of patients with chronic neurologic involvement died within seven years. Half of patients die within three years after the onset of hemoptysis.