Behcet Disease Clinical Presentation
- Author: Fatima A Alnaimat, MBBS; Chief Editor: Herbert S Diamond, MD more...
In 1990, the International Study Group (ISG) for Behçet's Disease clarified criteria for the diagnosis of Behçet disease. The ISG group compared the clinical findings of 914 patients with a history of aphthous ulcers with those of controls. Initial criteria for diagnosis require the occurrence of at least three episodes of oral herpetiform or aphthous ulcerations within a 12-month period observed directly by a physician or reported by the patient. To confirm the diagnosis, at least two of the following must also be demonstrated:
Recurrent painful genital ulcers that heal with scarring
Ophthalmic lesions, including anterior or posterior uveitis, hypopyon, or retinal vasculitis
Skin lesions, including erythema nodosum–like lesions, pseudofolliculitis, or papulopustular or acneiform lesions
Positive results from pathergy skin testing, defined as the formation of a sterile erythematous papule 2 mm in diameter or larger that appears 48 hours following a skin prick with a sharp sterile needle (22-24 gauge [a dull needle may be used as a control])
Considering the above diagnostic criteria, case presentation often includes the following characteristics:
Multiorgan system involvement, often beginning with mucocutaneous involvement and usually sparing the liver, kidneys, and heart
Age of 25-35 years at onset
Organ-specific manifestations characterized by exacerbations and a relapsing/remitting course
Skin and mucous membrane manifestations
Painful oral lesions (aphthous or herpetiform) are one of the criteria for diagnosis and may be the first manifestation (70% of cases). See the image below.
Oral lesions are commonly found in keratinized areas of the oropharynx, often excluding the nonkeratinized surfaces of the dorsal tongue, gums, and hard palate. The lesions are usually not distinguishable from those due to other causes but often have a high recurrence rate (often more than five times per year, despite only three times per year specified in ISG criteria) and appear as multiple lesions or crops (often more than six simultaneous lesions at a given time).
Skin lesions often occur in the genital region of both sexes. In males, scrotal involvement is most characteristic; however, lesions can also develop on the penile shaft. In females, the labial area is most commonly involved, with lesions occasionally developing in the vagina and on the perineum. Genital ulcerations typically heal with scarring and are more painful in men. Development of ulcerations in women may correlate with menstruation.
Nodules that resemble erythema nodosum are more common in the lower extremities of females. They are tender, erythematous, and nodular and usually resolve after 2-3 weeks but often recur. Erythema nodosum may be an indicator of mild Behçet disease.
Acneiform papulopustular lesions are more common in men and are usually found on the trunk and extremities, although they may develop anywhere on the body.
Extragenital ulcerations that heal with scarring are rare and affect only 3% of patients. These are very specific for Behçet disease. They can be found in the axillae, neck, breast, interdigital skin of the feet, and groin.
Positive pathergy test is more common in Turkish and Japanese populations, as well as patients with ophthalmic and neurologic manifestations.
Ocular presentations (anterior or posterior uveitis, hypopyon, retinal vasculitis, cystoid macular degeneration) represent the first manifestation of disease in 10% of patients with Behçet disease but usually occur following oral ulceration.
Symptoms commonly include blurred vision, periorbital pain, photophobia, scleral injection, and excessive lacrimation.
Men, particularly of Iranian and Japanese descent, tend to present with more severe eye involvement.
Highly recurrent posterior uveitis can lead to blindness.
Ocular symptoms usually present in the first years of illness. Cases that cause blindness commonly develop within the first 7 years. The prognosis is better for persons who develop symptoms later in the disease course.
Collectively, neurologic symptoms tend to be an unusual late manifestation, 1-8 years after disease onset.
Memory tends to be affected in most cases, particularly affecting recall and learning.
Orientation, arithmetic, and language are often unaffected.
Symptoms are usually parenchymal in nature, predominantly with brainstem involvement.
Behavioral changes, primarily apathy or disinhibition, occur in 54% of patients.
Seizures and bulbar signs with ophthalmoplegia are less common. Other less common findings include infarctions due to vasculitis or thrombosis, meningoencephalitis, lymphocytic meningeal infiltration, or demyelinization.
Behçet disease can cause aneurysms in the pulmonary arterial tree that often prove to be fatal. Pulmonary artery aneurysmal involvement is associated with right-sided cardiac thromboses and can manifest as hemoptysis, cough, chest pain, or dyspnea.
Vasculitis of the small and large vessels can cause a panoply of symptoms depending on location of the lesions.
Arterial disease predominantly affects males and only rarely occurs in women.
Venous involvement (usually in the form of superficial thrombophlebitis) is more common than arterial involvement. Superficial thrombophlebitis presents in a linear fashion with overlying erythema and is often confused with erythema nodosum. In males, formation of these linear areas of vasculopathy leads to sclerosis and stringlike thickening in the affected areas.
Symptoms correlate with the vessel involved and may be devastating. For example, extension of an inferior vena caval clot to the hepatic vein may be the mechanism of Budd-Chiari syndrome in Behçet disease.
Arthritis and arthralgias occur in as many as 60% of patients and primarily affect the lower extremities, especially the knee. Ankles, wrists, and elbows can also be primarily involved.
The arthritis is nondeforming and asymmetric in nature and can assume a monoarticular, oligoarticular, or polyarticular pattern of involvement.
Symptoms relapse and remit and rarely become chronic.
Diffuse arthralgias are also common.
Gastrointestinal (GI)/genitourinary manifestations (GU)
GI involvement affects 3-16% of patients with Behçet disease. Areas affected often include the esophagus and ileocecal area. Symptoms include abdominal pain, bloating, and GI bleeding. Complications often result from deep ulceration of intestinal sections.
Renal manifestations may be underreported. One study found that 1-29% of patients with Behçet disease developed such manifestations.
Associated amyloidosis may develop.
The first presentation is often nephritic-range proteinuria found incidentally. Crescenteric and proliferative glomerulonephritis, as well as IgA nephritis, have also been reported in some cases.[29, 30, 31]
Cardiac manifestations include coronary vasculitis and thrombosis, pericarditis, myocarditis, endocarditis with granulomatous changes or fibrosis, regurgitation, and diastolic dysfunction (5-17% of cases).
Lung involvement occurs in up to 18% of patients with Behçet disease. Pulmonary vasculitis, hypertension, and pleural effusions have been reported. Aneurysms represent a dreaded complication of Behçet disease and may result in massive hemoptysis. The detection of a pulmonary aneurysm in the setting of a vasculitic illness is highly suggestive of Behçet disease.
Ulcers are aphthous or herpetiform in nature and can occur in various keratinized areas of the oral cavity. They can be very painful, can last up to 3-5 weeks, and can vary in size. Large ulcers (>10 mm in diameter) heal with scarring, as do their genital counterparts.
Pseudofolliculitis and acneiform lesions, found more commonly in males with Behçet disease, primarily affect the trunk and extremities.
Erythema nodosum, which is more common in females with the disease, are occasionally differentiated from alternate etiologies based on ulceration, which is a characteristic more unique to Behçet disease.
Eye findings may include the following:
Anterior uveitis with and without hypopyon formation
Posterior uveitis that may cause blindness
Edematous appearance of the disc, with retinal detachment
Leaky retinal vessels revealed by fluorescein angiography, leading to atrophy and fibrosis in some cases
In a retrospective observational case series of 132 patients with Behçet-associated uveitis, the most common presentation was panuveitis, which occurred in 118 patients (89.4%). Bilateral episodes were observed in 100 patients (75.8%). At baseline, best-corrected visual acuity (BCVA) was 20/125 in both eyes.
Other ocular manifestations at presentation included retinal vasculitis (61 eyes, 26.3%), occlusive vasculitis in (59 eyes, 25.4%), and macular edema (42 eyes, 18.1%). Anterior segment complications included glaucoma in 44 eyes (19%) and cataracts in 34 eyes (14.7%). Optic nerve atrophy was the most commonly observed posterior segment complication. BCVA was better than 20/50 at last follow-up in 131 eyes (56.5%).
Pyramidal tract lesions with spastic paralysis and dementia have been demonstrated in some patients with Behçet disease. Neurologic signs may include the following:
Mental status changes
Positive Babinski sign
Difficulty with speech and swallowing
Apathy or disinhibition is common. Difficulty with recall and learning has been demonstrated. Peripheral nerve involvement is rare.
Lower-extremity superficial thrombophlebitis often presents in a linear fashion with overlying erythema and tenderness. Palpation of sclerosed thrombophlebitis yields subcutaneous stringlike quality.
Deep venous thrombosis (DVT) develops in some cases and typically manifests as local tenderness or as disparity in limb girth.
Saadoun et al found that cerebral venous thrombosis (CVT) was present in 7.8% of a large cohort of patients with Behçet disease. The main complication of CVT was severe visual loss due to optic atrophy. Papilledema and concurrent prothrombotic risk factors were independently associated with the occurrence of sequelae; peripheral venous thrombosis and concurrent prothrombotic risk factors were associated with relapse of thrombosis. Anticoagulant therapy proved safe and effective in up to 90% of patients.
Arterial vasculitis may manifest as claudication symptoms.
The arthritis has predominance for the lower extremities but may occur in any pattern.
Arthritis is usually not destructive or deforming. Joint-fluid content often reflects only inflammatory properties. Aseptic necrosis develops in rare cases.
Ulcerative lesions can cause abdominal pain, bloody diarrhea, and occasional intestinal perforation. GI lesions are indistinguishable from those associated with inflammatory bowel disease but commonly occur in the ileocecal region.
In females, genital lesions commonly appear in the labial folds but can also be found in the vulva and vagina. In males, they are usually scrotal in nature but can also develop in the perianal region and penile shaft. Epididymitis manifests as scrotal tenderness.
Genital ulcers last longer than oral lesions, are deeper, and typically scar after healing.
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