Oral ulceration is the hallmark of the disease, tends to be the earliest manifestation, and is required for the diagnosis of Behçet disease (Table 38–1). Oral ulcers are painful, shallow or deep, round or oval, with a white or yellow base and red halo (Figure 38–1). They vary in size from 1–20 mm. The ulcers most frequently affect the buccal mucosa, tongue, lips, gingivae, palate, tonsils, uvula, or pharynx. During an attack, patients usually have two to five lesions, but some patients may have a single ulcer or too many to count. The aphthae may be so painful that the patient has trouble eating or drinking. Usually the aphthous lesions heal without scarring over 10–20 days.
Table 38–1. Frequency of Clinical Manifestations of Behçet Disease. ||Download (.pdf)
Table 38–1. Frequency of Clinical Manifestations of Behçet Disease.
|Central nervous system disease||10–20|
A and B: Multiple aphthous ulcers behind the upper and lower lips of a man with Behçet disease.
Genital aphthae occur slightly less often than oral ulceration (Table 38–1). However, genital ulcers tend to be larger and deeper, and often heal with scarring. In men, the ulcers develop most commonly on the scrotum and less commonly on the shaft of the penis, and in women ulcers affect the vagina and vulva. Genital lesions in men are often associated with epididymitis.
Cutaneous manifestations of Behçet disease, which develop in 60–90% of patients, are protean. Erythema nodosum occurs most commonly, especially in women. Erythema nodosum in Behçet disease tends to ulcerate and heal with scarring and hyperpigmentation, compared with erythema nodosum associated with sarcoidosis and inflammatory bowel disease, which does not ulcerate and heals without scarring. In men, pseudofolliculitis and acneiform nodules develop frequently over the neck and face. Pathergy—the phenomenon of developing an aseptic nodule or ulcer larger than 2 mm in diameter 24–48 hours following a sterile needle prick to the forearm—occurs frequently in Japanese and Turks but in only approximately one third of Americans with Behçet disease. Migratory thrombophlebitis also commonly occurs in Behçet disease.
Ocular inflammation, one of the hallmark manifestations of Behçet disease, tends to occur early in the course. Recurrent or persistent ocular inflammation frequently leads to visual loss, making eye inflammation one of the most common causes of disability in Behçet disease. Behçet disease is one of the few autoimmune diseases that can cause both anterior and posterior uveitis. Anterior uveitis typically presents with a red eye, intense photophobia, and blurred vision. The anterior uveitis may be so intense that a grossly visible layer of pus in the anterior chamber (hypopyon) develops. The posterior uveitis and vasculitis of the carotid and retina occur less commonly but pose a greater threat to vision.
Peripheral arthritis or spondylitis develops in approximately half of patients with Behçet disease. The peripheral arthritis may be monarticular or polyarticular, while the spondylitis usually presents as sacroiliitis (with low back or buttock pain). The peripheral arthritis is usually not deforming.
Gastrointestinal involvement develops in about one-quarter of patients. Although gastrointestinal involvement can appear at any time, it typically emerges several years after the onset of oral ulcers. Behçet disease of the gastrointestinal tract most commonly presents as aphthous ulcers affecting the ileum and cecum. However, any portion of the gut from the mouth to the anus can be involved. The most frequent manifestations of bowel involvement are pain, anorexia, rectal bleeding, vomiting, and diarrhea. In American patients, esophageal ulceration appears especially common. In addition, ischemia of the bowel may result from vasculitis of the medium- and large-sized mesenteric arteries. The unusual predilection for Behçet disease to involve veins explains why the Budd-Chiari syndrome develops in some patients.
Central nervous system disease, which develops in 10–20% of patients, resembles gastrointestinal involvement in following oral ulceration by 3–5 years. The neurologic features are variable and include headache and confusion (from recurrent sterile meningitis) and meningoencephalitis. Meningoencephalitis in Behçet disease most commonly affects the brainstem but can also affect the thalamus, basal ganglia, thalamus, cortex and white matter, spinal cord, or cranial nerves. Other complications are thrombotic or hemorrhagic hemispheric stroke, dural venous thrombosis, seizures, hearing and vestibular involvement, progressive dementia, and psychiatric disease including personality changes. Behçet disease rarely involves the peripheral nervous system.
Large-vessel vasculitis explains why bruits develop in some patients’ chest or abdomen. The most commonly involved sites are the pulmonary, carotid, aortic, iliac, femoral, and popliteal arteries. Affected vessels—especially in the pulmonary and mesenteric circulation—may occlude, develop aneurysm swelling, or rupture. Hemoptysis and pulmonary nodules are common manifestations of lung involvement. Aneurysms of the proximal pulmonary arteries develop commonly in those with lung disease. The Hughes-Stovin syndrome, defined by pulmonary artery thrombosis and aneurysms occurring with peripheral thrombophlebitis, develops most commonly in patients with Behçet disease. Clinically important cardiac disease (most typically with coronary artery vasculitis) develops infrequently, and renal disease occurs rarely.
Behçet disease produces no specific blood test abnormalities. Nonspecific markers of inflammation, such as anemia, mild leukocytosis, and an elevated erythrocyte sedimentation rate, are common during attacks of active inflammation. Patients with active Behçet disease also often show elevated levels of serum IgD. Cerebrospinal fluid analysis in patients with meningoencephalitis usually reveals elevations of protein and IgG and a pleocytosis of either polymorphonuclear cells or lymphocytes.
Patients with neurologic disease can have abnormalities evident on computed tomography (CT) scans or magnetic resonance imaging (MRI). The most frequent MRI abnormalities are seen with T2 weighting and consist of multiple high-intensity focal lesions that are widely distributed. Angiograms or magnetic resonance angiography can demonstrate large-artery thrombosis and aneurysm, typically seen in the chest or abdomen.
Biopsies of mucocutaneous lesions and gastrointestinal ulcers reveal a neutrophilic vascular reaction. True vasculitis is rare. The pathergy phenomenon is uncommon in Americans.