# 19 - 376 Behçet Syndrome

### 376 Behçet Syndrome

Yusuf Yazici

Behçet Syndrome
PART 11
Immune-Mediated, Inflammatory, and Rheumatologic Disorders 
Behçet syndrome is a systemic vasculitis, first described by Hulusi 
Behçet, a Turkish dermatologist. It can present with oral and genital 
ulcers, skin lesions, uveitis, arthritis, major arterial and venous ves­
sel disease, and gastrointestinal and neurologic manifestations. These 
manifestations can be present in various combinations and sequences 
over time. Patients are most commonly from the Middle East, the 
Mediterranean region, and the Far East; it is most prevalent in Turkey, 
with a prevalence of 1 in 250 adults. It is relatively rare before the late 
teens and after age 50. Males and females are equally affected; however, 
males frequently have more severe disease and poorer outcomes. Some 
manifestations may show regional differences; for example, gastroin­
testinal involvement, rare in Turkey, is more common in Japan and is 
seen in ~30% of patients in the United States.
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■DIAGNOSIS
Behçet syndrome is diagnosed clinically. There are no specific labora­
tory, imaging, or histologic features that can help in the diagnosis of a 
patient with suggestive symptoms. However, these can be used in rul­
ing out conditions that may mimic Behçet syndrome and the diagnosis 
is based on a combination of clinical features in the setting of ruling 
out other potential causes. In this regard, some patients may require 
months to years to develop the array of symptoms that would lead 
to a definitive diagnosis, although a tentative diagnosis may be made 
well before. The most commonly used and best performing diagnostic 
criteria are the International Study Group (ISG) criteria (sensitivity 
~95%, specificity ~96%); patients need to have recurrent oral ulcers 
plus two of the following four clinical manifestations: recurrent genital 
ulcers, skin lesions, eye lesions, or a positive pathergy test (Table 376-1). 
Additional clinical manifestations may involve various organ systems, 
including the gastrointestinal, vascular, pulmonary, and central ner­
vous systems. Up to 50–60% of patients, depending on where they 
are from, can be positive for HLA B∗51; however, it is not used as a 
diagnostic test because it is also found in around 20% of the normal 
population.
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■PATHOGENESIS
The pathogenesis and etiology of Behçet syndrome are unknown. 
Family studies show a possible genetic predisposition, and increased 
inflammation and immunologic mechanisms play a role. Both innate 
and adaptive immune systems may be involved. Unlike other auto­
immune diseases, however, Behçet syndrome is not typically associated 
with autoantibodies, Raynaud’s phenomenon, Sjögren’s syndrome, 
thrombocytopenia, hemolytic anemia, sun hypersensitivity, serosal 
involvement, or an increased risk for other autoimmune diseases. 
On the other hand, features that separate it from autoinflammatory 
conditions include tendency to abate with time, absence of mutations 
TABLE 376-1  International Study Group Criteria for the Diagnosis of 
Behçet Syndrome
CRITERIA
FREQUENCY
COMMENTS
Oral ulcers
~98%
At least 3 times in a 12-month period
Plus 2 out of 4 from below:
 
 
Recurrent genital ulcers
~80%
Usually scarring
Skin lesions
~80%
Erythema nodosum, pseudofolliculitis, 
papulopastular or acneiform nodules 
(postadolescent, not receiving 
corticosteroids)
Eye lesions
~50%
Anterior or posterior uveitis, cells in 
vitreous or retinal vasculitis
Pathergy
~50%
Evaluated in 24–48 h, after dermal 
insertion of a 20-gauge needle

associated with autoinflammatory diseases, and higher prevalence 
than typical autoinflammatory diseases such as familial Mediterranean 
fever (Chap. 381). There is neutrophil hyperreactivity; however, it is 
not clear whether this is primary or secondary to cytokine-directed 
activation. There is also evidence from retrospective patient cohort 
analyses that there may be different clusters of disease presentation; 
for example, acne lesions are more commonly seen with arthritis and 
associated with enthesitis, and each of these clusters may have a differ­
ent pathogenesis.
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■CLINICAL PRESENTATION
The most common symptoms are associated with mucocutaneous tis­
sues. Oral ulcers are seen in virtually all patients and are commonly the 
first manifestation (Fig. 376-1). Commonly, like ordinary canker sores, 
they are usually multiple. They last around 10 days but recur unless 
treated. Only the uncommon, major ulcers tend to scar. Beneficial 
effects of dental and periodontal therapies suggest that decreased oral 
health is associated with disease severity.
Genital ulcers are the most specific lesions, most commonly occur­
ring on the scrotum or labia (Fig. 376-1). They are larger and deeper 
and take longer to heal than oral ulcers and tend to form scars.
Acne-like or papulopustular lesions are indistinguishable from acne 
vulgaris in appearance and pathology. They are seen both at the usual 
acne sites as well as at uncommon sites such as lower extremities. Other 
skin findings are the nodular lesions, which are of two types: erythema 
nodosum lesions due to panniculitis and superficial vein thromboses. 
Superficial thrombophlebitis often occurs in men and is associated 
with deep-vein thrombosis; it should trigger workup for other vascular 
involvement, including pulmonary artery aneurysms.
Pathergy reaction is a nonspecific hyperreactivity of the skin 
to trauma. Typically, a papule or pustule forms in 24–48 h after a 
A
B
FIGURE 376-1  Clinical findings in Behçet syndrome. A. Behçet oral ulcer. B. Behçet 
scrotal ulcer.