Behçet's disease is a systemic inflammatory disorder of unknown cause, which has a broad spectrum of clinical features (1). Four major symptoms, oral recurrent aphthous ulcer, genital ulcers, ocular lesions, and skin lesions, are commonly seen in patients with Behçet's disease, whereas less frequent minor symptoms such as the neurological, vascular, and gastrointestinal symptoms can be lethal or leave serious complications.
Intestinal Behçet's disease is a subtype of the disease causing abdominal pain, diarrhea, and melena (2, 3). In serious cases, massive bleeding and intestinal perforation require surgical treatment (2). The ileocoecal region is the most frequently affected, though lesions can be distributed in any parts of the gastrointestinal tract (3). Rounded or oval punched-out type ulcerations like simple ulcers are the most characteristic pathological feature, while non-specific diffuse ulcerations and granulomatous lesions are similar to inflammatory bowel diseases such as Crohn's disease and ulcerative colitis. It is a general rule that major symptoms precede the development of gastrointestinal lesions in Behçet's disease. However, it is not rare that the diagnosis is not to be definitively established until an intestinal symptom appears, because typical ocular and skin symptoms occur less frequently in the patients with intestinal disease than in those with other subtypes of the disease. On the other hand, some patients with inflammatory bowel diseases show "Behçet's disease like symptoms" such as oral ulcers, erythema nodosum, arthritis, and uveitis. Recurrent oral ulcers also appear in patients with simple intestinal ulcers. Thus, it is sometimes difficult to make differential diagnoses of intestinal bowel diseases from Behçet's disease based on extraintestinal symptoms as well as intestinal lesions. Moreover, the confusion may arise from different diagnostic procedures among these diseases. A diagnosis of Behçet's disease relies on systemic symptomatology which is mostly evaluated by rheumatologists, dermatologists and ophthalmologists, whereas that of inflammatory bowel diseases is made on the basis of endoscopic findings which are assessed by gastroenterologists and pathologists.
In this issue, Kobashigawa et al reported a patient who was diagnosed with Behçet's disease after the diagnosis of ulcerative colitis had been established for more than 15 years (4). A barium enema showed a lead-pipe appearance as a typical finding of ulcerative colitis, while the patient also had recurrent oral ulcers, erythema nodosum, a positive pathergy test, elevated serum IgD, and HLA-B51, suggesting Behçet's disease. It is likely that a similar pathogenesis mediates the development of Behçet's disease and inflammatory bowel diseases.
Although the etiology of inflammatory bowel diseases remains undetermined, both genetic and environmental factors are implicated in the pathogenesis, as in Behçet's disease (5). The genetic factors of the diseases seem different from those in Behçet's disease (5). For example, it is well established that HLA-B51 is closely linked with Behçet's disease (1), whereas associations of DR4 and DQ4 with Crohn's disease (6), and those of B52 and DR2 with ulcerative colitis have been noted (7). Thus, analysis of HLA phenotypes may give some clue to the differential diagnosis.
Epidemiological studies have shown that Behçet's disease is prevalent in the ancient Silk Road, from the eastern Asia to the Mediterranean basin, whereas incidence of inflammatory bowel diseases is somewhat lower in the prevalent area than in the other parts of the world. Geographical distribution of the patients is partially related to frequency of the disease-related HLA phenotypes. Interestingly, frequency of intestinal symptoms is much higher in patients with Behçet's disease from Japan and Korea than in those from the other areas where the disease is prevalent, though the reasons remain unknown (1).
There is accumulating evidence that autoimmune responses and abnormal immune functions are involved in the development of these diseases. Immunological abnormalities of Behçet's disease are characterized by autoimmune responses against 60 kDa heat shock protein, neutrophil hyperfunction, and relative Th1 polarization with excessive production of inflammatory cytokines including tumor necrosis factor (TNF)-α (1). These features were also documented in patients with Crohn's disease (5). Accordingly, the recently developed therapeutic options have targeted immunological dysfunctions, though aminosalicylates, sulfasalazine, and corticosteroids are still the first line therapies for both disease entities (1, 5). Anti-TNF-α monoclonal antibody therapy has already been introduced into clinical application for patients with Crohn's disease (5) and has shown favorable outcomes in clinical trials for Behçet's disease. Thalidomide, another TNF inhibitor, has also revealed beneficial effects for these diseases (1, 5). Granulocyte and monocyte apheresis is applicable for patients with ulcerative colitis (8), whereas the clinical trial has been under way for patients with Behçet's disease.
Japanese physicians are expected to play a leading role in this field, because intestinal Behçet's disease clusters in eastern Asia. It is important to establish diagnostic consensus of the confused disease entities with similar manifestations among all physicians concerning intestinal Behçet's disease through mutual cooperation.