D. Serologic findings
2. pANCA Indirect Immunofluorescence Assay
Table 8. shows that pANCA test result of patients with RAU, BD and healthy volunteers.
Only one patient of intestinal BD was positive. There were no significant differences between patients with RAU, BD and healthy volunteers.
Table 8. pANCA test result of patients with RAU, BD and healthy control RAU(%)
(n=12)
BD(%) (n=16)
Healthy control(%) (n=4) pANCA
Positive 0(0) 1(6) 0(0)
Negative 12(100) 15(94) 4(100)
RAU, recurrent aphthous ulcer; BD, Behçet’s disease; ASCA,Anti-Saccharomyces cerevisiae Mannan antibody; pANCA, perinuclear antineutrophil cytoplasmic autoantibody
IV. DISCUSSION
The clinical diagnosis of BD may pose considerable difficulties. Since the disease is multi-systemic and does not have any pathognomonic symptom or laboratory findings, the diagnosis is made solely on the basis of the criteria proposed by ISGBD in 1990, based on a cluster of clinical manifestations. Nonetheless, the diagnosis might be delayed for several years, until all ISG criteria have been fulfilled. Thus, the presence of a relatively specific laboratory marker can substantially facilitate the diagnosis of BD, and possibly support a diagnosis before all disease manifestations have occurred.
RAU is seen in most patients with BD; it commonly precedes other systemic features and can be of major, minor or herpetiform types. However, it is difficult to predict with any certainty those patients initially presenting with RAU who will subsequently proceed to develop multisystem involvement as part of BD. Two studies have addressed this problem; in one, a clinical comparison between 38 patients with BD and RAU-only controls showed an increased number of concurrent ulcers and involvement of the soft palate and oropharynx in those diagnosed with BD(Main and Chamberlain, 1992). No differences were detected with respect to duration, frequency, age of onset or family history. Scrutiny of clinical photographs taken of BD patients in this study suggested that both ‘herpetiform-type’ and ‘aphthous type’
ulcers appeared atypical(Main and Chamberlain, 1992). Clinical observations in oral medicine clinics suggest that aphthous ulcers in patients with BD appear to be associated with increased
tissue edema and appear to have an intensely erythematous border. The aphthae in BD often occur in the soft palate and oropharynx and have been observed on the hard palate, which is an unusual site for RAU in patients without BD(Main and Chamberlain, 1992). Patches of mucosal erythema may be observed in patients with the disease, indicating possible instability of the oral mucosa prior to ulceration. Patients may paradoxically report no painful symptoms during active disease, despite extensive oral ulceration being clinically evident. Bang et al examined the prognosis of the clinical relevance of recurrent oral ulceration in BD, and investigators found that approximately half the patients who were initially diagnosed as RAU-only developed other manifestations of BD at an average of 7.7 years after onset(Bang, 1995). They reported that highly recurrent RAU had appeared to be a warning signal for BD.
Many authors consider the onset to be the age at which the patient fulfilled the diagnostic criteria. The third decade is the most commonly reported age of onset for BD(Chajek and Fainaru, 1975; Bang et al, 1997; Yoo et al, 1997), and the fourth decade for intestinal BD(Kasahara et al,1981). In our study, intestinal BD occurred at a mean age of 29.0 years and RAU occurred at a mean age of 34.7 years. Althougt the mean age of RAU was higher than BD, no difference was found between the two groups in statistical analysis.
The male to female ratio in BD also differs geographically (Shimizu et al, 1979;
Kaklamani et al, 1998); however, the gender ratio in terms of intestinal BD has not been well characterized in Mediterranean and Western countries, probably because of its relative rarity.
in Korea (0.7–1.3:1) (31,35,36) and Japan(1.7:1)(Kasahara et al, 1981). But there were no signicicant differences with BD and RAU(0.8:1).
It has been well known for many years that BD is often accompanied by such gastrointestinal symptoms as nausea, vomiting, and abdominal pain.(Lehner, 1977; Bayraktar, 2000). About 22 percent of patients with intestinal BD developed appendicitis-like symptoms during the clinical course(Kodama, 1977). This study showed that the most common presenting symptom in intestinal BD and RAU with GI symptoms is abdominal pain(66% and 54%). Diarrhea and indigestion were second common presenting symptoms in this two groups.
The pathologic hallmark of intestinal BD is known to be the presence of a few punched-out ulcers of variable size and appearance(Lee, 1986). The smaller ulcers (“aphthoid ulcers”) have been considered histologically to be similar to the oral aphthous ulcers of BD(Thach and Cummings, 1976). Larger ulcers usually have an oval or irregular configuration.
The depth of penetration of the ulcers varies. Superficial ulcers occasionally have been shown to resolve(Smith et al, 1973; Empey, 1972; Lebwohl et al, 1977), but deeper ulcers, often with a narrow fissuring appearance, can extend through the bowel wall. Intestinal perforation is, therefore, a common complication(Shimizu et al, 1979; Kasahara et al, 1981; Ha et al,1998;
Lee et al, 1997). Although intestinal BD is diagnosed radiologically or endoscopically in many cases, relatively few descriptions about the endoscopic characteristics of intestinal BD exist in the literature. Morphological characteristics of intestinal BD have been reported to be discrete
ulcerations that have a confluent and discrete border, appearing most commonly in the ileocecal region(Kasahara et al,1981; Bayraktar et al, 2000; Baba et al, 1976; Lee et al, 1997).
In our series, most of the ulcers in intestinal BD and RAU on colonoscopy were found in the ileocecal areas, but they may be present at any site throughout the digestive system. Many of the patients had single or relatively few ulcers with localized distribution. The colonoscopic characteristics of intestinal BD could be summarized as large sized, round /oval or geographically shaped, deep and discrete ulcer with elevated margins. Because just we have examined the photography of endoscopy, we were difficult to find out differences of an ulcer including its shape, and location and the distribution pattern of lesions in intestinal BD and RAU.
The ulcers from the intestinal BD tend to be deep and penetrating and, thus, frequently required surgical interventions(Sayek et al, 1991; Ketch et al, 1980; Kim et al, 1994; Kim et al, 2000). Complications of GI ulceration in BD may include perforation and enterocutaneous fistula. Surgical treatment is often necessary, but postoperative recurrence is as high as 68%(Choi et al, 2000). In the current study, we found that two cases of intestinal BD were recurred after operation. Therefore, more attention should be paid in patients with perforating type of intestinal BD
The intestinal ulcer of BD is characterized not only by absence of the granulomatous formation of Crohn’s disease, but also by a deeper penetration of ulcer to a region nearer the
diagnos of BD. Of course, it is necessary to examine carefully the clinical symptoms and signs and the histopathological appearance, since in many cases the differential diagnosis is very difficult.
In our study, most common histopathologic findings of intestinal ulcers in BD were vasculitis, patched mixed lymphocyte dominant infiltration. There were no significant differences between patients with intestinal BD and RAU.
Since 1990, perinuclear anti-neutrophil cytoplasmatic antibodies (pANCAs), which show a specific staining on indirect immunofluorescence, have been consistently found in 40–80%
of patients suffering from ulcerative colitis(Rump et al, 1990; Duerr et al, 1991; Oudkerk et al, 1993; Peeters et al, 2001). These are spontaneously produced by lamina propria and mesenteric node lymphocytes(Targan et al, 1995). In ulcerative colitis, the antigen recognized by pANCAs is located in the inner side of the nuclear periphery and is DNase sensitive, but the exact epitope remains as yet unknown. It is hypothesized that pANCAs are due to cross-reactivity with bacterial antigens(Seibold et al, 1998; Cohavy et al, 2000).
Antibodies to baker’s yeast and brewer’s yeast (ASCA) have been described in up to 65%
of patients with Crohn’s disease(Main et al, 1988; McKenzie et al, 1990; Giaffer et al, 1992;
Sendid et al,1996). It has been demonstrated that the specific antigen is a mannan localized in the yeast cell wall(Sendid et al,1996). The significance of ASCAs in Crohn’s disease is completely unknown, but one hypothesis links them to increased intestinal permeability(Vermeire et al, 2001). Due to this presumed break in the epithelial barrier,
increased exposure of the epithelium to common food antigens such as yeasts may result in an exaggerated antibody response.
Kim et al have reported that ASCA may be associated with Crohn’s disease and BD and pANCA with ulcerative colitis. Positivity for ASCA with pANCA negativity was associated with Crohn’s disesae and Behçet’s disease , whereas a positive pANCA in combination with a negative ASCA result was strongly correlated with ulcerative colitis. A combination of both tests may aid the differential diagnosis of inflammatory bowel disease(Kim et al, 2002).
Recently, Krause et al have reported the significantly higher ASCA values in BD patients compared with patients with RAU, SLE or in healthy volunteers imply that ASCA, taken in appropriate clinical context, could become a useful diagnostic tool for BD(Krause et al, 2002).
Monselise et al have reported ASCA titers were significantly higher in BD patients companied to their healthy family members(Monselise et al, 2002). ASCA seem to be strongly related to BD expression and are not associated with environmental or genetic factors.
But in our study, there were neither clinically, endoscopically, histopathologically nor serologically differences between patients with intestinal BD, RAU and healthy volunteers in ASCA and pANCA. Further prospective studies including more numbers of patients are needed to make a diagnosis of intestinal BD and RAU.
V. CONCLUSIONS
There were a wide range of clinical features for gastrointestinal involvement including abdominal pain, indigestion, diarrehea, melena, nausea, vomiting in the two groups, RAU with gastrointestinal symptoms and BD with gastrointestinal involvement.
In the two groups, localized ulcer was most common colonoscopic findings and most ulcers were discovered in ileocecal region. There are many hisopathologic findings of ulcer were lymphocyte dominant, mixed, patched infiltration and vasculitis.
Although median level of ASCA was highest in serum of patients with BD, there were no significant differences in clinical, endoscopic, histopathologic findings between the two groups.
ASCA and pANCA levels were not different between the two groups unlike previous reports.
Patient of RAU with gastrointestinal involvement need to be closed follow up.
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