surgeons need to be aware of the lethal complication of behet s disease with intestinal ulcers , which tend to perforate at multiple sites3,4 . a review of the literature reveals that involvement of the gastrointestinal tract is not infrequent . we report here a series of 22 cases of intestinal behet s disease with multiple perforations , treated by emergency surgical resections . during the 25  years from july 1979 to june 2004 , 125 patients with behet s disease were encountered at the cardinal tien hospital and tri - service general hospital , taipei , taiwan . eighty - two patients were diagnosed as having intestinal behet s disease , which was based on the mason 22 had intestinal perforations ( see table  2 for the details of these 22 cases ) . barnes criteriamajor symptomsminor symptomsbuccal ulcerationsgastrointestinal lesionsgenital ulcerationsthrombophlebitisocular lesionscardiovascular lesionsskin lesionsarthritisneurologic lesionsfamily historythree major or two major and two minor criteria are required to establish the diagnosis of behet s diseasetable  2intestinal perforation in behet s disease encountered at cth and tsgh ( from 1979 to 2004 , n  =  22)case no.age ( years)sexoral ulcergenital ulcergi s & socular signsskin lesionpathergic reactionarthritis or arthalgia138m+++++245m++++++326f+++447m+++++528f+++++636f++++722m++++842m++++922m++++++1028f++++1165m++++1223m++++1332f++++1424m++++++1534m+++1641f++++1738m++++++1833m++++1925m++++++2048f++++2129m++++2250f+++++plus signs mean that the feature is present ; minus signs mean that the feature is not present.cth = cardinal tien hospital , tsgh = tri - service general hospital , s & s = symptoms and signsreperforations at ileum after partial resection of ileumreperforation at ileum after ileocecal resection the mason barnes criteria three major or two major and two minor criteria are required to establish the diagnosis of behet s disease intestinal perforation in behet s disease encountered at cth and tsgh ( from 1979 to 2004 , n  =  22 ) plus signs mean that the feature is present ; minus signs mean that the feature is not present . cth = cardinal tien hospital , tsgh = tri - service general hospital , s & s = symptoms and signs reperforations at ileum after partial resection of ileum reperforation at ileum after ileocecal resection in 13 of these 22 cases , the diagnosis was confirmed at surgical resection for multiple perforations . nine of the 22 cases had behet s disease with intestinal involvement , which was confirmed preoperatively , six were confirmed by endoscopic examination ; two by radiological examination ; and one patient had gastrointestinal symptoms of intermittent abdominal pain , diarrhea , and nausea . the ages of the patients with perforated intestinal behet s disease ranged from 22 to 65  years , with a mean age of 35.3  years . the age at onset of symptoms of behet s disease varied from 18 to 64  years on diagnosis , with a mean age of 33.1  years . in table  2 , oral ulcers with gastrointestinal symptoms and signs were found concurrently in all 22 cases , genital ulcers in 19 cases , ocular lesions in 12 cases , and skin lesions in 11 cases . they varied from 2 to 8  mm in size and invariably healed without scarring . 2 ) resembled the oral ulcers in appearance and course , except that vaginal ulcers were painless . four patients had anterior uveitis and eight had a mild relapsing conjunctivitis as their sole ocular lesion . 3 ) , and legs . biopsy of dermal subcutaneous lesions had been done in 10 cases . in each of them , figure  1buccal ulcer.figure  2penile ulcer.figure  3nodular cutaneous lesion on the back.figure  4vasculitis characterized by lymphocytic and plasmacytic infiltration of perivascular tissue ( hematoxylin and eosin ; 10    40 ) . vasculitis characterized by lymphocytic and plasmacytic infiltration of perivascular tissue ( hematoxylin and eosin ; 10    40 ) . there were no specific immunologic abnormalities in any of the 16 patients tested ( table  3 ) . igg was increased in 3 of 16 patients , iga in 5 patients , and igm in 3 patients . there was a significant decrease of igg in two patients and of iga in one patient . alpha-2 globulin was increased in 9 of 16 patients , and gamma globulin was increased in seven patients . table  3laboratory datacase no.immunoglobulins ( mg / dl)serum complement ( mg / dl)globulin ( % ) iggigaigmc3c411,9763752501453813.823.821,726245174924012.010.842,1504002401104514.224.651,500590300382510.518.077401856090387.814.381,18019514059326.612.292,2704642621274614.016.2111,8503802501905012.523.5121,30032023588399.615.0142,3504902951804813.325.01668098561503513.021.8171,65047528076349.412.5181,8002901501054513.823.2192,4185812091664014.428.0211,8803302501803510.520.0221,9853862281683813.824.2normal range9502,110170410542624719127524.812.18.822.8reperforations at ileum after partial resection of ileumreperforation at ileum after ileocecal resection reperforations at ileum after partial resection of ileum reperforation at ileum after ileocecal resection multiple concurrent penetrating ulcers ( fig . 5 ) were found in all 22 cases , with multiple perforation sites identified from terminal ileum to the ascending colon ( table  4 ) . the size and number of perforated ulcers were variable , ranging from 0.2 to 6  cm in size , and 4 to 16 in number . the perforations were found at the ileocecal region and ascending colon in 10 cases , at the terminal ileum in 8 cases , and at the cecum and ascending colon in 4 cases . figure  5surgical specimen of ileocecal region showing multiple penetrating ulcers.table  4operative findings and operation performed in 22 perforated intestinal behet s disease patientscase no.location of perforated ulcersno . of perforationsoral / genital ulceroperation performed1terminal ileum4+/+partial resection of the ileum2terminal ileum6+/+partial resection of the ileum3ileocecal region and ascending colon10+/right hemicolectomy and ileocecal resection4ileocecal region and ascending colon16+/+right hemicolectomy and ileocecal resection5cecum and ascending colon5+/ileocecal resection6terminal ileum5+/+partial resection of the ileum7terminal ileum4+/+partial resection of the ileum8cecum and ascending colon9+/+right hemicolectomy and ilececal resection9terminal ileum8+/+partial resection of the ileum10ileocecal region and ascending colon11+/+right hemicolectomy and ileocecal resection11ileocecal region and ascending colon10+/+right hemicolectomy and ileocecal resection12terminal ileum5+/+partial resection of the ileum13terminal ileum7+/partial resection of the ileum14ileocecal region and ascending colon11+/+right hemicolectomy and ileocecal resection15ileocecal region and ascending colon5+/+right hemicolectomy and ileocecal resection16ileocecal region and ascending colon13+/+right hemicolectomy and ileocecal resection17cecum and ascending colon4+/+ileocecal resection18ileocecal region and ascending colon7+/+right hemicolectomy and ileocecal resection19ileocecal region and ascending colon9+/+right hemicolectomy and ileocecal resection20cecum and ascending colon6+/+ileocecal resection21terminal ileum4+/+partial resection of the ileum22ileocecal region and ascending colon12+/+right hemicolectomy and ileocecal resectionreperforations at ileum after partial resection of ileumreperforation at ileum after ileocecal resection surgical specimen of ileocecal region showing multiple penetrating ulcers . operative findings and operation performed in 22 perforated intestinal behet s disease patients reperforations at ileum after partial resection of ileum reperforation at ileum after ileocecal resection all 22 perforated intestinal behet s disease cases were confirmed at operation , with nine of them correctly diagnosed preoperatively . surgical resection of the perforated intestinal ulcers was done in all cases , with right hemicolectomy and ileocecal resection in 11 cases , partial ileum resection in 8 cases , and ileocecal resection in 3 cases . no reperforation occurred in the group of patients who underwent right hemicolectomy and ileocecal resection . however , two reperforations ocurred in patients who underwent partial ileum resection alone and one in the ileocecal resection group . the pathologic study of the resected specimens showed nonspecific inflammatory reactions with the infiltration of lymphocytes and plasma cells as the predominant finding ( fig . histological sections from the ulcer walls showed changes consistent with a nonspecific ulcerative inflammatory process and infiltration containing both plasma cells and chronic inflammatory cells . figure  6chronic inflammatory response and perivascular infiltration ( hematoxylin and eosin ; 10    10 ) . chronic inflammatory response and perivascular infiltration ( hematoxylin and eosin ; 10    10 ) . after operation on these 22 patients with behet s disease and intestinal perforation , four patients died during the postoperative course due to septic shock , which was present prior to the surgical intervention ; three died from complications of hypertension and diabetes mellitus ; and three were lost to follow - up . thus , only 12 patients are still under observation , without evidence of gastrointestinal complications up to this date . the remaining 60 cases of intestinal behet s disease , without perforations , are still under surveillance . the ages of the patients with perforated intestinal behet s disease ranged from 22 to 65  years , with a mean age of 35.3  years . the age at onset of symptoms of behet s disease varied from 18 to 64  years on diagnosis , with a mean age of 33.1  years . in table  2 , oral ulcers with gastrointestinal symptoms and signs were found concurrently in all 22 cases , genital ulcers in 19 cases , ocular lesions in 12 cases , and skin lesions in 11 cases . they varied from 2 to 8  mm in size and invariably healed without scarring . 2 ) resembled the oral ulcers in appearance and course , except that vaginal ulcers were painless . four patients had anterior uveitis and eight had a mild relapsing conjunctivitis as their sole ocular lesion . 3 ) , and legs . biopsy of dermal subcutaneous lesions had been done in 10 cases . in each of them , figure  1buccal ulcer.figure  2penile ulcer.figure  3nodular cutaneous lesion on the back.figure  4vasculitis characterized by lymphocytic and plasmacytic infiltration of perivascular tissue ( hematoxylin and eosin ; 10    40 ) . vasculitis characterized by lymphocytic and plasmacytic infiltration of perivascular tissue ( hematoxylin and eosin ; 10    40 ) . there were no specific immunologic abnormalities in any of the 16 patients tested ( table  3 ) . igg was increased in 3 of 16 patients , iga in 5 patients , and igm in 3 patients . there was a significant decrease of igg in two patients and of iga in one patient . alpha-2 globulin was increased in 9 of 16 patients , and gamma globulin was increased in seven patients . table  3laboratory datacase no.immunoglobulins ( mg / dl)serum complement ( mg / dl)globulin ( % ) iggigaigmc3c411,9763752501453813.823.821,726245174924012.010.842,1504002401104514.224.651,500590300382510.518.077401856090387.814.381,18019514059326.612.292,2704642621274614.016.2111,8503802501905012.523.5121,30032023588399.615.0142,3504902951804813.325.01668098561503513.021.8171,65047528076349.412.5181,8002901501054513.823.2192,4185812091664014.428.0211,8803302501803510.520.0221,9853862281683813.824.2normal range9502,110170410542624719127524.812.18.822.8reperforations at ileum after partial resection of ileumreperforation at ileum after ileocecal resection reperforations at ileum after partial resection of ileum reperforation at ileum after ileocecal resection multiple concurrent penetrating ulcers ( fig . 5 ) were found in all 22 cases , with multiple perforation sites identified from terminal ileum to the ascending colon ( table  4 ) . the size and number of perforated ulcers were variable , ranging from 0.2 to 6  cm in size , and 4 to 16 in number . the perforations were found at the ileocecal region and ascending colon in 10 cases , at the terminal ileum in 8 cases , and at the cecum and ascending colon in 4 cases . figure  5surgical specimen of ileocecal region showing multiple penetrating ulcers.table  4operative findings and operation performed in 22 perforated intestinal behet s disease patientscase no.location of perforated ulcersno . of perforationsoral / genital ulceroperation performed1terminal ileum4+/+partial resection of the ileum2terminal ileum6+/+partial resection of the ileum3ileocecal region and ascending colon10+/right hemicolectomy and ileocecal resection4ileocecal region and ascending colon16+/+right hemicolectomy and ileocecal resection5cecum and ascending colon5+/ileocecal resection6terminal ileum5+/+partial resection of the ileum7terminal ileum4+/+partial resection of the ileum8cecum and ascending colon9+/+right hemicolectomy and ilececal resection9terminal ileum8+/+partial resection of the ileum10ileocecal region and ascending colon11+/+right hemicolectomy and ileocecal resection11ileocecal region and ascending colon10+/+right hemicolectomy and ileocecal resection12terminal ileum5+/+partial resection of the ileum13terminal ileum7+/partial resection of the ileum14ileocecal region and ascending colon11+/+right hemicolectomy and ileocecal resection15ileocecal region and ascending colon5+/+right hemicolectomy and ileocecal resection16ileocecal region and ascending colon13+/+right hemicolectomy and ileocecal resection17cecum and ascending colon4+/+ileocecal resection18ileocecal region and ascending colon7+/+right hemicolectomy and ileocecal resection19ileocecal region and ascending colon9+/+right hemicolectomy and ileocecal resection20cecum and ascending colon6+/+ileocecal resection21terminal ileum4+/+partial resection of the ileum22ileocecal region and ascending colon12+/+right hemicolectomy and ileocecal resectionreperforations at ileum after partial resection of ileumreperforation at ileum after ileocecal resection surgical specimen of ileocecal region showing multiple penetrating ulcers . operative findings and operation performed in 22 perforated intestinal behet s disease patients reperforations at ileum after partial resection of ileum reperforation at ileum after ileocecal resection all 22 perforated intestinal behet s disease cases were confirmed at operation , with nine of them correctly diagnosed preoperatively . surgical resection of the perforated intestinal ulcers was done in all cases , with right hemicolectomy and ileocecal resection in 11 cases , partial ileum resection in 8 cases , and ileocecal resection in 3 cases . no reperforation occurred in the group of patients who underwent right hemicolectomy and ileocecal resection . however , two reperforations ocurred in patients who underwent partial ileum resection alone and one in the ileocecal resection group . the pathologic study of the resected specimens showed nonspecific inflammatory reactions with the infiltration of lymphocytes and plasma cells as the predominant finding ( fig .  6 ) . histological sections from the ulcer walls showed changes consistent with a nonspecific ulcerative inflammatory process and infiltration containing both plasma cells and chronic inflammatory cells . figure  6chronic inflammatory response and perivascular infiltration ( hematoxylin and eosin ; 10    10 ) . chronic inflammatory response and perivascular infiltration ( hematoxylin and eosin ; 10    10 ) . after operation on these 22 patients with behet s disease and intestinal perforation , four patients died during the postoperative course due to septic shock , which was present prior to the surgical intervention ; three died from complications of hypertension and diabetes mellitus ; and three were lost to follow - up . thus , only 12 patients are still under observation , without evidence of gastrointestinal complications up to this date . the remaining 60 cases of intestinal behet s disease , without perforations , are still under surveillance . in 1937 , behet described a chronic relapsing triple - symptom complex of oral ulceration , genital ulceration , and ocular inflammation5 . over the years , it has become apparent that the process is a systemic recurrent inflammatory disease affecting a number of organs consecutively6 . in 1940 , bechgaard first described intestinal involvement in behet s disease . baba et al.4 . agreed to this proposal and cited 49 cases of the disease treated from 1975 . since then , the number of operations reported has increased rapidly3 , but perforated intestinal behet s disease is still rarely reported . in a large review series , oshima and colleagues reported that 40% of patients with behet s disease had gastrointestinal complaints , such as nausea , vomiting , and abdominal pain24,8,9 . the age at onset of these symptoms ranges from 16 to 67  years , and the male - to - female ratio ranges from 1.5:1 to 2:12,5 . the third decade is the most commonly reported age of onset for behet s disease6,8,10,30 and the fourth decade for intestinal behet s disease3 . in our study , however , behet s disease and intestinal involvement were diagnosed simultaneously in some of these patients , most of whom had already experienced systemic manifestations . the exact cause of this disease still remains an enigma . current hypotheses include allergic vasculitis of small vessels , autoimmune disease , and immunologic deficiency2,4,11,12 . the deposition of immune complexes in the walls of small blood vessels was found by the laboratory results of three of our cases , and this process has been proposed as one of the underlying pathologic mechanisms in intestinal behet s disease12 . since no clinicopathologic findings are pathognomonic in this disease , the diagnosis is made on the basis of combinations of various clinical symptoms and signs13 . they suggested the triad of buccal ulceration , genital ulceration , and eye lesion and skin lesion as major symptoms . the minor symptoms included gastrointestinal lesions , arthritis , thrombophlebitis , cardiovascular lesions , neurologic lesions , and family history . three major criteria or two major criteria and two minor criteria are necessary for diagnosis . if we hold the original triple - symptom complex as a prerequisite for the diagnosis , cases may be missed . in 1990 , the international study group for behet s disease14 introduced a diagnostic criteria requiring the presence of oral ulcerations plus any two of the following : genital ulcerations , typical eye lesions , typical skin lesions , or positive results to a pathergy test . however , some reports have shown that almost 20% of patients with behet s disease presented without oral lesions initially15,16 . furthermore , 25% of patients did not show any oral lesions at all16,17 . in our series , all perforated cases present oral or genital ulcerations at the same time . because we warned that patients of intestinal behet s disease may have abdominal pain and oral or genital ulcerations concurrently , a phenomenon of pathergy was first described by blobner in 1937 and was further elaborated by katzenellenbogen in 1968 . it consists of an itradermal test applied to behet s disease patients with a sharp needle prick causing skin hypersensitivity , which is characterized by the formation of a sterile pustule 24 to 48  h after the trauma . biopsy at the intradermal puncture site is taken 48  h after for histopathologic evaluation . in a study conducted by tuzum et al . , this reaction was found to be positive in 84% of 58 patients with the disease , as compared to 3% of 90 healthy controls1 . a positive pathergic reaction should make us aware of the possibility of the disease in the presence of any of the accepted symptoms of this process . however , the recent results and interpretations of pathergy tests have varied widely according to the technical aspects of the tests18,19 and ethnic differences of the patients . nonspecific perivascular infiltrations of plasma cells and lymphocytes are usually found in the cutaneous and mucosal lesions5,20 . the intestinal ulcers in behet s disease are characterized not only by the absence of the granulomatous formation of crohn s disease , but also by deeper penetration of the ulcers to areas nearer to serosa membrane than the ulcers of ulcerative colitis3,4,21 . the ulcers tend to be undermined , and the submucosal connective tissues are usually destroyed . the bases of the ulcers are avascular with edema - like swelling and crater - shaped formation around the ulcer margin.2,2224 these ulcers are usually found in the terminal ileum and the cecum , but they may be present at any site throughout the digestive system and tend to perforate at multiple sites2529 . the gross pathologic characteristics of our intestinal behet s disease included perforations at multiple sites concurrently in variable sizes and configurations , extending from the ileocecal region to ascending colon , in accordance with the reported literature3,4,8,30,31 . . topical application of corticosteroids decreases the ocular inflammation , and is also useful in relieving the pain of oral ulcers . haim and sherf reported a favorable response to fresh blood and plasma in cases of behet s disease , but the nature of the useful component in hematotherapy is unknown5 . in our two patients with perforations , resection of the ileocecal region or the right half of the colon is the usual operation in the treatment of gastrointestinal complications3,4 . in our series , perforations at multiple sites were found in all cases ; right hemicolectomy and ileocecal resection were performed in 11 cases without reperforation ; ileocecal resection in 3 cases with one reperforation ; and partial resection of the ileum in 8 cases with two reperforations . because concurrent oral and genital ulcers were found in all patients in our series , the presentation of this seemingly innocuous clinical manifestation along with gastroinstestinal symptoms should raise the level of suspicion that intestinal involvement and complications of perforations may have already happened . the other constant finding among our 22 patients is that all the intestinal perforations were located between the terminal ileum and the ascending colon . therefore , to prevent reperforations , wide excision of the terminal ileum with right hemicolectomy is recommended for perforated intestinal behet s disease . we found out that the specimens of the resected bowel of the 19 nonreperforated patients all had more than 60  cm of terminal ileum , but those of the three reperforated cases had less than 60  cm . furthermore , the perforation sites were all at 10 to 12  cm proximal to the anastomosis . this is the main reason we recommend the resection of up to 80  cm of ileum from the ileocecal valve at the time of right hemicolectomy4,31 .
behet s disease accompanied by intestinal involvement is called intestinal behet s disease . 
 the intestinal ulcers of behet s disease are usually multiple and scattered and tend to perforate easily , so that many patients require emergency operation . 
 the aim of this study is to determine the extent of surgical resection necessary to prevent reperforation and to point out the findings of concurrent oral and genital ulcers and multiple intestinal perforations in all patients of our series . during a 25-year study period 
 , information of 125 behet s disease cases was gathered . among the 82 patients who were diagnosed with intestinal behet s disease , 22 cases had intestinal perforations needing emergency laparotomy . 
 we investigated and analyzed these cases according to the patients demographic characteristics , clinical presentations , laboratory data , and surgical outcome . 
 there were 14 men and 8 women ranging from 22 to 65  years of age . 
 nine cases were diagnosed preoperatively , and the diagnoses were confirmed in all 22 cases during the surgical intervention . 
 surgical resection was performed in every patient , with right hemicolectomy and ileocecal resection in 11 cases , partial ileum resection in 8 cases with two reperforations , and ileocecal resection in 3 cases with one reperforation .