Spontaneous free perforation of the small intestine in Crohn ’ s disease

Department of Medicine (Gastroenterology), University of British Columbia, Vancouver, British Columbia Correspondence and reprints: Dr Hugh Freeman, Gastroenterology, ACU F-137, University of British Columbia Hospital, 2211 Wesbrook Mall, Vancouver, British Columbia V6T 1W5. Telephone 604-822-7216, fax 604-822-7236 Received for publication July 23, 2001. Accepted August 21, 2001 HJ Freeman. Spontaneous free perforation of the small intestine in Crohn’s disease. Can J Gastroenterol 2002;16(1):23-27.

C rohn's disease is characterized by a transmural intes- tinal inflammatory process with deep ulcers and the formation of abscesses or fistulous tracts into adjacent, often adherent intestinal and nonintestinal structures.Free spontaneous perforation into the peritoneal cavity is a dramatic event that is, fortunately, rare but necessitates urgent surgical intervention.It was initially described in 1935 as a fatal case of free perforation of the ileum (1).Since then, about 100 cases have been described.In part, this is due to differing criteria for the clinical definition of free perforation because sealed perforations or ruptured abscesses, as noted by others (2,3), may have been included in earlier reports.Moreover, there is only limited information on the subsequent clinical course of patients who have suffered from this intestinal complication, because of its rarity in patients with Crohn's disease.
In a previous report from this hospital (the University of British Columbia) (4), a clinical database of patients with Crohn's disease was described, including classification of the initial 877 patients.In this tertiary care teaching hospital setting, young adults, predominately females (56.1%), were affected with a high rate of intestinal complications.The present report further explores this specific complication of spontaneous free perforation of the small intestine in a single clinician series of Crohn's disease, with 1000 consecutively evaluated patients.This series not only provides, for the first time, data from a Canadian experience with this complication in patients with Crohn's disease, but also allows the evaluation of the longer term clinical course after initial treatment for this intestinal complication.

PATIENTS AND METHODS
A total of 1000 consecutively evaluated patients with Crohn's disease were evaluated.All patients were seen directly by the author, and, as previously noted (4), a diagnosis of Crohn's disease was established on the basis of defined criteria (5).Free perforation of the small intestine was defined by surgical and pathological definitions of a focal small intestinal perforation with peritonitis, and excluded sealed perforations or ruptured abscesses.No patient had undergone prior small intestinal instrumentation, and pathological evaluation of resected tissues in all patients confirmed the pathological diagnosis of Crohn's disease.No patient had another or superimposed cause for small intestinal ulceration or perforation, including carcinoma (6,7) or lymphoma (3,8).
Patients with colonic perforation or appendiceal disease were excluded, and no patients have been seen to date with spontaneous free esophageal or gastroduodenal perforation (9,10).

Fifteen patients (nine female [60%] and six male [40%]
) with Crohn's disease were seen with spontaneous free perforation of the small intestine in this series of 1000 consecutively evaluated patients (1.5%) -consistent with the estimated frequency of this complication in the literature from the United States and the United Kingdom (2,3,11).In one patient (patient 12), two perforations were detected at the time of the event, one in the jejunum and one in the ileum; for the other 14 cases, there was a single perforation with only one other jejunal free perforation.One patient (patient 9) had two independent episodes of free ileal perforation, separated by a period of six years.

Crohn's disease
Table 1 details the characteristics of the Crohn's disease for each patient.In this series, the mean age of diagnosis of Crohn's disease was 23.2 years (range 14 to 32 years) for female patients and 25.6 years (range 17 to 34 years) for male patients.All patients had ileal involvement, while three also had extensive small intestinal disease in both the jejunum and the ileum; most also had colonic disease.In nine of 14 patients, spontaneous free perforation of the small intestine was the presenting clinical manifestation of Clinical features of Crohn's disease in 15 patients with spontaneous free perforation of the small intestine previously undiagnosed Crohn's disease.In three of the remaining six patients who had a pre-existent diagnosis of Crohn's disease, initiation of corticosteroid therapy (such as oral prednisone) was recorded during the month preceding free perforation.Except for renal calculi in two cases, extraintestinal manifestations of Crohn's disease were not recorded.All patients are currently alive, and none has developed a superimposed malignant disorder.Two patients have moved from the province and are no longer followed up by the author.

Free perforation
Table 2 details the clinical features of the small intestinal perforations.In 14 cases, the perforation was usually a single dramatic clinical event.In addition, one patient in this series (patient 9) had an independent, second ileal free perforation six years after the first free perforation.
Recurrent free perforation of the ileum has been previously recorded, but it was not clear whether Crohn's disease had been present (12).In the present series, all patients had single free perforations of the small intestine with peritonitis, except for one patient (patient 12) who had multiple perforations, as recorded elsewhere (3), in the jejunum and ileum.Moreover, almost all of the perforations occurred in the ileum, except in two of three patients who had extensive jejunal involvement with Crohn's disease and an associated jejunal perforation.Associated colonic free perforation was not seen.In all patients, the cause of the perforation was attributed to the Crohn's disease and not to a superimposed carcinoma (6,7) or lymphoma (3,8).All patients required urgent surgical treatment with resection and anastomosis or diversion; no patient was treated with plication alone.Subsequent laparotomy was required to reanastomose bowel for those requiring an initial diversion, and two patients (patients 4 and 12) required further surgical treatment for a subsequent enterocutaneous fistula.In this series, most patients required a modest small intestinal resection, with only three having more than 50 cm of small intestine removed (see Table 2).

Subsequent clinical course
Table 3 details the clinical course of patients after free perforation.The mean length of follow-up for all patients was 11.4 years (range three to 22 years).During their course, all patients were treated with a form of 5-acetylsalicylic acidcontaining medication such as sulfasalazine or mesalamine, but only 40% required corticosteroids or immunosuppressive medications.In addition, 40% had a further ileocolic resection for fibrostenosing disease or an enteric fistulous tract.One patient with an ileal perforation required a second resection for another ileal free perforation.Interestingly, in spite of a dramatic presentation with free small intestinal perforation, over 40% of pattients with follow-up data for over 10 years have had no significant clinical disease requiring either corticosteroid treatment or further surgical treatment.

DISCUSSION
Spontaneous free perforation of the small intestine in patients with Crohn's disease is an uncommon, even rare clinical event, occurring in less than 2% (3).In a large group of 1010 patients reported from Mount Sinai Hospital in New York, New York, from 1960 to 1980, that is comparable with the present series, free intestinal perforation was seen in 15 patients, but only six in the small intestine, including two in the jejunum and four in the ileum (2).Similarly, five small intestinal perforations occurred in 360 cases of Crohn's disease reported from Birmingham, United Kingdom, from 1943 to 1972 (13).Using similar rigorous criteria for definition of free perforation, 15 patients with 16 independent episodes of spontaneous free small intestinal perforation were seen in 1000 consecutive cases of Crohn's disease observed during a similar time frame of over 20 years.While large series of patients with Crohn's disease with this complication are limited (2,3,13), this Canadian experience confirms the unusual frequency of this intestinal complication reported from American and British hospitals.
The site distribution and multiplicity of free perforations were reported in this series.Although there were two jejunal perforations (patients 4 and 12), similar to the number in the Mount Sinai series (2), there were 15 free ileal perforations, including one occuring concomitantly with a jejunal perforation (patient 12) and one occuring as a second independent episode of free ileal perforation (patient 9).Others have also recorded a significant preponderance of ileal perforations compared with other sites in the gastrointestinal tract (4,13).In a previous study of 877 patients (4), approximately 13.1% of patients with Crohn's disease had involvement of the upper gastrointestinal tract that frequently included the jejunum.The relative proportion of jejunal and ileal perforations in this series suggests that patients with Crohn's disease do not have a specific siterelated propensity to develop spontaneous free small intestinal perforation.Rather, the dramatic appearance of this complication likely reflects the overall distribution of involvement with Crohn's disease in the gastrointestinal tract.
The pattern of clinical behaviour for patients with a free perforation was evaluated.Previous studies of Crohn's disease have suggested that patients with either fibrostenosing (stricturing) or fistulizing (penetrating/perforating) disease tend to redevelop a similar pattern of recurrent fibrostenosing or fistulizing disease.Although one patient developed a second spontaneous free ileal perforation about six years later as a completely independent event, this is rare.In those who required subsequent surgical treatment after the initial treatment for the perforation, it was usually for a subsequent stricture rather than for a perforating or penetrating complication, eg, fistula or abscess.Perhaps most significant in the present series was the frequent occurrence of free perforation as the initial event in the clinical course of Crohn's disease and the relatively benign clinical course after surgical treatment for this initial event, even though extensive ileocolonic disease was usually present.Only six cases have required recurrent surgical treatment to date, after over 10 years of follow-up, and most have not required any form of immunosuppression, including corticosteroids.Earlier reports (2,3,14) emphasized the high morbidity and mortality of this complication in patients with Crohn's disease, possibly reflecting the historical reluctance to treat surgically or the use of suture plication of the defect alone as the definitive treatment -approaches that were not used in the present series.In spite of the initial emergent clinical presentation for each case, the prognosis appeared to be sat-

Freeman
Can J Gastroenterol Vol 16 No 1 January 2002 24 TABLE 1

TABLE 3 Follow-up of patients with Crohn's disease after free perforation
There were no mortalities, and only a limited number of cases have required any further surgical resections.