CHRONIC ULCERATIVE JEJUNITIS

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1 GASTROENTEROLOGY Copyright " 1971 by The Williams & Wilkins Co. Vol. 60, No. 1 Printed in U. S. A. CHRONIC ULCERATIVE JEJUNITIS Report of a case and discussion of classification MORDEKHAI MORITZ, M.D., JOHN M. MORAN, M,D., AND JAMES F. PATTERSON, M.D. Gastroenterology Service and Department of Surgery, Tufts-New England Medical Center, Boston, Massachusetts Recurring ulceration and strictures of the upper jejunum were accompanied by a malabsorption syndrome in this patient. Resection of strictures on two occasions resulted in clinical remissions and survival thus far of 7 years. Previous reports of this syndrome have classified it in two ways-chronic ulcerative jejunitis with secondary malabsorption and celiac sprue with intestinal ulceration. Since it may be impossible to document celiac sprue once ulceration has occurred, it is very difficult to separate these two classifications. We would suggest a single classification of "chronic ulcerative jejunitis." This patient's course is unusual in the development of multiple strictures, the good response to surgical excision, and the long survival. Chronic ulcerating jejunitis was first described in 1949 by Nyman, I who reported 2 cases with a clinical picture resembling celiac. sprue apparently caused by a nonspecific ulcerative process in the jejunum. In 1967, Bayless et al. 2 described a patient with well documented celiac sprue who developed jejunal ulcerations. On the basis of this and other cases, they felt that the ulcerative process was a complication of celiac sprue. Shortly thereafter, Jeffries et al. 3 described patients with abdominal pain, diarrhea, fever and malabsorption with ulceration, and patchy atrophy of the small intestinal mucosa, and felt that this was a distinct clinicopathological entity. The disease is rare, Received April 10, Accepted July 17, Address requests for reprints to: Dr. James F. Patterson, Gastroenterology Service, Tufts-New England Medical Center, 171 Harrison Avenue, Boston, Massachusetts This study was supported by United States Public Health Service Training Grant AM 5424 and a grant from the John A. Hartford Foundation, Inc. Dr. Moritz' present address is: Lemuel Shattuck Hospital, 170 Morton Street, Boston, Massachusetts only 24 cases have been reported, and it is usually rapidly fatal. It is the purpose of this report to describe a patient with ulcerative jejunitis and malabsorption in whom surgical resections of the ulcerated and strictured segments of jejunum were followed by prolonged clinical remissions. Because of differences of opinion concerning the nature of this disorder, its classification is discussed. Case Report A 58-year-old white male was in good health until April 1962, when he began to have intermittent abdominal cramps, nausea, and gradualloss of weight. In October 1962, radiological examination showed a stringlike narrowing in the proximal jejunum with effacement of duodenal mucosa and irregular segmentation of barium in the rest of the small bowel. The hematocrit, serum albumin, calcium, cholesterol, and plasma prothrombin were within normal limits. Exploratory laparotomy showed that a 2-foot segment of small bowel starting at the ligament of Treitz was markedly reddened and indurated; its mesentery was swollen and contained a conglomerate of enlarged lymph nodes. The rest of the small bowel was

Histologically, there was severe nonspecific inflammation with many lymphocytes, plasma cells, and polymorphonuclear leukocytes. Microabcesses were seen in the submucosa, but no granulomas were found.

2 January 1971 CASE REPORTS 97 normal. Resection of 30 inches of proximal jejunum with end-to-end anastomosis was performed. The resected jejunum was grossly thickened, the mucosa was injected, and many superficial punched out ulcerations were seen. Histologically, there was severe nonspecific inflammation with many lymphocytes, plasma cells, and polymorphonuclear leukocytes. Microabcesses were seen in the submucosa, but no granulomas were found. The patient did well on no medication or diet until October 1965, when he began to have diarrhea, anorexia, and recurrent abdominal pain. In January 1966, he was admitted to the Tufts-New England Medical Center for the first time. He was pale and cachectic with a protuberant abdomen. The tongue was beefy red and there was cheilosis. Sigmoidoscopy showed no abnormalities. The hematocrit was 37%, and a white blood cell count was 5800 per mm 3 The serum iron was 64 /lg per 100 ml, and total iron-binding capacity was 164 /lg per 100 ml. Serum albumin was 2.5 g per 100 ml and globulin was 2.5 g per 100 ml. Serum calcium was 8.6 mg per 100 ml and serum carotene was O. The 5-hr urinary excretion of 0- xylose after a 25-g oral dose was 2.7 g. The 72- hr fecal fat was 114 g during ingestion of a normal diet. The plasma prothrombin, as well as serum vitamin B12 and folate, were normal. X-ray studies of the upper gastrointestinal tract showed dilation of the proximal twothirds of the duodenum with loss of mucosal pattern. At the ligament of Treitz there was a 1-cm long area of marked narrowing of the jejunum with maximum lumen diameter of 0.5 cm; this was followed by a short dilated segment and another similar stricture. The rest of the small bowel showed a pattern of malabsorption but no other strictures. The terminal ileum was normal. The barium enema showed a normal colon. The patient improved clinically on a gluten-free diet and gained 14 lb in 1 month. An attempt, a few months later, to restore gluten to his diet was followed by a relapse of his symptoms which were then refractory to elimination of gluten. In May 1967, he was readmitted for further evaluation. Physical examination was unchanged. The hematocrit was 28%. Serum albumin was 2.0 g per 100 ml and the globulin was 1.4 g per 100 ml. Serum calcium was 7.3 mg per 100 ml and carotene was 22 /lg per 100 ml. The prothrombin was 19% of normal. Serum FIG. 1. Resected segment of the,proximal jejunum showing circumferential ulceration with cicatrization.

vitamin B12 and folate were normal. The 5-hr urinary excretion of D-xylose after a 25-g oral dose was 0.6 g.

3 98 CASE REPORTS Vol. 60, No.1 FIG. 2. Section through the ulcerated segment of the resected jejunum (X 40) showing granulation tissue overlying the ulcer with heavy infiltration of inflammatory cells in the submucosa. vitamin B12 and folate were normal. The 5-hr urinary excretion of D-xylose after a 25-g oral dose was 0.6 g. Serum immunoelectrophoresis disclosed normal levels of IgA and IgG globulins with a slight decrease of IgM. Gastric analysis showed a basal acid output of 0.76 meq per hr. No ova or parasites were found on three stool examinations. X-ray study again showed the presence of jejunal strictures and a pattern of malabsorption in the small bowel with thickening of the folds. Abdominal aortogram and selective superior and inferior mesenteric arteriograms did not show any abnormalities. Two attempts to obtain a small bowel biopsy were unsuccessful because the capsule failed to pass the pylorus. On June 12, 1967, exploratory laparotomy disclosed a tight stricture of the jejunum at the ligament of Treitz. Beyond this was a 3-inch dilated segment of jejunum and then a second area of stenosis just distal to the previous site of the surgical anastomosis. The next 5 to 6 inches of jejunum had five remarkably similar strictures at 2-cm intervals, as well as some extension of fat onto the serosa of the bowel. The mesentery contained a moderate number of enlarged lymph nodes. The remainder of the exploration was negative. A 15-cm segment of the involved jejunum was resected and an endto-end anastomosis was performed. The mucosa of the resected bowel showed five circumferential ulcers, 2 to 3 mm wide, spaced at 2-cm intervals (fig. 1), which were clearly associated with the pronounced strictures. In addition, there was one irregular shaped ulcer 1.5 cm in diameter. Histologically (fig. 2), the small bowel showed interruption in the continuity of the mucosa, muscularis mucosa, and submucosa with inflammation, ulceration, and bleeding. There was no granuloma formation and no fistula. The serosa was slightly involved in a nonspecific inflammatory reaction, and the mesenteric lymph nodes showed an accumulation of histiocytes in the sinuses. There was

4 January 1971 CASE REPORTS no arteritis or phlebitis. The lesion was nonspecific and resembled neither tuberculosis nor regional enteritis. The mucosa adjacent to the ulcer site showed villous atrophy but did not show gastric metaplasia (fig. 3). The liver biopsy did not reveal any abnormalities. On a gluten-free diet, he gained 27 Ib during the next 4 months and had no more abdominal cramps or diarrhea. The laboratory data showed a normal hemogram and normal level of serum albumin. Radiological study performed in December 1967 (fig. 4) disclosed the reappearance of strictures in the segments of duodenum and jejunum adjacent to the ligament of Treitz. During 1968, he had fluctuations in his weight and hemoglobin level in spite of careful adherence to gluten-free diet. In February 1969, his hematocrit dropped to 25.5% with a serum iron of 37 p.g per 100 ml and total iron-binding capacity of 370 p.g per 100 ml. The iron deficiency anemia was studied by 99 Dr. Lewis Weintraub of the Blood Research Laboratories of the New England Medical Center using an oral dose of Fe 59 -labeled heme and intravenous injection of autologous red blood cells labeled with Cr51! This showed a daily blood loss of 2.0 to 6.1 ml per day and normal absorption of heme Fe 59 iron. Schilling test with intrinsic factor showed excretion of 6.1% of the administered dose of C060 -cyanocobalamine in the urine in 24 hr. Mter a 2-week course of tetracycline 2.0 g daily, the Schilling test showed a 24-hr urinary excretion of 4.2% of the given dose, and the 72hr fecal fat was 184 g, indicating that bacterial overgrowth was not a contributing factor to either the steatorrhea or malabsorption of vitamin B\2. Pancreatic insufficiency as an additional cause of malabsorption 5 was studied by determining the 72-hr fecal fat before and after a I-week course of pancreatic extract (Viokase), 1.0 g taken with each meal. Before Viokase, the fat content was 83.4 g and after Viokase it FIG. 3. Section from jejunal mucosa adjacent to an ulcer site (X 100) showing marked villous atrophy and dense infiltrate of chronic inflammatory cells.

$Coproantibodies to gluten fraction III were not found. 6 During hospitalization, intramuscular injection of a sorbitol iron complex (Jectofer) was begun, and 7 weeks later the hematocrit was 44.5%.$ Because of gradual loss of weight, medium chain triglycerides in a quantity to supply 680 cal per day were added to the gluten-free diet.

Because of gradual loss of weight, medium chain triglycerides in a quantity to supply 680 cal per day were added to the gluten-free diet.

5 100 CASE REPORTS Vol. 60, No.1 FIG. 4. Dilated duodenum with loss of n ormal mucosal structure. Arrows show strictured areas in duodenum and jejunum. was 72.9 g. Coproantibodies to gluten fraction III were not found. 6 During hospitalization, intramuscular injection of a sorbitol iron complex (Jectofer) was begun, and 7 weeks later the hematocrit was 44.5%. Because of gradual loss of weight, medium chain triglycerides in a quantity to supply 680 cal per day were added to the gluten-free diet. Following this, a gradual gain of weight was noted and, by the end of 6 weeks of this diet, the patient gained 9 lb and was feeling well. Discussion This patient exhibited a clinical picture of abdominal pain, diarrhea, weight loss, iron deficiency anemia, and malabsorption (as documented by xylose test, stool fat, and Schilling test) with nonspecific ulceration and strictures of the jejunum. On two occasions, surgical resection of jejunal strictures resulted in clinical remission.

6 JulUUlry 1971 CASE REPORTS 101 It was clear from examination of the two surgical specimens that the jejunal ulcerations were nonspecific, and there was no histological evidence of infection (fungous or bacterial), neoplasm, or Whipple's disease. Although granulomatous bowel disease (regional enteritis) was strongly considered, the lesions did not seem compatible with this diagnosis. There had been no ingestion of enteric coated potassium, and there was no hypersecretion of acid by the stomach. He did not have hypogammaglobulinemia or evidence of diffuse vascular disease, and there was no improvement in absorption of vitamin Bl2 or fat during tetracycline administration. The combination of malabsorption and nonspecific ulceration of the small intestine suggested that he might have celiac sprue with intestinal ulceration as summarized by Bayless et al. 2 (16 cases) or chronic ulcerative jejunoileitis as reviewed by Jeffries et al. 3 (13 cases). That these two syndromes are not easily distinguished is evidenced by the fact that 7 cases in the literature are listed in both series. Thus, the 22 different patients listed in these two series and two reported subsequently7,8 all demonstrated malabsorption and nonspecific intestinal ulceration. Bayless' own case had well documented celiac sprue before the ulcerative disease developed, while Jeffries' report emphasized ulceration as a primary feature with a patchy atrophy of mucosa and poor response to a gluten-free diet. It seems to us that a clear distinction cannot be made among these 24 patients. It is possible that several disorders are represented, i.e., celiac sprue complication by an ulcerative process, diffuse nonspecific inflammation causing malabsorption and lymphoma (1 of Jeffries' cases later turned out to have lymphoma of the small intestine). Since the ulcerative process apparently makes the celiac sprue patient refractory to the gluten-free diee and in itself can cause patchy atrophy of intestinal mucosa,3 it would seem impossible in most cases to tell whether celiac sprue had existed prior to the ulcerative process. The present case demonstrates some of the problems of classifying this disorder. Our patient's jejunal mucosa showed total villous atrophy adjacent to the ulcers, although specimens further away were not available. He had a typical malabsorption pattern by X-ray and a diffuse disturbance of absorption of fat, xylose, and vitamin Bl2, and for a time, even after the ulcerative disease was present, he responded to a gluten-free diet. Thus he had some evidence of celiac sprue as well as ulcerative jejunitis and could be classified in either group. Our patient's disorder is characterized by regularly occurring strictures in the upper jejunum which are associated with, and probably caused by, circumferential linear ulcerations. Although 3 previously reported cases have had one or several strictures in the distal duodenum,2, 9 none have been reported with multiple recurring strictures and a chronic course as occurred here. On two occasions, surgical excision of the upper jejunal strictures in our patient resulted in clinical remission of 3 1 /2 and 2 V2 years. In 1 reported case, 9 a short clinical remission followed bypassing of a duodenal stricture, but bleeding subsequently occurred and further bypassing and excision were not successful. In 2 other cases cited by Bayless from Creamer,10 surgical resection of an ulcerated area of small bowel resulted in prolonged clinical improvement. Of the 24 reported patients, 19 are known to be dead, the longest survival being 8 years, but most patients died within 5 years. Our patient has now survived 7 years with treatment consisting of gluten-free diet and two surgical resections of involved jejunum. REFERENCES L Nyman E: Ulcerous jejuno ileitis with symptomatic sprue. Acta Med Scand 134: , Bayless TM, Kapelowitz RF, Shelley WM, et al: Intestinal ulceration-a complication of celiac disease. New Eng J Med 276: , Jeffries GH, Steinberg H, Sleisenger. MH: Chronic ulcerative (Nongranulomatous) jejunitis. Amer J Med 44:47-59, Kimber C, Patterson JF, Weintraub L: The

7 102 CASE REPORTS Vol. 60, No. I pathogenesis of iron deficiency anemia following partial gastrectomy. JAMA 202: , DiMagno EP, Go VLW, Summerskill WHJ: Pancreozymin secretion is impaired in sprue (abstr). Gastroenterology 56:1149, Katz J, Kantor FS, Herskovic T: Intestinal antibodies to wheat fractions in celiac disease. Ann Int Med 69: , Case records of the Massachusetts General Hospital (Case ). New Eng J Med 280: , Davidson AR: Recurrent benign ileal ulcer occurring with the coeliac syndrome. Brit Med J 3: , Goulston KJ, Skyring AP, McGovern VJ: Ulcerative jejunitis associated with malabsorption. Aust Ann Med 14:57-64, London DR, Bamforth J, Creamer B: Steatorrhea presenting with gastrointestinal protein loss. Lancet 2:18-19,1961

Small Intestinal Biopsy in a Patient with Crohn's Disease of the Duodenum

GASTROENTEROLOGY 76:1009-1014, 1979 Small Intestinal Biopsy in a Patient with Crohn's Disease of the Duodenum The Spectrum of Abnormal Findings in the Absence of Granulomas MICHAEL D. SCHUFFLER and ROBERT