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

Transcription

1 GASTROENTEROLOGY 76: , 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 G. CHAFFEE Department of Medicine, University of Washington and United States Public Health Service Hospital, Seattle, Washington The case is reported of a patient who presented with an occult anemia that was due to Grohn's disease of the duodenum. The initial evaluation revealed low serum levels of iron, folate, and carotene, and a small bowel series was abnormal but not diagnostic of Grohn's disease. Numerous small intestinal biopsy specimens were obtained from the duodenum and proximal jejunum in an unsuccessful attempt to make a diagnosis. It was shown by radiography and laparotomy 2 yr later that the patient had Grohn's disease of the proximal small intestine. This report provides a detailed analysis of the spectrum of abnormalities found by peroral mucosal biopsy in this patient. These abnormalities were patchy and included flattened mucosa, an abnormal surface epithelium which was infiltrated by large numbers of polymorphonuclear leukocytes, increased plasma cells and polymorphonuclear leuckocytes within the lamina propria, crypt abscesses, erosions, granulation tissue, and pyloric gland metaplasia, all in the absence of granulomas. Grohn's disease should always be considered in the differential diagnosis of a proximal small bowel mucosal disease, especially when a constellation of acute inflammatory changes is present. Received November 27, Accepted January 8, Address requests for reprints to: Michael D. Schumer, M.D., U.S. Public Health Service Hospital, P.O. Box 3l45, Seattle, WA This study was supported in part by Public Health Service grant 5 R01 AM and by Federal Health Programs Service project SEA The opinions and views expressed are those of the authors and do not necessarily represent the policy of the Division of Hospitals and Clinics of the Bureau of Medical Services or of the Department of HEW by the American Gastroenterological Association /79/ $02.00 Crohn's disease of the duodenum is an increasingly recognized entity. More than 200 cases have been reported, and between 0.5 and 4% of all patients with Crohn's disease have duodenal involvement! Although it is fairly easy to diagnose when the distal bowel is affected, isolated proximal involvement is less common and may be very difficult to diagnose!-4 We recently evaluated an adolescent girl who had Crohn's disease of the duodenum and who presented because of iron deficiency anemia that was thought to be secondary to iron malabsorption. Because her serum concentrations of folate and carotene were low and a small bowel series was nonspecifically abnormal, multiple small intestinal biopsy specimens were obtained in an attempt to make a diagnosis. Although the biopsies demonstrated a variety of abnormalities, no diagnosis could be made; it was only after 4 yr of follow-up that it became apparent that the patient had Crohn's disease of the stomach and proximal small intestine. This case illustrates some of the difficulties in diagnosing Crohn's disease of the duodenum and it details the spectrum of histologic abnormalities that may be found on small bowel biopsy in the absence of granulomas. Case Report A 16-yr-old girl presented to the U.S. Public Health Service Hospital in 1971 complaining of lethargy and a 20- Ib weight loss. She denied gastrointestinal symptoms, her physical examination was unremarkable, and two stools for occult blood were negative. She had an iron deficiency anemia with a hematocrit of 33%, and the erythrocyte sedimentation rate was 39. She was treated with ferrous sulfate, 300 mg t.i.d., which she continued to take intermittently over the next 2 yr. When seen 2 yr later, the patient's hemogram was unchanged, her stools were negative for occult blood, and

2 1010 CASE REPORTS GASTROENTEROLOGY Vol. 76, No.5, Part 1 she denied all symptoms except for fatigue. Upper intestinal radiographs showed prominence and irregularity of the folds in the duodenum and proximal jejunum, and a bone marrow aspirate demonstrated absent iron stores. A total of eight small bowel biopsy specimens were obtained with the Rubin multipurpose tube on two occasions (see below). Although abnormal, no diagnosis could be made. Aside from several days of epigastric pain, nausea, vomiting, and diarrhea, the patient's clinical condition remained unchanged over the next 2 yr. Additional laboratory tests revealed an albumin of 2.9 g% (N = g%), a carotene of 13JLg% (N = I-'g%), and a serum folate of 1 I-'g/ml. One-hour basal gastric acid output was 0 and maximal acid output after Histalog was 15.8 meq/hr. The patient absorbed 92% of a measured fat intake, and a sigmoidoscopy, barium enema, and rectal biopsies showed no diagnostic abnormalities. Because of the progression of her symptoms, steady weight loss, and the lack of a diagnosis, 20 additional biopsy specimens were obtained in 1975 from the proximal small intestine with a hydraulic biopsy tube in an attempt to make a diagnosis (see below). Because the biopsies suggested a diagnosis of Crohn's disease, the radiographs of the stomach and small intestine were repeated and now demonstrated narrowing of the antrum, pylorus, and duodenum along with a markedly abnormal mucosal pattern. The proximal jejunum was also abnormal, in some areas demonstrating a cobblestone pattern. The rest of the small intestine and colon were normal. The progression and characteristics of the radiographic abnormalities were characteristic of Crohn's disease." Because the patient's epigastric pains and vomiting progressed, she was taken to surgery and an ante-colic gastrojejunostomy was performed. The distal stomach, duodenum, and jejunum to 36 in. beyond the ligament of Treitz were moderately thickened. The jejunal involvement was patchy, and the mesenteric lymph nodes were swollen. The distal jejunum, ileum, and colon were normal. The surgeons concluded that the patient had Crohn's disease. No full-thickness biopsy specimen of the involved area was obtained because of fear of subsequent fistula formation at the biopsy site. Histology of the stomach from the anastomotic sjte demonstrated nonspecific acute inflammation, whereas that from the uninvolved jejunum was normal. The patient has had occasional mild obstructive symp- toms during 3 yr of follow-up but has gained 30 Ib and generally feels well. Small Intestinal Biopsy Findings Each biopsy specimen was oriented mucosal side up on monofilament plastic mesh. After initial processing, each was serially sectioned perpendicular to the mucosa and stained with hematoxylin and eosin. A total of 28 biopsy specimens were examined. These were obtained from an area extending from the third part of the duodenum to one loop beyond the ligament of Treitz. A spectrum of mucosal abnormalities was found (Table 1). Villous architecture varied from normal to complete loss of villi (Figure 1), with the most severe damage occurring proximal to the ligament of Treitz. Virtually all of the biopsies were characterized by acute inflammatory changes. At a minimum, this consisted of focal collections of polymorphonuclear leukocytes within the lamina propria and surface epithelium (Figure 2A). Some biopsy specimens had micro eros ions (Figure 2B) and others had large erosions and crypt abscesses. Two specimens consisted wholly of acute exudate and necrotic debris, as would be expected if a biopsy of the base of an ulcer were done. Surface cells varied from normal to cuboidal to completely flat. Many were grossly vacuolated and others were frankly megaloblastic, probably due to the patient's folic acid deficiency (Figure 3) Very few lymphocytes were seen within the surface epithelium, whereas polymorphonuclear leukocytes were frequent. Crypts were numerous and obviously increased in length, with some mitoses reaching close to the surface. Our overall impression (without counting) was that mitoses were not increased in number. In five biopsy specimens the normal intestine crypts were replaced by pyloric gland metaplasia (Figure 4). No parietal or chief cells were seen. The majority of the moderate and severely abnormal specimens contained increased numbers of plasma cells in the lamina propria, whereas lymphocytes were not increased in number. Granulomas and giant cells were never identified within any of the serial sections. Discussion The clinical features of Crohn's disease of the stomach and proximal small intestine include: (a) Table 1. Small Bowel Biopsy Results Date Location Normalo Mildo 8/ 9/ 73 Treitz 1 2 9/ 22/ 73 Treitz 1 3/ 11/ 75 One loop beyond Treitz 5 2 Treitz 3 Just proximal to Treitz Third part of duodenum Total 10 4 ModerateO Severeo Mixedo Acute exudate Total b e These columns report the severity of villous changes (see Ref. 13). b Normal-severe. C Mild-moderate

3 May 1979 CASE REPORTS 1011 Figure 1. A. Normal appearing mucosa from the patient's proximal small intestine (H&E, Xl84). B. The mucosa from an immediately adjacent area is flattened. The crypts are elongated and there are increased round cells in the lamina propria and polymorphonuclear leukocytes in the flattened surface epithelium (H&E. X184).

4 1012 CASE REPORTS GASTROENTEROLOGY Vol. 76, No.5, Part 1 Figure 2. A. The surface epithelium contains focal collections of polymorphonuclear leukocytes (H&E, Xl60). B. The surface epithelium is broken by an eruption of polymorphonuclear leukocytes. This micro erosion is located immediately above a small lymphoid folicle (H&E, X 160). episodic or continuous pain of the upper abdomen associated with nausea, vomiting, and weight loss; (b) episodic diarrhea; (c) gastric retention; (d) gastrointestinal bleeding; and (e) evidence of malabsorption of fat, fat-soluble vitamins, carbohydrates, and ;>roteins.'-3 When initially seen, our patient had weight loss, but none of the other abnormalities. Her mly additional symptom was fatigue, which remlted, presumably, from her iron deficiency anemia. fhe iron deficiency may well have been secondary :0 iron malabsorption, although this was not un!quivocally proved. The anemia was not due to )lood loss and was unresponsive to oral iron but N'as fully responsive to parenteral iron. This patient presented a diagnostic dilemma. Crohn's disease was not considered because of the relative lack of clinical symptoms and the nonspecific appearance of the small bowel radiographs. The small bowel biopsy specimens were abnormal, however, and did have several features consistent with Crohn's disease. First, the damaged mucosa was patchy and interspersed with normal mucosa. Second, the marked polymorphonuclear leukocytic infiltration of the lamina propria and surface epithelium and the erosions, crypt abscesses, and acute exudate are features of Crohn's disease. 6,7 The absence of granulomas should not have ruled out the diagnosis, since granulomas may be absent in Crohn's disease of the duodenum. 1 There are only a limited number of reports of per-

5 May 1979 CASE REPORTS 1013 Figure 3. The surface epithelial cells in the center are extremely large and vacuolated. Polymorphonuclear leukocytes are scattered throughout the surface epithelium (H&E. X640). oral small intestine mucosal biopsy in Grohn's disease of the proximal intestine. Hermos et al. reported on 2 patients, each of whom had two small intestinal biopsies. a One biopsy specimen from each patient showed abnormalities consisting of granulomas, microulcerations, and infiltrations of polymorphonuclear leukocytes. The mucosal architecture was abnormal, but only in the immediate vicinity of the granulomas. Harrer et al. reported on 2 patients with diffuse Grohn's disease of the small intestine who had granulomas in their small intestinal biopsy specimens." Aside from hypercellularity of the lamina propria, no striking abnormalities of mucosal architecture were described. Several other reports mention granulomas, acute inflammation, and mild changes of villous architecture, but either the descriptions are sketchy or no pictures are shown o In this report, we have detailed the variety of abnormalities that may be found on small bowel biopsy in patients who present with Grohn's disease of the duodenum. Some of these abnormalities such as flat mucosa unassociated with granuloma formation and pyloric gland metaplasia have not pre- ~ &._ ,, ;; :-...- Figure 4. This biopsy, obtained at the ligament of Treitz, shows glands containing clear, columnar cells, characteristic of pyloric gland metaplasia (H&E. X160).

6 1014 CASE REPORTS GASTROENTEROLOGY Vol. 76, No.5, Part 1 viously been described in mucosal biopsy specimens obtained from the proximal small intestine of patients with Crohn's disease. Pyloric metaplasia is a nonspecific finding that has been described in patients with Crohn's disease of other areas of the intestine, in normal people, and in a variety of pathologic states. ll Although none of the findings by themselves indicated a diagnosis of Crohn's disease, the constellation of findings should have strongly suggested the diagnosis even in the absence of granulomas. Although polymorphonuclear leukocytes and crypt abscesses may be present in celiac sprue and ulcerations may rarely occur,12 normal appearing biopsy specimens should not be seen in the proximal duodenum in symptomatic, malabsorbing patients, as they were in our patient.13 In addition, the surface epithelium in celiac sprue is full of lymphocytes rather than polymorphonuclear leukocytes. The only other diseases in which the mucosal findings resemble those of our patient are the Zollinger-Ellison syndrome and nongranulomatous ulcerative jejunoileitis.'4.15 The small intestinal mucosa in these disorders may also be characterized by flattened mucosa, polymorphonuclear infiltration, erosions, and crypt abscesses. Zollinger-Ellison syndrome was ruled out in our patient by the absence of basal acid secretion. Patients with nongranulomatous ulcerative jejunoileitis usually have marked abdominal pain, severe diarrhea, and fever and they usually have obvious involvement of the jejunum and ileum. Our patient had none of these. In summary, the histologic findings excluded the diagnosis of celiac sprue, and the clinical-laboratory findings excluded diagnoses of Zollinger-Ellison syndrome and nongranulomatous ulcerative jejunoileitis. As there were no other diseases that could have produced the abnormalities in our patient, Crohn's disease should have been diagnosed early in her course as the disease that best fit the data. Because of the infrequency of Crohn's disease of the duodenum and the fact that it may present with malabsorption rather than with pain, obstruction, and diarrhea, the diagnosis may be quite difficult to achieve. This case emphasizes that Crohn's disease should be considered in the differential diagnosis of any proximal small bowel mucosal disease, especially when acute inflammatory changes are prominent. References 1. Nugent FW, Richmond M, Park SK: Crohn's disease of the duodenum. Gut 18: , Comfort MW, Weber HM, Baggenstoss AH: Nonspecific granulomatous inflammation of the stomach and duodenum: its relation to regional enteritis. Am J Med Sci 220: , Jones GW, Dooley MR, Schoenfield NJ: Regional enteritis with involvement of the duodenum. Gastroenterology 51: , Wise L, Kyriakos M, McCown A, et al: Crohn's disease of the duodenum. Am J Surg 121: , Thompson WM, Cockrill H, Rice RP: Regional enteritis of the duodenum. Am J Roentgenol Radium Ther Nucl Med 123: , Hermos JA, Cooper HL, Kramar P, et al: Histological diagnosis by peroral biopsy of Crohn's disease of the proximal intestine. Gastroenterology 59: , Wilder MW, David WD: Duodenal enteritis. South Med J 59: , Harrer WV, Goldstein F, Wirts CW: Granulomas in suction biopsies of distal duodenum. Gastroenterology 59: , Kusakcioglu 0, Norton RA: Granulomatous duodenitis, clubbed digits and psoriasis. Report of a case. Lahey Cl Found Bull 16: , Law SW, Searle NB, Barton HL, et al: Regional enteritis of the duodenum. Arch Surg 89: , Lee FD: Pyloric metaplasia in the small intestine. J Pathol Bacteriol 87: , Bayless TM, Kapelowitz RF, Shelley WM, et al: Intestinal ulceration-a complication of celiac disease. N Engl J Med 276: , Perera DR, Weinstein WM, Rubin CE: Small intestinal biopsy. Hum Pathol 6: , Shimoda SS, Saunders DR, Rubin CE: The Zollinger-Ellison syndrome with steatorrhea. II. The mechanisms of fat and vitamin B12 malabsorption. Gastroenterology 55: , Jeffries GH, Steinberg H, Sleisenger MH: Chronic ulcerative (nongranulomatous) jejunitis. Am J Med 44:47-59, 1968