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Eosinophilic Gastroenteritis
Vol. 58, No.4 Printed in U.S.A.
GASTROENTEROLOGY
Copyright © 1970 by The Williams & Wilkins Co.
CASE REPORTS
EOSINOPHILIC GASTROENTERITIS Report of a case with malabsorption and protein-losing enteropathy STEPHEN M. KAPLAN, M.D., FRANZ GOLDSTEIN, M.D., AND O. DHODANAND KOWLESSAR, M.D. Division of Gastroenterology, Department of Medicine, Jefferson Medical Col/ege, Philadelphia, Pennsylvania
The case of a 77 -year-old white woman with eosinophilic gastroenteritis of long duration is presented. The occurrence of malabsorption and protein-losing enteropathy is well documented. The diagnosis was made by means of peroral jejunal biopsy, making exploratory laparotomy unnecessary. The response to corticosteroids was prompt and sustained, although incomplete and could be maintained on an alternating day schedule of steroid administration. In 1937, Kaijser 1 described 3 cases of eosinophilic infiltration of the stomach and small bowel. In 1961, Ureles and associates,2 after a review of the world literature, proposed a classification of the 75 reported cases into a diffuse type, or eosinophilic gastroenteritis (26 cases), and a circumscribed type, or eosinophilic granuloma. Eosinophilic gastroenteritis can be differentiated readily from eosinophilic granuloma on clinical, pathological, laboratory,2 and radiological bases. s,4 Isolated cases of eosinophilic gastroenteritis with either protein -losing gastroenteropathy,S Received July 24, 1969. Accepted October 8, 1969. Address requests for reprints to: Dr. O. Dhodanand Kowlessar, Department of Medicine, Jefferson Medical College, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. This work was supported in part by Contract/ Grant DADA 17-68-C-8092 from the United States Army Medical Research and Development Command, by Themis Grant NOO014-680516 from the Office of Naval Research, United States Navy, and by Grants FR-72 and AM-5572 from the National Institutes of Health, United States Public Health Service.
malabsorption,5 or both6 have been reported, but none were supported by complete data. This disease probably is not identical with allergic gastroenteropathy,7, 8 which occurs in early childhood and is characterized by food intolerances and other allergic manifestations. The present report concerns a case of eosinophilic gastroenteritis in an septuagenarian manifesting extensive small bowel involvement associated with malabsorption and protein loss. Case Report F. S., a 77-year-old white woman, was admitted to the Jefferson Medical College Hospital on May 17, 1967, with a 12-year history of intermittent, crampy epigastric pain, relieved by vomiting undigested food. Four years prior to admission she developed anorexia, weakness, easy bruising, and muscle cramps. She gradually lost 30 lb of weight and developed more frequent episodes of vomiting with associated abdominal distention, ankle swelling, and diarrhea consisting of two to six light colored, semisolid to watery stools per day. During her hospitalization in 1963 in another hospital she was observed to have a blood eosinophilia of over 30%. In May 1967 her symptoms worsened and she was referred to
540
541
CASE REPORTS
April 1970
our hospital. There was no pertinent history of past illness except for a fractured right hip incurred 2 years earlier. There was no history of allergies or food intolerances. The patient had never traveled outside the United States and Canada. On admission, she was emaciated, with decreased subcutaneous tissue and muscle mass. Vital signs were normal. Weight was 75.5 Ib and fell to 65 Ib after diuresis. The tongue was smooth and red. The abdomen was distended markedly and gurgling peristaltic sounds were heard. Rectal examination was normal. The stool was free of occult blood, but contained stainable fat. There was marked pitting edema of both ankles and legs. Multiple ecchymoses were noted over the extremities. The deep tendon reflexes were diminished. Pertinent laboratory studies on first admission are summarized in table 1. Serum electrolytes were normal except for refractory hypokalemia, hypocalcemia, and hypophosphatemia. The patient had a severe normocytic, TABLE
normochromic anemia. Serum iron, total ironbinding capacity, folate, haptoglobin, and vitamin B12 levels were normal. However, the patient had received several vitamin B12 injections prior to admission. The bone marrrow showed eosinophilic hyperplasia representing 30% of the total cells, normoblastic erythropoiesis, and stainable iron. A plain film of the abdomen demonstrated distended loops of small bowel. A small bowel biopsy revealed well preserved villi with normal epithelial cells; the lamina propria showed edema, hemorrhages, and infiltration with predominantly plasma cells and eosinophils. Because or excessive aerobic bacterial growth in the upper small intestine (table I), the patient was treated with 5-day courses of tetracycline and ampicillin, 250 mg q.i.d., each, but failed to improve. However, on a daily dose of 20 mg of prednisone she showed marked clinical improvement. Her fecal fat excretion on a 100-g daily fat intake decreased from 47 to 4.5 g
1. Results of laboratory tests
Testa
First admission (May 1967)
Second admission (October 1967)
Third admission (January 1969)
Hemoglobin (12-15 g/100 ml) White blood count (5,000-10,000 cells/ mm) Range of eosinopbils (1-3%) Serum potassium (4.1-5.2 mEq/liter) Serum calcium (4.5-5.5 mEq/liter) Serum phosphorus (2-4 mg/100 ml) Serum alkaline phosphatase (1.5-4.0 Bodansky units) Schilling test (>7% excreted) Schilling test with intrinsic factor of proven potency (>7% excreted) Fecal fat «5 g/24 hr) with patient receiving 100-gm fat diet d-Xylose excretion «5.0 g/5 hr) Prothrombin time (80-100%) Serum carotene (60-260l'g/100 ml) Total protein (6.2-7.8 g/100 m!) Albumin (2.9-4.5 g/IOO ml) -y-Globulin (0.7-1.9 g/100 ml) Immunoglobulin G (600-1800 mg/100 ml) Immunoglobulin A (40-380 mg/100 ml) Immunoglobulin M (20-200 mg/IOO ml) Aerobic distal duodenal bacterial culture (0-5 X 10' CFU/ml)' Anaerobic distal duodenal bacterial culture «2.5 X 10' CFU/ml)lO Urinary indican excretion (40-100 mg/ 24 hr) Secretin test volume (1.1-4.6 cc/kg/hr)l1 Maximum bicarbonate concentration (65-121.5 mEq/liter)l1 Stools for ova and parasites Protein-bound iodine (4-8I'g/100 ml) Dry weight after diuresis
7.1 15,150
13.1 13,250
13.9 13,100
12-45 3.5 3.1 1.8 9.6
12-17 4.3 4 2.6 5.7
8-21 4.0 4.2 2.9 4.8
5.6 1.6
3.0 <1
3.9
6.1
9.1 7.7 2.6 88 19 4.8 3.1 0.4 480
47 1.5
10 4.0 2.5 0.4 650 187 70 1. 7 X 10' Escherichia coli 1. 5 X 10' a"Streptococcus
a Normal values given in parentheses.
1.7 100 <19 4.8 2.7 0.6
4.3 X 10' a-Streptococcus 9.2 X 10' E. coli 1 X J07 47.52
8.4 70
5.3 82
Neg X 2 6.0 65
Neg X 2 74.5
200 60 1. 4 X 10' a-Streptococcus 4 X 10' E. coli
75,96.25-97.50
Neg X 2 4.5 75
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CASE REPORTS
Vol. 58, No.4
daily. Stool frequency decreased to two formed movements a day and a weight gain ensued without recurrence of edema. She was discharged taking prednisone, diuretics, vitamins, oral calcium, potassium, and diphenoxylate. The patient was readmitted in October 1967. She reported less vomiting and diarrhea, an improved appetite, and a weight gain of 8 lb. The physical examination showed only slight abdominal distention and minimal ankle edema; otherwise, her condition remained unchanged. Laboratory results during second admission are summarized in table 1. The most striking changes from the earlier admission were the normal hemoglobin concentration and near normal fat absorption. An upper gastrointestinal series with small bowel follow-through showed an atrophic mucosal pattern in the stomach and nearly total absence of the normal mucosal folds in the proximal small bowel (figs. 1 and 2). Augmented histamine gastric analysis demonstrated achlorhydria. The peroral small bowel biopsy remained essentially unchanged. Treatment was continued with
FIG. 2. Radiological appearance of stomach and small intestine, showing grossly abnormal mucosal pattern of entire length of small bowel.
FIG. 1. Radiological appearance of stomach, demonstrating partial effacement of gastric folds consistent with gastric atrophy. Duodenal diverticulum also is present.
prednisone, 10 mg daily. A course of ampicillin, 250 mg q.i.d. for 5 days, did not produce any measurable improvement. Following discharge the patient maintained her weight between 74 and 77 Ib with occasional episodes of vomiting and variable diarrhea. Her appetite remained good. She was readmitted on January 22, 1969, after 1 week of increased abdominal distention and ankle edema. Physical examination showed moderate abdominal distention, occasional gurgling peristaltic sounds, and moderate ankle and pretibial edema. Laboratory results of the third admission, summarized in table 1, show further improvement in hematological and chemical parameters. The dose of prednisone was increased from 10 to 15 mg daily with a subsequent decrease in bowel frequency and less abdominal distention. This improvement was maintained after changing therapy to 30 mg of prednisone every other day. A small bowel biopsy remained unchanged and again showed moderate inflammatory cell infiltrates. Upper gastrointestinal and small bowel series were similar to those in the previous examina-
CASE REPORTS
April 1970
tion. Chromium51-labeled chloride was injected intravenously and stools were collected for 72 hr with 19% of the injected radioactivity appearing in the stools (normal, 0.35 to 1.25%).12 Distal duodenal fluid showed no free bile salts with a normal pattern of conjugated bile salts by thin layer chromatography.'· A lactose tolerance test was low normal. The patient was discharged taking 30 mg of prednisone every other day, oral calcium and potassium supplements, vitamins, and a moderately salt-restricted diet. As of June 30, 1969, she was asymptomatic and gaining additional weight.
Discussion
The clinical and laboratory features of our patient are typical of the polyenteric type of eosinophilic gastroenteritis as defined by Ureles,2 except that our patient developed the disease in her seventh decade while most patients develop it between the second and fifth decades. 2 The prolonged clinical history (14 years) without any other manifestations of malignancy, the persistent eosinophilia, and the lack of evidence of malignant lymphoid cells in the lamina propria of three small bowel biopsies make a lymphoma of the small bowel unlikely. The normal jejunal epithelial cells and villous architecture militate against a diagnosis of adult celiac disease. Allergic gastroenteropathy 7. 8 is probably a separate clinical entity with peripheral eosinophilia and eosinophilic infiltration of the lamina propria of the small bowel. Allergic gastroenteropathy develops in the first and second decades of life and is characterized by a history of atopy, by periorbital or generalized edema, extreme hypoalbuminemia, hypogammaglobulinemia, growth retardation,anemia secondary to chronic blood loss, occasional episodes of diarrhea or vomiting after milk ingestion, and by a tendency for the gastrointestinal manifestations and hypoproteinemia to become less severe as the patients grow older. The radiological features of the stomach and small intestine in our case seem somewhat unusual in that the X-rays of the stomach suggested gastric atrophy and the entire length of the small bowel showed a nearly total absence of the mucosal pattern
543
usually observed radiologically. Typically, the gastric involvement in eosinophilic gastroenteritis is limited to the distal half of the stomach, resulting in an irregular gastric outline with antral or pyloric narrowing and often with gastric retention. The small bowel in eosinophilic gastroenteritis often shows irregular segmental narrowing with thickening and rigidity of the wall interspersed with dilated loops; these changes are usually more pronounced in the proximal and middle small intestine. Eosinophilic gastritis involved the entire stomach in 2 cases reviewed by Ureles et a1. 2 and involved the stomach from the cardioesophageal junction to the midantrum in 1 case of Culver and co-workers,14 but in these cases the stomach showed prominent rugal folds . It is likely that our patient has both eosinophilic gastroenteritis and pernicious anemia, the co-existence of small intestinal disease and pernicious anemia having been noted by others.15 Carmel and Herbert16 believe that gastric atrophy with loss of intrinsic factor secretion can occur as a result of long term vitamin B12 or folate defici ency caused by intestinal malabsorption. In the majority of the previously reported cases of eosinophilic gastroenteritis, the diagnosis was made by exploratory laparotomy and the gross and microscopic pathology of this disease has been based largely on resected specimens. The surgical specimens show the most extensive eosinophilic infiltration to be present in the submucosa, muscularis, and serosa, with relative sparing of the mucosa. 1-4 Peroral small bowel biopsy has been used rarely to diagnose this disease. Bentlif et al. reported 3 cases with typical clinical , laboratory, and radiological features confirmed by peroral small bowel biopsies. Their biopsies showed moderate edema of the villi with a diffuse infiltration of eosinophils and plasma cells in the lamina propria.5 The similarity of the descriptive features between the peroral small bowel biopsies in our case and in those of Bentlif5 and Leinbach and Rubin 6 is apparent. These latter authors also pointed out the patchy nature of the eosinophilic infiltrate, finding it in 20 of 28 proximal
544
CASE REPORTS
small bowel biopsies in their patient. 6 It is not clear, however, whether their case represents eosinophilic or allergic enteropathy. Since this disease can involve the entire small bowel or any part of it,17 it is surprising that malabsorption has not been reported more often. Bentlif et al. 5 described a 36-year-old woman with abdominal pain, vomiting, diarrhea, distention, and weight loss. They state that stools stained with Sudan IV contained fat particles and that there was deficient absorption of P3l-labeled triolein and dxylose, but give no quantitative data on these abnormalities. Leinbach and Rubin's case, reported in abstract,6 manifested steatorrhea with a coefficient of fat absorption of 79%. On her initial admission our patient showed severe malabsorption characterized by a stool fat excretion of 47 g per day, a low urinary d-xylose excretion (1.5 g per 5 hr), marked hypocarotenemia, low serum calcium and phosphorus with elevated alkaline phosphatase, the latter three measurements suggesting osteomalacia, and abnormal Schilling tests with and without added intrinsic factor. Thus, our patient had clear cut evidence of malabsorption. The precise mechanism for the malabsorption in eosinophilic enteritis has not been established. Distal duodenal bacterial cultures in our patient showed moderately increased total bacterial growth on all admissions (up to 107 CFU per ml), but there was no clinical or laboratory improvement with antibiotic treatment. In addition, malabsorption due to bacterial overgrowth was unlikely since the distal duodenal fluid showed a normal pattern of conjugated bile salts with no free bile salts and the urinary indican levels were normal. Secretin tests showed high volumes of secretion with low normal bicarbonate concentrations. Serum immunoglobin G, M, and A levels were low normal. It is possible that the inflammatory cell infiltration of the small intestinal mucosa, presumably extending throughout the small intestine as evidenced by the diffuse radiological changes, interferes with the normal absorptive function of the mucosal cell
Vol. 58, No.4
and/or may constitute a diffusion barrier to absorption of simple substances. The malabsorption was improved only after treatment with prednisone and improvement was maintained with low doses of steroids, administered most recently in a single dose every other day. Others have reported symptomatic remissions of eosinophilic gastroenteritis with adrenocorticotropin 2 , 18 or corticosteroids,!- 5, 19 but with the possible exception of the case noted. by Leinbach and Rubin 6 there have been no reports on the effectiveness of these drugs in the treatment of the malabsorption of eosinophilic gastroenteritis. Edelman and March3 reported a case of a 16-year-old male whose upper gastrointestinal and small bowel series showed persistent narrowing of the distal antrum with multiple polypoid filling defects having a cobblestone appearance and a normal appearing small bowel. The patient's total serum protein concentration was 4.7 g per 100 ml with 3.3 g per 100 ml of albumin; his stools were positive for occult blood and his serum iron was 20 mcg per 100 ml. According to these authors, the P3l-labeled albumin turnover studies indicated protein loss into the gastrointestinal tract in excess of what could be attributed to bleeding, but no quantitative data were given. Exploratory laparotomy revealed thickening of the pyloric portion of the stomach and jejunum, with a pathological diagnosis of eosinophilic gastroenteritis. Our patient presented initially with low serum albumin and y-globulin values. Even after striking improvement in the steatorrhea these values remained low (see table 1), suggesting a mechanism other than malabsorption as their cause. The presence of substantial protein exudation into the gut lumen was demonstrated by the Cr5l CI fecal excretion of 19% of the injected dose. The small bowel biopsies in our case did not show dilated lacteals nor have resected surgical specimens, thus making the diagnosis of primary intestinal lymphangiectasis very unlikely. The etiology of eosinophilic gastroenteritis remains unknown. 1 - 5 , 14, 17-19
April 1970
CASE REPORTS REFERENCES
1. Kaijser, R . 1937. Zur K enntnis der aller-
2.
3.
4.
5.
6.
7.
8.
9.
gischen Affektionen des Verdaungskanal vom Standpunkt des Chirurgen. Arch. Klin. Chir.i88: 36-64. Ureles, A. L., R. Alochibaja, D. Lodico, and S. J. Stabins. 1961. Idiopathic infiltration of the gastrointestinal tract, diffuse and circumscribed. A mer. J. M ed. 30: 894-899. Edelman, J . J., and T . L. March . 1964. Eosinophilic gastroenteritis. Amer. J. Roentgen. 91: 773-778. Burhenne, H . J., and J . V. Carbone. 1966. Eosinophilic (allergic) gastroenteritis. Amer. J. Roentgen. 96: 332-338. Bentlif, P. S., J. W. McBee, W. R. Beach, and W. T. Hill. 1966. Eosinophilic gastroenteritis. Texas M ed. 62: 51-56. Leinbach, G. E., and C. E. Rubin. 1969. Is eosinophilic gastroenteritis caused by food allergy? Gastroenterology 56: 1177, 1969. Waldman, T . A ., R . D . Wochner, L . Laster, and R. S. Gordon. 1967. Allergic gastroenteropathy . A cause of excessive gastrointestinal protein loss. New Eng. J. M ed. 276: 761- 769. Greenberger, N. J., J. 1. Tennenbaum, and R. D . Ruppert. 1967. Protein-losing enteropathy associated with gastrointestinal allergy. Amer. J. Med. 43: 777-784. Goldstein, F., G. Salen, and C. W. Wirts. 1964. Small bowel bacterial cultures in controls and in patients with achlorhydria and with intestinal obstruction . Clin. Res. 12 :
44', . 10. Goldstein, F . C. W. Wirts, G. Salen, and R. J. MandIe. 1969. Diverticulosis of the small
intestine. Clinical, bacteriologic, and meta-
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bolic observations in a group of seven patients. Amer. J. Dig. Dis. 14: 170-181. 11. Choi, H . J ., F. Goldstein, C. W. Wirts, and H . Menduke. 1967. Normal duodenal trypsin values in response to secretinpancreozymin stimulation with preliminary data in patients with pancreatic disease. Gastroenterology 53: 397-402. 12. Rootwelt, K. 1966. Direct intravenous injection of I5l chromic chloride compared with 12IiI-polyvinylpyrrolidone and lOll-albumin in the detection of gastrointestinal protein loss. Scand. J . Clin. Lab . Invest. 18: 406-416. 13; Hofmann, A. 1962. Thin-layer absorption chromatography of free and conjugated bile acids on silicic acid. J. Lipid Res. 3: 127-128. 14. Culver, G. J., H. S. Puson, M. Montex, and H. K. Palanker. 1967. Eosinophilic gastritis. J. A . M . A 200: . 641--643. 15. Brody, E. A., S. Estren, and V. Herbert. 1966. Coexistent pernicious anemia and
malabsorption in four patients. Ann. Intern. Med. 6.~: 1246-1257. 16. Carmel, R., and V. Herbert. 1967. Correctible intestinal defect of vitamin B .. absorption in pernicious anemia. Ann. Intern. Med. 67: 1201-1207. 17. Swartz, J . M ., and J. M. Young. 1955. Primary infiltrative eosinophilic gastritis, enteritis and peritonitis. Gastroenterology 28: 431-452. 18. Orr, 1. M., A. A. Miller, and J. Y. W. Russel. 1954. Eosinophilic infiltration of the stom,. ach and bowel. Postgrad. M ed. J. 30: 485493. 19. Duvall, C. P., and W. A. Coleman. 1967.
Conservative management of eosinopbilic infiltration of the gastrointestinal tract. Amer. J. Dig . Dis. 12: 107-109.
GASTROENTEROLOGY
Copyright © 1970 by The Williams & Wilkins Co.
CASE REPORTS
EOSINOPHILIC GASTROENTERITIS Report of a case with malabsorption and protein-losing enteropathy STEPHEN M. KAPLAN, M.D., FRANZ GOLDSTEIN, M.D., AND O. DHODANAND KOWLESSAR, M.D. Division of Gastroenterology, Department of Medicine, Jefferson Medical Col/ege, Philadelphia, Pennsylvania
The case of a 77 -year-old white woman with eosinophilic gastroenteritis of long duration is presented. The occurrence of malabsorption and protein-losing enteropathy is well documented. The diagnosis was made by means of peroral jejunal biopsy, making exploratory laparotomy unnecessary. The response to corticosteroids was prompt and sustained, although incomplete and could be maintained on an alternating day schedule of steroid administration. In 1937, Kaijser 1 described 3 cases of eosinophilic infiltration of the stomach and small bowel. In 1961, Ureles and associates,2 after a review of the world literature, proposed a classification of the 75 reported cases into a diffuse type, or eosinophilic gastroenteritis (26 cases), and a circumscribed type, or eosinophilic granuloma. Eosinophilic gastroenteritis can be differentiated readily from eosinophilic granuloma on clinical, pathological, laboratory,2 and radiological bases. s,4 Isolated cases of eosinophilic gastroenteritis with either protein -losing gastroenteropathy,S Received July 24, 1969. Accepted October 8, 1969. Address requests for reprints to: Dr. O. Dhodanand Kowlessar, Department of Medicine, Jefferson Medical College, 1025 Walnut Street, Philadelphia, Pennsylvania 19107. This work was supported in part by Contract/ Grant DADA 17-68-C-8092 from the United States Army Medical Research and Development Command, by Themis Grant NOO014-680516 from the Office of Naval Research, United States Navy, and by Grants FR-72 and AM-5572 from the National Institutes of Health, United States Public Health Service.
malabsorption,5 or both6 have been reported, but none were supported by complete data. This disease probably is not identical with allergic gastroenteropathy,7, 8 which occurs in early childhood and is characterized by food intolerances and other allergic manifestations. The present report concerns a case of eosinophilic gastroenteritis in an septuagenarian manifesting extensive small bowel involvement associated with malabsorption and protein loss. Case Report F. S., a 77-year-old white woman, was admitted to the Jefferson Medical College Hospital on May 17, 1967, with a 12-year history of intermittent, crampy epigastric pain, relieved by vomiting undigested food. Four years prior to admission she developed anorexia, weakness, easy bruising, and muscle cramps. She gradually lost 30 lb of weight and developed more frequent episodes of vomiting with associated abdominal distention, ankle swelling, and diarrhea consisting of two to six light colored, semisolid to watery stools per day. During her hospitalization in 1963 in another hospital she was observed to have a blood eosinophilia of over 30%. In May 1967 her symptoms worsened and she was referred to
540
541
CASE REPORTS
April 1970
our hospital. There was no pertinent history of past illness except for a fractured right hip incurred 2 years earlier. There was no history of allergies or food intolerances. The patient had never traveled outside the United States and Canada. On admission, she was emaciated, with decreased subcutaneous tissue and muscle mass. Vital signs were normal. Weight was 75.5 Ib and fell to 65 Ib after diuresis. The tongue was smooth and red. The abdomen was distended markedly and gurgling peristaltic sounds were heard. Rectal examination was normal. The stool was free of occult blood, but contained stainable fat. There was marked pitting edema of both ankles and legs. Multiple ecchymoses were noted over the extremities. The deep tendon reflexes were diminished. Pertinent laboratory studies on first admission are summarized in table 1. Serum electrolytes were normal except for refractory hypokalemia, hypocalcemia, and hypophosphatemia. The patient had a severe normocytic, TABLE
normochromic anemia. Serum iron, total ironbinding capacity, folate, haptoglobin, and vitamin B12 levels were normal. However, the patient had received several vitamin B12 injections prior to admission. The bone marrrow showed eosinophilic hyperplasia representing 30% of the total cells, normoblastic erythropoiesis, and stainable iron. A plain film of the abdomen demonstrated distended loops of small bowel. A small bowel biopsy revealed well preserved villi with normal epithelial cells; the lamina propria showed edema, hemorrhages, and infiltration with predominantly plasma cells and eosinophils. Because or excessive aerobic bacterial growth in the upper small intestine (table I), the patient was treated with 5-day courses of tetracycline and ampicillin, 250 mg q.i.d., each, but failed to improve. However, on a daily dose of 20 mg of prednisone she showed marked clinical improvement. Her fecal fat excretion on a 100-g daily fat intake decreased from 47 to 4.5 g
1. Results of laboratory tests
Testa
First admission (May 1967)
Second admission (October 1967)
Third admission (January 1969)
Hemoglobin (12-15 g/100 ml) White blood count (5,000-10,000 cells/ mm) Range of eosinopbils (1-3%) Serum potassium (4.1-5.2 mEq/liter) Serum calcium (4.5-5.5 mEq/liter) Serum phosphorus (2-4 mg/100 ml) Serum alkaline phosphatase (1.5-4.0 Bodansky units) Schilling test (>7% excreted) Schilling test with intrinsic factor of proven potency (>7% excreted) Fecal fat «5 g/24 hr) with patient receiving 100-gm fat diet d-Xylose excretion «5.0 g/5 hr) Prothrombin time (80-100%) Serum carotene (60-260l'g/100 ml) Total protein (6.2-7.8 g/100 m!) Albumin (2.9-4.5 g/IOO ml) -y-Globulin (0.7-1.9 g/100 ml) Immunoglobulin G (600-1800 mg/100 ml) Immunoglobulin A (40-380 mg/100 ml) Immunoglobulin M (20-200 mg/IOO ml) Aerobic distal duodenal bacterial culture (0-5 X 10' CFU/ml)' Anaerobic distal duodenal bacterial culture «2.5 X 10' CFU/ml)lO Urinary indican excretion (40-100 mg/ 24 hr) Secretin test volume (1.1-4.6 cc/kg/hr)l1 Maximum bicarbonate concentration (65-121.5 mEq/liter)l1 Stools for ova and parasites Protein-bound iodine (4-8I'g/100 ml) Dry weight after diuresis
7.1 15,150
13.1 13,250
13.9 13,100
12-45 3.5 3.1 1.8 9.6
12-17 4.3 4 2.6 5.7
8-21 4.0 4.2 2.9 4.8
5.6 1.6
3.0 <1
3.9
6.1
9.1 7.7 2.6 88 19 4.8 3.1 0.4 480
47 1.5
10 4.0 2.5 0.4 650 187 70 1. 7 X 10' Escherichia coli 1. 5 X 10' a"Streptococcus
a Normal values given in parentheses.
1.7 100 <19 4.8 2.7 0.6
4.3 X 10' a-Streptococcus 9.2 X 10' E. coli 1 X J07 47.52
8.4 70
5.3 82
Neg X 2 6.0 65
Neg X 2 74.5
200 60 1. 4 X 10' a-Streptococcus 4 X 10' E. coli
75,96.25-97.50
Neg X 2 4.5 75
542
CASE REPORTS
Vol. 58, No.4
daily. Stool frequency decreased to two formed movements a day and a weight gain ensued without recurrence of edema. She was discharged taking prednisone, diuretics, vitamins, oral calcium, potassium, and diphenoxylate. The patient was readmitted in October 1967. She reported less vomiting and diarrhea, an improved appetite, and a weight gain of 8 lb. The physical examination showed only slight abdominal distention and minimal ankle edema; otherwise, her condition remained unchanged. Laboratory results during second admission are summarized in table 1. The most striking changes from the earlier admission were the normal hemoglobin concentration and near normal fat absorption. An upper gastrointestinal series with small bowel follow-through showed an atrophic mucosal pattern in the stomach and nearly total absence of the normal mucosal folds in the proximal small bowel (figs. 1 and 2). Augmented histamine gastric analysis demonstrated achlorhydria. The peroral small bowel biopsy remained essentially unchanged. Treatment was continued with
FIG. 2. Radiological appearance of stomach and small intestine, showing grossly abnormal mucosal pattern of entire length of small bowel.
FIG. 1. Radiological appearance of stomach, demonstrating partial effacement of gastric folds consistent with gastric atrophy. Duodenal diverticulum also is present.
prednisone, 10 mg daily. A course of ampicillin, 250 mg q.i.d. for 5 days, did not produce any measurable improvement. Following discharge the patient maintained her weight between 74 and 77 Ib with occasional episodes of vomiting and variable diarrhea. Her appetite remained good. She was readmitted on January 22, 1969, after 1 week of increased abdominal distention and ankle edema. Physical examination showed moderate abdominal distention, occasional gurgling peristaltic sounds, and moderate ankle and pretibial edema. Laboratory results of the third admission, summarized in table 1, show further improvement in hematological and chemical parameters. The dose of prednisone was increased from 10 to 15 mg daily with a subsequent decrease in bowel frequency and less abdominal distention. This improvement was maintained after changing therapy to 30 mg of prednisone every other day. A small bowel biopsy remained unchanged and again showed moderate inflammatory cell infiltrates. Upper gastrointestinal and small bowel series were similar to those in the previous examina-
CASE REPORTS
April 1970
tion. Chromium51-labeled chloride was injected intravenously and stools were collected for 72 hr with 19% of the injected radioactivity appearing in the stools (normal, 0.35 to 1.25%).12 Distal duodenal fluid showed no free bile salts with a normal pattern of conjugated bile salts by thin layer chromatography.'· A lactose tolerance test was low normal. The patient was discharged taking 30 mg of prednisone every other day, oral calcium and potassium supplements, vitamins, and a moderately salt-restricted diet. As of June 30, 1969, she was asymptomatic and gaining additional weight.
Discussion
The clinical and laboratory features of our patient are typical of the polyenteric type of eosinophilic gastroenteritis as defined by Ureles,2 except that our patient developed the disease in her seventh decade while most patients develop it between the second and fifth decades. 2 The prolonged clinical history (14 years) without any other manifestations of malignancy, the persistent eosinophilia, and the lack of evidence of malignant lymphoid cells in the lamina propria of three small bowel biopsies make a lymphoma of the small bowel unlikely. The normal jejunal epithelial cells and villous architecture militate against a diagnosis of adult celiac disease. Allergic gastroenteropathy 7. 8 is probably a separate clinical entity with peripheral eosinophilia and eosinophilic infiltration of the lamina propria of the small bowel. Allergic gastroenteropathy develops in the first and second decades of life and is characterized by a history of atopy, by periorbital or generalized edema, extreme hypoalbuminemia, hypogammaglobulinemia, growth retardation,anemia secondary to chronic blood loss, occasional episodes of diarrhea or vomiting after milk ingestion, and by a tendency for the gastrointestinal manifestations and hypoproteinemia to become less severe as the patients grow older. The radiological features of the stomach and small intestine in our case seem somewhat unusual in that the X-rays of the stomach suggested gastric atrophy and the entire length of the small bowel showed a nearly total absence of the mucosal pattern
543
usually observed radiologically. Typically, the gastric involvement in eosinophilic gastroenteritis is limited to the distal half of the stomach, resulting in an irregular gastric outline with antral or pyloric narrowing and often with gastric retention. The small bowel in eosinophilic gastroenteritis often shows irregular segmental narrowing with thickening and rigidity of the wall interspersed with dilated loops; these changes are usually more pronounced in the proximal and middle small intestine. Eosinophilic gastritis involved the entire stomach in 2 cases reviewed by Ureles et a1. 2 and involved the stomach from the cardioesophageal junction to the midantrum in 1 case of Culver and co-workers,14 but in these cases the stomach showed prominent rugal folds . It is likely that our patient has both eosinophilic gastroenteritis and pernicious anemia, the co-existence of small intestinal disease and pernicious anemia having been noted by others.15 Carmel and Herbert16 believe that gastric atrophy with loss of intrinsic factor secretion can occur as a result of long term vitamin B12 or folate defici ency caused by intestinal malabsorption. In the majority of the previously reported cases of eosinophilic gastroenteritis, the diagnosis was made by exploratory laparotomy and the gross and microscopic pathology of this disease has been based largely on resected specimens. The surgical specimens show the most extensive eosinophilic infiltration to be present in the submucosa, muscularis, and serosa, with relative sparing of the mucosa. 1-4 Peroral small bowel biopsy has been used rarely to diagnose this disease. Bentlif et al. reported 3 cases with typical clinical , laboratory, and radiological features confirmed by peroral small bowel biopsies. Their biopsies showed moderate edema of the villi with a diffuse infiltration of eosinophils and plasma cells in the lamina propria.5 The similarity of the descriptive features between the peroral small bowel biopsies in our case and in those of Bentlif5 and Leinbach and Rubin 6 is apparent. These latter authors also pointed out the patchy nature of the eosinophilic infiltrate, finding it in 20 of 28 proximal
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CASE REPORTS
small bowel biopsies in their patient. 6 It is not clear, however, whether their case represents eosinophilic or allergic enteropathy. Since this disease can involve the entire small bowel or any part of it,17 it is surprising that malabsorption has not been reported more often. Bentlif et al. 5 described a 36-year-old woman with abdominal pain, vomiting, diarrhea, distention, and weight loss. They state that stools stained with Sudan IV contained fat particles and that there was deficient absorption of P3l-labeled triolein and dxylose, but give no quantitative data on these abnormalities. Leinbach and Rubin's case, reported in abstract,6 manifested steatorrhea with a coefficient of fat absorption of 79%. On her initial admission our patient showed severe malabsorption characterized by a stool fat excretion of 47 g per day, a low urinary d-xylose excretion (1.5 g per 5 hr), marked hypocarotenemia, low serum calcium and phosphorus with elevated alkaline phosphatase, the latter three measurements suggesting osteomalacia, and abnormal Schilling tests with and without added intrinsic factor. Thus, our patient had clear cut evidence of malabsorption. The precise mechanism for the malabsorption in eosinophilic enteritis has not been established. Distal duodenal bacterial cultures in our patient showed moderately increased total bacterial growth on all admissions (up to 107 CFU per ml), but there was no clinical or laboratory improvement with antibiotic treatment. In addition, malabsorption due to bacterial overgrowth was unlikely since the distal duodenal fluid showed a normal pattern of conjugated bile salts with no free bile salts and the urinary indican levels were normal. Secretin tests showed high volumes of secretion with low normal bicarbonate concentrations. Serum immunoglobin G, M, and A levels were low normal. It is possible that the inflammatory cell infiltration of the small intestinal mucosa, presumably extending throughout the small intestine as evidenced by the diffuse radiological changes, interferes with the normal absorptive function of the mucosal cell
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and/or may constitute a diffusion barrier to absorption of simple substances. The malabsorption was improved only after treatment with prednisone and improvement was maintained with low doses of steroids, administered most recently in a single dose every other day. Others have reported symptomatic remissions of eosinophilic gastroenteritis with adrenocorticotropin 2 , 18 or corticosteroids,!- 5, 19 but with the possible exception of the case noted. by Leinbach and Rubin 6 there have been no reports on the effectiveness of these drugs in the treatment of the malabsorption of eosinophilic gastroenteritis. Edelman and March3 reported a case of a 16-year-old male whose upper gastrointestinal and small bowel series showed persistent narrowing of the distal antrum with multiple polypoid filling defects having a cobblestone appearance and a normal appearing small bowel. The patient's total serum protein concentration was 4.7 g per 100 ml with 3.3 g per 100 ml of albumin; his stools were positive for occult blood and his serum iron was 20 mcg per 100 ml. According to these authors, the P3l-labeled albumin turnover studies indicated protein loss into the gastrointestinal tract in excess of what could be attributed to bleeding, but no quantitative data were given. Exploratory laparotomy revealed thickening of the pyloric portion of the stomach and jejunum, with a pathological diagnosis of eosinophilic gastroenteritis. Our patient presented initially with low serum albumin and y-globulin values. Even after striking improvement in the steatorrhea these values remained low (see table 1), suggesting a mechanism other than malabsorption as their cause. The presence of substantial protein exudation into the gut lumen was demonstrated by the Cr5l CI fecal excretion of 19% of the injected dose. The small bowel biopsies in our case did not show dilated lacteals nor have resected surgical specimens, thus making the diagnosis of primary intestinal lymphangiectasis very unlikely. The etiology of eosinophilic gastroenteritis remains unknown. 1 - 5 , 14, 17-19
April 1970
CASE REPORTS REFERENCES
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