The Journal of the Royal Medico-Chirurgical Society of Glasgow, the Scottish Society for Experimental Medicine and the Aberdeen Medico-Chirurgical Society. ISSN: 0036-9330
Volume 35
EOSINOPHILIC GASTROENTERITIS A review was undertaken of 220 case reports of eosinophilic gastroenteritis involving the gastrointestinal tract, with particular regard to its clinical presentation and management. The stomach was the single commonest site of involvement (43%), while 36% were found to have two or more sites of disease at the time of presentation. The most common presenting symptoms were episodic abdominal pain (77%) and diarrhoea (42%). A history of allergy was present in 52% of patients, while 8% reported aggravation of symptoms following the ingestion of certain foods. Two thirds of patients had reported symptoms of more than six months duration prior to diagnosis, while in 26%, five years or more had elapsed. Although surgical intervention was undertaken in 44% of patients at some stage in their management, the most successful mode of management was the institution of steroid therapy, where 90% reported rapid clinical improvement. There is no evidence that patients with eosinophilic gastroenteritis have a higher incidence of subsequent gastrointestinal malignancies. Introduction Eosinophilic gastroenteritis, a benign condition of unknown aetiology, characterised clinically by recurrent abdominal- pain and diarrhoea and pathologically by tissue oedema, a dense eosinophilic infiltrate and in the majority of patients a peripheral eosinophilia, was first described by Kaijserin 1937.1 Despite an excess of 300 case reports in the world literature, many clinicians remain unaware of this disease, though this may in part be due to the large number of terms ascribed to the disease since its first description (Table I). Although the disease process may also involve the urinary tract,2.3 this review deals with the clinical features in 220 cases of eosinophilic gastroenteritis reported in the English speaking literature, where the disease primarily involved the gastrointestinal system. Table I Terms used to describe eosinophilic gastroenteritis
idiopathic gastrointestinal eosinophilic infiltration eosinophilic gastroduodenitis infiltrative eosinophilic gastritis gastric lesion of Loeffler's syndrome pyloric hypertrophy with eosinophilic infiltration eosinophilic Crohn's disease eosinophilic linitis plastica eosinophilic phlegmonous gastritis gastric lesions of disseminated collagenosis of Bousser Pathological features Macroscopic features The affected area of bowel may present as diffusely thickened and oedematous segment(s), or as discrete masses. There is frequently an associated serosal reaction and adjacent mesenteric lymph nodes may be enlarged. The mucosa is rarely ulcerated, but may be thrown into thickened folds. Frank bowel wall necrosis is rare, though the disease has been severe enough to obliterate tissue planes" and cause intestinal perforation in three cases.>? Microscopic features The universal feature is a dense transmural eosinophilic infiltrate, particularly in the submucosa, where it is associated with varying degrees of oedema and minimal fibrous stroma. Although eosinophilic infiltration of the intestinal wall is recognised in a variety of gastrointestinal pathologies, the degree is small in comparison to that seen in eosinophilic gastroenteritis. While the disease process tends to be transmural, predominant involvement of one or more levels of the bowel wall can produce different modes of disease presentation," which will be discussed later. Enlarged lymph nodes demonstrate benign reactive hyperplasia, with diffuse eosinophilic infiltration of the sinusoids. Sites of disease The principal sites of involvement are detailed in Table II. The most common site was the stomach (43%), usually involving the antrum and pylorus, where a discrete mass, often mistaken for carcinoma, was encountered. With the exception of the oesophagus, the frequency of
Number 6
December 1990
Scottish
Medical Journal
involvement decreased distally through the gastrointestinal tract. In 64% of patients, only one segment of the intestine was involved at a single presentation, while in 15%, three or more sites of disease were simultaneously present. Table II Sites of involvement in 220 cases of eosinophilic gastroenteritis
Principal
stomach ileum jejunum duodenum colon and rectum diffuse serosal
Others:
gallbladder liver oesophagus spleen pancreas appendix perianal cholangitis
43% 33% 31% 19% 11% 7% 3.0% 2.0% 1.3% 1.3% 1.3% 1.3% 0.5% '0.5%
Clinical features Eosinophilic gastroenteritis affects all races and is not exclusive to the human species."!' There is no sex preference and it tends to occur in the third to fourth decades. Eosinophilic gastroenteritis has been documented in siblings, 12-14 though identical haplotypes have not been reported. 14. The principal clinical features are detailed in Table III. Recurrent abdominal pain (77%) and diarrhoea (42%) were the commonest presenting symptoms, usually in association with anorexia, nausea or vomiting (48%). One asymptomatic patient, whose diagnosis was made following autopsy, has also been reported.P Predominant involvement of the mucosa is associated with diarrhoea and less commonly gastrointestinal blood loss and protein and fat malabsorption. Predominant involvement of the muscle layers of the gastrointestinal tract, frequently presenting as a discrete mass, produces obstructive symptoms affecting the gastric outlet, small bowel and colon. Diffuse serosal disease causes ascites, which may mask underlying abdominal masses. Table III Clinical features in 220 cases of eosinophilic gastroenteritis
abdominal pain anorexia, nausea, vomiting diarrhoea weight loss abdominal distension gastrointestinal blood loss stool positive for occult blood fresh rectal bleeding haematemesis melaena constipation ascites palpable abdominal mass protein malabsorption fat malabsorption others: intestinal perforation dysphagia jaundice peripheral oedema perianal disease asymptomatic
77% 48% 42% 17% 12% 6% 6% 3% 3% 5% 5% 5% 9% 3% 1.4% 1.4% 1.0% 1.0% 0.5% 0.5%
In one third of patients, the duration of symptoms prior to diagnosis was less than four weeks, while in 26% five years or more had elapsed before a definitive diagnosis was made. The longest reported case was admitted to hospital on 38 occasions Over a 32 year period.!" A history of allergy was present in 52% of patients, while 8% reported aggravation of symptoms following the ingestion of certain foodstuffs (usually egg, milk, wheat or
163
Comment
beef extracts). Direct observations have demonstrated rapid endoscopic and histological changes in the stomach and proximal jejunum following infusion of allergenic substances8.17,18 and serum IgE levels have been noted to treble during a food challenge, during which the patient reported a recurrence of symptoms. 19 In this review, IgE levels were only reported in 18% of patients and were normal in two thirds of these. While tissue eosinophilia is a universal feature in eosinophilic gastroenteritis, a peripheral blood eosinophilia is not. A periperal eosinophilia (in excess of 5% of the total white cell count) was present in 79% of patients, though in 52%, eosinophils comprised more than 20% of the differential. The aetiology of eosinophilic gastroenteritis remains unknown. Factors such as a personal history of allergy, aggravations of symptoms with certain foodstuffs, rapid histological and endoscopic changes during dietary challenge, tissue and usually peripheral eosinophilia, correlation of symptoms with skin and RAST testing and IgE levels'? and the fact that the majority of patients respond to steroid therapy suggest an underlying allergic mechanism. Cello has proposed that food antigens may react with specific IgE antibodies bound to mast cells at their Fe receptor sites. Mast cell degranulation releases an eosinophilatactic agent and other substances, which may themselves cause tissue damage.F" Attractive as this theory seems, it is only relevant to patients with a positive RAST and raised serum IgE titres and does not explain involvement of the deeper layers of the bowel or involvement of the gallbladder or spleen. Recent work using monoclonal antibodies has shown activated and degranulating eosinophils in biopsy specimens of patients with eosinophilic gastroenteritis and it was proposed that eosinophilic cationic protein (released by the eosinophils) may be responsible for the subsequent tissue injury and symptoms. 14. This is an important point as most authors suggest that the eosinophilic infiltrate is not responsible for the tissue injury. While there is considerable evidence for an immunological basis to eosinophilic gastroenteritis, there are a number of inconsistencies including the absence of allergy in half of the study group (though not all were tested for hidden allergies), 21% did not have a peripheral eosinophilia (despite being tested during a period of active disease), over 90% did not report an association between symptoms and certain foodstuffs (despite the fact that 45% described episodic symptoms for more than one year) and a trial of dietary elimination was unsuccessful in 70% in whom it was tried. The underlying pathogenesis of eosinophilic gastroenteritis therefore remains unknown. In view of ongoing immunological theories, it is hoped that future case studies will include details of complement profiles, immune complex deposition, monoclonal antibody studies and IgE titres both before and, where possible, after therapy. One final factor which has been intermittently implicated in the aetiology of eosinophilic gastroenteritis is the role of intestinal parasites. Of the patients reviewed in this study, 9% were found to have either the herringworm (Eustoma rotundaturn) or some other parasite within the diseased segment of bowel, though none were identified in any extra-intestinal site. The majority of these cases were in fact reported by Kaijser in his original description of the disease! and very few recent case reports have identified any parasites. The principal differential diagnoses in patients with eosinophilic gastroenteritis are gastrointestinal tumours, gastroduodenal ulceration, inflammatory bowel disease and inflammatory fibroid potyp." In the majority of early reports, the diagnosis was made following histological examination of resected bowel. With increasing awareness of the disease, cases are now diagosed without recourse to surgery using clinical suspicion supplemented by contrast radiography and fibreoptic examination and biopsy, Clinical suspicion may be aroused in patients presenting with recurrent symptoms, a history of allergy and a peripheral eosinophilia. Aspiration of ascitic fluid may yield fluid rich in eosinophils22- 35 and Charcot-Leyden crystals, which may also be identified in stooI 8,14,26 and jejunal aspirates." Increased numbers of eosinophils may be identified in stool specimens using specific staining techniques, 27 Unfortunately, the radiographic and fibreoptic appearances of eosinophilic gastroenteritis are rather non-specific, indicating the need for a tissue diagnosis from biopsy specimens. Those radiographic features that that have been reported include; thickening and flattening of the valvulae conniventes, an occasional saw-tooth pattern, nodular intra-luminal filling defects, narrowing, rigidity and increased secretions20,28.29 making differentiation from inflammatory bowel disease understandably difficult. Because of the capacity for simultaneous biopsy, fibreoptic examination has reduced the requirement for diagnostic laparotomy. Few clear endoscopic descriptions have been published and the general features reported tend to be non-specific; diffuse erythema, thickened mucosal folds, nodularity, contact bleeding and rarely ulceration.Pv" Because of the non-specific nature of these observations, it is essential that any minor endoscopic abnormalities are biopsied. Despite advances in awareness and fibreoptic tissue diagnosis, a proportion of patients will still require surgery for definitive diagnosis, particularly to exclude tumours and in the relief of bowel obstruction.
164
Where the diagnosis of eosinophilic gastroenteritis is suspected peroperatively, a full-thickness biopsy or frozen section may provide a diagnosis." though on occasions, the latter has proved misleadingP A review of the management regimes of the 220 patients has revealed certain trends. Half of those managed expectantly (usually presenting with milder symptoms) developed recurrent or ongoing symptoms during follow-up, as did 66% and 70% of those treated with disodium cromoglycate and dietary elimination respectively. Surgical intervention was undertaken in 44% of patients at some stage in their management, 80% as the initial mode of management. Overall, 43% developed recurrent symptoms during follow-up and 13% continued to have symptoms in the early post-operative period. Two thirds of those treated by laparotomy or intestinal bypass alone developed recurrent symptoms (usually at a different site) though patients receiving post-operative steroid had a lower recurrence rate (25%). Resection of the diseased segment was the most commonly performed surgical procedure, with 8% having continued symptoms following surgery and 28% developing recurrent symptoms during follow-up. The most successful mode of management was the institution of steroid therapy (usually prednisolone 20-4Omg daily) with 90% showing a rapid improvement. Reduction to a maintenance dose (lOmg) resulted in 15% developing recurrent symptoms, while 55% developed symptoms on cessation of steroids, though not all required reintroduction of prednisolone. Long-term prednisolone therapy is not without its own problems and beclomethasone diproprionate has been successfully employed without suppression of the hypothalamic-pituitaryadrenal axis.P" In summary, it would seem appropriate to try an elimination diet in patients whose symptoms are aggravated by specific foodstuffs, but for the majority, a course of prednisolone or beclomethasone is indicated. The introduction of steroid therapy without a definitive tissue diagnosis should be discouraged as serious pathology such as intestinal malignancies may be missed." Recurrent symptoms may be treated by reintroduction of steroid if warranted. Patients suspected of having the disease at operation may be treated by biopsy and post-operative steroid, but in some, resection will be necessary either becasue of obstruction, perforation, unremitting disease despite steroid therapy.t-" or simply because the operator cannot exclude a carcinoma at the time of operation. It would seem reasonable to adopt an expectant approach in the latter patients and treat any recurrent symptoms with steroid if required. There have been four deaths attributable to eosinophilic gastroenteritis, three following complications of surgery.6.7.36 In the majority of patients, the disease follows a relatively benign course, punctuated by recurrent symptoms. In a very small proportion of patients, the disease can be much more aggressive and even fatal. In one patient, the disease was so severe that all intra-abdominal tissue planes were obliterated and resection of a huge phlegmonous mass impossible, This patient subsequently died despite high dose steroid therapy." A second patient with eosinophilic colitis and extensive perianal disease was also unresponsive to steroid therapy and required a total colectomy for control of symptoms. 35 There is however, no evidence that patients with eosinophilic gastroenteritis have a higher risk of subsequent gastrointestinal malignancies. ACKNOWLEDGEMENT: I would like to thank Dr R.C. Heading (Depart-
ment of Medicine) for his help in the preparation of this manuscript. A.R. Naylor Department of Surgery The Royal Infirmary Lauriston Place, Edinburgh REFERENCES I Kaijser R. Zur kenntnis der allergischen affektionen des verdaungskanal vom standpunkt des chirurgen aus. Arch Klin Chir. 1937; 188: 36-64. 2 ~ubin L, Pincus MB. Eosinopilic cystitis. The relationship of allergy 10 the urinary tract to eosinophilic cystitis and the pathophysiology of eosinophilia. J. Uro11974; 112: 457-460. 3 Stewart MJ, Wray S. Hall M, Allergic prostatis in asthmatics. J. Path and Bact 1954; 67: 423-430. 4 Tytgat GN, Grijm WD, Dekker W, den Hartog NA. Fatal eosinophilic enteritis, Gastroenterology 1976; 71: 479-483. 5 Houghton PW. The gastric lesion of disseminated eosinophilic collagenosis of Bousser. Br. J. Surg. 1959; 47: 238-240. 6 Russell JYW, Evangelou G. Eosinophilic infiltration of the stomach and duodenum complicated by perforation. Postgrad Med. J. 1965; 41: 30-33. 7 Felt-Bersma RJF, Meuwissen SGM, van Velzen D. Perforation of the small intestine due to eosinophilic gastroenteritis. Am. J. Gastroentero11984; 79: 442-445.
Comment
8 Klein NC, Hargrove RL, Sleisenger MH, Jeffries GH. Eosinophilic gastroenteritis. Medicine (Baltimore) 1970;49: 299-319. 9 Pass DA, Bolton JR. Chronic eosinophilic gastroenteritis in the horse. Vet. Pathol. 1982; 19: 486-496. 10 Citino SB, Bush M, Phillips LG, Montali RJ, Wang KP, Ravich WJ. Eosinophilic gastroenteritis in a juvenile orangutan. J. Am.Vet. Assoc. 1985; 187: 1279-1280. 11 Legendre AM, Krehbiel JD. Eosinophilic gastroenteritis in a Chesapeak Bay Retriever. J. Am. Vet. Assoc. 1973; 163: 258-259. 12 Lynch MIG, Hutchinson WE, Sprague JD. Pyloric obstruction due to muscular hypertrophy and massive eosinophil infiltration. Gastroenterology 1956;31: 571-580. 13 Leegard M. Eosinophilic cholecystitis. Acta. Chir. Scand. 1980; 146: 295-296. 14 Keshavarzian A, Saverymuttu SH, Tai P-C, Thompson M, Barter S, Spry CJF, Chadwick VS. Activated eosinophils in familial eosinophilic gastroenteritis. Gastroenterology 1985;88: 1041-1049. 15 Pal AK. Eosinophilic gastroenteritis: Report of an unusual case with sigmoid coloniclesion. J. Assoc. Phys. India. 1982;29: 967-970. 16 Weisberg SC, Crosson JT. Eosinophilic gastroenteritis, a report of a case of 32 years duration. Dig. Dis. Sci. 1973; 18: 1005-1014. 17 Pollard HM, Stuart GJ. Experimental reproduction of gastric allergy in human beings with controlled observations on the mucosa. J. Allergy 1942; 13: 467-473. 18 Greenberger MJ, Tennenbaum II, Ruppert RD. Protein losing enteropathy associated with gastrointestinal allergy. Am. J. Med. 1967;43: 777-784. 19 Caldwell JH, Tennenbaum II, Bronstein HA. Serum IgE in eosinophilic gastroenteritis. N. Eng. J. Med. 1975; 292: 1388-1390. 20 Cello JP. Eosinophilic gastroenteritis - a complex disease entity. Am. J. Med. 1979;67: 1097-1104. 21 Johnstone JM, Morson BC. Eosinophilic gastroenteritis Histothology 1978; 2: 335-348. 22 Harley JB, Glushien AS, Fisher ZR. Eosinophilic peritonitis. Ann. Int. Med. 1959; 51: 301-308.
23 Salmon PR, Paulley JW. Eosinophilic granuloma of the gastro-intestinal tract. Gut. 1967;8: 8-14. 24 Duval CP, Coleman A. Conservative management of eosinophilic infiltration of the gastrointestinal tract: Report of a case. Am. J. Dig. Dis. 1967; 12: 107-109. 25 Higgins GA, Lamm ER, Yutzy CV. Eosinophilic gastroenteritis. Arch. Surg. 1965; 92: 476-483. 26 Leinbach GE, Rubin CEo Eosinophilic gastroenteritis. A simple reaction to food allergens? Gastoenterology 1970; 59: 874-889. 27 Martin DM, Goldman JA, Gilliam J, Nasrallah SM. Gold induced eosinophilic enterocolitis: Response to oral cromolyn sodium. Gastroenterology 1981; 80: 1567-1570. 28 Edelman MJ, March TL. Eosinophilic gastroenteritis. Am. J. Roent. Rad. Ther. and Nuc. Med. 1964;91: 773-778. 29 Marshak RH, Lundner A, Maklansky D, Gelb A. Eosinophilic gastroenteritis. JAMA 1981;245: 1677-1680. 30 Partyka EK, Sanowski RA, Kozarek RA. Colonoscopic features of eosinophilic gastroenteritis. Dis. Colon and Rectum 1980; 23: 353-356. 31 Tedesco FJ, Huckaby CB, Hamby-Allen M, Ewing GC. Eosiinophilic ileocolitis - Expanding spectrum of eosinophilic gastroenteritis. Dig. Dis. Sci. 1981; 26: 943-948. 32 Jacobsen LB. Diffuse eosinophilic gastroenteritis. An adult form of allergic gastroenteropathy. Am: J. Gastroenterol1970; 54: 580-588. 33 Freundlich 1M, Schaupp R, Stauffer Lehman J. Eosinophilic gastroenteritis. A case report with extensive jejunal involvement. Radiology 1966; 86: 493-495. 34 Elkon KB, Sher R, Seftel HC. Immunological studies of eosinophilic gastroenteritis and treatment with disodium cromoglycate and beclomethasone diproprionate. SA. Med. J. 1977; 52: 838-841. 35 Lee FI, Costello FT, Cowley DJ, Murray SM, Srimankar J. Eosinophilic colitis with perianal disease. Am. J. Gastroenterol1983; 78: 164-166. 36 Rodriguez JJV, Saez S, Vega JS, Serrano MCL, Vallejo C. Pancreatitis and eosinophilic gastroenteritis. Int. Surg. 1973; 58: 415-419.
165
Volume 35
EOSINOPHILIC GASTROENTERITIS A review was undertaken of 220 case reports of eosinophilic gastroenteritis involving the gastrointestinal tract, with particular regard to its clinical presentation and management. The stomach was the single commonest site of involvement (43%), while 36% were found to have two or more sites of disease at the time of presentation. The most common presenting symptoms were episodic abdominal pain (77%) and diarrhoea (42%). A history of allergy was present in 52% of patients, while 8% reported aggravation of symptoms following the ingestion of certain foods. Two thirds of patients had reported symptoms of more than six months duration prior to diagnosis, while in 26%, five years or more had elapsed. Although surgical intervention was undertaken in 44% of patients at some stage in their management, the most successful mode of management was the institution of steroid therapy, where 90% reported rapid clinical improvement. There is no evidence that patients with eosinophilic gastroenteritis have a higher incidence of subsequent gastrointestinal malignancies. Introduction Eosinophilic gastroenteritis, a benign condition of unknown aetiology, characterised clinically by recurrent abdominal- pain and diarrhoea and pathologically by tissue oedema, a dense eosinophilic infiltrate and in the majority of patients a peripheral eosinophilia, was first described by Kaijserin 1937.1 Despite an excess of 300 case reports in the world literature, many clinicians remain unaware of this disease, though this may in part be due to the large number of terms ascribed to the disease since its first description (Table I). Although the disease process may also involve the urinary tract,2.3 this review deals with the clinical features in 220 cases of eosinophilic gastroenteritis reported in the English speaking literature, where the disease primarily involved the gastrointestinal system. Table I Terms used to describe eosinophilic gastroenteritis
idiopathic gastrointestinal eosinophilic infiltration eosinophilic gastroduodenitis infiltrative eosinophilic gastritis gastric lesion of Loeffler's syndrome pyloric hypertrophy with eosinophilic infiltration eosinophilic Crohn's disease eosinophilic linitis plastica eosinophilic phlegmonous gastritis gastric lesions of disseminated collagenosis of Bousser Pathological features Macroscopic features The affected area of bowel may present as diffusely thickened and oedematous segment(s), or as discrete masses. There is frequently an associated serosal reaction and adjacent mesenteric lymph nodes may be enlarged. The mucosa is rarely ulcerated, but may be thrown into thickened folds. Frank bowel wall necrosis is rare, though the disease has been severe enough to obliterate tissue planes" and cause intestinal perforation in three cases.>? Microscopic features The universal feature is a dense transmural eosinophilic infiltrate, particularly in the submucosa, where it is associated with varying degrees of oedema and minimal fibrous stroma. Although eosinophilic infiltration of the intestinal wall is recognised in a variety of gastrointestinal pathologies, the degree is small in comparison to that seen in eosinophilic gastroenteritis. While the disease process tends to be transmural, predominant involvement of one or more levels of the bowel wall can produce different modes of disease presentation," which will be discussed later. Enlarged lymph nodes demonstrate benign reactive hyperplasia, with diffuse eosinophilic infiltration of the sinusoids. Sites of disease The principal sites of involvement are detailed in Table II. The most common site was the stomach (43%), usually involving the antrum and pylorus, where a discrete mass, often mistaken for carcinoma, was encountered. With the exception of the oesophagus, the frequency of
Number 6
December 1990
Scottish
Medical Journal
involvement decreased distally through the gastrointestinal tract. In 64% of patients, only one segment of the intestine was involved at a single presentation, while in 15%, three or more sites of disease were simultaneously present. Table II Sites of involvement in 220 cases of eosinophilic gastroenteritis
Principal
stomach ileum jejunum duodenum colon and rectum diffuse serosal
Others:
gallbladder liver oesophagus spleen pancreas appendix perianal cholangitis
43% 33% 31% 19% 11% 7% 3.0% 2.0% 1.3% 1.3% 1.3% 1.3% 0.5% '0.5%
Clinical features Eosinophilic gastroenteritis affects all races and is not exclusive to the human species."!' There is no sex preference and it tends to occur in the third to fourth decades. Eosinophilic gastroenteritis has been documented in siblings, 12-14 though identical haplotypes have not been reported. 14. The principal clinical features are detailed in Table III. Recurrent abdominal pain (77%) and diarrhoea (42%) were the commonest presenting symptoms, usually in association with anorexia, nausea or vomiting (48%). One asymptomatic patient, whose diagnosis was made following autopsy, has also been reported.P Predominant involvement of the mucosa is associated with diarrhoea and less commonly gastrointestinal blood loss and protein and fat malabsorption. Predominant involvement of the muscle layers of the gastrointestinal tract, frequently presenting as a discrete mass, produces obstructive symptoms affecting the gastric outlet, small bowel and colon. Diffuse serosal disease causes ascites, which may mask underlying abdominal masses. Table III Clinical features in 220 cases of eosinophilic gastroenteritis
abdominal pain anorexia, nausea, vomiting diarrhoea weight loss abdominal distension gastrointestinal blood loss stool positive for occult blood fresh rectal bleeding haematemesis melaena constipation ascites palpable abdominal mass protein malabsorption fat malabsorption others: intestinal perforation dysphagia jaundice peripheral oedema perianal disease asymptomatic
77% 48% 42% 17% 12% 6% 6% 3% 3% 5% 5% 5% 9% 3% 1.4% 1.4% 1.0% 1.0% 0.5% 0.5%
In one third of patients, the duration of symptoms prior to diagnosis was less than four weeks, while in 26% five years or more had elapsed before a definitive diagnosis was made. The longest reported case was admitted to hospital on 38 occasions Over a 32 year period.!" A history of allergy was present in 52% of patients, while 8% reported aggravation of symptoms following the ingestion of certain foodstuffs (usually egg, milk, wheat or
163
Comment
beef extracts). Direct observations have demonstrated rapid endoscopic and histological changes in the stomach and proximal jejunum following infusion of allergenic substances8.17,18 and serum IgE levels have been noted to treble during a food challenge, during which the patient reported a recurrence of symptoms. 19 In this review, IgE levels were only reported in 18% of patients and were normal in two thirds of these. While tissue eosinophilia is a universal feature in eosinophilic gastroenteritis, a peripheral blood eosinophilia is not. A periperal eosinophilia (in excess of 5% of the total white cell count) was present in 79% of patients, though in 52%, eosinophils comprised more than 20% of the differential. The aetiology of eosinophilic gastroenteritis remains unknown. Factors such as a personal history of allergy, aggravations of symptoms with certain foodstuffs, rapid histological and endoscopic changes during dietary challenge, tissue and usually peripheral eosinophilia, correlation of symptoms with skin and RAST testing and IgE levels'? and the fact that the majority of patients respond to steroid therapy suggest an underlying allergic mechanism. Cello has proposed that food antigens may react with specific IgE antibodies bound to mast cells at their Fe receptor sites. Mast cell degranulation releases an eosinophilatactic agent and other substances, which may themselves cause tissue damage.F" Attractive as this theory seems, it is only relevant to patients with a positive RAST and raised serum IgE titres and does not explain involvement of the deeper layers of the bowel or involvement of the gallbladder or spleen. Recent work using monoclonal antibodies has shown activated and degranulating eosinophils in biopsy specimens of patients with eosinophilic gastroenteritis and it was proposed that eosinophilic cationic protein (released by the eosinophils) may be responsible for the subsequent tissue injury and symptoms. 14. This is an important point as most authors suggest that the eosinophilic infiltrate is not responsible for the tissue injury. While there is considerable evidence for an immunological basis to eosinophilic gastroenteritis, there are a number of inconsistencies including the absence of allergy in half of the study group (though not all were tested for hidden allergies), 21% did not have a peripheral eosinophilia (despite being tested during a period of active disease), over 90% did not report an association between symptoms and certain foodstuffs (despite the fact that 45% described episodic symptoms for more than one year) and a trial of dietary elimination was unsuccessful in 70% in whom it was tried. The underlying pathogenesis of eosinophilic gastroenteritis therefore remains unknown. In view of ongoing immunological theories, it is hoped that future case studies will include details of complement profiles, immune complex deposition, monoclonal antibody studies and IgE titres both before and, where possible, after therapy. One final factor which has been intermittently implicated in the aetiology of eosinophilic gastroenteritis is the role of intestinal parasites. Of the patients reviewed in this study, 9% were found to have either the herringworm (Eustoma rotundaturn) or some other parasite within the diseased segment of bowel, though none were identified in any extra-intestinal site. The majority of these cases were in fact reported by Kaijser in his original description of the disease! and very few recent case reports have identified any parasites. The principal differential diagnoses in patients with eosinophilic gastroenteritis are gastrointestinal tumours, gastroduodenal ulceration, inflammatory bowel disease and inflammatory fibroid potyp." In the majority of early reports, the diagnosis was made following histological examination of resected bowel. With increasing awareness of the disease, cases are now diagosed without recourse to surgery using clinical suspicion supplemented by contrast radiography and fibreoptic examination and biopsy, Clinical suspicion may be aroused in patients presenting with recurrent symptoms, a history of allergy and a peripheral eosinophilia. Aspiration of ascitic fluid may yield fluid rich in eosinophils22- 35 and Charcot-Leyden crystals, which may also be identified in stooI 8,14,26 and jejunal aspirates." Increased numbers of eosinophils may be identified in stool specimens using specific staining techniques, 27 Unfortunately, the radiographic and fibreoptic appearances of eosinophilic gastroenteritis are rather non-specific, indicating the need for a tissue diagnosis from biopsy specimens. Those radiographic features that that have been reported include; thickening and flattening of the valvulae conniventes, an occasional saw-tooth pattern, nodular intra-luminal filling defects, narrowing, rigidity and increased secretions20,28.29 making differentiation from inflammatory bowel disease understandably difficult. Because of the capacity for simultaneous biopsy, fibreoptic examination has reduced the requirement for diagnostic laparotomy. Few clear endoscopic descriptions have been published and the general features reported tend to be non-specific; diffuse erythema, thickened mucosal folds, nodularity, contact bleeding and rarely ulceration.Pv" Because of the non-specific nature of these observations, it is essential that any minor endoscopic abnormalities are biopsied. Despite advances in awareness and fibreoptic tissue diagnosis, a proportion of patients will still require surgery for definitive diagnosis, particularly to exclude tumours and in the relief of bowel obstruction.
164
Where the diagnosis of eosinophilic gastroenteritis is suspected peroperatively, a full-thickness biopsy or frozen section may provide a diagnosis." though on occasions, the latter has proved misleadingP A review of the management regimes of the 220 patients has revealed certain trends. Half of those managed expectantly (usually presenting with milder symptoms) developed recurrent or ongoing symptoms during follow-up, as did 66% and 70% of those treated with disodium cromoglycate and dietary elimination respectively. Surgical intervention was undertaken in 44% of patients at some stage in their management, 80% as the initial mode of management. Overall, 43% developed recurrent symptoms during follow-up and 13% continued to have symptoms in the early post-operative period. Two thirds of those treated by laparotomy or intestinal bypass alone developed recurrent symptoms (usually at a different site) though patients receiving post-operative steroid had a lower recurrence rate (25%). Resection of the diseased segment was the most commonly performed surgical procedure, with 8% having continued symptoms following surgery and 28% developing recurrent symptoms during follow-up. The most successful mode of management was the institution of steroid therapy (usually prednisolone 20-4Omg daily) with 90% showing a rapid improvement. Reduction to a maintenance dose (lOmg) resulted in 15% developing recurrent symptoms, while 55% developed symptoms on cessation of steroids, though not all required reintroduction of prednisolone. Long-term prednisolone therapy is not without its own problems and beclomethasone diproprionate has been successfully employed without suppression of the hypothalamic-pituitaryadrenal axis.P" In summary, it would seem appropriate to try an elimination diet in patients whose symptoms are aggravated by specific foodstuffs, but for the majority, a course of prednisolone or beclomethasone is indicated. The introduction of steroid therapy without a definitive tissue diagnosis should be discouraged as serious pathology such as intestinal malignancies may be missed." Recurrent symptoms may be treated by reintroduction of steroid if warranted. Patients suspected of having the disease at operation may be treated by biopsy and post-operative steroid, but in some, resection will be necessary either becasue of obstruction, perforation, unremitting disease despite steroid therapy.t-" or simply because the operator cannot exclude a carcinoma at the time of operation. It would seem reasonable to adopt an expectant approach in the latter patients and treat any recurrent symptoms with steroid if required. There have been four deaths attributable to eosinophilic gastroenteritis, three following complications of surgery.6.7.36 In the majority of patients, the disease follows a relatively benign course, punctuated by recurrent symptoms. In a very small proportion of patients, the disease can be much more aggressive and even fatal. In one patient, the disease was so severe that all intra-abdominal tissue planes were obliterated and resection of a huge phlegmonous mass impossible, This patient subsequently died despite high dose steroid therapy." A second patient with eosinophilic colitis and extensive perianal disease was also unresponsive to steroid therapy and required a total colectomy for control of symptoms. 35 There is however, no evidence that patients with eosinophilic gastroenteritis have a higher risk of subsequent gastrointestinal malignancies. ACKNOWLEDGEMENT: I would like to thank Dr R.C. Heading (Depart-
ment of Medicine) for his help in the preparation of this manuscript. A.R. Naylor Department of Surgery The Royal Infirmary Lauriston Place, Edinburgh REFERENCES I Kaijser R. Zur kenntnis der allergischen affektionen des verdaungskanal vom standpunkt des chirurgen aus. Arch Klin Chir. 1937; 188: 36-64. 2 ~ubin L, Pincus MB. Eosinopilic cystitis. The relationship of allergy 10 the urinary tract to eosinophilic cystitis and the pathophysiology of eosinophilia. J. Uro11974; 112: 457-460. 3 Stewart MJ, Wray S. Hall M, Allergic prostatis in asthmatics. J. Path and Bact 1954; 67: 423-430. 4 Tytgat GN, Grijm WD, Dekker W, den Hartog NA. Fatal eosinophilic enteritis, Gastroenterology 1976; 71: 479-483. 5 Houghton PW. The gastric lesion of disseminated eosinophilic collagenosis of Bousser. Br. J. Surg. 1959; 47: 238-240. 6 Russell JYW, Evangelou G. Eosinophilic infiltration of the stomach and duodenum complicated by perforation. Postgrad Med. J. 1965; 41: 30-33. 7 Felt-Bersma RJF, Meuwissen SGM, van Velzen D. Perforation of the small intestine due to eosinophilic gastroenteritis. Am. J. Gastroentero11984; 79: 442-445.
Comment
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