Fatal Eosinophilic Enteritis

GUTROENTEROLOG. 11:479-483. 1976 Copyri~ht @ 1976 hy The Williams &

Vol. 71. No.3

Printed In U.S.A.

Wilkins Co.

CASE REPORTS FATAL EOSINOPHILIC ENTERITIS G.

N.

TV-l'GAT,

M.D., R

M.D., W. DEKKER, M.D.,

GRIJM,

AND

N. A.

DEN HARTOG,

M.D.

Departments of Medicine and Pathology, Division of Gastroenterology, University of Amsterdam, Wilhelmina Gasthuis, Amsterdam, The Netherlands

A patient is reported with eosinophilic enteritis of the jejunum with fatal evolution. Surgical resection was considered impossible and medical treatment with corticosteroids, elemental diet, parenteral nutrition, and antimicrobials to combat the intestinal bacterial overgrowth failed to control the disease. The destructive and fatal nature of the reported eosinop~ilic enteritis raises the problem of classification of such disease entity, refractory to corticosteroid therapy. Eosinophilic infiltration of the gastrointestinal tract of unknown etiology may occur diffusely or as localized polypoid lesions .... Major clinicopathological features of the diffuse variety are abdominal symptomatology (abdominal cramps, nausea, vomiting, diarrhea, and weight loss), transmural eosinophilic infiltration of the intestinal wall, peripheral eosinophilia, a personal or family history of allergy, and prompt clinical remission with corticosteroid therapy or after surgical resection. A fatal evolution has never been described to the best of our knowledge. 3 • • A patient is presented with eosinophilic enteritis in whom the disease caused impressive destruction of the involved bowel. The disease appeared refractory to any form of treatment, raising the problem of classification of such fatal form of eosinophilic enteritis. . Case Report L.n. was a 66-year-old man, ex-supervisor of a shipbuilding yard. He had enjoyed an excellent health in the past. Lately he had been treated for about 3 years with allopurinol for intermittent painful swelling of the left big toe and mild arthralgias together with a slightly elevated serum uric acid level. A year before, pyrvinium pamoate was given for oxyuriasis. For the last 6 months he started suffering from chronic steady periumbilical pain, particularly at night. The pain was not related to meals or to bowel action. Furthermore he complained of marked anorexia and nausea, intermittent vomiting, mild constipation, and a l3-kg weight loss. Past medical history was noncontributory. There was no personal or family history of allergy, asthma, urticaria, hay fever, or eczema. He had never been in the tropics. Physical examination of heart and lung was normal. His blood pressure was 130/60 mm Hg. There was a firm periumbilical mass, difficult to delineate toward the left costal margin. His skin was dry and slightly. scaly. Biochemical analysis, summarized in table 1, revealed hypochromic anemia and an increased number of leukocytes, Received January 5, 1976. Accepted February 27, 1976. Address requests for reprints to G. N. Tytgat, M.D., Wilhelmina Gasthuis, Division of Gastroenterology, Ie Helmersstraat 104, Amsterdam, The Netherlands.

of which 40 to 50% were eosinophilic leukocytes. Alkaline phosphatase was slightly raised. All other liver function tests were normal. Protein electrophoresis and immunoelectrophoresis were noncontributory. There was no evidence of paraproteinemia. Serum IgE was normal. Urinalysis did not show any abnormality. Stool examination was 2+ for occult blood and showed mild steatorrhea. There was obvious intestinal protein loss and the Schilling test showed an abnormally low vitamin Bit absorption. There was no evidence of parasites, ova, or fecal pathogens on repeated stool examination, except for a few cysts of Entamoeba coli. Bone marrow examination revealed a markedly activated eosinophilic granulopoiesis and a somewhat reduced erythropoietic activity. X-ray examination of the small intestine via the enteroclysis technique' revealed two areas of marked irregularity and narrowing, with a coarse nodular destruction of the fold pattern in the jejunum, the proximal one starting 5 cm distally from the ligament of Treitz (fig. 1). The diseased area was not freely movable but appeared to be fixed to the dorsal abdominal wall. The distal jejunum and ileum, as well as the esophagus, stomach, and colon were normal. Because of the impressive abdominal physical and radiological findings, the marked eosinophilia, and the difficult differential diagnosis among Hodgkin's disease, lymphoma, adenocarcinoma, and eosinophilic gastroenteritis, all diseases requiring a different therapeutic approach, an exploratory laparotomy was carried out. Upon opening the abdomen, the surgeon (Dr. H. Linschoten) noted a small amount of slightly hemorrhagic fluid in the peritoneal cavity and found a huge firm inflammatory mass involving the proximal 60 cm of jej4num. The bowel loops were markedly inflamed, firmly adhering to each other, and covered by a thick layer of fibrinous exudate. There was no macroscopic evidence of malignancy. Because the inflammatory process was so extensive and firmly adhering to all surrounding structures and fixed to the posterior abdominal wall, the surgeon thought that it was impossible to remove the inflammatory mass. A transmural biopsy was taken at the level of the transition of normal and diseased gut and also an enlarged mesenteric lymph node was biopsied. Pathological examination showed that the whole thickness of the bowel wall was infiltrated by a dense inflammatory infiltrate consisting of granulation tissue, lymphocytes, and plasmocytes, but above all, huge amounts of mature-looking eosinophils as shown in fig. 2. This extensive eosinophilic infiltration eroded the overlying mucosa, producing acute

479

Therapy prednisone, mg/dl chloramphenicol, g/dl tetracyclin, gldl nystatin, u/dl neomycin, g/dl elemental diet parenteral nutrition

Intestinal bacterial overgrowth

Erythrocyte sedimentation rate Hemoglobin Leukocytes Eosinophil count Platelets Serum cholesterol Serum lipids Fecal fat Iron Iron-binding capacity Folic acid VitaminB l1 Schilling Total protein Albumin IgO leA IgM IgE Intestinal protein 1088 ("CrCl.)

Plramrter

11-32 "mole./1 45-72 "molea/1 3-2Onc/ml 150-800 pglml > 18%I48hr 6O-80g/l 35-50g/l 600-1900 mg/l00 ml 60-330 mgllOO ml 50-150 mg/l00 ml 3-445 V/ml plasma 2-23 ml plasmaldl

<6e/d

~e/1

8.7-10.6 mmoles/1 4-10 x 10'/1 50-300 x 10'/1 150-350 x 10'/1 3.9-7.8 mmoles/1

<12mm

Normal v.lues

5.6 13.5 5710 420 4.1 3.9 14.8 4.0 93 5.6 253 5.3 52 24 1438 532 140 28 150

94

Upon

edmiMion

+

15 2

1 x 10' Escherichia coli 1 x 10' Klebsiella pneumoniaI'

+

2

15

+

3 x 10' 4

30-100

26

30

3.8

36

3.5

6.5 14.9 788

59

after IUrgel)'

7_0

53

16 x 10' E. coli 288 x 10' Proteus mirabili. 176 x 10' Candida

2633

6.5 12.4

60

after .urgel)'

5 weeo

61

4.5 45

U 5.0

2090

8.7 14.7

56

liter .urg"1)'

2woeb

TABLE I. Laboratory findings and treatment schedule COJ' patient L. D.

+

3 x 10'

75

5 x 10' K.pneumoniar 9 x 10' Indifferent streptococci 9 x 10· Staphylococcus epidermis

52 28

4.8

8.7 7.6 767

11

.urgeD'

.~r

9woeo

+

3 x 10'

37.5

2 x 10· Indifferent streptococci 20 x 10' Lactobacillus

5 x 10' E. coli 9 x 10' Candida

8.5 7.9 0

44

after surgeI)'

12woeU

~

~

~

~ ....

:-

C;1

~::a

::a

t>l

CIl

~

September 1976

CASE REPORTS

481

Treatment was started with prednisone. at first at a low dose of 15 mg per day and after :!.5 weeks with 30 mg per day. without much clinical improvement. In the meantime it became obvious that the patient had developed bacterial overgrowth in his proximal small bowel for which he was treated with various antimicrobial preparations and elemental diet. however without much success. as shown in table I. Short periods of slight clinical improvement were always followed by further deterioration of his general condition. with exacerbation of watery diarrhea. nausea. intermittent vomiting of foul-smelling material. and further progressivp weight loss. In the face of such a rather dismal outlook we seriousl\' Questioned whether surgical removal of all diseased gut should be attempted. although previously judged impossible. or whether an ultimate medical attempt with total parenteral nutrition and high doses of steroids (100 mg of prednisone per day intravenously) should he tried. Upon the latter therapy there was slight but obvious improvement in the patient's well-being and general condition together with a decrease of his abdominal complaints and featurps of hactprial overgrowth. Moreover. a further drop of his peripheral eosinophilia, already decreasing during the previous oral prednisone treatment. was observed as shown in table I. However, as soon as his oral feeding was resumed. the steady downhill course reappeared, with further weil(ht loss. exacerbation of his abdominal pains, nausea, and liquid diarrhea, leading finally to death in cachexia, The autopsy findinl(s were most remarkahle in that the

Fu;. 1 Two area, la and!>1 are shown in th,' proximal WJunum with narrowing of ttw lunwn and effan'ml'nt and distortion of tht, fold puttt'rn togt:'tlwT with coarse nodular irr('gularit.\, oftht, t:ontoliTS. TIlt'Tt' is dilation proximal to each involvl'd segmt>rlt

superfi(,ial uln'rat ion. Tht· Ivmph node showed evidence of reactin' h.vperpla"ia to~eth('r with man~' eosinophi'" and some plasmon'tes in the sinu"oi(b. In one area, there was a tiny cukificaiion, There was no t'vidt'nce of malil!;lHlllc~', Hod~kin's disease. parasites. or vas(,ulitis su('h as periart£'ritis nodosa. and the patholol!;il'al dial!;nosis wa" made of eosinophilic enteritis tfig. :11. EXIl'nsin' postopt'ratin' investi~ation failPd to reveal a l'allSP lor tl](' destructive p,,,inophilic inl1ammation 01 thp small bowpl. Hppeatt'd stool examination did not show evi· dpncp of parasit ic il1lpcl ion. Sprological t pst ing for toxoplasmo. sis. anisakiasis. b toxo('ara. ascariasis. trichinosis. etc. was Ill'gatin'. Skill tt·sting tor mumps, Candida, Trichophyton, and tllbt'n'ul,,,i, ,howpd Iwnreactivitv. D,·taill·d dil'tarv screpnillg did lIot givl' any dlll'S for possihl,: food allt'rgy. Fiberendos('(.pv of e:--lophaglls. stonHH'h. and duodpflurn and signll1idos('op~.:

"' .. n· normal. \Iull iplt· suet ion biopsies from antrum, fundus. and r{'ctlllll were wit hout abnormal it i,". DlSt al bophageal hiopsi," show!'d a f,'w sl'
Fit;. :!. l.ow power \"it'Yo of thf' ~urgi{'al hiop:-;~. uhtairlt'd from thl' art'a of transition hetYol'('n macro:-.("opically It':-.s in\oln·d lind oh\lou:-.h disf'ltspd gut TtwrL' is {'xtt'Hsin' ulceration and ht'cl\"~' infiltration, part Il'ldarl~' rlPllsP in t hl' uln'ratPd art'a and t hr(lugh11ut t hI:' ~uhmu cosa. and dimilllshing to""ards tht· mllsl"lIlari~ propria and :".{'ro:-.a \ . 101.

482

Vol. 71 , No.3

CASE REPORTS

FIC; . :1. A, detail of mucosal area hordering the ulceration. Note the changes in villous architecture and the pseudopyloric metaplasia (armu') :101. B, detail of the pro('ess in the submucosa . consisting of fibroblasts , proliferating endothelial cells forming capillaries, and numerous eosinophilic leukm'ytes ( . :101. C, detail of the muscular and serosal area. !'Iote the extensive fibrosis together with the infiltration of both layers ( , :(0) . IJ. low and bil(h detailed view of the dense infiltrate and granulation tissue in the submucosal area . The most conspicuous feature is the hillh number of eosinophilic leukocytes, spread out throughout proliferating mesenchymal tissue (,. 100: , 6:(0). «

}o"'H ; . . 1. Cro!';s-section through the convolute of jejunal loops, found

Ht autopsy . There is impressive fibrous thickening of the bowel wall and formation of an irregularly outlin ed eavity . This cavity probably o(' c.: llrr~d

through confluenc£, of intestinal lumina after extensive

uircralion and breakdown of the howel wall , which was remarkahly conspicuous in t his pat icnt . ,"ote al,o the deep cleft (arroLL·). indicating the possihle mechanism through whic h ('onfluent'e and ca vity fnrmalion rnu~' have ot.Turrl'd.

eosinophilic enteritis had resulted in a huge firm mass in which it was difficult, if not impossible, to recognize the individual bowel loops. As seen in a cross-section shown in figure 4, only the distorted lumina of several loops were recognizable, connected by the monotonous extensive eosinophilic int1ammation. In several areas nearly total obliteration of the lumen was present. The entire thickness of the intestinal wall was infiltrated and destroved to such an extent that it became impossihle to see on c~oss-section where the thickened wall of one bowel loop ended and the adjacent one started. Mixed in between the infiltrate were focal collections of purulent exudate and microorganisms . Similar (metastatic0) microabscesses were present in several other organs , especially the kidneys. In none of these foci of int1ammation was there a conspicuous number of eosinophilic leukocytes and certainly not substantial enough to suggest a ny connection with the eosinophilic disease in the small bowel. There was no evidence upon careful study of helminthic disease or of carcinoma, Hodgkin's disease or other malignancy.

Discussion A patient tS presented with a fatal illness due to an eosinophilic enteritis of the jejunum . The unrelenting course of the disease was unamenable to any form of

September 1976

483

CASE REPORTS

treatment. Surgical resection was considered impossible because of its extensiveness and adherence to all surrounding structures. Bacterial overgrowth was of major clinical importance and appeared resistant to medical treatment. Extensive studies did not reveal a parasitic infection; particularly. anisakiasis· was carefully looked for. How does one classify the illness in this patient? We wonder whether such a fatal destructive process has to be considered as the end of the spectrum of eosinophilic gastroenteritis. more in particular the circumscribed eosinophilic intestinal infiltration variant. , .• However, several findings militate against this hypothesis. There was no personal or family history of any allergy or specific food intolerance. There was no history of recurring episodes of nausea, vomiting, diarrhea and abdominal discomfort, or cramps. Furthermore there was a striking lack of control of the disease by corticosteroid therapy despite disappearance of the eosinophilic leukocytes from the peripheral blood. This is markedly different from the usual nearly immediate clinical improvement and responsiveness of eosinophilic gastroenteritis even to rather low doses of steroids. I. 4 Finally the eosinophilic enteritis, limited to the small bowel, caused impressive transmural obliterating destruction, resulting in a huge convolute of adhering inflamed ulcerated bowel. We also wonder whether the described illness might fit in the spectrum of the usually fatal "disseminated eosinophilic collagen disease" (DECD)7-t or the "hypereosinophilic syndrome" (HES).'o Again, several findings do not support this possibility. There were no obvious eosinophilic infiltrations in other organs outside the small bowel, which is different from the widespread

multiorgan involvement in DECO or HES. In particular there were no cardiac or pulmonary manifestations, which usually dominate the clinical picture. Furthermore, there was no evidence of hepatosplenomegaly, organic heart murmur, congestive heart failure, or diffuse or focal central nervous system abnormality. Only careful clinical observation and publication of similar case reports will allow us to define whether such fatally evolving eosinophilic enteritis has to be considered as a separate disease entity and will possibly allow us to unravel its pathogenesis and to select a more appropriate treatment. REFERENCES 1. Ureles AI.. Alschibasa T. Iodico D. et al: Idiopathic eosinophilic infiltration ofthe gastrointestinal tract. diffuse and circumscribed. Am J Med 30:899-909. 1961 2. Edelman MJ. March TL: Eosinophilic gastroenteritis. Am J Roentgenol 91:773-778. 1964 3. Kazil P: Eosinophilic granuloma. eosinophilic gastroenteritis and eosinophilic peritonitis. Acta Univ Carol Med 15:581-611. 1969 4. Klein NC. Hargrove RL, Sleisenger MH. et al: Eosinophilic Gastroenteritis. Medicine 49:299-319. 1970 5. Sellink JL: Examination of the Small Intestine by Means of Duodenal Intubation. Leiden. HE Stenfert Kroese NV. 1971 6. Kuipers FC, Van Thiel PH, Roskam ET: Eosinofiele flegmone van de dunne darm. veroorzaakt door een niet aan het lichaam van de mens aangepaste worm. Ned T Geneesk 104:422-427. 1960 7. Engfeldt B. Zetterstrom R: Disseminated eosinophilic collagen disease. Acta Med Scand 153:337-359, 1956 8. Manko MA. Cooper JH. Meyers RN: Disseminated Hypereosino. philic disease. Am J Gastroenterol 57:318-325. 1972 9. Fossgreen J: Eosinophile granulomatosis. Acta Pathol Microbiol Scand 56: 143-154, 1962 10. Chusid MJ. Dale DC, West BC. et al: The hypereosinophilic syndrome. Medicine 54:1-27. 1975