Miliary Crohn’s Disease

Vol. 67, No.3

GA STR OENTE ROLOGY 67: 527-530, 1974 Copy right © 1974 by The Williams & Wilkins Co.

Printed in U.S.A.

MILIARY CROHN'S DISEASE FREDRIC DAUM M.D ., S corr J. BoLEY, M .D ., AND MICHAEL I. CoHEN, M.D.

Division of Adolescent M edicine, Departm ent of Pedia trics and th e P ediatric Surgical Service, Department of Surgery, Montefiore Hospital and Medical C enter and the Albert Einstein College of M edicine, Bronx , N ew York

The 5th case of miliary Crohn's disease is reported in a 13-year-old boy. Several features of the presentation of this illness raise the question as to whether this entity is a unique form or early phase of classic Crohn 's disease . The experience with this teenager and follow-up of 2 previously reported cases supports the belief that miliary Crohn's disease represents an early phase of classic Crohn's disease . Miliary Crohn's disease is a term first applied by Heaton et al. , 1 in 1967, to an unusual presentation of regional enteritis characterized macroscopically by multiple minute white nodules similar in appearance to those of peritoneal seeding by a malignancy or to the serosal tubercles of tuberculosis . These lesions are noted over the surface of the involved small intestine along the distribution of serosal lymphatics (fig. 1) and may also be seen on the surface of adjacent mesentery and peritoneum. The case reported below is the 5th case of miliary Crohn's disease recorded to date, and it is noteworthy that, of the 5 patients, 4 have been under 21 years of age at the time of diagnosis . 1• 2 The young age of these patients and the course of their illness raises several signifiGant questions regarding the implications of miliary Crohn's disease, its natural history, and its relation to classic Crohn's disease. Moreover, this adolescent illustrates the importance of recognizing the etiology of the miliary lesions at the time of laparotomy.

Case History

This 13-year-old white male was admitted to the adolescent unit with a 6-month history of diarrhea , abdominal pain, and a 20-lb weight loss. There was no history of fever, emesis, jaundice, melena , arthralgias , or skin rashes. There had been no previous operations. There was no famil y history of intestinal disease or arthritis. A jejunal biopsy obtained at another institution was suggestive of celiac disease (fig. 2) , but symptoms did not abate with a glutenfree diet. The patient was afebrile, pale, and chronically ill. His height was 162 em and weight was 42 kg. The abdomen was slightly distended, nontender, and no masses were palpated. The skin and mucus membranes were pale, and there was pitting edema of the lower extremities. Pertinent laboratory data included an hematocrit of 32%, reticulocyte count 0.5%, and a normal peripheral white blood cell count. The erythrocyte sedimentation rate was 25 mm per hr. Bone marrow aspiration revealed a decrease in erythroid precursors without megaloblasts or malignant cells. Serum concentrations of Na, K, Cl , C0 2 , urea nitrogen , creatinine, glutamic oxaloacetic transaminase , bilirubin, and alkaline phosphatase were normal. Serum cholesReceived D ecember 17, 1973. Accepted February 5, terol was 115 mg per 100 ml , the total protein 1974. 4.3 g per 100 ml with an albumin of 1.9 g per 100 Address requests for reprints to: Dr. Fredric Daum, ml, total calcium in serum 7.6 mg per 100 ml , Montefiore H ospital and Medical Center, 111 East phosphorus 3.7 mg per 100 ml , and magnesium 210th Street, Bronx, New York 10467. 1.4 mEq per liter. The stool was guaiac positive. The authors wish t o th ank Dr. K . W. Heaton for Studies for pathogenic bacteria and ova and follow-up information regardin g his cases previously parasites were negative. A sweat electrolyte test and 72-hr stool collection for fat were normal. A reported. 527

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FIG. 1. Involved portion of jejunum as seen at operation . Multiple white nodules (arrow) are seen on the serosa in the distribution of the lymphatics .

second strength purified protein derivative and chest X-ray were negative. Proctosigmoidoscopy and barium enema were normal. Barium examination of the small intestine revealed irregular mucosal thickening and nodular defects in the distal jejunum and proximal ileum suggestive of either an intestinal lymphoma or regional enteritis (fig. 3). A laparotomy performed to exclude an intestinal lymphoma revealed that several feet of distal jejunum and proximal ileum were thickened, and that the serosal surface was studded with pale, white nodules distributed along the lines of distended serosal lymphatics. Similar lesions were seen on the adjacent mesentery and peritoneum, and the mesenteric nodes were noted to be enlarged. Frozen section examination of multiple miliary lesions and mesenteric nodes revealed noncaseating granulomas with multinucleated giant cells (fig. 4). The operative diagnosis was Crohn's disease with attention focused on the unusual miliary presentation. No intestinal resection was performed. Review of paraffin sections corroborated the impression of noncaseating granulomas, and no

acid fast bacilli or fungi were seen. Cultures of the biopsy material were negative for mycobac· terium tuberculosis. The patient was placed on a 6-week regimen of total parenteral nutrition with no oral intake. During this period of time in which no medications were given there was clinical and radiographic resolution of the disease. Fourteen months later the patient relapsed with symptoms and signs similar to those initially described. Barium examination revealed small bowel changes similar to those seen prior to therapy and consistent with Crohn 's disease .

Discussion Whether miliary Crohn's disease is a unique form, or, as Heaton et al. 1 had suggested, an early phase of classic regional enteritis, is as yet unestablished. The dearth of reported cases would appear to militate against these miliary lesions representing an early phase of Crohn's disease. However, the lack of documented

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FIG. 2. Small intestinal biopsy showing flattening of the villi and edema of the lamina propria interpreted as suggesting celiac sprue but also consistent with Crohn's disease. •

cases may not reflect the true incidence of the disease as the literature is replete with descriptive accounts of patients with similar pathology who may have been erroneously diagnosed as having intestinal sarcoidosis or tuberculosis. Indeed, the first report of miliary Crohn's disease may have been in 1954, when Cowdell 3 described a 15-year-old girl with sarcoidosis with tubercle-like structures and flat white plaques over most of the ileum. The presence of noncaseating granulomas in biopsies of miliary lesions does demand that sarcoidosis be included in the histological differential diagnosis. However, Scadding 4 provided good evidence that intestinal sarcoidosis does not exist as he was unable to find a single instance in which small intestinal involvement occurred in a patient with generalized sarcoidosis. It is a distinct possibility that many more patients with miliary Crohn's disease have been seen but

mistakenly diagnosed as having intestinal sarcoidosis. Evidence to support the postulate that this miliary presentation is an early stage of Crohn's disease is provided by the young age of 4 of the 5 patients now reported. Of special interest in this regard would be the subsequent course of the miliary lesions after their initial observation. Inquiries regarding the 3 patients described previously by Heaton et al., reveal that, of these, the latter 2 have undergone subsequent laparotomies without mention of the miliary lesions seen at previous operation. The disappearance of these lesions but persistence of regional enteritis would indicate that miliary Crohn's disease does in fact represent a transient early stage of the classic disease. Although miliary Crohn's disease has unique macroscopic characteristics seen at operation, clinically it has the manifesta-

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FIG. 3 (left). Small bowel study prior to therapy demonstrates a rigid loop of jejunum, nodularity, and edema of the 'rriesentery. FIG: 4 (right). Biopsy of nodule from serosa of jejunum revealing a noncaseating granuloma with a multinu· cleated giant cell.

tions ' and natural history of Crohn's dis- of Crohn's disease, proper identification by ease. One possible exception is the distri- the operating surgeon is essential for apbution of intestinal involvement. Four of propriate therapy. Only a keener awarethe 5 patients had disease of the jejunum ness of those patients with miliary Crohn's alone or in combination with other seg- disease and careful observation of the ments of small and large bowel. This inci- course of their disease will permit conclu" dence of jejunal pathology is significantly sions as to the significance of this entity. greaterthan that seen generally in Crohn's REFERENCES disease. ·. The diagnosis of miliary Crohn's disease 1. Heaton KW, McC arthy CF, Horton RE , et al: can only be made at laparotomy and then Miliary Crohn's disease . Gut 8:4- 7, 1967 only by biopsy of the miliary lesions. De- 2. Manns JJ: Miliary Crohn's disease. Br Med J 4:152, 1972 spite gross similarities between regional enteritis and intestinal tuberculosis, mi- 3. Cowdell RH : Sarcoidosis: with special reference to diagnosis and prognosis. Q J Med 23:29-55, 1954 croscopic characteristics are distinguisha4. Scadding JG: Sarcoidosis. London, Eyre and Spot· 5 ble without much difficulty. The absence tiswoode, 1967 of caseation and acid-fast bacilli within 5. Tandon HD, Prakash A: Pathology of. intesti nal the lesions with a negative screening evaltuberculosis and its distinction from Crohn's dis· uation for tuberculosis should suggest miliease. Gut 13:260- 269, 1972 ary Crohn's disease as the definitive diag- 6. Shiner M , Drury RAB : Abnormalities of the small nosis. Whether miliary Crohn's disease intestinal mucosa in Crohn 's disease (regional represents an early phase or a unique form enteritis). Am J Dig Dis 7:744- 759, 1962