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September 14, 1979, Vol 242, No. 11 >
ARTICLE | September 14, 1979

The Local and Systemic Complications of Inflammatory Bowel Disease FREE

Joseph B. Kirsner, MD, PhD
[+] Author Affiliations

Reprint requests to University of Chicago Hospitals and Clinics, Box 319, 950 E 59th St, Chicago, IL 60637 (Dr Kirsner).


JAMA. 1979;242(11):1177-1183. doi:10.1001/jama.1979.03300110049028
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Article
References

THE NONSPECIFIC inflammatory bowel diseases (IBDs), ulcerative colitis and Crohn's disease, continue to present challenging problems.1-3 The rising incidence of IBD, especially of Crohn's disease, in recent years has generated increased interest in these disorders and the variety of their local and systemic complications that influence the response to therapy and the course of the illness. The complications may assume primary importance in the health of the patient, while in other cases, they may be the initial overt clinical manifestations of an existing underlying IBD. Some complications, eg, iritis, probably reflect an underlying generalized tissue abnormality. Others, such as "intestinal" arthritis and pericholangitis, may reflect intestinal bacterial overgrowth in Crohn's disease. In yet other circumstances, complications such as skin rashes, bone marrow suppression, superinfections, and electrolyte imbalance are among the many iatrogenic complications associated with the treatment of IBD.

The pathophysiology of IBD complications probably represents several pathogenetic mechanisms.

REFERENCES

1 +
Kirsner JB, Shorter RG: Inflammatory Bowel Disease . Philadelphia, Lea & Febiger Publishers, 1975;.
2 +
Kirsner JB:  Observations on the etiology and pathogenesis of inflammatory bowel disease , in Bockus HL (ed): Gastroenterology , ed 4. Philadelphia, WB Saunders Co, 1976;, vol 2, pp 521-539.
3 +
Kirsner JB:  Inflammatory bowel disease: Considerations of etiology and pathogenesis . Am J Gastroenterol 69:253-271, 1978;.
4 +
Shorter RG, Shepard DAE:  Frontiers in inflammatory bowel diseases: Extraintestinal complications of inflammatory bowel disease: Are these natural experiments instructive? Am J Dig Dis 20:639-670, 1975;.
5 +
Farmer RG, Hawk WA, Turnbull RB Jr:  Clinical patterns in Crohn's disease: A statistical study of 615 cases . Gastroenterology 68:627-635, 1975;.
6 +
Greenstein AJ, Janowitz HD, Sachar DB:  The extraintestinal complications of Crohn's disease and ulcerative colitis: A study of 700 patients . Medicine 55:401-412, 1976;.
7 +
Drenick EJ, Ament ME, Finegold SM, et al:  Bypass enteropathy: Intestinal and systemic manifestations following small bowel bypass . JAMA 236:269-272, 1976;.
8 +
Roth JLA, Valdes-Dapena A, Stein GN, et al:  Toxic megacolon in ulcerative colitis . Gastroenterology 37:239-255, 1959;.
9 +
Norland CC, Kirsner JB:  Toxic dilation of the colon (toxic megacolon) . Medicine 48:229-250, 1969;.
10 +
Kappelman WB, Burrell M, Toffler R:  Megacolon associated with celiac sprue: Report of four cases and review of the literature . AJR 128:65-68, 1971;.
11 +
Goldgraber MB, Kirsner JB:  Carcinoma and ulcerative colitis—a clinicalpathological study: I. Cancer deaths . Gastroenterology 34:809-839, 1958;.
12 +
Goldgraber MB, Kirsner JB:  Carcinoma and ulcerative colitis—a clinicalpathological study: II. Statistics . Gastroenterology 34:840-846, 1958;.
13 +
Goldgraber MD, Kirsner JB:  Carcinoma and ulcerative colitis—a clinicalpathological study: III. Survivors . Gastroenterology 36:613-630, 1959;.
14 +
Goldgraber MB, Kirsner JB:  Carcinoma of the colon in ulcerative colitis . Cancer 17:657-665, 1974;.
15 +
Edwards FC, Truelove SC:  The course and prognosis of ulcerative colitis: IV. Carcinoma of the colon . Gut 5:15-22, 1964;.
16 +
Morson BC, Pang LS:  Rectal biopsy as an aid to cancer control in ulcerative colitis . Gut 8:423-434, 1967;.
17 +
De Vroede GJ, Taylor WF, Saucer WG, et al:  Cancer risk and life expectancy of children with ulcerative colitis . N Engl J Med 285:17-21, 1971;.
18 +
Lennard-Jones JE, Morson BC, Ritchie JK, et al:  Cancer in colitis: Assessment of the individual risk by clinical and histological criteria . Gastroenterology 73:1280-1289, 1977;.
19 +
Yardley JH, Bayless TM, Diamond MP:  Cancer in ulcerative colitis . Gastroenterology 76:221-225, 1979;.
20 +
Reddy BS, Martin CW, Wynder EL:  Fecal bile acids and cholesterol metabolites of patients with ulcerative colitis: A high risk group of development of colon cancer . Cancer Res 37:1697-1701, 1977;.
21 +
Morowitz DA, Block GE, Kirsner JB:  Adenocarcinoma of the ileum complicating chronic regional enteritis . Gastroenterology 55:397-402, 1968;.
22 +
Lightdale CJ, Sternberg SS, Posner G, et al:  Carcinoma complicating Crohn's disease . Am J Med 59:262-268, 1975;.
23 +
Weedon DD, Shorter RG, Ilstup DM, et al:  Crohn's disease and cancer . N Engl J Med 289:1099-1103, 1975;.
24 +
Goodman MJ, Skinner JM, Truelove SC:  Abnormalities in the apparently normal bowel mucosa in Crohn's disease . Lancet 1:275-278, 1976;.
25 +
Allan R, Steinberg DM, Dixon K, et al:  Changes in the bidirectional sodium flux across the intestinal mucosa in Crohn's disease . Gut 16:201-204, 1975;.
26 +
Dunne WT, Cook WT, Allan RM:  Enzymatic and morphometric evidence for Crohn's disease as a diffuse lesion of the gastrointestinal tract . Gut 18:290-294, 1977;.
27 +
Gerson CD, Fabry EM:  Ascorbic acid deficiency and fistula formation in regional enteritis . Gastroenterology 67:428-433, 1974;.
28 +
Filipsson I, Haltern L, Lindstedt G, et al:  The metabolic consequences of surgery in Crohn's disease . Scand J Gastroenterol 13:471-479, 1978;.
29 +
Moossa AR, Hall AW, Skinner DB, et al:  Effect of 50% small bowel resection on gastric secretory function in rhesus monkeys . Surgery 80:208-213, 1976;.
30 +
Acheson ED:  An association between ulcerative colitis, regional enteritis and ankylosing spondylitis . Q J Med 29:489-499, 1969;.
31 +
McEwen C, Lingg C, Kirsner JB, et al:  Arthritis accompanying ulcerative colitis . Am J Med 33:923-941, 1962;.
32 +
Bowen G, Kirsner JB:  The arthritis of ulcerative colitis and regional enteritis ("intestinal arthritis") . Med Clin North Am 49:17-32, 1965;.
33 +
Wands JR, LaMont JT, Mann E, et al:  Arthritis associated with intestinal bypass procedure for morbid obesity . N Engl J Med 294:121-124, 1976;.
34 +
Hodgson HJF, Potter BJ, Jewell DP:  Immune complexes in ulcerative colitis and Crohn's disease . Clin Exp Immunol 29:187-196, 1977;.
35 +
Flasse R, Lurhume AZ, Cambiaso CL:  Circulating immune complexes and disease activity in Crohn's disease . Gut 19:611-617, 1978;.
36 +
Kleckner MS, Stauffer MH, Bargen JA, et al:  Hepatic lesions in the living patient with chronic ulcerative colitis as demonstrated by needle biopsy . Gastroenterology 22:13-33, 1952;.
37 +
Mistilis SP, Skyring AP, Goulston SJM:  Pericholangitis and ulcerative colitis: I. Pathology, etiology and pathogenesis. II. Clinical aspects . Ann Intern Med 63:1-26, 1965;.
38 +
Eade MN:  Liver disease in ulcerative colitis: I. Analysis of operative liver biopsy in 138 consecutive patients having colectomy . Ann Intern Med 72:475-487, 1970;.
39 +
Eade MN:  Liver disease in ulcerative colitis: II. The long-term effect of colectomy . Ann Intern Med 72:489-497, 1970;.
40 +
Dordal E, Glagov S, Kirsner JB:  Hepatic lesions in chronic inflammatory bowel disease . Gastroenterology 52:239-253, 1967;.
41 +
Baker AL, Kaplan MM, Norton RA, et al:  Gallstones in inflammatory bowel disease . Am J Dig Dis 19:109-112, 1974;.
42 +
Warren KE, Athanassiades S, Monge JI:  Primary sclerosing cholangitis . Am J Surg 111:23-38, 1966;.
43 +
Morowitz DA, Glagov S, Dordal E, et al:  Carcinoma of the biliary tract complicating chronic ulcerative colitis . Cancer 27:356-361, 1971;.
44 +
Kelley ML Jr:  Skin lesions associated with chronic ulcerative colitis . Am J Dig Dis 7:255-272, 1962;.
45 +
McCallum DI, Kinmont PDC:  Dermatological manifestations of Crohn's disease . Br J Dermatol 80:1-8, 1968;.
46 +
Gelernt IM, Kreel J:  Pyoderma gangrenosum in ulcerative colitis: Prevention of the gangrenous component . Mt Sinai J Med 43:467-470, 1976;.
47 +
Crawford SE, Sherman R, Favara B:  Pyoderma gangrenosum with response to cyclophosphamide therapy . J Pediatr 71:255-258, 1967;.
48 +
Kirsner JB, Sheffner L, Palmer WL:  Studies on amino acid excretion: V. Chronic ulcerative colitis and regional enteritis . J Clin Invest 39:874-880, 1950;.
49 +
Beeken WL, Busch HJ, Sylvester DL:  Intestinal protein loss in Crohn's disease . Gastroenterology 62:207-215, 1972;.
50 +
Dyer NH, Child JA, Mollin DL, et al:  Anemia in Crohn's disease . Q J Med 44:419-436, 1972;.
51 +
Earnest DL:  Enteric hyperoxaluria . Adv Intern Med 24:407-427, 1979;.
52 +
Franklin JL, Rosenberg IH:  Impaired folic acid absorption in inflammatory bowel disease: Effects of salicylazosulfapyridine (Azulifidine) . Gastroenterology 64:517-525, 1973;.
53 +
Benson RE, Bargen JA:  Chronic ulcerative colitis as a cause of retarded sexual and gonadic development . Gastroenterology 1:147-159, 1943;.
54 +
McCaffrey TD, Nasr K, Lawrence AM, et al:  Severe growth retardation in children with inflammatory bowel disease . Pediatrics 42:386-393, 1970;.
55 +
Berger M, Griebetz D,  Korelitz BI: Growth retardation in children with ulcerative colitis: The effect of medical and surgical therapy . Pediatrics 55:459-467, 1975;.
56 +
Kirschner BS, Voinchet OH, Rosenberg IH:  Growth retardation in inflammatory bowel disease . Gastroenterology 75:504-511, 1978;.
57 +
Basu MK, Asquith P, Thompson RA, et al:  Oral manifestations of Crohn's disease . Gut 16:249-254, 1975;.
58 +
Li Volsi VA, Jaretzki A III:  Granulomatous esophagitis: A case of Crohn's disease limited to the esophagus . Gastroenterology 64:313-319, 1972;.
59 +
Danzi JT, Farmer RG, Sullivan BH Jr, et al:  Endoscopic features of gastroduodenal Crohn's disease . Gastroenterology 70:9-13, 1976;.
60 +
Das KM, Eastwood MA, McManus JPA, et al:  Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype . N Engl J Med 289:491-495, 1973;.
61 +
Schroder H, Evans DAP:  Acetylator phenotype and adverse effects of sulphasalazine in healthy subjects . Gut 13:278-284, 1972;.
62 +
Goldstein MJ, Gelzayd EA, Kirsner JB:  Some observations on hazards of corticosteroid therapy in patients with inflammatory disease . Trans Am Acad Ophthalmol Otolaryngol 71:254-261, 1967;.
63 +
Gelzayd EA, Breuer RI, Kirsner JB:  Nephrolithiasis in inflammatory bowel disease . Am J Dig Dis 13:1027-1034, 1968;.
64 +
Graef V, Baggenstoss AH, Sauer WG, et al:  Venous thrombosis occurring in non-specific ulcerative colitis . Arch Intern Med 117:377-382, 1966;.
65 +
Block GE, Enker WE, Kirsner JB:  Significance and treatment of occult obstructive uropathy complicating Crohn's disease . Ann Surg 178:322-332, 1973;.
66 +
Mukhopadhyay D, Nasr K, Grossman BJ, et al:  Pericarditis associated with inflammatory bowel disease . JAMA 211:1540, 1970;.

Figures

Tables

Interactive Graphics

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Kirsner JB, Shorter RG: Inflammatory Bowel Disease . Philadelphia, Lea & Febiger Publishers, 1975;.
2 +
Kirsner JB:  Observations on the etiology and pathogenesis of inflammatory bowel disease , in Bockus HL (ed): Gastroenterology , ed 4. Philadelphia, WB Saunders Co, 1976;, vol 2, pp 521-539.
3 +
Kirsner JB:  Inflammatory bowel disease: Considerations of etiology and pathogenesis . Am J Gastroenterol 69:253-271, 1978;.
4 +
Shorter RG, Shepard DAE:  Frontiers in inflammatory bowel diseases: Extraintestinal complications of inflammatory bowel disease: Are these natural experiments instructive? Am J Dig Dis 20:639-670, 1975;.
5 +
Farmer RG, Hawk WA, Turnbull RB Jr:  Clinical patterns in Crohn's disease: A statistical study of 615 cases . Gastroenterology 68:627-635, 1975;.
6 +
Greenstein AJ, Janowitz HD, Sachar DB:  The extraintestinal complications of Crohn's disease and ulcerative colitis: A study of 700 patients . Medicine 55:401-412, 1976;.
7 +
Drenick EJ, Ament ME, Finegold SM, et al:  Bypass enteropathy: Intestinal and systemic manifestations following small bowel bypass . JAMA 236:269-272, 1976;.
8 +
Roth JLA, Valdes-Dapena A, Stein GN, et al:  Toxic megacolon in ulcerative colitis . Gastroenterology 37:239-255, 1959;.
9 +
Norland CC, Kirsner JB:  Toxic dilation of the colon (toxic megacolon) . Medicine 48:229-250, 1969;.
10 +
Kappelman WB, Burrell M, Toffler R:  Megacolon associated with celiac sprue: Report of four cases and review of the literature . AJR 128:65-68, 1971;.
11 +
Goldgraber MB, Kirsner JB:  Carcinoma and ulcerative colitis—a clinicalpathological study: I. Cancer deaths . Gastroenterology 34:809-839, 1958;.
12 +
Goldgraber MB, Kirsner JB:  Carcinoma and ulcerative colitis—a clinicalpathological study: II. Statistics . Gastroenterology 34:840-846, 1958;.
13 +
Goldgraber MD, Kirsner JB:  Carcinoma and ulcerative colitis—a clinicalpathological study: III. Survivors . Gastroenterology 36:613-630, 1959;.
14 +
Goldgraber MB, Kirsner JB:  Carcinoma of the colon in ulcerative colitis . Cancer 17:657-665, 1974;.
15 +
Edwards FC, Truelove SC:  The course and prognosis of ulcerative colitis: IV. Carcinoma of the colon . Gut 5:15-22, 1964;.
16 +
Morson BC, Pang LS:  Rectal biopsy as an aid to cancer control in ulcerative colitis . Gut 8:423-434, 1967;.
17 +
De Vroede GJ, Taylor WF, Saucer WG, et al:  Cancer risk and life expectancy of children with ulcerative colitis . N Engl J Med 285:17-21, 1971;.
18 +
Lennard-Jones JE, Morson BC, Ritchie JK, et al:  Cancer in colitis: Assessment of the individual risk by clinical and histological criteria . Gastroenterology 73:1280-1289, 1977;.
19 +
Yardley JH, Bayless TM, Diamond MP:  Cancer in ulcerative colitis . Gastroenterology 76:221-225, 1979;.
20 +
Reddy BS, Martin CW, Wynder EL:  Fecal bile acids and cholesterol metabolites of patients with ulcerative colitis: A high risk group of development of colon cancer . Cancer Res 37:1697-1701, 1977;.
21 +
Morowitz DA, Block GE, Kirsner JB:  Adenocarcinoma of the ileum complicating chronic regional enteritis . Gastroenterology 55:397-402, 1968;.
22 +
Lightdale CJ, Sternberg SS, Posner G, et al:  Carcinoma complicating Crohn's disease . Am J Med 59:262-268, 1975;.
23 +
Weedon DD, Shorter RG, Ilstup DM, et al:  Crohn's disease and cancer . N Engl J Med 289:1099-1103, 1975;.
24 +
Goodman MJ, Skinner JM, Truelove SC:  Abnormalities in the apparently normal bowel mucosa in Crohn's disease . Lancet 1:275-278, 1976;.
25 +
Allan R, Steinberg DM, Dixon K, et al:  Changes in the bidirectional sodium flux across the intestinal mucosa in Crohn's disease . Gut 16:201-204, 1975;.
26 +
Dunne WT, Cook WT, Allan RM:  Enzymatic and morphometric evidence for Crohn's disease as a diffuse lesion of the gastrointestinal tract . Gut 18:290-294, 1977;.
27 +
Gerson CD, Fabry EM:  Ascorbic acid deficiency and fistula formation in regional enteritis . Gastroenterology 67:428-433, 1974;.
28 +
Filipsson I, Haltern L, Lindstedt G, et al:  The metabolic consequences of surgery in Crohn's disease . Scand J Gastroenterol 13:471-479, 1978;.
29 +
Moossa AR, Hall AW, Skinner DB, et al:  Effect of 50% small bowel resection on gastric secretory function in rhesus monkeys . Surgery 80:208-213, 1976;.
30 +
Acheson ED:  An association between ulcerative colitis, regional enteritis and ankylosing spondylitis . Q J Med 29:489-499, 1969;.
31 +
McEwen C, Lingg C, Kirsner JB, et al:  Arthritis accompanying ulcerative colitis . Am J Med 33:923-941, 1962;.
32 +
Bowen G, Kirsner JB:  The arthritis of ulcerative colitis and regional enteritis ("intestinal arthritis") . Med Clin North Am 49:17-32, 1965;.
33 +
Wands JR, LaMont JT, Mann E, et al:  Arthritis associated with intestinal bypass procedure for morbid obesity . N Engl J Med 294:121-124, 1976;.
34 +
Hodgson HJF, Potter BJ, Jewell DP:  Immune complexes in ulcerative colitis and Crohn's disease . Clin Exp Immunol 29:187-196, 1977;.
35 +
Flasse R, Lurhume AZ, Cambiaso CL:  Circulating immune complexes and disease activity in Crohn's disease . Gut 19:611-617, 1978;.
36 +
Kleckner MS, Stauffer MH, Bargen JA, et al:  Hepatic lesions in the living patient with chronic ulcerative colitis as demonstrated by needle biopsy . Gastroenterology 22:13-33, 1952;.
37 +
Mistilis SP, Skyring AP, Goulston SJM:  Pericholangitis and ulcerative colitis: I. Pathology, etiology and pathogenesis. II. Clinical aspects . Ann Intern Med 63:1-26, 1965;.
38 +
Eade MN:  Liver disease in ulcerative colitis: I. Analysis of operative liver biopsy in 138 consecutive patients having colectomy . Ann Intern Med 72:475-487, 1970;.
39 +
Eade MN:  Liver disease in ulcerative colitis: II. The long-term effect of colectomy . Ann Intern Med 72:489-497, 1970;.
40 +
Dordal E, Glagov S, Kirsner JB:  Hepatic lesions in chronic inflammatory bowel disease . Gastroenterology 52:239-253, 1967;.
41 +
Baker AL, Kaplan MM, Norton RA, et al:  Gallstones in inflammatory bowel disease . Am J Dig Dis 19:109-112, 1974;.
42 +
Warren KE, Athanassiades S, Monge JI:  Primary sclerosing cholangitis . Am J Surg 111:23-38, 1966;.
43 +
Morowitz DA, Glagov S, Dordal E, et al:  Carcinoma of the biliary tract complicating chronic ulcerative colitis . Cancer 27:356-361, 1971;.
44 +
Kelley ML Jr:  Skin lesions associated with chronic ulcerative colitis . Am J Dig Dis 7:255-272, 1962;.
45 +
McCallum DI, Kinmont PDC:  Dermatological manifestations of Crohn's disease . Br J Dermatol 80:1-8, 1968;.
46 +
Gelernt IM, Kreel J:  Pyoderma gangrenosum in ulcerative colitis: Prevention of the gangrenous component . Mt Sinai J Med 43:467-470, 1976;.
47 +
Crawford SE, Sherman R, Favara B:  Pyoderma gangrenosum with response to cyclophosphamide therapy . J Pediatr 71:255-258, 1967;.
48 +
Kirsner JB, Sheffner L, Palmer WL:  Studies on amino acid excretion: V. Chronic ulcerative colitis and regional enteritis . J Clin Invest 39:874-880, 1950;.
49 +
Beeken WL, Busch HJ, Sylvester DL:  Intestinal protein loss in Crohn's disease . Gastroenterology 62:207-215, 1972;.
50 +
Dyer NH, Child JA, Mollin DL, et al:  Anemia in Crohn's disease . Q J Med 44:419-436, 1972;.
51 +
Earnest DL:  Enteric hyperoxaluria . Adv Intern Med 24:407-427, 1979;.
52 +
Franklin JL, Rosenberg IH:  Impaired folic acid absorption in inflammatory bowel disease: Effects of salicylazosulfapyridine (Azulifidine) . Gastroenterology 64:517-525, 1973;.
53 +
Benson RE, Bargen JA:  Chronic ulcerative colitis as a cause of retarded sexual and gonadic development . Gastroenterology 1:147-159, 1943;.
54 +
McCaffrey TD, Nasr K, Lawrence AM, et al:  Severe growth retardation in children with inflammatory bowel disease . Pediatrics 42:386-393, 1970;.
55 +
Berger M, Griebetz D,  Korelitz BI: Growth retardation in children with ulcerative colitis: The effect of medical and surgical therapy . Pediatrics 55:459-467, 1975;.
56 +
Kirschner BS, Voinchet OH, Rosenberg IH:  Growth retardation in inflammatory bowel disease . Gastroenterology 75:504-511, 1978;.
57 +
Basu MK, Asquith P, Thompson RA, et al:  Oral manifestations of Crohn's disease . Gut 16:249-254, 1975;.
58 +
Li Volsi VA, Jaretzki A III:  Granulomatous esophagitis: A case of Crohn's disease limited to the esophagus . Gastroenterology 64:313-319, 1972;.
59 +
Danzi JT, Farmer RG, Sullivan BH Jr, et al:  Endoscopic features of gastroduodenal Crohn's disease . Gastroenterology 70:9-13, 1976;.
60 +
Das KM, Eastwood MA, McManus JPA, et al:  Adverse reactions during salicylazosulfapyridine therapy and the relation with drug metabolism and acetylator phenotype . N Engl J Med 289:491-495, 1973;.
61 +
Schroder H, Evans DAP:  Acetylator phenotype and adverse effects of sulphasalazine in healthy subjects . Gut 13:278-284, 1972;.
62 +
Goldstein MJ, Gelzayd EA, Kirsner JB:  Some observations on hazards of corticosteroid therapy in patients with inflammatory disease . Trans Am Acad Ophthalmol Otolaryngol 71:254-261, 1967;.
63 +
Gelzayd EA, Breuer RI, Kirsner JB:  Nephrolithiasis in inflammatory bowel disease . Am J Dig Dis 13:1027-1034, 1968;.
64 +
Graef V, Baggenstoss AH, Sauer WG, et al:  Venous thrombosis occurring in non-specific ulcerative colitis . Arch Intern Med 117:377-382, 1966;.
65 +
Block GE, Enker WE, Kirsner JB:  Significance and treatment of occult obstructive uropathy complicating Crohn's disease . Ann Surg 178:322-332, 1973;.
66 +
Mukhopadhyay D, Nasr K, Grossman BJ, et al:  Pericarditis associated with inflammatory bowel disease . JAMA 211:1540, 1970;.

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