72 Inflammatory Bowel Disease

The inflammatory bowel diseases (IBD) - ulcerative colitis and Crohn’s disease - constitute a group of disorders of the small and large intestine whose causes and interrelationships remain obscure (Kirs- ner and Shorter 1988).

Ulcerative Colitis

Clinical Manifestations, Pathology, and Diagnosis

The principal symptoms of ulcerative colitis are rectal bleeding, constipation early (in ulcerative proctitis), diarrhea usually, abdominal cramping pain, rectal urgency, fever, anorexia, fatigue, and weight loss. The physical findings depend upon the severity of the colitis, ranging from normal in mild disease, to fever, pallor from loss of blood, dehydra­tion and malnutrition, and the signs of associated complications. X-ray and endoscopic examinations demonstrate diffuse inflammation and ulceration of the rectum and colon in 50 percent of patients, and the adjoining terminal ileum. Ulcerative colitis be­gins in the mucosa and submucosa of the colon (the inner bowel surface); in severe colitis the entire bowel wall may be involved. The principal histo­logical features are the following: vascular conges­tion, diffuse cellular infiltration with polymorpho­nuclear cells, lymphocytes, plasma cells, mast cells, eosinophils, and macrophages; multiple crypt ab­scesses; and shallow ulcerations. Chronic ulcerative proctitis is the same disease as ulcerative colitis, except for its restriction to the rectum and its milder course.

The laboratory findings reflect the severity of the colitis. The white blood cell count usually is normal except in the presence of complications. The hemoglo­bin, red cell, and hematocrit are decreased in propor­tion to the loss of blood. The sedimentation rate may be elevated but frequently is normal. Blood proteins including serum albumin often are diminished. The stools contain blood. Cultures are negative for known pathogenic bacteria.

Complications are numerous. In the colon, they include pericolitis, toxic dilatation, perforation, peri­tonitis, hemorrhage, obstruction, polyps, carcinoma, and lymphoma. The many systemic complications include iron-deficiency anemia, hemolytic anemia, protein loss, malnutrition, retardation of growth in children, arthritis, iritis, sacroileitis, metabolic bone disease, skin problems (erythema nodosum, pyo­derma gangrenosum), pyelonephritis, nephrolith­iasis, liver disease (fat infiltration, hepatitis, peri­cholangitis, sclerosing cholangitis), and vascular thromboses.

The differential diagnosis includes specific bacte­rial infections, ischemic colitis, diverticulitis, and Crohn’s disease of the colon.

Treatment

The therapeutic emphasis in ulcerative colitis in­volves a general program of nutritional restoration, emotional support, sulfasalazine, 5-aminosalicylic acid, antispasmodics, antibacterial drugs, adrenocor­ticotropin (ACTH), and adrenal corticosteroids. Proc­tocolectomy and ileostomy is a highly successful op­eration for ulcerative colitis. The Kock continent pouch, and total colectomy together with ileoanal anastomoses, with and without ileal pouch, offer use­ful surgical alternatives in selected patients. The prognosis of ulcerative colitis has improved consider­ably, and the mortality has diminished to less than 1 percent as a result of the many medical and surgical therapeutic advances.

Etiology

Ulcerative colitis is common among young people, es­pecially below the age of 40 years, but no age range is exempt and the number of older patients is in­creasing.

Various circumstances such as acute respiratory illness, enteric infections, and antibiotics may act as a “trigger mechanism,” precipitating the disease in genetically “vulnerable” persons. Genetic influences may be expressed through the immune response genes and the mucosal immune system of the bowel. Emotional disturbances are common in patients with ulcerative colitis, but they probably do not ini­tiate the disease. The important interactions among the central nervous system, the gut, and the endo­crine and immune systems now under investigation may clarify these issues.

Crohn’s Disease

Crohn’s disease, also called regional enteritis, jeju- noileitis, ileocolitis, and Crohn’s colitis, is an acute and chronic inflammatory disease of the small intes­tine, especially the terminal ileum, but actually in­volving the entire gastrointestinal tract, from the mouth to the anus. The disease occurs frequently among children, adolescents, and young adults, but is increasing in people over the age of 60.

Clinical Manifestations

The clinical manifestations include fever, diarrhea, cramping abdominal pain, anemia, and weight loss. Initial symptoms may include arthralgias suggest­ing an arthritis, gynecological difficulties, urinary symptoms (frequency, dysuria), or a combination of severe loss of appetite, weight loss, and depression, suggesting anorexia nervosa. Slowing or retardation of growth may be the first clinical indication of ill­ness in children. Occasionally, the initial presenta­tion is indistinguishable from an acute appendicitis.

The physical findings include fever, “toxemia,” ten­derness in the mid abdomen and right lower abdomi­nal quadrant, and often a tender loop of bowel or an inflammatory mass composed of adherent inflamed bowel, thickened mesentery, and enlarged abdomi­nal lymph nodes, palpated in the right lower abdomi­nal quadrant. The laboratory findings include a nor­mal or elevated white blood cell count, increased sedimentation rate, anemia, decreased total proteins and serum albumin, and evidence of Undemutrition. By X-ray, the intestinal lumen is found to be ulcer­ated and narrowed. Fistulas to adjacent structures are not uncommon. The histological features include transmural disease, knifelike ulcerations overlying the epithelium of lymphoid aggregates in Peyer’s patches, profuse cellular accumulations, lymphatic dilatation, prominent lymphoid follicles, and granu­loma formation.

The complications of regional enteritis include most of the problems enumerated for ulcerative coli­tis and, in addition, perianal abscess, perineal fistu­las, abdominal abscess and fistual formation, intesti­nal narrowing and obstruction, carcinoma of the small and large intestine, and obstructive hydrone­phrosis. In patients with multiple bowel resections and significant loss of intestinal digestive capacity, the complications include altered bile salt metabo­lism, steatorrhea, increased absorption of dietary oxalate and hyperoxaluria, increased frequency of kidney stones, zinc and magnesium deficiencies, other nutritional deficits including vitamins B₁₂ and D, bone demineralization, and osteopenia.

Treatment

As in ulcerative colitis, medical treatment is symp­tomatic, supportive, and individualized, with em­phasis upon restoration of nutrition, antispasmodic medication, and antibacterial and antiinflamma­tory medication. Corticotropin and adrenal steroids reduce the inflammatory reaction, but do not neces­sarily cure the disease. Immunosuppressive drugs (6-mercaptopurine, azathioprine) may be helpful adjuncts but require continuing administration. Surgical treatment is necessary for complications, especially abscess and fistula formation, unrelent­ing intestinal obstruction, and uncontrollable hem­orrhage. The recurrence rate is high.

Etiology

As in ulcerative colitis, etiologic hypotheses vary widely, from the excessive eating of cornflakes, re­fined sugars, or margarine, to bottle-feeding rather than breastfeeding, environmental pollutants, the in­discriminate administration of antibiotics, and the use of oral contraceptives among young women. A wide vειriety of bacteria and viruses have been impli­cated, and although none has achieved etiologic sta­tus, the “new” microbial pathogens now being identi­fied have renewed interest in microbial possibilities including mycobacteria. Other suggested but un­proven etiologies have included blunt trauma to the abdominal wall (e.g., seat belt injury); the ingestion of foreign material (e.g., talc), producing an obstruc­tive lymphangitis; sarcoidosis; altered intestinal neu­rohumoral mechanisms; and nutritional deficiencies.

Ulcerative Colitis and Crohn’s Disease: General Aspects

Epidemiology, Distribution, and Incidence Ulcerative colitis and Crohn’s disease share similar epidemiological and demographic features. The inci­dence of ulcerative colitis, still considerable, appar­ently has stabilized or possibly diminished in many areas of the world, with several exceptions (Norway, Japan, Faroe Islands, northeast Scotland). Ulcera­tive colitis appears to be more prevalent in the United Kingdom, New Zealand, Australia, the United States, and northern Europe.

Similarly Crohn’s disease is most common in the United Kingdom, the United States, and Scandina­via, on the rise in Japan, but less frequent in central and northern Europe and uncommon in Africa and South America. The incidence of Crohn’s disease has been increasing throughout much of the world (Great Britain, the United States, Norway, Finland, Switzer­land, Israel, and South Africa) but appears to have stabilized in such diverse cities as Aberdeen (Scot­land), Baltimore (United States), Cardiff (Wales), and Stockholm (Sweden). B. M. Mendeloff and A. I. Calkins (1988) estimate that in the United States the annual incidence “for the sum of both disorders” is 5 to 15 new cases per 100,000 population. The world­wide prevalence of Crohn’s disease, especially in in­dustrialized areas, and the worldwide similarity of its clinical, radiological, and pathological features, re­gardless of geographic, ethnic, dietary, and sociocul­tural differences, are noteworthy.

The inflammatory bowel diseases are more fre­quent among white than black populations; but Crohn’s disease in particular is increasing among the black populations of the United States and Great Britain. Ulcerative colitis and especially Crohn’s dis­ease are much more common among the Jewish popu­lation of the United States, the United Kingdom, and Sweden than among other members of the popu­lation. In Israel, Crohn’s disease is more common among Ashkenazi than among Sephardic Jews. Over­all, ulcerative colitis and Crohn’s disease occur among all ethnic groups, including the Maoris of New Zealand, Arabs (e.g., Kuwait, Saudi Arabia), and probably the Chinese, albeit infrequently. An intriguing and unexplained epidemiological observa­tion has to do with the scarcity of cigarette smokers in patients with ulcerative colitis and the appar­ently increased vulnerability of former smokers to ulcerative colitis, whereas by contrast there is an excess of smokers in Crohn’s disease populations. It should be noted that the “smoking connection” does not obtain among children with IBD.

Genetic (Familial) Aspects

Ulcerative colitis and Crohn’s disease are not “classic” genetic disorders. There are no inheritable protein or metabolic abnormalities, no antecedent chromosomal defects, no genetic markers, no con­sanguinity, and no Mendelian ratios. However, genetic influences are important in the develop­ment of ulcerative colitis and even more so in Crohn’s disease, as reflected in their familial clus­tering (20 percent for ulcerative colitis and up to 40 percent for Crohn’s disease). In addition to the initial patient, one more member of the family is usually affected, but up to 8 patients in a single family have been observed. IBD occurs with a high degree of concordance among monozygotic twins. The nature of the genetic influence in IBD is not known. Thus far, no universally distinctive histo­compatibility haplotype linkage has been demon­strated. The occasional occurrence of Crohn’s dis­ease or ulcerative colitis in adopted children or later in the initially healthy mate of a patient with IBD supports an environmental (possibly viral) rather than a genetic mechanism. Current etiologic studies focus upon a genetically mediated abnormal­ity in the immune response genes (defective immu­noregulation in the bowel’s mucosal immune sys­tem), possible linkage with a known genetic locus, or with specific T-cell antigen receptor genes.

Comparisons and Contrasts

Is there a pathogenetic relationship between ulcera­tive colitis and regional ileitis/colitis? In the absence of differentiating biological markers, a definitive answer to this important question is not possible at present. The simultaneous presence or sequential evolution of both active ulcerative colitis and active regional ileitis/colitis, and the sequential develop­ment of ulcerative colitis followed by Crohn’s dis­ease in a single patient, though they may occur, probably have never been documented to everyone’s satisfaction.

The Similarities. Both disorders have significant familial associations. Approximately 25 percent of families with multiple instances of IBD show an inter­mingling of ulcerative colitis and Crohn’s disease. Both diseases share the same epidemiological and demographic features. They also share many symp­toms (abdominal pain, diarrhea, weight loss, rectal bleeding), local complications (hemorrhage, perfora­tion, toxic dilatation of the colon), and systemic com­plications (erythema nodosum, pyoderma gangre­nosum, arthritis, liver disease, kidney stones).

The Differences. Ulcerative colitis is a continuous mucosal disease, at least initially, with diffuse in­volvement of the colon. Crohn’s disease is a trans­mural process, focal in distribution, penetrating through the bowel wall, and producing microab­scesses and fistulas. Histologically, granulomas and prominent lymphoid aggregates are much more com­mon in Crohn’s disease than in ulcerative colitis.

Ulcerative colitis is limited to the colon and occa­sionally a short segment of terminal ileum; Crohn’s disease focally may involve any segment of the ali­mentary tract, mouth to anus. Ulcerative colitis is a continuous inflammatory reaction; Crohn’s disease, wherever located, is a discontinuous, focal process. Perianal suppuration and fistula formation (entero- cutaneous, enteroenteric, enterocolonic, enteroves- ical, enterouterine) characterize Crohn’s disease, but not ulcerative colitis. Immune-modulating drugs are more helpful in Crohn’s disease than in ulcera­tive colitis. Proctocolectomy and ileostomy are cura­tive in ulcerative colitis, but the same operation in Crohn’s disease carries a recurrence rate of approxi­mately 15 to 20 percent.

The answer to the question whether the two ailments are related would seem to be that ulcerative colitis and Crohn’s disease are probably separate disorders, with limited morphological and clinical expressions accounting for overlapping manifestations.

History of IBD

Ulcerative Colitis

Early Literature to 1920

In all probability, we shall never know for certain who first described ulcerative colitis (UC)... for although the disease was initially referred [to] by name in the latter half of the century, it seems likely that its existence was recognized for over two millennia before that time. (Goligher et al. 1968)

Hippocrates was aware that diarrhea was not a single disease entity, whereas Aretaeus of Cappado­cia in the second century described many types of diarrhea, including one characterized by “foul evacua­tions,” occurring chiefly in older children and adults. Instances of an “ulcerative colitis” apparently were described by Roman physicians, including Ephesus in the eleventh century. "Noncontagious diarrhea” flourished for centuries under a variety of labels, such as the “bloody flux” of Thomas Sydenham in 1666. In 1865, medical officers of the Union Army during the American Civil War described the clinical and pathological features of an “ulcerative colitis­like” process in patients with chronic diarrhea. Sev­eral of these cases actually suggested Crohn’s disease more than ulcerative colitis but in the absence of modern microbiological studies, the question is moot (Kirsner and Shorter 1988).

S. Wilks and W Moxon (1875) wrote: “We have seen a case affected by discharge of mucus and blood, where, after death, the whole internal surface of the colon presented a highly vascular soft, red surface covered with a tenacious mucus and adherent lymph.... In other examples there has been exten­sive ulceration.” Because the concept of microbial illnesses had not yet emerged, the possibility of a specific infection, in at least some instances, cannot be excluded. W H. Allchin (1885), W. Hale-White (1888), and H. Folet, writing in 1885, are among those cited by G. Placitelli and colleagues (1958), who provided accurate clinical accounts. G. N. Pitt and A. E. Durham in 1885 described a woman of 29 years with a 5-year history of diarrhea:

[M]ore than half of the area of the whole colon was covered with small friable villous polypi... the intervening de­pressed white areas in the muscular coat, the mucous coat having entirely ulcerated away.... the circumference of the bowel is only 1½ — 2 inches, being narrower than the small intestine. (Kirsner 1988)

During the 1880s and 1890s, instances of an ul­cerative colitis were reported by numerous physi­cians from England, France, Germany, Italy, and other European countries (Kirsner 1988). In 1888 Hale-White, a contemporary of Wilks at Guy’s Hospi­tal, described 29 cases of ulcerative colitis and re­marked that “[t]he origin of this ulceration is ex­tremely obscure... it is not dysentery.” He cited similar observations by W Leube (Ziemssen’s Cyclo­pedia), K. Rokitansky (“Pathological Anatomy”), H. Nothnagel (Beitrage zur Physiologie und Pathologie des Darmes, 1884), and A. Bertrand and V. Fontana (“De Fenterocolite chronique endemique des Pays Chauds”), but again complete confirmation is not possible.

In 1895 Hale-White reported the association of liver disease and ulcerative colitis, and in 1920 R. F Weir performed the operation of appendicostomy to facilitate “colonic drainage” in ulcerative colitis. J. P. Lockhart-Mummery (1907) described seven in­stances of colon carcinoma among 36 patients with ulcerative colitis, and emphasized the diagnostic value of sigmoidoscopy at the Royal Society of Medi­cine. By 1909, approximately 317 cases of patients with “ulcerative colitis” had been collected (between 1888 and 1907) from London hospitals, and in 1909 Allchin recorded perhaps the first instance of “famil­ial” ulcerative colitis. Additional instances of ulcera­tive colitis were noted at the Paris Congress of Medi­cine in 1913. J. Y. Brown (1913) of the United States may have been the first to suggest the procedure of ileostomy in the surgical management of ulcerative colitis.

American and European Literature, 1920—45. Dur­ing the 1920s, the number of reports increased steadily and included those by H. Rolleston, C. E. Smith, J. M. Lynch and J. Felsen of New York, A. F Hurst, and E. Spriggs. During the same decade, Her­mann Strauss of Berlin may have been the first to recommend blood transfusions in the treatment of ulcerative colitis. In 1924 J. A. Bargen of the Mayo Clinic published his experimental studies implicat­ing the diplostreptococcus in the etiology of ulcera­tive colitis - a notion later discarded. More impor­tant was his (1946) comprehensive clinical study of the course, complications, and management of “thrombo-ulcerative colitis.” C. D. Murray first drew public attention to the psychogenic aspects of ulcera­tive colitis in 1930, which were confirmed by A. J. Sullivan and C. A. Chandler (1932). This initiated the period (1930-60s) of intense psychiatric interest in ulcerative colitis.

Worldwide attention was directed to “colites ul- cereuses graves non-ambienne” at the 1935 Interna­tional Congress of Gastroenterology in Brussels; the amount of literature on the disease increased rap­idly after this, with clinical contributions initiated by many physicians from many countries.

By the 1940s, ulcerative colitis, if not increasing in prevalence, at least was recognized more often than regional ileitis and was the dominant IBD disease. However, by the end of World War II, Crohn’s disease (regional enteritis, Crohn’s colitis) had become more frequent. Concurrently with an apparent stabiliza­tion of the frequency of ulcerative colitis in the United States, Crohn’s disease has been the more prominent of the two prototypes of nonspecific IBD.

Crohn’s Disease

Literature before 1900. The initial description of Crohn’s disease may date back to Giovanni Battista Morgagni who, in 1761, described ileal ulceration and enlarged mesenteric lymph nodes in a young man who died of an ileal perforation; or, perhaps even earlier, to the “iliac passion” - claims that can never be substantiated. More suggestive early in­stances of Crohn’s disease include an 1806 report by H. Saunders and that by C. Combe and Saunders (1813). Nineteenth-century descriptions of ileocecal disease consistent with today’s concept of Crohn’s disease, regional ileitis, or ileocolitis were authored by J. deGroote, J. Abercrombie, J. S. Bristowe, N. Moore, and Wilks. Wilks’s (1859) description of the postmortem examination on the celebrated Isabella Bankes is of interest:

The intestines lay in a coil adherent by a thin layer of lymph indicative of recent inflammation; the ileum was inflamed for three feet from the ileo-caecal valve though otherwise the small intestine looked normal. The large intestine was ulcerated from end to end with ulcers of various sizes mostly isolated [t]hough some had run to­gether.... Inflammation was most marked at the proxi­mal colon and the caecum appeared to be sloughing caus­ing the peritonitis.

Thirty years later, Samuel Fenwick (1889) de­scribed the necropsy findings suggestive of Crohn’s disease, in a 27-year-old female:

Many of the coils of intestine were adherent and a commu­nication existed between the caecum and a portion of the small intestine adherent to it, whilst the sigmoid flexure was adherent to the rectum, and a communication also existed between them. The lower end of the ileum was much dilated and hypertrophied, and the ileocecal valve was contracted to the size of a swan’s quill.

Literature after 1900. Early in this century, T. Ken­nedy Dalziel (1913) of Glasgow described a group of 13 patients dating back to 1901 with findings closely resembling those recorded by B. B. Crohn, L. Ginz­burg, and G. D. Oppenheimer (1932): “The affected bowel gives the consistence and smoothness of an eel in a state of rigor mortis, and the glands, though enlarged, are evidently not caseous.” Many reports of single instances of a chronic stenosing inflamma­tion of the last portion of the small bowel (“terminal ileitis”) appeared subsequently. In addition, F. J. Nuboer (1932) of Holland described two patients with “chronic phlegmonous ileitis,” manifesting the same gross and histological findings that Crohn and associates described. Similarly, M. Golob (1932) re­ported a “chronic infectious granuloma” involving the ileocecal region in a 44-year-old male presenting with rectal bleeding.

Soon after Crohn’s (1932) paper, A. D. Bissell (1934) of the University of Chicago reported on two patients. The first patient was a 39-year-old male with symptoms of 4 years’ duration, including ab­dominal cramps, diarrhea, and weight loss who re­quired resection of an ileocecal mass. The second patient, a 28-year-old male, also required resection of the terminal ileum and cecum. These early case reports depicted Crohn’s disease (“regional ileitis”) as a mass-producing, bowel-narrowing process, virtu­ally always requiring surgical intervention.

The principal clinical differentiation in the early part of the twentieth century included intestinal tuberculosis and granuloma formation simulating tumor in the bowel. E. Moschowitz and A. D. Wilensky (1923), from New York’s Mount Sinai Hos­pital, reflecting that center’s interest in granulo­matous inflammations of the bowel, described four patients with nonspecific granulomatous disease of the intestine. Ginzburg and Oppenheimer, in the Pathology Department of the same hospital, identi­fied a dozen instances of a localized hypertrophic, ulcerative stenosis of the distal 2 or 3 feet of the terminal ileum. Specific causes such as amebiasis, actinomycosis, intestinal tuberculosis, and syphilis were ruled out. In 1930, Crohn had two patients with a similar process. Crohn’s first case was a 16- year-old boy with diarrhea, fever, a mass in the right lower abdominal quadrant, and pain, requiring ileo­cecal resection. Interestingly, the patient’s sister also required an operation for regional ileitis several years later - the first recorded instance of “familial regional ileitis.” Bargen, anticipating the more ex­tensive involvement of the small intestine, sug­gested the term regional enteritis instead of “termi­nal ileitis.”

In 1925 T. H. Coffen of Portland, Oregon, referring to earlier reports of intestinal granulomas, described a 20-year-old man with abdominal symptoms since 1915, diagnosed as phlegmonous enteritis. In 1916,8 inches of thickened bowel were removed because of obstruction. A second obstruction 5 months later necessitated the removal of 24 inches of ileum. Eight months later a third resection was performed for the same condition. The pathological description of the resected bowel today would be consistent with a diag­nosis of Crohn’s disease.

In other notable articles, H. Mock in 1931 and R. Colp in 1933 chronicled involvement of the colon. C. Gotlieb and S. Alpert (1937) described regional jejunitis, and J. R. Ross (1949) identified “regional gastritis.” W. A. Jackman and J. L. Kantor in 1934 and R. Marshak in 1951 described the roentgeno- graphic appearance of Crohn’s disease of the small bowel and the colon, and in 1936 Harold Edwards described a resected terminal ileum, with “the consis­tency of a hosepipe” from a 23-year-old woman with a history of persistent diarrhea, abdominal pain, and weight loss. R. Shapiro (1939) comprehensively re­viewed the literature through the 1930s and identi­fied numerous case reports mainly in the earlier German surgical literature of “inflammatory tu­mors” of the gastrointestinal tract, especially the colon; some of these probably were instances of Crohn’s disease.

Authoritative descriptions of the pathological fea­tures of Crohn’s disease have been provided by S. Warren and S. C. Sommers (1948), G. Hadfield (1939), and H. Rappaport and colleagues (1951). In 1952, Charles Wells of Liverpool distinguished be­tween ulcerative colitis and what he termed “seg­mental colitis,” and suggested that this latter form of colonic lesion was a variant of Crohn’s disease. In 1955 Bryan Brooke and W Trevor Cooke OfEngland were among the first to recognize “right-sided coli­tis” as Crohn’s disease of the colon rather than as ulcerative colitis, but it was not until reports in 1959 and 1960 by Lockhart-Mummery and B. C. Morson (1960) that Crohn’s disease of the colon was gener­ally accepted as a valid entity.

Eponym of Crohn’s Disease. New instances of granulomatous inflammation of the small bowel were reported in Great Britain, occasionally desig­nated as Crohn’s disease, in 1936. In America the term “Crohn’s disease” was first employed as a syn­onym by F. Harris and colleagues (1933) and later by Hurst of Great Britain. But others have also claimed priority. In Poland this entity was called ^uLesniowski-Crohn’s disease,” whereas in Scotland the eponym of “Dalziel’s disease” was recorded. H.

I. Goldstein designated the condition “Saunders- Abercrombie—Crohn’s ileitis.”

To some American observers, this entity might well have been called “CGO disease,” to include the important contributions of not only Crohn, but also Ginzburg and Oppenheimer, who provided 12 of the 14 cases constituting the (1932) JAMA paper. What­ever the “labeling” circumstances, the entity today carries the eponym “Crohn’s disease” as the most convenient designation, which is now sanctioned by worldwide usage to designate a unique inflamma­tory process involving any part of the gastrointesti­nal tract. It is to the credit of Crohn, Ginzburg, and Oppenheimer that their clinical description stimu­lated worldwide interest in this disease. Certainly much credit belongs to Crohn for his long clinical interest in the illness, his many publications and lectures on the subject, and his encouragement of others in the further investigation of the problem.

On the matter of eponyms, the comment of Thomas Lewis (1944) seems appropriate: “Diagnosis is a system of more or less accurate guessing, in which the end point achieved is a name. These names applied to disease come to assume the impor­tance of specific entities... whereas they are, for the most part, no more than insecure and therefore temporary conceptions.”

Joseph B. Kirsner

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