Crohn's Disease in the Jewish Population of Tel-A viv-yafo

Transcription

1 Crohn's Disease in the Jeish Population of Tel-A viv-yafo Epidemiologic and Clinical Aspects PAUL ROZEN, M.D., JULIO ZONIS, M.D., PERETZ YEKUTIEL, M.D., and TUVIA GILAT, M.D. Department of Gastroenterology, the Municipal Governmental Medical Center Ichilov Hospital, and the Departments of Gastroenterology and Preventive and Social Medicine of the Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel A survey of the incidence and prevalence of Grahn's disease in the Jeish population of Tel-A vi v-yafo as carried out from 1970 to The annual incidence rate as 1.28, and the prevalence as per 10 5 population. The prevalence of per 10 5 population among Ashkenazi Jes as significantly higher than that found in "non-ashkenazi" Jes, 4.19 per 10 5 population. Even so, Grahn's disease is significantly less common in Tel-Aviv than outside Israel, according to most recently published surveys. Similarly, the complication, surgery, and mortality rates are less marked than those reported from other studies. These figures confirm the authors' impression that inflammatory boel disease in general is less common and possibly less severe in Tel-Aviv than in the United States and Western Europe. The strikingly higher prevalence in the Ashkenazi community, especially in the Israeli-born population, suggests a hereditary predisposition. The apparent differences among Ashkenazi Jes in various parts of the orld may relate to environmental factors. Inflammatory boel disease, including Grohn's disease, has a relatively high and possibly rising incidence among the affluent societies of Western Eu- Received June 30, Accpeted August 14, Part of this ork as included in the doctoral thesis of J. Zonis at the Sackler School of Medicine, Tel-Aviv University, Address requests for reprints to: Dr. P. Rozen, Gastroenterology Department, Ichilov Hospital, Weizmann Street, Tel-Aviv, Israel. Dr. Gilat is an established investigator of the Chief Scientist's Bureau, Ministry of Health, Tel-Aviv, Israel. The authors acknoledge Reuven Terdiman, M.Sc., for the statistical evaluation by the American Gastroenterological Association rope, Scandinavia, and North America. 1-7 In certain areas of the United States, Seden, and South Africa, inflammatory boel disease has been noted to occur ith excessive frequency among the Jeish population. B - 12 Hoever, a recently performed epidemiologic study of ulcerative colitis in the Jeish population of the Tel-Aviv area shoed that it occurs less frequently than it has been reported to occur in the United States and Europe. 13 The authors believed that this finding applied also to Grohn's disease. Because Grohn's disease is a disease of unknon etiology, valuable information may be derived from studies of geographic and ethnic pathology.1 The authors therefore determined the incidence and prevalence of Grohn's disease among the Jeish population of Tel-Aviv-Yafo and its distribution in the different community groups comprising the population, and compared the clinical features of the disease ith those reported in other published series. Materials and Methods During the period chosen for the study, January 1, 1970, to December 31, 1976, hich as the prevalence date, the population of Tel-Aviv-Yafo averaged 356,133 inhabitants. For determination of incidence, only subjects residing in Tel-Aviv-Yafo at the time of diagnosis ere included. For calculation of prevalence, all subjects resident in the area at the time of the prevalence date ere included. The population at this time as estimated to be 341, Students, tourists, and soldiers transiently located in the area ere not included. The governmental and municipal population statistics shoed that the Ashkenazi community (mostly immigrants from Europe and America and their descendents) represented, on the average, 65 of the population during this time period. 14 Oing to the small numbers involved,

2 26 ROZENETAL. GASTROENTEROLOGY Vol. 76, No.1 the authors designated the remainder of the population as "non-ashkenazi," hich represented the Sephardi (mostly immigrants from the Mediterranean area) and Oriental (mostly immigrants from the Middle East and Asia) population. The patients ith Crohn's disease ere located by personal revie of the medical records of institutions and gastroenterology clinics in and around Tel-Aviv. Gastroenterologists, leading surgeons, and internists in the area ere also approached; the diagnosis of Crohn's disease is rarely made in Tel-Aviv ithout the patient's passing through one of these channels. Moreover, records of the same patient ere often found in more than one institution. The authors thus feel that the search for patients ith knon Crohn's disease as effective. A questionnaire as then filled out for each patient, including personal, demographic, and medical data. The criteria for diagnosing chronic Crohn's disease ere pathologic, surgical or clinical, and radiologic, as described by Morson,15 Lennard-Jones,'6 and Marshak and Linder.17 All X-ray films, pathology specimens, and surgical reports ere reexamined in light of the required diagnostic criteria. No cases of acute ileitis ere included, and in each case the changes ere typical of the disease. Definite Crohn's disease as diagnosed in cases ith a histologic diagnosis or in cases ith typical roentgenic and clinical features. Probable Crohn's disease as considered present in cases in hich no pathological study as performed; hoever, a typical roentgenic picture and incomplete clinical data ere available, or vice versa. Cases ith equivocal histology but typical roentgenic and clinical features ere also included in this group. Results Forty-four patients ith Crohn's disease ere living ithin the municipal boundaries of Tel-Aviv Yafo at time of diagnosis. One patient moved to another area before the prevalence date, and 1 patient died 4 yr before the prevalence date. Thirty-eight patients ere considered to have definite Crohn's disease and 6 patients had probable Crohn's disease. In 21 of the definite cases the diagnosis as confirmed histologically and/or surgically. To patients ere never hospitalized; the diagnosis as made and the patients ere treated in a gastroenterology clinic. The diagnosis as made, on an average, 3.7 yr after the onset of symptoms. Incidence In 32 patients, Crahn's disease as diagnosed during the period January 1, 1970, to December 31, The annual incidence rate for this period per 10 5 of population is shon in Figure 1. There ere fluctuations in the incidence, ith a rising trend noted over the period. The average annual incidence ~ 1.0 '" U Z 0.5 O+---~--~----r---~--~--~ PERIOD STUDIED Figure 1. Annual incidence rates ( ) of Crohn's disease per 10 5 population for males, females, and total group. rate for the period studied as 1.28 per 10 5 population (Table 1). Prevalence Forty-to patients ere living in the municipal area of Tel-Aviv-Yafo at the time of the prevalence date, December 31, The prevalence of Crohn's disease as per 10 5 population. Demographic Features Fifty-nine percent of the patients ere born in Europe or America, 27.3 in Israel, 9 in Asia, 2.3 in Africa, and the remainder unknon. As seen from Table 1, these figures are significantly different from those of the general population of Tel-Aviv Yafo, and the disease is more common in European and American born Jes and less common in Israeli or Asian and African born Jes (P < 0.01, using the chi-squared Pearson test). The prevalence rate for those born in Europe or America as per 10 5 population. This as significantly different from the prevalence rate for Israeli born 7.85 per 10 5 population, and Asian-African born, 8.19 per 10 5 population. The authors also divided the same cases and population into Ashkenazi and non-ashkenazi. Israeli born subjects ere included in either one of these community groups according to the origin of their parents, and all ere found to be Ashkenazi. The prevalence rate for Ashkenazi Jes as per 10 5 population and for non-ashkenazi Jes 4.19 per 10 5 population. These figures are also significantly different. Both differences ere significant at the level of P < 0.01 ith the fourfold table test (Table 1). Almost 20 of the European-American born patients ere ill ith Crahn's disease before emigrating to Israel. All other non-israeli born had lived in Israel 5-47 yr before

3 January 1979 CROHN'S DISEASE IN TEL-AVIV 27 Table 1. Demographic Data of Jeish Patients ith Crohn's Disease, Tel-A vi v-yafo, No. of Expected patients () distributiono Incidence Prevalence Place of birth Europe and America 26 (59.1) Israel 12 (27.3) Asia and Africa 5 (11.3) Unknon 1 ( 2 3). Total 44 Community group Ashkenazi 37 (88) Non-Ashkenazi 5 (12) b c C 1.28(32) 12.31(42) (26) b c a According to the population of Tel-Aviv-Yafo." 5 b is significantly different from C (P < 0.01). Figures in parentheses indicate the number of patients used in calculating prevalence and incidence rates, respectively. the prevalence date, and the onset of their disease occurred 6 mo to 2 yr before the diagnosis as established. Sex At prevalence date, there ere 22 male and 20 female patients. The female/male ratio as 0.91, hereas the female/male ratio in the population as For the entire series of 44 patients, the female/male ratio as These differences ere not of statistical significance. Age The ages of onset and diagnosis of Crohn's disease paralleled each other (Figures 2 and 3). To peaks ere found: the larger in the teen-age group and early adult life, the smaller in the sixth and seventh decades of life. Anatomic localization of the disease shoed that the terminal ileum as the main area involved in 59; 18 had other small boel changes; 16 had mainly large boel disease; and the remainder had both small and large boel involvement. Clinical Manifestations The most common symptoms at the time of diagnosis ere abdominal pains (86), diarrhea (77), eight loss (61), and fever (56). Rectal bleeding occurred in 18, and a mass as palpated in the right loer abdomen in 7. The extraintestinal manifestations of the disease included abnormal liver function tests in 18, arthritis or arthralgias in 11, skin lesions in 5, and iritis or uveitis in 2 during the course of the disease. Diagnostic procedures included macroscopic and/ or microscopic confirmation of the disease in 21 patients. Tenty-six of 39 small boel films taken ere typical of Crohn's disease, as ere seven of 39 large boel X-rays. Thirty-one surgical procedures ere performed Total If) > u.,.., :>... o 0' z 10 If) 5 If) > u.,.., :> If)... o 10 0' Z 5 O~--~--~--r-~--~--~--~--~ ( AGE GROUP Figure 2. Age at onset of Crohn's disease for males, females, and total group. 0L-~~~~--~--~-4~~--~--~ AGE GROUP Figure 3. Age at diagnosis of Crohn's disease for males, females, and total group.

4 28 ROZEN ET AL. GASTROENTEROLOGY Vol. 76, No.1 on 23 patients. These included four exploratory laparotomies and 15 boel resections as ell as surgery of fistulae, drainage of abscesses, and so on. Medical treatment included administration of steroids, salicylazosulfapyridine, metronidazole, trimethoprimsulphamethoxazole, and ampicillin. Complications occurred in 17 patients. One patient died; thus, there as a case mortality rate of 2.3. The clinical status as classified in 23 patients available for intervie and revie. Their Crohn's disease activity index as calculated 1 ": Six ere very good, eight ere good, six ere poor, and three ere very poor. Discussion This study as performed in the municipal area of Tel-Aviv-Yafo, hich is ell defined geographically ith a relatively stable urban population due to a balance beteen immigration and births on the one hand and emigration and deaths on the other. The Jeish population of Tel-Aviv-Yafo ith its various community groups has characteristics that make it highly suitable for an epidemiologic investigation of Crohn's disease.' 19 The incidence and prevalence rates of Crohn's disease found in Tel-Aviv are belo the usual range as estimated by Mendeloff, based on his revie of United States and European data. 12 Similarly, the authors' figures are significantly loer than those in most of the recent published series summarized in Table 3. In addition, the authors' series includes 5 patients ho developed Crahn's disease before immigrating to Israel and thereby increased the prevalence rate for Tel-Aviv residents. Similarly, this explains hy the prevalence rate for American born Jes of European descent approaches the rate found in several European countries (Tables 1 and 2). Be- cause of the semisocialized medical system in the the Tel-Aviv area, it is unlikely that the authors have significantly underestimated the incidence of clinically apparent Crohn's disease. Crohn's disease may be misdiagnosed; for example, colonic cases may be mistaken for ulcerative colitis. Hoever, even this disease is less frequent among the Tel-Aviv population as compared ith that of the United States, England, and Denmark. 13 Chronic infectious diseases such as tuberculosis, amebic colitis, and so on are rare in the Tel-Aviv area. Similarly, intestinal lymphoma, hich must be considered in the differential diagnosis, has also been rare in recent years among the Tel-Aviv population. 22 As shon in Figure 1, there as a rising incidence of Crohn's disease up to the prevalence date. Although Hoj et al. believed that the rising incidence in Copenhagen as due to a loer diagnostic threshhold,z3 the authors believe that this can be explained only in part by an increased aareness of the disease and thus represents a true tendency. Since the survey, the authors have been very much impressed by the number of ne patients seen ith recent Crohn's disease, especially colonic, diagnosed ith colonoscopy. This rising incidence has been ell noted in many other recent publications.'-7 The lo incidence and prevalence of Crohn's disease in the total Jeish population of Tel-Aviv-Yafo in general and even in the Ashkenazi community specifically are of even greater interest because the disease has been considered to be more prevalent among urban Jes in the United States irrespective of their country of origin."-1o.12 The validity of some of these observations has already been discussed by Gilat et al. in relation to ulcerative colitis.'3 The main criticism is that only a fe series relate to a defined population; the others either are based on hospital- Table 2. Comparison of Complication, Surgery, and Mortality Rates ith Recently Published Series of Crohn's Disease Series Perianal disease Internal Fistulae Both External Intestinal obstruction Surgery Mortality Present series Williams 20 Farmer et al!1 Novis et al." Bergman and Krause 5 de Dombal 22 Cook 23 Miller et af Fahrlander and Baerlocher 3 Brahme et al. B Evans (0.04) (0.14) (O.lW ( ) Per 10 5 of population.

5 January 1979 CROHN'S DISEASE IN TEL-AVIV 29 Table 3. Comparison of Incidence and Prevalence (per 10" population) of Crahn's Disease in Recent Series Series Area Period Incidence Prevalence Present series Total Ashkenazim Mendeloff12 Novis et aly Bergman and Krause 5 Brahme et a\.6 Miller et au Hoj et a\.23 Fahrliinder and Baerlocher 3 Myren et a\.4 Kyle 2 de DombaF" Tel-Aviv Tel-Aviv USA and Europe Cape Ton Central Seden Malmo Nottingham Copenhagen Basle Noray (hospitals) Scotland Leeds (hite population) 2.8" (Jeish population) o Significantly different from this series (total and Ashkenazim) (P < 0.01) ith the Student's t-test. izations or referrals or are confined to selected population groups. Even so, this disproportionately high incidence among Ashkenazi Jes as also noted by Brahme et a1. in Malm0 6 and by Novis et a1. in Cape Ton. ll In both these series, the authors ere dealing ith a defined population, and this strengthened the American vie that the disease occurs excessively among Ashkenazi Jes. On the other hand, other ell-defined English and European surveys have not confirmed a higher prevalence among Jes: This difference possibly indicates the presence of a variable environmental factor, although inaccuracies associated ith small numbers and a dearth of demographic data, especially concerning the number of Jes in the population, are difficult to exclude. As indicated, Crohn's disease occurs in all the Jeish community groups found in Tel-Aviv-Yafo, although significantly more frequently in Ashkenazi Jes (those born in Europe or America), and is uncommon in Israeli born or non-ashkenazi Jes. This finding is consistent ith the author's previous report of lo incidence of ulcerative colitis among the Tel-Aviv Jeish population and parallels its distribution among the community groups.'3 Considering that the prevalence of Crohn's disease in the Tel Aviv Ashkenazi population is apparently loer than that found in the Ashkenazi population of America, South Africa, and so on, it may suggest that the (genetic?) predisposition to the disease is affected by environmental factors. It is of interest that all the Israeli-born Jes ith Crohn's disease ho ere located are Ashkenazim. Among the environmental factors considered ere the dietary habits of the Tel-Aviv population. In general, the Tel-Aviv population consumes more carbohydrate and fiber and less fat and meat than the American population, hereas Ashkenazim eat more meat, milk, and eggs than the non-ashkenazim, ho eat more nonmeat protein. 27 These moderate differences in diet, especially the importance of meat protein, must be further investigated in order to establish their relevance to the etiology of Crohn's disease. Given the rising incidence, it can also be speculated that there is an infectious agent peculiar to the United States and Europe that causes this chronic granulomatous disease and that it has no been introduced into this geographic area. The bimodal age distribution and lack of significant difference of incidence beteen the sexes are consistent ith many other series.' 5. ' 2 The authors agree ith Mendeloff that the number of pediatric cases may be underestimated, as their screening as not aimed at this group.12 In comparison ith recently published data on Crohn's disease regarding complication, surgery, and mortality rates, the authors' data ere relatively lo (Table 3). Even though their series is small, it raises the question as to hether Crohn's disease in the Tel-Aviv area is a less severe form of disease. A similar question as raised ith regard to ulcerative colitis. 2B The results of this survey confirm the authors' clinical impression that inflammatory boel disease in general and Crohn's disease in particular are not common in the Jeish population of Tel-Aviv, and the severity of the disease may also be less marked than in the United States and Europe. The strikingly higher prevalence in the Ashkenazi community, especially in the Israeli born population, suggests a hereditary predisposition. The apparent differences of incidence of Crohn's disease among Ashkenazi Jes in various parts of the orld may relate to environmental factors.

6 30 ROZEN ET AL. GASTROENTEROLOGY Vol. 76, No.1 References 1. Evans J G: The epidemiology of Crohn's disease. In Clinics in Gastroenterology: Crohn's Disease. Edited by BN Brooke. London, W.B. Saunders Co., 1972, p Kyle J: An epidemiological study of Crohn's disease in Northeast Scotland. Gastroenterology 61: , Fahrliinder H, Baerlocher CH: Clinical features and epidemiological data on Crohn's disease in the Basle area. Scand J Gastroenterol 6: , Myren J, Gjone E, Hertzberg IN, Rygvold D, Semb LS, Fretheim B: Epidemiology of ulcerative colitis and regional enterocolitis (Crohn's disease) in Noray. Scand J Gastroenterol 6: , Bergman L, Krause U: The incidence of Crohn's disease in central Seden. Scand J Gastroenterol 10: , Brahme F, Lindstrom C, Wenckert A: Crohn's disease in a defined population. An epidemiological study of incidence, prevalence, mortality and secular trends in the city of Malmo, Seden. Gastroenterology 69: , Miller DS, Keighley AC, Langman MJS: Changing patterns in epidemiology of Crohn's disease. Lancet 2: , Acheson ED: The distribution of ulcerative colitis and regional enteritis in United States veterans ith particular reference to the Jeish religion. Gut 1: , Monk M, Mendeloff AI, Siegel CI, Lilienfeld A: An epidemiological study of ulcerative colitis and regional enteritis among adults in Baltimore. II. Social and demographic factors. Gastroenterology 56: , Rogers BHG, Clark LM, Kirsner JB: The epidemiologic and demographic characteristics of inflammatory boel disease: and analysis of a computerized file of 1400 patients. J Chronic Dis 24: , Novis BH, Marks IN, Bank S, Lou JH: Incidence of Crohn's disease at Groote Schuur Hospital during S Afr Med J 49: , Mendeloff AL: The epidemiology of idiopathic inflammatory boel disease. In Inflammatory Boel Disease. Edited by JB Kirsner, RG Shorter. Philadelphia, Lea & Febiger, 1975, p Gilat T, Ribak J, Benaroya Y, Zemishlany Z, Weissman I: Ulcerative colitis in the Jeish population of Tel-Aviv-Yafo. I. Epidemiology. Gastroenterology 66: , Statistical Year Book for Department of Research and Statistics, Tel-Aviv-Yafo Municipality. 15. Morson BC: Pathology of Crohn's disease. In Clinics in Gastroenterology: Crohn's Disease. Edited by BN Brooke. London, W.B. Saunders Co., 1972, p Lennard-Jones JE: Differentiation beteen Crohn's disease, ulcerative colitis and diverticulitis. In Clinics in Gastroenterology: Crohn's Disease. Edited by BN Brooke. London, W.B. Saunders Co., 1972, p Marshak RH, Linder AE: Roentgen features of Crohn's disease. In Clinics in Gastroenterology: Crohn's Disease. Edited by BN Brooke. London, W. B. Saunders, 1972, p Best WR, Becktel JM, Singleton JW, Kern F: Development of a Crohn's disease activity index. National cooperative Crohn's disease study. Gastroenterology 70: , Shorter RG, Shephard DHE: Frontiers in inflammatory boel disease. The proceedings of a conference sponsored by the McReynolds Foundation. Part 1. Am J Dig Dis 20: , Williams JA: Surgery and management of Crohn's disease. In Clinics in Gastroenterology: Crohn's Disease. Edited by BN Brooke. London, W. B. Saunders Co., 1972, p Farmer RG, Hak WA, Turnbull RB Jr: Clinical patterns in Crohn's disease: a statistical study of 615 cases. Gastroenterology 68: , Rozen p, Flatau E, Schujman E, Gefel A: Variability of splenomegaly in Crohn's disease. Am J Gastroenterol 67: , Hoj L, Brix Jensen P, Bonnevie 0, Riis P: An epidemiological study of regional enteritis and acute ileitis in Copenhagen county. Scand J Gastroenterol 8: , Keighley A, Miller DS, Hughes AO, Langman MJS: The demographic and social characteristics of patients ith Crohn's disease in the Nottingham area. Scand J Gastroenterol11: , Cooke WT: Survey of results of treatment of Crohn's disease. In Clinics in Gastroenterology: Crohn's Disease. Edited by BN Brooke. London, W. B. Saunders Co., 1972, p de Dombal IT: Symposium on Crohn's disease: epidemiology and natural history. Proc R Soc Med 64:161, Bavly S: Levels of nutrition in Israel 1968/9. Central Bureau of Statistics, Special Services No. 368, Jerusalem Gilat T, Lilos P, Zemishlany Z, Ribak J, Benaroya Y: Ulcerative colitis in the Jeish population of Tel-Aviv-Yafo. III. Clinical course. Gastroenterology 70:14-19, 1976