Inflammatory bowel disease in African-American children living in Georgia

I

Inflammatory bowel disease in African-American

children living in Georgia Sesi O. Ogunbi, MD, James A. Ransom, MPH, Kevin Sullivan, PhD, MPH, MHA, Bess T. Schoen, MD, and Benjamin D. Gold, MD

We describe the clinical characteristics of inflammatory bowel disease (IBD) in African-American compared with non-African-American children. We identified 172 children with IBD; forty-nine (29%) were African-American. Median symptom duration before IBD diagnosis in African-American children (6 months) was shorter than that of non-African-American children (10 months). The most frequent presenting symptom was hematochezia (ulcerative colitis) and abdominal pain (Crohn’s disease) in both racial groups. The estimated incidence of Crohn’s disease in African-Americans ranged from 7 per 100,000 to 12 per 100,000, whereas the observed incidence in those with ulcerative colitis was between 5 and 7 per 100,000 during the 10 years of the study. Our pilot study suggests that IBD may be more common in African-American children than previously reported. Prospective population-based studies would be useful to determine whether inheritable factors linked with ethnicity are associated with IBD. (J Pediatr 1998;133:103-7.)

The epidemiology of inflammatory bowel disease including Crohn’s disease and ulcerative colitis has been studied since the first description of regional ileitis by Crohn et al.1 65 years ago. However, since the National Cooperative Crohn’s Disease Study, no major population-based investigations have changed our understanding of the ethnic distribution of IBD.2 In particular, the characteristics of IBD in African-American children are poorly established. A few studies have described the characteristics of IBD in people of African descent in South Africa3,4 and North America,5-8 and these studies fo-

cused primarily on adult patients with IBD. Epidemiologic studies of IBD by race, ethnicity, age, and geographic origin could identify inheritable and environmental factors contributing to the development of this disease. Our aim was to describe the epidemiology of IBD in children treated by us at Emory University, a major referral center for metropolitan Atlanta and the state of Georgia, from 1986 to 1995. In this study the clinical characteristics of Crohn’s disease and UC among African-American and non-African-American children are described. Furthermore we questioned whether significant differ-

From the Division of Pediatric Gastroenterology and Nutrition, the Department of Pediatrics, Emory University School of Medicine, Centers for Disease Control and Prevention, Rollins School of Public Health at Emory University, Atlanta, Georgia. Presented in part at the Annual Meeting of the North American Society for Pediatric Gastroenterology and Nutrition, November 2-4, 1995. Submitted for publication July 14, 1997; revision received Dec. 12, 1997; accepted Apr. 1, 1998. Reprint requests: Benjamin D. Gold, MD, Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, Emory University School of Medicine, 2040 Ridgewood Dr., NE, Atlanta, Georgia 30322. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/21/90769

ences exist between African-American and non-African-American children with IBD based on age group, sex, disease distribution (Crohn’s disease or UC), and presenting symptoms. IBD UC

Inflammatory bowel disease Ulcerative colitis

METHODS The diagnosis of IBD was defined in accordance with the Ninth Revision of the International Classification of Diseases.9 The codes used for initial chart evaluation encompassed the following diagnoses: UC, granulomatous colitis, regional or segmental colitis, Crohn’s disease or regional enteritis, granulomatous enterocolitis, and IBD. Charts of all children (both inpatients and outpatients) with these diagnoses monitored by us from 1986 and 1995 (inclusive of complete calendar years) were reviewed. Two children’s hospitals in metropolitan Atlanta are covered by our group; one is an 80-bed hospital affiliated with the Dekalb/Fulton county public medical complex and is located in downtown Atlanta, and the other is a tertiary care, subspecialty, 200-bed referral facility located on the Emory campus. Children with indeterminate colitis or intestinal infection (stool analysis with positive identification of enteric pathogens) were excluded. Diagnosis of Crohn’s disease or UC was based on endoscopic evaluation and histopathologic examination of endoscopic biopsy specimens or a surgical specimen in addition to clinical signs and symptoms, laboratory results, and radiologic findings. Clinical data extracted from the patients’ 103

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Table I. Description of ulcerative colitis and Crohn’s disease by race, sex, family history of IBD, age at diagnosis, and duration of symptoms, Emory University, 1986-1995

Ulcerative colitis Crohn’s disease Total Ulcerative colitis Males Females Total Ratio M:F Crohn’s disease Males Females Total Ratio M:F Family history of IBD Ulcerative colitis Crohn’s disease Total Age at diagnosis (yr) mean ± SE Ulcerative colitis Crohn’s disease Median duration of symptoms (mo) Ulcerative colitis Crohn’s disease

African-American No. (%)

Other No. (%)

Total No. (%)

15 (31) 34 (69) 49 (100)

37 (30) 86 (70) 123 (100)

52 (30) 120 (70) 172 (100)

7 (47) 8 (53) 15 (100) 0.9:1

17 (46) 20 (54) 37 (100) 0.9:1

24 (46) 28 (54) 52 (100) 0.9:1

23 (68) 11 (32) 34 (100) 2.1:1

51 (59) 35 (41) 86 (100) 1.5:1

74 (62) 46 (38) 120 (100) 1.6:1

0 (0) 4 (12) 4 (8)

13. 5 ± 0.5 12.9 ± 0.5

6.1 7.6

records included sex, race, age at diagnosis, presenting symptoms, duration of symptoms before diagnosis, family history of IBD (Crohn’s disease or UC), surgical procedures, and their indications and complications. Presenting symptoms were defined as follows: (1) bright red blood per rectum, hematochezia, (2) fever (any history or physical examination findings of temperature >38° C or 100.4° F), (3) joint problems (any history of joint complications or physical examination findings of stiffness, swelling, tenderness, limitation of passive/active motion), and (4) perianal disease (any history or physical examination findings of tags, fissures, abscesses, or fistulas). Patients with UC were categorized by degree of colonic involvement, namely proctitis, left-sided colonic, and pancolonic disease. Patients with Crohn’s disease were categorized by gastrointestinal tract site involved including gas104

5 (14) 20 (23) 25 (20)

5 (10) 24 (20) 29 (17)

11.4 ± 0.6 11.8 ± 0.4

10.3 9.7

troduodenal, diffuse small bowel disease, ileal, ileocolonic, and colonic. Race and ethnicity in all records were recorded consistent with divisions made in Georgia census data and included African-American (black, non-Hispanic), non-Hispanic white, Hispanic, and others. Denominators for both prevalence and incidence rates were taken from Georgia vital statistics report, and population trends over the past 10 years were evaluated. Referral patterns based on patient postal codes were also reviewed to determine whether there were changes in referral patterns over the study period. All rates are expressed per 100,000 population per year. Age- and sex-adjusted rates were calculated directly with the 1990 Georgia census figures as the standard.10 In the Atlanta metropolitan area (five counties) African-Americans numbered 327,473 (40.7%) and non-African-Americans 476,777 (59.3%) of the population 19

years of age and under compared with 748,256 (35.9%) and 1,336,696 (64.1%), respectively, for the state. All data were entered and maintained in Epi-info 6.0, and the statistical component was used to obtain frequencies and descriptive statistics. Fisher exact tests and χ2 analysis were performed. In addition, 2 × 2 tables were constructed to determine whether outcome (Crohn’s disease or UC) was independent of ethnicity, and within ethnicity, whether outcome was independent of sex. Differences between groups were considered significant at p < 0.05.

RESULTS In this study 172 children with the coding for IBD satisfied all inclusion/exclusion criteria for Crohn’s disease and UC; 49 African-American children with IBD were identified (28.5% of the study cohort; Table I). Among the non-AfricanAmerican children, 3 were Asian, 1 Hispanic, and the remaining 119 white. Of the 49 African-American children with IBD, 15 (31%) had UC, and 34 (69%) had Crohn’s disease. The corresponding distribution of UC and Crohn’s disease was similar for the 123 non-AfricanAmerican patients, 37 (30%) and 86 (70%), respectively (Table I). African-Americans were given diagnoses at an older age for both diseases (Table I). There was little difference in the ratio of males to females among patients with UC of both racial groups. However, a difference between sexes was noted for Crohn’s disease, with a male predominance in both AfricanAmerican (23 vs 11) and in non-AfricanAmerican children (52 vs 35). No family history of IBD was revealed in AfricanAmerican children with UC compared with 5 (14%) of 37 non-African-American children. However, 4 (15.4%) of 26 African-American children with Crohn’s disease and 20 (23%) of 87 non-AfricanAmerican patients with Crohn’s disease had first- or second-degree relatives with IBD. Detailed family pedigrees (>three generations) were available only on 20 (41%) of the African-American children. However, of these 20, 6 (30%) reported a history of first- or second-degree rela-

THE JOURNAL OF PEDIATRICS VOLUME 133, NUMBER 1 tives of European ancestry, evidence of racial intermixing in these patients. The presenting symptoms (Table II) and the location and extent of disease (Table III) were comparable in both racial groups. Eight (51%) African-American patients with UC had extensive pancolonic involvement (both endoscopic and histologic evidence) compared with 73% of all others with UC. The AfricanAmerican children with Crohn’s disease presented with multiple sites of involvement, which was comparable to the presentation in other racial groups. The ileum and colon were the most commonly involved areas of the gastrointestinal tract for both ethnic groups with Crohn’s disease (Table III). Three (20%) AfricanAmerican children with UC underwent total colectomy for fulminant colitis (two patients) or lack of response to medical therapy (one patient). Five (13.5%) nonAfrican-American patients with UC did not respond to medical therapy and underwent colectomy; however, no colectomies were performed on non-AfricanAmerican children with fulminant colitis. The most commonly observed complications among those African-American patients with Crohn’s disease were fistulas, 3 (9%), and strictures, 8 (24%). Indications for surgery in both racial groups with Crohn’s disease were comparable; 12 (35%) of the African-American children and 27 (31%) of the non-African-American children had major surgery including bowel resection as a result of their refractory disease (Table IV). The incidence of Crohn’s disease in African-American children seen by us over the 10-year period appeared to increase from 7 to 12 per 100,000, with a crude incidence rate of 8.8 per 100,000 for all children with Crohn’s disease. The incidence of UC for African-American children at our center appeared stable over the 10-year period, varying from 5 to 6.9 per 100,000, with a crude incidence rate of 5.3 per 100,000.

DISCUSSION Although the definitive genetic basis for IBD has not been characterized, a complex hereditary pattern may predis-

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Table II. Presenting symptoms of pediatric IBD in African-American compared with nonAfrican-American children

Ulcerative colitis

Abdominal pain Diarrhea BRBPR Anorexia Weight loss Growth failure Vomiting Fever Joint problems Perianal disease

Crohn’s disease

AfricanAmerican No. (%)

Other No. (%)

AfricanAmerican No. (%)

Other No. (%)

12 (80) 10 (67) 12 (80) 3 (20) 8 (53) 1 (7) 2 (13) 2 (13) 2 (13) 0 (0)

27 (73) 27 (72) 32 (87) 13 (35) 17 (47) 6 (17) 5 (14) 5 (14) 3 (8) 0 (0)

28 (82) 21 (64) 16 (49) 17 (52) 25 (76) 14 (41) 8 (24) 19 (59) 7 (21) 16 (50)

76 (92) 45 (55) 33 (41) 46 (62) 57 (74) 25 (30) 29 (36) 29 (38) 21 (26) 28 (33)

BRBPR, Bright red blood per rectum. Comparisons between African-American and non-African-American patients with Crohn’s disease and the presentation of fever demonstrated a statistically significant difference by χ2 analysis; Mantel-Haenszel at p < 0.05. No statistically significant differences were found between all other comparisons.

Table III. Disease location on presentation of IBD for African-American compared with non-African-American patients

Location

African-American (N)

Other (N)

4 3 8

1 9 27

0 0 5 15 6 8

1 2 16 39 15 13

Ulcerative colitis Rectum Left-sided Pancolonic Crohn’s disease Gastroduodenal Duodenum, jejunum and ileum Ileal Ileal colonic Colonic Not specified

Comparison of location of disease presentation in African-American versus non-African-American children with ulcerative colitis revealed a statistically significant difference (p < 0.05) by χ2 analysis. Comparison of location of disease presentation in African-American children with Crohn’s disease compared with non-African-American children with Crohn’s disease revealed no statistically significant differences.

pose susceptible individuals by means of environmental exposures to have IBD.11-14 Several studies demonstrated a higher prevalence of IBD in whites of European descent, particularly those of Jewish ancestry,2,15-18 compared with nonwhites. Other studies have reported a higher prevalence of IBD in developed countries compared with developing countries.19-21 Our preliminary study results show that IBD may be more preva-

lent in African-Americans than previously believed. The number of AfricanAmerican children with Crohn’s disease and UC was greater than one fourth of the IBD cohort followed by our center over the past 10 years; this number is higher than previously published pediatric and adult studies.8,19,20 One group estimated the incidence of Crohn’s disease among African-Americans to be 0.04 per 100,000 compared with an inci105

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Table IV. Indications for surgery comparing African-American versus non-African-American patients with IBD

Ulcerative colitis AfricanAmerican (N) Location Perianal disease Failed medical rx. Fulminant colitis Fistula Abscess Stricture Bleeding None

Crohn’s disease

Other (N)

0 0 2 0 0 0 0 13

0 5 0 0 1 0 6 25

AfricanAmerican (N) 0 2 0 3 0 8 0 22

Other (N) 0 3 1 6 9 8 0 59

Comparison of African-American children with ulcerative colitis versus non-African-American children by indications for surgery revealed a statistically significant difference dependent on ethnicity (p = 0.03).

dence of 1.35 per 100,000 in the general white population and 7 per 100,000 for American Jews.15 This is in contrast to estimated incidence rates in our IBD cohort, in which IBD was diagnosed in 7 to 12 per 100,000 African-American children per year, with crude incidences of 5.3 per 100,000 for UC and 8.8 per 100,000 for Crohn’s disease. The relatively large proportion of African-American children with IBD in our study may or may not be the result of the ethnic demographics of metropolitan Atlanta and the state of Georgia compared with previous studies in adults.8,19,22,23 Recent studies demonstrated a relatively small proportion of black patients with IBD (i.e., 3% of the entire study cohort) in Baltimore, Maryland, which has similar ethnic and racial demographics to Atlanta.23,24 The increased incidence of IBD at our center cannot be explained simply by an increased growth of the African-American population in the city or state over the 10year study period. The relative proportion of African-Americans has remained consistent from 1986 to 1995 in the face of an overall population increase in Atlanta and Georgia. We could not ascertain whether increased incidence rates could be explained by a change in access of African-Americans from public hospitals to the tertiary care university-affiliated children’s hospital. However, both the county public hospitals and the children’s 106

hospital are covered by our group, enabling us to assess and care for these patients at either site. Moreover, because there are other pediatric gastroenterologists in Georgia, the overall prevalence and incidence of IBD in African-American children at our center is more likely an underrepresentation of the true rates of disease in this group. In addition, when we tracked postal codes for our patients with IBD over the past 10 years, no dramatic changes in patient referral patterns were identified; therefore the latter factor could not be an explanation for the increasing incidence rates. The lack of data on IBD in black patients in African countries could be due either to lack of suspicion or to difficulties in making a diagnosis of IBD.20 This may have implications for the role of environmental exposures such as dietary changes, changes in infant feeding practices, or exposure to infectious pathogens or other environmental agents as etiologic factors leading to the development of IBD in African-Americans living in the United States. Recent studies provide compelling evidence for the role of environmental triggers in the genetically susceptible host in the development of IBD. Podolsky11 proposed two possible mechanisms: (1) IBD is initiated by an appropriate host gastrointestinal immune response to a yet-tobe identified enteric pathogen, or (2) IBD is caused by an abnormal, self-prop-

agating, intestinal immune response to a luminal antigen (i.e., infectious pathogen). Examples of environmental cofactors, particularly the possible role of an infectious agent, can be found in a mouse model of IBD; intestinal disease does not develop in immune-deficient animals reared in germfree conditions.25-28 Other environmental cofactors such as domestic hygiene were demonstrated in studies that observed an increase in Crohn’s disease incidence in households with increased amenities such as hot water and separate bathrooms.29 Others have shown an increased incidence of Crohn’s disease in populations moving from developing (i.e., India) to developed countries (i.e., United Kingdom).30 Whether racial intermixing and increased genetic susceptibility accompanied by environmental agents has contributed to the increased prevalence of IBD in AfricanAmericans remains to be determined. In our study the diagnosis of IBD was made at a later age but with a shorter duration of symptoms in African-American children compared with non-AfricanAmericans. No differences were observed in sex distribution in African-American children with IBD. However, there do not appear to be consistent patterns of sex distribution for children affected by either UC or Crohn’s disease reported in the literature.18,31-33 Multicenter studies will be necessary to determine whether access to health care and referral patterns compared with ethnic or environmental influences affect both age and duration of symptoms before diagnosis and sex distribution of children with IBD. We found a predominance of ileocolitis and colitis among our African-American children with Crohn’s disease, which is comparable to other descriptions of Crohn’s disease presentation in the pediatric population.34-37 In addition, the need for major abdominal surgery among the African-American children with Crohn’s disease was similar to surgery rates among the non-African-American children followed by us. Other studies have demonstrated more destructive disease and an increased need for major surgery in black children and adults with Crohn’s disease compared with whites.38,39 The predominance of total colonic disease in

THE JOURNAL OF PEDIATRICS VOLUME 133, NUMBER 1 all of our patients with UC <10 years of age (both racial groups) is also similar to that found in other studies.40,41 Our study is limited in being a retrospective chart review. Data collection and case ascertainment could not be controlled for, and patient data were not entirely uniform. Despite these limitations, we believe this preliminary study “challenges” the accepted dogma of the racial predisposition and prevalences in IBD. If the true prevalence of IBD is higher in African-Americans than previously thought, it suggests that IBD may be an inheritable disease influenced by a cohort effect consisting of racial changes and environmental exposures over time. Prospective and cross-sectional studies involving multiple geographic regions and centers are critical to allow better understanding of the epidemiology and possibly the pathogenesis of these chronic diseases. The authors thank Sandra M. Dubro for preparation of the article.

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