Israel has a high rate of Jewish immigration and a high prevalence of inflammatory bowel disease (IBD).

To compare IBD prevalence in first-generation immigrants vs Israel-born Jews.

Patients with a diagnosis of IBD as of June 2020 were included from the validated epi-IIRN (Israeli IBD Research Nucleus) cohort that includes 98% of the Israeli population. We stratified the immigration cohort by IBD risk according to country of origin, time period of immigration, and age group as of June 2020.

A total of 33544 patients were ascertained, of whom 18524 (55%) had Crohn's disease (CD) and 15020 (45%) had ulcerative colitis (UC); 28394 (85%) were Israel-born and 5150 (15%) were immigrants. UC was more prevalent in immigrants (2717; 53%) than in non-immigrants (12303, 43%, P < 0.001), especially in the < 1990 immigration period. After adjusting for age, longer duration in Israel was associated with a higher point prevalence rate in June 2020 (high-risk origin: Immigration < 1990: 645.9/100000, ≥ 1990: 613.2/100000, P = 0.043; intermediate/low-risk origin: < 1990: 540.5/100000, ≥ 1990: 192.0/100000, P < 0.001). The prevalence was higher in patients immigrating from countries with high risk for IBD (561.4/100000) than those originating from intermediate-/low-risk countries (514.3/100000; P < 0.001); non-immigrant prevalence was 528.9/100000.

Lending support to the environmental effect on IBD etiology, we found that among immigrants to Israel, the prevalence of IBD increased with longer time since immigration, and was related to the risk of IBD in the country of origin. The UC rate was higher than that of CD only in those immigrating in earlier time periods.

There are currently no nationwide data on the epidemiology of inflammatory bowel diseases (IBD) in Israel. We aimed to determine the population-based epidemiological trends of IBD in the diverse Israeli population.

Health-administrative data were retrieved from all 4 Israeli health maintenance organizations, insuring 98% of the population, using validated identification algorithms. National trends were determined using Joinpoint regression analysis calculating annual percent change and average annual percent change (AAPC).

By 2019, there were 46,074 patients with IBD in Israel, corresponding to a national prevalence of 519/100,000 (0.52%), of whom 54.1% had Crohn disease (CD) and 45.9% had ulcerative colitis (UC). The number of Jewish patients doubled from 18,701 in 2005 (354/100,000) to 38,950 (589/100,000) in 2018 (AAPC, +4.0%; P < 0.05), and the number of Arab patients increased 3-fold from 1096 (102.1/100,000) to 3534 (240.7/100,000; AAPC, +6.8%; P < 0.05) during the same years. However, the increase rate has gradually decelerated over time (annual percent change during 2005-2008, 2009-2014, and 2005-2018 was +6.7%, +4.2%, and +2.3%, respectively; P < 0.05). Pediatric prevalence increased from 37.4 to 52.2/100,000, with CD predominating in both Jews and Arabs. The incidence of CD remained stable (from 15.9/100,000 to 14.9/100,000) and the incidence of UC decreased (15.4/100,000 to 10.5/100,000 (AAPC, -3.2%; P < 0.001)). In contrast, pediatric incidence of CD increased from 7.3/100,000 to 8.3/100,000 (AAPC, +1.9%; P < 0.05) and that of UC increased from 2.6 to 4.4/100,000 (AAPC, +5.8%; P < 0.05).

The IBD prevalence rate in Israel is still increasing but gradually decelerating, probably due to the decreasing overall IBD incidence. Nonetheless, incidence rate in children is still increasing. Ongoing narrowing in the rates between Jews and Arabs over time may indicate shared environmental factors.

The influence of cutaneous cellular infiltration on the phenotype of bullous pemphigoid (BP) remains to be established.

To evaluate the main histopathological characteristics of patients with BP and to assess the association between the composition of lesional inflammatory infiltrate and the various clinical, immunological and immunopathological aspects of the disease.

Retrospective study encompassing patients diagnosed with BP throughout the years 2009-2020 in a specialized tertiary referral centre.

The study encompassed 136 patients with BP, of whom 27 (19.9%) demonstrated a cell-poor inflammatory infiltrate in lesional skin specimens. Overall, 78 (57.4%), 71 (52.2%) and 5 (3.7%) specimens were found to include eosinophil-predominant, lymphocyte-predominant and neutrophil-predominant inflammatory infiltrates, respectively. Relative to the remaining patients with BP, those with an eosinophil-predominant inflammatory infiltrate had higher (90.8% vs. 77.2%; P = 0.030) whilst those with a cell-poor inflammatory infiltrate lower (70.3% vs. 88.7%; P = 0.017) seropositivity of anti-BP180 NC16A IgG. The latter subgroup presented with higher prevalence of mucosal involvement (25.9% vs. 8.3%; P = 0.011) and a non-inflammatory clinical phenotype (50.0% vs. 17.1%; P = 0.041). Patients with lymphocyte-predominant inflammatory infiltrate manifested with higher severity BPDAI scores and a lower frequency of the non-inflammatory subtype (11.1% vs. 36.4%; P = 0.035), whilst those with a neutrophilic infiltrate presented with lower mean (SD) levels of anti-BP180 NC16A IgG [269.3 (227.6) vs. 722.7 (1499.6) U/mL; P = 0.003].

Eosinophil-predominance and high cellularity in the lesional inflammatory infiltrate of BP skin are associated with increased seropositivity of anti-BP180 NC16A IgG. Lymphocyte-predominant infiltrates predict a more severe phenotype, pointing towards a pathogenic role of autoreactive lymphocytes.

Although Crohn's disease (CD) is an established underlying disease in pyoderma gangrenosum (PG), studies comparing patients with PG and controls with respect to the presence of CD are lacking. Consequently, the relative risk imposed by CD for the development of PG is yet to be elucidated.

The study aims to quantify the magnitude of the association between CD and subsequent development of PG, thus enabling to evaluate the risk of PG with CD.

A matched case-control study was conducted in Israel comparing PG patients (N = 302) with age-, sex- and ethnicity-matched control subjects (N = 1497) regarding the presence of CD. Logistic regression model was used for multivariate analysis.

The prevalence of CD was higher in patients with PG than in control subjects (7.0% vs. 0.3%, respectively; p < .001). There was a 28-fold increase in the odds of PG with CD (OR, 28.08; 95% CI, 9.56-82.41). This association was robust to a sensitivity analysis excluding CD cases diagnosed up to 3 years prior to PG (OR, 30.30; 95% CI, 8.82-104.09), and to a multivariate analysis adjusting for confounding factors (OR, 21.57; 95% CI, 7.20-64.58). The median latency between the diagnosis of CD and the development of PG was 8.08 years. Patients with both PG and CD were younger and had a higher prevalence of smoking when compared to other patients with PG.

CD increases the odds of having PG by 28-folds. Patients with CD should be advised to avoid additional precipitating factors of PG like pathergy and smoking.

Limited evidence supports a link between hidradenitis suppurativa (HS) and Crohn disease (CD), and this relationship has not been established in the United States.

To evaluate the prevalence of CD among patients with HS in the United States and to determine the strength of association between the 2 conditions.

Cross-sectional analysis of data from 51 340 patients with HS identified using electronic health records data in the Explorys multiple health system data analytics and research platform, which includes data from more than 50 million unique patients across all US census regions.

Primary outcome was diagnosis of CD.

Of the 18 455 660 total population considered, 51 340 had HS (35 000 women). Of these patients with HS, 29 010 (56.5%) were aged 18 to 44 years; 17 580 (34,2%), 45 to 64 years; and 4750 (9.3%), 65 years or older. Prevalence of CD among patients with HS was 2.0% (1025/51 340), compared with 0.6% (113 360/18 404 260) among those without HS (P < .001). Prevalence of CD was greatest among patients with HS who were white (2.3%), aged 45 to 64 years (2.4%), nonobese (2.8%), and tobacco smokers (2.3%). In univariable and multivariable analyses, patients with HS had 3.29 (95% CI, 3.09-3.50) and 3.05 (95% CI, 2.87-3.25) times the odds of having CD, respectively, compared with patients without HS. Crohn disease was associated with HS across all patient subgroups. The association was strongest for men (OR, 3.61; 95% CI, 3.24-4.03), patients aged 45 to 64 years (OR, 3.49; 95% CI, 3.16-3.85), nonobese patients (OR, 4.09; 95% CI, 3.69-4.54), and nonsmokers (OR, 3.44; 95% CI, 3.10-3.82).

These data suggest that patients with HS are at risk for CD. Gastrointestinal symptoms or signs suggestive of CD warrant additional evaluation by a gastroenterologist.

The incidence and prevalence trends of inflammatory bowel disease (IBD) vary between developed and developing countries.

To investigate the prevalence and associated sociodemographic factors of IBD in Israeli Jewish adolescents METHODS: The files of the army medical corps were reviewed for adolescents recruited in 2002-2016 with confirmed IBD. Covariate data included birth date, patient and parental country of birth, number of children in the household, age at diagnosis, and socioeconomic status. Findings were compared with the remaining recruits without IBD.

Of the 1,144,213 adolescents recruited, 2372 (0.2%) had IBD (Crohn's disease, 68%). Median age of the cohort was 17.1 years (interquartile range, 16.9-17.3). Over the study period, the annual point prevalence per 100,000 examinees significantly increased: total IBD, 58 to 373; Crohn's disease, 42 to 425; ulcerative colitis, 16 to 128. Mean age at IBD diagnosis decreased from 15.0 ± 2.8 years in 2002-2008 to 14.3 ± 3.1 years in 2009-2016 (P < 0.0001). Significance was maintained on separate analyses of Crohn's disease and ulcerative colitis. Both diseases were significantly less prevalent in subjects from families with at least one parent born in a developing country and ≥3 children. There was a significant association of lower socioeconomic status with lower prevalence of Crohn's disease (odds ratio 0.41, 95% confidence interval, 0.31-0.54) and ulcerative colitis (odds ratio 0.25, 95% confidence interval, 0.15-0.42).

The point prevalence of Crohn's disease and ulcerative colitis in Israeli Jewish adolescents increased six-fold and eight-fold, respectively, over 15 years along with a decrease in age at diagnosis.

Data on inflammatory bowel disease (IBD) phenotypes among the Arab population in Israel or in the neighboring Arab countries is scarce.

We aimed to assess differences in disease phenotype among Arab and Jewish children living in Israel.

We performed a retrospective chart review of pediatric IBD cases, which were diagnosed at the Schneider Children's Medical Center and Ha'Emek Medical Center in Israel between 2000 and 2014. Demographic, clinical, and phenotypic variables were compared between Arabs and Jews from Eastern (Sephardic) and Western (Ashkenazi) origin.

Seventy-one Arab children with IBD were compared with 165 Ashkenazi and 158 Sephardic Jewish children. Age and gender did not differ between groups. Sephardic and Ashkenazi Jewish Crohn's disease (CD) patients had significantly more stenotic behavior (24 and 26 vs. 5%, p = 0.03) and less fistulzing perianal disease (15 and 11 vs. 31%, p = 0.014) compared with Arab patients. Arab children with ulcerative colitis (UC) had more severe disease at diagnosis compared to Sephardic and Ashkenazi Jews reflected by higher Pediatric UC Activity Index (45 vs. 35 and 35, respectively, p = 0.03). Arab patients had significantly lower proportion of anti-Saccharomyces cerevisiae antibodies positivity (in CD) and perinuclear anti-neutrophil cytoplasmic antibodies positivity (in UC) than both Sephardic and Ashkenazi Jewish children (23 vs. 53 and 65%, p = 0.002 and 35 vs. 60 and 75%, respectively, p = 0.002).

Arab and Jewish children with IBD differ in disease characteristics and severity. Whether genetic or environmental factors are the cause for these differences is yet to be determined.

The incidence of Crohn's disease has been increasing in developed countries; whether this trend has extended to countries in Middle East, especially in the Arab world, remains unclear. Our aim was to study the epidemiology, incidence, time trends and clustering of Crohn's disease within the population of the Kingdom of Bahrain.

A retrospective case-cohort study was conducted on patients diagnosed with Crohn's disease at Bahrain Specialist Hospital between 1990 and 2015. The diagnosis was based on clinical, radiological, endoscopic, and histological examinations.

Five hundred twenty-two cases were eligible for analysis; 14.5% were below the age of 19 with a male-to-female ratio of 1.1:1. The overall incidence was 4.8/100,000 person-years and significantly increased from 5.5/100,000 person-years during the 1990's to 8.0/100,000 person-years during the last study period [incidence rate ratio (IRR) 0.32, 95% CI = 0.26-0.42]. This trend was persistent for adults, children, men and women. There were 129 patients with at least one family member diagnosed with Crohn's disease consisting of 40 families. Three clusters were identified based on first or second degree relationship of the family member. The mean interval for diagnosis between family members was significantly shorter between siblings than second degree relatives; (2.0 ± 1.2 years) versus (5.0 ± 2.8 years), respectively; (P = 0.04).

The incidence rate of Crohn's disease in Bahrain is comparable to the U.S.A and has increased for men and women in all age groups. Crohn's disease clusters were common among families and included up to 3 generations consistent with presence of a common source or common genetic factors.

The development and characteristics of inflammatory bowel disease (IBD) in Ethiopian Jewish immigrants to Israel were investigated.

A case-control study was conducted in 7 tertiary care hospitals in Israel. Patients of Ethiopian origin with IBD >6 months were included. Time of disease onset after immigration and age at diagnosis were recorded. Randomly chosen patients with IBD of Ashkenazi Jewish origin served as controls. Demographics and clinical parameters were compared between the 2 cohorts.

Thirty-two Ethiopian patients with IBD were compared with 33 Ashkenazi Jewish patients with IBD. Crohn's disease (CD) was more prevalent than ulcerative colitis (UC) in the Ethiopian group compared with the Ashkenazi group (94% versus 73%, P = 0.02). No Ethiopian-origin patient had a positive family history of IBD compared with 42% of Ashkenazi-origin patients (P < 0.001). Arthritis was more common in Ashkenazi than in Ethiopian patients (27% versus 3%, P < 0.01). One Ashkenazi patient with CD had upper gastrointestinal involvement compared with 7 (23%) in the Ethiopian group (P < 0.02). All other clinical measures were similar between the 2 cohorts. The Ethiopian group lived in Israel with a mean of 13 ± 5 years, and 75% were born in Ethiopia. The shortest time between immigration and developing IBD was 8 years (range, 8-26; median 16 yrs). No Ethiopian patient was diagnosed before immigration.

Ethiopian Jews migrating to Israel are at risk of developing IBD. Larger cohorts are needed to determine the relative importance of environmental and genetic factors that cause IBD in these patients.

Inflammatory bowel disease (IBD) has been associated with genetic and environmental factors, including urban living. IBD was rare in the Israeli Bedouin community 30 years ago. Over recent decades, a large proportion of this community has undergone a transition from a nomadic to a western lifestyle. Our aim was to carry out an updated evaluation of the clinical and epidemiological features of IBD in the Bedouin sector of southern Israel.

All Bedouin patients with a known diagnosis of Crohn's disease (CD) or ulcerative colitis (UC) were included in the retrospective study.

The cohort included 31 CD patients and 31 UC patients. The mean age of the patients at diagnosis was 29±10.9 and 35±17.5 years for CD and UC, respectively. The prevalence rate for CD was 15.5/100,000 and the incidence rate was 0.8-3.55/100,000. Fourteen of the CD patients (45%) had ileal disease and 64.5% had inflammatory disease behavior according to the Montreal classification. Eleven of the CD patients (35%) were treated with anti-TNF-α and 26% had undergone surgery. Over the previous decade, the prevalence of UC was 14/100,000 and the incidence was 0.5-2.39/100,000. Eighteen UC patients (58%) had left-sided colitis. Three (9.7%) had undergone total colectomy for severe disease.

We found an increased prevalence of IBD in the Bedouin population, associated with their change in lifestyle over previous decades. However, the prevalence is still markedly lower than that in other population groups. A high percentage of patients were treated with anti-TNF-α and/or surgery.

Inflammatory bowel diseases (IBD) are idiopathic chronic diseases of the gastrointestinal tract well known to be associated with both genetic and environmental risk factors. Permissive genotypes may manifest into clinical phenotypes under certain environmental influences and these may be best studied from migratory studies. Exploring differences between first and second generation migrants may further highlight the contribution of environmental factors towards the development of IBD. There are few opportunities that have been offered so far. We aim to review the available migration studies on IBD, evaluate the known environmental factors associated with IBD, and explore modern migration patterns to identify new opportunities and candidate migrant groups in IBD migration research.

To determine the prevalence of inflammatory bowel disease among the 1.5 million Arab residents in Israel who represent 20% of the total population.

Family physicians in all Arab towns and villages were contacted to obtain information on patients with inflammatory bowel disease. Relevant clinical data were retrieved and updated to December 31, 2009.

Information was obtained from 23/71 municipalities approached (representing 200,000 out of 1.5 million Arabs). There were 64 confirmed cases of Crohn's disease indicating a prevalence rate of 32/100,000. The rate of smoking within this cohort was lower than in the general population (1.5% vs. 40%; P<0.001). There were 44 confirmed cases of ulcerative colitis with a prevalence rate of 22/100,000. The percentage of active smokers in this cohort was 18%. Clinical remission or mild activity was observed in 75% of patients in both cohorts at the time of the survey. Fourteen patients (21%) had undergone surgery for Crohn's disease, whereas none had undergone surgery for ulcerative colitis. Twenty-eight (42%) patients with Crohn's disease and 20 (45%) with ulcerative colitis were on maintenance therapy with 5-aminosalicylic acid. Only 18% with Crohn's disease and 6.8% with ulcerative colitis had received anti-tumor necrosis factor. The most prevalent extra-intestinal manifestations were perianal disease (18%) in Crohn's disease, and arthralgia or arthritis (6.8%) in ulcerative colitis.

We found a low prevalence rate of inflammatory bowel disease in the Israeli Arab population.

Crohn's disease is a chronic inflammatory disorder affecting any part of the gastrointestinal tract, but frequently involves the small and large bowel. Typical presenting symptoms include abdominal pain and diarrhea. Patients with this disorder may also have extraintestinal manifestations, including arthritis, uveitis, and skin lesions. The PillCam™SB capsule is an ingestible disposable video camera that transmits high quality images of the small intestinal mucosa. This enables the small intestine to be readily accessible to physicians investigating for the presence of small bowel disorders, such as Crohn's disease. Four meta-analyses have demonstrated that capsule endoscopy identifies Crohn's disease when other methods are not helpful. It should be noted that it is the best noninvasive procedure for assessing mucosal status, but is not superior to ileocolonoscopy, which remains the gold standard for assessment of ileocolonic disease. Mucosal healing along the small bowel can only be demonstrated by an endoscopic procedure such as capsule endoscopy. Achievement of long-term mucosal healing has been associated with a trend towards a decreased need for hospitalization and a decreased requirement for corticosteroid treatment in patients with Crohn's disease. Recently, we have developed and validated the Capsule Endoscopy Crohn's Disease Activity Index (also known as the Niv score) for Crohn's disease of the small bowel. The next step is to expand our score to the colon, and to determine the role and benefit of a capsule endoscopy activity score in patients suffering from Crohn's ileocolitis and/or colitis. This scoring system will also serve to improve our understanding of the impact of capsule endoscopy, and therefore treatment, on the immediate outcome of this disorder. As the best procedure available for assessing mucosal status, capsule endoscopy will provide important information about the course and outcome of Crohn's disease.

To compare the cost versus utility of four guideline-recommended biologic treatments-infliximab, adalimumab, certolizumab pegol, and natalizumab-for the treatment of Crohn's disease from a United States payer perspective.

Cost-utility decision analytic model using a Monte Carlo simulation of 10,000 cases.

Published primary and tertiary literature.

Patients with moderate-to-severe Crohn's disease, as categorized by the Crohn's Disease Activity Index, that failed to respond to standard therapy and who were treatment naive to biologics.

The decision analytic model base case was a 35-year-old patient weighing 70 kg with moderate-to-severe Crohn's disease. Therapeutic efficacy data were obtained from published clinical trials. Online prescription drug, hospitalization data, and Current Procedural Terminology codes were used to estimate cost. Utility measures were estimated using published data obtained from patients with Crohn's disease. The time end point used for the model was 54 weeks. The analysis demonstrated considerable overlap in quality-adjusted life years gained with the four agents (i.e., mean values across four treatments 0.79-0.80). Although infliximab had the lowest median cost, there was overlap in the 95% confidence intervals (CIs) compared with the other three biologic products: mean (95% CI) cost for infliximab $22,663 ($19,105-26,433), adalimumab $27,515 ($23,796-31,584), certolizumab pegol $29,062 ($24,952-33,882), and natalizumab $31,166 ($25,915-37,195). However, the cost-effectiveness acceptability curve demonstrated that infliximab had the most scenarios (95.2%) when it was the most cost-effective biologic therapy using a willingness-to-pay threshold of $100,000/quality-adjusted life years gained.

Patients with moderate-to-severe Crohn's disease that failed to respond to standard treatment should preferentially receive infliximab as their initial biologic treatment, since this agent had the highest probability of being the most cost-effective therapy compared with the other biologic treatment options.

We conducted a systematic review to determine changes in the worldwide incidence and prevalence of ulcerative colitis (UC) and Crohn's disease (CD) in different regions and with time.

We performed a systematic literature search of MEDLINE (1950-2010; 8103 citations) and EMBASE (1980-2010; 4975 citations) to identify studies that were population based, included data that could be used to calculate incidence and prevalence, and reported separate data on UC and/or CD in full manuscripts (n = 260). We evaluated data from 167 studies from Europe (1930-2008), 52 studies from Asia and the Middle East (1950-2008), and 27 studies from North America (1920-2004). Maps were used to present worldwide differences in the incidence and prevalence of inflammatory bowel diseases (IBDs); time trends were determined using joinpoint regression.

The highest annual incidence of UC was 24.3 per 100,000 person-years in Europe, 6.3 per 100,000 person-years in Asia and the Middle East, and 19.2 per 100,000 person-years in North America. The highest annual incidence of CD was 12.7 per 100,000 person-years in Europe, 5.0 person-years in Asia and the Middle East, and 20.2 per 100,000 person-years in North America. The highest reported prevalence values for IBD were in Europe (UC, 505 per 100,000 persons; CD, 322 per 100,000 persons) and North America (UC, 249 per 100,000 persons; CD, 319 per 100,000 persons). In time-trend analyses, 75% of CD studies and 60% of UC studies had an increasing incidence of statistical significance (P < .05).

Although there are few epidemiologic data from developing countries, the incidence and prevalence of IBD are increasing with time and in different regions around the world, indicating its emergence as a global disease.

Common gastrointestinal diseases often exhibit geographic, cultural, and gender variations. Diseases previously less common in certain areas of the world have shown a recent increase in prevalence. Industrialization has traditionally been noted as a major cause for this epidemiologic evolution. However, environmental factors such as diet, hygiene, and exposure to infections may play a major role. Moreover, the way one disease presents in a certain location may vary significantly from the way it manifests in another culture or location. This article discusses global variations of inflammatory bowel disease, Helicobacter pylori, irritable bowel disease, fecal incontinence, hepatitis B, and hepatocellular cancer.

In the West, the incidence and prevalence of inflammatory bowel diseases has increased in the past 50 years, up to 8-14/100,000 and 120-200/100,000 persons, respectively, for ulcerative colitis (UC) and 6-15/100,000 and 50-200/100,000 persons, respectively, for Crohn's disease (CD). Studies of migrant populations and populations of developing countries demonstrated a recent, slow increase in the incidence of UC, whereas that of CD remained low, but CD incidence eventually increased to the level of UC. CD and UC are incurable; they begin in young adulthood and continue throughout life. The anatomic evolution of CD has been determined from studies of postoperative recurrence; CD begins with aphthous ulcers that develop into strictures or fistulas. Lesions usually arise in a single digestive segment; this site tends to be stable over time. Strictures and fistulas are more frequent in patients with ileal disease, whereas Crohn's colitis remains uncomplicated for many years. Among patients with CD, intestinal surgery is required for as many as 80% and a permanent stoma required in more than 10%. In patients with UC, the lesions usually remain superficial and extend proximally; colectomy is required for 10%-30% of patients. Prognosis is difficult to determine. The mortality of patients with UC is not greater than that of the population, but patients with CD have greater mortality than the population. It has been proposed that only aggressive therapeutic approaches, based on treatment of early recurrent lesions in asymptomatic individuals, have a significant impact on progression of these chronic diseases.

The hygiene hypothesis offers an explanation for the correlation, well-established in the industrialized nations of North and West, between increased hygiene and sanitation, and increased rates of asthma and allergies. Recent studies have added to the scope of the hypothesis, showing a link between decreased exposure to certain bacteria and parasitic worms, and increased rates of depression and intestinal auto-immune disorders, respectively. What remains less often discussed in the research on these links is that women have higher rates than men of asthma and allergies, as well as many auto-immune disorders, and also depression. The current paper introduces a feminist understanding of gender socialization to the epidemiological and immunological picture. That standards of cleanliness are generally higher for girls than boys, especially under the age of five when children are more likely to be under close adult supervision, is a robust phenomenon in industrialized nations, and some research points to a cross-cultural pattern. I conclude that, insofar as the hygiene hypothesis successfully identifies standards of hygiene and sanitation as mediators of immune health, then attention to the relevant patterns of gender socialization is important. The review also makes clear that adding a feminist analysis of gender socialization to the hygiene hypothesis helps explain variation in morbidity rates not addressed by other sources and responds to a number of outstanding puzzles in current research. Alternative explanations for the sex differences in the relevant morbidity rates are also discussed (e.g., the effects of estrogens). Finally, new sources of evidence for the hygiene hypothesis are suggested in the form of cross-cultural and other natural experiments.

Inflammatory bowel diseases (IBD) are chronic diseases of the intestinal tract which principally are composed of ulcerative colitis (UC) and Crohn's disease (CD). The prevalence and incidence of both forms of IBD have historically been higher in developed countries with decreasing North-South gradient. However, more recent evidence demonstrate changing demographics as countries become more developed and immigration increases from underdeveloped countries to developed countries. Typically these changes are marked by an increase in ulcerative colitis followed by an increase in CD. Thus, most if not all human populations appear to be susceptible to IBD under certain environmental influences. Several hypothesis have been advanced to explain these changing demographics including alterations in the bowel microflora, but direct experimental evidence is lacking in most cases. Celiac disease or gluten-sensitive enteropathy is a related inflammatory condition which is induced in susceptible individuals when exposed to gluten-containing foods. Similarly, the prevalence of celiac disease is increasing as the consumption of gluten-containing foods is increasing worldwide.

Previous studies have estimated a prevalence of a broad grouping of autoimmune diseases of 3.2%, based on literature review of studies published between 1965 and 1995, and 5.3%, based on national hospitalization registry data in Denmark. We examine more recent studies pertaining to the prevalence of 29 autoimmune diseases, and use these data to correct for the underascertainment of some diseases in the hospitalization registry data. This analysis results in an estimated prevalence of 7.6-9.4%, depending on the size of the correction factor used. The rates for most diseases for which data are available from many geographic regions span overlapping ranges. We also review studies of the co-occurrence of diseases within individuals and within families, focusing on specific pairs of diseases to better distinguish patterns that may result in insights pertaining to shared etiological pathways. Overall, data support a tendency for autoimmune diseases to co-occur at greater than expected rates within proband patients and their families, but this does not appear to be a uniform phenomenon across all diseases. Multiple sclerosis and rheumatoid arthritis is one disease pair that appears to have a decreased chance of coexistence.