Global patterns of seasonal variation in gastrointestinal diseasesA Fares
Department of Medicine, Knappschafts Krankenhaus, Ruhr-University, Bochum, Germany
Objectives: This study reviewed previous studies to explore the global patterns of seasonal variation in gastrointestinal diseases. Study Design and Methods: A series of systematic literature reviews were undertaken to identify studies reporting seasonal and monthly data on clinical onset or relapse of gastrointestinal diseases (Acute pancreatitis, inflammatory bowel disease, Peptic ulcer diseases (PUD), gastroesophageal reflux disease, colon cancer and colonic diverticulitis). Thirty-two primary studies (published 1970-2012) from 17 countries were identified. Results: Upon review of the evidence, it appears that the seasonal peaks of PUD are most prominent in colder months while the peak of incidence rate of Crohn diseases in most of the countries subjects were found during the spring and summer seasons. Seasonal trend in the onset of acute pancreatitis exhibits a summer peak in some countries. There were no clearly seasonal peaks noted for the ulcerative colitis. Conclusions: Future experimental and observational studies should consider how the environmental factors (infection, cold, air pollution etc.) or other triggers (dietary habit, alcohol consumption) promotes or hinders such diseases.
Keywords: Digestive system diseases, periodicity, seasons
Although seasonality is a well-known phenomenon in the epidemiology of many diseases, simple analytical tools for the examination, evaluation and comparison of seasonal patterns are limited. Analyses of disease seasonality have also been restricted by the lack of precision inherent in using monthly or weekly means. Gastrointestinal diseases have been reported to be present throughout the year, but some particular months are associated with higher incidences.
Although the exact mechanism underlying the seasonal fluctuation of diseases is still not completely clear, several researchers have suggested that the heterogeneous extrinsic factors such as, gastrointestinal infection, , air pollution,  dietary habit, , could be contribute to the higher incidence of these diseases. However, predisposing factors such as age, sex, genetic pre-disposition, bacterial, parasites and helminthes infections and parallel changes in humidity, vascular disorders, stressful life, are also being suggested by some researchers.
The present study aimed to verify the existence of seasonal variability of gastroentistinal diseases in various parts of the world, by describing intensively the data available on the incidence of diseases during specific seasons of the year. Understanding seasonal patterns of diseases and related trigger factors may aid clinicians developing effective strategies for preventing these diseases and also, help policy makers plan for appropriate healthcare resource distribution and seasonal availability during the peak-incidence season.
To examine global trends in the seasonality of gastrointestinal diseases, we reviewed the results of epidemiological studies of gastrointestinal diseases from a wide range of countries on the seasonal and monthly incidence. The studies were identified from a Medline search of papers published over the period 1970-2012, using the following keywords: "Periodicity" "seasons" and "acute pancreatitis" or "inflammatory bowel disease (IBD)" or "peptic ulcer diseases (PUD)" or "gastroesophageal reflux disease (GERD)" or "colon cancer" or "colonic diverticulitis." This list was extended by including also references from a recent review of gastroentistinal diseases epidemiology. Studies were selected based on the following inclusion criteria: (1) Written in the English language, (2) conducted continuously for 1 year or more, (3) the primary outcome was a clinical and laboratory confirmed diagnosis of the diseases of interest in human subjects, (4) Studies had to be used data on patients in primary or secondary care setting stratified by months, weeks or season.
As a majority of the data in this review came from countries in the Northern Hemisphere, seasons were defined based on their occurrence in the Northern Hemisphere: Winter (December-February), spring (March-May), summer (June-August) and autumn (September-November). Owing to lack of consistency among the statistical methods used in most of the studies it was not possible to do statistical analysis to integrate the results.
The initial search identified
Across all diseases, a total of 1494 references were identified. Thirty-two studies from 17 countries conducted between 1970 and 2012 were included in the review of the seasonality of gastrointestinal diseases. Key data from these studies are summarized in [Table 1]. The studies included in the table employed the following diseases: Acute pancreatitis, IBDs, peptic ulcer disease, colon cancer, GERD and colonic diverticulitis. Four studies included in this review do not contain information about the number of participants and the duration of studies were not available in eight selected studies. Identification of seasonal patterns and the possible mechanism to explain seasonal fluctuation for each disease are given bellow:
Four studies specifically addressed seasonal variation in the onset of acute pancreatitis. Two of these, , from Finland, reported a higher frequency of events during the summer and autumn season. In Italy, Gallerani et al.  observed a different seasonal peak in the onset of acute pancreatitis characterized by a higher frequency in the spring. On the other hand, a study conducted in German hospital on 263 cases observed for a period of 9 years, no correlation between admissions and a specific month or season was found.  Furthermore, there was no significant correlation between the onset of symptoms and a specific weekday in German hospital. In Finland, Räty et al.  observed that months with holiday seasons, summer and autumn, were associated with the highest alcohol consumption and the highest prevalence of acute alcoholic pancreatitis. A seasonal variation in the secretion of pancreatic enzymes, biliary acids, oxygen free radicals has been proposed by some authors.  Furthermore, Pathologic and radiologic evidence of pancreatitis associated with infection have been noted with viruses (mumps, coxsackie, hepatitis B, cytomegalovirus, varicella-zoster virus, herpes simplex virus), bacteria (Mycoplasma, Legionella, Leptospira, Salmonella More Details), fungi (Aspergillus) and parasites (Toxoplasma, Cryptosporidium, Ascaris).  Interestingly, most of these pathogens exhibit a summer peak in some countries. , How often these agents are responsible for seasonal pattern of acute pancreatitis is unclear. Further studies are required to confirm this hypothesis.
Seasonal variations in the onset or relapse of chronic diseases such as IBD have been reported in several countries, with conflicting results. Most of studies have dealt with relapses, but there are also a few analyzing seasonal variations in the onset of disease. All studies have used retrospectively assembled data or hospital admission, which may have led to a bias in the results.
In this review, nine studies specifically addressed seasonal variation of IBDs, eight of them dealt with ulcerative colitis (UC) ,,,,,,, and others with Crohn diseases (CD). ,,,, Spring and summer peaks were prominent in most of the countries subjects in China, Italy, Slovakia and Spain. On the other hand, Moum et al.,  found that the presentation of UC were high in winter while CD peaked in the spring. In Greece, the peak was reported in spring and autumn and early autumn and late winter were in UK noted. One of two studies in Italy, peaking of IBD presentation in spring and summer were noted while in another study, found no evidence of seasonality.
Most patients with IBD run a relapsing course in spring and summer. The reasons why such relapses occur in these times of the year remain unknown. Emotional stress, upper respiratory tract infection, drug ingestion and diarrheal episodes have all been implicated.  a study conducted in the UK revealed similar seasonal fluctuations in hospital admissions for CD, UC and bacterial intestinal infections.  The similarity in the time trends of CD, UC and bacterial intestinal infections suggests that infection by intestinal bacteria are responsible for the fluctuations in hospital admissions for inflammatory bowel disease.  Interestingly, most of the bacterial intestinal infections exhibit a summer peak in some countries. 
As upper respiratory tract infections have been suggested to be associated with relapses in UC and CD and as in most of the country, both colds and upper respiratory tract infections show a seasonal distribution, with higher frequencies in the winter. These findings may partly explain the winter peak of IBD in Sweden. Upper respiratory tract infections could precipitate or activate a latent IBD. 
Peptic ulcer disease
PUD is representative of a group of ulcerative disorders of the upper gastrointestinal tract (GIT), mainly involving the stomach and duodenum that share a common acid-pepsin pathogenesis. Fifteen studies specifically addressed seasonal variation in the incidence of PUD. Some studies have focused on PUD or on gastric ulcer (GU) or duodenal ulcer (DU). Two of three regional studies conducted in India found increased admissions for PUD in winter and spring , and in the third study, autumn and winter were noted.  Autumnal and winter peaks were also reported in Norway.  Autumn-winter and spring peaks, were also reported in Italy. , Winter and spring were also reported in Taiwan , while in Greece spring and autumn peak were noted.  On the other hand, Autumn-winter and summer-autumn have been observed in Israel, ,, and autumn peak in Denmark.  The number of cases of hematemesis caused by GU in Japan showed significant monthly and seasonal fluctuations it decreased in summer and increased in autumn-winter. In contrast, the number of cases of hematemesis caused by DU did not show any monthly or seasonal fluctuations.  There are large variations in the published works as to the season of PUD presentation. However, autumnal and winter peaks were most prominent in most of countries. Nomura et al.  found that the incidence of hematemesis in Japan due to GU over the year showed an inverse temporal relationship to temperature and relative humidity and a parallel relationship with atmospheric pressure. On the other hand, a study conducted in Taiwan by Xirasagar et al.  found DU admissions were negatively associated with temperature, with a winter peak. The mechanism action of temperature on the occurrence of PU in colder months has been linked to the higher air pressure and ambient temperature. It was reported that severe cold and changing temperature result in acute stress actions in the human body, causing excitation of sympathetic nerve and adrenal gland marrow and rapid secretion of adrenaline and noradrenalin.  Cold stimulation and oxygen shortage stimulation may accelerate secretion of endothelin. Adrenaline, hypertensin II and endothelin may cause contraction of duodenal mucosa and blood vessel, leading to mucosa blood flow fall and mucosa damage. When blood supply is insufficient in the duodenal mucosa and the protection barrier is damaged due to insufficient oxygen, the increase of hydrochloric acid in gastric juice accelerates the occurrence is of PUD. 
Seasonality of Helicobacter pylori infection is another possible factor, which may affect PUD onset. Indeed, acid hypersecretion, which is commonly observed in PUD, is more likely the result of H. pylori infection Savarino et al.,  however, did not find any difference in the percentage of H. pylori-positive DU cases between seasons or a parallel annual fluctuation in gastric acidity and H. pylori infection. These findings are in line with another study showing no significant correlation between the seasonal differences in the diagnosis of ulcer disease and presence of H. pylori infection. 
In addition to temperature, several medications such as non-steroidal anti-inflammatory drugs, which are known to damage the epithelium of the GIT, play a role in the seasonal pattern of PUD. There is general agreement that the rheumatoid or osteoarthritis, chronic obstructive pulmonary disease and asthma exhibits seasonal variation and commonly peaks in winter. Not surprisingly, increasing medication usage during acute exacerbations of these diseases would increase the occurrence of PUD. 
In Sweden, a study of 604 patients exhibit showed a summer peak in presentations of colon cancer.  Two studies show the survival of colon cancer patients was highest for summer and autumn diagnosis, corresponding to maximal serum vitamin D levels, which found to be the highest in late summer. , Low level of fiber diets intake during the summer, when individuals were most likely to be outside, could be contributed in emergency presentation of colon cancer in the summer. In one study conducted in Japan, a decreasing risk of colon cancer was found with increasing intakes of calcium and insoluble dietary fiber.  The Potential mechanisms for a protective effect of dietary fiber include dilution of fecal carcinogens and procarcinogens, reduction of transit time of feces through the bowel, production of short chain fatty acids, which promote anticarcinogenic action, and binding of carcinogenic bile acids. 
One study conducted in Taiwan on 76,636 patients suffering from GERD.  The flndings of this study show that the incidence of GERD was high in late autumn and early winter. A possible explanation for the seasonal appearance of GERD has been closely linked to body weight and fat content of the diet. Dietary fat has been shown to release cholecystokinin and subsequently reducing the lower esophageal sphincter (LES) pressure.  High dietary intake of fat was reported to be increased in winter compared with that in summer.  Furthermore, this increase also resulted in increased body mass index in the winter.  In addition to dietary factors, several medications such as nitroglycerins, anticholinergics, ß adrenergicagonists, aminophyllines, α-adrenergic antagonists, nicotine derivatives, tricyclic antidepressants, chlorpromazines, and calcium-channel blockers has been reported promote gastroesophageal reflux by decreasing the pressure of LES.  ß-adrenergicagonists and aminophyllines are commonly used in treatment for chronic obstructive pulmonary disease and asthma. There is general agreement that the chronic obstructive pulmonary disease and asthma exhibits seasonal variation and commonly peaks in winter. Not surprisingly, increasing medication usage during acute exacerbations of chronic obstructive pulmonary disease and asthma would increase the occurrence of GERD. 
Only two studies have specifically addressed seasonal variation in hospital admissions for diverticulitis. One of these studies conducted in USA found the higher number of hospital admission for diverticulitis during summer months  while no evidence of seasonality has been reported in another study conducted in Canada.  Diverticulosis is thought to be caused by the combination of an increase in intraluminal pressure and weakening of the colonic wall,  both of which are exacerbated by aging, and a low-fiber diet. , Low-fiber diet has been reported to be associated with high prevalence of constipation, which can lead to increased intraluminal pressure in the large bowel. The increasing number of "fast food" restaurants where mainly high-carbohydrate, low-fiber diets, confectionaries and sweets are served, when individuals were most likely to be outside in summer. Furthermore, a pilot study, conducted in Canada found that people eat more fresh fruits and vegetables in the summer months.  One could speculate that such dietary variation fits nicely with the long-held belief that diverticulitis results from ingestion of indigestible food items that impact the lumen of a diverticulum. ,
Alcohol has been linked to an increased risk of constipation. Interestingly, Summer time have been observed to be associated with the highest alcohol consumption.  This could be contributed in emergency presentation of diverticulitis in summer. However, the absence of seasonality in the Canadian study does may be linked with food habit and availability of fruits and vegetable year around.
The data presented here show that the seasonal peaks of PUD are most prominent in colder months while the peak of incidence rate of CD in most of the countries subjects were found during spring and summer seasons. Seasonal trend in the onset of acute pancreatitis exhibits a summer peak in some countries. There were no clearly seasonal peaks noted for the UC. However, our understanding of seasonality of diseases remains poor and will require a combination of experimental and observational studies. Further understanding of the role of environmental factors (infection, cold, air pollution etc.) or other triggers (dietary habit, alcohol consumption) could be used to improve prevention measures and educational strategies, especially in people with a highest risk of gastrointestinal diseases.