Skip to main content
PMC home page
World Journal of Gastroenterology logoLink to World Journal of Gastroenterology
. 2004 Nov 15;10(22):3328–3331. doi: 10.3748/wjg.v10.i22.3328

Seasonal variation in the onset of acute pancreatitis

Massimo Gallerani 1,2, Benedetta Boari 1,2, Raffaella Salmi 1,2, Roberto Manfredini 1,2
PMCID: PMC4572305  PMID: 15484310

Abstract

AIM: A circannual variation in the onset of several acute diseases, mostly dealing with cardiovascular system, has been reported. The present study was to verify the possible existence of a seasonal variability in the onset of acute pancreatitis.

METHODS: All patients consecutively admitted to the Hospital of Ferrara, Italy, between January 1998 to December 2002, whose discharge diagnosis was acute pancreatitis, were considered. According to the time of admission, cases were categorized into twelve 1-mo intervals and in four periods by season. χ2 test for goodness of fit and partial Fourier series were used for statistical analysis.

RESULTS: During the study period, 549 cases of acute pancreatitis were observed. A significant peak of higher incidence was found in March-May, both for total population, males and subgroups with and without cholelithiasis or alcoholism. Fourier analysis showed the existence of a circannual rhythmic pattern with its main peak in March (95%C.L.: February-April, P = 0.005), and a secondary one in September. Death occurred more frequently in December-February, compared to the other periods (P = 0.029), and chronobiologic analysis yielded a seasonal peak in November-December (P < 0.001).

CONCLUSION: This study shows the existence of a circannual variation in the onset of acute pancreatitis, with a significantly higher frequency of events in the spring, especially for patients with cholelithiasis or alcoholism. Moreover, events occurring during the colder months seem to be characterized by a higher mortality rate.

INTRODUCTION

Many studies have shown a circannual variation in the onset of several diseases mostly dealing with cardiovascular system, characterized by an abrupt onset, e.g., fatal pulmonary embolism[1,2], ischemic and hemorrhagic stroke[3,4] and rupture of aortic aneurysms[5,6]. Seasonal specific patterns have also been reported for a series of miscellaneous diseases characterized by an acute onset, treated by the Emergency Department, including paralysis of cranial nerves[7], microcristalline arthritis[8], herpes zoster infection[9], epistaxis[10], urinary retention[11]. In the last few years several studies have investigated gastroenterologic diseases, and seasonal etiological patterns have been reported for the onset of peptic ulcer[12-15] and exhacerbation of inflammatory bowel diseases[16-18]. The aim of the present study was to determine by means of a validated chronobiological analysis, whether acute pancreatitis, a common but potentially harmful entity, might show a rhythmic seasonal variation as well.

MATERIALS AND METHODS

All cases of acute pancreatis (International Classification of Diseases, 9th Revision, Clinical Modification, ICD9-CM code: 577.0-8) consecutively observed from 1 January 1998 to 31 December 2002 at the St. Anna Hospital of Ferrara, Italy, were considered for the study. Ferrara is a small town in northern Italy particularly well suited for epidemiological studies. It has a stable population of approximately 150000 inhabitants, almost exclusively white. The only available hospital in this community is St Anna Hospital, which also serves as the sole teaching center for the School of Medicine. The day and month of each event were categorized both into four 3-mo periods (according to seasons) and into twelve 1-mo intervals. Diagnosis was always made on the basis of clinical features, physical examination, laboratory data (serum amylase, isoamylase, lipase, and urinary amylase), and instrumental examinations, when necessary. For all subjects with acute pancreatitis the presence or absence of the two leading specific risk factors (alcoholism and biliary tract disease), was carefully investigated.

For statistical analysis, two different methods were used: χ2 test for goodness of fit and partial Fourier series. To investigate possible differences in frequency peaks, χ2 test for goodness of fit was applied to the total sample population and subgroups by gender, comparing observed against expected events during the four intervals season[19]. On the other hand, to verify the possible existence of a reproducible rhythmic pattern, cosinor analysis and partial Fourier series were applied to the time series, using specific commercially available software written for the Apple Macintosh computer[20]. The program allows, among all the possible combinations of the periods chosen by the user, the selection of the harmonic or the combination of harmonics that best explain the variance of data. The percentage of rhythms (PR: percentage of overall variability of data about the arithmetic mean attributable to the fitted rhythmic function) and the probability value resulting from the F statistic used to test the hypothesis of zero amplitude, were chosen to be reported in the results as representative parameters of goodness of fit and statistical significance of each fitted function, respectively. The program was used to calculate the midline estimating statistic of rhythm (MESOR: the rhythm-adjusted mean over the time period analyzed) and the amplitude (half the distance between the absolute maximum and minimum of the function) of the best-fitting-curve. The program was also used to calculate peak (ortophase) and trough (bathyphase) times of the fitted curves (times of occurrence of the absolute maximum and minimum) and the acrophase of each single harmonic change, together with the 95% confidence limits (CL). Significance levels were always assumed for P < 0.05. Conventional statistical analysis was performed using Student's t test for unpaired data. Significance levels were always set at P < 0.05.

RESULTS

From January 1998 to December 2002, 549 consecutive cases of acute pancreatitis were observed, 285 cases were males (51.9%) and 264 were females (48.1%), their mean age was 65 ± 17 years (difference between sexes t = 2.7, P = 0.007). Two hundred and eighty-six had cholelithiasis (52.1%) and 48 had chronic alcoholism (8.7%).

Deaths from acute pancreatitis were 18 (14 males and 5 females), accounting for 3.2%. Their mean age was 56 ± 16 years, significantly lower than that of survived subjects (65 ± 17 years, t = 2.20, P = 0.028). Among the subgroups of fatal events, 3 had gallstones (16.6%, χ2 = 1.91 P = 0.178), and 4 had chronic alcoholism (22.2%, χ2 = 3.78 P = 0.075). Table 1 shows the monthly distribution by gender, and subgroups by risk factors. A peak of higher frequency of events was found in the period March-May for the total samples and in particular for males and subgroups of subjects with and without gallstones and chronic alcoholism (Table 2). The percentage of fatal events was significantly higher in December-February (n = 9, 17.3% of acute pancreatitis observed in that period, 50% of total deaths, χ2 = 9.11, P = 0.029, compared to the other periods).

Table 1.

Monthly distribution of acute pancreatitis by gender and risk factors

Month Total (n = 549) Males (n = 285) Females (n = 264) Biliary tract disease (n = 286, 52.1%) No bil. tract disease (n = 263, 48.9%) Alcoholism (n = 48, 8.7%) Fatal cases (n = 18, 3.2%)
January 34 18 16 17 17 1 3
February 46 19 27 22 24 2 2
March 62 35 27 28 34 8 1
April 61 33 28 31 30 7 0
May 56 32 24 35 21 5 0
June 44 23 21 19 25 3 0
July 40 20 20 23 17 2 1
August 45 25 20 30 15 4 1
September 39 20 19 22 17 4 1
October 40 20 20 19 21 2 2
November 46 25 21 22 24 6 3
December 36 15 21 17 19 3 4
Open in a new tab

Table 2.

Seasonal distribution of acute pancreatitis (χ2 test for goodness of fit)

n (%) December- February n (%) March-May n (%) June-August n (%) September- November n (%) χ2 P
Total 549 116 (21.1) 179 (32.6) 129 (23.5) 125 (22.8) 17.5 0.001
Males 285 (51.9) 52 (18.2) 100 (35.1) 68 (23.9) 65 (22.8) 17.05 0.001
Females 264 (48.1) 64 (24.2) 79 (29.9) 61 (23.1) 60 (22.7) 3.55 0.316
Biliary tract disease 286 (52.1) 56 (19.5) 94 (32.8) 73 (25.4) 64 (22.3) 11.02 0.011
No bil. tract disease 263 (47.9) 60 (22.9) 85 (32.4) 56 (21.4) 61 (23.3) 7.93 0.049
Chronic alcoholism 48 (8.7) 6 (12.5) 20 (41.7) 10 (20.8) 12 (25) 8.67 0.035
Fatal cases 18 (3.2) 9 (50) 1 (5.6) 2 (11.1) 6 (33.3) 9.11 0.029
Open in a new tab

Chronobiologic analysis (Table 3) showed the existence of a circannual rhythmic variation characterized by a main peak in March (PR 84.8, 95%CL: February-April, P = 0.005), and a secondary peak in September. This pattern was confirmed also for subgroups by gender (men: PR 75.4, 95%CL: February-April, P = 0.027), and (women: PR 73.3, 95%CL: February-April, P = 0.035). Moreover, a highly significant peak was noticed for fatal cases in late November (PR 97.1, 95%CL: October- December, P < 0.001). NO statistically significant trend for a peak in March was found for subgroups of subjects with or without cholelithiasis (respectively: PR 61.8, 95%CL: February-April, P = 0.109; and PR 69.9, 95%CL: February-April, P = 0.052).

Table 3.

Seasonal variation of acute pancreatitis (chronobiologic parameters by Fourier analysis)

n Period (h) PR (%) MESOR Amplitude Peak 95%CL P
Total 549 8766 51.1 March February-April 0.006
4383 33.7 September August-October 0.017
Overall 84.8 45.68 3.28 March February-April 0.005
Males 285 8766 42.6 March February-April 0.030
4383 32.7 September NS 0.052
Overall 75.4 23.71 9.06 March February-April 0.027
Females 264 8766 50.9 March February-April 0.024
4383 22.3 September NS 0.121
Overall 73.3 21.97 4.52 March February-April 0.035
Biliary tract disease 286 8766 42.2 March NS 0.074
4383 19.5 August NS 0.234
Overall 61.8 23.72 7.60 March NS 0.108
No bil. tract disease 263 8766 44.8 March February-April 0.041
4383 25.1 October NS 0.119
Overall 69.9 21.96 7.66 March NS 0.052
Chronic alcoholism 48 8766 13.2 March NS 0.415
4383 40.7 September NS 0.109
Overall 53.9 3.91 2.51 March NS 0.192
Fatal cases 18 8766 86.2 November November-December < 0.001
4383 10.9 June May-July 0.004
Overall 97.1 1.50 1.90 November November-December < 0.001
Open in a new tab

PR = percentage of rhythm (percentage of overall variability of data about arithmetic mean attributable to the rhythmic fitted function MESOR = midline estimated statistics of rhythm, the rhythm-adjusted mean over the time period analysed amplitude: half the distance between the absolute maximum and minimum of the function of the best-fitting curve 95%CL = 95% confidence limits NS = not significant, (when acrophase did not reach the significance level, 95%CL could not be given).

DISCUSSION

Identification of patients with acute pancreatitis is important due to the increased risk of death.

To our knowledge, there was only one recent study in medical literature, which aimed to evaluate the seasonal variation in the onset of acute pancreatitis[20]. In a total of 263 cases observed for a period of 9 years in a German hospital, no correlation between admissions and a specific month or season was found, other earlier reports were mostly hypotheses[21,22]. Our study instead showed a clear seasonal variation in the onset of acute pancreatitis characterized by a higher frequency in the spring, with a maximum in March-May. This pattern was particularly evident for patients with cholelithiasis and chronic alcoholism. It is difficult to give an exhaustive explanation for such a temporal pattern. Seasonal and circannual patterns have been reported for the prevalence of Helicobacter pylori infection[14], or for relapses of inflammatory bowel disease for hospital admissions[15,23].

As for circadian aspects, some acute dramatic clinical events, e.g., variceal and gastrointestinal bleeding[24-26] showed obvious circadian patterns. Daily variations of some biologic functions have also been found as possible co-factors in several gastrointestinal diseases, e.g., fibrinolysis in liver cirrhosis and esophageal varices[27], electrical uncoupling and ectopic pacemaker activity in intestinal motor dysfunction[28], melatonin and duodenal ulcer[29,30], colonic motility in diverticular disease[31] and rectal motor activity in constipation[32].

At present we do not know enough about seasonal biological changes potentially affecting onset of acute pancreatitis, e.g., secretion of pancreatic enzymes, biliary acids. However, it is possible that variations in physiological functions with seasonal change may be associated with an increased risk of pancreatitis. Oxygen free radicals, for example, were known to be a meaningful index for the severity of pancreatitis[33], but possible variations in free radical generation have not been investigated yet. Our results seemed to be able to identify a higher mortality for colder months (November-December). This is particularly interesting when considering that both the mean age of subjects and the incidence of risk factors (gallstones, alcoholism) in the subgroup of fatal cases were significantly lower compared with those in the subgroup of non fatal events. Thus, it seems that acute events of pancreatitis occurring in the colder months may be more at risk in terms of severity and mortality. Further studies conducted on larger samples and addressed to other countries of different latitudes would be needed.

ACKNOWLEDGEMENTS

The authors thank Mr. Franco Guerzoni, from the Statistical Service of Ferrara St Anna Hospital, for his helpful assistance in collection of cases and analysis of data.

Footnotes

Supported by a Research Grant "ex-60%" From the University of Ferrara

Edited by Wang XL Proofread by Xu FM

References

  • 1.Gallerani M, Manfredini R, Ricci L, Grandi E, Cappato R, Calò G, Pareschi PL, Fersini C. Sudden death from pulmonary thromboembolism: chronobiological aspects. Eur Heart J. 1992;13:661–665. doi: 10.1093/oxfordjournals.eurheartj.a060232. [DOI] [PubMed] [Google Scholar]
  • 2.Manfredini R, Gallerani M, Salmi R, Zamboni P, Fersini C. Fatal pulmonary embolism in hospitalized patients: evidence for a winter peak. J Int Med Res. 1994;22:85–89. doi: 10.1177/030006059402200203. [DOI] [PubMed] [Google Scholar]
  • 3.Gallerani M, Trappella G, Manfredini R, Pasin M, Napolitano M, Migliore A. Acute intracerebral haemorrhage: circadian and circannual patterns of onset. Acta Neurol Scand. 1994;89:280–286. doi: 10.1111/j.1600-0404.1994.tb01681.x. [DOI] [PubMed] [Google Scholar]
  • 4.Gallerani M, Portaluppi F, Maida G, Chieregato A, Calzolari F, Trapella G, Manfredini R. Circadian and circannual rhythmicity in the occurrence of subarachnoid hemorrhage. Stroke. 1996;27:1793–1797. doi: 10.1161/01.str.27.10.1793. [DOI] [PubMed] [Google Scholar]
  • 5.Manfredini R, Portaluppi F, Salmi R, Zamboni P, La Cecilia O, Kuwornu Afi H, Regoli F, Bigoni M, Gallerani M. Seasonal variation in the occurrence of nontraumatic rupture of thoracic aorta. Am J Emerg Med. 1999;17:672–674. doi: 10.1016/s0735-6757(99)90156-0. [DOI] [PubMed] [Google Scholar]
  • 6.Mehta RH, Manfredini R, Hassan F, Sechtem U, Bossone E, Oh JK, Cooper JV, Smith DE, Portaluppi F, Penn M, et al. Chronobiological patterns of acute aortic dissection. Circulation. 2002;106:1110–1115. doi: 10.1161/01.cir.0000027568.39540.4b. [DOI] [PubMed] [Google Scholar]
  • 7.Gallerani M, Delli Gatti C, Salmi R, Kuwornu Afi H, la Cecilia O, Manfredini R. Seasonal variations in the incidence of cranial nerve paralysis. J Int Med Res. 1999;27:130–133. doi: 10.1177/030006059902700303. [DOI] [PubMed] [Google Scholar]
  • 8.Gallerani M, Govoni M, Mucinelli M, Bigoni M, Trotta F, Manfredini R. Seasonal variation in the onset of acute microcrystalline arthritis. Rheumatology (Oxford) 1999;38:1003–1006. doi: 10.1093/rheumatology/38.10.1003. [DOI] [PubMed] [Google Scholar]
  • 9.Gallerani M, Manfredini R. Seasonal variation in herpes zoster infection. Br J Dermatol. 2000;142:588–589. doi: 10.1046/j.1365-2133.2000.03400.x. [DOI] [PubMed] [Google Scholar]
  • 10.Manfredini R, Gallerani M, Portaluppi F. Seasonal variation in the occurrence of epistaxis. Am J Med. 2000;108:759–760. doi: 10.1016/s0002-9343(00)00437-x. [DOI] [PubMed] [Google Scholar]
  • 11.Braverman DZ, Morali GA, Patz JK, Jacobsohn WZ. Is duodenal ulcer a seasonal disease A retrospective endoscopic study of 3105 patients. Am J Gastroenterol. 1992;87:1591–1593. [PubMed] [Google Scholar]
  • 12.Tivon K, Cohen P. Seasonality in duodenal ulcer disease: possible relationship with circannually cycling neurons enclosed in the biological clock. Am J Gastroenterol. 1995;90:1189–1190. [PubMed] [Google Scholar]
  • 13.Thomopoulos KC, Katsakoulis EC, Margaritis VG, Mimidis KP, Vagianos CE, Nikolopoulou VN. Seasonality in the prevalence of acute upper gastrointestinal bleeding. J Clin Gastroenterol. 1997;25:576–579. doi: 10.1097/00004836-199712000-00004. [DOI] [PubMed] [Google Scholar]
  • 14.Raschka C, Schorr W, Koch HJ. Is there seasonal periodicity in the prevalence of Helicobacter pylori. Chronobiol Int. 1999;16:811–819. doi: 10.3109/07420529909016947. [DOI] [PubMed] [Google Scholar]
  • 15.Sonnenberg A, Jacobsen SJ, Wasserman IH. Periodicity of hospital admissions for inflammatory bowel disease. Am J Gastroenterol. 1994;89:847–851. [PubMed] [Google Scholar]
  • 16.Moum B, Aadland E, Ekbom A, Vatn MH. Seasonal variations in the onset of ulcerative colitis. Gut. 1996;38:376–378. doi: 10.1136/gut.38.3.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Zeng L, Anderson FH. Seasonal change in the exacerbations of Crohn's disease. Scand J Gastroenterol. 1996;31:79–82. doi: 10.3109/00365529609031631. [DOI] [PubMed] [Google Scholar]
  • 18.Ott L, Memdenhall W, Larson R. Statistical test of hypotheses: the one sample case. In: Statistics , editor. Boston, MA: Duxbury Press; 1978. pp. 242–246. [Google Scholar]
  • 19.Mojón A, Fernández JR, Hermida RC. Chronolab: an interactive software package for chronobiologic time series analysis written for the Macintosh computer. Chronobiol Int. 1992;9:403–412. doi: 10.3109/07420529209064552. [DOI] [PubMed] [Google Scholar]
  • 20.Lankisch PG, Assmus C, Pflichthofer D. The calendar and acute pancreatitis. Pancreas. 1998;16:465–467. doi: 10.1097/00006676-199805000-00001. [DOI] [PubMed] [Google Scholar]
  • 21.Poikolainen K. Seasonality of alcohol-related hospital admissions has implications for prevention. Drug Alcohol Depend. 1982;10:65–69. doi: 10.1016/0376-8716(82)90086-2. [DOI] [PubMed] [Google Scholar]
  • 22.Reimann HA. Letter: Three periodic diseases as causes of recurrent abdominal pain in childhood. Arch Dis Child. 1976;51:244–245. doi: 10.1136/adc.51.3.244. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Minoli G, Imperiali G, Colombo E, De Franchis R, Mortara G, Prada A, Rocca F. Biphasic annual periodicity in relapses of inflammatory bowel diseases. Gruppo di Studio per le Malattie Infiammatorie Intestinale. J Clin Gastroenterol. 1995;21:27–29. [PubMed] [Google Scholar]
  • 24.Manfredini R, Gallerani M, Salmi R, Calò G, Pasin M, Bigoni M, Fersini C. Circadian variation in the time of onset of acute gastrointestinal bleeding. J Emerg Med. 1994;12:5–9. doi: 10.1016/0736-4679(94)90003-5. [DOI] [PubMed] [Google Scholar]
  • 25.Siringo S, Bolondi L, Sofia S, Hermida RC, Gramantieri L, Gaiani S, Piscaglia F, Carbone C, Misitano B, Corinaldesi R. Circadian occurrence of variceal bleeding in patients with liver cirrhosis. J Gastroenterol Hepatol. 1996;11:1115–1120. doi: 10.1111/j.1440-1746.1996.tb01838.x. [DOI] [PubMed] [Google Scholar]
  • 26.Mann NS, Hillis A, Mann SK, Buerk CA, Prasad VM. In cirrhotic patients variceal bleeding is more frequent in the evening and correlates with severity of liver disease. Hepatogastroenterology. 1999;46:391–394. [PubMed] [Google Scholar]
  • 27.Piscaglia F, Siringo S, Hermida RC, Legnani C, Valgimigli M, Donati G, Palareti G, Gramantieri L, Gaiani S, Burroughs AK, et al. Diurnal changes of fibrinolysis in patients with liver cirrhosis and esophageal varices. Hepatology. 2000;31:349–357. doi: 10.1002/hep.510310214. [DOI] [PubMed] [Google Scholar]
  • 28.Der T, Bercik P, Donnelly G, Jackson T, Berezin I, Collins SM, Huizinga JD. Interstitial cells of cajal and inflammation-induced motor dysfunction in the mouse small intestine. Gastroenterology. 2000;119:1590–1599. doi: 10.1053/gast.2000.20221. [DOI] [PubMed] [Google Scholar]
  • 29.Malinovskaya N, Komarov FI, Rapoport SI, Voznesenskaya LA, Wetterberg L. Melatonin production in patients with duodenal ulcer. Neuro Endocrinol Lett. 2001;22:109–117. [PubMed] [Google Scholar]
  • 30.Kato K, Murai I, Asai S, Takahashi Y, Nagata T, Komuro S, Mizuno S, Iwasaki A, Ishikawa K, Arakawa Y. Circadian rhythm of melatonin and prostaglandin in modulation of stress-induced gastric mucosal lesions in rats. Aliment Pharmacol Ther. 2002;16 Suppl 2:29–34. doi: 10.1046/j.1365-2036.16.s2.11.x. [DOI] [PubMed] [Google Scholar]
  • 31.Bassotti G, Battaglia E, Spinozzi F, Pelli MA, Tonini M. Twenty-four hour recordings of colonic motility in patients with diverticular disease: evidence for abnormal motility and propulsive activity. Dis Colon Rectum. 2001;44:1814–1820. doi: 10.1007/BF02234460. [DOI] [PubMed] [Google Scholar]
  • 32.Rao SS, Sadeghi P, Batterson K, Beaty J. Altered periodic rectal motor activity: a mechanism for slow transit constipation. Neurogastroenterol Motil. 2001;13:591–598. doi: 10.1046/j.1365-2982.2001.00292.x. [DOI] [PubMed] [Google Scholar]
  • 33.Park BK, Chung JB, Lee JH, Suh JH, Park SW, Song SY, Kim H, Kim KH, Kang JK. Role of oxygen free radicals in patients with acute pancreatitis. World J Gastroenterol. 2003;9:2266–2269. doi: 10.3748/wjg.v9.i10.2266. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from World Journal of Gastroenterology : WJG are provided here courtesy of Baishideng Publishing Group Inc

RESOURCES