Digestive and Liver Disease 38 (2006) 319–323

Alimentary Tract

Seasonal variations in onset of symptoms in Crohn’s disease A. Aratari a,b,∗ , C. Papi b , B. Galletti c , E. Angelucci a , A. Viscido a , V. D’Ovidio a , A. Ciaco b , M. Abdullahi b , R. Caprilli a a

Department of Clinical Sciences, University “La Sapienza”, Rome, Italy b Gastrointestinal Unit, San Filippo Neri Hospital, Rome, Italy c Gastrointestinal Unit, University of L’Aquila, L’Aquila, Italy Received 6 July 2005; accepted 3 October 2005 Available online 10 November 2005

Abstract Background. Seasonal variations in onset of symptoms have been reported in ulcerative colitis but not in Crohn’s disease. Aim. To investigate whether our inflammatory bowel diseases patients presented seasonal variations in onset of symptoms. Patients and methods. Patients with a diagnosis of inflammatory bowel diseases established between 1995 and May 2004, and consecutively observed from June 2003 to May 2004, were included in the study. Onset of symptoms (year, season and month) was recorded. Expected onsets with a uniform distribution during the year were calculated and compared to observed onsets. Statistical analysis: chi-square test, odds ratio (95% confidence interval). Results. Overall 425 inflammatory bowel diseases patients were enrolled. Onset of symptoms (year and season) was established in 353/425 patients (83%; 150 Crohn’s disease; 203 ulcerative colitis). Onset of symptoms in inflammatory bowel diseases patients as a whole occurred more frequently in spring–summer compared to autumn–winter (odds ratio 1.39; 95% confidence interval 1.03–1.87; p < 0.03). This variation was observed in Crohn’s disease (odds ratio 1.59; 95% confidence interval 1.00–2.51; p < 0.05) and a similar trend, although not significant, was observed in ulcerative colitis (odds ratio 1.27; 95% confidence interval 0.86–1.88; p = 0.27). Conclusions. These data indicate that onset of Crohn’s disease symptoms occurred more frequently during spring-summer. A similar trend was observed in ulcerative colitis. Environmental factors, such as associated infections, smoking, use of drugs and seasonal changes in immune function may be responsible for triggering the clinical onset of inflammatory bowel diseases. © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Clinical onset; Crohn’s disease; Seasonality; Ulcerative colitis

1. Introduction Inflammatory bowel diseases (IBD) are the result of a complex interaction between genetic susceptibility and stimulation by bacterial antigens in the lumen and occasional environmental triggers that damage the mucosal barrier. Seasonality, in the onset of symptoms, has been investigated in many diseases to better understand the epidemiology and ∗ Corresponding author at: Department of Clinical Sciences, University of Rome “La Sapienza”, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy. Tel.: +39 064 460 009; mobile: +39 329 972 7967; fax: +39 064 463 737. E-mail address: [email protected] (A. Aratari).

pathogenesis. Seasonal variations have been shown to predispose to the development of a number of different diseases, such as deep vein thrombosis [1], heart failure [2], asthma [3], schizophrenia [4], peptic ulcer [5,6], upper gastrointestinal (GI) bleeding [7] and post-operative small bowel obstruction [8]. Seasonal variations in the occurrence of relapse [9–13] and hospital admission [14] have been reported in IBD. In retrospective studies, flare-ups of ulcerative colitis (UC) occurred more frequently in spring and autumn [9–12]; conversely, relapses of Crohn’s disease (CD) occurred more frequently in autumn, winter and spring [12,13]. Hospital admissions have been reported to occur more often in winter, but no seasonality has been reported for emergency admission [14].

1590-8658/$30 © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2005.10.002

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A. Aratari et al. / Digestive and Liver Disease 38 (2006) 319–323

Few studies have investigated the seasonal variations in the onset of symptoms of IBD and results are conflicting. Acute onset of symptoms has been reported to occur more frequently in January and July in CD and in December in UC [15]. However, other studies have reported no seasonal variations in the onset of symptoms in UC [16]. The only prospective study addressing seasonality in the onset of symptoms was performed in Norway [17]: symptomatic onset of UC occurred more frequently in December and January but no seasonality was observed in CD. Aim of the present study was to establish whether a seasonal variation exists in the onset of symptoms in our cohort of Mediterranean IBD patients.

2. Patients and methods This study was performed in three Italian GI Units (Department of Clinical Science, University of Rome “La Sapienza”, San Filippo Neri Hospital, Rome, and University of L’Aquila, L’Aquila). Patients with a diagnosis of IBD established, according to standard criteria [18], between 1995 and May 2004, consecutively observed from June 2003 to May 2004 were included and were investigated regarding the onset of symptoms. Data concerning onset of symptoms were retrospectively assessed using a standard interview focusing on symptoms considered “specific” for IBD (1, diarrhoea; 2, rectal bleeding; 3, abdominal pain; 4, fever; 5, weight loss; 6, perianal fistula/abscess; 7, extra-intestinal manifestations) and the period of time (month and year) in which such symptoms occurred for the first time. The date of diagnosis was established according to the first investigation (endoscopy and histology, radiology or surgery) in which a diagnosis of IBD could be defined. The temporal sequence of events and circumstances such as jobs, house moves, births, etc. were introduced in the interview providing a context to better identify symptoms onset. Only those patients who were able to precisely indicate the exact month or season when symptoms first appeared were included in the statistical analysis. The expected onsets with a uniform distribution during the year, taking into account the differences in the number of days in the month, were calculated and compared to the onsets observed. Statistical analysis was performed using the chi-square test and odds ratio (OR) (95% confidence interval (CI)).

Table 1 Clinical characteristics of IBD patients Patients enrolled Patients excluded Patients included in analysis Crohn’s disease Ulcerative colitis Male/female Median age at diagnosis (range) Median duration of symptoms before diagnosis (range) Duration of symtoms ≤2 years Duration of symtoms >2 years Smokers at the time of symtoms onset

425 72 353 150 203 187/166 37 years (11–81) 2 months (0–385)

CD

79.5% 20.5% 28%

UC

17%, p = 0.02

established. The median age at diagnosis was 37 years (range: 11–81 years); the median duration of symptoms before diagnosis was 2 months (range: 0–385 months). In the majority of patients (79.5%) the duration of symptoms before diagnosis was less than 2 years and in 20.5% of patients the duration of symptoms was over 2 years indicating a more insidious onset. Data concerning smoking habit at the time of onset of symptoms were also collected. The percentage of smokers was significantly higher in CD than in UC patients (28% versus 17%, p = 0.02). The clinical characteristics of patients are reported in Table 1. The distribution of onset of symptoms according to month is shown in Table 2. Comparing the observed and expected onset of symptoms, no statistical difference was found in IBD, in general, or in CD and UC, separately. As far as the distribution of onset of symptoms season by season is concerned, a trend in seasonality was observed in IBD population as a whole (Fig. 1). Onset of symptoms in IBD patients occurred more frequently in spring and summer compared to autumn and winter

3. Results A total of 425 consecutive IBD patients (193 CD; 232 UC) were interviewed. Year, season and month of onset of symptoms were established in 320 of 425 patients (75.3%) while year and season of symptomatic onset were established in 353 of 425 patients (83%; 150 CD; 203 UC; male/female: 187/166). Seventy-two patients were excluded because month or season of symptoms onset could not be

Fig. 1. Distribution of symptoms onset in all IBD patients according to season. Symptoms onset occurs more frequently in spring and summer compared to autumn and winter (␹2 for trend 1 df = 5.11; p = 0.02).

A. Aratari et al. / Digestive and Liver Disease 38 (2006) 319–323

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Table 2 Monthly distribution of onset of symptoms IBD (n = 320)

CD (n = 129)

UC (n = 191)

Observed

Expected

Observed

Expected

Observed

Expected

January February March April May June July August September October November December

28 14 25 32 31 31 23 30 31 23 19 33

27.17 24.54 27.17 26.30 27.17 26.30 27.17 27.17 26.30 27.17 26.30 27.17

9 5 9 19 11 10 9 17 8 8 11 13

10.95 9.29 10.95 10.60 10.95 10.60 10.95 10.95 10.60 10.95 10.60 10.95

19 9 16 13 20 21 14 13 23 15 8 20

16.22 14.65 16.22 15.69 16.22 15.69 16.22 16.22 15.69 16.22 15.69 16.22

␹2 11 df p-value

6.97 0.80

6.83 0.81

Table 3 Seasonal distribution of onset of symptoms Observed

Expected

OR (95% CI)

p-value

IBD (n = 353) Spring–summer Autumn–winter

206 147

177 176

1.39 (1.03–187)