Digestive and Liver Disease 38 (2006) 319–323
Seasonal variations in onset of symptoms in Crohn’s disease
A. Arataria,b,∗, C. Papib, B. Gallettic, E. Angeluccia, A. Viscidoa,
V. D’Ovidioa, A. Ciacob, M. Abdullahib, R. Caprillia
aDepartment of Clinical Sciences, University “La Sapienza”, Rome, Italy
bGastrointestinal Unit, San Filippo Neri Hospital, Rome, Italy
cGastrointestinal Unit, University of L’Aquila, L’Aquila, Italy
Received 6 July 2005; accepted 3 October 2005
Available online 10 November 2005
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.
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).
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
Inflammatory bowel diseases (IBD) are the result of a
complex interaction between genetic susceptibility and stim-
ulation by bacterial antigens in the lumen and occasional
environmental triggers that damage the mucosal barrier. Sea-
sonality, 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: firstname.lastname@example.org (A. Aratari).
pathogenesis. Seasonal variations have been shown to pre-
schizophrenia , peptic ulcer [5,6], upper gastrointestinal
(GI) bleeding  and post-operative small bowel obstruction
hospital admission  have been reported in IBD. In retro-
spective 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 sea-
sonality has been reported for emergency admission .
1590-8658/$30 © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
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
tive study addressing seasonality in the onset of symptoms
was performed in Norway : 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 sea-
sonal 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 Univer-
sity of L’Aquila, L’Aquila). Patients with a diagnosis of IBD
and May 2004, consecutively observed from June 2003 to
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 symp-
toms 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 bet-
ter identify symptoms onset. Only those patients who were
able to precisely indicate the exact month or season when
ysis. 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
chi-square test and odds ratio (OR) (95% confidence interval
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 estab-
lished 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
Clinical characteristics of IBD patients
Patients included in analysis
Median age at diagnosis (range)
Median duration of symptoms before
Duration of symtoms ≤2 years
Duration of symtoms >2 years
Smokers at the time of symtoms
37 years (11–81)
2 months (0–385)
11–81 years); the median duration of symptoms before diag-
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 smok-
ers 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.
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 fre-
Fig. 1. Distribution of symptoms onset in all IBD patients according to
pared to autumn and winter (?2for trend 1 df=5.11; p=0.02).
A. Aratari et al. / Digestive and Liver Disease 38 (2006) 319–323
Monthly distribution of onset of symptoms
IBD (n=320)CD (n=129) UC (n=191)
ObservedExpected ObservedExpectedObserved Expected
Seasonal distribution of onset of symptoms
ObservedExpectedOR (95% CI)
1.27 (0.85–1.68) 0.27
(OR 1.39; 95% CI 1.03–1.87; p<0.03). This seasonal vari-
ation was observed in CD (OR 1.59; 95% CI 1.00–2.51;
p<0.05). Also in UC, the onset of symptoms occurred more
frequently in spring–summer compared to autumn–winter
although the difference did not reach statistical significance
(OR 1.27; 95% CI 0.86–1.88; p=0.27) (Table 3).
season or year in which symptoms actually began. To avoid
recalling bias, only patients in whom a diagnosis of IBD has
been established since 1995 were included in this study, thus
patients with a long history of disease were excluded. In this
study population, in fact, the median duration of symptoms
before diagnosis was fairly short (2 months, range 0–385).
of onset of symptoms could not be established, these patients
were not included in the statistical analysis thus giving rise
to possible sample bias.
the onset of CD symptoms occurred more frequently dur-
ing spring and summer than autumn and winter. No seasonal
variations were observed in UC. These observations are in
contrast to those reported by Moum et al. , who found
no seasonality in the onset of CD symptoms, but winter sea-
sonality in UC patients. This difference could be related to
the larger number of CD patients and the smaller number of
UC patients enrolled in our study, albeit a difference related
to the geographic area cannot be excluded. The different sea-
sonal patterns observed in different countries (e.g. Italy and
Norway) could reflect variations in the climate and related
environmental triggering factors in the onset of these dis-
Few studies concerning factors that may trigger the onset
of UC and CD have been published. Although several infec-
tious agents have been suggested to play a role in the patho-
genesis of CD, there is no conclusive evidence of specific
microbial agents as aetiologic factors [19–22]. It is well-
known, however, that bacteria and bacterial antigens modu-
inflammation. Some GI infections show a seasonal pattern of
occurrence that peaks in summer [23–25]. In this season,
furthermore, some psychotropic bacteria, capable of surviv-
ing or developing at low temperatures, as hypothesised by
Hugot et al. in the cold chain hypothesis, could contribute
to the disease through refrigeration, the standard of modern
Western way of life and domestic hygiene . Recently, the
causative role, in CD, of Micobacterium avium subspecies
paratuberculosis was reevaluated . Interestingly, it was
reported that tuberculosis shows a summer peak unlike other
respiratory tract disorders in which a winter peak is observed
Smoking is a very well-known environmental factor in
IBD, particularly since it is protective in UC but has negative
effects on the course of CD . Cigarette sales and onset
A. Aratari et al. / Digestive and Liver Disease 38 (2006) 319–323
of smoking peak in the summer months, i.e., June–August
[30,31]. It is tempting to hypothesise that smoking could
enhance the effects of other seasonal environmental factors.
Intestinal mucosa damage and/or alteration of intestinal
microflora could be due, in part, to the non-steroidal anti-
inflammatory drugs (NSAIDs) and antibiotics used [32,33];
abuse of these drugs seems to occur more frequently during
cold seasons probably due to seasonality of respiratory tract
infections and arthritic pain [33,34].
Oral contraceptives, often considered to be implicated in
IBD flare-up, have been reported to be interrupted during the
winter months [35,36].
IBD leads to an inappropriate immune activation, which
manifests as an increase in the immuno-inflammatory cells
and mediators. Seasonal variations in immune response have
been reported [37–48]. Immune function, in fact, decreases
unlike in summer and spring [39,40]. A possible role of the
warmer temperature could be the increase in mitosis , in
moving of white cells [41,42] and in the release of inflam-
ulin levels, has been reported .
These seasonal changes in immune function could also be
mediated by the pineal hormone, melatonin . It induces
a proinflammatory action by enhancing the release of T-
helper cell Type 1 cytokines, and by modulating the release
in fact, increased in winter and decreased in summer .
Therefore, melatonin could be part of an integrative sys-
tem to coordinate the neuroendocrine and immune systems
 and may play a negative role in autoimmune disease
In conclusion, data emerging from the present study indi-
cate that the clinical onset of CD occurs primarily during
the warm months. Associated infections, smoking, use of
drugs and seasonal changes in immune function may be
responsible for triggering the clinical onset of IBD. These
vate a latent IBD . Bearing in mind that environmental
exposure varies with the seasons over the year, more studies
are needed to identify those factors possibly responsible for
triggering symptomatic onset of a latent CD.
Conflict of interest statement
List of abbreviations
IBD, inflammatory bowel disease; CD, crohn’s dis-
ease; UC, ulcerative colitis; NSAIDs, non-steroidal
anti-inflammatory drugs; OR, odds ratio; CI, confi-
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On pages 319 to 323 an interesting article by Aratari et al.
 is published which deals with the seasonal variations in
the onset of symptoms in Crohn’s disease, reporting results