Digestive Diseases and Sciences, Vol. 50, No. 3 (March 2005), pp.

581–586 (

C 2005)

DOI: 10.1007/s10620-005-2478-z

Efficacy of Mesalazine in the Treatment of

Symptomatic Diverticular Disease
FRANCESCO DI MARIO, MD,* GIOVANNI ARAGONA, MD,* GIOACCHINO LEANDRO, MD,†
GIUSEPPE COMPARATO, MD,* LIBERA FANIGLIULO, MD,* LUCAS G. CAVALLARO, MD,*
GIULIA M. CAVESTRO, MD,* VERONICA IORI, MD,* MARTA MAINO, MD,* ALÌ M. MOUSSA, MD,*
ALESSANDRO GNOCCHI, MD,‡ GIANCARLO MAZZOCCHI, MD,§ and ANGELO FRANZÉ, MD‡

We aimed to improve symptoms by means of mesalazine in symptomatic colonic diverticular disease

patients. One hundred seventy outpatients (98 M, 72 F; age, 67.1 years; range, 39–84 years) were
assigned to four different schedules: rifaximin, 200 mg bid (Group R1: 39 pts), rifaximin, 400 mg
bid (Group R2: 43 pts), mesalazine, 400 mg bid (Group M1: 40 pts), and mesalazine, 800 mg bid
(Group M2: 48 pts), for 10 days per month. At baseline and after 3 months we recorded 11 clinical
variables (upper/lower abdominal pain/discomfort, bloating, tenesmus, diarrhea, abdominal tender-
ness, fever, general illness, nausea, emesis, dysuria), scored from 0 = no symptoms to 3 = severe.
The global symptomatic score was the sum of all symptom scores. After 3 months in all schedules
but Group R1, 3 of the 11 symptoms improved (P < 0.03); the global score decreased in all groups
but Group R1 (P < 0.0001). Mesalazine-treated patients had the lowest global score at 3 months
(P < 0.001). Mesalazine is as effective as rifaximin (higher dosage schedule) for diminishing some
symptoms, but it appears to be better than rifaximin for improving the global score in those patients.

KEY WORDS: mesalazine; diverticular disease; diverticula; rifaximin.

Acquired diverticular disease (DD) of the colon is very
common in developed countries and its prevalence in-
creases with age, varying from less than 10% of subjects
under 40 years to an estimated 50–66% of patients over age
80 (1). According to a recent report by the American Gas-
troenterological Association on the burden of digestive
illnesses in the United States, DD represents, in terms of
direct and indirect costs, the fifth most important gastroin-
testinal disease, with a mortality rate of 2.5 per 100,000
per year (2).
Manuscript received July 2, 2004; accepted September 9, 2004.
From the *Chair of Gastroenterology, University of Parma, Parma,
†Gastroenterological Hospital “S. De Bellis,” IRCCS, Castellana Grotte,
Bari, ‡Gastroenterology and Endoscopy Unit, Az. Ospedaliera, Parma,
and §U.O. Chirurgia Borgovalditaro, AUSL, Parma, Italy.
This work was carried out under the auspices of the Roberto Farini
Foundation for Gastroenterological Research.
Address for reprint requests: Prof. Francesco Di Mario, Uni-
versità degli Studi di Parma, Dipartimento di Scienze Cliniche,
sezione di Gastroenterologia, Via Gramsci 14, 43100 Parma, Italy;
francesco.dimario@unipr.it.
To refer to an acquired alteration present in about two-
thirds of the elderly as a “ disease” seems inaccurate, par-
ticularly as, in the majority of patients, colonic divertic-
ula are asymptomatic (diverticulosis) (1). Nevertheless,
an estimated 20% of affected individuals develop symp-
toms in their lifetime, such as abdominal pain and/or
discomfort, bloating, and disturbance of bowel habits.
This clinical condition is termed DD (3), which may be
symptomatic uncomplicated, recurrent symptomatic, or
complicated (4–6).
Inflammation of the bowel surface leads to a condition
called uncomplicated diverticulitis. Some authors empha-
size that clinical diverticulitis virtually always represents
a micro perforation, even if the colonic mucosa appears
macro- and microscopically normal, despite considerable
inflammation of the pericolonic tissue (7). The presence
of free perforation, fistula, abscesses, or obstruction is
termed complicated acute diverticulitis. Lower gastroin-
testinal tract bleeding from diverticula is not associated
with underlying acute inflammation; rather, the presumed

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cause of this complication is erosion of submucosal blood
vessels by impacted stool at the neck of a diverticulum (7).
Treatment of DD is aimed to relieve symptoms and to
prevent major complications (8). Bran and bulking agents
are commonly used in the treatment of symptomatic DD
but their real efficacy is still controversial. Although some
controlled clinical trials have shown a benefit of high-fiber
diets in obtaining symptomatic relief (9, 10), other stud-
ies have failed to show positive results (11, 12). However,
there is no evidence that such diets prevent diverticuli-
tis (3). Anticholinergic drugs and spasmolytic agents are
widely used in the treatment of symptomatic DD. The ob-
served hypermotility of the sigmoid colon in many symp-
tomatic patients provides the rationale for using these
drugs (13). However, the efficacy of spasmolytic agents
has never been clearly documented (3). Antibiotics are
widely used in the treatment of diverticulitis (3), and
in a subset of patients with symptomatic DD where an
inflammatory component may be clinically suspected, a
course of antibiotics is advisable (8). Rifaximin (a broad-
spectrum, poorly absorbable antibiotic) appeared to be of
some advantage in obtaining symptom relief in uncom-
plicated DD (14, 15) and in reducing the incidence of the
main complications of this disease (16, 17). The rationale
for antibiotic therapy in these patients is the role of intesti-
nal microflora in determining symptoms by fiber degra-
dation and gas production (18). Nevertheless, an Italian
study has reported an increase in pulmonary hydrogen ex-
cretion in DD and the therapeutic effect of rifaximin does
not seem to be due to a persistent correction of this alter-
ation. In addition, this drug appears to cause no significant
imbalance in the intestinal ecosystem (19).
Mucosal inflammation seems to play an important role
in the etiophatogenesis of diverticulitis by an imbalance
among proinflammatory (IL-1, TNF) and antinflammatory
(IL-1 ra, IL-4, IL-10, IL-11) cytokines (20), with a conse-
quent increase in the intramucosal secretion of NO (21).
Luminal mucosal inflammation may also occur, not only
in acute attacks of diverticulitis and peridiverticulitis, but
also, although unusually, in uncomplicated DD (22, 23).
This kind of diverticular colitis is wholly confined to the
segment affected by DD and may closely mimic inflam-
matory bowel disease (IBD), with its complex flogistic
characteristics (24). Many of these cases of diverticular
colitis seem to respond favorably to treatment similar to
that given for IBD (22).
Two clinical studies reported that supplementary treat-
ment with mesalazine in patients with colonic DD or with
recurrence diverticulitis proved to be well tolerated and
promising for the management of these diseases (25, 26).
The aim of our study was to compare the efficacy of
cyclic administration of rifaximin versus mesalazine in
582
DI MARIO ET AL.
obtaining symptom relief in patients with symptomatic
uncomplicated colonic DD.
MATERIALS AND METHODS
The study was structured as a monocentric, prospective, ran-
domized, open trial. Over a period of 2 years a total of 170
consecutive outpatients with uncomplicated DD of the colon, di-
agnosed by double-contrast barium enema and/or colonoscopy,
were screened at our Gastroenterological Unit and randomly as-
signed to four different treatment regimens: 39 patients received
rifaximin, 200 mg bid (Group R1), and 43 patients received ri-
faximin, 400 mg bid (Group R2), for 10 days during the first
part of every month; 40 patients received mesalazine, 400 mg
bid (Group M1), and 48 patients received mesalazine, 800 mg
bid (Group M2), for 10 days every month. No selective dietary
regimen was prescribed at entry except the recommendation for
all patients to follow a high-fiber diet.
Some main criteria had to be fulfilled to enter the trial: age
between 18 and 85 years, endoscopic and/or radiologic evidence
of DD (with the presence of more than five diverticula) of the left
colon and the presence of symptoms attributable to the DD of
the colon such as upper and/or lower abdominal pain/discomfort,
bloating, tenesmus, diarrhea, abdominal tenderness, fever, and
dysuria. Only patients who experienced two or more symptoms
for at least 1 month before enrolment entered the study.
Exclusion criteria were solitary diverticulum of the colon,
signs of diverticulitis, previous colonic surgery, concomitant
colonic or extracolonic cancer, use of antibiotics in the previ-
ous 4 weeks, chronic hematological and/or hepatic and/or renal
diseases, immunodeficiency, pregnancy or lactation, proven in-
tolerability to rifaximin or mesalazine, and questionable ability
to cooperate. All criteria were assessed by means of a com-
plete history, physical examination, endoscopy/double-contrast
X-ray, and analysis of biochemical blood samples. Diverticuli-
tis was excluded on the basis of clinical and laboratory signs
(absence of rebound tenderness or other signs of peritoneal in-
flammation and normal values of body temperature, leukocytes,
and erythrocyte sedimentation rate) with radiographic or endo-
scopic examinations (plain abdominal film, barium enema or
colonoscopy, ultrasonography or computed tomography, specif-
ically performed on the basis of clinical findings) excluding the
local inflammatory process of the colonic wall, perforation, ab-
scesses, or stenosis (3, 5).
Clinical evaluation was performed by an interview ques-
tionnaire and a clinical visit at admission and after 3 months,
taking into account 11 clinical variables (upper abdominal
pain/discomfort, lower abdominal pain/discomfort, bloating,
tenesmus, diarrhea, abdominal tenderness, fever, general illness,
nausea, emesis, dysuria) scored as follows: 0 = no symptoms;
1 = mild, symptoms easily tolerated; 2 = moderate, symptoms
sufficient to cause interference with usual daily activities; and
3 = severe, incapacitating symptoms with inability to perform
normal activities. Furthermore, the patients were invited to return
for control visits whenever they considered it necessary.
The Global Symptomatic Score (GSS) (15, 16), calculated as
the sum of all symptom scores, was assigned to each patient at
every clinical evaluation (maximum score = 33). It was assessed
to evaluate the effect of the administered therapy on the over-
all severity of the combined symptoms. It therefore reflects the
overall clinical conditions of the patients during the follow-up.
Digestive Diseases and Sciences, Vol. 50, No. 3 (March 2005)