World J Surg (2010) 34:210–215
DOI 10.1007/s00268-009-0349-z
Pain as the Only Consistent Sign of Acute Appendicitis:
Lack of Inflammatory Signs Does Not Exclude the Diagnosis
Olivier Monneuse • S. Abdalla • F. Pilleul •
V. Hervieu • L. Gruner • E. Tissot •
X. Barth
Published online: 30 December 2009
Ó Société Internationale de Chirurgie 2009
Abstract
Background The clinical diagnosis of acute appendicitis
in adults remains tricky, but radiological examinations are
very helpful to determine the diagnosis even when the adult
patient presents atypically. This study was designed to
quantify the proportion of patients with a preoperative
diagnosis of acute appendicitis that had isolated right lower
quadrant pain without biological inflammatory signs and
then to determine which imaging examination led to the
determination of the diagnosis.
Methods In this monocentric study based on retrospec-
tively collected data, we analyzed a series of 326 patients
with a preoperative diagnosis of acute appendicitis and
isolated those who were afebrile and had isolated right
lower quadrant pain and normal white blood cell counts
and C-reactive protein levels. We determined whether the
systematic ultrasonography examination was informative
enough or a complementary intravenous contrast media
computed tomography scan was necessary to determine the
diagnosis, and whether the final pathological diagnosis fit
the preoperative one.
O. Monneuse (&)
S. Abdalla
L. Gruner
E. Tissot

X. Barth
Surgical Emergency and Trauma Department, Hôpital Edouard
Herriot, Pavillon G visceral, 5 place d’Arsonval, 69437 Lyon
Cedex 03, France
e-mail: olivier.monneuse@chu-lyon.fr
F. Pilleul
Radiology Department, Hôpital Edouard Herriot,
Lyon Cedex 03, France
V. Hervieu
Pathology Department, Hôpital Edouard Herriot,
Lyon Cedex 03, France
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Results A total of 15.6% of the patients with a preoper-
ative diagnosis of acute appendicitis had isolated rebound
tenderness in the right lower quadrant, i.e., they were
afebrile and their white blood cell counts and C-reactive
protein levels were normal. In 96.1% of the cases, the
ultrasonography examination, sometimes complemented
by an intravenous contrasted computed tomography scan if
the ultrasonography result was equivocal, fit the histopa-
thological diagnosis of acute appendicitis.
Conclusions The diagnosis of acute appendicitis cannot
be excluded when an adult patient presents with isolated
rebound tenderness in the right lower quadrant even
without fever and biological inflammatory signs. In our
study, ultrasonography and computed tomography were
very helpful when making the final diagnosis.
Introduction
Acute appendicitis (AA) is a common surgical emergency
in adults. The diagnosis is usually based on clinical and
biological criteria making up the clinical presentation of
acute appendicitis: fever[100°F, rebound tenderness in the
right lower quadrant, and leucocytosis.
Technical progress in ultrasonography (US) [1, 2] and
intravenous contrast computed tomography (CT) [3] now
allow clinicians to make the diagnosis of AA with visual
evidence and questions the use and the accuracy of bio-
logical parameters, such as white blood cell (WBC) count
and C-reactive protein (CRP) level [4–6]. Active obser-
vation also is efficient when associated with repeated
clinical, biological, and radiological examinations [7, 8],
but induces a significant increase in cost.
In the Department of Emergency Surgery of Edouard
Herriot Hospital in Lyon, France, we are frequently
World J Surg (2010) 34:210–215 211

confronted with the diagnosis of acute appendicitis. We

retrospectively observed that among patients with a pre-
operative diagnosis of AA who were subsequently oper-
ated on for this pathology, some of them presented only
with pain located in the right lower quadrant and without
fever, leucocytosis, or any increase in the CRP level.
Very few studies have put forward similar observations
[9]. The main purpose of our study was to quantify the
exact proportion of the patients without fever, leucocy-
tosis, or increase in the CRP level among patients with a
preoperative diagnosis of AA. We double-checked that
the histopathological diagnosis fit the preoperative diag-
nosis of AA and that the final diagnosis matched the
radiological one.

Patients and methods

This study was a descriptive, monocentric study based on

retrospectively collected data: from January 2002 to March
2005, we included 326 consecutive patients from our
database (aged 18–80 years; 184 men = 56.3%) who had a
preoperative diagnosis of AA and who underwent an
appendectomy in our surgical emergency department of
Edouard Herriot Hospital.
On admission, all patients underwent physical exami-
nation, which included abdominal palpation and a mea-
surement of their auricular temperature. The auricular
temperature was measured with an electronic thermometer.
Their WBC counts and CRP levels also were determined
on admission. We considered them to be afebrile if their
body temperature was B99.5°F (37.5°C). According to the
standard values of our laboratory, the WBC count was
considered as normal when it was B12.109/l and the CRP
level was considered as normal when it was B5 IU/l.
All patients, with or without inflammatory signs,
underwent the same diagnostic imaging protocol: each
patient had an ultrasound (US) examination that explored
the whole anterior abdominal wall with a percutaneous
probe (Elegra, Siemens) initially using a 3.5-MHz convex
array transducer and it was completed by a 7.5-MHz
linear array transducer. This examination was performed
in the emergency room before the decision was made to
hospitalize the patient. The US examinations were per-
formed by resident or staff radiologists. The US criteria
for making the diagnosis of AA were the following direct
signs: thickness of the appendix wall [5 mm, widening of
the appendix, noncompressible appendix, and inflamma-
tion of the periappendiceal fat (Fig. 1a). Indirect signs
included the presence of a stercolith in the appendix
(Fig. 1b). When the final diagnosis could not be made
based on the US examination, patients underwent an
additional CT scan of the abdomen and pelvis with
Fig. 1 a US examination identified an acute appendicitis with
enlarged appendix (diameter 6 mm) and periappendiceal inflamma-
tion (with star). b Acute appendicitis with fluid retention in the distal
lumen (white arrow) caused by an appendicolith (star)
intravenous (IV) contrast media—Somatom, Siemens 10
detectors, helical acquisition—without digestive prepara-
tion. This examination also was performed in the emer-
gency room by resident or staff radiologists before the
decision was made to hospitalize the patient. Every US
examination or CT with IV contrast media performed by
a resident radiologist was validated by a senior staff
radiologist. The CT criteria were all the same as the US
criteria except for the incompressibility of the appendix.
For the US and CT with IV contrast media, the diagnosis
of AA was made when the patient presented with at least
three of the four direct signs or two direct signs associ-
ated with the indirect sign.
With a preoperative diagnosis of AA, all 326 patients
were operated on using general anesthesia and underwent
appendectomy by laparoscopy or laparotomy depending on
the decision of the operator. The resected appendix was
systematically sent for pathological examination.
The histopathological protocol consisted of a standard-
ized sampling. The resected appendix was fixed in 10%
buffered formalin, the base of the appendix was stained
with ink as a marker, and the pathologist proceeded to the

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212 World J Surg (2010) 34:210–215

macroscopic examination of the whole piece. Then, sam- Results

ples of the appendix were impacted in paraffin and cut into
5-lm-thick slices. The slices were stained with hematox-
ylin, phloxine, and saffron and were interpreted by the
pathologist. The diagnosis of isolated acute appendicitis
(IAA) was made when the histopathological examination
of the appendix showed acute inflammatory lesions with a
focal layout characterized by edema associated with
polymorphic inflammatory infiltration in nonulcerated
mucosa. The diagnosis of complicated acute appendicitis
(CAA) was made when the histopathological examination
of the appendix showed acute inflammatory lesions char-
acterized by polymorphic inflammatory infiltration of the
whole appendicular wall from the submucosa to the sub-
serosa and wide ulceration foci covered with a fibrino-
leukocytic coating with numerous clusters of altered neu-
trophilic polynuclear leukocytes. The diagnosis of chronic
appendicitis (CA) was made when the histopathological
examination of the appendix showed chronic-looking
inflammatory changes: absence of purulent changes, pres-
ence of focal fibrosis of the submucosa and the muscularis
mucosae with focal adipose involutions, rare polynuclear
neutrophils, and the presence of some polynuclear eosin-
ophils. In no cases were there histopathological signs of
malignancy. The histopathological result was considered as
the ‘‘gold standard’’ to confirm or invalidate the preoper-
ative diagnosis.
The patients were followed up in the surgical depart-
ment, with the length of hospitalization depending on the
state of health of the patient. One month after their dis-
charge from hospital, all of the patients were examined by
their surgeon in search of possible postoperative compli-
cations, such as a ventral rupture of the scar, parietal
suppuration, or parietal hematoma.
Among the 326 patients who had a preoperative diagnosis
of AA, we recorded that 51 of them (15.6%, 26 men; aged
18–80 (median, 27.5) years) complained of isolated pain in
the right lower quadrant (Table 1). Clinical examination
revealed right lower quadrant tenderness in 19 patients
(37.3%) or right lower quadrant guarding in 32 patients
(62.7%), but no fever. The biological examinations
revealed neither hyperleukocytosis nor an increase in the
CRP level. The duration of the symptoms before arrival at
the hospital was B24 h for 24 patients (47.1%), between 24
and 48 h for 17 patients (33.3%), and [48 h but \8 days
for 10 patients (19.6%). With regard to medical history,
there were three pregnant women (5.9%), two diabetic
patients (3.9%), and one patient (1.96%) who had been
treated with antibiotic therapy during 5 days for abdominal
pain before his arrival at the hospital.
Two patients (3.9%) underwent repeated US examina-
tions (Table 1); in both cases, the first US examination was
normal, and the persistence of the pain led to a need to
repeat the US examination either 3 or 7 days later, at which
point there were direct signs of AA. In one case (1.96%),
the patient was overweight and diabetic with a past medical
history of myocardial infarction and bilateral carotid sur-
gery, so he underwent CT scan with IV contrast media
directly, without receiving an US examination. Three
patients (5.9%) underwent other radiological examinations
(refer to the ‘‘other’’ category in Table 1): one patient
(1.96%) underwent an US examination that only showed
inflammation of the periappendiceal fat with an ileocecal
effusion and the appendix could not be clearly identified.
Despite the unavailability of CT, the indication of appen-
dectomy was set. One patient (1.96%) underwent first an

Table 1 Gender, duration of

Radiological preoperative examinations
symptoms, and
histopathological results by US examination US examination and Repeated US IV contrasted Other
imaging diagnostic strategies only complementary IV examinations CT without US
contrasted CT

Men 20 4 1 1 –
Women 14 7 1 – 3
Duration of symptoms
B24 h 15 5 0 1 3
24–48 h 12 4 1 – –
[48 h 7 2 1 – –
US ultrasonography, IV Pathological results
intravenous, CT computed
tomography, IAA isolated acute Misdiagnosis 2 – – – –
appendicitis, CAA complicated IAA 9 1 1 – 1
acute appendicitis (abscess or CAA 21 9 1 1 2
peritonitis), CA chronic
CA 2 1 – – –
appendicitis

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World J Surg (2010) 34:210–215 213

US examination and then a CT scan with IV contrast media
that could neither identify the appendix nor find any indi-
rect signs of AA. This patient underwent a complementary
endovaginal US examination, which was normal. The
second interpretation of the CT found a partial portal
thrombosis. One day later, a third US examination was
used to make the diagnosis of AA. In one last case (1.96%),
the patient underwent an US examination and a CT scan
with IV contrast media, which were both nonconclusive;
the complementary endovaginal US examination was used
to make the diagnosis of AA.
After the histopathological analysis of the appendix of
the 51 patients, the diagnosis of AA was confirmed for 49
of them (15.3% of 326 patients, 96.1% of 51 patients). Two
patients were misdiagnosed (3.9% of 51 patients): one
patient presented with Crohn’s disease associated with a
terminal ileitis, which was revealed by this atypical clinical
presentation and another patient presented with lymphoid
hyperplasia. Thus, there were two unnecessary appendec-
tomies (3.9%). There were 49 inflammatory appendices
(96.1%), including 12 IAAs (23.5%), 34 CAAs (66.7 %),
and 3 CAs (5.9%), which we chose to include in our study
among the AA because of the acute symptomatology.
Among the 51 patients, we recorded no normal appendices
after the histopathological examination. Thus, among the
51 patients, the imaging diagnosis fit the histopathological
one in 96.1% of the cases (diagnostic value = 96.1%). The
histopathological examination showed that the patient who
was operated on with a noncontributive US examination
that could not be complemented by CT with IV contrast
media did in fact present with a CAA.
The mean hospital stay duration was 4 (range, 2–15)
days. One month after discharge from the hospital, we
recorded two incision abscesses and two parietal
hematomas (morbidity = 7.8%, mortality = 0%). There
were no incisional hernias or recurrent surgeries in the
series.
Discussion
Despite the fact that AA in adults is a common surgical
emergency [10], its diagnosis remains tricky [11, 12],
particularly when the patient presents with as clinical signs
isolated rebound tenderness in the right lower quadrant
with no biological signs of inflammation. Few studies put
forward similar cases [9], and some authors exclude the
diagnosis of acute appendicitis in the face of a similar
clinical picture [13, 14]. This context is why we sought to
quantify the proportion of acute appendicitis cases with
normal laboratory findings and then to determine how the
diagnosis was made. Our diagnostic strategy is based on
several steps: after a clinical examination and blood sam-
pling, every patient presenting to the emergency room with
abdominal pain undergoes an US examination. This US
examination is performed at any time of the day or night by
a staff or resident radiologist, specialized in digestive
radiology or having attended a specialized training in
digestive radiology during their degree training. Thus, if
ultrasound is considered to be an operator-dependant
modality, we benefit from highly reliable radiological
diagnoses [2]. This examination displays several advanta-
ges, including its noninvasive nature, absence of radiation
exposure, and ability to be rapidly performed. Moreover, it
is considered to be a sensitive and specific examination for
the diagnosis of acute appendicitis in adults [1, 15]. The CT
scans with IV contrast media (Table 2) has the same
advantages for the diagnosis of acute appendicitis in adults,

Table 2 Summary of the available literature

Predictive value of Helpful diagnostic value Doubtful diagnostic value

US examination Systematic US examination in suspected AA is US examination is less accurate than WBC count and
recommended for adults [1, 2] neutrophil count for the diagnosis of AA [26]
US is better for diagnosing positive findings, CT is more sensitive and specific than US in patients
whereas CT is better for excluding diagnosis of with an equivocal presentation of AA [29]
AA [4]
IV contrasted CT IV contrast media CT has a good diagnostic US is better for diagnosing positive findings, while CT
precision, especially in patients with equivocal is better for excluding diagnosis of AA [4]
presentation of AA [3, 6, 17]
IV contrast media CT is the initial test of choice for
the evaluation of the adult patient suspected of
having AA [30]
US combined to CT US eventually completed by an IV contrast media CT and even IV contrast media CT completed by an US
examination improve the diagnostic accuracy of AA [10, 31, 32]
Laboratory findings AA is unlikely in adult patients with normal Diagnostic accuracy of WBC count, CRP, and
leukocyte count and CRP value [13, 14, 33, 34] temperature is low [4, 19, 21, 23, 25]
AA acute appendicitis, US ultrasonography, IV intravenous, CT computed tomography, WBC white blood cell

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although it involves radiation exposure [16–18], which is
why we perform it when the radiologist cannot rule out
appendicitis from the results of the US. In our department,
we do not practice diagnostic laparoscopy and we consider
this procedure to be a surgical approach to performing the
surgical treatment rather than a diagnostic modality. All of
these examinations are performed before the decision to
hospitalize and operate on the patient is made, and their
results condition this decision.
As far as the laboratory findings are concerned, we
chose to include the results of the CRP level and WBC
count because we use them routinely even if their use and
accuracy are controversial [11, 12, 14, 19] and if other
inflammatory markers, such as the neutrophil-lymphocyte
ratio, interleukin-6 [20], or interleukin-10 [21], and mea-
surement modalities, such as repeated laboratory examin-
ations [11, 22], were proposed. Yet, one can question the
choice of the cutoff values, especially for the WBC count
because we considered values \12.109/l as normal,
although other studies chose other cutoff values [23–25].
Indeed, at the time the diagnoses and the decision to
operate on the patients were made, our laboratory cutoff
point for hyperleukocytosis was 12.109/l. To be rigorous,
we decided to keep this cutoff point. If we consider the
international standards and our current laboratory cutoff
point for hyperleukocytosis, which is 10.109/l, our rate of
patients with a preoperative diagnosis of AA presenting
with isolated RLQ pain is 11.3% (37 patients instead of
51), which is still higher than the results of the other
studies. Nevertheless, we stress the fact that the goal of this
study was not to evaluate the diagnostic accuracy of CRP
levels and WBC counts for the diagnosis of acute
appendicitis.
Our results were different from those presented in other
studies concerning the rate of acute appendicitis in adults
with no typical biological signs of inflammation [24, 26].
We also noticed that we obtained one of the lowest rates of
unnecessary appendectomies [2]. On the other hand, for the
two misdiagnoses—Crohn’s disease and lymphoid hyper-
plasia—the diagnosis was made by the US examination,
which means that the images fit the criteria that we cited
earlier. Moreover, we chose to include three cases of
chronic appendicitis according to the pathological results,
which remain the ‘‘gold standard’’ for making the final
diagnosis, as already reported [27]. A few cases put for-
ward in other studies [28] and ours illustrate that chronic
appendicitis often is mistaken for acute appendicitis and
treated as such.
Finally, we will keep in mind that the particularities of a
population determine the diagnostic strategy to choose.
Indeed, when an adult patient presents with a typical
clinical picture of acute appendicitis, the combination of
clinical, biological, and radiological signs make the
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World J Surg (2010) 34:210–215
diagnosis [4, 23]. This study clearly suggests that any adult
patient presenting with isolated right lower quadrant pain
without fever or elevation of WBC counts and CRP levels
should undergo an US examination eventually comple-
mented by a CT scan with IV contrast media to rule out the
diagnosis of acute appendicitis. In fact, we normally use
this imaging strategy in our department. A prospective
study evaluating the cost/benefit ratio of this imaging
diagnostic strategy versus the CT scan with IV contrast
media only or no imaging examination could build upon
our work.
Conclusions
Among the patients with a preoperative diagnosis of acute
appendicitis, 15.6% presented with an atypical overall
picture: isolated rebound tenderness in the right lower
quadrant, apyrexia, and normal WBC counts and CRP
levels. This proportion is higher than those presented in
other surveys. In our population, such patients systemati-
cally underwent an US examination complemented by a
CT scan with IV contrast if the result of the US exami-
nation was equivocal. The imaging diagnosis of acute
appendicitis fit the histopathological one in 96.1% with all
inflammation stages included. Thus, the diagnosis of acute
appendicitis cannot be excluded in adult patients presenting
with such an overall picture, and for these patients radio-
logical examinations, in particular ultrasonography, are
very helpful in making the diagnosis.
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