Eur J Pediatr (2017) 176:199–205

DOI 10.1007/s00431-016-2822-7

ORIGINAL ARTICLE

Characteristics of mesenteric lymphadenitis in comparison

with those of acute appendicitis in children
Itai Gross 1 & Yael Siedner-Weintraub 1 & Shir Stibbe 2 & David Rekhtman 3 & Daniel Weiss 4 &
Natalia Simanovsky 5 & Dan Arbell 6 & Saar Hashavya 3

Received: 20 August 2016 / Revised: 3 December 2016 / Accepted: 7 December 2016 / Published online: 16 December 2016
# Springer-Verlag Berlin Heidelberg 2016

Abstract Mesenteric lymphadenitis (ML) is considered
as one of the most common alternative diagnosis in a
child with suspected acute appendicitis (AA). In this
retrospective study, patients diagnosed with ML
(n = 99) were compared in terms of demographic, clin-
ical, and laboratory findings to patients diagnosed with
AA (n = 102). This comparison was applied for both
lymph nodes smaller and larger than 10 mm. When
compared to patients with AA, patients with ML had
significantly longer duration of symptoms prior to emer-
gency department (ED) presentation (2.4 ± 2.6 vs
1 .4 ± 1. 4 d ay s , P = 0 . 0 0 2 ) a n d m u l t i p l e E D
presentations (1.3 ± 0.7 vs 1.05 ± 0.3, P < 0.001) and
had longer duration of stay in the ED (9.2 ± 5.9 vs
5.2 ± 4 h, P < 0.001), respectively. They also had
significantly lower WBC (10.16 ± 4.7 × 10 3 /dl vs
15.8 ± 4.4 × 103/dl, P < 0.001) with lymphocyte pre-
dominance (24.6 ± 14 vs 13 ± 8.7%, P < 0.001) and
lower CRP levels (0.48 vs 1.6 mg/dl). Migration of pain
(28 vs 7%), vomiting (62 vs 34%), and classic abdom-
inal findings of AA (72 vs 20%) were all significantly
more common for children with AA. When comparing
lymph node size, no significant difference was found
between those presenting with small and large nodes.

Communicated by Jaan Toelen

* Itai Gross Saar Hashavya

itaigross@gmail.com saarha@gmail.com

Yael Siedner-Weintraub 1
Department of Pediatrics, Hadassah Medical Center, Ein Kerem,
weinyael@gmail.com
Kiryat Hadassah, POB 12000, 91120 Jerusalem, Israel
Shir Stibbe 2
Faculty of Medicine, Hebrew University, Ein Kerem,
shirs59@gmail.com Jerusalem, Israel
David Rekhtman 3
Department of Pediatric Emergency Medicine, Hadassah Medical
crazy_jek@yahoo.com Center, Jerusalem, Israel
Daniel Weiss 4
Department of General Surgery, Hadassah and Hebrew University
danielweiss33@gmail.com Hospital, Jerusalem, Israel
Natalia Simanovsky 5
Medical Imaging, Hadassah and Hebrew University Hospital,
natalias@hadassah.org.il Jerusalem, Israel
6
Dan Arbell Pediatric Surgery, Hadassah and Hebrew University Hospital,
arbell@hadassah.org.il Jerusalem, Israel
200
Conclusion: This study highlights multiple clinical and lab-
oratory findings that differentiate ML and AA. Moreover, the
absence of any difference with regard to the lymph nodes size
might suggest that lymph nodes enlargement is a non-specific
finding.
What is Known:
• Mesenteric lymphadenitis is a very common diagnosis in children with
suspected acute appendicitis.
• Despite its prevalence, only few studies addressed the clinical
characteristics of this clinical entity and their comparison with acute
appendicitis.
What is New:
• Mesenteric lymphadenitis and acute appendicitis could be differentiated
by multiple clinical and laboratory parameters.
• No significant difference was found between those presenting with small
and large lymph nodes.
Keywords Mesenteric lymphadenitis . Acute appendicitis .
Lymph nodes . Abdominal pain
Abbreviations
AA Acute appendicitis
CT Computerized tomography
ED Emergency department
ML Mesenteric lymphadenitis
RLQ Right lower quadrant
URTI Upper respiratory tract infection
US Ultrasound
Introduction
Abdominal pain is one of the most common presenting
symptoms of children brought to medical attention and
encompasses a differential diagnosis of many variable
etiologies [12, 16]. Among children presenting to emer-
gency departments or outpatient clinics with abdominal
pain, acute appendicitis (AA) is the most frequent sur-
gical etiology [10] and exclusion or conformation of
appendicitis is a matter of great importance. ML is con-
sidered the most common cause of pseudo-appendicular
syndrome in children and differentiation between AA,
and mesenteric lymphadenitis (ML) remains challenging
even for the astute physician [14].
The term ML is used to describe an inflammatory process
of the mesenteric lymph nodes that can be of primary
(idiopathic) etiology or secondary to various infective, malig-
nant, or inflammatory disorders. It is commonly defined as a
cluster of three or more lymph nodes visualized on CT scan or
US measuring more than 5 mm on their short axis [13, 14].
Surprisingly, there is no consensus among clinicians regarding
Eur J Pediatr (2017) 176:199–205
both the radiologic definition and the clinical semiology of
this common disorder. While several recent publications chal-
lenged the traditional radiographic definition of enlarged mes-
enteric lymph nodes in the pediatric population [8, 18], only
few studies have addressed the clinical and laboratory charac-
teristics of this entity [19].
The aims of this study were to assess clinical and laboratory
parameters of patients with symptomatic ML and compare
them with those of AA, and then to further analyze those
parameters based on lymph nodes size.
Materials and methods
Records of all patients aged 3–14 years who presented in the
Hadassah Medical Center Emergency Department (ED) be-
tween the years 2011–2014 and were diagnosed with either
AA or ML were retrospectively analyzed. Of these, 99 chil-
dren with ML and 102 children with AA were randomly se-
lected in order to match the same age group.
Analyses of records included demographic, clinical, and
laboratory data. Ultrasonographic examinations were evaluat-
ed for the presence of enlarged lymph nodes in the RLQ, and
the shortest diameter of the lymph nodes was measured. As
RLQ evaluation with a high frequency linear transducer is part
of routine abdominal US examination in our hospital, appro-
priate images were available in all patients.
AA was defined based on pathological specimen findings
after surgery. Symptomatic ML was defined as the clinical
diagnosis on the discharge summary in patients presenting
with RLQ pain or tenderness and based on sonographic find-
ings of enlarged mesenteric lymph nodes.
This study was approved by the Research Ethics Board at
the Hadassah Medical center, Jerusalem, Israel.
We used descriptive statistics to summarize our results
using SPSS software. Continuous variables were analyzed
using t test or Mann-Whitney U test (for asymmetrical distri-
butions). Proportions were analyzed using Chi-square test or
Fisher’s exact test (when sample size was small). Levene’s test
was used to assess the equality of variances. A two-sided 95%
confidence interval was used for all measures.
Each criterion was analyzed separately to determine wheth-
er there is a statistically significant difference between the two
groups. WBC and CRP levels underwent further analysis to
determine a cutoff point distinguishing between the groups,
using ROC curves.
Results
Demographic data is presented in Table 1. There was no sig-
nificant difference in age or gender among the two groups.
Children with ML had longer duration of symptoms prior to
Eur J Pediatr (2017) 176:199–205 201

Table 1 Comparison of demographic findings in children of the AA vs Table 3 Comparison of clinical signs and symptoms in children of the
ML study groups AA vs ML study groups

Characteristic AA no. (%) ML no. (%) P value (%) ML AA P value

Sex 37.0 Vomiting 34 (34.3%) 63 (61.8%) p < 0.001

Female 41 (40.2) 46 (46.5) Nausea 14 (14.1%) 17 (16.7%) 0.62
Male 61 (59.8) 53 (53.5) Migrating pain 7 (7.1%) 28 (27.5%) p < 0.001
Age (years) 54.5 Anorexia 29 (29.3%) 45 (44.1%) 0.02
Mean (range) 9.80 (3–14) 9.59 (4–14) Constipation 8 (8.1%) 5 (4.9%) 0.36
Diarrhea 20 (20.2%) 19 (18.6%) 0.77
Characteristics of the two study populations, including number (N) of
Dysuria 15 (15.2%) 6 (5.9%) 0.03
participants, percentages of males vs females and age for children with
acute appendicitis (AA) and children with mesenteric lymphadenitis High fever (>39 °C) 28 (28.3%) 5 (4.9%) p < 0.001
(ML) Appendicitis signs 20 (20.2%) 73 (72.3%) p < 0.001

Clinical signs and symptoms of the two groups on presentation in the

presentation in the ED (2.4 ± 2.6 vs 1.4 ± 1.4 days, P = 0.002);
they also had a longer duration of stay in the ED (9.2 ± 5.9 vs
5.2 ± 4 h, P < 0.001) and eventually more presentations in the
ED (1.3 ± 0.7 vs 1.05 ± 0.3, P < 0.001) (Table 2).
High fever, defined as axillary temperature above 39 °C,
and dysuria were more common in children with ML with
28.3 vs 4.9% (P < 0.001) and 15.2 vs 5.9% (P = 0.03), re-
spectively, whereas vomiting (34.3 vs 61.8%, P < 0.001), mi-
gration of pain (7.1 vs 27.5%, P < 0.001), and anorexia (29.3
vs 44.1%, P = 0.03) were all significantly associated with AA
(Table 3). Classic signs of appendicitis (e.g., percussion ten-
derness, rebound tenderness, positive Rovsing’s sign) were
also significantly associated with AA (20.2 vs 72.3%,
P < 0.001) (Table 3).
There was no significant difference between the groups in
terms of serum electrolytes and renal function. Higher lym-
phocyte percentage (24.6 ± 14 vs 13 ± 8.7%, P < 0.001) was
significantly associated with ML. WBC (10.16 ± 4.4 × 10 vs
15.8 ± 4.7X103/dl, P < 0.001), CRP levels (0.48 vs 1.6 mg/dl,
emergency room. Appendicitis signs—percussion tenderness, rebound,
and Rovsing’s sign
ML mesenteric lymphadenitis, AA acute appendicitis
P < 0.001), and neutrophil percentage (65.5 ± 16.8 vs
78.9 ± 11%, P < 0.001) were all significantly higher in the
AA group compared to the ML group (Table 4). The best
cutoff points for WBC and CRP were calculated by ROC
curve analysis; a cutoff point of 12,400 WBC/dl had a sensi-
tivity of 80.8% and specificity of 75.8%. No good cutoff point
was found for CRP. Using multivariate logistic regression,
WBC higher than 12,400 cells/dl marked an OR of 8.11 for
AA compared to ML. The OR was even higher when CRP
was elevated. For every increase of 1 CRP unit, the OR for
AA grow by 1.12.
As there is no consensus in the literature as to what mes-
enteric lymph node size should be considered pathological,
we compared lymph node larger vs smaller than 10 mm on
their short axis, as visualized by the USA. Forty children had

Table 2 Comparison of
hospitalization characteristics in Study group Number Mean Std. deviation P value
children of the AA vs ML study
groups Length of hospitalization (days) ML 99 0.98 1.29 p < 0.001
AA 102 4.81 1.87
Length of stay in the ER (hours) ML 99 9.18 5.88 p < 0.001
AA 102 5.20 4.03
Number of presentations to the ER ML 99 1.30 0.65 p < 0.001
AA 102 1.05 0.26
Number of hospitalizations ML 99 0.43 0.54 p < 0.001
AA 102 1.01 0.10
Days of complaints prior to presentation ML 98 2.39 2.65 0.002
AA 102 1.44 1.37
Days of fever prior to presentation ML 99 0.83 1.44 0.08
AA 102 0.52 0.99

Hospitalization characteristics of the two study populations, including length of hospitalization and length of stay
in the emergency room (ER), number of ER presentations, hospitalizations, number of days of fever >38 °C, and
complains prior to presentation in the ER for children with acute appendicitis (AA) and children with mesenteric
lymphadenitis (ML)
202 Eur J Pediatr (2017) 176:199–205

Table 4 Comparison of laboratory findings in children of the AA vs ML study groups

Study group Number Mean Std. deviation P value*

CRP*** (mg%) AA 84 1.6**** 0–29.1***** p < 0.001

ML 84 0.475**** 0–19.3*****
WBC (109/l) AA 99 15.82 4.67 p < 0.001
ML 99 10.16 4.36
NE%** AA 98 78.90 10.97 p < 0.001
(%) ML 99 65.45 16.82
BA% AA 97 0.36 0.42 0.01
(%) ML 99 0.50 0.40
EO%** AA 98 1.01 1.43 0.003
(%) ML 99 1.85 2.29
LY%** AA 98 13.00 8.65 p < 0.001
(%) ML 99 24.56 14.04
MO% AA 98 6.69 3.53 0.054
(%) ML 99 7.64 3.41
HGB AA 99 13.12 1.03 0.97
(Gr%) ML 99 13.11 0.90
PLT AA 99 294.86 69.91 0.06
(109/l) ML 99 275.95 75.14

Laboratory findings of the two groups on presentation in the emergency room

AA acute appendicitis, ML mesenteric lymphadenitis, CRP C-reactive protein, WBC white blood cells, BA basophiles, EO eosinophiles, LY lymphocytes,
MO monocytes, HGB hemoglobin, RDW red cell distribution width, RBC red blood cells, HCT hematocrit, MCHC mean cell hemoglobin concentration,
MCH mean cell hemoglobin, MCV mean corpuscular volume, MPV mean platelet volume, PLT platelets
*t test for equality of means, 2 tailed
**Equal variances not assumed
***Mann-Whitney U test was used, instead of t test
****Median instead of mean
*****Range instead of S.D.

lymph nodes larger than 10 mm and 32 had lymph nodes
smaller than 10 mm. No significant difference in any clinical
or laboratory parameter was found (Tables 5 and 6).
Discussion
Abdominal pain in the pediatric age group presents a diagnos-
tic challenge even to the astute physician. The differential
diagnosis for RLQ abdominal pain and tenderness is long
and ranges from surgical emergencies such as AA and ovarian
torsion to benign clinical entities as gastroenteritis, constipa-
tion, and ML [9, 12]. The differentiation between AA and ML
is of special interest as ML is the most common entity mim-
icking AA [5, 17].
Surprisingly, despite its prevalence and importance as
an alternative diagnosis for AA, recent clinical publica-
tions depicting ML are sparse. To the best of our knowl-
edge, only one recent publication in the English literature
addressed the clinical and laboratory characteristics of
ML [19].
ML was first described by Wilensky et al. in the early
twentieth century [20] and was soon followed by several pub-
lications of case series [1, 4] that established ML as a clinical
entity. Further delineation of ML as a pathologic finding oc-
curred in the late twentieth century and early twenty-first cen-
tury as ultrasound became a leading diagnostic modality in
children with abdominal pain, and radiologic studies evaluat-
ed the clinical relevance of mesenteric lymph node size and its
correlation with abdominal pain and surgical conditions [14,
18–20, 22].
The aim of this study was to characterize the anamnestic,
clinical, and laboratory findings of large and small mesenteric
lymph nodes and their differentiation from those of AA.
Demographic, anamnestic and physical examination
characteristics of ML versus AA
Children with ML had a longer duration of symptoms includ-
ing fever prior to presentation in the ED; they tended to have
multiple presentations and spent more time in the ED before
Eur J Pediatr (2017) 176:199–205 203

Table 5 ML—comparison of clinical characteristics of children with lymph nodes larger and smaller than 10 mm

Lymph nodes size P Value*

Smaller than 10 mm Larger than 10 mm

n (%) n (%)

Admissions 16 (40) 15 (46.9) 0.55

Vomiting 16 (40) 12 (37.5) 0.82
Nausea 6 (15) 4 (12.5) 1.0**
Migrating pain 1 (2.5) 4 (12.5) 0.16**
Anorexia 13 (32.5) 11 (34.4) 1.0**
Constipation 4 (10) 3 (9.38) 1.0**
Diarrhea 7 (17.5) 6 (18.8) 0.89
Urinary complaints 7 (17.5) 4 (12.5) 0.74**
High fever 11 (27.5) 11 (34.4) 0.52
Appendicitis signs 5 (12.5) 8 (25) 0.17

Clinical signs and symptoms on presentation in the emergency room of the children diagnosed with mesenteric lymphadenitis. Comparison of those with
lymph nodes larger and smaller than 10 mm. Appendicitis signs—percussion tenderness, rebound, and Rovsing’s sign
*Pearson Chi-Square, 2 sided
**Calculated using Fisher’s exact test

Table 6 ML—comparison of
laboratory characteristics of Lymph nodes size P Value*
children with lymph nodes larger
and smaller than 10 mm Smaller than 10 mm Larger than 10 mm

WBC N 40 32 0.35
Mean 10.70 (3.15–30.90) 9.70 (4.20–17.88)
SD 5.56 3.42
CRP N 33 27 0.55**
median (range) 2.02 (0–14.79) 2.0 (0–19.30)
SD 3.04 4.4
NE% N 40 32 0.86
Mean (range) 66.86 (32.3–94.10) 67.55 (42.20–91.50)
SD 17.43 16.14
LY% N 40 32 0.85
Mean (range) 23.83 (2.60–5.60) 23.23 (3.90–44.50)
SD 15.1 13.42
MO% N 40 32 0.98
Mean (range) 7.43 (2.90–22.90) 7.41 (2.80–18.30)
SD 3.54 3.22
HGB N 40 32 0.6
Mean (range) 13.14 (10.20–15.40) 13.03 (11.50–14.40)
SD 1.11 0.73
PLT N 40 32 0.56
Mean (range) 281.95 (101.0–428.0) 270.56 (109.0–618.0)
SD 68.07 97.09

Laboratory characteristics on presentation in the emergency room of the children diagnosed with mesenteric
lymphadenitis. Comparison of those with lymph nodes larger and smaller than 10 mm
AA acute appendicitis, ML mesenteric lymphadenitis, CRP C-reactive protein, WBC white blood cells, LY lym-
phocytes, MO monocytes, HGB hemoglobin, PLT platelets
*t test for equality of means, 2-tailed
**Calculated using Mann-Whitney U test, instead of t test
204
the decision regarding discharge or admission was reached;
43% of them were eventually hospitalized (Table 2). These
findings might be the result of the uncertainty of the diagnosis.
We found no significant association between signs and
symptoms of upper respiratory tract infection (URTI) with
ML. Gastrointestinal complaints (constipation, diarrhea, nau-
sea) other than vomiting failed to show any difference as well.
The lack of reported URTI symptoms is striking as initial
reports found correlation between ML and intercurrent URTI
symptoms [20]. Interestingly, the only recent study assessing
clinical parameters of ML did not find any correlation with
URTI signs and symptoms either [19].
In concordance with the Alvarado [3] and PAS [15] scoring
systems, migration of pain, vomiting, anorexia, and physical
examination findings consistent with AA (e.g., tenderness on
percussion) were all significantly associated with AA in our
study. Surprisingly, in our study, high fever was associated
with ML rather than AA, as fever is usually reported as a sign
of appendicitis [6] rather than non-specific abdominal pain. It
is possible that children with ML represent a subclass of chil-
dren with non-appendicitis-related abdominal pain in which
fever is more common than in children with AA.
Laboratory findings
ML was associated with a significantly higher lymphocyte
percentage, whereas higher CRP levels and a higher WBC
count were associated with AA. There were no significant
findings in terms of electrolytes or renal function tests be-
tween the two groups (Table 4). The importance of a high
white blood cell count and elevated CRP in the diagnosis of
AA has been previously demonstrated [2, 11].
To the best of our knowledge, our report is the first to find
an association between lymphocytosis and ML. Previous
studies have demonstrated the usefulness of neutrophil to lym-
phocyte count ratio in the diagnosis of AA [7, 21, 22]. Our
study supports the role of lymphocytosis as a negative predic-
tor of AA and its association with ML.
Clinical and laboratory differences between different
mesenteric lymph node sizes
Our study did not demonstrate any clinical or laboratory dif-
ference between smaller and larger than 10 mm, on their short
axis, mesenteric lymph node subgroups.
Based on imaging studies, the size of lymph nodes in
symptomatic ML is still under debate; while traditionally (as
extrapolated from adults findings), a cluster of three or more
lymph nodes measuring more than 5 mm along their short axis
is considered pathologic [13]; studies in the pediatric popula-
tion revealed that 64% of asymptomatic children will have an
Eur J Pediatr (2017) 176:199–205
incidental finding of enlarged mesenteric lymph nodes if the
traditional criteria are applied. According to these findings, a
cutoff point of 8 mm and even 10 mm was suggested for the
definition of pathologic ML in children [18].
The lack of any significant difference between small and
large lymph nodes in our study might imply that enlarged
mesenteric lymph nodes are a radiographic finding, rather
than the direct cause for symptomatic ML and that mesenteric
lymph node enlargement occurs due to different and non-
specific etiologies.
Study limitations
Our study has several limitations, first, due to its retrospective
nature. The data we gathered was based on chart documenta-
tion, thus incomplete documentation can explain the lack of
association between anamnestic details and ML (e.g., URTI).
Secondly, since we arbitrarily defined symptomatic ML as
RLQ pain or tenderness and the presence of mesenteric lymph
node enlargement, we could not assess the role of ML in the
presentation of children with abdominal pain and other clini-
cal entities such as gastroenteritis or intussusception. The lack
of a control group which consists of asymptomatic patients
with an incidental finding of enlarged mesenteric lymph nodes
is a limitation of our study. We decided to limit the scope our
study to the differentiation between acute appendicitis and
symptomatic mesenteric lymphadenitis, due to previous stud-
ies which suggested that enlarged mesenteric lymph nodes are
a common incidental finding in non-symptomatic pediatric
population [8, 18].
Conclusions
Our study is one of few to describe the clinical and laboratory
findings of ML in comparison to AA in the pediatric age
group and is the most comprehensive.
The observation of no clinical difference between small
and large lymph nodes might support those who regard mes-
enteric lymph node enlargement as a non-specific finding
rather than a clinical diagnosis.
Our study highlights the elusive nature of this diagnosis in
terms of the time spent in the emergency department before
diagnosis is established and the high rate of representations in
the emergency department in comparison to AA.
Our findings may be incorporated into algorithms assessing
the risk of AA vs ML which could prove a powerful clinical
tool, especially in places where ultrasound is not available.
Authors’ contributions Dr. Hashavya, Dr. Rekhtman, Dr.
Arbell, and Dr. Simanovsky conceptualized and designed
Eur J Pediatr (2017) 176:199–205
the study, reviewed and revised the manuscript, and approved
the final manuscript as submitted.
Dr. Gross, Dr. Siedner-Weintraub, Dr. Weiss, and Mrs.
Stibbe designed the data collection instruments, coordinated
and supervised data collection, carried out the preliminary
analyses, drafted the initial manuscript, and approved the final
manuscript as submitted.
All authors approved the final manuscript as submitted and
agree to be accountable for all aspects of the work.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Funding No external funding for this manuscript.
Ethical approval This article does not contain any studies with human
participants or animals performed by any of the authors.
Financial disclosure All authors have indicated they have no financial
relationships relevant to this article to disclose.
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