Mesenteric lymphadenopathy in children with chronic abdominal pain

Background: Mesenteric lymphadenopathy is a common finding described by abdominal ultrasonography in children. Objective: To estimate incidence and significance of mesenteric lymphadenopathy (MLN) in children with chronic abdominal pain (CAP) as compared to healthy children. Method: A prospective observational study was conducted in the paediatric department of a tertiary care hospital. Cases included children of age group 5–15 years with CAP who were subjected to abdominal ultrasonography during the study period. Controls included children in whom abdominal sonography was performed for reasons other than abdominal pain. Descriptive statistics were used for the analysis of baseline characteristics of the study group. For the variables following normal distribution curve, mean and standard deviation were computed. The presence of enlarged nodes, their location, size and other significant findings were recorded. Pearson’s Chi-square test was used to analyse categorical variables between groups. Results: Three hundred and eighteen children were enrolled in the study. After excluding those who did not meet the criteria, the final study population included 110 cases and 138 controls. CAP was almost equal in both sexes with male: female ratio of 1:1.07. Mesenteric lymph nodes were detected by ultrasonography in 84 (72.1%) cases and in 41 (13.4%) controls. Significant MLN (≥5 mm short axis or >10mm long axis) was present in 62 (56.4%) of 110 children with CAP, in contrast to 16 (11.6%) of 138 controls (p <0.001). Most common location of the nodes was in the right iliac fossa (79%) followed by peri-umbilical location (77.4%). _________________________________________ Junior Resident, Professor, Assistant Professor, Senior Resident, Kasturba Medical College, Manipal Academy of Higher Education, Manipal,India *Correspondence: bksandydoc@gmail.com (Received on 02 March 2018: Accepted after revision on 20 April 2018) The authors declare that there are no conflicts of interest Personal funding was used for the project. Open Access Article published under the Creative Commons Attribution CC-BY License Conclusion: MLN, with lymph nodes more than 5mm on their short axis, is a significant finding in children presenting with CAP. DOI: http://dx.doi.org/10.4038/sljch.v47i4.8598 (


Introduction
In developed countries, chronic abdominal pain (CAP) is a complaint of 10-12% school children 1 . However, an organic cause is found only in 5-10% of children with CAP 2 . There are very few studies that mention the prevalence and significance of mesenteric lymphadenopathy (MLN) in CAP 3 .

Objective
To estimate the incidence and significance of MLN in children with CAP as compared to healthy children.

Method
A prospective, single centre study was conducted in the paediatric department of Kasturba Medical College, Manipal, from October 2015 to July 2017, a period of 1 year and 9 months. Children aged 5-15 years, presenting with CAP, who were subjected to abdominal ultrasonography, were included as cases. Children who were subjected to abdominal sonography for reasons other than abdominal pain were included in the control group. Children with known organic causes for CAP (pancreatitis, dysmenorrhoea, abdominal TB, renal calculi etc.) were excluded from cases. Children with known cause for MLN e.g. gastroenteritis, malignancy, abdominal tuberculosis, rheumatic disorders etc. were excluded from cases as well as from controls. The study protocol was approved by the Institutional Ethics Committee. (IEC No. 641/2015). Written informed consent was obtained from the parents before inclusion in the study.
Data collected from history, physical examination and abdominal ultrasonography were recorded in a proforma designed for the study. Ultrasonography was performed by 2 experienced radiologists using Epiq-5G and Affiniti-50G units (Philips health care) with 8 MHz convex-array transducer and 12 MHz linear transducer. The presence of enlarged nodes, their location, size and other significant findings were recorded. Each lymph node was measured in two dimensions (short axis and long axis). A size of more than 5mm in short axis or more than 10mm in the long axis was considered significant. Basic investigations were done according to case merit and the details were included.
The study data was processed using the Statistical Package for the Social Sciences (SPSS) V21.0. Descriptive statistics were used for the analysis of baseline characteristics of study group. For the variables following normal distribution curve, mean and standard deviation were computed. Pearson's Chi-square test was used in the analysis of categorical variables between groups. Significance was assessed at 5% level using non parametric 2 tailed test. A p-value of <0.05 was considered statistically significant.

Results
A total of 318 children were enrolled in the study, which included 149 children with CAP (cases) and 169 controls. Among the 149 cases with CAP, 39 were excluded whilst 31 subjects were excluded from the control group. Thus, the final study population included 110 cases and 138 controls ( Figure 1).
Of the 138 controls, 46 had congenital anomalies and genetic syndromes where abdominal sonography was done to rule out renal/ gastrointestinal malformations, 42 had renal disorders, 37 had hepatic disorders, 9 had pyrexia of unknown origin and 4 had miscellaneous disorders. CAP was almost equal in both sexes with a male: female ratio of 1:1.07. Mean age of the study group was 9.13 ± 3.3 years ranging from 5-15 years. In the present study there were 73 (66.3%) children aged from 5 to 10 years and 37 (33.7%) children aged from 10-15 years. Higher frequency of CAP was observed in the younger age group. Mean weight of all children with CAP was 24.34 ± 9.8kg and control was 26.79 ± 12.65kg. Mean height of all the cases was 126.05 ± 17.9cm and controls was 127.25 ± 22.77cm. Out of the 110 cases, 33 (30%) and out of the 138 controls 33 (23.9%) were undernourished with BMI <3rd centile (Table 1).   . Most common location of the nodes was in the right iliac fossa (RIF) region (79%) followed by peri-umbilical location (77.4%) ( Table 4).

Discussion
Recurrent abdominal pain (RAP) was described as a symptom complex by a British paediatrician John Apley and he defined it as "pain that waxes and wanes, occurring at least 3 times over a period longer than 3 months and severe enough to affect a child's activities" 4 . The American Academy of Paediatrics (AAP) Subcommittee on Chronic Abdominal Pain 2005 replaced the term RAP with CAP and defined the latter as "long-lasting intermittent or constant abdominal pain that is either functional or organic". Abdominal pain lasting for more than 1-2 months is considered chronic 5 . Both RAP and CAP are being used interchangeably in clinical practice. However, CAP is currently the preferred term as it encompasses RAP as well.
CAP is common among school children and young adolescents with prevalence ranging from 0.5 to 19% 6-9 . Boey et al. reported a prevalence of CAP of 10.2% among Malaysian school children 6,7 . Two age peaks are often seen; one at 4-6 years and the other at 7-12 years [8][9][10] . Incidence is uncommon in children below 5 years and those above 15 years of age. In our study, higher frequency of CAP was observed in the age group of 5-10 years. Both boys and girls were equally affected in our study, though many studies have shown female preponderance 8,9 .
Most of the studies have reported that only 10% cases of CAP have an organic pathology. Studies done in India have reported intestinal parasitic infection as one of the most important cause of CAP 10 . Gastroesophageal reflux disease (GERD) and constipation are the commonest causes of CAP in the developed countries [11][12][13][14][15] . An association between H. pylori and CAP has been postulated, but is controversial. 14 Studies have shown the presence of social and family stressors being associated with CAP. Some of the stressors include parental separation, domestic violence, school issues etc. 11,13 . As per ROME IV criteria, the term FGID (Functional gastrointestinal disorders) was replaced by the new terminology 'disorders of gutbrain interaction'-"a group of disorders classified by GI symptoms related to any combination of motility disturbances, visceral hypersensitivity, altered mucosal and immune function, gut microbiota, and/or central nervous system processing" 16 .
Abdominal ultrasonography is an important diagnostic tool performed to rule out an underlying organic abnormality. MLN is the commonest ultrasonographic finding in children with CAP, but its significance is rarely mentioned in the literature. Radiologically, MLN is used to describe the presence of 3 or more lymph nodes of size greater than 5mm in its short axis [17][18][19] . MLN is called primary, when there is no other ultrasonographically identified abnormality and secondary, when an associated pathology is detected 19 . A short axis of <5mm is considered insignificant 20 . MLN is commonly reported in children with acute abdominal pain and a few researchers have reported the significance of MLN in CAP as well [17][18][19][20] .
MLN was believed to be associated with acute appendicitis, lymphoma and intussusception 21 . Common aetiologies for MLN include viral infections, mainly adenovirus, Crohn's disease, gastroenteritis, HIV and Yersinia entercolitica [22][23][24] . Significant MLN is defined as a size of more than 5mm in short axis (more than 10mm in the long axis) 23,24 . Similar to our study, a few studies have reported right lower quadrant of abdomen as the common site of location of MLN followed by the periumbilical region 22-24 . This is a single centre prospective case control study to determine the presence and significance of mesenteric lymphadenopathy in children with CAP. This study showed that MLN is a common finding in children with CAP compared to asymptomatic children. Clinically significant MLN i.e. lymph nodes >5mm in short axis was significantly associated with chronic abdominal pain. Comprehensive laboratory investigations targeted to explore the aetiology of MLN were not performed in this study. We did not perform long-term follow-up of the subjects which would be useful to evaluate the natural history of MLN. These are limitations of this study. Abdominal ultrasonography is a useful tool in the evaluation of CAP to rule out organic causes. When MLN is the only finding in abdominal ultrasonography, parents can be reassured regarding the benign nature of this finding and possible good prognosis.

Conclusions
MLN, with lymph nodes more than 5mm on their short axis, is a significant finding in children presenting with CAP.