What Is Known/What Is New
What Is Known
- Children with chronic abdominal pain are frequently diagnosed with irritable bowel syndrome.
- Up to 12% of children with irritable bowel syndrome may suffer from anterior cutaneous nerve entrapment syndrome.
What Is New
- A 17-item questionnaire can distinguish anterior cutaneous nerve entrapment syndrome from irritable bowel syndrome in pediatric populations with chronic abdominal pain.
Chronic abdominal pain (CAP) in children poses a considerable burden to patients, parents, and care providers. A definite cause may not always be identified. As a consequence, relative large numbers of children with CAP are diagnosed per exclusionem with irritable bowel syndrome (IBS) (1,2).
Recent studies have shown that there are certain patients including children, originally diagnosed with IBS, who in fact suffered from a chronic abdominal wall pain syndrome (CAWP), such as anterior cutaneous nerve entrapment syndrome (ACNES) (3,4). This type of anterior abdominal pain is neuropathic in character and is often interfering with daily functioning and school attendance. The exact pathophysiology of ACNES is poorly understood, but the syndrome is likely caused by irritation of the anterior portions of intercostal thoracic nerve endings at the level of the rectus abdominis muscle (thoracic 7–12) (5,6). The treatment of ACNES consists of nerve blocks or surgery in both adult ACNES patients as well as in children (7).
We previously found at our pediatric outpatient department that 1 of 8 children with CAP was diagnosed with ACNES (8). Correctly diagnosing these children conferred immediate therapeutic consequences as 92% was successfully treated with injections or surgery. Unfortunately, ACNES is often overlooked and objective diagnostic criteria are currently lacking. Therefore, a simple tool that is potentially able to distinguish between IBS and ACNES would aid in shortening doctor's delay in children, who in fact have a pain syndrome of the abdominal wall. The objective of the present study was to investigate whether a modified pediatric version of an existing adult questionnaire was also useful in distinguishing IBS from ACNES in a pediatric population.
Following protocol approval by Máxima Medical Center's (MMC) local ethical board (METC#-1306), the present study was conducted at surgical and pediatric outpatient clinics. MMC is a teaching hospital housing a surgical center of excellence for abdominal wall and groin pain syndromes (SolviMáx). Pediatricians treat the entire spectrum of pediatric illnesses including gastrointestinal (GI) disorders. A number of GI pediatricians have interest in diagnosing and treating CAWP syndromes and closely collaborate with surgeons.
A surgeon and a pediatrician who are actively involved in the management of children with CAP were invited to modify the wording of a recently published questionnaire that distinguished CAWP syndromes from IBS in adults (9). Aim was to make all questions understandable for children of 8 years and older. This modified paper questionnaire included 18 randomly sequenced questions regarding ACNES (n = 11) and IBS (n = 7) symptoms. All questions are either closed ended, dichotomous (‘yes,’ ‘no’; n = 12) or dichotomized 4-point Likert scale questions (‘mostly’ or ‘regularly’; ‘sometimes’ or ‘never’; n = 6).
Three Different Study Populations
Results of this questionnaire were obtained from 2 ACNES groups and 1 IBS group. All children were between 9 and 18 years of age. Group 1 consisted of children who were previously treated for ACNES in our hospital. They had more than 50% pain reduction (measured by a 0–10 numeric rating scale) 4 to 6 weeks after a surgical neurectomy for ACNES that was executed between January 2006 and December 2013 by surgeons at MMC. The outcome of surgery in some patients in this group was reported previously (7). It was reasoned that a successful outcome after surgery was indicative of the correct diagnosis of ACNES. This definition (>50% reduction in pain after surgery) was, therefore, considered ‘gold standard’ in the absence of other generally accepted outcome measures. Following a surgical chart analysis, eligible children were invited to complete the questionnaire that was sent by mail. A reminding phone call was performed 2 weeks after the first contact, whereas the inclusion was terminated 1 month after the last invitation. As all questionnaires were completed some time after surgery, data were considered as obtained in a retrospective model.
Group 2 consisted of children referred to our surgical outpatient clinic for evaluation of a suggested ACNES pain syndrome (June 2013–December 2015). The questionnaire was obtained before the first clinical evaluation. All children with a completed questionnaire were examined by 1 of 3 surgeons with ample experience in the management of CAWP syndromes. ACNES was confirmed following a strict physical examination and with the use of criteria listed in Table 1(7).
Group 3 consisted of children with abdominal pain who were assessed by the pediatrician. Diagnostic workup was performed at discretion of the attending pediatrician with no minimum requirements for laboratory testing and imaging. The questionnaire was completed during or following the first outpatient evaluation (June 2013–December 2015). Questionnaires of children diagnosed with IBS and negative diagnostic tests for ACNES (Table 1) were analyzed.
Statistical analysis was performed with “IBM SPSS Statistics” software V. 20 for Windows (IBM Corp., Armonk, NY). Continuous data are presented as median and range. Categorical data are reported as counts and percentages. Before analysis, the final diagnosis was checked in pediatric and surgical charts of the children. As a consequence, results of a questionnaire were excluded if the final diagnosis was neither IBS nor ACNES, or if the moment of its completion was uncertain. Questionnaire responses with more than 1 missing item were also excluded from analysis. The distinctive power of each of both ACNES and IBS items of the questionnaire was measured using a chi-square test. Items with P > 0.01 were defined as nondistinctive and were excluded from the questionnaire. The reliability of the questionnaire was determined using Cronbach α. An α > 0.9 is considered excellent, α > 0.8 is good, α > 0.7 is acceptable, α > 0.6 is questionable, α > 0.5 is poor, and α < 0.5 is unacceptable (10).
The scoring system was adapted from a questionnaire that was validated in adults (9). Briefly, each ACNES-related question may score 1 point for a positive answer (Yes or mostly/regularly), whereas an IBS-related question scores 1 point for a negative answer (No or sometimes/never). Patients most likely having ACNES will acquire high scores, whereas a low score is attained by a typical IBS patient. Scores may range from 0 (IBS likely, ACNES not likely) to 18 (IBS not likely, ACNES likely). Subsequently, discriminating diagnostic test properties (sensitivity, specificity, positive likelihood ratio [LR+], negative likelihood ratio (LR−) were calculated for several cut-off values. Positive and negative predictive values (PPV and NPV) were assessed based on a prevalence of ACNES of 12.5% as determined in a previous study (8). In addition, we determined the accuracy, which is reflected by the area under the receiver operating characteristic (ROC) curve (AUC). An area of 1 represents a perfect test whereas an area of 0.5 represents the least possible accuracy (flipping a coin). A good accuracy is associated with an AUC between 0.8 and 0.9 whereas an AUC > 0.9 represents an excellent accuracy (11). A proposal for the cut-off point was made using a calculation of Youden's J index. This index combines sensitivity and specificity into a single measure (sensitivity + specificity − 1) and has a value between 0 and 1. In a perfect test, Youden's index equals 1 (12).
Questionnaire Response Rates
A total of 45 responses were obtained from 61 eligible children who were operated for ACNES (group 1, 74% response rate). As 3 questionnaires were excluded because of missing items, 42 children were available for analysis (median age 14 years, range 9–17 years, girls 75%). In the prospective ACNES group (2), a total of 59 responses were obtained from 64 eligible children (92% response rate). As 2 responders were excluded because of missing items, complete questionnaires of 57 children were eligible for validation (median age 13 years, range 9–17 years, girls 71%). In the prospective IBS group (3), 53 complete questionnaires in children (12 years, 9–17, girls 42%) were eligible for validation (69% response rate, 4 responses excluded because of missing items).
Content Validity and Internal Consistency
Table 2 shows discriminating symptoms associated with either ACNES or IBS. In both ACNES groups, ACNES-related items were mainly positive whereas IBS items were mostly negative. One item (pain dominates over discomfort) showed no discriminative value between both ACNES patient groups and the IBS group (P = 0.4) and was deleted from the final questionnaire. All the remaining 17 items showed discriminative power (P < 0.01). For this set of 17 items, a Cronbach α of 0.74 was calculated. In this final set of items, 13 items investigated qualities of pain whereas 4 items concerned additional complaints.
Cut-off Point and Predictive Values
As depicted in Table 3, a median score of 13 points (range 8–17) was found in both ACNES groups (1 and 2). In contrast, a median 8-point score was found in children with IBS (group 3, range 3–13). Questionnaire score was similar for younger and older children. However, scores of 14 and more were exclusively found in ACNES patients (Fig. 1). Table 4 depicts test properties that were calculated for several cut off values. A cut-off value of 11 points offered the highest Youden's J index (0.75) with an AUC of 0.94. Using the previously determined 12.5% ACNES prevalence rate, positive, and negative predictive values were 54% and 98%, respectively (8).
The present study describes the construction and validation of a 17-item questionnaire as an objective screening tool for ACNES in children. The results show that all children with a score of 14 or more were having ACNES. Conversely, children with scores of 7 or less were all having IBS. At a 11-point cut-off threshold, the test has excellent accuracy (AUC 0.94) with an 86% sensitivity and an 89% specificity. The corresponding negative predictive value of 98% makes the questionnaire a reliable screening tool for exclusion of ACNES.
ACNES is a largely unknown entity and often overlooked as the source of abdominal pain. ACNES is considered a representative of the family of CAWP syndromes. An important discriminative feature of ACNES is the altered skin sensation covering the point of maximal pain. Unfortunately, physicians are not trained to test the skin sensation in patients with abdominal pain. A survey among internal medicine residents found that only a quarter was able to recognize abdominal wall involvement (13). Moreover, ACNES has overlapping symptoms with IBS. As described in Rome IV criteria, IBS is defined as recurrent abdominal pain (at least 1 day/week) in the last 3 months, associated with defecation and/or a change in frequency of stool and/or a change in appearance of stool. As previously described, children suffering from ACNES also report complaints related to bowel movement (8). Therefore, we strongly feel that increased awareness of abdominal wall involvement as provided by a simple questionnaire will likely decrease diagnostic delay in potential ACNES cases.
In addition to its use in clinical practice, this questionnaire could promote reliability of research in the field of ACNES. The lack of objective diagnostic tests has been reported in recent literature reviews (14–16). At present, studies objectively validating the diagnostic criteria of ACNES were not published. ACNES is currently diagnosed following a strict physical examination including Carnett's test and pain relief following a local anesthetic injection. In daily practice, this method may be sufficient. For scientific use, however, this approach may be too limited potentially introducing various types of bias. An objective measure that is provided by a questionnaire may decrease selection bias in future ACNES trials.
Although there is a strong tendency to rely on laboratory testing or ultrasound whenever diagnosing abdominal pain syndromes, the very first step in the diagnostic process is the child's history. This is even more true in syndromes that lack characteristic blood abnormalities or imaging. Reported diagnostic clues suggesting ACNES are all related to pain. This pain is often debilitating, sharp or stabbing/burning, and predictably localized in anterior portions of the abdomen (area of the rectus muscle) whereas the benefit of medication is often limited (17–27). Specific circumstances that aggravate (lifting, stretching, lying on the painful side) or alleviate the discomfort (rest) were reported (8,26). In our IBS population, however, a substantial number of children also confirmed pain-related symptoms. For example, 42% of the IBS population reported pain characteristics traditionally associated with neuropathic pain (sharp/burning), and over 80% reported a pain spot that did not migrate. Both items were even more suggestive ACNES (78% and 98%, respectively). As depicted in Table 2, 86% of our ACNES children reported aggravation of pain because of exercise compared with 28% of the IBS children. In addition, coughing, sneezing, and even laughing aggravated the pain in half of these young patients suggesting a serious disease burden during these normal daily life activities. Therefore, a child who suddenly avoids hobbies or sporting activities because of abdominal pain should be evaluated for the potential presence of an abdominal wall involvement including ACNES.
The present study has limitations. For instance, test-retest reliability of the questionnaire was not assessed. Selection bias may have been present as questionnaire response rates that were obtained from the 3 different populations ranged from just 69% to up to 92%. Moreover, the survey responses of groups 1 and 3 may have been biased because of screening for ACNES. To a lesser extent, questionnaire outcomes in group 2 may have been biased as the patients and parents knew they were referred to a center of expertise for ACNES.
In conclusion, making a distinction between ACNES and IBS is difficult, even if a pediatrician is familiar with characteristics of the 2 conditions. The present questionnaire proved valuable in the identification of the abdominal wall as the source of abdominal pain (Supplemental Digital Content, http://links.lww.com/MPG/B638).
This study is in part supported by a grant from “Nuts-Ohra Fonds.”
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