Table 4 shows the Rome diagnoses, based on symptom clusters at presentation and absence of alarm symptoms. As can be seen from the table, a functional diagnosis according to the Rome criteria did not exclude the possibility of an organic cause of the abdominal pain. At the end, the clinical diagnoses made clear which patients had an organic and which patients had a functional diagnosis.
The performance of the Rome criteria (Rome diagnosis) to detect a functional disorder (clinical diagnosis) is based on the 2 × 2 table depicted in Table 5: sensitivity 0.35 (95% confidence interval 0.27–0.43), specificity 0.60 (0.46–0.73), PPV 0.71 (0.61–0.82), NPV 0.24 (0.17–0.32), LR pos 0.87 (0.59–1.29), LR neg 1.09 (0.85–1.40).
This is the first study to validate the Rome criteria for the functional pain syndromes as to their capacity to differentiate between organic and functional causes of abdominal pain in children and to assess the significance of alarm symptoms in children with abdominal pain.
Our main finding is that the Rome III criteria are not able to differentiate between organic and functional causes of abdominal pain and that alarm symptoms suggesting organic causes of RAP are present in the same percentage in patients with a clinical diagnosis of a functional condition as in patients with an organic condition, implicating insufficient capacity to differentiate between organic disease and functional causes of abdominal pain.
Alarm symptoms are considered a reason for more extensive clinical investigations (2,4,10). In this study we found 57.5% of the patients presenting with 1 or more alarm symptoms. Remarkably, alarm symptoms were found as frequently in patients with functional disorders as in patients with organic disease. Although alarm symptoms are important for the recognition of more severe conditions such as Crohn disease, they are not helpful in the diagnostic process of RAP. In this population of 200 patients, we did not find any patient with Crohn disease because at presentation in this secondary care center, the patients with Crohn disease had other main symptoms than merely RAP, and therefore could not be included in the study.
It is noteworthy that the individual alarm symptoms all showed roughly the same distribution in the various clinical diagnosis groups. Rectal blood loss is not unusual in children with constipation; in most patients blood loss was probably caused by fissures, which, however, were not seen at physical examination. Other alarm symptoms in children with a functional diagnosis are more difficult to understand. In a study on the frequency of Rome III pain diagnoses in children with abdominal pain, Helgeland et al (11) found 7% to have alarm symptoms, also suggesting that a better definition of alarm symptoms is needed.
The low sensitivity of the Rome criteria is inherent to the Rome procedure and the high prevalence of alarm symptoms: before a Rome diagnosis of a functional disorder can be made, patients with alarm symptoms need to be investigated for organic disease. Unfortunately, alarm symptoms appear to be at least as frequent in functional as in organic disorders, and many patients with alarm symptoms end up to have a functional cause of their pain.
The Rome symptoms are developed to enable the diagnosis of a functional disorder in the absence of alarm symptoms with sufficient certainty, without the need of further investigations. The PPV indicates the reliability of this approach. Organic disease would have been missed (1-PPV) in 21 of 73 patients (29%) with a Rome diagnosis. This percentage is higher than that in the study by Helgeland et al (11), who found that 8 of 152 children (5.3%) with organic diagnoses would have been missed had the investigations been limited to medical history, clinical examination, and stool examination for blood.
The history of the Rome criteria starts with the Manning criteria for adult IBS, published in 1978 (3). In 1990, Talley et al (12) evaluated the validity of the Manning criteria for the discrimination of patients with IBS from healthy controls, from patients with other gastrointestinal diseases and from patients with nonulcer dyspepsia. Sensitivity and specificity of the Manning score with respect to differentiation of IBS from organic disease were 58% and 74%, respectively. Two systematic reviews on the validation of symptom based criteria in adults with IBS concluded that insufficient studies are performed to validate the diagnostic criteria for IBS but that until now none of the symptom-based criteria can accurately exclude organic disease (13,14).
It is noteworthy that the process of validation of the Rome criteria is complicated by the requirement of “No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject's symptoms” as a prerequisite for a functional diagnosis. Obviously, it is unclear how to establish “no evidence” of organic disease. The Rome Working Team advises diagnosis of IBS when symptoms meet the IBS criteria, in the presence of a normal physical examination and growth curve with the absence of alarm symptoms; for FAP and FD comparable advices are given (4,10). Our study shows that more organic causes can be found when more thorough investigation is performed. As we have shown earlier, the majority of children with an organic cause can be identified with a limited number of tests (8). We are not the only ones drawing this conclusion. Several authors disputed the clinical utility of the Rome criteria because of insufficient differentiation between functional and organic disease and insufficient help with identification of individualized therapeutic strategies that are based on etiologic mechanisms (15,16).
Additionally, this study provides no evidence that differentiation between the functional pain syndromes makes any difference with respect to therapy or outcome. For clinical use, the added value of the Rome classification is limited. This is reflected in the use of the Rome criteria in children with abdominal pain by only 39% of members of North American Society of Pediatric Gastroenterology, Hepatology, and Nutrition (17). With respect to research, the gain of the Rome classification for functional gastrointestinal pain syndromes lies in the more restricted symptom clusters as opposed to the broad Apley criteria. More uniformity of presentation presumably is a better basis for research, especially with respect to pathophysiology; however, diagnostic disagreement with respect to Rome classification is a recognized problem, in view of the considerable inter- and intraobserver variability and the limited diagnostic agreement between physicians, parents, and children, with respect to both Rome II and Rome III criteria (18–21).
The strength of this study lies in the way of establishing the diagnoses, based on preset criteria including therapeutic intervention to establish a causal relation in every patient, as a basis for validation of the Rome criteria for the functional pain syndromes, and the independent scoring of the Rome criteria.
The limitations lie first in the difficulty to prove causal relationships with certainty. Therefore, we strictly adhered to 3 criteria for the assessment of a clinical diagnosis: the patients should be pain free after the intervention; there should be an appropriate, diagnosis-specific interval between therapeutic intervention and the patient becoming pain free; and the therapeutic effect should last at least 6 months. Thus, we aimed to evade the risk of considering spontaneous recovery or temporary relief as caused by the intervention, as well as that of confusing the treatment result with a placebo effect—which has been shown to seldom last as long as 6 months (8,22). A second limitation is that the categorization of Rome diagnoses was performed by 1 specialist only. This approach was chosen, however, because the observer in question was himself a member of the Rome III committee, and because we were less interested in differentiating between the various Rome diagnoses—which is the main cause of interobserver variation—than in their presence or absence. Obviously, this has had no influence with respect to the major effect of alarm symptoms.
In conclusion, we provide evidence that the clinical symptom-based Rome III criteria are not specific enough to rule out organic causes of abdominal pain. Moreover, the presence of alarm symptoms does not differentiate between organic and functional abdominal pain.
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alarm symptoms; chronic abdominal pain; functional gastrointestinal disorders; Rome criteria; validation
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