Discussion

The diagnosis of IBS remains a perennial challenge for primary care. Despite attempts to identify symptom complexes that allow for a positive diagnosis, limited sensitivity and specificity mean that a confident diagnosis is often elusive. This places a significant burden upon secondary care gastroenterology services. Ideally, what is needed is a locally available screening test. The test should be sufficiently powerful for a positive diagnosis of functional intestinal disease to be made, providing necessary reassurance to the patient and allowing the primary care physician to focus on symptomatic treatments.7 Such therapy could be delivered locally sparing expensive and unnecessary referral into secondary care. Tibble et al4 first demonstrated the utility of faecal calprotectin as a possible screening test for distinguishing between IBS and IBD. While faecal calprotectin does have a role in the assessment and monitoring of IBD, it is not a sufficiently specific test to permit its positive diagnosis. In a range of disease processes, drug or alcohol induced, infective, inflammatory, ischaemic and malignant, the faecal calprotectin may be elevated. The present study confirms this observation, as 15 diagnoses other than IBD were made during the period of review.

The hypothesis upon which this study was based is that the strength of testing faecal calprotectin lies in the predictive value of a normal result rather than that of an abnormal one. It is postulated that a normal faecal calprotectin allows for the safe and cost-effective local management of IBS within primary care based upon a confident diagnosis. Dolwani et al8 had already demonstrated an NPV of 100% in a small cohort of patients. And in a recent meta-analysis it had been concluded that measuring ‘faecal calprotectin is a useful screening tool for identifying patients who are most likely to need endoscopy for suspected IBD.’9 The authors however expressed reservations about its utility in primary care. To date, no studies have been performed in the primary care setting to refute this.10 11

Presented in this current study are the outcomes of 500 consecutive patients referred from primary care with intestinal symptoms and followed from the point of referral for almost 5 years. This represents a clinically relevant and heterogeneous cohort of patients and for the first time demonstrates both the clinical advantages and difficulties that would arise from using faecal calprotectin as a screening tool. Inflammatory markers and screens for coeliac disease were routinely performed and appropriate investigation and management were consultant led in almost all cases. Patients with fast-track symptoms require definitive investigation and so were excluded from the study. A broad range of patient symptomatology was described, characterised by any change in bowel habit or abdominal pain and bloat and a small but substantial group with what proved to be anal canal bleeding. Within this disparate group of patients a normal faecal calprotectin predicted for functional intestinal disease with 96.4% accuracy. Those aged over 60 years were excluded from the study because of the increase in significant incidental intestinal disease noted with ageing. Potential cost savings are implicit from this study. Sixty-three per cent fewer outpatient management contacts occurred in patients where the diagnosis of a functional disorder was made positively without recourse to investigations. If a normal faecal calprotectin was able to bring a cohort of patients into this management group, considerable savings would accrue. And of those referred, approximately 40% required three consultations or less before discharge. It seems reasonable to conclude that simple medical and dietetic guidance in the setting of a confident diagnosis might be sufficient for many patients. Based on such data, the NHS Centre for Evidence-based Purchasing has recently conducted an economic evaluation of the use of faecal calprotectin.12 The findings from this current study support their projected savings of £13 464 per hypothetical cohort of 1000 patients.

Set against these safety and cost-effectiveness headlines a number of challenges are highlighted by this study. First, within the normal faecal calprotectin cohort, significant incidental non-intestinal and intestinal diseases were identified. Such occurrences would be inevitable in practice and while not directly relevant to the exclusion of intestinal organic disease in patients with symptoms nonetheless result in health benefits. To this end, it is worth noting that the referrals resulted in the diagnosis of five malignancies. Next, it is clear that, with or without a formal diagnosis, the management of functional intestinal symptoms can be very challenging and the data confirm that many patients required prolonged follow-up. Within our unit, this would have involved conventional consultations, close dietetic liaison, IBS nurse specialist input, with access to hypnotherapy, and clinical psychology. Whether primary care can currently offer such a resource is uncertain. Finally, the cost benefit of a normal faecal calprotectin result has to be offset against the unnecessary investigations that arise from false positives. Evidence from the patient record system confirms that patients with a positive faecal calprotectin were more extensively investigated, often with formal small and large bowel investigations, attending hospital on an average approximately eight times compared with five and a half times for those with a normal result. The cost of this would need to be taken into account when considering the merits of a normal faecal calprotectin as a screening test. However, with approximately 39 false positive results for 482 true negatives during the period of review one might infer that only a small proportion of patients would be over investigated compared with the number spared such investigations. The PPV of a raised calprotectin can be improved simply by repeating the test. A subsequent normal result should be interpreted as such. An alternative area to pursue is the cut-off for a normal calprotectin in clinical practice. Increasing the normal range improved the PPV of a raised result but this was offset by a gradual reduction in the NPV of the test. Clearly, maintaining a very high NPV is the key to its value as a screening tool but perhaps increasing the ‘normal’ threshold to 60 would be reasonable from this study.13 14

In conclusion, this retrospective feasibility study demonstrates that a normal faecal calprotectin has the potential to become an integrated screening tool for use in patients with intestinal symptoms. However, the study also exemplifies the challenges that would arise should such a test be adopted. Its negative predictive power makes it a safe test and estimates of cost savings have been projected. However, care must be taken when interpreting these retrospective data. Bias is an inevitable variable; it is unlikely that all patients were recruited and the faecal calprotectin results were not blinded. What now is needed is a well-constructed prospective assessment of its safety and efficacy in a primary care setting. A clinic based qualitative assay is now available to facilitate such a study (PreventID CalDetect).15 16Aside from economic savings, the significant additional benefit is the promise of accelerated diagnosis of those patients hidden among the majority with IBS who have IBD.