There is increasing evidence to suggest that FAC may represent early stages of IBD. This causal relationship appears most prevalent in children and less so in adult patients. This is likely because of fewer confounding factors, such as recommendations for children not to receive bowel preparations prior to endoscopy [8] and less long-term treatment with drugs linked to colitis, such as NSAIDs, PPIs and corticosteroids, in this population [9–15]. Furthermore, children are less likely to suffer from bowel ischaemia and diverticulosis that may predispose patients to infective colitis [16]. Due to the apparent higher rates of IBD in children with FAC, Osmond et al suggested that FAC warrants more aggressive follow-up in children compared to adults. However, there is growing evidence that FAC may also be associated with IBD in adults, although distinguishing between high and low risk groups remains challenging.
Due to the relatively low diagnostic yield and the non-specific nature of FAC, most studies have been limited to retrospective data collection and small sample sizes. To date, our study is the largest retrospective study performed in an adult population that analyses the eventual clinical outcome following a diagnosis of FAC. In addition, this is the first study to explore the relationship of endoscopic and biochemical predictors with the eventual clinical evolution and outcome of FAC.
Consistent with previous studies, a large proportion of patients had FAC related to infection. Only 3 of 14 (21%) patients had a definitive diagnosis of infective colitis from stool cultures, of which 2 (67%) cases were secondary to Clostridium difficile infection, and 1 (33%) case was related to Shigella dysenteriae infection. Other studies have identified Entamoeba histolytica and Campylobacter jejuni as infective causes of FAC [2, 7], and the heterogeneity of microbiological detection between studies emphasises the nonspecific histology of FAC in infective colitis. The higher ratio of infective colitis seen in adults compared to children may be due to higher incidence of diverticulosis and bowel ischaemia, as well as higher usage of antibiotics and anti-acid secretion medications, all of which predispose to colonic dysbiosis17.
Due to the high rates of ‘incidental’ findings of FAC among different studies, various bowel preparations have been speculated to be implicated in the pathogenesis of localised mucosal inflammation and resulting histological findings consistent with FAC [18–20]. Although difficult to categorically exclude this, the low detection rates of FAC in the UK population, where bowel preparations for both sigmoidoscopy and colonoscopy are standardised, makes this hypothesis less credible [2].
Contrary to other studies, we detected a relatively low number of patients who were later diagnosed with drug-induced FAC. All 3 (7%) patients diagnosed with drug-induced FAC were taking NSAIDs and symptoms improved upon drug cessation. Interestingly, 4 out of 10 (40%) patients diagnosed with incidental FAC were on acid suppressive medication, and 2 of 10 (20%) patients were prescribed statins. Both classes of drugs have been implicated in the development of drug-induced colitis and this may have been a contributory factor to these patients’ symptoms and histological findings. It is well-established that NSAIDs are associated with colitis, and therefore the low detection rates of drug-induced colitis in our cohort may reflect a paucity of awareness amongst clinicians of alternative drugs as a cause of colitis [9, 14].
Our study identified 5 patients (12%) with FAC who were later diagnosed on follow up with IBD (endoscopy and histology), of which 4 (80%) were diagnosed with UC and 1 (20%) with unspecified IBD. This is in contrast to other studies where there has been a stronger correlation between FAC and CD. This discrepancy, and the underrepresentation of UC, may be incidental and reflect the small sample sizes of each study. Another explanation is that FAC may actually be an early finding consistent with all forms of IBD. However, given the close proximity of clinical presentation and histological findings, it is unlikely that the presence of FAC in patients later diagnosed with IBD is incidental.
90% of patients with UC have been shown to have at least 1 episode of relapse and remission from diagnosis. The relapse/remission rate is prognostically important, and early changes in disease activity (within 2 years) have been associated with a more aggressive trajectory [21–22]. In our study, all 5 patients diagnosed with IBD were followed up for more than 2 years after diagnosis, and none developed symptoms necessitating hospital admission, biological therapy or surgical resection. Although not statistically significant, we observed a trend towards milder disease course when FAC is associated with IBD.
Due to our limited sample size, we could not identify any statistical significance in differentiating a causal relationship between FAC and IBD and non-IBD pathologies based on symptoms, duration of symptoms, or blood markers. Nonetheless, we identified that adult patients with an eventual diagnosis of IBD had raised inflammatory markers (CRP and WCC) when initially presenting with FAC, in contrast to non-IBD patients, these findings being consistent with Osmond et al in the paediatric population. We postulate that markers of inflammation, namely CRP and WCC levels may be additional diagnostic markers for IBD in the context of FAC.
In addition, and most importantly, our study found that adult patients with a histological diagnosis of FAC were statistically unlikely to develop IBD if at presentation the endoscopic features and faecal calprotectin levels were normal. These findings augment clinical decision making, particularly with respect to active surveillance for IBD. The worried well can be reassured without unnecessary further investigations and follow-up.
Based on the 2017/18 Archived Reference Costs published by NHS Improvement [23], the average cost per unit for an outpatient lower gastrointestinal flexible sigmoidoscopy and colonoscopy with biopsies are £176 and £370, respectively. The cost of a follow-up clinic ranges from £90 to £149 depending on whether these are conducted face to face. In a large district general hospital such as our institution, serving 450,000 patients, FAC is diagnosed on average once per month. Factoring in a £36 per unit cost of FC level [24], a total of £3709 to £4347 can be saved per annum by eliminating costs of unnecessary repeated endoscopy and follow-up clinics. Extrapolating this nationally, we estimate an annual cost savings to be between £533,000 and £638,000 for the UK. This is likely to be an underestimate as unanticipated inpatient spells surrounding procedures are not included.