The relationship between perianal fistula activity and abdominal adipose tissue in Crohn’s disease: an observational study

In the present study, pelvic MRI and abdominal CT were analyzed in 136 patients with perianal fistulizing CD, and our results revealed differences in adipose tissue features among CD patients with different active perianal fistulas, that is, lower SAT and VAT density, higher SAI and VAI and lower VA/TA index correspond to lower perianal fistula activity, reflecting the relationship between perianal fistula and inflammatory load in CD patients.

CT body composition parameters have been used to reflect disease activity in CD patients and predict their prognosis. Feng et al. found that the λHU of creeping fat (CF) in CD patients increased with the severity of intestinal inflammation, and the λHU of CF around the intestinal segments without lesions was significantly higher than that in the controls [20]. Zhou et al. showed an increased risk of poor prognosis in CD patients with high SAT and VAT density [22]. Similarly, we observed higher VAT density at all levels in the high activity group (p < 0.01). Increased VAT density on CT images is often associated with elevated inflammation, suggesting increased inflammatory exudation in the diseased intestines. Therefore, VAT density is not only a distinguishing indicator of CD activity, but also reflects perianal fistula activity to some extent.

In Thiberge's study [21], CD patients with low SAI and VAI were at greater risk of adverse outcomes, which is supported by Zhou's results [22]. And the latter proposed standardizing SAT and VAT area with L1–L5 vertebral height instead of height to reduce reliance on clinical data, and the new standardized indexes obtained proved to be highly relevant to the traditional method. We adopted Zhou's standardized scheme and found lower SAI and VAI in the high activity group. However, some studies pointed out that high VAI in CD patients was associated with the occurrence of postoperative complications and increased risk of recurrence [28, 29], and they focused on demonstrating the role of VAT in the pathogenesis of CD. In fact, these indicators do not apply to patients with different nutritional status. Patients with longer disease duration tend to have lower contents of SAT and VAT as a result of disease consumption. But for some overweight or obese patients with a short course of disease, their SAT and VAT contents are generally higher than the former, but the disease activity is not necessarily lower. Therefore, if only the area or standardized indices are compared, the conclusions obtained tend to ignore their nutritional status.

In order to avoid the influence of absolute content parameters on conclusions, many studies have introduced relative content parameters Previous studies have shown that VSR or VA/TA index in CT images are higher in aggressive CD or patients with adverse outcomes [18, 22]; Buning et al. also found that high VAT/FM (total fat mass) ratio (the ratio of VAT to total body fat mass, similar to VA/TA index) was associated with more complex behaviors and higher activity by using MRI [30]. Moreover, in Bryant's study, in addition to finding higher VSR in patients with low life quality, they also found a positive correlation between VSR and stricturing disease behavior in ileocolonic CD patients [31]. We used the same parameters, and although the difference in VSR was not apparent between the two groups, higher VA/TA index at the L5 level was observed in the high activity group. It is also worth noting that patients in the high activity group had a higher percentage of stricturing disease behavior. Therefore, we believe that relative content indexes are more reliable when evaluating the negative impact of VAT on the course of CD. In addition, our analysis also shows a high correlation between the same parameters at the three lumbar levels. Therefore, researchers should consider possible differences at the L4 and L5 levels in addition to the L3 level commonly used in previous analyses when analyzing CD patients.

Previous studies mentioned that perianal disease can be the initial manifestation of CD, predating the onset of intestinal lesions [1, 32]. In our study, before being diagnosed with CD, forty-five patients underwent perianal fistula surgery, with a median time interval of two years, and the longest even reaching nine years. Usually, CD-induced perianal fistulas could not be cured with conventional treatment alone [33]. Patients with previous surgery in our study developed recurrent fistulas months or years later because they did not receive appropriate CD-related treatment. Therefore, it is necessary for clinicians to investigate the possibility of CD in patients who present with only perianal fistula. Even if patients do not show related gastrointestinal signs, they should be advised to pay attention to the occurrence of intestinal lesions in future routine physical examination.

Waheed’s study suggests that a complex or high perianal fistula on MRI images may be the initial presentation of CD, which differs from the general population [34]. By analyzing our patients, we found that 61.0% (83/136) presented with complex fistulas, whereas high fistulas were uncommon, only 8.1% (11/136). Oliveira et al. showed that the characteristics of perianal fistulas were actually similar in the CD and non-CD populations, as evidenced by abscess incidence, volume, and signs of fistula activity (high signal on T2WI images as well as focal enhancement); however, they also found that compared to the non-CD population, the CD population was younger (28.6 ± 14.9 y vs. 42.4 ± 14.7 y) and rectal inflammation was more common (30.2% vs. 6.7%) [35]. The mean age of our patients was 27.5 ± 10.2 years and the incidence of rectal involvement was 34.6% (47/136), similar to the CD population of Oliveira et al. (p = 0.51 and 0.49, respectively). Although we did not analyze the non-CD patients, our results support their conclusion that young patients with concomitant rectal inflammatory perianal fistulas are more likely to be further diagnosed with CD, which is associated with the involvement of the colorectum [2, 36].

Although no studies have verified consistency between perianal fistula activity and activity of intestinal or extraintestinal lesions in CD patients, it has been suggested that patients may have better outcomes after surgery when the intestinal disease is in a quiescent phase [37], reflecting the impact of systemic inflammation on perianal fistula treatment and prognosis. In the simple grouping we developed based on Van Assche's classification (low and high activity group), the high activity group had higher PDAI and laboratory inflammatory markers (CRP and ESR) and a higher proportion of complaints of perianal fistula-related symptoms (50.8% vs. 23.4%, p = 0.002), suggesting the validity of our grouping and revealing a correlation between perianal fistula activity and systemic activity in CD patients. Although we did not observe differences in CT parameters between patients with different outcomes, patients with low PDAI tended to be more responsive to treatment and had a better short-term prognosis in both low and high activity group, in line with the findings of Pikarsky et al. [38].

Our study has some limitations. Due to the retrospective design, the follow-up time and treatment were not controlled, and they did affect the outcome. Although the baseline results have not been affected, a rigorous prospective study should be carried to reveal the influence of CT parameters on the prognosis of perianal fistula.

In conclusion, we can simply divide perianal fistulas in CD patients into two states of high and low activity by using pelvic MRI, and fistula with high activity is related to higher VAT density and VA/TA index, suggesting higher overall inflammatory load.

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