The presence of PD in CD patients usually indicates a distinct and aggressive disease course [2, 21, 22]. There is some evidence that the prevalence of PCD was higher in Asian than Western countries, and the outcomes of Asian PCD patients may differ from those of Western patients . The increasing tendency in China over the past few decades calls for more attention to be paid to the natural course of PCD in these newly developed disease population. However, Chinese studies evaluating the characteristics and outcomes of PCD patients are limited, and the significance of PD development at different ages is unclear. This is the first comparative study to investigate this issue among a Chinese 10-year observational cohort study in the first years of the biologic treatment era. Thus, this study allowed us to obtain key updated knowledge about the differences between PCD patients with paediatric and adult‐onset PD concerning the need for abdominal surgery. Firstly, we found that CD patients who developed PD during childhood had a more serious perianal phenotype and earlier PCD diagnosis and IFX treatment, while more aggressive luminal disease, current smoking and a higher rate of abdominal surgery were more common in AOP patients. Secondly, AOP and stricturing luminal behaviour were associated with an increased incidence of abdominal surgery. Finally, IFX administration could decrease the rate of abdominal surgery in AOP patients. These results indicate that more attention should be paid to patients with AOP and highlight the important role of early diagnosis and IFX therapy in achieving better clinical outcomes.
Previous studies have shown that approximately one-quarter of CD patients are diagnosed in childhood . Paediatric CD patients usually show distinct features, which are characterized by more severe disease activity and biological therapy than adult CD cases [15, 23]. In our study, 28.7% of PCD patients developed their first perianal symptoms during the paediatric period, and they presented with more complex perianal fistulas. However, the stricturing phenotype of luminal CD and CD-related abdominal surgery were more common in AOP patients. Thus, early-onset (paediatric-onset) PD presents more complicated local manifestations of PD, but late-onset (adult-onset) PD is more prone to progress to severe luminal damage progression. These results not only indicate distinct clinical characteristics and monitoring focus in CD patients who develop PD at different ages but also suggest the presence of distinct disease patterns for perianal and luminal CD.
Moreover, we found that PCD patients with POP had earlier use of IFX and a higher cumulative risk of IFX treatment. In the past decade, IFX was the only available biological agent for Chinese CD patients . Due to its efficacy in treating complicated CD, IFX has been recommended widespreadly in cases of early-onset or fistulizing PCD as a top-down treatment strategy in recent years [4-10]. We found that POP has been increasing over time, which means there is a trend for POP patients to be diagnosed and treated more recently. PCD diagnosis was performed earlier in POP patients than AOP patients. Therefore, the higher percentage of complex perianal fistulas, early-onset and recent diagnosis of PD in the POP group may contribute to the more frequent and earlier use of IFX.
The presence of PD speeds up the complexity of the natural history of CD, accelerates the development of luminal stenosis, and increases the risk of abdominal surgery in some studies of the pre-biologic era [2, 21, 22]. However, most of these studies focused on the adult-onset cohort, they neglected the influence of age of the PD development and biological agents on the CD outcomes. Recently, a Korean study reported that the presence of PD at CD diagnosis did not increase the risk for abdominal surgical intervention . And a Danish population-based study found that the occurrence of PD at CD diagnosis was not predictive of the risk for undergoing intestinal resection, whereas the development of PD during follow-up was . These results raise the possibility that the impact of the PD development time on the intestinal resection of CD patients may differ. The later the PD developed, the more common the complicated luminal damage and abdominal surgery presented. This result is inconsistent with the previous conclusion that the early-onset CD was associated with an increased incidence of CD-related surgery . But our results are similar to a recent study. They showed that there were more intestinal strictures and abdominal operations in adult CD patients than in paediatric CD patients, which was related to the longer diagnostic delay in adults . Similarly, we found the patient with AOP (late-onset PD) presented a higher rate of structuring behaviour and abdominal surgery. Factors including AOP and stricturing behaviour were predictive for increased CD-related abdominal surgery among all PCD patients. The use of IFX treatment also showed a negative correlation with the rate of abdominal surgery in patients with AOP. This verified the conclusion that the increased use of biologics is positively correlated with a reduced need for abdominal surgery . Furthermore, we observed that the time from the onset of PD to the diagnosis of PCD and the time from the diagnosis of PCD to the first use of IFX were longer in the adult-onset cohort. These results all suggest a later disease course and later IFX treatment in AOP patients. It has become increasingly apparent that the early use of IFX can decrease the occurrence of CD-related surgery in adult CD [17, 27]. Therefore, the more complicated luminal disease, underuse of IFX treatment and delayed initiation of IFX may contribute to the higher rate of abdominal surgery in AOP patients.
In addition, smoking has been reported as a definite factor associated with recurrence after surgery and a poor response to medical therapy in CD patients . Thus, the greater proportion of current smokers also explained the higher rate of abdominal surgery in AOP patients. These findings indicate that a close monitoring of luminal lesions and a positive therapeutic strategy, including the early and extensive use of IFX treatment and cessation of smoking, should be undertaken in PCD patients with AOP to reduce the rate of abdominal surgery.
One of the strengths of our study is the inclusion of all kinds of PCD, leading to a reduction in selection bias. The different clinical characteristics and outcomes of PCD patients with POP and AOP were directly compared in this study. We focused on the influence of PD onset age on the rate of abdominal surgery in CD patients, and found that there was an higher risk of abdominal surgery in PCD patients who developed PD at adults. These findings should alert physicians to pay close attention to these patients to ensure that they receive intensive treatment and close monitoring to achieve better outcomes in clinical practice.
However, there are some limitations to our study. The first limitation is the retrospective and single-centre design. Secondly, all of the PCD patients included in our study were hospitalized patients, who may have had relatively serious manifestations. Lastly, because of the nature of the general hospital, we only receive patients over 14 years old, so we cannot investigate the clinical characteristics and outcomes of CD patients with very early onset PD. And no factor was found to predict CD-related abdominal surgery in POP patients. Therefore, prospective, large-scale and multi-centre or population-based studies are required.
In summary, the age of PD development in PCD patients plays an important role in clinical prognoses. PCD patients with AOP showed a delay PCD diagnosis, underuse of IFX treatment and a higher risk for abdominal surgery than those with POP. These results suggest that the clinical impact of PD on the luminal outcomes of CD patients may be less prominent in patients with POP than those with AOP in this Chinese IBD centre. Early diagnosis and IFX treatment of CD in patients with AOP may therefore allow for earlier identification and management of potential CD-related luminal damage and reduce the incidence of abdominal surgery.