Early diagnosis of appendicitis in children not only prevents perforation, abscess formation, and postoperative complications, but also reduces costs by shortening hospital stay.13 In young or preverbal children, history taking is difficult, and physical examination findings are equivocal.6,14,15 Clinicians have difficulties in diagnosing appendicitis immediately in these cases. Abdominal computed tomography is often used in these children with suspected appendicitis because of the fast result and high accuracy. However, the exposure to ionizing radiation and high healthcare costs should be considered.10 These concerns have led to the search for new diagnostic tools for predicting appendicitis. Thus, we tested the use of sCD40L as a predictor of pediatric appendicitis and perforated appendicitis in our study.
Our study demonstrated that sCD40L levels may be a good predictor for acute appendicitis and perforated appendicitis. As far as we know, this is the first study that sCD40L could be evaluated as a potential serum biomarker for predicting appendicitis in children. Based on our results, once children with clinically suspected acute appendicitis have serum sCD40L levels less than 90.04 pg/ml, primary clinicians may exclude the possibility of acute appendicitis. However, once children have serum sCD40L levels exceeding 301.00 pg/ml, the diagnosis of acute appendicitis could be confirmed. Furthermore, sCD40L may also serve as a potential predictor for perforated appendicitis. Clinically, sCD40L levels less than 180.95 pg/ml may be used to rule out perforation of the appendix while sCD40L levels exceeding 342.80 pg/ml could be evaluated to confirm perforated appendicitis. In contrast, primary clinicians need to pay more attention to an indeterminate zone in clinical practice because it is not easy to make decisions about children with clinically suspected appendicitis. In this indeterminate zone, primary care clinicians need more diagnostic aids to achieve accurate diagnosis for appendicitis and determine whether perforation has occurred or not. In addition, it is important to prevent progression to septic peritonitis. In this study, we found that sCD40L may be helpful in discriminating between children with acute appendicitis and those with normal appendices. Clinically, once the cutoff point of delta sCD40L is greater than 178.00 pg/ml, the probability of acute appendicitis will decidedly increase. In addition, once sCD40L is greater than 308.26 pg/ml, the probability of perforated appendicitis will significantly increase. Based on our findings, the large AUCs of sCD40L may indicate its use as a helpful parameter in predicting both acute appendicitis and perforated appendicitis.
Our study revealed that sCD40L has a high sensitivity and specificity in predicting pediatric appendicitis. However, the role of sCD40L in appendicitis is novel, and it is possible that there are similarities with mechanisms observed in inflammatory and infectious diseases such as sepsis.12 CD40, a type I transmembrane receptor protein that belongs to the TNF receptor superfamily, is expressed on a variety of cell types including platelets, immunity cells, endothelial cells, fibroblasts, and smooth muscle cells. CD40 becomes active within the cell after binding to CD40L, which is stored in unstimulated platelets. When the platelets are activated, CD40L migrates to the platelet surface. Then, CD40L is cleaved and released becoming sCD40L, which binds to circulating monocytes and CD40 on endothelial cell surfaces. This stimulates the nuclear factor-κB signaling pathway with subsequent up-regulation of proinflammatory and prothrombotic factors. Thus, sCD40L plays an important role between immune responses and inflammation.16–19 Based on the related studies, we believe that sCD40L may be a useful inflammatory biomarker and could be applied in the diagnosis of appendicitis. Until now, none of the previous studies have reported about the association between sCD40L levels and appendicitis in children. Our study confirms that sCD40L is a potentially useful biomarker in diagnosing pediatric appendicitis and perforation of the appendix.
In conclusion, sCD40L may help the diagnosis of acute appendicitis and the prediction of perforation of the appendix in children. Therefore, we propose the addition of serum sCD40L testing to blood tests as a helpful diagnostic method in pediatric patients suspected of having acute appendicitis.