The incidence of periappendiceal abscess accounts for 9.7% of complex appendicitis in the pediatric population (1). However, its optimal treatment (surgery or conservative treatment) is still controversial (2). Although recent guidelines have recommended units with skilled laparoscopy to perform an immediate emergency appendectomy to shorten the hospital stay (3), considering the high incidence of complications in emergency surgery, conservative management (antibiotics with or without percutaneous drainage) is still the preference of most doctors (4, 5).

Traditional Chinese medicine (TCM) has been widely used in Asian countries with a long history. Recent studies have shown that TCM plays an important role in treating coronavirus disease 2019 (COVID-19) and controlling mild hypertension (6, 7). Meanwhile, rhubarb peony decoction (RPD) is one of the most famous TCM formulas in China. From the Eastern Han Dynasty, RPD (also called “Dahuang-Mudan decoction”) has been extensively used to treat intra-abdominal inflammatory diseases, such as appendicitis, pancreatitis, and inflammatory bowel disease, usually achieving satisfactory effectiveness (8, 9). However, most of these studies focus on adults, and the use of RPD in treating periappendiceal abscess in children is rarely reported. To this end, the present study aimed to evaluate the effect of RPD by comparing the therapeutic effects of intravenous antibiotics alone and antibiotics combined with RPD on pediatric periappendiceal abscess.

A total of 142 patients (77 girls and 65 boys) diagnosed with periappendiceal abscess and having received conservative treatment were enrolled, 52 in the C-group and 90 in the I-group (a flowchart of the study is shown in Figure 1). The groups were similar in their gender (P = 0.082), age (P = 0.301), weight (P = 0.505), and duration of symptoms (P = 0.310). The abscess size at admission (25.85 ± 16.68 cm² vs. 26.71 ± 13.99 cm²; P = 0.744), WBC count (16.93 ± 6.06 × 10⁹/L vs.18.72 ± 6.11 × 10⁹/L; P = 0.095), and CRP level (62.14 ± 29.35 vs. 73.67 ± 50.28; P = 0.133) were also similar between the two groups. The demographics and clinical characteristics of the patients in the two groups before treatment are presented in Table 1.

There were no significant differences in the length of total intravenous antibiotic use (12.96 ± 4.69 days vs. 14.02 ± 3.88 days, P = 0.150) and LOS (10.69 ± 4.11 days vs. 11.85 ± 3.52 days, P = 0.077) between the two groups. The mean total course of RPD in the I-group was 11.82 days. Compared with the C-group, the I-group had a significantly higher cure rate (93.33% vs. 80.77%, P = 0.029), and the time to treatment failure was earlier in the C-group (median 4.0 days vs. 5.5 days, P = 0.008). Laparoscopic appendectomy was performed on all 16 patients who received unsuccessful treatment. During the entire treatment and postoperative follow-up, no patients had a liver injury caused by RPD (Table 2).

Among those who succeeded in conservative treatment, four patients developed recurrent appendicitis in both groups, and no significant difference (9.52% vs. 4.76%, P = 0.439) was observed in the recurrence rate between the two groups. The median time appearing relapse was 35 (9–53) days in the C-group and 30 (15–45) days in the I-group (P > 0.05). Among the recurrent patients, two chose to continue nonoperative management, while six received emergency laparoscopic appendectomy (P = 1.000). In addition, no significant difference was observed in the operation time (98.75 ± 37.24 min vs. 89.50 ± 37.92 min, P = 0.740) and the length of hospital stay (9.25 ± 4.57 days vs. 11.25 ± 5.85 days, P = 0.610). Additionally, most of the recurrent patients were found to be girls (F:M = 7:1) (Table 3).

Finally, 107 patients received interval appendectomy and completed the follow-up, except for 11 (3 in C-group and 8 in I-group) who did not return to the hospital for surgery within 12 weeks. The operation time (61.40 ± 15.18 min vs. 67.90 ± 20.68 min, P = 0.101), length of stay (5.51 ± 1.99 days vs. 5.73 ± 1.85 days, P = 0.572), and rate of postoperative complications (2.86% vs. 1.39%, P = 0.549) were not significantly different between the two groups. One patient had an intestinal obstruction in the C-group, and one developed pelvic fluid collection. Both of them were discharged after conservative treatment (Table 4).

Appendicitis is the most common acute abdominal disease in the pediatric population. Due to the delay in diagnosis and stercolith in the appendix cavity, it often contributes to perforation and periappendiceal abscess formation, accounting for 3% of appendicitis cases (10). In this situation, emergency surgery may be difficult since the appendix and surrounding tissues are edematous and fragile. The risk of intestinal resection is up to 25%, and that of complications is 57% (11). However, the success rate of conservative treatment can reach 90% (12), and there are fewer complications, even without an IA, after conservative management. In this case, conservative treatment is accepted by most doctors and parents, which includes antibiotics with or without percutaneous drainage (4, 13). Double-agent antibiotic therapy can provide equal efficacy and is more cost-effective than triple-agent therapy in the case of treating periappendiceal abscess. Additionally, percutaneous drainage is required when the treatment is ineffective (14, 15). For children, CT guidance percutaneous drainage needs anesthesia and increases the risk of radiation exposure, and some studies recognize drainage as a risk factor for the recurrence of appendicitis (16, 17). To this end, considering the treatment characteristics of TCM, antibiotics combined with RPD are often adopted by our institute for the conservative treatment of periappendiceal abscess, and favorable effects are achieved.

In China, TCM plays a major role in the conservative treatment of inflammatory diseases. Chinese people and their children are more willing to accept TCM treatment and have a high recognition of its efficacy. As early as 1979, Nan Kai Hospital in China reported using Chinese and Western medicine to treat acute abdominal diseases, including acute appendicitis, intestinal obstruction, pancreatitis, and biliary tract infection. Among 1,200 patients with acute appendicitis, 130 cases of periappendiceal abscess were treated with integrated traditional Chinese and Western medicine. The total cure rate was 94.2%, and the recurrence rate was 14.5% (18). However, the report did not provide details of the TCM prescriptions for treating periappendiceal abscess and the distribution of the included patients (adults and children). The cure rate of antibiotics combined with RPD in the present study was 93.33%, which was similar to that reported by Nan Kai Hospital and was significantly higher than that of intravenous antibiotics alone. However, the recurrence rate after successful conservative treatment was 4.76% in the I-group, lower than the reported 14.5%, which might be attributed to the different treatment strategies, such as the types of TCM and antibiotics. During the follow-up, the operation time, LOS, and the incidence of postoperative complications were similar between the two groups after receiving interval appendectomy. In recent years, an increasing number of traditional medicines (including traditional Japanese medicine) have achieved satisfactory results in the treatment of pediatric surgical diseases, such as perianal abscess (19), biliary atresia (20), and spermatic cord hydrocele (21).

In TCM, the patients can be categorized according to the principles of syndrome differentiation. Periappendiceal abscess is also called “intestinal carbuncle” and belongs to the accumulated damp-heat syndrome. The treatment should be based on the principle of heat-clearing and blood circulation promotion to remove the meridian obstruction. Rhubarb and moutan bark are the main components of RPD, which are also known as the monarch herb (Jun herb) in the TCM theory. Rhubarb provides the functions of heat-clearing, fire-expelling, blood-cooling, and toxin-relieving. Moutan bark is endowed with the functions of promoting blood circulation to dissipate blood stasis, heat-clearing, and detoxifying. The therapeutic effect will be more effective in the case of a drug combination. The minister drug (Chen herb), such as prunus persica, wax gourd kernel, and mirabilite, helps strengthen the curative effect of the monarch drug or is generally used to treat accompanying symptoms.

According to the opinion of contemporary medical research, the above therapeutic effects are attributed to the main bioactive constituents of RPD. The main bioactive constituents extracted from the RPD include emodin, aloe-emodin, rhein, paeoniflorin, and amygdalin, which have been shown to have extensive anti-inflammatory and antioxidant activities in modern pharmacological studies (22–25). Nong et al. confirmed that RPD dealt with colitis by restoring the balance of multiple disturbed pathways and regulating to a normal condition (26). Apart from efficacy, the safety of TCM is another factor to be considered in the treatment. There are reports that TCM may induce liver injury (27). In this study, the average number of days of oral RPD was 10.48, and no RPD-induced liver damage was found during the treatment, suggesting the safety of taking RPD for the treatment of periappendiceal abscess in the short term.

There are some limitations in our study. First, this is a single-center retrospective study with limited sample size. In addition, it may be difficult for children to receive traditional medicine formulations because of the uncomfortable taste. Finally, although antibiotics combined with RPD are found to be capable of improving the success rate in the treatment of pediatric periappendiceal abscess, the RPD includes several different herbs, such as Rhei Radix Et Rhizoma, Moutan cortex, semen persicae, waxgourd seed, and Natrii sulfas, and which chemical substance plays a key role in this pathology process and its complex composition make the specific mechanism still unclear.

To the best of our knowledge, this study was the first report on the effect of RPD in children with periappendiceal abscess and showed that intravenous antibiotics combined with RPD demonstrated high effectiveness and safety for the treatment of pediatric periappendiceal abscess. Given the limitations of this study, the efficacy of RPD in treating pediatric periappendiceal abscess needs to be further justified by a prospective randomized study in the future.