Abstract
Importance
Childhood recurrent anterior epistaxis (RAE) commonly coexists with allergic rhinitis (AR), causing significant symptoms and distress to patients; however, treatment remains controversial.
Objective
To compare the clinical outcomes of pediatric patients with RAE and AR treated intraoperatively with silver nitrate cauterization (SNC) or radiofrequency coagulation (RFC).
Study Design
Prospective, randomized controlled study.
Setting
Tertiary referral center.
Participants
Pediatric patients presenting with RAE and AR.
Exposure or Intervention
Patients received SNC or RFC in a double-blind, prospective cohort study.
Main Outcome Measures
The Epistaxis Severity Score (ESS) and Visual Analog Scale (VAS) scores for AR-related symptoms were recorded at baseline, 4thweek, 3rd month, and 12th month.
Results
The rebleeding rate in the SNC group was 18.0% at the 4th week, 46.0% at the 3rdmonth, and 58.0% at the 12th month, whereas the RFC group demonstrated rates of 2.0%, 0%, and 0%, respectively (P < .05). At each follow-up time point, the mean ESS was significantly lower in the RFC group than in the SNC group. In addition, mean VAS scores for nasal crusting and impact on daily life (IDL) were significantly lower in the RFC group at all postoperative time points. Moreover, the RFC group exhibited significantly-lower mean VAS scores for runny nose and itchy nose at the 3rd and 12th month postoperatively. Similarly, the mean VAS score for nasal obstruction was significantly lower in the RFC group at the 12th month postoperatively. No cases of septal necrosis or perforation were observed in the SNC group. However, septal perforation occurred in 1 patient among the 4 who underwent RFC using the ablation mode.
Conclusion/Relevance
The thermocoagulation mode of RFC is a safe and effective treatment modality for bilateral RAE in pediatric patients. It significantly improves epistaxis and alleviates associated nasal symptoms. Furthermore, compared with patients treated with SNC, those receiving RFC exhibited a significantly-prolonged nosebleed-free period and a reduced likelihood of recurrent epistaxis within 1 year of treatment.
Key Points
This is a double-blind randomized controlled study of 100 children aged below 14 years with underlying allergic rhinitis, with the presentation of epistaxis to the outpatient clinic.
Patients were randomized to 2 different regimens to treat recurrent anterior epistaxis (RAE): silver nitrate cauterization (SNC) or radiofrequency coagulation (RFC).
The thermocoagulation mode of RFC is a safe and effective treatment modality for bilateral RAE in pediatric patients. It significantly improves epistaxis and alleviates associated nasal symptoms. Furthermore, compared with patients treated with SNC, those receiving RFC exhibited a significantly-prolonged nosebleed-free period and a reduced likelihood of recurrent epistaxis within 1 year of treatment.
Introduction
Recurrent anterior epistaxis (RAE), a common presentation in pediatric rhinology clinics, primarily originates from the cartilaginous portion of the anterior septum. Although topical antiseptic creams are effective in the management of crusting, silver nitrate cauterization (SNC) has traditionally been the initial intervention for visible septal vessels. 1 However, the efficacy of SNC varies considerably, with reported success rates of 45.7% to 89.0%.2 -4 The therapeutic outcome of SNC largely depends on the factors such as the concentration of silver nitrate and the duration of contact. 5 Recent studies have emphasized a significant association between RAE and allergic rhinitis (AR).6,7 Although intranasal corticosteroids (INCS) and allergen immunotherapy are effective treatment options for AR, the requirement for prolonged use often results in poor patient adherence.7,8 Notably, RAE associated with AR frequently presents bilaterally. Bilateral SNC significantly elevates the risk of septal perforation.
Radiofrequency coagulation (RFC) is an advanced technology that enables simultaneous soft tissue incision and hemostasis at relatively low temperatures (40 °C-70 °C), minimizing collateral tissue damage and promoting faster and less painful recovery.9,10 Although RFC has been widely used in the management of epistaxis, particularly in adults with hereditary hemorrhagic telangiectasia (HHT), limited studies exist regarding its application in pediatric RAE associated with AR.9 -11 This may be attributable to concerns regarding the incomplete development and relative thinness of the pediatric nasal septum.12,13 Some scholars reported that the thickness of the septal cartilage in the thinnest area was 0.4 to 0.5 mm in the newborn 14 and 0.74 to 0.97 mm in the adult. 15 We compared the clinical outcomes and complication rates of pediatric patients with RAE and AR who underwent intraoperative treatment with SNC or RFC.
Materials and Methods
Ethical Considerations
The prospective, randomized controlled study was conducted following approval by the Institutional Ethical Review Board of Yiwu Central Hospital. However, the study was not registered in the Chinese Clinical Trial Registry. Written informed consent was obtained from the parents or legal guardians of all participants prior to enrollment.
Methods
This prospective, randomized, double-blind, controlled study included pediatric patients with RAE associated with AR who visited the outpatient clinic of the Department of Otolaryngology between January 1, 2021, and December 30, 2023. Patients aged 6 to 14 years with bilateral epistaxis, recurrent epistaxis associated with AR as the primary reason for the initial outpatient visit, bleeding originating from the anterior nasal septum, and duration of epistaxis >3 months, with or without prior treatment using INCS or antiseptic creams, were included. Exclusion criteria included a history of prior electrocautery intervention; the presence of significant nasal anatomical abnormalities, except for nasal septal deviation; absence of AR symptoms; isolated mucosal bulge; comorbid systemic diseases, including hematological disorders, immune system diseases, hepatic diseases, and renal diseases; and secondary epistaxis caused by nasal foreign bodies, tumors, or recent trauma.
All participants underwent a comprehensive otorhinolaryngological examination, with particular attention paid to the identification of the bleeding source and the assessment of rhinitis, sinusitis, or potential neoplastic lesions. Laboratory investigations included a complete blood count, serum-specific immunoglobulin E measurement, skin-prick testing (SPT), blood chemistry for liver and kidney function, bleeding time, prothrombin time, and activated partial thromboplastin time. Parents were systematically queried regarding their children’s nasal symptoms. The diagnosis of AR was based on the Chinese Guideline for Diagnosis and Treatment of Pediatric Allergic Rhinitis (2022, revision), a positive serum-specific immunoglobulin E or SPT result, and the presence of at least one of the following symptoms: sneezing, rhinorrhea, nasal obstruction, nasal itching, or ocular itching. 16
Sample Size
We considered an absolute difference of 25% between groups to be clinically meaningful. To achieve 75% power to test for such a difference at the 5% significance level (α = .05), a total sample size of 100 patients was required.
Randomization and Allocation
Participants were randomly assigned to one of the two treatment groups using sealed envelopes. An office nurse uninvolved in patient selection or surgical procedures performed the randomization. A random number table was employed to generate group assignments. If the terminal digit of the random number was 0 to 4, the participant was allocated to the SNC group; if the terminal digit was 5 to 9, the participant was allocated to the RFC group. All nasal procedures, regardless of the assigned treatment, were conducted in the operating room under general anesthesia.
The group assignments were placed into opaque, sequentially-numbered envelopes, which were then sealed. As eligible children were enrolled in the trial, these envelopes were opened in sequential order, providing each child with their randomized group assignment. The envelopes were opened after parental consent was obtained, immediately prior to the procedure.
This study was conducted as a double-blind trial. Both the children and their parents were blinded to the treatment allocation since all procedures were performed under general anesthesia. Outcome assessments were carried out in follow-up clinics on separate days by different surgeons from those who conducted the procedures, ensuring that the assessors remained blinded to the original treatment assignments.
Techniques
SNC group
Cauterization was performed using 75% silver nitrate-tipped sticks. Silver nitrate was directly applied to visible vessels on the anterior nasal septum until the mucosa developed a dark grey discoloration. The duration of the application was ~5 s/focus. Subsequently, the same procedure was performed on the contralateral anterior nasal septum. Upon completion, any residual silver nitrate particles were removed from the mucosal surface.
RFC group
Epistaxis management was performed using the Evac 70 coblation system (China Micro Medical Limited-Shanghai Micro Medical Devices, Shanghai, China). Under endoscopic guidance with a 0° endoscope, the coagulation mode was used to treat visible telangiectatic vessels. The coagulation power setting of the Evac 70 wand was standardized at level 5. The ablation mode was selectively used for a limited number of large-caliber blood vessels.
All identifiable telangiectatic areas were coagulated to achieve a characteristic gray-white ablation zone. Multiple passes of coagulation were applied as needed to address distinct regions and adjacent areas of the nasal mucosa (Figure 1). Bilateral treatment was performed to ensure coagulation of telangiectasia on both sides of the nasal septum.
RFC procedure of the bilateral nasal cavity in an 8 year-old boy. (A) Diffuse telangiectasia (blue triangle). (B) Coagulation zone. (C) Complete coagulation. RFC, radiofrequency coagulation.
Postoperative Follow-Up
All children were discharged the day after surgery. Standard postoperative care included oral desloratadine for 4 weeks and an INCS spray for 4 weeks. In addition, the application of antibiotic ointment was recommended for a minimum of 4 weeks. Follow-up assessments were scheduled at the 4th week, 3rd month, and 12th month postoperatively. Recurrent epistaxis was defined as any bleeding episode confirmed by a physician that required intervention during the follow-up period. Interventions included the application of digital pressure to the nose for >5 min or the performance of repeat SNC. Furthermore, the parents of all participants were requested to complete questionnaires at each follow-up visit. These questionnaires documented any unscheduled hospital visits due to recurrent epistaxis or other nasal symptoms and systematically recorded changes in symptom severity, as reported by parents throughout the follow-up period.
Outcome Measures
The Epistaxis Severity Score (ESS) was used to assess the frequency and severity of epistaxis. The total ESS ranges from 0 to 10, where a score of 0 indicates the absence of epistaxis, and 10 reflects the most severe bleeding. Severity is further categorized as mild (0-4), moderate (4-7), or severe (7-10). 17
In addition, a Visual Analog Scale (VAS) was used as a nonvalidated tool to assess symptom severity. Patients were instructed to indicate the severity of their symptoms by marking a point on a 10 cm line, with 0 indicating the absence of symptoms and 10 denoting the most severe symptoms imaginable. The evaluated symptoms included nasal obstruction, rhinorrhea, nasal pruritus, nasal crusting, and the overall impact on daily life (IDL).
The primary outcome measure was the recurrence of epistaxis at the 4th week, 3rd month, and 12th month posttreatment. Secondary outcome measures included the ESS and VAS assessments, recorded at baseline (4 weeks before treatment) and at the 4th week, 3rd month, and 12th month posttreatment. Additional secondary outcomes included the development of synechiae, septal mucosal necrosis, and septal perforation.
Statistical Analysis
Statistical analyses were performed using the SPSS software (v. 22.0; IBM, Inc, Armonk, NY, USA). Continuous variables are presented as mean ± standard deviation, whereas categorical variables are presented as frequencies or percentages. Fisher’s exact tests and Mann-Whitney U tests were used to assess intergroup differences in patient characteristics, surgical parameters, and mean ESS and VAS scores at each follow-up interval, as appropriate. Friedman’s test was used to assess significant differences in repeated ESS and VAS outcome measures within each treatment group over time. P < .05 were considered statistically significant.
Results
Demographic Data
In total, 100 pediatric patients with bilateral RAE and AR were included. Of these patients, 50 underwent SNC, and 50 received RFC. Baseline demographic and clinical characteristics, including sex, age, duration and frequency of epistaxis, prior use of antiseptic cream or INCS, and baseline ESS, were comparable between the treatment groups (Table 1). All participants declined allergen-specific immunotherapy during the study period.
Contrast of Demographic Data for Both Treatment Groups.
Abbreviations: ESS, Epistaxis Severity Score; RFC, radiofrequency coagulation; SNC, silver nitrate cauterization.
Primary Outcome
Table 2 presents the rebleeding rates. In the SNC group, the rebleeding rate was 18.0% at the 4th week, 46.0% at the 3rd month, and 58.0% at the 12th month. Conversely, the RFC group demonstrated a rebleeding rate of 2.0% at the 4th week and 0% at both 3rd and 12th months (P < .05). Furthermore, significant differences were observed between the groups regarding the number of patients who actively sought medical attention for recurrent epistaxis at the 4th week, 3rd month, and 12th month posttreatment.
Rebleeding and Seeking Medical Help at the 3rd, 6th, and 12th month for Both Treatment Groups.
Abbreviations: RFC, radiofrequency coagulation; SNC, silver nitrate cauterization.
Secondary Outcome
Epistaxis Severity Score
Table 3 presents the ESS at baseline and 4th week, 3rd month, and 12th month posttreatment. The mean ESS at the 4th week was significantly reduced compared with that at baseline in both groups. In the SNC group, there was no statistically-significant difference in mean ESS between baseline and 3 or 12 months. Conversely, the RFC group demonstrated a significant reduction in mean ESS between baseline and both 3 and 12 months. Moreover, at each follow-up time point, the mean ESS score in the RFC group was significantly lower than that in the SNC group.
VAS and ESS Score at Baseline and 3rd, 6th, and 12thmonth for Both Treatment Groups.
Abbreviations: ESS, Epistaxis Severity Score; IDL, impact on daily life; RFC, radiofrequency coagulation; SNC, silver nitrate cauterization; VAS, Visual Analog Scale.
Visual Analog Scale
VAS scores, reflecting patient-reported nasal symptoms, are presented in Table 3. The proportion of patients actively seeking medical intervention for nasal symptoms did not differ significantly between the 2 groups at the 4th week postoperatively. However, significant differences were observed at the 3rd and 12th month. At the 4 week postoperatively, the mean VAS scores for nasal obstruction, rhinorrhea, and pruritus did not demonstrate significant intergroup differences. Conversely, the RFC group demonstrated significantly lower mean VAS scores for nasal crusting and overall impact on daily life at all postoperative time points than the SNC group. Furthermore, the RFC group exhibited significantly lower mean VAS scores for rhinorrhea and nasal itching at the 3rd and 12th month postoperatively. Furthermore, the severity of nasal obstruction, as measured by the mean VAS score, was significantly lower in the RFC group than in the SNC group at the 12th month postoperatively.
Complications
The RFC group exhibited a significantly-thicker mucosal scar than the SNC group. Notably, the scar thickness in the RFC group increased over time (Figure 2), whereas the mucosal scar in the SNC group remained relatively unchanged. The SNC group exhibited no instances of synechiae formation, septum necrosis, or septum perforation. Conversely, among the 4 patients in the RFC group undergoing ablation mode, 1 patient developed a septum perforation (Figure 3), who refused to further treat.
An 11 year-old boy. (A) Preoperative diffuse telangiectasia. (B) Mild crust formation at the 2nd week postoperatively. (C) Thickened nasal mucosa at the 12th month postoperatively.
An 11 year-old girl. (A) Preoperative diffuse telangiectasia. (B) Mild crust formation at the 2nd week postoperatively. (C) Thickened nasal mucosa with septal perforation at the 12th month postoperatively (green triangle indicates the septal perforation).
Discussion
RFC for Pediatric Bilateral RAE With AR
In clinical practice, the symptoms of AR in children are often overlooked by both patients’ families and community health care providers, leading to underdiagnosis and inadequate treatment. Recurrent epistaxis was the primary complaint that prompted patients to seek medical attention at the outpatient clinic. Commonly-used antiseptic creams may help alleviate chronic inflammation but do not effectively address nasal itching or rhinorrhea. Furthermore, RFC has been widely used for hemostasis in endoscopic surgeries involving sinonasal and skull base tumors, 18 and in the management of HHT.9 -11 However, its utility in the treatment of RAE with AR remains uncertain. A possible explanation for this is that, in children, RAE with AR is frequently bilateral, and the nasal septal cartilage is not yet fully developed. This raises concerns regarding the potential risk of septal perforation if RFC is applied bilaterally to the anterior nasal septum. In addition, although bipolar electrocautery has previously been reported for the treatment of unilateral RAE in children, 19 RFC offers the advantage of lower operating temperatures and minimal surrounding tissue damage than bipolar electrocoagulation. 20
Advantages and Disadvantages of SNC for RAE
SNC is considered a first-line treatment for RAE in children. However, SNC is often ineffective in controlling active bleeding from large-caliber blood vessels. 21 In addition, although contact times of ≤ 10 s are unlikely to cause full-thickness mucosal injury, the resulting superficial burns may be insufficient to adequately treat larger vessels. 3 Consequently, the efficacy of SNC varies considerably depending on the follow-up duration, with reported success rates in the range of 45.7% to 89% at 2 to 3 months.2 -4 Overall, SNC demonstrates limited effectiveness in preventing recurrent or persistent bleeding in RAE. 22
Advantages of RFC in the Management of RAE With AR
In our study, the rebleeding rate in the SNC group was significantly higher than that in the RFC group at all follow-up time points. Although the mean ESS at the 4th week exhibited significant improvement from baseline in both groups, the RFC group consistently exhibited significantly-lower mean ESS values than the SNC group at each follow-up time point. These findings indicate that RFC is more effective than SNC in the treatment of RAE associated with AR.
RFC integrates ablation, coagulation, and suction functions within a single instrument. Unlike SNC, RFC is not affected by active bleeding in the operative field. RFC can penetrate the submucosa to reach the perichondrium, enabling adequate coagulation of intramucosal capillaries and submucosal nourishing blood vessels. Moreover, RFC promotes faster epithelial regeneration and fibrous tissue repair, with the underlying seromucinous glands replaced by mild fibrosis. 23 At the 14th day postoperatively, the epithelium is thicker, and collagen bundles are denser, following RFC than through other treatments. 24 Consistent with these findings, 23 we observed a thicker mucosal scar in the RFC group at the 12th month postoperatively. In contrast, the short contact time of SNC limits its effect to the superficial mucosal layers, resulting in superficial scar formation. Consequently, SNC is more likely to permit vascular regeneration, necessitating repeated cauterization. Notably, RFC has demonstrated a significant ability to eliminate Staphylococcus aureus, 24 whose colonization contributes to persistent inflammation and neovascularization, increasing the risk of epistaxis. However, unfortunately, the limitation of RFC is that it cannot be performed in the outpatient setting. On the contrary, the greatest advantage of SNC is the ability to perform this outpatient and this is why it is the first-line therapy for epistaxis. Therefore, if the patient required operation room intervention, then at that point it may be beneficial to consider RFC.
RFC Improves Other Nasal Symptoms
In our study, nasal symptoms were evaluated preoperatively and postoperatively. Although VAS scores at the 4th week exhibited significant improvement from baseline in both groups, no significant differences were observed between baseline and 3rd or 12th month in the SNC group. Conversely, the RFC group demonstrated significant improvements in VAS scores at the 3rd and 12th month compared to baseline, and significantly-better outcomes than the SNC group at the same time points. We hypothesize that the initial improvement in nasal symptoms at the 4th week may be attributed to the concurrent use of INCS and antihistamines in both groups. 7 However, the sustained improvements observed at the 3rd and 12th month in the RFC group are likely attributable to the therapeutic effects of RFC.
The precise mechanisms by which RFC ameliorates the nasal symptoms associated with anterior septal pathology remain unclear. Numerous studies suggest that nasal mucosal epithelial cells play a crucial role in the pathogenesis of allergic inflammation, with the integrity of the epithelial barrier serving as a critical defense against allergen penetration.25,26 The anterior septum and anterior inferior turbinate are typically the primary sites of allergen exposure, whereas the anterior septal mucosa is particularly susceptible to mechanical injury caused by habitual nose-picking and rubbing. Consequently, disruption of the epithelial barrier in the anterior septum is a key factor in the exacerbation of allergic symptoms.25,26 Therefore, restoration of epithelial integrity is considered essential for the effective control of nasal symptoms. 25 RFC facilitates mucosal epithelial regeneration and restores epithelial structural integrity; furthermore, it induces the formation of dense mucosal and submucosal scars, providing an effective barrier against allergen uptake. 23 In addition, RFC partially destroys secretory glands and nerve fibers and inhibits the local immune response. 23 Similarly, several studies investigating laser surgery for the treatment of AR have demonstrated that laser intervention effectively decreases the expression of local inflammatory cytokines and reduces eosinophil infiltration following nasal allergen challenge.27 -29 These findings suggest that the therapeutic efficacy of RFC in alleviating nasal symptoms is likely attributable to the remodeling of the mucosal epithelial structure and the suppression of specific inflammatory cytokines. However, the precise mechanisms underlying these effects remain uncertain.
Safety of RFC
Historically, bilateral SNC was thought to increase the risk of septal perforation.1,3,5 However, this association has not been confirmed by recent studies,3,21,22 including the present study. Previous studies evaluated the safety of RFC in the management of cartilaginous tissue and have demonstrated that RFC did not result in cartilage necrosis or infection.30,31 In our study, most patients underwent RFC using the thermocoagulation mode, whereas 4 patients were treated with the ablation mode. Septal perforation was observed in a single patient who underwent ablation mode. These findings suggest that RFC in coagulation mode is a safe approach for the coagulation of bilateral RAE.
Our study has several limitations: first, lack of comparison of ages, small number of participants, short follow-up, the evaluation of mucosal scar hyperplasia based solely on morphological observations, without pathological confirmation in either group; second, improvements in nasal symptoms were assessed through self-reported data from pediatric patients, limiting the reliability of our findings.
Conclusion
The thermocoagulation mode of RFC is a safe and effective treatment modality for bilateral RAE in pediatric patients. RFC significantly improves epistaxis and alleviates associated nasal symptoms. Furthermore, compared with patients treated with SNC, those receiving RFC exhibited a significantly-prolonged nosebleed-free period and a reduced incidence of recurrent epistaxis within 1 year of treatment.
Footnotes
Acknowledgements
No.
Author’s Note
Author Contributions
Zhengcai Lou: interpretation of data for the work, design of the work, analysis of data for the work, drafting the work, agreement to be accountable for all aspects of the work, final approval of the version to be published. Zihan Lou: interpretation of data for the work, analysis of data for the work, drafting the work and technical the diagram, agreement to be accountable for all aspects of the work, and final approval of the version to be published. Zhengnong Chen: interpretation of data for the work, design of the work, final approval of the version to be published.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by Technology Agency of Yiwu city, China (grant #21-3-55).
Ethical Considerations
The prospective, randomized controlled study was conducted following approval by the Institutional Ethical Review Board of Yiwu Central Hospital (approval number: K2021-IRB-097). However, the study was not registered in the Chinese Clinical Trial Registry. Written informed consent was obtained from the parents or legal guardians of all participants prior to enrollment.