Headache attributed to rhinosinusitis in pediatric patients: clinical insights and diagnostic implications

Introduction

Headache is a common cause of pain and a leading cause of disability. Headache attributed to rhinosinusitis (HRS) is a condition in which inflammation of the nasal passages and paranasal sinuses is the underlying cause of headache (1). HRS is relatively rare and frequently misdiagnosed as a primary headache disorder, with approximately 3% of patients diagnosed with HRS (2). Differentiating between HRS and other types of headache, particularly in children, can be challenging. Accurately distinguishing HRS from other types of headache is crucial for proper diagnosis and treatment. In patients with HRS, symptoms of rhinosinusitis, such as rhinorrhea and cough, are often present at the time of diagnosis, wherein headache improvement is typically observed following treatment. However, in 60.3% of these patients, treatment of rhinosinusitis did not alleviate their headaches (3). This finding suggests that not all headaches in patients with suspected HRS originate from the sinuses. Misdiagnosis can occur because headache can be referred from or mimic pain in the sinuses. In a pediatric study, Senbil et al. (3) reported that approximately 40% and 60% of individuals with migraines and tension-type headaches, respectively, were erroneously diagnosed with HRS.

Although primary care physicians routinely diagnose rhinosinusitis based on patient history and physical examination, including anterior rhinoscopy and oropharyngeal examination, the paranasal sinuses are relatively insensitive to pain (4). Headache can originate from adjacent anatomical structures, such as the nasal cavity or surrounding muscles, and the sinuses may both contribute to pain and serve as sites of referred pain. These complexities highlight the challenges in accurately diagnosing headache origins and underscore the need for cautious interpretation of symptoms.

According to the International Headache Society, migraines without aura can manifest with autonomic symptoms in the nose or can be triggered by nasal changes, such as allergic or non-allergic rhinitis, sinus inflammation, or structural abnormalities in the nasal passages (5). Peripheral irritants affecting the nasal mucosa may activate the neurogenic inflammatory pathway, potentially leading to migraines. Rhinosinusitis symptoms such as rhinorrhea, nasal obstruction, and facial pain may arise from shared neuroanatomical pathways, including the trigeminal autonomic reflex and nerve involvement (6,7). This overlap likely contributes to frequent misdiagnosis of migraine as HRS.

Physicians’ understanding of how HRS fits into the differential diagnosis of headache is crucial for avoiding overdiagnosis in patients with primary headaches and preventing underdiagnosis in those with serious HRS. However, few studies have employed diagnostic imaging of the paranasal sinuses in large populations to evaluate the relationship between rhinosinusitis and headaches. In this study, we investigated the clinical features of children exhibiting concurrent headaches with rhinosinusitis detected on brain imaging and evaluated the effects of antibiotic therapy for rhinosinusitis on headache relief. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-24-481/rc).

Methods

Pediatric patients aged <19 years who presented to two medical institutions affiliated with the University [Incheon (Incheon, Republic of Korea; Hospital A) and Daejeon St. Mary’s Hospitals (Daejeon, Republic of Korea; Hospital B)] between January 2014 and December 2023 with a primary manifestation of headache participated in the present study. The results of brain imaging studies, including computed tomography (CT) and magnetic resonance imaging (MRI), were reviewed. A diagnosis of paranasal sinusitis was established when thickening of mucosa measuring ≥3 mm or an air-fluid level was observed in the sinus (8). Patients with intracranial lesions or a head trauma history within three months prior to brain imaging study were excluded. The medical records of the participants were retrospectively reviewed to extract data on demographics, including sex and age, along with clinical data such as headache type, features, and duration; accompanying symptoms; headache family history; underlying disease; previous history of allergies; medications prescribed for managing headache; antibiotics administered; surgical intervention for rhinosinusitis; clinical response to therapy; and location and number of inflamed sinuses.

Headache was classified according to the International Classification of Headache Disorders-3 beta (ICHD-3β). Migraine, the most common headache type in pediatric cases, typically lasting for <72 h, and symptoms of acute bacterial rhinosinusitis (BRS) usually shows improvement during 72 h after antibiotic therapy (9). Although determining the analgesic or antibiotic effects on headache 72 h after treatment is ideal, the interval for follow-up visits varied in each patient. Therefore, therapeutic efficacy was assessed according to improvements in symptoms at the first follow-up visit after treatment initiation. The patients wherein headaches improved after treatment with antibiotics therapy or surgery for rhinosinusitis were allocated into the BRS group. Those wherein headaches showed improvement without treatment with antibiotics or did not improve despite administering appropriate antibiotics were assigned to the non-BRS group. The patients wherein headaches did not improve or exhibited improvement using concurrent antibiotic and analgesic therapies were not categorized into either group. Demographic and clinical data were compared between the two groups.

Statistical analysis

Continuous and categorical factors were compared between the BRS and non-BRS groups using the Student’s t-test and Fisher’s exact test, respectively. Significant factors from this univariate analysis were fitted in the multivariate analysis; binary logistic regression analysis was performed to identify the prognostic factors for BRS. All statistical analyses were performed using the R Statistical Software (v4.3.3, R Core Team 2024; R Foundation for Statistical Computing, Vienna, Austria). Statistical significance was set at P value <0.05.

Ethical consideration

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the Institutional Review Board of Catholic Medical Center (approval numbers: DC24RASI0047 for Daejeon St. Mary’s Hospital and OC23RASI0159 for Incheon St. Mary’s Hospital). Individual informed consent for this retrospective analysis was waived.

Results

Within the study duration at Hospital A, 1,217 pediatric cases exhibited headaches, of whom 714 (58.7%) underwent brain imaging studies [35 (4.9%) on CT and 679 (95.1%) using MRI]. Neuroimaging abnormalities were observed in 141 (19.7%) patients and rhinosinusitis was identified in 93 (13.0%). At Hospital B, brain imaging studies were performed on 1,063 [38.0%; CT in 118 (11.1%) and MRI in 945 (88.9%)] of the 2,795 pediatric patients presenting with headaches. Among them, 184 (17.3%) and 110 (10.3%) patients had neuroimaging abnormalities and rhinosinusitis, respectively. Combining data from Hospital A and Hospital B, a total of 1,777 out of 4,012 pediatric patients (44.3%) presenting with headaches underwent brain imaging studies. Among them, 203 patients (11.4%) were diagnosed with HRS.

Characteristics of headache and brain imaging studies

Table 1 summarizes the characteristics of the 203 patients diagnosed with HRS, including 118 male (58.1%) and 85 female patients (41.9%). The median age of the patients was 9 years (range, 3–17 years). Among the patients, 56 (27.6%) were diagnosed with unspecified headache according to the ICHD-3β criteria. Migraine without aura was the most common diagnosis, affecting 57 patients (28.1%). The most frequently reported type of headache was throbbing pain, observed in 56 (27.6%) patients. Headaches predominantly occurred in the temporal/parietal area, as reported in 73 (36.0%) patients.

Nausea or vomiting (n=108, 53.2%) was the most commonly accompanied symptom, followed by respiratory symptoms (n=79, 38.9%). Neurological symptoms were present in 15 (7.4%) patients, including muscle weakness in five, paresthesia in three, loss of consciousness (syncope) in three, dysarthria in two, tremor in two, gait disturbance in one, and myoclonic movement in one. Among the brain imaging studies, maxillary sinusitis was the most frequently observed abnormality (n=137, 67.5%), with inflammation detected in two or more sinuses in 55.7% of the cases (Table 2). Abnormal imaging findings other than rhinosinusitis were identified in 8 patients (3.9%), including four cases of arachnoid cysts, and one case each of mega cisterna magna, Dandy-Walker malformation, Rathke’s cleft cyst, and sequelae of periventricular leukomalacia.

Comparison between the BRS and non-BRS groups

After excluding 15 patients who were not followed up after the evaluation or treatment of headache, the response to treatment was assessed in the remaining 188 patients. Headache improved in 146 patients (77.7%). Antibiotics were administered to 89 patients (47.3%), three of whom (1.6%) underwent sinus surgery. Among them, 47 patients (25.0%) were classified into the BRS group, which included those who demonstrated improvement after sinus surgery (n=3), improvement after taking headache medication as needed along with antibiotics (n=13), and improvement after antibiotics alone without headache medication (n=31). Ninety patients (47.9%) were assigned to the non-BRS group, including those who received antibiotics after headache improvement (n=8), improved after receiving headache medication without antibiotics (n=34), improved without any treatment (n=37), and those who did not improve despite appropriate antibiotic treatment (n=11).

The BRS group had a higher proportion of males compared to the non-BRS group (P=0.02; Table 1). Although HRS was more frequent in the BRS group than in the non-BRS group (P<0.001), headache characteristics were similar between the two groups (Table 1). There were no significant differences between the groups in terms of underlying medical conditions or allergy history (Table 2). Among the symptoms accompanying headache, the frequency of respiratory symptoms, including nasal symptoms, was significantly higher in the BRS group than in the non-BRS group (P<0.001), whereas blurred vision was more common in the non-BRS group (P=0.03; Table 2). The frequencies of maxillary (P=0.01) and ethmoid (P<0.001) sinusitis were significantly higher in the BRS group compared with the non-BRS group, as were cases involving two or more sinuses (P<0.001) and bilateral sinuses (P=0.044; Table 2).

Considering that patients diagnosed with HRS were included in the BRS group, a higher frequency of secondary headaches was expected in this group. Bilateral sinusitis was defined as the involvement of two or more sinuses. Therefore, after excluding these factors, multivariate analysis was conducted to identify independent predictors of BRS, focusing on sex, respiratory symptoms, blurred vision, and the number of involved sinuses. The analysis revealed significant associations between BRS and respiratory symptoms (P=0.008) and inflammation in three (P=0.002) or more (P<0.001) sinuses (Table 3).

Discussion

In this study, pediatric patients with concurrent headaches and rhinosinusitis exhibited headache characteristics similar to those of migraines, which is the most common diagnosis among pediatric patients with headache. Patients with BRS who required antibiotic therapy were more likely to present with respiratory symptoms and inflammation of three or more sinuses compared with others. According to the ICHD-3β, the diagnostic criteria for HRS include clinical, endoscopic, and/or evidenced rhinosinusitis based on imaging associated with at least two of the following: (I) a temporal relationship between headache and sinusitis; (II) concurrent worsening and/or improvement in headache and sinusitis symptoms; (III) headache exacerbation due to pressure over the sinuses; and (IV) ipsilateral headache consistent with sinusitis. However, our findings showed no significant association between imaging evidence of rhinosinusitis, such as paranasal sinus opacification and headache in general, including migraines, tension-type headaches, or unclassified headache (10-12). This suggests that a diagnosis of HRS based solely on imaging evidence of rhinosinusitis is not rational.

In our study, 50.2% of the patients exhibited bilateral sinusitis, and 55.7% had involvement of two or more sinuses, complicating the application of criteria (III) and (IV) in approximately half of the patients. Therefore, evaluating respiratory symptoms and applying criteria (I) and (II) are essential for assessing the causal relationship between sinusitis and headache. The presence of respiratory symptoms demonstrated a significant association with BRS, reinforcing that its diagnosis should be based on respiratory symptoms rather than imaging studies (9). According to the ICHD-3β, HRS includes headaches caused by viral infections or allergic rhinosinusitis. Previous studies have reported a significantly higher frequency of rhinosinusitis confirmed using MRI in children with respiratory symptoms than in those without (13,14). However, in this study, we did not assess whether persistence (>10 days) or worsening of nasal discharge and/or daytime cough, or concurrent purulent nasal discharge and fever for ≥3 days, aligned with the diagnosis criteria for BRS. Therefore, some patients with viral or allergic rhinosinusitis may have been included in the BRS group. Considering that 72.3% of the patients with BRS were also treated with nasal medications such as antihistamines and nasal steroids, antibiotic treatment may have been less effective in these patients. Furthermore, given that approximately half of the patients with BRS achieved headache improvement without treatment with antibiotics, implementing optimal treatment based on respiratory symptoms that align with the BRS diagnostic criteria is necessary, rather than routinely administering antibiotics for headaches confirmed to be related to sinusitis through brain imaging studies.

Due to the overlapping symptoms between sinusitis-related headaches and migraines, particularly in younger patients with limited ability to describe symptoms, clinicians often encounter diagnostic challenges that can lead to overreliance on imaging. In this regard, osmophobia and heightened sensitivity to odors that can lead to avoidance or exacerbation of headaches may serve as useful tools for distinguishing HRS from migraines. Osmophobia is often associated with anosmia in patients with HRS but is more common in those with migraines. A study involving 235 patients demonstrated that osmophobia had a positive predictive value of 87.6% for migraine (15). Migraines are more common during adolescence, with the average age of primary headaches in this study being 11 years. In contrast, the average age of the BRS and rhinosinusitis cases was 9 years, indicating a slightly earlier onset. This age distribution might aid in differentiating sinusitis-related headaches from migraines.

This study also found a significant association between an increased number of involved sinuses and BRS. In children, a Lund-Mackay score ≥5 showed high sensitivity and specificity for diagnosing chronic rhinosinusitis (CRS) based on CT findings (16). The Lund-Mackay score was developed to stage CRS using CT findings, with each sinus scored based on the extent of opacification and the ostiomeatal complex assessed for obstruction, yielding a total score ranging between 0 and 24 (17). These findings suggest that the extent of inflammation in each sinus, or the involvement of multiple sinuses, can be used to predict BRS. However, as approximately half of our patients had headaches lasting for <3 months, they did not meet the symptom duration criteria for CRS. Although brain MRI is commonly conducted in patients with headache, applying the Lund-Mackay score based on CT findings may not be appropriate in this population. Unlike patients with CRS, for whom imaging studies are performed under a surgical treatment plan, imaging studies are not recommended for managing patients with acute BRS who respond well to medical treatment. Pediatric patients are often less likely to undergo imaging studies due to concerns about radiation exposure, resulting in their underrepresentation in studies investigating the use of imaging for the diagnosis of BRS. Therefore, developing diagnostic scales tailored to pediatric patients based on MRI findings could enhance the accuracy of predicting BRS in children with headaches, ultimately supporting more precise and effective treatment decisions.

The limitations of this study include its retrospective design, which led to nonuniform application of analgesic and antibiotic treatments among patients, as well as inadequate documentation of respiratory symptoms in some cases. Consequently, approximately one-third of the study participants were not classified into the BRS or non-BRS groups. Additionally, as previously noted, the duration of respiratory symptoms that met the diagnostic criteria for BRS was not assessed, nor were adjustments made for the influence of nasal medications. This omission might have resulted in the inclusion of patients with rhinosinusitis caused by viral or allergic factors in the BRS group. The retrospective design of this study also limited the assessment of clinical features such as osmophobia and heightened sensitivity to odors, which are important for distinguishing sinusitis-related headaches from migraines. Moreover, comorbidities such as allergic rhinitis and asthma were not systematically controlled in this study. The lack of adjustment for these confounding factors may have introduced bias into the findings. Future prospective studies are warranted to incorporate a more comprehensive evaluation and control for allergy history and respiratory conditions, ensuring more robust and generalizable findings. Although imaging findings were a critical component of the diagnostic criteria in this study, acknowledging the limitations of imaging-based diagnosis is important. However, imaging findings alone might not always correlate with clinical symptoms, particularly in acute or subacute cases. Therefore, combining imaging findings with clinical and microbiological confirmation is necessary to improve diagnostic accuracy and classification of HRS, thereby reducing the likelihood of misclassification and enhancing diagnostic precision. Nevertheless, the findings of this study support limiting antibiotic treatment in pediatric patients with headaches and rhinosinusitis identified in imaging studies, thereby minimizing the potential impact of selection bias.

Conclusions

This study highlights that pediatric patients with concurrent headaches and rhinosinusitis exhibit headache characteristics similar to those shown in patients with migraines. The average age of onset for rhinosinusitis and BRS cases was significantly lower than that in pediatric patients with primary headaches. We found significant associations between BRS and respiratory symptoms as well as inflammation involving multiple sinuses, suggesting that these factors are reliable predictors of BRS. These findings highlight the importance for evaluating respiratory symptoms in diagnosing BRS rather than relying solely on imaging studies. Moreover, based on the study findings, we advocate a cautious approach to antibiotic use and emphasize the necessity for tailored treatment strategies based on comprehensive clinical evaluations rather than routine imaging findings alone.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-24-481/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-481/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-481/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-481/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the Institutional Review Board of Catholic Medical Center (approval numbers: DC24RASI0047 for Daejeon St. Mary’s Hospital and OC23RASI0159 for Incheon St. Mary’s Hospital). Individual informed consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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