The Laryngoscope Lippincott Williams & Wilkins 2008 The American Laryngological, Rhinological and Otological Society, Inc.

Treatment of Sinus Headache as Migraine: The Diagnostic Utility of Triptans

Elina Kari, MD; John M. DelGaudio, MD

Objective: To determine the response rate to triptans in alleviating sinus headache in patients with endoscopy- and computed tomography (CT)-negative sinus examinations. Study Design: Prospective clinical trial. Methods: Patients who presented to a tertiary care center Otolaryngology Department with primary complaints of facial pain, pressure, or headache localized over the area of the sinuses, and a self- or physician-diagnosis of sinus headache were enrolled. Patients underwent directed history, physical examination, rigid nasal endoscopy, a sinus CT scan, and completed a headache questionnaire. Those patients that had negative findings were treated empirically with triptans. Patients completed a headache diary for each headache, using a visual analogue scale to rate the headache before and after triptan use. Response was considered as significant improvement (greater than 50% reduction of pain), partial (2550% reduction), and no response. Results: Fifty-four patients were enrolled. Thirtyeight (69%) completed follow-up, 63% were women. The mean age was 41 years (2370). Thirty-one patients (82%) had significant reduction of headache pain with triptan use. Thirty-five patients (92%) had a significant reduction in headache pain in response to migrainedirected therapy. Seventeen patients (31%) withdrew or failed to follow-up, often reluctant to accept a diagnosis of migraine. Conclusions: This study demonstrated that the demographics of patients with self-described sinus headaches who did not have findings of sinusitis on endoscopy and CT scan closely reflected the demographics of patients afflicted with migraines. It also showed that 82% of these patients had a significant response to empiric treatment for sinus headaches with triptans. These findings support that sinus headaches may represent migraines, and response to triptans may aid in diagnosis.

Key Words: Sinus headache, migraine, triptan, diagnosis. Laryngoscope, 118:22352239, 2008

INTRODUCTION
Sinus headaches are estimated to affect millions of Americans every year. Patients often describe episodes of pain or pressure over the area of their sinuses (i.e., frontal, maxillary, ethmoid) or around their eyes. Associated symptoms of nasal congestion, nasal drainage, and lacrimation often lead to a diagnosis, either self-ascribed or by another physician, of sinus headaches. These patients are often treated with multiple courses of antibiotics, steroids, decongestants, and occasionally undergo sinus surgery, often with little or no relief of their symptoms. A number of products are available on the market targeted at sufferers of sinus headaches, despite there not being a precise clinical definition of what constitutes a sinus headache.1 In 1997, the Rhinosinusitis Task Force defined major and minor factors in the diagnosis of sinusitis (Table I). In 2003, the Rhinosinusitis Task Force redefined the criteria to also include clinical or radiographic evidence of inflammation (Table II).2 Note should be made that facial pressure or pain alone is not diagnostic for chronic sinusitis and is only considered a major factor when combined with another major factor. In a series of 51 patients, Shields et al. demonstrated that facial pain and headache did not correlate with disease severity on computed tomography (CT) scan.3 The International Headache Society (IHS), has published diagnostic criteria for migraines (Table III). It is interesting to note that many patients who experience migraines have associated unilateral cranial autonomic symptoms, which can mimic those associated with sinusitis. In their series of 177 patients, Barbanti et al. reported that 45.8% of patients with migraines reported symptoms such as lacrimation, conjunctival injection, eyelid edema, rhinorrhea, and nasal congestion in association with their headaches.4 Other researchers have also presented data that patients who present with sinus headache meet IHS criteria for migraine and have associated autonomic symptoms that may be mistaken for sinus symptoms.57

From the Department of Otolaryngology, Emory University School of Medicine, Atlanta, Georgia, U.S.A. Editors Note: This Manuscript was accepted for publication June 11, 2008. Presented at The Triological Society 2008 Annual Meeting, Orlando, Florida, U.S.A., May 1, 2008. Send correspondence to Department of Otolaryngology, Emory University School of Medicine, 1365-A Clifton Road, NE, Atlanta, GA 30322, U.S.A. E-mail: john.delgaudio@emoryhealthcare.org DOI: 10.1097/MLG.0b013e318182f81d

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TABLE I. Rhinosinusitis Task Force Definition Major and Minor Factors in the Diagnosis of Sinusitis in Adults.20 Major factors Facial pain/pressure must be associated with ANOTHER major factor Facial congestion/fullness Nasal obstruction/blockage Nasal discharge/drainage Hyposmia/anosmia Fever (in acute) Headache Fever must be associated with another major nasal symptom Hallitosis Fatigue Dental pain Cough Ear pain/pressure/fullness Duration 4 or less weeks 2 or more major factorsOR 1 major 2 minor factorsOR Nasal purulence on exam Duration 12 or more weeks 2 or more major factorsOR 1 major 2 minor factorsOR Nasal purulence on exam

The patient with sinus headache frequently refers themselves or is referred by their primary care physician to the Otolaryngologist. The Otolaryngologist should be familiar with the clinical presentation and workup of the patient diagnosed with sinus headache. The aim of this study was to evaluate the efficacy of and demonstrate the diagnostic utility of triptans in treating sinus headache. It is our hypothesis that sinus headache in the absence of clinical and radiographic evidence for sinusitis is often, in fact, migraine headache and should be treated appropriately as such.

Minor factors

MATERIALS AND METHODS

Fifty-five patients were enrolled prospectively from a referral academic rhinology practice. Emory University Institutional Review Board approval was obtained. Inclusion criteria were as follows: primary complaint of facial pain, pressure, or headache localized over the area of the paranasal sinuses, a self or physician diagnosis of sinus headache, clinical examination including rigid nasal endoscopy that was negative for findings of sinusitis, and CT scan that was negative for findings of sinusitis. CT scans need to be performed within 6 months of entry into the study and be interpreted as normal or minimal disease that was not clinically significant. Contraindications to enrollment were as follows: patient had contraindications to use of triptans (coronary artery disease, vasospasm, Raynauds disease, mitral valve prolapse, tachycardia, and previous adverse reaction to triptan medications) or there existed other identifiable causes of their headache. A previous diagnosis of migraine headache or previous treatment for migraine was not a contraindication to participation in this study. Patients who had previously undergone sinus surgery were also included if they meet the other criteria for inclusion. On enrollment, patients were asked to fill out a sinus headache assessment questionnaire that reviewed associated symptoms, frequency, disability, and previous treatments for the headaches. Patients were treated for migraine headaches with the abortive medication eletriptan 40 mg at the onset of headache and repeated within 2 hours if the headache was not relieved. Patients were asked to follow-up within 1 to 3 months, depending on the frequency of their headaches, or earlier if their symptoms worsened. They were given headache diaries to document the frequency of the headaches, associated symptoms, the amount of medication used, and the response to medication. If the eletriptan was not effective in adequately improving the headache (as determined by the patients subjective assessment of improvement and a 50% or greater reduction in the frequency and severity of the patients headaches) then the patient was tried on either sumatriptan or rizatriptan. Medication was selfadministered and recorded by enrolled patients. Patients were asked to report any adverse effect of the treatment medications to the primary investigator. At follow-up, patients returned their headache diaries. Patients with relief with the abortive migraine medicine were kept on their medications and followed appropriately. Patients that did not respond to treatment were referred to a neurologist for further management.

Acute sinusitis

Chronic sinusitis

Adult rhinosinusitis affects approximately 14% of the American population and accounts for about $2.4 billion annually in direct medical costs.8 In 1989, the American Migraine Study demonstrated that approximately 23.6 million Americans (18% of women and 6% of men) suffered from migraine.9 Furthermore, it seems that migraine continues to be an under-diagnosed problem. Lipton et al., reported that only half of IHS-defined migraineurs reported a physician diagnosis of migraine.10 In other words, many people who suffer from migraines are not being diagnosed and treated appropriately. In fact, this same study reported that 43.1% of physician-diagnosed and 42% of undiagnosed migraineurs had also been diagnosed with sinus headaches.10

TABLE II. 2003 RTF Revised Criteria to also Include One of the Following for the Diagnosis of Chronic Sinusitis.2 Discolored nasal drainage from the nasal passages, nasal polyps, or polypoid swelling as identified on physical examination with anterior rhinoscopy after decongestion or nasal endoscopy Edema or erythema of the middle meatus or ethmoid bulla on nasal endoscopy Generalized or localized erythema, edema, or granulation tissue (If the middle meatus or ethmoid bulla is not involved, radiologic imaging is required to confirm a diagnosis.) CT scanning demonstrating isolated or diffuse mucosal thickening, bone changes, or air-fluid levelsOR Plain sinus radiography revealing air-fluid levels or greater than 5 mm of opacification of one or more sinuses

RESULTS
Fifty-five patients were enrolled. Of the enrolled patients, most were women (67%). The age range was 23 to 70 years with a median age of 39 years and an average age of 41 years. Fourteen (25%) patients had previous diagnoses of migraine, 4 of which did not seem to meet IHS criteria based on history.

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TABLE III. Diagnostic Criteria for Migraines.21

Migraine With Aura Migraine Without Aura

1) At least 2 attacks fulfilling criteria 24 if aura is present 2) Headache lasts 472 hours 3) Headache that has 2 of the following: unilateral, pulsating quality, moderate or severe pain intensity, aggravated by or causing avoidance of routine physical activity 4) One of following occurs during headache: nausea, vomiting, photophobia, phonophobia 5) Headache cannot be attributed to another disorder

1) At least 5 attacks fulfilling criteria 24 2) Headache lasts 472 hours 3) Headache that has 2 of the following: unilateral, pulsating quality, moderate or severe pain intensity, aggravated by or causing avoidance of routine physical activity 4) One of following occurs during headache: nausea, vomiting, photophobia, phonophobia 5) Headache cannot be attributed to another disorder

Forty patients (73%) met criteria for the IHS diagnosis of migraine, 31 (56% of enrolled patients) of who had not received a previous diagnosis of migraine. The vast majority of patients reported having headaches that occurred daily, or multiple times per week, and that lasted hours. After completing an evaluation for sinusitis and having been found to not have any clinical or radiographic evidence of sinusitis, 38 of 55 patients (69%) completed follow-up. Seven patients of all enrolled patients (13%) were found to have contact points on clinical examination. Of note, all of these patients were in the group that followed up to complete the study, comprising 18%. Of those patients that followed up, 37% were men and 63% were women (Fig. 1). Table IV shows the response to triptan use or migraine-directed therapy in this study group. Response was graded as significant improvement (greater than 50% reduction of pain), partial (2550% reduction), and no response. Of the 37 patients that followed up, 31 (81.6%) had a significant relief of headache pain with triptan use. One patient (2.6%) responded to dihydroergotamine. One patient (2.6%) had a 25 to 50% improvement and three patients (7.9%) had no re-

sponse. None of these three patients elected to attempt a second triptan trial. Seven patients (18%) required changing from eletriptan to either sumatriptan or rizatriptan secondary to lack of response to eletriptan. Two patients (5%) required changing from eletriptan to sumatriptan or rizatriptan secondary to side effects. Six patients (16%) reported the following side effects: nausea, light-headedness or dizziness, chest pressure, rebound headaches, and palpitations. Three (7.9%) patients were able to better control their headaches with lifestyle and diet changes. Seven patients (18%) subsequently required the initiation of topiramate for the long-term management of their migraine headaches due to the frequency of use of triptans, despite a positive response to abortive therapy (Table IV). Seventeen patients (31%) withdrew or failed to followup. Many of these patients articulated that they did not believe they had migraine headaches and were certain that sinus disease was responsible for their headaches.

DISCUSSION
Complicating the diagnostic evaluation of sinus headache is the similarity of its symptoms with migraines. Wolff

Study Participants by S
70%
63%

60%

50%

40%

37%

30%

20%

Fig. 1. Distribution by sex of study participants. Thirty-eight of the 55 enrolled patients completed the study. Of these, 63% were female. The demographics were not significantly different from those that enrolled.

10%

0%

Male

Female

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TABLE IV. Results of Patient Responses to Triptan or Migraine-Directed Therapy.

Number of Patients Percent

50% reduction in headache with triptan use 2550% reduction in Headache with triptan use No response with triptan use Significant reduction in headache with migrainedirected therapy, lifestyle or diet changes

31 1 3 3

81.6 2.6 7.9 7.9

conducted a number of experiments that demonstrated that traction on numerous regions of the meninges produced referred pain into the face and sinus area suggesting that sinus pain could be referred from meningeal irritation that occurs in migraine.11,12 There are some authors that present data to support the theory that structural abnormalities, or contact points within the sinonasal system, in the absence of findings consistent with chronic sinusitis, can lead to headache. Furthermore, they suggest that certain surgical procedures in appropriately-selected patients can help relieve headache.13,14 In our study, seven patients (13%) were found to have contact points, all of who had significant reduction in their headaches in response to triptans. This supports the idea that some individuals have contact points that act as a trigger to a migraine. However, what is unclear is if this acts as their sole trigger. As many individuals had no improvement or recurrence of their headache after contact point surgery, this may be due to the presence of multiple different triggers, not just contact points, for migraines in these patients. The presence of what some have described cranial autonomic symptoms4 often leads patients to believe that their headaches are due to sinus disease. Nasal congestion, rhinorrhea, lacrimation, and eyelid edema are not classic migraine symptoms and are presented in the lay media to be due to sinus pathology or allergies. The diagnosis of sinus headache often leads to medical and surgical interventions that do not relieve the patients headaches. The appropriate recognition of migraine in patients who complain of sinus headaches could help minimize suffering and unnecessary and expensive interventions. Ishkanian et al. recently reported in a randomized, double-blind, placebo-controlled study that sumatriptan was effective and well-tolerated in the treatment of patients with self-described or physician-diagnosed sinus headaches.15 Their report demonstrated that 69% of patients treated with a single 50 mg dose of sumatriptan achieved a positive headache response, compared with 43% of those treated with placebo at 2 hours. At 4 hours, the response was 76% compared with 49% with placebo. Our study demonstrates that sinus headache is a common diagnosis, both self-ascribed and physiciandiagnosed, in the absence of any clinical or radiographic Laryngoscope 118: December 2008

evidence for sinus disease. Furthermore, our patient population closely mirrors the demographics of individuals afflicted with migraines. Forty patients in our enrolled study population (73%) met IHS criteria for migraine headaches, the vast majority of which had gone previously undiagnosed. This finding further emphasizes the problem of misdiagnosis in patients who complain of sinus headache. The significance of response to triptan use in our data supports the finding of other researchers that migraine headache should be considered in the evaluation of a patient with the complaint of sinus headache.5,16,17 Paulson and Graham described 104 patients who presented with the primary complaint of facial pain, normal sinus CT scans, and normal nasal endoscopic examiantions. These patients were then referred to a neurologist for further evaluation, 75 of whom attended this appointment. Thirty-seven percent of those that followed up were diagnosed with migraine headaches, 17% were diagnosed with rebound headache, 17% were diagnosed with chronic daily headache, and 16% were diagnosed with obstructive sleep apnea.16 In another study, 2,991 patients with a history of self-described or physician-diagnosed sinus headache were screened and 80% were found meet IHS criteria for migraine headaches.5 The Sinus, Allergy, and Migraine Study of 2007 reported that of 100 subjects with self-diagnosed sinus headache, 52% met IHS criteria for migraine with or without aura.7 Our study also highlights the diagnostic utility of response to triptans in diagnosing migraine headache, particularly in individuals who may not meet the IHS criteria for migraine. Cady and Schreiber report similar findings in patients with self-diagnosed sinus headaches in which patients were asked to treat their headaches with sumatriptan. The percentage of headaches that were reduced to mild or no pain was 66%. The authors further describe that patients who respond to migraine-specific therapy suggest that these patients are actually suffering from migraines.18 Studies that examined the efficacy of triptans in patients with the diagnosis of migraine reported similar rates of success with triptan use. A review of several randomized, double-blind, placebo-controlled trials showed that patients response rates at 2- and 4-hours after receiving 100 mg oral sumatriptan were 51 to 58% and 65 to 78%, respectively, compared with 17 to 31% and 19 to 40% in the placebo group.19 In contrast to the studies by Ishkanian and Cady and Schreiber, our study was not limited to a single dose of a single agent given at one interval. Our patients were instructed to treat every headache and to use a second dose if their headache persisted after the first and they were also initiated on alternative therapies if the first failed. This may account for our slightly higher success rates than those reported in the literature. A potential weakness to our study was its design as an open-label, nonrandomized study without a placebo control. Our patient population was, by design, a group selected for the absence of sinus pathology to eliminate the confounding variable of sinus disease leading to headache. For those patients who were found to have sinus disease, they were treated with appropriate medical therapy for

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rhinosinusitis. Those patients who continued to have headaches despite having evidence of resolved sinus disease were then offered the opportunity to enroll in our study. Given the highly selective nature of our study, the placebo effect should be considered in evaluating the data. The Ishkanian study and other studies looking at the efficacy of triptans in migraines19 report response rates to placebo. Although triptans showed an effect above that of placebo, placebo was still shown to reduce headaches in a group of patients. This effect cannot be excluded in our study. A significant number of patients did not complete our study, weakening the statistical power of our findings. However, the reason behind the loss to follow-up was often related to patient reluctance to accept the diagnosis of migraine thereby itself highlighting an important barrier to appropriately diagnosing and treating patients headaches. Sinus headache is a difficult clinical presentation that we argue may often represent migraine headache. Otolaryngologists should be prepared to not only include migraine in the differential diagnosis in evaluating patients who present with sinus headache, but to also be prepared and willing to initiate treatment, as these patients will benefit greatly. Our study also demonstrates that response to triptans may be a useful diagnostic tool in evaluating sinus headache patients.

CONCLUSION
Eighty-two percent of 38 patients in our study had a significant response to triptan use. Our findings highlight the importance of considering migraine headaches in the differential diagnosis of patients presenting with sinus headaches in the context of negative clinical and radiographic evidence. Our findings also demonstrate the diagnostic utility of triptan use in evaluating patients for sinus headaches who may not meet strict IHS criteria for migraine headache.

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