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The LaryngoscopeLippincott Williams & Wilkins

2008 The American Laryngological,Rhinological and Otological Society, Inc.

Treatment of Sinus Headache as Migraine:

The Diagnostic Utility of TriptansElina Kari, MD; John M. DelGaudio, MD

Objective: To determine the response rate totriptans in alleviating sinus headache in patients withendoscopy- and computed tomography (CT)-negative si-nus examinations.

Study Design: Prospective clinical trial.

Methods: Patients who presented to a tertiary carecenter Otolaryngology Department with primary com-plaints of facial pain, pressure, or headache localized overthe area of the sinuses, and a self- or physician-diagnosisof sinus headache were enrolled. Patients underwentdirected history, physical examination, rigid nasal endos-copy, a sinus CT scan, and completed a headache ques-tionnaire. Those patients that had negative findings weretreated empirically with triptans. Patients completed aheadache diary for each headache, using a visual ana-logue scale to rate the headache before and after triptanuse. Response was considered as significant improvement(greater than 50% reduction of pain), partial (2550%reduction), and no response.

Results: Fifty-four patients were enrolled. Thirty-

eight (69%) completed follow-up, 63% were women. Themean age was 41 years (2370). Thirty-one patients (82%)had significant reduction of headache pain with triptanuse. Thirty-five patients (92%) had a significant re-duction in headache pain in response to migraine-directed therapy. Seventeen patients (31%) withdrewor failed to follow-up, often reluctant to accept adiagnosis of migraine.

Conclusions: This study demonstrated that the de-mographics of patients with self-described sinus head-aches who did not have findings of sinusitis on endoscopyand CT scan closely reflected the demographics of pa-tients afflicted with migraines. It also showed that 82% ofthese patients had a significant response to empiric treat-ment for sinus headaches with triptans. These findingssupport that sinus headaches may represent mi-graines, and response to triptans may aid in diagnosis.

Key Words: Sinus headache, migraine, triptan,diagnosis.

Laryngoscope, 118:22352239, 2008

INTRODUCTIONSinus headaches are estimated to affect millions of

Americans every year. Patients often describe episodes ofpain or pressure over the area of their sinuses (i.e., frontal,maxillary, ethmoid) or around their eyes. Associatedsymptoms of nasal congestion, nasal drainage, and lacri-mation often lead to a diagnosis, either self-ascribed or byanother physician, of sinus headaches. These patientsare often treated with multiple courses of antibiotics, ste-roids, decongestants, and occasionally undergo sinus sur-gery, often with little or no relief of their symptoms. Anumber of products are available on the market targetedat sufferers of sinus headaches, despite there not being a

precise clinical definition of what constitutes a sinusheadache.1

In 1997, the Rhinosinusitis Task Force defined majorand minor factors in the diagnosis of sinusitis (Table I). In2003, the Rhinosinusitis Task Force redefined the criteriato also include clinical or radiographic evidence of inflam-mation (Table II).2 Note should be made that facial pres-sure or pain alone is not diagnostic for chronic sinusitisand is only considered a major factor when combined withanother major factor. In a series of 51 patients, Shields etal. demonstrated that facial pain and headache did notcorrelate with disease severity on computed tomography(CT) scan.3

The International Headache Society (IHS), has pub-lished diagnostic criteria for migraines (Table III). It isinteresting to note that many patients who experiencemigraines have associated unilateral cranial autonomicsymptoms, which can mimic those associated with sinus-itis. In their series of 177 patients, Barbanti et al. reportedthat 45.8% of patients with migraines reported symptomssuch as lacrimation, conjunctival injection, eyelid edema,rhinorrhea, and nasal congestion in association with theirheadaches.4 Other researchers have also presented datathat patients who present with sinus headache meetIHS criteria for migraine and have associated autonomicsymptoms that may be mistaken for sinus symptoms.57

From the Department of Otolaryngology, Emory University School ofMedicine, Atlanta, Georgia, U.S.A.

Editors Note: This Manuscript was accepted for publication June11, 2008.

Presented at The Triological Society 2008 Annual Meeting, Orlando,Florida, U.S.A., May 1, 2008.

Send correspondence to Department of Otolaryngology, Emory Uni-versity School of Medicine, 1365-A Clifton Road, NE, Atlanta, GA 30322,U.S.A. E-mail: [email protected]

DOI: 10.1097/MLG.0b013e318182f81d

Laryngoscope 118: December 2008 Kari and DelGaudio: Diagnostic Utility of Triptans in Sinus Headache

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Adult rhinosinusitis affects approximately 14% of theAmerican population and accounts for about $2.4 billionannually in direct medical costs.8 In 1989, the AmericanMigraine Study demonstrated that approximately 23.6

million Americans (18% of women and 6% of men) sufferedfrom migraine.9 Furthermore, it seems that migraine con-tinues to be an under-diagnosed problem. Lipton et al.,reported that only half of IHS-defined migraineurs re-ported a physician diagnosis of migraine.10 In other words,many people who suffer from migraines are not beingdiagnosed and treated appropriately. In fact, this samestudy reported that 43.1% of physician-diagnosed and 42%of undiagnosed migraineurs had also been diagnosed withsinus headaches.10

The patient with sinus headache frequently refersthemselves or is referred by their primary care physicianto the Otolaryngologist. The Otolaryngologist should befamiliar with the clinical presentation and workup of thepatient diagnosed with sinus headache. The aim of thisstudy was to evaluate the efficacy of and demonstrate thediagnostic 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 appro-priately as such.

MATERIALS AND METHODSFifty-five patients were enrolled prospectively from a refer-

ral academic rhinology practice. Emory University InstitutionalReview Board approval was obtained. Inclusion criteria were asfollows: primary complaint of facial pain, pressure, or headachelocalized over the area of the paranasal sinuses, a self or physi-cian diagnosis of sinus headache, clinical examination includingrigid nasal endoscopy that was negative for findings of sinusitis,and CT scan that was negative for findings of sinusitis. CT scansneed to be performed within 6 months of entry into the study and

be interpreted as normal or minimal disease that was not clini-cally significant. Contraindications to enrollment were as follows:patient had contraindications to use of triptans (coronary arterydisease, vasospasm, Raynauds disease, mitral valve prolapse,tachycardia, and previous adverse reaction to triptan medica-tions) or there existed other identifiable causes of their headache.

A previous d iagnosis of migraine headache or previous treatmentfor migraine was not a contraindication to participation in thisstudy. Patients who had previously undergone sinus surgerywere also included if they meet the other criteria for inclusion. Onenrollment, patients were asked to fill out a sinus headacheassessment questionnaire that reviewed associated symptoms,frequency, disability, and previous treatments for the headaches.Patients were treated for migraine headaches with the abortivemedication eletriptan 40 mg at the onset of headache and re-peated 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 theirsymptoms worsened. They were given headache diaries to docu-ment the frequency of the headaches, associated symptoms, theamount of medication used, and the response to medication. If theeletriptan was not effective in adequately improving the head-ache (as determined by the patients subjective assessment ofimprovement and a 50% or greater reduction in the frequency andseverity of the patients headaches) then the patient was tried oneither sumatriptan or rizatriptan. Medication was self-administered and recorded by enrolled patients. Patients wereasked to report any adverse effect of the treatment medications tothe primary investigator.

At follow-up, patients returned their headache diaries. Pa-tients with relief with the abortive migraine medicine were kepton their medications and followed appropriately. Patients thatdid not respond to treatment were referred to a neurologist forfurther management.

RESULTSFifty-five patients were enrolled. Of the enrolled pa-

tients, most were women (67%). The age range was 23 to70 years with a median age of 39 years and an average ageof 41 years. Fourteen (25%) patients had previous diag-noses of migraine, 4 of which did not seem to meet IHScriteria based on history.

TABLE II.

2003 RTF Revised Criteria to also Include One of the Followingfor the Diagnosis of Chronic Sinusitis.2

Discolored nasal drainage from the nasal passages, nasal polyps,or polypoid swelling as identified on physical examination withanterior rhinoscopy after decongestion or nasal endoscopy

Edema or erythema of the middle meatus or ethmoid bulla onnasal endoscopy

Generalized or localized erythema, edema, or granulation tissue (Ifthe middle meatus or ethmoid bulla is not involved, radiologicimaging is required to confirm a diagnosis.)

CT scanning demonstrating isolated or diffuse mucosalthickening, bone changes, or air-fluid levelsOR

Plain sinus radiography revealing air-fluid levels or greater than 5mm of opacification of one or more sinuses

TABLE I.

Rhinosinusitis Task Force Definition Major and Minor Factors inthe Diagnosis of Sinusitis in Adults.20

Major factors Facial pain/pressure must be associatedwith ANOTHER major factor

Facial congestion/fullness

Nasal obstruction/blockage

Nasal discharge/drainage

Hyposmia/anosmia

Fever (in acute)

Minor factors Headache

Fever must be associated with anothermajor nasal symptom

Hallitosis

Fatigue

Dental pain

Cough

Ear pain/pressure/fullness

Acute sinusitis Duration 4 or less weeks

2 or more major factorsOR

1 major 2 minor factorsORNasal purulence on exam

Chronic sinusitis Duration 12 or more weeks

2 or more major factorsOR

1 major 2 minor factorsOR

Nasal purulence on exam


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Forty patients (73%) met criteria for the IHS diagno-sis of migraine, 31 (56% of enrolled patients) of who hadnot received a previous diagnosis of migraine.

The vast majority of patients reported having head-aches that occurred daily, or multiple times per week, andthat lasted hours. After completing an evaluation for si-nusitis and having been found to not have any clinical orradiographic evidence of sinusitis, 38 of 55 patients (69%)completed follow-up. Seven patients of all enrolled pa-tients (13%) were found to have contact points on clinicalexamination. Of note, all of these patients were in thegroup that followed up to complete the study, comprising18%. Of those patients that followed up, 37% were menand 63% were women (Fig. 1).

Table IV shows the response to triptan use ormigraine-directed therapy in this study group. Re-sponse was graded as significant improvement (greaterthan 50% reduction of pain), partial (2550% reduc-tion), and no response. Of the 37 patients that followedup, 31 (81.6%) had a significant relief of headache painwith triptan use. One patient (2.6%) responded to dihy-

droergotamine. 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 attempta second triptan trial. Seven patients (18%) requiredchanging from eletriptan to either sumatriptan orrizatriptan secondary to lack of response to eletriptan.Two patients (5%) required changing from eletriptan tosumatriptan or rizatriptan secondary to side effects. Sixpatients (16%) reported the following side effects: nau-sea, light-headedness or dizziness, chest pressure, re-bound headaches, and palpitations. Three (7.9%) pa-tients were able to better control their headaches withlifestyle and diet changes. Seven patients (18%) subse-quently required the initiation of topiramate for thelong-term management of their migraine headaches dueto the frequency of use of triptans, despite a positiveresponse to abortive therapy (Table IV).

Seventeen patients (31%) withdrew or failed to follow-up. Many of these patients articulated that they did notbelieve they had migraine headaches and were certain thatsinus disease was responsible for their headaches.

DISCUSSION

Complicating the diagnostic evaluation of sinus head-ache is the similarity of its symptoms with migraines. Wolff

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 1) At least 5 attacks fulfilling criteria 24

2) Headache lasts 472 hours 2) Headache lasts 472 hours

3) Headache that has 2 of the following: unilateral, pulsatingquality, moderate or severe pain intensity, aggravated by orcausing avoidance of routine physical activity

3) Headache that has 2 of the following: unilateral, pulsating quality,moderate or severe pain intensity, aggravated by or causingavoidance of routine physical activity

4) One of following occurs during headache: nausea, vomiting,photophobia, phonophobia

4) One of following occurs during headache: nausea, vomiting,photophobia, phonophobia

5) Headache cannot be attributed to another disorder 5) Headache cannot be attributed to another disorder

Study Participants by S

37%

63%

0%

10%

20%

30%

40%

50%

60%

70%

elameFelaM

Fig. 1. Distribution by sex of study par-ticipants. Thirty-eight of the 55 enrolledpatients completed the study. Of these,63% were female. The demographicswere not significantly different fromthose that enrolled.


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conducted a number of experiments that demonstrated thattraction on numerous regions of the meninges produced re-ferred pain into the face and sinus area suggesting thatsinus pain could be referred from meningeal irritation thatoccurs in migraine.11,12

There are some authors that present data to supportthe theory that structural abnormalities, or contactpoints within the sinonasal system, in the absence offindings consistent with chronic sinusitis, can lead toheadache. Furthermore, they suggest that certain surgicalprocedures in appropriately-selected patients can help re-lieve headache.13,14 In our study, seven patients (13%)were found to have contact points, all of who had signifi-cant reduction in their headaches in response to triptans.This supports the idea that some individuals have contactpoints that act as a trigger to a migraine. However, whatis unclear is if this acts as their sole trigger. As manyindividuals had no improvement or recurrence of theirheadache after contact point surgery, this may be due to

the presence of multiple different triggers, not just contactpoints, for migraines in these patients.

The presence of what some have described cranialautonomic symptoms4 often leads patients to believe thattheir headaches are due to sinus disease. Nasal conges-tion, rhinorrhea, lacrimation, and eyelid edema are notclassic migraine symptoms and are presented in the laymedia to be due to sinus pathology or allergies.

The diagnosis of sinus headache often leads to med-ical and surgical interventions that do not relieve thepatients headaches. The appropriate recognition of mi-graine in patients who complain of sinus headaches couldhelp minimize suffering and unnecessary and expensive

interventions.Ishkanian et al. recently reported in a randomized,

double-blind, placebo-controlled study that sumatriptanwas effective and well-tolerated in the treatment of pa-tients with self-described or physician-diagnosed sinusheadaches.15 Their report demonstrated that 69% of pa-tients treated with a single 50 mg dose of sumatriptanachieved a positive headache response, compared with43% 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 acommon diagnosis, both self-ascribed and physician-diagnosed, in the absence of any clinical or radiographic

evidence for sinus disease. Furthermore, our patient pop-ulation closely mirrors the demographics of individualsafflicted with migraines.

Forty patients in our enrolled study population (73%)met IHS criteria for migraine headaches, the vast major-ity of which had gone previously undiagnosed. This find-ing further emphasizes the problem of misdiagnosis inpatients who complain of sinus headache.

The significance of response to triptan use in our datasupports the finding of other researchers that migraineheadache should be considered in the evaluation of a pa-tient with the complaint of sinus headache.5,16,17 Paul-son and Graham described 104 patients who presentedwith the primary complaint of facial pain, normal sinusCT scans, and normal nasal endoscopic examiantions.These patients were then referred to a neurologist forfurther evaluation, 75 of whom attended this appoint-ment. Thirty-seven percent of those that followed up werediagnosed with migraine headaches, 17% were diagnosedwith rebound headache, 17% were diagnosed with chronicdaily headache, and 16% were diagnosed with obstructivesleep apnea.16 In another study, 2,991 patients with ahistory of self-described or physician-diagnosed sinusheadache were screened and 80% were found meet IHScriteria for migraine headaches.5 The Sinus, Allergy, andMigraine Study of 2007 reported that of 100 subjects withself-diagnosed sinus headache, 52% met IHS criteria formigraine with or without aura.7

Our study also highlights the diagnostic utility ofresponse to triptans in diagnosing migraine headache,particularly in individuals who may not meet the IHScriteria for migraine. Cady and Schreiber report similarfindings in patients with self-diagnosed sinus headachesin which patients were asked to treat their headacheswith sumatriptan. The percentage of headaches that were

reduced to mild or no pain was 66%. The authors furtherdescribe that patients who respond to migraine-specifictherapy suggest that these patients are actually sufferingfrom migraines.18 Studies that examined the efficacy oftriptans in patients with the diagnosis of migraine re-ported similar rates of success with triptan use. A reviewof several randomized, double-blind, placebo-controlledtrials showed that patients response rates at 2- and4-hours after receiving 100 mg oral sumatriptan were 51to 58% and 65 to 78%, respectively, compared with 17 to31% and 19 to 40% in the placebo group.19 In contrast tothe studies by Ishkanian and Cady and Schreiber, ourstudy was not limited to a single dose of a single agent

given at one interval. Our patients were instructed totreat every headache and to use a second dose if theirheadache persisted after the first and they were also ini-tiated on alternative therapies if the first failed. This mayaccount for our slightly higher success rates than thosereported in the literature.

A potential weakness to our study was its design asan open-label, nonrandomized study without a placebocontrol. Our patient population was, by design, a groupselected for the absence of sinus pathology to eliminate theconfounding 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

TABLE IV.

Results of Patient Responses to Triptan orMigraine-Directed Therapy.

Number of Patients Percent

50% reduction inheadache with triptan use

31 81.6

2550% reduction inHeadache with triptan use

1 2.6

No response with triptan use 3 7.9

Significant reduction inheadache with migraine-directed therapy, lifestyleor diet changes

3 7.9


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rhinosinusitis. Those patients who continued to haveheadaches despite having evidence of resolved sinus dis-ease were then offered the opportunity to enroll in ourstudy.

Given the highly selective nature of our study, theplacebo effect should be considered in evaluating the data.The Ishkanian study and other studies looking at theefficacy of triptans in migraines19 report response rates to

placebo. Although triptans showed an effect above that ofplacebo, placebo was still shown to reduce headaches in agroup of patients. This effect cannot be excluded in ourstudy.

A significant number of patients did not complete ourstudy, weakening the statistical power of our findings.However, the reason behind the loss to follow-up was oftenrelated to patient reluctance to accept the diagnosis ofmigraine thereby itself highlighting an important bar-rier to appropriately diagnosing and treating patientsheadaches.

Sinus headache is a difficult clinical presentationthat we argue may often represent migraine headache.Otolaryngologists should be prepared to not only includemigraine in the differential diagnosis in evaluating pa-tients who present with sinus headache, but to also beprepared and willing to initiate treatment, as these pa-tients will benefit greatly.

Our study also demonstrates that response totriptans may be a useful diagnostic tool in evaluatingsinus headache patients.

CONCLUSIONEighty-two percent of 38 patients in our study had a

significant response to triptan use. Our findings highlightthe importance of considering migraine headaches in thedifferential diagnosis of patients presenting with sinus

headaches in the context of negative clinical and radio-graphic evidence. Our findings also demonstrate the diag-nostic utility of triptan use in evaluating patients for sinusheadaches who may not meet strict IHS criteria for mi-graine headache.

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