Review

Cephalalgia
0(0) 1–11
Headache and rhinosinusitis: A review ! International Headache Society 2020
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DOI: 10.1177/0333102420959790
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Claire EJ Ceriani and Stephen D Silberstein

Abstract
Purpose of review: To explain our current understanding of headache attributed to rhinosinusitis, an often inappro-
priately diagnosed secondary headache.
Recent findings: Recent studies have shown that headache attributed to rhinosinusitis is often over-diagnosed in
patients who actually have primary headache disorders, most commonly migraine. Failure to recognize and treat
rhinosinusitis, however, can have devastating consequences. Abnormalities of the sinuses may also be treatable by
surgical means, which may provide headache relief in appropriately selected patients.
Summary: It is important for the practicing physician to understand how rhinosinusitis fits into the differential diag-
nosis of headache, both to avoid overdiagnosis in patients with primary headache, and to avoid underdiagnosis in patients
with serious sinus disease.

Keywords
Headache, sinusitis, rhinosinusitis, sphenoid sinusitis, contact point headache, migraine
Date received: 1 October 2019; revised: 10 December 2019; 29 May 2020; 24 July 2020; 11 August 2020; accepted: 13 August 2020

Introduction
Headache and rhinosinusitis are two of the most
common reasons that patients visit physicians, and
the two often co-occur. Rhinosinusitis affects 32 mil-
lion adults in the United States each year and
accounted for about 13 million physician visits in
2000 (1). There is evidence that “sinus headache” due
to rhinosinusitis is over-diagnosed, and antibiotics for
rhinosinusitis are over-prescribed (2,3). Conversely,
sphenoid rhinosinusitis is often underdiagnosed, lead-
ing to poor clinical outcomes when treatment is delayed
(4,5). An understanding of the appropriate workup for
suspected rhinosinusitis and the diagnostic criteria for
headache attributed to rhinosinusitis is essential to
guide diagnosis and management.
Anatomy and physiology of the sinuses
Rhinosinusitis is the result of infection of one or more
of the paranasal sinuses (Figure 1). The paranasal
sinuses are air-filled cavities lined with pseudostratified
ciliated epithelial tissue covered with a thin layer of
mucus. The sinuses communicate with the nasal pas-
sages via openings known as ostia. The coordinated
beating of the cilia lining the sinuses moves mucus
and inhaled debris toward the ostia to be expelled
into the nasal passageway (6,7). This mechanism
allows for the clearance of bacterial contamination
(7). The primary sites for mucociliary drainage are
the middle meatus and the sphenoethmoidal recess
(7). The middle meatus drains the frontal sinus, anteri-
or ethmoidal air cells, and maxillary sinus via a channel
known as the ostiomeatal complex (Figure 2).
Obstruction of the ostiomeatal complex can lead to
maxillary, frontal, and ethmoid sinus disease (6,8).
The sphenoethmoidal recess drains the posterior eth-
moidal air cells and the sphenoid sinus. There may be a
communication between the posterior ethmoidal air
cells and the sphenoid sinus. Obstruction of the ostia
disrupts normal mucociliary flow and creates an anaer-
obic environment, facilitating bacterial growth (6).
Because of the functional relationship between the
ostia and the sinuses, the ethmoid sinus is a common
site of primary infection that leads to infection of the
frontal and maxillary sinuses (7). Anatomic
Jefferson Headache Center, Philadelphia, PA, USA
Corresponding author:
Stephen D Silberstein, Jefferson Headache Center, 900 Walnut Street,
Suite 200, Philadelphia, PA 19107-4824, USA.
Email: stephen.silberstein@jefferson.edu
2 Cephalalgia 0(0)
Figure 1. The paranasal sinuses.
Figure 2. The ostiomeatal complex.
abnormalities may also predispose to recurrent or
chronic rhinosinusitis (7).
Rhinosinusitis
In 1997, the Task Force on Rhinosinusitis (RSTF)
agreed that the term rhinosinusitis was preferred over
sinusitis. This is because sinusitis commonly presents
with nasal discharge and is typically preceded by rhini-
tis, and purulent sinusitis without rhinitis is rare (9).
Rhinosinusitis is divided into four categories, defined
by the RSTF (9). Acute rhinosinusitis (ARS) lasts from
1 day to 4 weeks and has complete resolution of symp-
toms. Recurrent ARS is four or more episodes of ARS
each lasting at least 7 days and occurring in a 1-year
period. Subacute rhinosinusitis lasts from 4 to 12
weeks. Chronic rhinosinusitis (CRS) persists beyond
12 weeks and may be punctuated by acute infectious
episodes (9).
ARS is caused by infection of one or more of the
paranasal sinuses. The infection may be viral, bacterial,
or fungal. Most cases of ARS begin with a viral upper
respiratory tract infection that extends into the para-
nasal sinuses, which may be followed by bacterial infec-
tion (10). It is estimated that 0.5–2% of cases of viral
ARS in adults are complicated by bacterial rhinosinu-
sitis (1). The most common pathogens associated with
acute bacterial rhinosinusitis (ABRS) are Streptococcus
Ceriani and Silberstein
pneumoniae and Haemophilus influenzae (1). Other fre-
quently reported bacteria are Neisseria species,
Streptococcus pyogenes, a-hemolytic and non-group A
b-hemolytic streptococci, Moraxella catarrhalis, and
Staphylococcus aureus (1). Common viruses cultured
from sinus isolates include rhinoviruses, influenza
viruses, and parainfluenza viruses (1).
Some factors predispose to bacterial rhinosinusitis,
including prior upper respiratory tract infection, aller-
gic rhinitis, dental infections, anatomic variations,
secretory disturbances (such as cystic fibrosis), immu-
nodeficiency, and iatrogenic factors (mechanical venti-
lation, nasogastric tubes, nasal packing, dental
procedures) (11). The most common predisposing
factor is mucosal inflammation from a viral upper
respiratory infection or allergic rhinitis (12). In a
study of computed tomography (CT) scans in healthy
adults with colds, 77% had occlusion of the ethmoid
infundibulum, 87% had maxillary sinus abnormalities,
65% had ethmoid sinus abnormalities, 32% had fron-
tal sinus abnormalities, and 39% had sphenoid sinus
abnormalities (13). After 2 weeks, some patients (none
of whom received antibiotics) had repeat imaging, and
the abnormalities of the sinuses and infundibulum had
cleared or markedly improved in 79% (13). In patients
for whom these abnormalities do not spontaneously
resolve, secondary bacterial infection becomes more
likely (10).
Clinical presentation
Guidelines published in 2015 by the American
Academy of Otolaryngology – Head and Neck
Surgery (AAO-HNS) Foundation define rhinosinusitis
as purulent (not clear) nasal discharge (either reported
by the patient or observed on physical examination)
accompanied by nasal obstruction, facial pain-
pressure-fullness, or both (10). Nasal obstruction may
be described by the patient as congestion, blockage, or
stuffiness, or may be seen on exam (10). Facial pain-
pressure-fullness may be localized in the anterior face
or periorbital region, or may present as a localized or
diffuse headache (10). It is important to note that the
presence of purulent nasal discharge is required for
diagnosis. This is at odds with guidelines published in
2016 by the International Forum of Allergy and
Rhinology (IFAR), which state that symptoms must
include nasal obstruction or nasal discharge, and
facial pain/pressure or reduction/loss of smell (14).
The guidelines issued by the AAO-HNS state that the
differential diagnosis for isolated facial pain is broad,
and the specificity for ABRS increases when coupled
with purulent nasal discharge (10). This reduces the
likelihood that a primary headache presenting with
facial pain will be misdiagnosed as rhinosinusitis but
3
could miss a diagnosis of sphenoid rhinosinusitis,
which may not present with purulent drainage until
obstruction is relieved by surgery. Sphenoid rhinosinu-
sitis is discussed in more detail later in this review.
Other symptoms of rhinosinusitis include altered
sense of smell, cough, halitosis, fever, dental pain,
pharyngitis, and otologic symptoms (9).
Much of the medical literature on rhinosinusitis and
headache was published prior to 2015 and uses older
diagnostic guidelines. The original 1997 RSTF pub-
lished diagnostic criteria for rhinosinusitis that
required the presence of two or more major factors
or one major and two minor factors (9). Major factors
included facial pain/pressure, nasal obstruction/block-
age, nasal purulent discharge, hyposmia/anosmia, or
purulence in the nasal cavity on examination. Minor
factors included headache, fever, halitosis, dental pain,
cough, or ear pain/pressure (9). Hwang and colleagues
found these criteria to have a sensitivity of 89%, but a
specificity of only 2% in CRS (15). The RSTF criteria
were updated in the AAO-HNS 2007 guidelines to
include the presence of two or more major factors
and either radiographic or endoscopic evidence of
inflammation for the diagnosis of CRS (16). These
guidelines are still widely cited, even in some studies
that postdate the most recent 2015 guidelines.
Several studies have characterized the headache phe-
notypes of patients presenting with rhinosinusitis (17–
22). These findings are summarized in Table 1, along
with case reports of more unusual presentations (23–
27). All of these studies used imaging and/or diagnostic
nasal endoscopy (DNE) to confirm the diagnosis of
rhinosinusitis, with the exception of Aaseth and col-
leagues (19), who used anterior rhinoscopy. Not all
studies included patient follow-up, but those that did
demonstrated improvement of pain following treat-
ment for rhinosinusitis in the majority of patients, sup-
porting the authors’ initial diagnoses of headache
attributed to rhinosinusitis (17,19,22). Note that
Tarabichi only included patients who had pain resolu-
tion following endoscopic sinus surgery (ESS) to ensure
that all patients included in the analysis were most
likely to have had rhinosinusitis as the underlying
cause of their headache (17). In all of the studies that
evaluated patient-reported descriptions of headache,
most were phenotypically similar to tension-type head-
ache: Pressure-like, dull, aching, or tightening (17–
19,21). Patient reports of pulsating or throbbing pain
are variable within these studies, with some finding it
uncommon, but DeConde and colleagues reporting it
in the majority of patients (21). Migrainous features
such as nausea, photophobia, and phonophobia were
seen in a minority of patients in all studies that assessed
these symptoms, with nausea being the most frequently
seen (ranging from 15.2% to 46.2%) (17,19,20). It
 4
Table 1. Clinical characteristics of headache attributed to rhinosinusitis.

Subjects Headache/facial pain presentation

Age: Mean Treatment

Study # (Range) M/F Basis for Dx Character/features Severity Location outcome

Tarabichi (2000) (17): 45 32 29/16 CT, DNE Pinching/pressing/gnawing/ Above/between All had complete
Study of pts with CRS cramping/crushing: 87% eyes: 55% resolution of
and facial pain that Dull/sore/hurting/aching/ Below eyes: 17% both pain and
improved after ESS heavy: 76% Above/below/ signs of CRS on
Worsened by leaning for- between eyes: DNE at 1 year
ward: 78% 20% follow up after
Worse in AM: 71% Pain radiated to the ESS (these were
Nausea: 20% ears: 58% inclusion criteria)
Bilateral: 91%
Busaba (2008) (18): 514 45.4 (18–86) 241/273 CT, DNE % men, % women
Prospective study of Pressure pain: 32.8%, 52.4%
consecutive CRS pts Stabbing pain: 2.5%, 6.6%
Pulsating pain: 4.2%, 11.4%
Pricking pain: 0.8%, 1.5%
Aaseth (2010) (19): 46 Mean age of 7/39 RSTF, AR Pressing/tightening: 98% Mild/ moderate: Bilateral: 93% 38 f/up at 3 yrs: 27
Subjects diagnosed with onset 22.7 Not aggravated by activity: 96% Unilateral: 7% had significant
HACRS from a cross- 96% Severe: 4% reduction of pain
sectional epidemiologi- Mild nausea: 26% with treatment
cal survey of 30,000 Photophobia: 4% (8 nasal surgery,
people Phonophobia: 4% 4 nasal steroids,
Pulsating: 2%Vomiting: 0% 3 stopped use of
decongestants,
12 unspecified)
Hsueh (2013) (20): 1: 33 1: 43.2 1: 15/18 AAO–HNS % cohort a, % cohort b Moderate/severe: Unilateral:
Pts with CRS in two 2: 39 2: 39.3 2: 18/21 2007, DNE, Pulsating/throbbing: 15.2%, 1: 27.2% 2: 64.1% 1: 6.7%
cohorts from 1) retro- CT 56.4% 2: 53.8%
spective review of ENT- Exacerbated by physical
documented symptoms activity: 15.2%, 43.6%
and 2) prospective col- Nausea: 15.2%, 46.2%
lection of pt-reported Photophobia: 18.2%, 46.2%
symptoms on ROS Phonophobia: 9.1%, 41.0%
form Osmophobia: NA, 33.3%
Dizziness: 3.0%, 35.9%
Visual aura: 9.1%, 35.9%
Numbness/tingling: 0.0%,
20.5%
(continued)
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Table 1. Continued
Subjects Headache/facial pain presentation
Ceriani and Silberstein

Age: Mean Treatment

Study # (Range) M/F Basis for Dx Character/features Severity Location outcome

DeConde (2015) (21): 1: 25 1: 43.6 1: 16/9 AAO–HNS Most common descriptions: Mean VAS: Most common
Prospective, cross-sec- 2: 30 2: 51.1 2: 13/17 2007, CT, 1: Aching (80.0%), throbbing 1: 3.5 locations:
tional study of pts with DNE (75%), tiring/exhausting 2: 3.6 1: Above eye R, L
1) CRSwNP and 2) (73.9%), heavy (60.0%), (60.0%, 60.0%);
CRSsNP sharp (58.3%) below eye R, L
2: Tender (82.1%), throbbing (56.0%, 60.0%);
(76.7%), aching (72.4%), between eyes
tiring/exhausting (69%), (44.0%)
splitting (57.1%) 2: Above eye R, L
(53.3%, 56.7%);
between eyes
(56.7%), below
eye R, L (53.3%,
53.3%)
Yeo (2017) (22): Pts who 203 47 (18–76) 130/73 CT, DNE Mean VAS Periorbital: R 78 pts who had pain
underwent ESS for CRS score 4.8 51.3%, L 46.0% and underwent
(patients with nausea, Frontal: R 43.6%, L ESS: 68% were
vomiting, photophobia, 33.0%, vertex: R pain free, 32%
phonophobia were 33.3%, L 30.8% still had pain (less
excluded) Occipital: R 26.9%, severe in 17.9%)
L 26.9%
Facial: R 17.9%, L
19.0%
Non-specific: R
15.4%, L 15/4%
AAO-HNS: American Academy of Otolaryngology – Head Neck Surgery; Abx: antibiotics; AR: anterior rhinoscopy; ARS: acute rhinosinusitis; CRS: chronic rhinosinusitis; CRSsNP: CRS without nasal
polyps; CRSwNP: CRS with nasal polyps; DNE: diagnostic nasal endoscopy; Dx: diagnosis; ESS: endoscopic sinus surgery; f/up: follow-up; HACRS: headache attributed to chronic rhinosinusitis; Pt: patient;
ROS: review of systems; RSTF: Task Force on Rhinosinusitis; SUNCT: short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; Tx: treatment; VAS: visual analog scale.
5
6 Cephalalgia 0(0)
should be noted that Yeo and colleagues excluded
patients with migrainous features (22). Tarabichi
found that the headache is worse in the morning and
worsened by leaning forward in a majority of patients
(71% and 78%, respectively) (17). The headache is
more frequently bilateral, with the most common loca-
tions being periorbital and frontal, but vertex and
occipital pain are also seen (17,19–22). One study also
notes that pain radiates to the ears in 58% of patients
(17). Two studies specifically note that pain location
did not correlate with the location of the rhinosinusitis
on imaging (17,22). The pain is usually not reported as
severe or having a mean score greater than 5 on the
Visual Analog Scale (19–22). Three studies specifically
note that pain severity did not correlate with severity of
rhinosinusitis as seen on imaging (17,21,22).
These studies collectively give us a typical phenotype
for the headache caused by rhinosinusitis, but also
demonstrate the range of headache presentations that
can be seen.
It is not clear how common headache and facial pain
actually are in rhinosinusitis. Recent studies have
found it to be much less prevalent than historically
thought, except when there is acute bacterial infection
and the sinus cannot drain, which usually presents with
fever and unilateral nasal obstruction (28). In a study
of rhinogenic facial pain, only 29% of 108 patients with
purulent secretions on nasal endoscopy had facial pain
(29). Multiple studies have found that CRS is over-
diagnosed, and that headache and facial pain are
uncommon symptoms even in patients with confirmed
CRS (2). A cross-sectional epidemiological study of
30,000 people from the general population in Norway
found that the prevalence of headache secondary to
CRS as diagnosed by RSTF criteria was 0.33%
(0.13% in men and 0.48% in women) (19).
The International Headache Society (IHS) has
defined headache attributed to acute rhinosinusitis
and headache attributed to chronic or recurring sinus-
itis (30). Any headache phenotype is allowed by the
diagnostic criteria, which appropriately reflects the var-
iable presentation that is seen. More important is to
establish the presence of other signs and/or symptoms
of rhinosinusitis (clinically, endoscopically, or radio-
graphically) and evidence of causation.
Recommendations for which guidelines to use to diag-
nose rhinosinusitis are not given. Evidence of causation
is demonstrated by two of the following: Temporal
relation, worsening or improvement of the headache
and rhinosinusitis in parallel, exacerbation by pressure
over the sinuses, and headache localized and ipsilateral
to the site of rhinosinusitis if it is unilateral (30).
Tenderness to palpation over the sinuses is not neces-
sarily present in rhinosinusitis (9). As previously dis-
cussed, headache location has not been shown to
correlate with rhinosinusitis location on CT (17,22).
The last two criteria therefore may not be valid in all
patients.
Differential diagnosis
Migraine and tension-type headache should always be
considered in patients presenting with “sinus head-
ache”. Overlap in symptoms and high prevalence of
primary headache in the general population has led
to many patients being incorrectly diagnosed with
headache secondary to sinus disease, leading to inap-
propriate treatment. Migraine often presents with a
frontal headache, which may be accompanied by cra-
nial autonomic symptoms such as nasal congestion and
rhinorrhea, mimicking rhinosinusitis (31). The sinuses
are innervated by trigeminal nerve fibers, which may
activate parasympathetic nerves and cause these auto-
nomic symptoms that are common to both migraine
and rhinosinusitis (32). The rhinorrhea seen in primary
headache will be clear; purulent nasal discharge should
raise suspicion for rhinosinusitis (10).
Multiple studies in recent years have looked at
patients who met criteria for migraine diagnosis and
failed to respond to treatment for rhinosinusitis.
When treated for migraine, 50–82% improved (31). A
study by Cady and Schreiber found that 90% of phy-
sician and self-diagnosed sinus headaches meet IHS
criteria for migraine (33). Another study by Schreiber
evaluated 2991 patients with reported sinus headache
and found that 80% actually had migraine (34). At the
time of their initial office visit, 84% of patients
reported sinus pressure, 82% reported pain in the
sinus areas, 63% reported nasal congestion, and 40%
reported rhinorrhea (34). Eross and colleagues evaluat-
ed 100 consecutive patients with self-diagnosed sinus
headache and found that 52% had migraine, 23%
had probable migraine, 11% had chronic migraine,
9% had other unclassifiable headache, 1% had cluster
headache, and 1% had hemicrania continua (35). Only
3% were accurately diagnosed with headache second-
ary to rhinosinusitis (35).
Some patients may have comorbid sinus disease and
primary headache, requiring a multidisciplinary
approach. Lal and colleagues looked at 211 patients
who presented to otolaryngology with complaints of
sinus pressure, pain, or headache (36). About 70%
met criteria for sinusitis, but nearly half also had a
primary headache disorder, and nearly one third were
diagnosed with comorbid rhinologic-neurologic disease
(36). Hsueh and colleagues found that over 20% of
patients with CRS met International Headache
Society migraine criteria (20), and Aaseth and col-
leagues found that nearly half did (19). There is some
question of whether rhinosinusitis may exacerbate
Ceriani and Silberstein
pre-existing migraine, though this has not been thor-
oughly investigated in the literature. Most studies have
not focused on prior primary headache history in the
subjects.
Septal deformations with a mucosal contact point
on the lateral nasal wall may cause episodic headache.
These abnormalities are often missed on neuroimaging
and should be considered in patients with refractory
headache, as surgical removal of the mucosal contact
point may improve the headache (37). In a systematic
review of 39 articles encompassing 1577 patients who
underwent surgery for mucosal contact point headache,
Farmer and colleagues found that 85% of patients
reported partial or complete resolution of headaches,
with reported follow-up range of 1 month to 10 years
(38). Many of the studies reviewed did not include spe-
cific headache characteristics reported by the patients,
so a mucosal contact point headache phenotype could
not be defined, but improvement in headache symp-
toms was significantly associated with a positive
response to preoperative anesthetic testing using local
application of lidocaine (38). In a study of 42 patients
who had failed medical management of chronic daily
headache and subsequently underwent surgery for a
mucosal contact point, 19% were headache free and
62% had significant improvement in headache severity
and frequency throughout a postoperative follow-up
period ranging from 12–48 months (39). Of note,
mucosal contact points may be seen on CT in 40% of
asymptomatic individuals, raising the question of
whether a genetic predisposition to primary headache
such as migraine may be required to provoke headache
in patients with mucosal contact points (40).
Diagnostic testing
History and physical exam, including otoscopy and
anterior rhinoscopy to look for purulent discharge, is
often sufficient for routine diagnosis of ARS.
Tenderness on palpation of the sinuses may or may
not be present (9). Though once the traditional first
step in evaluating the sinuses, transillumination has
low sensitivity and specificity for rhinosinusitis (41).
The AAO-HNS recommends against obtaining imag-
ing in patients who meet criteria for ARS, unless there
is concern for complication or an alternative diagnosis
is suspected (10). A diagnosis of CRS should not be
made without objective documentation of sinonasal
inflammation using either anterior rhinoscopy, DNE,
or CT (10). All patients with symptoms lasting longer
than 12 weeks should therefore undergo CT imaging
and/or referral to otolaryngology.
The AAO-HNS and IFAR agree that CT is the opti-
mal study to assess the paranasal sinuses (10,14).
Imaging must be done in the coronal plane to
7
adequately assess the ethmoid complex (7). Because
the mucosa of the normal sinus approximates the
bone so closely that it cannot be seen on CT, any
soft tissue seen within a sinus is abnormal (42).
Clouding, air-fluid levels, and mucosal thickening
may all be signs of infection (43). The Lund-MacKay
scoring system is often used to stage CRS, with each
paranasal sinus assigned a score of 0 (no abnormality),
1 (partial opacification) or 2 (complete opacification),
and the ostiomeatal complex assigned either a 0 (not
obstructed) or a 2 (obstructed), for a total possible
score of 24 (44). In a study of 171 patients undergoing
ESS for CRS, sinus CT had sensitivity of 94% and
specificity of 41% when a Lund score cut-off of greater
than 2 was defined as abnormal (45). Test-retest reli-
ability of CT in the evaluation of CRS is high (46). It
should be noted that reversible CT abnormalities are
common in patients with viral upper respiratory infec-
tions, so CT may not be specific for bacterial infections
(13). Incidental anatomic abnormalities on CT are also
quite common and may occur in 27–45% of asymp-
tomatic individuals (45). About 40% of normal indi-
viduals have mucosal thickening on CT (47).
MRI should be considered an adjunct to CT in diag-
nosing sinus disease. In the normal nasal cycle, there is a
natural alternating congestion and decongestion phase.
During the congestion phase, the nasal mucosa in
normal individuals may appear pathologic on T2-
weighted images (7). MRI is more sensitive than CT in
identifying fungal infections and has superior soft tissue
resolution, which allows for more accurate differentia-
tion between inflammatory disease and neoplastic dis-
ease (7). If CT imaging demonstrates osseous
destruction, extra-sinus extension, or local invasion,
MRI should be obtained to differentiate between
benign obstructed secretions and neoplasia, and to
asses for spread outside the nasal cavity and sinuses (48).
DNE using the flexible rhinoscope is complementary
to neuroimaging. The rhinoscope allows for direct visu-
alization of the nasal passages and the ostiomeatal
complex. Purulent material is often seen in rhinosinu-
sitis, though may not be visualized in sphenoid rhino-
sinusitis (43). Mucosal sinus thickening on imaging is
often present in asymptomatic individuals. Endoscopy
should be positive for infection before a diagnosis of
rhinosinusitis is made in these cases, especially if sur-
gery is being considered (7,49). Negative imaging and
endoscopy usually, but not always, rules out sinus dis-
ease (7).
Treatment
When headache attributed to rhinosinusitis is sus-
pected, treatment of the underlying rhinosinusitis is
necessary to treat the headache (50). It is first
8 Cephalalgia 0(0)
important to distinguish viral from bacterial infection,
as viral infection is usually self-limited and requires no
specific treatment. Symptoms of viral ARS typically
peak within 3 days and resolve within 10 to 14 days
(10). AAO-HNS 2015 guidelines based on aggregated
evidence from randomized controlled trials and cohort
studies recommend symptomatic treatment with simple
analgesics (acetaminophen, NSAIDs), topical intrana-
sal steroids, and/or nasal saline irrigation (10). A sys-
tematic review found that topical nasal steroids relieved
facial pain in patients with ARS (51). It is difficult to
distinguish viral from bacterial rhinosinusitis clinically,
but bacterial infection should be suspected in patients
with symptoms persisting without improvement for at
least 10 days or worsening within 10 days after an ini-
tial improvement (10). These patients should be offered
symptomatic treatment, and antibiotics should be con-
sidered. If there is assurance of follow-up, watchful
waiting may be offered and antibiotics started if the
patient’s condition does not improve after 7 days or
worsens at any time (10).
The AAO-HNS guidelines recommend amoxicillin
with or without clavulanate for 5–10 days as first-line
therapy for ABRS (10). Analysis of multiple random-
ized controlled trials and meta-analyses did not show a
difference in outcomes of amoxicillin compared with
cephalosporins or macrolides, so amoxicillin is recom-
mended as first-line therapy due to its safety, efficacy,
low cost, and narrow microbiologic spectrum (10). The
use of amoxicillin with clavulanate is recommended for
adults who are at high risk of being infected with an
amoxicillin-resistant organism (recent antibiotic use,
smoker, moderate to severe symptoms, protracted
symptoms, working or living in a healthcare environ-
ment, frontal or sphenoidal sinusitis, age over 65,
immunocompromised, comorbid conditions such as
diabetes) (10). Penicillin-allergic patients may use doxy-
cycline, levofloxacin, or moxifloxacin (10).
For CRS, the AAO-HNS recommends saline nasal
irrigation and topical intranasal corticosteroids for
8–12 weeks to reduce inflammation (10). A 2016
Cochrane review of five randomized controlled trials
found little evidence that oral antibiotics are effective
in CRS, though there is moderate evidence that there
may be a moderate improvement in quality of life after
3 months of treatment with a macrolide (52). Some
cases of CRS may require ESS to reopen the sinus
ostia and ostiomeatal complex (41). Allergic etiology
should be included in the differential (53). The possi-
bility of co-occurrence of rhinosinusitis and primary
headache should always be considered in patients
with persistent symptoms that fail to resolve with anti-
biotics. These patients may require co-management
with neurology and otolaryngology. In a retrospective
review of patients who had undergone medical, surgi-
cal, and/or neurologic treatment for rhinosinusitis, ESS
was most successful in patients receiving concurrent
neurologic treatment (54).
Patients refractory to empiric management or with
signs of complication should be referred for evaluation
by a specialist and may require imaging if not already
done (9). Uncommon, but serious, complications
include meningitis, brain abscess, orbital cellulitis, orbit-
al abscess, and mucocele (10). A mucocele is a benign,
but potentially destructive, mucus-containing cyst that
can form in any of the sinuses and may present with a
progressive headache and cranial nerve palsies due to
compression, especially in the sphenoid sinus (55,56).
Sphenoid rhinosinusitis. Special consideration should be
given to sphenoid rhinosinusitis due to the difficulty
of diagnosis and high rate of serious complications. It
usually occurs in the setting of pansinusitis, but may
occur separately. Isolated sphenoid rhinosinusitis rep-
resents about 3% of cases of ARS (4). It is associated
with significant morbidity and mortality and requires
early diagnosis and aggressive treatment (4,57–59). The
sphenoid sinus is in close proximity to the cortical
venous system, cranial nerves, and meninges, some-
times separated by just a thin mucosal barrier.
Infectious spread to nearby structures may lead to
life-threatening neurologic disease (60).
The most common presenting symptom in isolated
sphenoid rhinosinusitis is headache, reported in over
80% of patients (5). The location is most often frontal
or vertex or diffuse, but it may also be occipital, tem-
poral, parietal, or retro-orbital (59,61–64). The pain
may be sharp or dull and may occur intermittently
for years (5). It may interfere with sleep (4) and may
be exacerbated by head movement (61). Sphenoid rhi-
nosinusitis may mimic migraine, trigeminal neuralgia,
cluster headache, aseptic meningitis, subarachnoid
hemorrhage, or tumor (4,65–67). It may occur with
photophobia, lacrimation, neck stiffness, paresthesias
in the trigeminal distribution, and cranial nerve palsies
(4,57,59,60,66–70). In a retrospective review of 39
cases, Ruoppi and colleagues reported that 28% of
patients had visual symptoms, 26% had dizziness,
21% had cranial nerve palsies (optic, oculomotor, or
trigeminal), and 18% had fever (63). A review of 31
cases by Wang and colleagues found that 19% had
visual symptoms, 3% had eye movement abnormali-
ties, and 35% had epistaxis (64).
DNE may show purulent discharge, but negative
DNE does not rule out sphenoid rhinosinusitis (5). In
a study of 14 patients with sphenoid rhinosinusitis,
Ceriani and Silberstein 9

recommendations for when to consider this diagnosis

Figure 3. Acute left sphenoid sinusitis.
only three had purulent exudate (58). Neuroimaging
with CT or MRI is necessary for definitive diagnosis
(Figure 3). Thin section CT scanning can also identify
complications such as cavernous sinus involvement,
abscess formation, and bony extension (57). The med-
ical literature has not established a symptom or char-
acteristic of the headache of sphenoid rhinosinusitis
that is sensitive and specific for this diagnosis. Most
of the literature has been contributed by otolaryngolo-
gists, not neurologists, and most studies do not go into
much depth on the presentation of the headache
beyond its location. Studies that address the history
of comorbid headache disorders in patients presenting
with sphenoid rhinosinusitis are also lacking. Further
research on the presentation, history, and natural pro-
gression of headache in patients with sphenoid rhino-
sinusitis is needed to formulate evidence-based
as a cause of headache.
Complications of sphenoid rhinosinusitis can be life-
threatening and include bacterial meningitis, cavernous
sinus thrombosis, abscess, cortical vein thrombosis,
and hypophysitis (4,57,60,65,68–71). Ophthalmic com-
plications may also occur, including ophthalmoplegia
and periorbital or orbital cellulitis (4,60,65,67–70).
Early treatment is essential to avoid serious morbidity
and mortality. In a classic report of 30 cases by Lew
and colleagues, all patients with delayed treatment suf-
fered serious complications or died (4). Sphenoid rhi-
nosinusitis without complication should be treated with
high-dose, broad-spectrum antibiotics and topical and
systemic decongestants for 10–14 days (5,57,58).
Intravenous antibiotics are often used, though patients
with minimal symptoms have been treated with oral
antibiotics and recovered well (57,58). Patients who
fail to respond to antibiotics or who show signs of
developing complications should undergo surgical
intervention to drain the sphenoid sinus (5,57).
Conclusion
Headache attributed to rhinosinusitis is often inappro-
priately diagnosed by both patients and physicians. In
cases where headache is secondary to rhinosinusitis,
early recognition is important to guide treatment and
to avoid potentially life-threatening complications in
the case of sphenoid rhinosinusitis. It is equally impor-
tant to recognize when headache with nasal symptoms
is in fact a primary headache disorder to spare patients
the frustration of unnecessary testing and ineffective
treatment.

Clinical implications
• Headache attributed to rhinosinusitis is an uncommon cause of secondary headache.
• Most patients presenting with headache in the area of the sinuses have migraine, and rhinosinusitis and
primary headache disorders may co-occur.
• The headache of rhinosinusitis is more often bilateral and tension-type in character, though migrainous
features may also be seen, and there should be evidence of causation as defined in the ICHD-3 criteria.
• Most cases of acute rhinosinusitis are viral and do not require antibiotics.
• Sphenoid rhinosinusitis should be considered in the differential for headache presenting with cranial nerve
abnormalities.

Declaration of conflicting interests Funding

The authors declared no potential conflicts of interest with The authors received no financial support for the research,
respect to the research, authorship, and/or publication of this authorship, and/or publication of this article.
article.
10
ORCID iD
Stephen D Silberstein https://orcid.org/0000-0001-9467-
5567
References
1. Sande MA and Gwaltney JM. Acute community-
acquired bacterial sinusitis: Continuing challenges and
current management. Clin Infect Dis 2004; 39:
S151–S158.
2. Pipolo C, Saibene AM and Felisati G. Prevalence of pain
due to rhinosinusitis: A review. Neurol Sci 2018; 39:
S21–S24.
3. Smith SS, Evans CT, Tan BK, et al. National burden of
antibiotic use for adult rhinosinusitis. J Allergy Clin
Immunol 2013; 132: 1230–1232.
4. Lew D, Southwick FS, Montgomery WW, et al.
Sphenoid sinusitis: A review of 30 cases. N Engl J Med
1983; 309: 1149–1154.
5. Charakorn N and Snidvongs K. Chronic sphenoid rhino-
sinusitis: Management challenge. J Asthma Allergy 2016;
9: 199–205.
6. Reilly JS. The sinusitis cycle. Otolaryngol – Head Neck
Surg 1990; 103: 856–862.
7. Zinreich SJ. Paranasal sinus imaging. Otolaryngol – Head
Neck Surg 1990; 103: 863–869.
8. McCaffrey TV. Functional endoscopic sinus surgery: An
overview. Mayo Clin Proc 1993; 68: 571–577.
9. Lanza DC and Kennedy DW. Adult rhinosinusitis
defined. Otolaryngol – Head Neck Surg 1997; 117: S1–S7.
10. Rosenfeld RM, Piccirillo JF, Chandrasekhar SS, et al.
Clinical practice guideline (update): Adult sinusitis.
Otolaryngol – Head Neck Surg 2015; 152: S1–S39.
11. Brooks I, Gooch WM, Jenkins SG, et al. Medical
management of acute bacterial sinusitis:
Recommendations of a clinical advisory committee on
pediatric and adult sinusitis. Ann Otol Rhinol Laryngol
Suppl 2000; 182: 2–20.
12. Diaz I and Bamberger DM. Acute sinusitis. Semin Respir
Infect 1995; 10: 14–20.
13. Gwaltney JM Jr, Phillips CD, Miller RD, et al.
Computed tomographic study of the common cold. N
Engl J Med 1994; 330: 25–30.
14. Orlandi RR, Kingdom TT, Hwang PH, et al.
International consensus statement on allergy and rhinol-
ogy: Rhinosinusitis. Int Forum Allergy Rhinol 2016; 6:
S22–S209.
15. Hwang PH, Irwin SB, Griest SE, et al. Radiologic corre-
lates of symptom-based diagnostic criteria for chronic
rhinosinusitis. Otolaryngol – Head Neck Surg 2003; 128:
489–496.
16. Rosenfeld RM, Andes D, Bhattacharyya N, et al.
Clinical practice guideline: Adult sinusitis. Otolaryngol
– Head Neck Surg 2007; 137: S1–S31.
17. Tarabichi M. Characteristics of sinus-related pain.
Otolaryngol Head Neck Surg 2000; 122: 842–847.
18. Busaba NY, Sin HJ and Salman SD. Impact of gender on
clinical presentation of chronic rhinosinusitis with and
without polyposis. J Laryngol Otol 2008; 122: 1180–1184.
Cephalalgia 0(0)
19. Aaseth K, Grande RB, Kværner K, et al. Chronic rhino-
sinusitis gives a ninefold increased risk of chronic head-
ache. The Akershus study of chronic headache.
Cephalalgia 2010; 30: 152–160.
20. Hsueh WD, Conley DB, Kim H, et al. Identifying clinical
symptoms for improving the symptomatic diagnosis of
chronic rhinosinusitis. Int Forum Allergy Rhinol 2013; 3:
307–314.
21. Deconde AS, Mace JC, Ashby S, et al. Characterization
of facial pain associated with chronic rhinosinusitis using
validated pain evaluation instruments. Int Forum Allergy
Rhinol 2015; 5: 682–690.
22. Yeo NK, Park WJ, Ryu IS, et al. Is facial or head pain
related to the location of lesions on computed tomogra-
phy in chronic rhinosinusitis? Ann Otol Rhinol Laryngol
2017; 126: 589–596.
23. Edvardsson B and Persson S. Cluster headache and acute
maxillary sinusitis. Acta Neurol Belg 2013; 113: 535–536.
24. Balgetir F, Avcı D, G€ onen M, et al. Acute rhinosinusitis
as an infrequent cause of symptomatic cluster headache:
Report of seven cases. J Oral Facial Pain Headache 2019;
39: 408–412.
25. Choi JY, Seo WK, Kim JH, et al. Symptomatic SUNCT
syndrome associated with ipsilateral paranasal sinusitis.
Headache 2008; 48: 1527–1530.
26. Bichuetti DB, Yamaoka WY, Bastos JRP, et al. Bilateral
SUNCT syndrome associated to chronic maxillary sinus
disease. Arq Neuropsiquiatr 2006; 64: 504–506.
27. Lin Y-W, Lin S-K and Weng I-H. Fatal paranasal sinus-
itis presenting as trigeminal neuralgia. Headache 2006;
46: 174–178.
28. Jones NS. Sinus headaches: Avoiding over-and mis-diag-
nosis. Expert Rev Neurother 2009; 9: 439–444.
29. Clifton NJ and Jones NS. Prevalence of facial pain in 108
consecutive patients with paranasal mucopurulent dis-
charge at endoscopy. J Laryngol Otol 2007; 121: 345–348.
30. Headache Classification Committee of the International
Headache Society. The International Classification
of Headache Disorders, 3rd edition. Cephalalgia 2018;
38: 1–211.
31. Godley FA, Casiano RR, Mehle M, et al. Update on the
diagnostic considerations for neurogenic nasal and sinus
symptoms: A current review suggests adding a possible
diagnosis of migraine. Am J Otolaryngol – Head Neck
Med Surg 2019; 40: 306–311.
32. Cady RK and Schreiber CP. Sinus headache or migraine?
Considerations in making a differential diagnosis.
Neurology 2002; 58: S10–S14.
33. Cady RK and Schreiber CP. Sinus headache: A clinical
conundrum. Otolaryngol Clin North Am 2004; 37:
267–288.
34. Schreiber CP, Hutchinson S, Webster CJ, et al.
Prevalence of migraine in patients with a history of self-
reported or physician-diagnosed ‘sinus’ headache. Arch
Intern Med 2004; 164: 1769–1772.
35. Eross E, Dodick D and Eross M. The sinus, allergy and
migraine study (SAMS). Headache 2007; 47: 213–224.
36. Lal D, Rounds A, Dodick DW. Comprehensive manage-
ment of patients presenting to the otolaryngologist for
Ceriani and Silberstein
sinus pressure, pain, or headache. Laryngoscope 2015;
125: 303–310.
37. Rozen TD. Intranasal contact point headache: Missing
the ‘point’ on brain MRI. Neurology 2009; 72: 1107.
38. Farmer RL, Garg RK and Afifi AM. Can functional
nasal surgery treat chronic headaches? A systematic
review. Plast Reconstr Surg 2018; 142: 1583–1592.
39. Abu-Samra M, Gawad OA and Agha M. The outcomes
for nasal contact point surgeries in patients with unsatis-
factory response to chronic daily headache medications.
Eur Arch Otorhinolaryngol 2011; 268: 1299–1304.
40. Herzallah IR, Hamed MA, Salem SM, et al. Mucosal
contact points and paranasal sinus pneumatization:
Does radiology predict headache causality?
Laryngoscope 2015; 125: 2021–2026.
41. Stafford CT. The clinician’s view of sinusitis. Otolaryngol
– Head Neck Surg 1990; 103: 870–875.
42. Schatz CJ and Becker TS. Normal CT anatomy of the
paranasal sinuses. Radiol Clin North Am 1984; 22:
107–118.
43. Castellanos J and Axelrod D. Flexible fiberoptic rhinos-
copy in the diagnosis of sinusitis. J Allergy Clin Immunol
1989; 83: 91–94.
44. Lund V and MacKay I. Staging in rhinosinusitis.
Rhinology 1993; 31: 183–184.
45. Bhattacharyya N and Fried MP. The accuracy of com-
puted tomography in the diagnosis of chronic rhinosinu-
sitis. Laryngoscope 2003; 113: 125–129.
46. Bhattacharyya N. Test-retest reliability of computed
tomography in the assessment of chronic rhinosinusitis.
Laryngoscope 1999; 109: 1055–1058.
47. Havas TE, Motbey JA and Gullane PJ. Prevalence of
incidental abnormalities on computed tomographic
scans of the paranasal sinuses. Arch Otolaryngol – Head
Neck Surg 1988; 114: 856–859.
48. Mafee MF, Tran BH and Chapa AR. Imaging of rhino-
sinusitis and its complications: Plain film, CT, and MRI.
Clin Rev Allergy Immunol 2006; 30: 165–185.
49. Kennedy DW. Surgical update. Otolaryngol – Head Neck
Surg 1990; 103: 884–886.
50. Gupta M and Silberstein SD. Therapeutic options in the
management of headache attributed to rhinosinusitis.
Exp Opin Pharmacother 2005; 6: 715–722.
51. Hayward G, Heneghan C, Perera R, et al. Intranasal
corticosteroids in management of acute sinusitis: A sys-
tematic review and meta-analysis. Ann Fam Med 2012;
10: 241–249.
52. Head K, Chong LY, Piromchai P, et al. Systemic and
topical antibiotics for chronic rhinosinusitis. Cochrane
Database Syst Rev 2016; CD011994.
53. Dykewicz MS. Rhinitis and sinusitis. J Allergy Clin
Immunol 2003; 111: 5S20–S529.
54. Lal D, Rounds A and Dodick DW. Comprehensive man-
agement of patients presenting to the otolaryngologist for
11
sinus pressure, pain, or headache. Laryngoscope 2015;
125: 303–310.
55. Djambazov KB, Kitov BD, Zhelyazkov CB, et al.
Mucocele of the sphenoid sinus. Folia Med (Plovdiv)
2017; 59: 481–485.
56. Lee KE and Kim KS. Headache induced by the sphenoid
sinus mucocele. Braz J Otorhinolaryngol 2015; 81:
113–114.
57. Goldman GE, Fontanarosa PB and Anderson JM.
Isolated sphenoid sinusitis. Am J Emerg Med 1993; 11:
235–238.
58. Kibblewhite DJ, Cleland J and Mintz DR. Acute sphe-
noid sinusitis: Management strategies. J Otolaryngol
1988; 17: 159–163.
59. Celenk F, Gulsen S, Gonuldas B, et al. Isolated sphenoid
sinus disease: An overlooked cause of headache.
J Cranio-Maxillofacial Surg 2015; 43: 1914–1917.
60. Deans JAJ and Welch AR. Acute isolated sphenoid
sinusitis: A disease with complications. J Laryngol Otol
1991; 105: 1072–1074.
61. Gilony D, Talmi YP, Bedrin L, et al. The clinical behav-
ior of isolated sphenoid sinusitis. Otolaryngol – Head
Neck Surg 2007; 136: 610–615.
62. Kim SW, Kim DW, Kong IG, et al. Isolated sphenoid
sinus diseases: Report of 76 cases. Acta Otolaryngol 2008;
128: 455–459.
63. Ruoppi P, Seppa J, Pukkila M, et al. Isolated sphenoid
sinus diseases: Report of 39 cases. Arch Otolaryngol Head
Neck Surg 2000; 126: 777–781.
64. Wang Z-M, Kanoh N, Dai C-F, et al. Isolated sphenoid
sinus disease: An analysis of 122 cases. Ann Otol Rhinol
Laryngol 2002; 111: 323–327.
65. Øktedalen O and Lilleås F. Septic complications to sphe-
noidal sinus infection. Scand J Infect Dis 1992; 24:
353–356.
66. Zanchin G, Rossi P, Licandro AM, et al. Clusterlike
headache. A case of sphenoidal aspergilloma. Headache
1995; 35: 494–497.
67. Brook I, Overturf GD, Steinberg EA, et al. Acute sphe-
noid sinusitis presenting as aseptic meningitis: A pachy-
meningitis syndrome. Int J Pediatr Otorhinolaryngol
1982; 4: 77–81.
68. Urquhart AC, Fung G and McIntosh WA. Isolated sphe-
noiditis: A diagnostic problem. J Laryngol Otol 1989;
103: 526–527.
69. Dale BAB and MacKenzie IJ. The complications of sphe-
noid sinusitis. J Laryngol Otol 1983; 97: 661–670.
70. Sofferman RA. Cavernous sinus thrombophlebitis sec-
ondary to sphenoid sinusitis. Lancet Neurol 1983; 93:
797–800.
71. El Malik EFB, Manoranjan B, Ajani O, et al.
Hypophysitis due to paranasal sinusitis: Neurosurgical
perspective from developing world. World Neurosurg
2018; 115: 162–165.