Headache & Pain
Migraine: pathogenesis and pathophysiology
Aug. 24, 2024
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Toll Free (U.S. + Canada): 800-452-2400
US Number: +1-619-640-4660
Support: service@medlink.com
Editor: editor@medlink.com
ISSN: 2831-9125
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Rhinosinusitis-related headache is commonly diagnosed when patients have facial pain and pressure accompanying their headache. However, it is not as common as believed; the headache must accompany acute or chronic rhinosinusitis, a diagnosis that is based both on clinical and radiologic evidence. Many patients who are diagnosed with rhinosinusitis-related headache and treated with antibiotics may actually suffer from a primary headache, usually migraine. Differentiation between rhinosinusitis-related headache and migraine is of paramount significance. The author explains the key points and updates pertinent advances in differentiating between these two overlapped headache disorders.
• Many patients with a primary diagnosis of "sinus headache" have migraine or tension-type headache; the differential diagnosis depends on the patient's history. | |
• Uncomplicated sinusitis, other than sphenoid sinusitis, should be treated with a broad-spectrum oral antibiotic for 10 to14 days. | |
• Sphenoid sinusitis may be associated with major complications (bacterial meningitis, cavernous sinus thrombosis, etc.) and should be managed with high-dose intravenous antibiotics. | |
• Treatment failure and recurrent sinusitis are indications for neuroimaging and endoscopy to search for a source of obstruction in the sinus ostia and ostiomeatal complex. |
Sinusitis is defined as the inflammation of at least one of the paranasal sinuses, which are the air-filled cavities in the facial bones that are lined with pseudostratified ciliated columnar epithelium and mucous goblet cells (33).
Caldwell noted a functional relationship between the ostia of the sinuses and the development of sinusitis (15). Hajek and associates emphasized that ostial stenosis was responsible for sinusitis (36). Hilding and Messerklinger demonstrated that ethmoid sinusitis is frequently a cause of frontal and maxillary sinusitis (39; 56). Obstruction of the ostiomeatal complex, the common drainage pathway for the ethmoid, frontal, and maxillary sinuses, was later demonstrated to be involved in the development of sinus disease (55).
In 1997, the American Academy of Otolaryngology-Head and Neck Surgery proposed guidelines for management of paranasal infections, which were later updated in 2007 and 2015 (03; 64; 65). The term rhinosinusitis was felt to be more appropriate than sinusitis because rhinitis typically precedes sinusitis, purulent sinusitis without rhinitis is rare, the mucosa of the nose and sinuses are contiguous, and symptoms of nasal obstruction and discharge are prominent in sinusitis (71). The diagnosis of rhinosinusitis is usually based on symptoms indicating maxillary or frontal sinus involvement. This may occur secondary to, and is frequently a result of, ethmoid disease. Obstruction of the sinus ostia is the usual precursor of sinusitis (79; 78). Both the International Headache Society and the American Academy of Otolaryngology-Head and Neck Surgery have attempted to define conditions that lead to headaches of rhinogenic origin but have done so from different perspectives and in isolation of each other (13).
Rhinosinusitis is divided into four categories based on the temporal course and the signs and symptoms of the disease (48).
(1) Acute rhinosinusitis is sudden in onset and lasts from 1 day to 4 weeks; there is complete resolution of the symptoms. | |
(2) Subacute rhinosinusitis is continuous with acute rhinosinusitis and lasts from 4 to 12 weeks. | |
(3) Recurrent acute rhinosinusitis requires four or more episodes of acute rhinosinusitis that last at least 7 days each in any 1-year period. | |
(4) Chronic rhinosinusitis requires that signs or symptoms persist for 12 weeks or longer and may be punctuated by acute infectious episodes. |
Classification |
Duration |
Strong History |
Include in Differential |
Special Notes |
Acute |
Fewer than 4 weeks |
More than two major factors, one major factor and two minor factors, or nasal purulence on examination |
One major factor or more than two minor factors |
Fever or facial pain does not constitute a suggestive history in the absence of other nasal signs or symptoms; consider acute bacterial rhinosinusitis if symptoms worsen after 5 days, persist for more than 10 days, or are out of proportion to those typically associated with viral infection |
Subacute |
4 to 12 weeks |
Same as chronic |
Complete resolution after effective medical therapy | |
Recurrent acute |
More than four episodes per year, with each episode lasting more than 7 to 10 days and no intervening signs and symptoms of chronic rhinosinusitis |
Same as acute | ||
Chronic |
More than 12 weeks |
More than two major factors, one major factor and two minor factors, or nasal purulence on examination |
One major factor or more than two minor factors |
Facial pain does not constitute a suggestive history in the absence of other nasal signs or symptoms. |
Acute exacerbations of chronic rhinosinusitis |
Sudden worsening of chronic rhinosinusitis, with return to baseline after treatment |
Most cases of acute infectious rhinosinusitis of less than 7 days' duration are viral. Acute bacterial sinusitis in adults most often presents with 7 or more days of purulent anterior rhinorrhea, nasal congestion, postnasal drip, facial or dental pain or pressure, and cough, frequently with a nighttime component.
Nasal congestion, purulent nasal discharge, and facial tenderness and pain are common manifestations of acute sinus infection. Other "classic" signs and symptoms include anosmia, pain on mastication, and halitosis. An upper respiratory infection or a history of an upper respiratory infection is often present (72). Although fever is present in about 50% of adults and 60% of children and headache is common, the symptoms of headache, facial pain, and fever are often of minimal value in the diagnosis of sinusitis. Williams and associates looked at the sensitivity and specificity of individual symptoms in making the diagnosis of sinusitis (76). No single item was both sensitive and specific. Maxillary toothache was highly specific (93%), but only 11% of patients had this symptom. Logistic regression analysis showed five independent predictions of sinusitis: maxillary toothache (odds ratio 2.9), abnormal transillumination (odds ratio 2.7, sensitivity 73%, specificity 54%), poor response to decongestants (odds ratio 2.4), purulent discharge (odds ratio 2.9), and colored nasal discharge (odds ratio 2.2). "Headache" had an odds ratio of 1.0 with 68% sensitivity and 30% specificity. The low specificity is due to lack of descriptive features of the headache.
Children with acute and chronic sinusitis almost always present with purulent nasal discharge and cough, which are not characteristic in adults. Fever is infrequent even with acute sinusitis and is usually associated with complicated acute sinusitis (59).
The International Headache Society (IHS) established new criteria for rhinosinusitis-related headache in 2018 (05). To qualify as headache attributed to acute rhinosinusitis (code 11.5.1), there must be clinical, nasal endoscopic, and/or imaging evidence of acute rhinosinusitis and at least two of the following:
(1) Headache has developed in temporal relation to the onset of the rhinosinusitis | |
(2) Either or both of the following: (a) headache has significantly worsened in parallel with worsening of the rhinosinusitis; (b) headache has significantly improved or resolved in parallel with improvement in or resolution of the rhinosinusitis | |
(3) Headache is exacerbated by pressure applied over the paranasal sinuses | |
(4) In the case of unilateral rhinosinusitis, the headache is ipsilateral to the rhinosinusitis |
In addition to acute rhinosinusitis, the IHS also identified headache attributed to chronic or recurring rhinosinusitis (code 11.5.2).
Nevertheless, these criteria may not be valid for sphenoid sinusitis as purulent discharge is often lacking, and headache may precede sinus drainage. Once drainage begins, obstruction is relieved and the headache may begin to abate.
Maxillary sinusitis pain is most typically located in the cheek, the gums, and the teeth of the upper jaw. Ethmoid sinusitis pain is generally felt between the eyes. The eyeball may be tender, and pain may be aggravated by eye movement. Frontal sinusitis pain is felt mainly in the forehead. Ethmoid and maxillary sinusitis are usually associated with rhinitis and are often referred to as rhinosinusitis.
Sphenoid sinusitis is an uncommon infection that accounts for approximately 3% of all cases of acute sinusitis. It is usually accompanied by pansinusitis; it is less common for it to occur alone. In contrast to other paranasal sinus infections, sphenoid sinusitis is frequently misdiagnosed because the sphenoid sinus is not accessible to direct clinical examination, even with the flexible endoscope, and is not adequately visualized with routine sinus x-rays (32). Although sphenoid sinusitis is an uncommon cause of headache, it is potentially associated with significant morbidity and mortality and requires early identification and aggressive management (50; 46; 32). However, for those patients with sphenoid sinus disease manifesting with headache, endoscopic surgery is a safe and effective treatment for this disease and results in resolved headaches (17).
Headache is the most common symptom of acute sphenoid sinusitis; that is, headache is present in all patients who are able to complain about acute sphenoid sinusitis. It is aggravated by standing, walking, bending, or coughing; it often interferes with sleep and is poorly relieved by narcotics. Its location is variable: vertex headache is rare, whereas frontal, occipital, or temporal headache or a combination of these locations is most common. Periorbital pain is common. This is in contrast to the common teaching that retro-orbital or vertex headache is the most common presenting symptom of sphenoid sinusitis (50; 46; 20; 32).
Fever occurs in over one half of patients with acute sphenoid sinusitis. Isolated sphenoid sinusitis has been subclassified into four groups (inflammatory, neoplastic, fibro-osseous disorders, and miscellaneous) in a series of 132 cases (49). Headache, visual loss, and cranial nerve palsy prevalence was determined in each group. Headache occurred in 98% of the inflammatory lesions, 90% of the benign tumors, and 71% of the malignant tumors. Visual disturbances (blurred vision and loss of visual acuity) were found in 12% of inflammatory lesions, 60% of benign tumors, and 50% of malignant neoplasms. Sixth cranial nerve palsy occurred in 6% of the inflammatory and 50% of the neoplastic cases. Eyelid ptosis (due to third nerve involvement) occurred in 7.5% of the cases. Other symptoms included CSF leaks, epistaxis, meningitis, and proptosis.
The new IHS criteria also proposed appendix criteria for headache attributed to disorders of the nasal mucosa, turbinates, or septum. Examples are concha bullosa and nasal septal spur. However, current research is not sufficient to validate the presence or causal relationship of pertinent headaches.
Sinus infection can result in acute suppurative meningitis, subdural or epidural abscess, and brain abscess. In addition, osteomyelitis and subperiosteal abscess can occur. Infection of the ethmoid and, to a lesser extent, the sphenoid sinuses, is responsible for orbital complications, which include edema, orbital cellulitis, and subperiosteal and orbital abscess. Thus, sinusitis can be a life-threatening condition and can lead to intracranial complications if neglected or mismanaged (70). In a review of patients admitted to the University of Virginia Health Sciences Center with a diagnosis of intracranial suppuration between 1992 and 1997, 15 patients who had 22 suppurative intracranial complications of sinusitis were found. These included epidural abscess (23%), subdural empyema (18%), meningitis (18%), cerebral abscess (14%), superior sagittal sinus thrombosis (9%), cavernous sinus thrombosis (9%), and osteomyelitis (9%). The diagnosis of suppurative intracranial complications of sinusitis requires a high index of suspicion and confirmation by imaging. Patients often present while on a regimen of antibiotics, which may mask or abolish neurologic as well as other symptoms and signs (30).
A mucocele is a mucus-containing cyst located in the sinuses. These are most common (and benign) in the maxillary sinus (mucus retention cyst). Those located in the frontal, sphenoid, or ethmoid sinus can enlarge and erode into the surrounding structures. A pyocele is an infected mucocele (40).
Sphenoid sinusitis is associated with most major complications, which include bacterial meningitis, cavernous sinus thrombosis, subdural abscess, cortical vein thrombosis, ophthalmoplegia, and pituitary insufficiency (50; 46; 32). In addition, sphenoid sinusitis can present as an aseptic meningitis due to a parameningeal focus (12). Patients can present with complications of sphenoid sinusitis, including visual loss mimicking optic neuritis, multiple cranial nerve palsies, or papilledema. Sudden onset, as a result of cavernous sinus thrombosis, can mimic a subarachnoid hemorrhage (19).
A study in the Netherlands estimates the incidence of severe complications in acute rhinosinusitis as 1:12,000 in pediatric cases and 1:32,000 in adult cases. The study also suggests that antibiotics treatment for acute rhinosinusitis in general practice does not play a role in preventing these complications because severe complications did not seem to be more frequent in The Netherlands where antibiotic use is very low compared to countries with high antibiotic prescription rates (38).
A 36-year-old man was referred to a headache subspecialty clinic for disabling and recurrent sinus headaches that had been resistant to medical and surgical therapy. His headaches started in childhood and were episodic at first, but the attacks gradually became more frequent and severe. Their character remained relatively consistent. Diary records revealed that the attacks occurred four times per month and each lasted 3 or 4 days. The headaches were frontal and bilateral, but occasionally the attacks would alternate sides. The pain intensity was invariably severe, throbbing, and sometimes pressured. Nausea and nasal congestion ipsilateral to the headache pain would be present but not purulent discharge. Movement aggravated his headache and weather changes, allergies, alcohol, and strong perfumes would consistently trigger them.
He had been diagnosed with recurrent “sinus” headache two years before and underwent debridement of the left frontal and maxillary sinus. Unfortunately, this did not reduce the frequency or intensity of his headaches. He was given several rounds of antibiotics, nasal steroids, and decongestants. However, none of these helped.
He brought a recent imaging study with him to consultation. This revealed mild mucosal edema in the left frontal and maxillary sinus. Previous films prior to surgery showed some mild thickening.
He was diagnosed with migraine without aura and treated with triptans for acute symptomatic relief, and all accompanying symptoms of the headache pain—the nausea, the nasal congestion, and the pressured feeling—were relieved. He declined preventive treatment, as the headaches lasted only 30 minutes after treatment.
All sinuses normally contain anaerobic bacteria, and more than one third harbor both anaerobic and aerobic organisms. Ciliary dysfunction and retention of secretions, commonly a result of ostia obstruction, is necessary for bacterial proliferation and the development of sinus infection. Aerobes that present in both normal and disease states include the gram-positive streptococci and Staphylococcus aureus, as well as the gram-negative Moraxella catarrhalis, Haemophilus influenzae, and Escherichia coli. Anaerobic organisms include the gram-positive Peptococci and Propionibacterium species. The bacteroides and fusobacterium species also play a role in chronic sinusitis (44; 63). Most adult cases of acute maxillary sinusitis are caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis (73). Although Staphylococcus aureus is an infrequent cause of maxillary sinusitis, it is the major cause of acute sphenoid and frontal sinusitis. Sinusitis of dental origin is commonly due to mixed anaerobic infection with bacterioids and anaerobic streptococcus (21).
Systemic diseases that predispose to sinusitis include cystic fibrosis (with impaired mucus production), immune deficiency, bronchiectasis, and the immobile cilia syndrome (with impaired mucus transport). In one study, patients with recurrent sinusitis were unable to produce secretions with high concentrations of antimicrobial factors in response to cholinergic stimulation (42). The concentrations of IgA, IgG, and IgM are decreased in purulent secretions of patients with sinusitis (25). Local factors include upper respiratory infection (usually viral), allergic rhinitis, overuse of topical decongestants, hypertrophied adenoids, deviated nasal septum, nasal polyps, tumors, and cigarette smoke (63). The cause of nasal polyp formation is still unknown. Infectious agents (including viruses, bacteria, fungi) may be potential primary activation factors (61). The most common predisposing factor is mucosal inflammation from viral upper respiratory infection of allergic rhinitis (21). The sinuses are involved in nearly 90% of viral upper respiratory infections. Eighty-seven percent of patients with a common cold and no previous history of rhinosinusitis had maxillary sinus abnormalities, 65% had ethmoid sinus abnormalities, and 30% to 40% had frontal or sphenoid sinus abnormalities on CT. The abnormalities are most likely due to highly viscid secretions in the sinuses. The infundibulum was occluded in 77% of patients. Most patients experienced spontaneous resolution of these abnormalities, but some developed secondary bacterial infections (34). Foreign bodies are a common cause of obstruction in children, and 10% of sinus infections are of dental origin (21). In one study, authors found odontogenic cause in 30% of sinusitis patients (74). Loss of immunocompetence due to HIV infection, chemotherapy, posttransplant immunosuppression, insulin-dependent diabetes mellitus, and some connective tissue disorders predisposes patients to rhinosinusitis and increases the likelihood of its persistence. Rhinosinusitis is common in the intensive care unit because prolonged supine positioning compromises mucociliary clearance and adds to the problems created by mucosal drying from transnasal supplemental oxygenation and sinus ostial obstruction from nasotracheal or nasogastric tubes. Rhinosinusitis occurred in 95.5% of bedridden intensive care unit patients who had had a nasogastric or nasotracheal tube in place for at least a week (66).
Unobstructed flow through the sinus ostia and its narrow communicating passage within the ostiomeatal complex is integral to mucociliary clearance and ventilation. Persistent low-grade inflammation in the ethmoid sinus may cause few localizing symptoms but can predispose to recurrent maxillary and frontal sinus infections (63; 55).
The maxillary and ethmoid sinuses, both present at birth, are the most common sites of clinical infection in children. The sphenoid sinus develops after two years of age and starts to pneumatize at 8 years of age. The frontal sinuses develop from the anterior ethmoid sinus at about 6 years of age. The frontal and sphenoid sinuses become clinically important in the teens, and they frequently become infected in pansinusitis. Isolated sphenoid sinusitis is rare (45; 63).
HIV-positive patients who are deficient in both cell-mediated and humoral immunity are more susceptible to bacterial infection. Sinusitis occurs in 75% of those with AIDS and is often extensive and difficult to treat, especially if the CD4 count is less than 200/mm3. As in HIV-negative patients, the ethmoid and maxillary sinuses are predominantly involved (27).
The lateral nasal wall is composed of the ethmoid bone, a T-shaped structure that supports the bilateral ethmoid labyrinth. The horizontal limb of the T is formed by the cribriform plate, from which is suspended the ethmoid labyrinth, a complex structure with multiple bony septa and the medial projections of the superior and middle turbinates. Lateral to the uncinate process, a secondary projection of the ethmoid bone, is the infundibulum, a recess into which the maxillary sinus drains. The frontal sinus drains into the frontal recess, which may drain into the middle meatus or the ethmoidal infundibulum. This region is known as the ostiomeatal complex (maxillary sinus ostium, infundibulum, hiatus semilunaris, middle turbinate, ethmoidal bulla, and frontal ostium) (55). The sphenoidal sinus and posterior ethmoidal cells drain into the sphenoethmoidal recess.
The primary functions of the nasal passages are humidification, warming, and removal of particulate material from the inspired air. The paranasal sinuses are air-filled cavities that communicate with the nasal airway. They are lined with pseudostratified-ciliated epithelium, which is covered by a thin layer of mucus that receives the largest deposits of inhaled large particulate matter. The cilia and this mucous layer are in constant motion in a predetermined direction. Mucus and debris are transported toward the ostia by the beating of the cilia and are expelled into the nasal airway (63; 78; 55).
Bacterial contamination of the sinuses is effectively cleared by this mechanism. If the sinus ostia are obstructed, mucociliary flow is interrupted. Obstruction causes the oxygen tension within the sinus to decrease and the carbon dioxide tension to increase. This anaerobic, high-carbon-dioxide, stagnant environment can facilitate bacterial growth (55).
Wolff showed that the sinuses themselves are relatively insensitive to pain (77). McAuliffe and associates, using touch, pressure, and faradic stimulation, found that the nasal turbinates and sinus ostia were much more sensitive than the mucosal lining of the septum and the paranasal sinuses (54). Most of the pain elicited was referred pain. It was of increased intensity and longer duration and was referred to larger areas in subjects who had swelling and engorgement of the nasal turbinates and the sinus ostia. Thus, the pain associated with sinusitis comes from engorged and inflamed nasal structures: nasofrontal ducts, turbinates, ostia, and superior nasal spaces.
In 1994, the National Health Interview Survey report on chronic sinusitis estimated that 35 million people were affected (02). A national health interview survey conducted in the United Sates between 1990 and 1992 found that chronic sinusitis was the second most frequent disease after orthopedic deformities, with an annual average of 33.1 million cases (18). The prevalence of acute sinusitis appears to be increasing, according to data from the National Ambulatory Medical Care Survey, from 0.2% of diagnoses at office visits in 1990 to 0.4% of diagnoses at office visits in 1995 (02). About 0.5% of upper respiratory infections in adults are complicated by sinusitis (21). Up to 38% of patients seen in adult general medicine clinics with symptoms of sinusitis may have acute bacterial rhinosinusitis. In otolaryngology practices, the prevalence was higher (50% to 80%). Although sinusitis is generally more common in children than adults, frontal and sphenoid sinusitis are rare in children. Between 6% and 18% of children in the primary care setting presenting with upper respiratory infections may have acute bacterial sinusitis (02). In the preantibiotic era the sphenoid sinus was involved in as many as 33% of cases of sinusitis. Today its incidence is about 3% (50). The global prevalence of chronic rhinosinusitis is less than 5% (69).
Methods of prevention include using a humidifier and treating the underlying causes of sinus obstruction (polyps, adenoid hypertrophy, tumors of the nasopharynx, and nasal obstruction from allergic rhinitis) (40). Decreased environmental exposure to mold, dust mites, and smoking may play a role in long-term improvement (60).
Migraine and tension-type headaches are often confused with true sinus headaches because of their similar locations. Some patients, in addition to all the features of migraine without aura, have head pain in the facial areas, associated congestion of the nose, and headache triggered by weather changes. None of these patients have the purulent nasal discharge or other abnormalities as seen in acute rhinosinusitis. Therefore, it is necessary to differentiate rhinosinusitis-related headaches from so-called “sinus headaches,” which are headache attacks that fulfill the criteria of migraine without aura with prominent autonomic symptoms in the nose or of migraine without aura triggered by nasal changes.
In a population-based study with 23,564 respondents, 4967 individuals called their headache “migraine,” and 3074 individuals had headache that met the IHS criteria for migraine (51). Among those with IHS migraine, only 53.4% recognized their headaches as migraine (sensitivity 54%; specificity 83.8%). Among migraineurs, stress headaches (n = 345) and sinus headaches (n = 365) were the most common erroneous labels.
A prospective, cross-sectional study conducted at two tertiary referral centers also revealed that the patients referred here under the diagnosis of "sinus headache" by primary care physicians had migraine in 68%, tension-type headache in 27%, and chronic sinusitis in 5% (29). Another multicenter research study followed patients admitted to otorhinolaryngology outpatient or emergency units due to sinus headache (n=98) (43). The endoscopic and CT findings in these patients were negative. At the end of 3-month follow-up, the diagnosis turned out to be migraine in 61 (62%), tension-type headache in 26 (27%), and cluster headache in 11 (11%).
Why did nearly half the people with migraine use a term other than migraine to characterize their headaches? People may be confused by their headache location. Because the sinuses are close to the eyes, individuals may attribute headaches located in the frontal, supraorbital, or infraorbital region to the sinuses.
Intriguingly, there has been a population study investigating the association between headache and opacification of the paranasal sinuses on MRI (37). Of the 844 participants, 302 (36%) reported having had headaches during the past 12 months. There was no significant difference in the proportion of participants with and without headache with paranasal sinus opacification above the cutoff values (sum thickness of fluid, mucosal thickening, or total opacification sum). This study implied that headache sufferers in the general population are not more likely to have paranasal sinus opacifications than those without headache.
Taken together, patients who believe they have sinus headache, with no signs or symptoms of rhinosinusitis and at least one symptom of migraine, may actually have migraine (14).
Some features useful in distinguishing between sinus headache and migraine are listed in Table 2 (16).
Features | Sinus headache | Migraine |
Severity of pain | Mild/moderate | Moderate/severe |
Quality of pain | Pressure/congestion | Pulsatile |
Triggers | Pressure changes, eg, flying, skiing | Exercise, menstrual cycle, certain foods |
Associated features | Rhinological; nasal congestion, hyposmia/anosmia, rhinorrhea | Nausea, vomiting, photo/phonophobia, aura |
ENT examination | Abnormal; nasal mucosal congestion, purulence | Normal +/- nasal mucosal congestion on anterior rhinoscopy |
Sphenoid sinusitis should be included in the differential diagnosis of any new-onset headache, especially those with severe, intractable pain that interferes with sleep. It can mimic trigeminal neuralgia, migraine, carotid artery aneurysm, brain tumor, aseptic meningitis, brain abscess, or frontal or ethmoid sinusitis (50; 46; 32; 52; 67). Other causes of sphenoid sinus disease include mucoceles and benign and malignant tumors (49; 47).
Pain or paresthesias in the facial distribution of the 5th nerve and photophobia or eye tearing are suggestive of sphenoid sinusitis (50; 32).
Hypertrophic turbinates, atrophic sinus membranes, and nasal passage abnormalities caused by septal deflection may cause headache, but these causes have not been validated by the IHS. Whether nasal obstruction can lead to chronic headache is controversial (68). Although the IHS does not consider nasal anatomical abnormality to be a validated cause of headache, clinical otolaryngology experience indicates that septal deviation or concha bullosa can cause rhinogenic headache de novo, and treatment with endoscopic sinus surgery or septoplasty or both did significantly improve the headache (13; 41).
The physical examination may not be helpful, particularly in sphenoid sinusitis. Not all patients are febrile, and sinus tenderness is not always present. Pus is not always seen in sphenoid sinusitis. Kibblewhite and associates found purulent exudate in only 3 of 14 patients (46). CTs of patients who have a common cold show the prevalence of reversible sinus abnormalities to be high (34). This suggests that CT may not be specific for bacterial infections (21).
Standard radiography is inadequate for evaluating sinusitis, as it does not evaluate the anterior ethmoid air cells, the upper two thirds of the nasal cavity, or the infundibular, middle meatus, and frontal recess air passages (78). However, 68% of a high-risk group of 300 patients with a clinical diagnosis of sinusitis had abnormal plain radiographs. None, however, had sphenoid sinus abnormalities (08).
Neuroimaging is necessary to definitively diagnose sphenoid sinusitis because plain x-rays are nondiagnostic in about 26% of cases (32). CT scanning is the gold standard for diagnosing sphenoid sinus disease, which may demonstrate mucosal thickening, sclerosis, clouding, or air-fluid levels (53). The test-retest reliability of CT in the assessment of chronic rhinosinusitis was high and stable in a prospective series of patients who were scheduled for endoscopic sinus surgery (09). Despite being an adjunct for sphenoid sinus disease, MRI is more sensitive than CT in detecting fungal infection or bone erosion due to neoplasm (53).
Incidental anatomical abnormalities within the paranasal sinuses are common. Twenty-seven percent to 45% of asymptomatic individuals have incidental anatomical abnormalities on CT scan. Bhattacharyya and Fried conducted a study to determine the sensitivity, specificity, and diagnostic accuracy of paranasal sinus CT in the diagnosis of chronic rhinosinusitis (11). Patients undergoing endoscopic sinus surgery for chronic rhinosinusitis were evaluated with CT and staged according to the Lund system. The Lund-Mackay system assigns for each paranasal sinus side (anterior ethmoid, posterior ethmoid, maxillary, frontal, and sphenoid sinus) a score of 0 for no opacification, 1 for partial opacification, or 2 for total opacification. The ostiomeatal complex is assigned a score of 0 for patent or 2 for obstructed. The Lund score ranges from 0 to 24.
According to the study results, Lund scores of 0 or 1 are unlikely to represent true chronic rhinosinusitis, whereas Lund scores of 4 or greater are likely to represent true chronic rhinosinusitis. Lund scores of 2 to 3 are ambiguous, and further clinical evaluation or follow-up is warranted.
Transillumination of the sinuses has low sensitivity and specificity (72). Ultrasonography has lower sensitivity and specificity than sinus x-rays (72), and routine anterior rhinoscopy performed with a headlight and nasal speculum allows only limited inspection of the anterior nasal cavity.
Ultrasound scans, similar to transillumination, are usually limited to frontal and antral disease and are most commonly used to follow the response to pharmacotherapy of a rhinosinusitis that has been documented by nasal endoscopy or CT (76; 26; 75; 28). Studies comparing sinus ultrasonography with puncture or sinus radiography were inconclusive in determining how well ultrasonography identifies patients with acute bacterial rhinosinusitis.
Diagnostic endoscopy with the flexible fiberoptic rhinoscope allows direct visualization of the nasal passages and sinus drainage areas (ostiomeatal complex) and is complementary to CT or MRI. However, the natural ostium of the maxillary sinus is hidden in the ethmoid infundibular behind the uncinate process, making it difficult to visualize and impossible to enter, even with angled scopes (35). Infection is easily diagnosed if purulent material is seen emanating from the sinus drainage region. Mucosal sinus thickening is frequently present in normal, nonsymptomatic patients. In these cases, endoscopy should be positive before a diagnosis of sinusitis can be made (45; 55). Sphenoid sinusitis is an exception to this generalization.
Endoscopy should be considered when a sinus-related problem is suspected and the patient fails to respond to conservative medical treatment and CT or MRI is inconclusive. Some use endoscopy prior to neuroimaging. The combination of negative neuroimaging and endoscopy usually, but not always, rules out sinus disease (78). Sinus aspirate culture remains the gold standard (35).
Management goals for the treatment of sinusitis include: (1) treatment of bacterial infection, (2) reduction of ostial swelling, (3) sinus drainage, and (4) maintenance of sinus ostia patency.
Most acute upper respiratory infections are viral and do not require antibiotic treatment. Symptoms that persist for 7 or more days makes acute bacterial sinusitis more likely and the use of antibiotics appropriate. Chronic sinusitis can have an infectious or noninfectious basis. Underlying disorders that predispose to chronic sinusitis should be identified and treated as part of the treatment of chronic sinusitis (24).
Uncomplicated sinusitis, other than sphenoid sinusitis, should be treated with a broad-spectrum oral antibiotic for 10 to 14 days. Nasal culture does not necessarily correlate with sinus pathogens and thus initial treatment is empiric (72). Treatment with any antibiotic reduces the rate of clinical failure by one half. For a large number of patients with uncomplicated acute bacterial rhinosinusitis, a course of inexpensive antibiotic is probably adequate first-line treatment (62). Amoxicillin-clavulanate is considered first-line treatment for mild to moderate acute bacterial rhinosinusitis in patients who have or have not received antimicrobials in the previous 6 weeks. If the patient has mild symptoms that last longer than 10 days and has not used an antibiotic, then a low dose of amoxicillin-clavulanate can be used. Patients who have used an antibiotic to treat the infection within the last 6 weeks or those who live in areas of high prevalence of penicillin-resistant S pneumoniae should be given a higher dose of amoxicillin-clavulanate. The quinolones should be reserved for those patients with moderately severe symptoms or for those who have taken an antibiotic in the last 6 weeks (04). Other antibiotics used are doxycycline, erythromycin-sulfisoxazole, azithromycin, clarithromycin, telithromycin, and trimethoprim-sulfamethoxazole. More research is needed to understand how the increasing rates of bacterial resistance may affect the choice of antibiotics (62).
Antimicrobial agent |
Adult dose |
Duration (days) |
Contraindications |
Penicillin | |||
Amoxicillin |
500 mg/875 mg every 8 hours |
7 | |
Amoxicillin-clavulanic acid (Augmentin) |
500 mg/125 mg every 8 hours |
7 |
Previous history of cholestatic jaundice or hepatic dysfunction associated with treatment with amoxicillin-clavulanic acid |
Amoxicillin-clavulanic acid (Augmentin XR) |
200 mg/125 mg every 12 hours |
10 |
Gastrointestinal upset |
Tetracycline | |||
Doxycycline |
100 mg every 12 hours on day 1, then 50 mg every 12 hours thereafter |
10 |
Photosensitivity neutropenia |
Macrolides | |||
Erythromycin-sulfisoxazole |
200 mg erythromycin ethyl-succinate and 600 mg sulfasoxazole fixed dose based on weight, for times per day |
10 |
Gastrointestinal distress; prescribe with caution in patients with arrhythmias, medications metabolized by P450 enzymes, or with liver disease. |
Azithromycin (Zithromax) |
500 mg every 12 hr |
3 | |
Clarithromycin (Biaxin) |
500 mg every 12 hr |
14 | |
Ketolides | |||
Telithromycin (Ketek) |
Everyday |
5 | |
Folate inhibitors | |||
Trimethoprim (160 mg)—sulfamethoxazole (800 mg) |
One tablet every 12 hours |
10 |
Hypersensitivity to sulfonamides; megaloblastic anemia due to folate deficiency; pregnancy |
Steam and saline prevent crusting of secretions in the nasal cavity and facilitate mucociliary clearance. Locally active vasoconstrictor agents provide symptomatic relief by shrinking inflamed and swollen nasal mucosa. Their use should be limited to 3 to 4 days to prevent rebound vasodilation. Oral decongestants should be used if prolonged treatment (longer than 3 days) is necessary. These agents are alpha-adrenergic agonists that reduce nasal blood flow without the risk of rebound vasodilation (72). Although phenylpropanolamine increased the nasal patency in controls, it was not more effective than placebo in patients with acute sinusitis (07). Nasal saline irrigation, anticholinergics, antihistamines, expectorants, and mucolytics have not been prospectively studied, but it is commonly believed that antihistamines are effective in the management of acute sinusitis in patients with an underlying allergy (21; 06). Anti-inflammatory topical corticosteroids may help maintain ostial patency. Intranasal flunisolide spray was shown to improve the symptoms of nasal obstruction in one controlled study (57). Topical antibiotics are also used, the best being the concentration-dependent antibiotics. These include the aminoglycosides and quinolones. They work better than the time-dependent topical antibiotics (penicillin, cephalosporins, macrolides, tetracyclines, sulfa, vancomycin) because they have a sufficient chance to kill bacteria before the cilia dilute and flush them out. Time-dependent antibiotics need a specific time period to sufficiently kill bacteria and usually are not able to accomplish this before they get flushed out (60).
Dolor and colleagues conducted a double-blind, randomized, placebo-controlled multicenter trial of 95 patients with a history of recurrent sinusitis or chronic rhinitis and evidence of acute infection by sinus radiograph or nasal endoscopy (22). Participants received two puffs of fluticasone (n = 47) or placebo (n = 48) nasal spray in each nostril once daily for 21 days; all received two puffs of xylometazoline hydrochloride in each nostril twice daily for three days and 250 mg of cefuroxime axetil twice daily for 10 days. Patients treated with fluticasone improved significantly more rapidly (median of 6.0 days to clinical success) versus patients in the placebo group (median of 9.5 days). The addition of fluticasone to xylometazoline and antimicrobial therapy with cefuroxime improves clinical success rates and accelerates the recovery of patients with a history of chronic rhinitis or recurrent sinusitis who present for treatment of acute rhinosinusitis. The symptomatic relief that revision endoscopic surgery can provide for patients with refractory chronic rhinosinusitis is similar to the results following the primary endoscopic sinus surgery and can result in significant improvement. However, many patients continue to require intensive medical management (10).
Treatment failure and recurrent infections are indications for neuroimaging and endoscopy to search for a source of obstruction. Sinus sampling for culture should be considered. Endoscopic nasal surgery may be necessary to reopen and maintain the patency of the sinus ostia and ostiomeatal complex (72).
Treatment of complications consists of high doses of intravenous antibiotics and surgical drainage, if appropriate, of any enclosed space.
Sphenoid sinusitis without complications may be managed with high-dose intravenous antibiotics and topical and systemic decongestants for 24 hours (46; 32). If the fever (if present) and the headache do not start to improve or if any complications are present or develop, sphenoid sinus drainage is indicated (23). Gilain and colleagues reviewed 12 cases of isolated sphenoid sinus disease secondary to: chronic inflammatory sinusitis in seven, mucoceles in two, aspergillus lesions in two, and an isolated polyp in one. All patients in this series were treated with functional endoscopic sphenoidotomy and improved. All were treated with appropriate postoperative antibiotics, nasal irrigation, oral corticosteroids, and washing and cleaning of the nasal cavity weekly for four weeks (31).
The effectiveness of photobiomodulation has been demonstrated in treating headaches associated with chronic rhinosinusitis. In a study with 31 patients, the treatment group received photobiomodulation therapy, whereas the control group received a sham laser (01). The treatment group showed significant improvements in headache, fatigue, and sinus opacification compared to the control group (p < 0.05).
Not all patients with headache improve. One patient treated by Gilain and colleagues with functional endoscopic surgery for chronic sphenoidal sinusitis continued to have headaches postoperatively despite CT-documented absence of sinus disease (31). This suggests that the headache and sinusitis were coincident unrelated conditions. A study showing the effect of endoscopic sinus surgery on the subjective headache scores of patients with chronic rhinosinusitis with or without nasal polyps showed an overall decrease in scores at 2-year follow-up (58).
All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.
Ravi Uniyal MD DM
Dr. Uniyal of King George's Medical University has no relevant financial relationship to disclose.
See ProfileShuu-Jiun Wang MD
Dr. Wang of the Brain Research Center, National Yang-Ming University, and the Neurological Institute, Taipei Veterans General Hospital, has no relevant financial relationships to disclose.
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