Rhinosinusitis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Rhinosinusitis is the inflammation of the nasal mucosa and paranasal sinuses. The terms sinusitis and rhinosinusitis are used interchangeably, although rhinosinusitis is preferred because inflammation of the paranasal sinuses rarely ever occurs without concurrent inflammation of the nasal mucosa. There are 4 pairs of sinus cavities, named for the skull bones they are located in: maxillary, ethmoid, frontal and sphenoidal. The cause of rhinosinusitis is mostly infectious, although it can be associated with other medical conditions such as allergies. The diagnosis is primarily clinical and imaging and other diagnostic studies are not necessary for diagnosis. A CT or MRI is indicated when rhinosinusitis is complicated by extension of the infection to surrounding structures, such as the orbit and brain. Rhinosinusitis is a self-limiting disease and treatment is supportive, in order to alleviate the respiratory symptoms and pain. Antibiotics may be indicated in select cases of acute bacterial and chronic rhinosinusitis.

• Between 3700 and 1500 BC, the paranasal sinuses were first identified by the ancient Egyptians. The ancient Egyptians are considered to have been the first in discovering sinus surgery; when mummifying a human body, they would remove the brain through the nasal cavity.^[1]
• Hippocrates later described the process of producing voice as “air passing through empty cavities,” which referred to the paranasal sinuses. He also documented in his writings about nasal polyps and how to remove them.^[1]
• In 1489, Leonardo Da Vinci was the first to illustrate the maxillary sinuses and their relationship with the teeth of the upper jaw. ^[2]
• In 1905, the first paper in literature was found on suppurative frontal sinusitis.^[3]

Rhinosinusitis can be classified based on the location of sinus involved into maxillary, frontal, ethmoidal, sphenoidal or pansinusitis.^[4][5][6]. It can also be classified according to the duration of the disease or etiology.^[7][8]

The pathophysiology for both acute and chronic rhinosinusitis involves blockage of the nasal sinuses and inflammation of the nasal sinuses. However, biofilms play a role in the pathogenesis of chronic rhinosinusitis. There are many associated conditions with rhinosinusitis, but most notably are those related to allergy and immunodeficiency.

The causes of rhinosinusitis can be divided according to the infectious group that causes it into: bacterial, viral and fungal.

Rhinosinusitis must be differentiated from other diseases that may present with a headache and/or respiratory symptoms.

The incidence of acute rhinosinusitis and prevalence of chronic rhinosinusitis have a wide range, depending on the setting.

Anatomical abnormalities of the nasal cavity, immunodeficiency and other diseases are all risk factors for the development of rhinosinusitis.

There are no recommendations for screening for rhinosinusitis.^[9]

Acute rhinosinusitis is a self-limiting disease. However, rarely acute and chronic rhinosinusitis can be complicated by extension of the infection to the surrounding structures, such as the eyes and brain.

Rhinosinusitis can present with a wide range of constitutional and respiratory symptoms.

Examination of the nose with a speculum or otoscope may reveal mucosal edema, narrowing of the middle meatus, purulent rhinorrhea and other findings.

There are several lab findings that can be done when suspecting rhinosinusitis, but these findings are nonspecific.

A plain x-ray of the sinuses has no role in the workup of rhinosinusitis. It may show a fluid level in the sinuses, but a plain x-ray is associated with a high negative and high positive rate for rhinosinusitis.^[10][11]

Although not routinely indicated for suspected cases of rhinosinusitis and findings are highly nonspecific, CT scan is the imaging modality of choice in cases of chronic or complicated rhinosinusitis. Positive CT scan findings are not essential for diagnosis, but negative CT scan findings rules out rhinosinusitis. Findings include mucosal thickening and narrowing of the osteomeatal sinuses.^{[11][12][13][7]}

MRI is an excellent alternative to CT scan in detecting orbital and intracranial complications of rhinosinusitis.^[14][15]

Nasal endoscopy and anterior rhinoscopy can be done in the case of rhinosinusitis to evaluate for nasal anatomy, nasal polyps and the paranasal sinuses. Endoscopy can be done as part of the functional endoscopic sinus surgery (FESS), which is used as a treatment in the case of chronic rhinosinusitis and nasal polyps.^[16][17]

Supportive therapy is the mainstay of treatment for both cases of acute and chronic rhinosinusitis. Antibiotics can be added in select cases of acute, as well as chronic rhinosinusitis.

Functional endoscopic sinus surgery (FESS) is reserved for cases of chronic rhinosinusitis not responding to medical therapy.

There are no clear guidelines on how to prevent the occurrence of rhinosinusitis.^[18]

Secondary prevention is mostly aimed at preventing the exacerbation of chronic rhinosinusitis or another episode of acute recurrent sinusitis. Methods such as abstinence from smoking, using saline nasal irrigation, and treatment of the underlying cause can be used to promote healthy sinuses. ^[19]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Rhinosinusitis can be classified based on the location of sinus involved, the duration of the disease, or its etiology.

There are several paired paranasal sinuses, including the frontal, ethmoid, maxillary and sphenoid sinuses. Rhinosinusitis can be classified by the sinus cavity that is affected:^[1][2][3]

• Maxillary sinusitis
• Frontal sinusitis
• Ethmoid sinusitis
• Sphenoid sinusitis
• Pansinusitis

Based on the duration and etiology of symptoms, rhinosinusitis may be classified into:^[4][5][6]

• Acute (symptoms lasting less than four weeks)
  • Acute Viral Rhinosinusitis
  • Acute Bacterial Rhinosinusitis
  • Recurrent Acute Rhinosinusitis (more than 3 episodes of acute rhinosinusitis in a year for at least 7-10 days without persistent symptoms in between the episodes)
• Subacute (symptoms lasting 4-12 weeks) or
• Chronic (symptoms lasting 12 or more weeks)
  • Chronic Sinusitis with Nasal Polyposis
  • Chronic Sinusitis without Nasal Polyposis
  • Allergic Fungal Sinusitis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

• Between 3700 and 1500 BC, the paranasal sinuses were first identified by the ancient Egyptians. The Egyptians are considered to be the first in discovering sinus surgery because when mummifying a human body, they would remove the brain through the nasal cavity.
• Hippocrates later described the process of producing voice as “air passing through empty cavities”, which referred to the paranasal sinuses. He also documented in his writings about nasal polyps and how to remove them.
• In 1489, Leonardo Da Vinci was the first to illustrate the maxillary sinuses and their relationship with the teeth of the upper jaw.
• In 1905, the first paper in literature was found on suppurative frontal sinusitis.

• Between 3700 and 1500 BC, the paranasal sinuses were first identified by the ancient Egyptians. The Egyptians are considered to be the first in discovering sinus surgery because when mummifying a human body, they would remove the brain through the nasal cavity.^[1]
• Hippocrates later described the process of producing voice as “air passing through empty cavities”, which referred to the paranasal sinuses. He also documented in his writings about nasal polyps and how to remove them.^[1]
• In 1489, Leonardo Da Vinci was the first to illustrate the maxillary sinuses and their relationship with the teeth of the upper jaw. ^[2]
• In 1905, the first paper in literature was found on suppurative frontal sinusitis.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

The pathophysiology for both acute and chronic rhinosinusitis involves blockage of the nasal sinuses and inflammation of the nasal sinuses. However, biofilms play a role in the pathogenesis of chronic rhinosinusitis. There are many associated conditions with rhinosinusitis, but most notably are those related to allergy and immunodeficiency.

Sinuses are made up of frontal, maxillary and anterior ethmoid bones of the face. They are lined with ciliated pseudostratified columnar epithelium with a protective layer of mucosa. The cilia by propelling the inhaled particles into the nose for disposal and the mucosa by trapping the particles, together protect the sinuses from irritants and potential immune reactions.^[1]

Pathophysiology of acute rhinosinusitis could be explained by several mechanisms ^[1]:

• Anatomic variants: Since imaging modalities are not necessary for uncomplicated ARS, there aren’t enough evident regarding the contribution of anatomy to the pathogenesis of ARS. However, several contributing factors have been proposed:
  • Anomalies of the unicate and middle turbinate
  • Stenosis of the infundibulum
  • Recirculation phenomenon
  • Infraorbital ethmoid cells
  • Nasoseptal deviation
• Allergy: Allergens trigger the recruitment of eosinophils into the maxillary sinus causing inflammation.
• Viruses: Viruses (e.g. Rhinovirus, H1N1), inhibit the mucociliary clearance and local swelling which in turn leads to the blockade of the sinus ostea and subsequent bacterial infection.
• Odontogenic infection: The proximity of maxillary sinus to the teeth roots causes rhinosinusitis in patients with dental maxillary pathology.

There are several proposed mechanisms for the pathophysiology of chronic rhinosinusitis ^[1][2]:

• Fungus: Proteins of the fungus trigger T cell response, causing cytokine storm which in turn leads to recruitment of the eosinophils to mucus. Degranulated eosinophils target the fungi causing collateral tissue damage.
• Bacteria, mostly contribute to the pathogenesis of chronic rhinosinusitis without nasal polyps and are composed of three hypotheses:
  • Super antigen: Staphylococcus aureus superantigenic exotoxins bind T cells outside their antigen binding site, bypassing the antigen recognition pathway, thus provoking polyclonal T cell response which in turn leads to cytokine storm.
  • Biofilm: Biofilms are composed of bacteria embedded in an extracellular matrix, protecting them from antibiotics.
  • Microbiome: It is suggested that external factors could change the normal microbiome of the nasal and sinus mucosa facilitating the growth of pathogens that were normally suppressed by the commensals.
• Host related factors:
  • Immune barrier:
    • Mechanical barrier: Defect in mucociliary clearance, increased susceptibility to exogenous protease and decreased tight junction proteins of the epithelium causing the formation of a porous barrier contribute to the increased access and transmit time of the foreign materials.
    • Innate immune response: Abnormal secretion of the antimicrobials of the mucosa (i.e. defensins, lysozyme, cathelicidins, collectins, lactoferrin, S100s and PLUNC) in response to pathogen recognition receptors (PRR), results in abnormal microbiome, increased exposure to foreign materials and increased compensatory response of the innate and adaptive immune system.
  • Anatomic variations: Variations that affect the ostio-meatal complex (i.e. anomalies in the middle turbinate, concha, cells of the infraorbital ethmoid and nasoseptal deviation) or the drainage of the frontal sinus contribute to chronic rhinosinusitis with polyps.

There are limited evidence proposing some other mechanisms involved in the pathogenesis of chronic rhinosinusitis:

• • Eicosanoids: Eicosanoids are the product of Arachidonic acid metabolism which function as signaling molecules. Defects in the Eicosanoid pathway causes an increased pro-inflammatory leukotriene and decreased anti-inflammatory prostaglandin resulting in the mucosal inflammation.
  • Vitamin D deficiency: Vitamin D has anti-microbial and anti-inflammatory effects. Thus, its deficiency results in increased Th2 and eosinophilic response resulting mostly in chronic rhinosinusitis without polyps.
  • Osteitis and neo-osteogenesis: Histopathological changes of the bone including inflammation, fibrosis and new bone formation were observed in harvested ethmoid bones of patients with chronic rhinosinusitis.
  • Reflux: Laryngopharyngeal reflux exposes the nasal cavity and sinuses to gastric acid and possible H. Pylori infection causing inflammatory response and defective mucociliary clearance. Also, the reflux triggers the esophagus resulting in stimulation of vagus nerve.

Chronic rhinosinusitis is believed to be the result of environmental and genetic factors combined. The role of genetic factors in chronic rhinosinusitis is not yet fully understood.^[3] However, in chronic rhinosinusitis with and without nasal polyposis, first and second degree relatives conferred an increased risk to receiving the same diagnosis.^[4]

• Allergies, such as hay fever^[5]
• Asthma^[6]
• Nasal Polyposis^[7]
• Cilia disorders, such as cystic fibrosis and Kartagener Syndrome^[8]
• Wegener’s Granulomatosis^[9]
• Humoral immunodefiency, such as IgA deficiency and X-linked agammaglobulinemia^[9]

On gross examination of the sinuses, polyps may appear as transparent and pedunculated masses. In sinusitis, changes include minimal edema and thickening of the mucosa.^[10]

Rhinosinusitis can present with the following microscopic findings;^[10]

• Acute Bacterial Sinusitis: Inflammatory infiltrate is dominated by neutrophils.
• Allergic Rhinosinusitis: Inflammatory infiltrate is dominated by eosinophils.
• Chronic Rhinosinusitis: Mixed inflammatory infiltrate of lymphocytes, plasma cells, eosinophils, neutrophils, and macrophages.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

The causes of rhinosinusitis can be divided according to the infectious group that causes it: bacterial, viral, and fungal.

Infectious causes of rhinosinusitis include viruses, bacteria, and fungi:^[1][2]

• Viruses
  • Rhinovirus
  • Influenza virus
  • Parainfluenza virus

• Bacteria
  • Streptococcus pneumoniae
  • Haemophilus influenzae
  • Moraxella catarrhalis
  • Streptococcus pyogenes
  • Staphylococcus aureus: common in chronic sinusitis
  • Pseudomonas aeruginosa: common in nosocomial sinusitis, cystic fibrosis patients and the immunocompromised
  • Anaerobes: Prevotella, Fusobacterium and Peptostreptococcus: common in chronic sinusitis
• Fungi
  • Aspergillus species
  • Fusarium species
  • The Mucorales

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Rhinosinusitis must be differentiated from other diseases that may present with a headache and/or respiratory symptoms.

Acute rhinosinusitis must be differentiated from ^[1][2]:

• Allergic rhinitis
• Headaches and midfacial pain syndromes: migraine, tension-type headache, cluster headache, paroxysmal hemicrania, atypical facial pain and midfacial segment pain ^[3][4][5]
• Orofacial pain syndromes (e.g. temporomandibular disorders)^[6]
• Ocular pain syndromes: glaucoma ^[7][8]
• Dental disease
• Chronic fatigue syndrome

Chronic rhinosinusitis must be differentiated from:^{[1][9][10][11]}

• Allergic rhinitis
• Eosinophilic nonallergic rhinitis
• Vasomotor rhinitis
• Migraine
• Tension headache
• Vascular headaches
• Temporal arteritis
• Nasal foreign body
• Gastroesophageal reflux
• Asthma
• Cerebrospinal fluid rhinorrhea
• Benign and malignant sinonasal neoplasia

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

The incidence of acute rhinosinusitis and prevalence of chronic rhinosinusitis have a wide range, depending on the setting.

Rhinosinusitis is a condition that is more common in adults (age 18-64) than children, mostly because of more developed sinus cavities. The incidence of acute sinusitis ranges between 1,500 to 4,000 per 100,000 cases per year, depending on the setting.^[1] Chronic sinusitis, on the other hand, is described in terms of prevalence. It is estimated that the prevalence of chronic sinusitis is 12,300 per 100,000 cases per year. ^[2] Conditions such as asthma, hay fever, and rhinosinusitis seem to be more prevalent in women than men.^[3]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Anatomical abnormalities of the nasal cavity, immunodeficiency, and other diseases are all risk factors for the development of rhinosinusitis.

Common risk factors to the development of rhinosinusitis include:^[1][2]

• Allergies
• Anatomical abnormalities:
  • Adenoid hypertrophy
  • Deviated nasal septum
  • Nasal polyps
• Asthma
• Foreign body
• Gastroesophageal reflux
• Primary and acquired immunodeficiency
• Primary and secondary ciliary dyskinesia
• Smoking
• Upper respiratory tract infection

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2]

Acute rhinosinusitis is a self-limiting disease. However, rarely acute and chronic rhinosinusitis can be complicated by extension of the infection to the surrounding structures, such as the eyes and brain.

Acute viral and bacterial rhinosinusitis are mostly self-limiting diseases, which resolve within 4 weeks. Rarely, acute bacterial sinusitis may be complicated by extension of the infection to the surrounding organs like theeye and the brain.^[1] If left untreated, chronic rhinosinusitis may be complicated by periorbital cellulitis, brain abscess and epidural abscess.^[2]

• Acute viral rhinosinusitis: may be complicated by a secondary bacterial infection.^[3]
• Acute bacterial rhinosinusitis: rare complications include periorbital and orbital cellulitis, meningitis, orbital subperiosteal and intracranial abscesses and septic cavernous sinus thrombosis.^[4][5][6]
• Chronic rhinosinusitis: complications include periorbital cellulitis, epidural abscess, subdural empyema and brain abscess.^[2]

The prognosis for acute viral and uncomplicated bacterial rhinosinusitis is excellent. The majority of morbidity and mortality seen in cases of rhinosinusitis result from its complications.^[7]

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