Author: Dr Andrew H. Murr University of California San Francisco 2008-07-28
INTRODUCTION
Inflammation of the sinuses (sinusitis) is the
most common chronic condition for which a patient seeks the advice of a
physician in the United States. There are about 30 million patient
visits per year pertaining to sinusitis, but the cause of the condition
remains unclear. Nasal polyps – known as chronic rhinosinusitis with
nasal polyposis – are a sub-category of sinusitis that represents
roughly two to five percent of patients with sinusitis.
Nasal polyps –
polyps are abnormal growths – are an inflammatory condition of the nasal
lining that produces diffuse swelling inside the nose. Eventually, the
polyps can become so extensive that they block the nose completely. It
is relatively rare that we can discern the exact cause of why a patient
has developed nasal polyps, but many theories abound with regard to
their ultimate cause. Unless a direct cause is found, treatment of
nasal polyps typically involves the use of anti-inflammation medicines.
Although polyps are technically “tumors” most polyps if they are
present on both sides of the nose are not malignant tumors. However, if
a polyp is present only on one side, suspicion is higher that an
unusual type of polyp may be present.
Endoscopic picture of a
nasal polyp. The black arrows point to the polyps. The white arrow
points to the middle turbinate and the red arrow points to the nasal
septum.
BACKGROUND
The
nose has several purposes. First and foremost it is an entry point for
the air that we breathe. However, the nose is also tasked with
processing this air before it enters the lungs. As such, the nose is a
very efficient humidifier that adds moisture to dry air. It is also a
filtration apparatus: by producing about two liters of mucous per day,
the nose traps particulate matter and prevents particles from entering
the lungs. Instead, the mucous that traps the particles is swallowed
and impurities breathed in through the nose are shunted to the stomach
and safely expelled by the gastrointestinal system. The nose is also a
radiator that warms air, preventing frigid air from irritating the
lungs.
In addition, the nose is the seat of the
sense of smell; this sense not only adds to our enjoyment of food but is
connected to the most ancient brain centers, which govern emotion.
Smell is also an important safety factor that prevents the ingestion of
spoiled food that would cause illness. A glimpse at the perfume and
food and beverage industries highlights the importance of smell
(olfaction) in our society. Finally, the nose and sinuses add resonance
to the voice. The American Rhinologic Society is an organization of
numerous physicians who have a solid professional interest in the nose.
It is a good source of information regarding various disease processes
and functions of the nose.
http://www.american-rhinologic.org/patientinfo.purposeofsinuses.phtml
The sinuses – air cavities in the head that are near or connect to the nose – consist of the ethmoid sinus, the maxillary sinus, the frontal sinus, and the sphenoid sinus. The ethmoids are next to the eyes, the maxillary sinuses are beneath the cheeks, the frontal sinuses are beneath the forehead, and the sphenoid sinus is located at the base of the skull. The sinuses have a complex anatomy, but they also have a consistent and reproducible physiology.
A CT scan showing the maxillary and ethmoid sinuses. The maxillary sinuses are pointed out by the white arrows, the ethmoid sinuses by the red arrows:
The sinuses – air cavities in the head that are near or connect to the nose – consist of the ethmoid sinus, the maxillary sinus, the frontal sinus, and the sphenoid sinus. The ethmoids are next to the eyes, the maxillary sinuses are beneath the cheeks, the frontal sinuses are beneath the forehead, and the sphenoid sinus is located at the base of the skull. The sinuses have a complex anatomy, but they also have a consistent and reproducible physiology.
A CT scan showing the maxillary and ethmoid sinuses. The maxillary sinuses are pointed out by the white arrows, the ethmoid sinuses by the red arrows:
A fiberoptic scope can transilluminate the frontal sinus beneath the forehead after surgery:
In general, mucous that is produced in the maxillary sinus drains through the natural ostium (small opening) of the sinus and through the infundibulum, a bone channel partially created by a portion of the ethmoid bone called the uncinate process. At the end of this channel is an opening called the hiatus semilunaris. The natural ostium, infundibulum, and hiatus semilunaris together are called the ostiomeatal complex. It is this ostiomeatal complex (or OMC) that is the key anatomical point in thinking about sinus disease. The OMC is just across from a portion of the ethmoid bone called the middle turbinate. In general, airflow through the nose is channeled past the uncinate process and the uncinate is the first area where particulate matter impacts and accumulates. This area is also the most common area for nasal polyps to develop. Sinus anatomy can be reviewed at this American Rhinological Society website: http://www.american-rhinologic.org/patientinfo.sinusnasalanatomy.phtml
If you look at polyps under a microscope, one sees that the nasal lining is swollen or hypertrophic. Mucous cells are numerous and are more prominent than in normal people. Also, certain blood cells – frequently the white blood cells called eosinophils – are often present in a higher proportion than normal. When blood cells are present in a high proportion, inflammation is said to be present. Polyps are actually gelatinous and flexible masses that form from inflamed tissue. As polyps grow they begin to block the nose. Also, they can block the critical OMC pathway as they enlarge and begin to cause sinusitis.
SYMPTOMS OF NASAL POLYPS
Patients with nasal polyps complain mostly of nasal obstruction. The polyps block the nose and the patient can not breathe through the nose. As polyps enlarge, they can block the olfactory lining from receiving odor signals. Anosmia (absence of smell) or a decreased ability to smell is a frequent complaint. Sometimes, patients with polyps will complain of facial pressure and fullness. They may have a heavy feeling in their face from the polyps. Ironically, pain is not typically a symptom of polyps. Polyps will sometimes bleed slightly if irritated but this is less frequent than expected. Headaches are not usually a symptom of polyps unless an acute infection complicates the presence of the polyps. Often patients with polyps will have severe postnasal drip and complain of constantly needing to clear mucous. Patients with polyps may also have asthma, but allergies are not particularly related to the presence of nasal polyps.DIAGNOSIS OF NASAL POLYPS
The mainstay of the diagnosis of nasal polyps is the physical examination by a doctor. Actually, the nose is not a familiar place for most physicians and the usual inspection of the nose in the office involves a quick glance with a light. Nasal anatomy can be complicated and confusing and the outer wall of the nose contains protuberances called turbinates which can easily be confused with nasal polyps. If the doctor suspects polyps, a referral to an Otolaryngologist-Head and Neck surgeon (ENT or Ear, Nose, and Throat doctor) would be common. The Otolaryngologist will have access to endoscopic equipment (an illuminated, flexible tube) that allows more thorough inspection of the nose to help diagnose the presence of polyps. Also, computerized imaging studies such as computed tomography (CT) scans will likely be ordered to help establish the presence of the polyps in the sinuses, to make sure that they are not growing large and causing other problems, and to act as a baseline picture against which one can judge future treatment of the polyps.
This picture shows two types of endoscopes used to diagnose nasal polyps:
CAUSES OF NASAL POLYPS
Although nasal polyps all look the same physically, the cause of polyps is quite varied. What follows is a list of potential causes of nasal polyps.Samter’s Triad: Samter’s Triad is the triad of aspirin sensitivity, asthma, and nasal polyposis (the development of numerous polyps). This is commonly referred to as “aspirin allergy.” It is an unfortunate misnomer as this problem is not based upon true allergy. Aspirin was first synthesized in 1853 and was released in the United States in 1910. In 1911, the first reported case of Aspirin Triad was noted and a series of cases was reported in 1922 by Widal. In 1968, Max Samter reported 1000 cases of this problem in the Annals of Internal Medicine. The mechanism behind this problem is that aspirin blocks a portion of the pathway designed to break down a substance called arachidonic acid. Because one leg of the metabolic breakdown path is blocked, a second pathway for breakdown is used to a greater extent. This produces a relative increase in the presence of substances called leukotrienes and these leukotrienes cause chronic inflammation which produces polyps and asthma. The diagnosis of this problem is based upon a clinical observation of worsening asthma with aspirin ingestion. This website has a nice summary diagram of the metabolism of arachidonic acid: http://www-ermm.cbcu.cam.ac.uk/03005854h.htm
Allergic Fungal Sinusitis (AFS): AFS is a true allergy to fungus, often Aspergillus. The presence of the fungus causes a release of inflammatory mediators and eosinophil blood cells which causes chronic inflammation and nasal polyps. AFS is diagnosed when certain criteria are met. The criteria include: a culture or other test showing the presence of fungus in the nose; the presence of certain crystals called Charcot-Leyden crystals on pathological examination of material removed from the nose; a characteristic CT scan showing predominantly one sided sinus involvement and a good clinical response to corticosteroid medication, and; an extremely high elevation in a blood test for the antibody IgE. Sometimes a few of these characteristics will be present, but it will take years to discover enough of these characteristics to make a firm diagnosis. This problem is similar to a pulmonary problem called Allergic Bronchopulmonary Aspergillosis. The American Academy of Otolaryngology-Head and Neck Surgery is a good source of information on this problem: http://www.entnet.org/healthinfo/sinus/fungal_sinusitis.cfm
Cystic Fibrosis (CF): Cystic fibrosis is a genetic disorder caused by mutations on chromosome 7. The national CF organization is an excellent source of information on the disease: http://www.cff.org/AboutCF/Testing/GeneticCarrierTest/ . One of the most common mutations is the Delta F 508 mutation. There is a subcategory of patients with CF who manifest with nasal polyps. The exact reason for this is not fully known, but it is thought to be due to a problem with chloride channels in the cell membranes. Patients with CF often have problems with their lungs and also with their digestion, which are all part of the same genetic malfunction. This problem can be diagnosed with a test called a sweat chloride level and with specialized genetic testing.
Human Papilloma Virus (HPV): HPV is known to cause a specific type of nasal polyp called an inverted papilloma. Generally, virus types 6 and 11 are most commonly known to cause nasal polyps. This type of polyp is usually on one side of the nose and can, over a long period of time, begin to erode the bones of the sinuses causing other problems. The diagnosis of this type of polyp must be made based upon tissue sampling of the polyp and review by the pathologist.
Staph. Aureus Bacteria: It is postulated that the presence of Staph. in the nose may cause polyps through a variety of different routes. One theory is that Staph. can produce a toxic substance called enterotoxin that triggers a chronic inflammation as the body produces IgE designed to combat the enterotoxin. This IgE directed at the Staph. Aureus enterotoxin is chronically produced and leads to polyp formation. Another theory focuses on the ability of Staph. to overgrow the nasal lining and produce a bacterial film known as a biofilm that may create a sinusitis condition or nasal polyps. These theories are not currently well developed and a number of different research groups are looking into these mechanisms. Currently the method used to diagnose this problem is not agreed upon.
Fungus: Fungal elements in mucous may potentially elicit a chronic inflammation – primarily from the eosinophil blood cells – that is theorized to cause sinusitis and perhaps nasal polyps. This theory was originally reported by the Mayo Clinic which then went on to obtain a method patent (U.S. Patent #6555556), patenting the use of antifungal medication to treat chronic inflammation in the nose and entire human body (http://www.scienceblog.com
/cms/mayo_clinic_receives_patent_for_new_treatment_of_chronic_sinus_infection
). Nevertheless, diagnosing this problem remains difficult and
uncertain. The Mayo Clinic predominantly used culture techniques to
isolate a theoretically causative fungus or utilizes a test for major
basic protein to suggest that his mechanism is the cause of the problem.
Other groups have used genetic diagnostic techniques to identify the
presence of fungus. Several companies are working on developing
antifungal medication to treat sinusitis based upon this fungal
causation theory (http://www.accentia.net/science/sinunase.php ).
Mucous Retention Cyst: About 10 % of the population will have a cyst present in the sinuses called a mucous retention cyst. These cysts can occur in any sinus but seem to occur most frequently in the maxillary sinuses. It is unknown exactly why these cysts develop, but it is thought to result from a plugged mucous gland. The cysts are normally completely asymptomatic unless they become very large and begin to block the normal sinus drainage pathway. The reason this is brought up in the polyp section is that many times when these are seen on CT scans or other films, the report of the film by the radiologist will call it a “polyp” or mass; sometimes the report will just refer to the cyst as an “opacification.” It is not usually necessary to recommend treatment for mucous retention cysts.
Antral-choanal polyps: This is a rare type of nasal polyp located only on one side of the nose. It is thought to arise from the lining of the maxillary sinus. The polyp seems to push from the maxillary sinus, through a narrow opening, and into the nose. It often presents as a one sided mass in the nose. For some reason, this type of polyp is sometimes found in children. It is also unusual in that surgery is the recommended treatment.
Mucous Retention Cyst: About 10 % of the population will have a cyst present in the sinuses called a mucous retention cyst. These cysts can occur in any sinus but seem to occur most frequently in the maxillary sinuses. It is unknown exactly why these cysts develop, but it is thought to result from a plugged mucous gland. The cysts are normally completely asymptomatic unless they become very large and begin to block the normal sinus drainage pathway. The reason this is brought up in the polyp section is that many times when these are seen on CT scans or other films, the report of the film by the radiologist will call it a “polyp” or mass; sometimes the report will just refer to the cyst as an “opacification.” It is not usually necessary to recommend treatment for mucous retention cysts.
Antral-choanal polyps: This is a rare type of nasal polyp located only on one side of the nose. It is thought to arise from the lining of the maxillary sinus. The polyp seems to push from the maxillary sinus, through a narrow opening, and into the nose. It often presents as a one sided mass in the nose. For some reason, this type of polyp is sometimes found in children. It is also unusual in that surgery is the recommended treatment.
COMPLICATIONS OF NASAL POLYPS
Because they obstruct the nose, nasal polyps can cause patients to have quite a lot of difficulty breathing comfortably. They may cause a decreased sense of smell, anosmia (absence of the sense of smell), or even cause snoring because breathing must be accomplished through the mouth. Over long periods of time, polyps can erode bone and cause brain or eye problems if left untreated.TREATMENT OF NASAL POLYPS
The treatment of nasal polyps is variable and can depend on the underlying cause of the polyps, which is not always known. In general, inflammatory polyps are treated with anti-inflammatory medication and this usually means corticosteroids. National Jewish Medical Center in Denver has a website that describes, in general, information pertaining to steroid medication: http://www.nationaljewish.org/disease-info/treatments/long-term/steroids/corticosteroids.aspx . Corticosteroids may be administered in topical preparations or oral preparations or both. In general these medications act to interrupt chronic inflammation and they have the ability to dramatically reverse nasal polyp formation. Unfortunately, the underlying inflammation triggers often remain and when a patient is taken off steroids the inflammatory cycle will creep back to form nasal polyps. Often, long term topical steroids are recommended in an attempt to minimize the need for oral steroids.Rarely, oral steroids must be recommended on a regular and frequent basis to control polyp formation. The reason oral steroids are used as sparingly as possible is that they have potential side effects that must be weighed against their known benefits in treating the polyp disease. Although any medication has the potential to cause problems, topical steroids are the safest way of delivering corticosteroids to patients who will often require long term therapy.
If a specific reason for the polyps can be found, then more specific treatments can sometimes be formulated. A good example can be seen in aspirin triad patients. In aspirin triad patients, often anti-leukotriene drugs are used in addition to corticosteroids. This can include drugs like montelukast sodium (Singulair) and zileutin (Zyflo). They are more directed at asthma control from a drug indication standpoint and it is not quite clear whether they have a discernable effect on nasal polyps specifically. Also in the aspirin triad patient, aspirin desensitization as described by Donald Stevenson (http://www.scripps.org/Doctors.aspx?ID=985 ) can be accomplished. This treatment depletes the leukotriene mediator reserve of a patient by administering large doses of aspirin in a controlled and monitored setting. When the inflammatory mediators are fully depleted, the patient is kept on a small dose of aspirin every day. This prevents the inflammatory leukotrienes from reaching a level where they can cause inflammation again. Dietary attention to minimizing salicylate (aspirin) ingestion can also be recommended in people who are sensitive to the inflammatory miscues that aspirin ingestion can cause. Several lists point out the varying content of aspirin or salicylates in common foods: http://www.zipworld.com.au/~ataraxy/Salicylates_list.html and http://www.foodcanmakeyouill.co.uk/sali/salfood.htm .
Surgery is also a potential treatment for nasal polyps, but surgery in the absence of trying to control the underlying inflammation is expected to produce short term results only and likely to produce long term failure. Surgical removal of inflammatory polyps would typically be expected to result in quick regrowth of the polyps in weeks to months. Yet, surgery as part of a strategic plan to control inflammation can be a beneficial management strategy for patients with difficult to manage nasal polyposis It is thought that surgery can remove enough polyp tissue to allow a decreased burden of inflamed tissue and to allow topical steroid medication to work better when anti-inflammatory medications alone do not improve the overall condition enough. In some rare cases, surgery is the treatment of choice like when the polyp is caused by human papilloma virus or when a special type of unilateral polyp occurs called an antral-choanal polyp.
Antibiotic regimens directed at removing Staph. Aureus bacteria may be recommended if Staph. is thought to be playing a role in the cause of the polyps. Also, anti-fungal medication, delivered through an aerosolized lavage or spray may be eventually standardized as a treatment for nasal polyps. Although rarely recommended in the United States, the use of Lasix (furosemide) nasal spray has been reported in Italy to help treat polyps in a study that had nine years of follow-up. In patients with cystic fibrosis, treatment of the chronic sinusitis and nasal polyposis may involve the use of aerosolized Tobramycin antibiotic irrigation. Some Japanese papers have shown that a certain type of antibiotics, called Macrolide antibiotics, may have anti-inflammatory effects in addition to their antibacterial effects. Finally, some doctors recommend saline irrigation as a method of helping reduce nasal problems including polyps. Saline is a mild decongestant and can help dilute mucous and so it may be helpful in managing polyps.
FUTURE TREATMENTS
Many different researchers are looking at treating polyps through a variety of different means. In the future, certain types of antifungal medication delivery may be available. In addition, novel ways of administering steroids may be released. Also, new drug categories are being investigated including certain types of receptor blockade drugs.CONCLUSION
Polyps are relatively common, but they can be frustrating to treat because there are many potential underlying causes and it is often not possible to pinpoint their exact cause. The work up includes a detailed history, a nasal examination, and often a CT scan. The mainstay of treatment is the use of corticosteroid drugs either through oral or topical administration. Surgery can sometimes be helpful to control the disease along with other methods of treatment.References
Articles:
1. Stevenson DD, Simon RA. Selection of patients for aspirin desensitization treatment.
J Allergy Clin Immunol. 2006 Oct;118(4):801-4. Epub 2006 Jul 24. Review. No abstract available. PMID: 17030229
2. Ponikau JU, Sherris DA, Kita H, Kern EB. Intranasal antifungal treatment in 51 patients with chronic rhinosinusitis. J Allergy Clin Immunol. 2002 Dec;110(6):862-6. PMID: 12464951
3. Bachert C, Zhang N, van Zele T, Gevaert P, Patou J, van Cauwenberge P. Staphylococcus aureus enterotoxins as immune stimulants in chronic rhinosinusitis.Clin Allergy Immunol. 2007;20:163-75. Review. No abstract available. PMID: 17534051 4: Patou J, Gevaert P, Van Zele T, Holtappels G, van Cauwenberge P, Bachert C. Staphylococcus
aureus enterotoxin B, protein A, and lipoteichoic acid stimulations in nasal polyps. J Allergy Clin
Immunol. 2008 Jan;121(1):110-5. Epub 2007 Nov 5. PMID: 17980412
5. Murr AH, Goldberg AN, Vesper S. Fungal speciation using quantitative polymerase chain reaction
(QPCR) in patients with and without chronic rhinosinusitis. Laryngoscope. 2006 Aug;116(8):1342-8.
PMID: 16885733
6. Bhattacharyya N. Influence of polyps on outcomes after endoscopic sinus surgery. Laryngoscope.
2007 Oct;117(10):1834-8. PMID: 17690616
7. Passàli D, Bernstein JM, Passali FM, Damiani V, Passàli GC, Bellussi L. Treatment of recurrent
chronic hyperplastic sinusitis with nasal polyposis. Arch Otolaryngol Head Neck Surg.
2003 Jun;129(6):656-9. PMID: 12810472