TITLE: Management of Chronic Rhinosinusistis
SOURCE: Grand Rounds Presentation, UTMB, Dept. of Otolaryngology
DATE: May 9, 2006
RESIDENT PHYSICIAN: Jean Paul Font, MD
FACULTY PHYSICIAN: Matthew Ryan, MD
SERIES EDITORS: Francis B. Quinn, Jr., MD and Matthew W. Ryan, MD
"This material was prepared by resident physicians
in partial fulfillment of educational requirements established for the
Postgraduate Training Program of the UTMB Department of Otolaryngology/Head and
Neck Surgery and was not intended for clinical use in its present form. It was
prepared for the purpose of stimulating group discussion in a conference
setting. No warranties, either express or implied, are made with respect to its
accuracy, completeness, or timeliness. The material does not necessarily
reflect the current or past opinions of members of the UTMB faculty and should
not be used for purposes of diagnosis or treatment without consulting
appropriate literature sources and informed professional opinion."
Introduction
Sinusitis is one of the most common health care
challenges in the
The word Rhinosinusitis is replacing the term
sinusitis because sinusitis is often preceded by rhinitis and rarely occurs
without concurrent nasal airway inflammation. Rhinosinusitis has been defined
by the American Academy of Otolaryngology as an inflammation of the nose and
sinuses. It is believe that this
condition comprise a spectrum of inflammatory and infectious diseases.
The site of sinus and nasal obstruction is important.
The ostiomeatal complex is a region of key importance for the development of
rhinitis induce sinusitis. The area comprise the hiatus semilunaris, a
curvilinear groove between the uncinate process and the bulla, and through
which the frontal, anterior ethmoid and maxillary sinuses drain into the nasal
cavity. Inflammation or anatomic
obstruction by a mass on this area block drainage from these three sinuses leading
to stagnation of secretion and creation of a culture medium for infection to
developed.
Unfortunately, the accuracy of reported rhinosinusitis
cases is difficult to ascertain. The diagnosis on the basis of symptoms is
common but can be unreliable. This concern is especially true for the accurate
diagnosis of chronic rhinosinusitis (CRS). A rhinosinusitis task force in 1997
outlined "major" and minor criteria for diagnosing sinusitis. The
major criteria include facial pain, nasal obstruction, hyposmia, purulence on
examination, and fever. While, minor criteria include headache, fatigue, dental
pain, and cough. Studies have found the criteria to be sensitive but not specific.
Currently the gold standard for the diagnosis of chronic rhinusinusitis is
computed tomography.
The classification of Rhinosinusitis is based on
duration of sign and symptoms into acute, subacute and chronic. Acute is
defined as lasting up to four weeks, with total resolution of symptoms. The
term recurrent acute has also been adopted and is defined as four or more
episodes per year, with resolution of symptoms between attacks. Subacute is
persistence of sing and symptoms for more than four weeks, but less than twelve
weeks with total resolution of symptoms.
Finally, Chronic is 12 weeks or more of signs and symptoms.
Successful management of rhinosinusitis via medical or
surgical treatment is achieved in the majority of patients. In some cases symptoms
resolve spontaneously. Treatment of
chronic rhinosinusitis is intended to reduce symptoms and signs, improve
quality of life, and prevent disease progression or recurrence.
Medical treatment is the initial treatment choice
before opting for surgery in patients who do not improve. Many medical
treatments have been recommended or employed. Evidence for their efficacy is
rarely strong, partly because of the poor-quality trials in unselected groups
of patients2. Chronic rhinosinusitis involves multifactorial
etiology. The condition does not respond by simply making an empiric antibiotic
selection. There are several predisposing factors in chronic rhinosinusitis
which include host factors like allergic rhinitis, viral illness (children in
daycare), gastroesophageal reflux, anatomic obstruction, immunodeficiency, genetics,
congenital. There are also environmental factors such as irritants (cigarette
smoke), microbial (viral, fungal and bacterial) and even medication inducing
rhinitis medicamentosa. The quest and identification of factors predisposing to
chronic rhinosinusitis is key to guide appropriate management.
The most common indication for sinus surgery is
failing medical therapy of chronic sinusitis. Approximately 200,000 U.S. adults
undergo sinus surgery per year. Relative
indication include persisting obstruction to sinus aeration (e.g., polyp,
concha, septum), specific area of recurring disease and chronic or recurrent
acute rhinosinusitis who have not responded adequately to medical therapy.
Absolute indication include complications like brain abscess, meningitis,
subperiosteal abscess, sinus mucocele or pyocele, fungal sinusitis (all
varieties), massive polyposis (obstructing sinuses) and neoplasm or suspected
neoplasm (causing sinus obstruction).
Frequently a
combination of measures is employed in an individual patient. Some management
are directed at improving sinus ventilation and drainage like oral hydration,
saline irrigation, mucolytics and decongestants. There are other designed to
reduce inflammation corticosteroids, antihistamines, macrolides and anti-leukotriens.
Finally, there are those designed to treat infection such as anti-biotics and
antifungals, treat an anatomic abnormality and those directed at avoidance of
allergens. The key to breaking a cycle
of recurrent or chronic sinusitis is the aggressive combination of antibiotics
with therapies directed at predisposing conditions for a length of time
adequate to allow for healing of upper respiratory tract mucosa with recovery
of local immune defense14.
Allergens and Irritants
Up to 30% of the adult population is allergic by skin
testing to at least one common aeroallergen, and the percentage is probably
much greater among patients presenting with a history of chronic sinusitis. Allergic
rhinitis is probably the second most common predisposing condition to chronic
sinusitis in children (after viral upper respiratory infection) and perhaps the
most common predisposing factor in adults14.
A combination of allergic history and positive skin prick testing is key
in the management of chronic sinusitis in a patient with allergic rhinitis. This
condition causes mucosal inflammation and hypertrophy predisposing to blockage
of the ostiomeatal complex. This is the reasoning behind innovating research
directed at treating the antiinflammatory response as a route of medical
management in chronic rhinosinusitis.
Sign and symptoms of chronic rhinosinusitis occur in response to irritant exposure. There is increasing evidence to support the theory that exposure to air pollution can impair mucociliary protection and potentiate sensitivities to common aeroallergens by stagnation of this agents. Avoidance and protection against smoke, pollution, and occupational irritants usually is advised to counteract these predisposing factors.
Saline Irrigation
Use of intranasal saline has been shown to decrease
nasal symptoms and improve quality of life in allergic rhinitis and chronic
rhinosinusitis. Saline spray increases mucociliary flow rates counter acting
the effects of irritants and other numerous factors that affect mucociliary
clearance. It also has a brief
vasoconstrictive effect that leads to some short term symptomatic relief. Also,
nasal saline irrigation mechanically rinse away predisposing agents such as
aeroallergens like pollen, mold, dust,
and particulate of air pollution. Although it has some symptomatic relief, patients
with chronic rhinosinusitis are told to use saline at least twice daily as a
preventative measure rather than starting when clinical symptoms manifest.
An acidic milieu is thought to cause the gel state (more viscous) of mucus to predominate, where as an alkaline milieu is thought to cause the sol state to predominate. This is the rationale for adding baking soda to saline irrigation solutions.
Mucolytics
Guaifenesin is the most commonly used mucolytic agent. High doses of this medication are required to obtain an effect on mucous. At these amounts, patients often experience emesis and abdominal pain. Wawrose in 1992 showed significant improvement of nasal congestion and symptomatic relief in patients with AIDS and low CD4 counts.
Corticosteroid
It is sometimes contradictory to use an anti-inflammatory
agent that can lead to immunosuppression like corticosteroids in the treatment
of sinusitis which is consider having a significant association with microbial
infection. Nonetheless, a short course of steroids can induce a significant
anti-inflammatory and beneficial effect in the management of severe nasal
mucosal congestion in allergic rhinitis patients. This brief period induce
symptomatic relief and reduction of nasal and sinus mucosal inflammation
promoting a better scenario for the management with topical agents, improving
compliance and rate of benefit.
Corticosteroids have multiple immunomodulator mechanisms including
stabilization of mast cells against mediator release, block formation of
inflammatory mediators, and inhibit chemotaxis of inflammatory cells. It is
important to keep in mind the adverse effect of systemic steroid use and the
contraindications that include diabetes, peptic ulcer disease, glaucoma, severe
hypertension, and advanced osteoporosis. Even a short course of steroids can
significantly increase the blood pressure and glucose levels in patients with
predisposition to hypertension and diabetes.
Close monitoring and immediate withdrawal for side effects is warranted.
Topical nasal corticosteroids are a very effective form of treatment for allergic rhinitis and chronic rhinosinusitis. Their anti-inflammatory effect is localized and their systemic absorption has been shown to be negligible. The local reduction of inflammation prevents blockage and improve patency of the ostiomeatal complex. After use by at least 7 days, nasal corticosteroids have been shown to inhibit both immediate and late-phase reactions to antigenic stimulation in patients with allergic rhinitis14. An estimated 90% of patients with allergic rhinitis will experience improvement in nasal allergy symptoms including chronic nasal congestion with topical nasal steroid preparations accounting for a marked increase in popularity of these medications over the last decade14.
Some common adverse effects of topical nasal steroid use include nasal irritation, mucosal bleeding, and crusting. Septal perforation is a rare complication and the risk can be increased for patients living in very dry climates. The ingredient propylene glycol contained in the preparations is responsible for this complains. This can be alleviated by switching to an aqueous delivery system. The addition of nasal saline wash in conjunction with topical steroids can lessen or eliminate these common adverse effects.
Decongestants
Decongestants are α-adrenergic agonists that
induce a sympathetic response leading to vasoconstriction of dilated mucosal
blood vessels. Decongestants are best used for short (35 days) courses at the
beginning of treatment for sinusitis or allergic rhinitis.
The most common oral decongestants are pseudoephedrine and phenylpropanolamine. This systemic agents achieve symptomatic relief, but lead to several adverse effects that are related to its sympathetic stimulation including insomnia, heart palpitations, and elevated blood pressure. Oral decongestants are indicated principally for symptomatic relief of nasal congestion and have not been shown to have therapeutic efficacy for the treatment of sinusitis14.
Topical agents include phenylephrine and oxymetazoline. This agents lead to a local excitation of alpha adrenergic receptors leading to a localize vasoconstriction and decrease of mucosal edema. All topical agents exhibit rebound vasodilation, which can be demonstrated by rhinometric analysis of nasal resistance as early as 3 days after beginning therapy. Clinical rebound congestion or rhinitis medicamentosa usually requires at least 10 days to 2 weeks of topical decongestant use to become apparent. This is the reasoning of using decongestants for short (35 days) courses at the beginning of treatment for sinusitis or allergic rhinitis.
Antibiotics
The use of antibiotics in chronic sinusitis is a topic of high controversy. Its efficacy, duration of therapy and agents to be use have been extensively debated. Some consensus is apparent on the idea that antibiotic therapy for chronic sinusitis should be based on culture results. This is based on the increase in antibiotic resistance that have been increasing consistently throughout the decades.
The culture can be obtained by direct visualization under endoscopy of purulent secretions from the middle meatus. Although the maxillary tap is the gold standard for culture diagnosis, this method is highly uncomfortable to the awake patient. Although there is not a definite large randomize control trial comparing both techniques, the endoscopic technique correlates well with the maxillary tap and is less traumatic to the alert patient. Nevertheless, the maxillary taps still a very effective tool especially on the ICU setting.
The first-line antibiotics for chronic rhinosinusitis include amoxicillin-clavulanate and second-or third-generation cephalosporins. The respiratory quinolones are helpful second line agents for refractory cases to firs line antibiotics.
Bacterias have developed multiple mechanisms of
resistance. Alteration of the penicillin binding proteins is the most common
reason for penicillin resistance in Streptococcus pneumoniae infections. This
mechanism of resistance is overcome by increasing the penicillin component to a
much higher dose. This is the rational behind dosing children with 60 to 90
mg/kg per day instead of 40 mg/kg for amoxicillin. Haemophilus influenzae also
utilize this type of resistance, but to a lesser degree.
According to the American Academy of Otolaryngology approximately 40% of Haemophilus. influenzae and greater than 90% of Moraxella catarrhalis produce beta-lactamase. This enzyme breaks down the b-lactam antibiotics. β-Lactamase-mediated resistance to the early second-generation cephalosporins is high among strains of Haemophilus influenzae and Moraxella catarrhalis. Stabilization of penicillin by adding clavulanate overcomes this enzymatic action.
Newer generation macrolides such as clarithromycin and
azithromycin achieve excellent mucosal levels but should be considered backup
drugs. Azithromycin appears to be more potent against Haemophilus Influenzae,
whereas clarithromycin may be slightly better against intermediate resistant Streptococus
pneumoniae.
Bacterias have also developed resistance against macrolide and even fluroquinolones. Streptococus pneumoniae have been shown to develop two different mechanism of resistance against these two antibiotic families. One of the resistant apparatus is the efflux pump which eliminates the antibiotic from the microorganism interior before it can exert its effect. The other mechanism of resistance is the development of altered target proteins which prevent the connection of the antibiotics to the cell wall or mitochondria stopping its action inside the bacteria.
Authors have noted a doubling of pneumococcal
resistance to macrolides over the past 10 years from approximately 10% to 20%
leading to recommendations that these drugs (and fluoroquinolones in adults)
not be used as first-line therapy for sinusitis14. Clindamycin is
another alternative which should be reserved for culture-documented resistant Streptococus
pneumoniae.
Most authors recommend treating chronic sinusitis with
a broad-spectrum antibiotic for up to 3 weeks. After 3 to 5 days of treatment
there should be symptomatic improvement. After 10 to 15 days of treatment, symptoms
should resolve. The logic of continuing therapy for another week is to allow
for further diminution of mucosal edema and mucociliary function thus gaining
resistance against new infection.
Many clinicians will follow the
3-week treatment course of antibiotics with a 3- to 6-week course of once-daily
prophylactic antibiotic therapy for patients with a history of rapid recurrence
after previous treatment. The goal is to get the patients through their window
of vulnerability to new infection while mucosal recovery.
Prolonged use of low-dose macrolides in patients with chronic rhinosinusitis was found to be effective even when the identified bacterial pathogen was not sensitive to this agent. This management has also been found to decrease the size of nasal polyps.
Antiinflamatory effect of Macrolide
The observation that macrolide antibiotics were steroid-sparing in patients who had steroid-dependent asthma has been present for decades. This was thought to be due to inhibition of steroid metabolism. The concept of using long-term, low-dose macrolides for treatment of Chronic rhinosinusitis evolved further, primarily in Japan4.
An interesting aspect of the pharmacokinetics of
macrolide antibiotics is their extensive tissue uptake and intracellular
accumulation. Macrolides accumulate in inflammatory cells at concentrations up
to several hundred-fold higher than concentrations in extracellular fluid. The
macrolide antibiotics decrease cytokine production (IL-5, IL-8, GM-CSF,
TGF-β, IL-6, IL-8, TNF-ɑ),
altered structure and function of biofilm, reduced expression of cell surface
leukocyte adhesion molecules, accelerate neutrophil apoptosis, impaired
neutrophil oxidative burst, decrease secretion and improve mucociliary
clearance, and Inhibited release of elastase, protease, phospholipase C, and
eotaxin A by P aeruginosa4.
Meta-analysis of anti-inflammatory effect of macrolides in
Chronic rhinosinusitis
|
Type of study |
Dosage 24h (mg) |
Duration
(months) |
Macrolide |
Results |
Reference |
|
Prospective, randomized, controlled trial, n = 90 |
1000 (2 wk) |
3 |
Clarithromycin |
As effective as surgery in chronic sinusitis |
Ragab, 2004 |
|
Prospective, open, n = 17 |
500 |
12 |
Erythromycin |
12 responders, mucocillary transport, headache, postnasal drip, all
improved, P<.05 |
Cervin, 2002 |
|
Prospective, open, n = 20 |
1000 |
0.5 |
Clarithromycin |
Improvement in CD68, IL-6, IL-8, TNF-ɑ and
clinical parameters |
Macleod, 2001 |
|
Prospective, open, n = 20 |
400 |
3 |
Clarithromycin |
Reduction of IL-8 in nasal lavage, decreased nasal polyp size |
Yamada, 2000 |
Cervin et al. 2005
The above table shows several of the prospective studies done in the use of macrolides in long term management of chronic rhinosinusitis (CRS). Clarithromycin is the macrolide most studied in CRS. While Azithromycin lack studies in CRS. The table shows the marked success of this management in the symptomatology, reduction of cytokines in the tissue, decrease in nasal polyp size and effectiveness in comparison to surgery. The long term use in the above table varies, but an average of 3-12 month is seen.
Gastroesophageal Reflux (GERD)
There is a new trend of research in the involvement of GERD in upper airway pathologies. Reflux is said to be associated to chronic rhinosinusitis. The mechanism is not cleared and studies are necessary to further enlighten this discussion. However, it is thought that the reflux of acid content reach the nasopharynx and nasal cavities leading to chronic mucosal irritation and sinusitis.
Adult patients with chronic sinusitis and a history of
heartburn could benefit from antireflux regimen including precautions and medication.
In young children the relation is more evident presumably due to the closer
proximity between the esophageal inlet and larynx to the soft palate and
nasopharynx. Suspicion should rise in children with chronic congestion, rhinorrhea,
excessive spitting up in infancy, low weight percentile, failure to thrive, chronic
stridor and reactive airway disease.
Viral infections
Viral infections are the most common predisposing factors for sinusitis in children. Day care is an important risk factor for the development of viral infections due to the proximity and relation characteristics of children in this environment. The current management for viral infections is prevention by frequent hand washing and decrease exposure. Children with chronic rhinosinusitis may benefit from changing to a day care with fewer numbers of children to reduce viral exposure. Also an alternative are vacation periods from the daycare to allow for resolution of symptoms and decrease mucosal inflammation and improve mucocialliary clearance as a measure for improving natural resistance to the condition.
Interferon alpha-2 (IFN α2) can potentially block
the penetration of viruses through respiratory mucosa. Intranasal IFN α2,
when used as a once-a-day nasal aerosol, has been shown to potentially prevent
colds in people exposed to family members with upper respiratory infections. Although
medications like Interferon alpha2 has shown some improvement its usage is
limited by its cost.
References