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MEDICAL MANAGEMENT OF SINUSITIS

 Dinaz K Irani*, Makarand V Damle**
 *Clinical Lecturer in ENT, **Senior Resident in ENT, Topiwala National Medical College and Nair Hospital, Mumbai 400008
Sinusitis is an inflammation of the paranasal sinuses. Clinical diagnosis can usually be made from the patient’s history and findings on physical examination only. A persistent mucopurulent discharge with associated coughing, pharyngeal irritation or sore throat may exist in combination or individually. Nasal obstruction, hyposmia and occasionally cachosmia may occur. Sinusitis may also cause headache, facial pain, or maxillary toothache. Occasionally the patient may complain of ear blocking or nasal bleeding with generalised fever, bodyache and malaise.

Chronic sinusitis is usually due to inadequate mucociliary function or obstructed drainage, the infecting organisms being a host of opportunistic bacteria especially anaerobes. Immunocompromised patients including those with HIV infection may develop sinusitis with common or opportunistic organisms including Pseudomonas species and fungi. Fungal infection is relatively rare in comparison with viral and bacterial infection. It is known to occur especially in patients having poorly controlled diabetes, those who are severely debilitated such as those with carcinomatoses and patients treated with immunosuppressant drugs. The commonest fungi involved are Aspergillus and Mucor.

Investigations include nasal endoscopy, radiology (sinus X - rays and Computerised Tomography), swabs and antral lavage and blood tests.

Multiple classes of drugs are used to provide symptomatic relief as well as to afford a cure. Antibiotics, analgesics, antihistaminics, decongestants, mucolytics, steroids, cromolyn and immunotherapeutic agents all are present in the armamentarium of the otorhinolaryngologist.

Acute sinusitis warrants treatment with an antibiotic at least for a period of 10 days.

Definition
A strict semantic definition of sinusitis would encompass any inflammatory condition of the sinuses, including viral infections, autoimmune processes, and non-specific rhinitis that involves contiguous sinuses. However, most of the published comparative therapeutic trials to date have applied restrictive clinical or microbiologic criteria in an effort to focus on bacterial sinusitis.

Aetiology of Rhinosinusitis

ALLERGY
Seasonal
Perennial
Occupational

INFECTION
Acute
Chronic
Specific-fungal
Non specific-local/systemic

STRUCTURAL
Ostiomeatal complex
Deviated septum
Turbinate variations
* Hypertrophic turbinates
* Concha bullosa
* Paradoxically curved turbinate

OTHERS
Idiopathic
Hormonal
Drug induced
Emotional
Atrophic
Dental

Clinical features of sinusitis
The most important diagnostic information can be gained from history. A patient with acute maxillary sinusitis will complain of pain over the cheek which may radiate to the frontal region, temporal area or teeth, and which is classically increased by straining or bending down. Specific localising signs are not always present as one sinus alone is rarely affected. There may be diffuse discomfort from pansinusitis. Examination is often unremarkable, though a degree of tenderness may be present over the maxillary sinus i.e. over the canine fossa. Significant tenderness and oedema may suggest a dental abscess or incipient complications. The nasal mucosa is swollen particularly in the region of the middle meatus. Careful examination may reveal presence of pus in the middle meatus.

Acute frontoethmoidal sinusitis presents with pain about the eye and frontal region. Externally there may be slight redness and swelling of the cheeks spreading to the lower eyelids from the maxillary antrum and to the upper eyelids from the frontal sinus. Tenderness on pressure over the floor of the frontal sinus immediately above the inner canthus is diagnostic of frontal sinusitis. However this is highly subjective and a number of people will complain of pain if sufficient pressure is exerted over a normal frontal sinus.

Acute sphenoidal sinusitis is a rare entity on its own (Fig. 1). It usually accompanies ethmoiditis or pansinusitis. Specific localising signs are an exception rather than the rule though classically a severe retro-orbital headache referred to the vertex, temple or the occiput is described. Similarly chronic sphenoiditis is a rare isolated occurrence, although it can occur if a tumour or other nasal pathology blocks the ostium.

 
Fig 1: Coronal CT Scan showing right acute sphenoiditis.

 

Examination of the nose reveals generalised hyperaemia and swelling of the nasal mucosa. After decongesting the mucosa it may be possible to see pus extruding into the middle meatus from the involved sinuses or into the superior meatus from the sphenoid and the posterior ethmoid sinuses.

The large majority of patients with acute sinusitis will be treated without recourse to investigations or specialist opinion. The otorhinolaryngologist is likely to see only those cases that have failed to respond to treatment, those with present or incipient complications, those with recurrent acute episodes or those in whom a transition from acute to chronic phase is occurring. Once symptoms have persisted for more than 3 months a chronic state is deemed to exist, although this is based empirically on history rather than on sound pathological grounds. Acute community-acquired sinusitis is considered a bacterial complication of the common cold. [1]

Clinical diagnosis can usually be made from the patient’s history and findings on physical examination only. A persistent mucopurulent discharge with associated coughing, pharyngeal irritation, sore throat or laryngitis may exist in combination or individually. Nasal obstruction, hyposmia and occasionally cachosmia may occur. This latter symptom sometimes indicates dental infection due to anaerobes. Sinusitis may also cause headache, facial pain, or maxillary toothache. Occasionally the patient may complain of ear blocking or nasal bleeding with generalised fever, bodyache and malaise.

Causative Micro-organisms
Acute bacterial sinusitis generally results from secondary bacterial invasion after viral rhinitis. Those viruses most commonly implicated are rhinoviruses, coronaviruses, influenza and parainfluenza viruses. Viruses avoid clearance in the gel layer and are capable of rapid adherence to the epithelium and the micropores in the cells. These factors favour secondary infection by the multitude of potentially dangerous bacteria present in the nasal cavity and pharynx.

The organisms commonly associated with maxillary sinusitis are :

VIRUSES

A number of factors may contribute to persistence of inflammation and a state of chronicity viz.:

    1. Viruses, streptococci, haemophilus and pseudomonas all produce toxins that paralyse the cilia and affect clearance. [2]
    2. Streptococci and haemophilus cause subversion of the immune system by producing IgA proteases, which break the immunoglobulin into its Fab and Fc fragments, thus masking the antigenic determinants and preventing more effective antibody attack. [3]
    3. Killian has suggested synergistic action between aerobes and anaerobes as a factor in persistent inflammation of the ethmoid sinus. [4]

Chronic sinusitis is usually due to inadequate mucociliary function or obstructed drainage, the infecting organisms being a host of opportunistic bacteria especially anaerobes. Sinusitis of dental origin is invariably caused by anaerobes and is often of mixed flora.

Immunocompromised patients including those with HIV infection may develop sinusitis with common or opportunistic organisms including Pseudomonas species and fungi. The treatment depends on the causative agent.

Fungal infection is relatively rare in comparison with viral and bacterial infection. It is known to occur in cases of trauma to the face, poorly controlled diabetes, severely debilitated patients such as those with carcinomatoses and patients treated with immunosuppressant drugs. [5] It may, however, occur in otherwise healthy patients. [6] The common est fungi involved are Aspergillus and Mucor.

Investigations

Nasal endoscopy
An endoscopic examination of the nose is central to the appropriate management of any patient with nasal symptoms, especially in cases resistant to treatment, to exclude aetiological factors and to obtain material for bacteriological examination. It provides accurate information regarding secretions, mucosal changes and the state of the ostiomeatal complex.

Radiology
a) Sinus X - rays
Plain X- rays are more appropriate in assessing a patient with acute rather than chronic inflammatory disease. They may show mucosal thickening, fluid levels, total opacity or rarely no abnormality at all. However it is important to remember that X- rays are not infallible. There is a significant incidence of false positive and false negative reporting.

b) Computerised Tomography
CT scan is the optimum imaging technique to demonstrate the extent and distribution of mucosal disease together with any anatomical variant that may be relevant to the diagnosis of acute, recurrent or chronic rhinosinusitis.7 Coronal views centred on the ostiomeatal complex are essential to fulfil these objectives (Fig. 2). The addition of axial views is needed to define the relationship of the optic nerve to the posterior ethmoidal cells when operative treatment is contemplated (Fig. 3).

c) Ultrasonography
A-mode ultrasonography of the maxillary and frontal sinuses appears useful for initial examination and follow up.8 The main advantage of using this technique to aid diagnosis is the freedom from the hazards of radiation to the orbit and the ability to use ultrasonography repeatedly. The main disadvantage is the relatively low sensitivity in diagnosis of sinus disease as compared to plain radiography.

Swabs and antral lavage
The difficulty of interpreting nasal swabs from antral washings is the difficulty in differentiating commensals from pathological organisms. This is shown by a review of 12 studies reporting the frequency of bacteria cultured from the nose in normal individuals.9 From the nasal vestibule they found 40-100 % incidence of staphylococcus epidermidis and micrococcus, 25-40% staphylococcus aureus, 90- 100% diphtheroids and 1% of Gram negative bacteria. From the posterior nares streptococcus pneumoniae was isolated in 15- 20%, Haemophilus influenzae in 6- 40%, Streptococcus pyogenes in 6%, Staphylococcus aureus in 12%, Neisseria meningitidis in 4- 27% and Gram negative bacteria in 13%. If these are regarded as normal commensal flora, one is left in serious doubt as to the usefulness of nasal swabs in the treatment of infective rhinosinusitis.

Thus swabs are carefully taken from the middle meatus of the actively infected nose to increase the chances that any cultured organism is responsible for the infection and not merely commensal. The optimal material for a culture is pus aspirated from the infected sinuses. Those cases in which no significant growth is found may relate to failure to culture the responsible organism or may be accounted for as according to Messerklinger’s suggestion that mucosal apposition can lead to stasis and persistent inflammation. [10] Swabs can be very useful for diagnosis of fungus, though it is better to take tissue biopsy from the sinuses and send it to the laboratory in saline without delay.

 

 
Fig 2 : Coronal CT scan showing acute sinusitis with air fluid level
 
Fig 3: Axial CT scan showing chronic ethmoidal sinusitis

Blood tests

Besides routine investigations like a complete blood count and a differential count and ESR, liver function tests are required to detect underlying diseases predisposing to infection. It is crucial to test immunological host defences. [11] This can be done by testing serum for deficiency of IgG, IgA and IgM. In this way panhypogammaglobulinaemia and selective antibody deficiency can be diagnosed.

Management

Rhinosinusitis involves interplay of a vast number of factors. Treatment remains on many occasions empirical and directed mainly towards symptomatic relief. Judicious use of pharmacological agents makes it possible in most instances to completely manage the patient by medical treatment. However, there do remain a few cases where surgery is strongly indicated. As a broad dictum, it may be borne in mind that presence of anatomical obstruction to sinus drainage makes surgery mandatory, whereas physiologic obstruction may be treated satisfactorily by pharmacotherapeutic agents. However the importance of medical management is that it is considered an adjunct even to surgery of the sinuses, both pre as well as post operatively.

Therapeutic Agents

Multiple classes of drugs are used to provide symptomatic relief as well as to afford a cure. Antibiotics, analgesics, antihistaminics, decongestants, mucolytics, steroids, cromolyn and immunotherapeutic agents all are present in the armamentarium of the otorhinolaryngologist.

Acute sinusitis warrants treatment with an antibiotic at least for a period of 10 days. They may sometimes be required for 2- 6 weeks. Inadequate or no response to appropriate antibiotic treatment implies either presence of anaerobic / atypical organisms or B lactamase producing organisms.

Analgesics help to provide symptomatic relief from headache, facial pain. Aspirin and codeine derivatives give adequate pain relief. Ibuprofen and paracetamol, either singly or in combination may be used.

Alpha adrenergic agents can be used topically as well as systemically. They reduce oedema of the mucous membranes, help aeration of the sinuses and facilitate drainage of mucus. Topical decongestants (Xylometazoline, Oxymetazoline) are preferred over systemic ones to avoid systemic side effects. However using them for more than 7 days causes a rebound effect thereby limiting their use in chronic sinusitis. Phenyl propylamine (upto 150 mg / day) and phenylephrine (upto 240 mg / day) are useful and preferred systemic decongestants. When combined with antihistaminics, they help combat sedation and thus prove useful adjuncts. But they cannot be used in patients with hypertension, benign enlargement of the prostate, narrow angle glaucoma and those on treatment with tricyclic antidepressants and MAO inhibitors.

Antihistaminics mainly help to combat symptoms and allergy. They cause drying of secretions and formation of thick viscid mucus. They may in fact occasionally cause aggravation of acute sinusitis. Terfenadine, cetirizine, astemizole and loratidine are among the commonly used ones. Fexofenadine is a new non-sedating antiallergic which promises to give good results. Levocabastine, a topical antihistaminic agent is currently under investigation.

Mucolytics help drainage of the sinuses by liquefying thick and viscid secretions. Acetylcysteine, carbocysteine, bromhexine and ambroxil are commonly used.

Nasal toilet plays a similar role by helping to dislodge mucus crusts and promote drainage. Saline nasal sprays, irrigations, steam inhalations can also be used.

Steroids are used locally as well as systemically. Systemic use is reserved for cases where a severe allergic component is present. Local steroids are preferred due to the lesser incidence of side effects. However regular follow up is required to detect local complications of therapy such as nasal crusting, epistaxis, septal perforations and localised candidiasis. Though steroids decrease oedema and inflammation, they need to be avoided or carefully used in patients with active infection. As the action of steroids used locally depends on the area of mucous membrane coming in contact with the drug, they should preferably be used after decongesting the nose. Continuous use for at least a week is required before clinical improvement is noticed. Different steroid preparations used are:

Dexamethasone 2 puffs / nostril twice daily

Beclomethasone 8 puffs / day, equivalent to 336 micrograms / day

Budesonide and Flunisolide are also used. Flutecasone, a newer steroid is currently under study.

Endoscopically guided sinus beclomethasone instillation should be considered for the treatment of refractory postoperative sinus polyposis or oedema.

Ipratropium, a semi-synthetic anti cholinergic is useful for perennial rhinitis to reduce watery rhinorrhoea. It is used as 40 - 80 micro grams, twice daily as a nasal spray.

Cromolyn sodium has been tried in allergic rhinitis with good results. It stabilises mast cells and inhibits release of histamine, leucotrienes, prostaglandins and thromboxane. It acts on the acute as well as the late phase of the allergic response. Cromolyn can be used locally to good effect with the help of a pump, 4 times a day.

Immunotherapy or hyposensitisation is yet another therapeutic modality targeted towards treating the allergic component of rhinosinusitis. It works on the principle that graded treatment with inciting antigens helps to develop IgG4 blocking antibodies. It is indicated in severe cases of allergic or perennial rhinitis not showing adequate response to pharmacotherapeutic agents or where the allergen is not easily avoidable. While employing immunotherapy one has to be ready at all times to tackle possible anaphylactic reactions.

Acute Sinusitis

Acute purulent sinusitis warrants antibiotic treatment for at least 10 days to prevent relapses and to effect a complete cure. No guidelines can take the place of knowledge of local trends of infection and antibiotic sensitivity patterns. Amoxycillin can be used as a first line drug, as it is active against streptococcus pneumoniae, haemophilus influenzae and branhamella catarrhalis. Staphylococcal, anaerobic, gram negative and Beta lactamase producing bacterial infection does not respond to amoxycillin. In such cases co-amoxyclav can be given. Azithromycin, cefixime and cefuroxime are other antibiotics that can be successfully used. In sinusitis not responding to the above treatment, antral lavage with aerobic and anaerobic culture of the washings is done and appropriate antibiotic therapy is instituted. In patients with anaerobic infections, metronidazole is added with amoxycillin, or co-amoxyclav or clindamycin is given. In immunocompromised patients it is better to reach a bacteriological diagnosis and then start therapy with the right antibiotic.

First and second line choices of therapy

First line therapy

First / Second line therapy

Agents for complications of sinusitis
With intracranial complications

Third generation cephalosporin (cephtriaxone, ceftazidime) + oxacillin / nafcillin or vancomycin æ metronidazole

With orbital complications

Third generation cephalosporin + clindamycin or antistaphylococcal PCN or vancomycin; cefuroxime axetil; ampicillin / sulbactam

With odontogenic sinus / soft tissue complications

Clindamycin æ Penicillin

Second or third generation cephalosporin + clindamycin / metronidazole

Ampicillin / sulbactam

Decongestants serve as useful adjuncts by shrinking infected swollen oedematous nasal mucosa and thereby improving airway and assisting drainage of the sinus. Analgesics are needed to provide symptomatic relief.

Failure of medical line of treatment is indicated by increase in pain and other symptoms, signs of incipient complications. In such cases, surgical intervention to drain pent up pus is required. It also helps to restore ciliary activity, achieves drainage and aids ventilation of the sinus helping the mucosa to regenerate.

Chronic Sinusitis

It presents a more challenging diagnostic and therapeutic problem. The fact that an infection has progressed to a chronic state indicates the presence of some anatomic or physiologic aberration. Ciliary dyskinesias are primarily the result rather than the cause of chronic sinusitis. Patients with chronic sinusitis of uncertain origin exhibit a prominent loss of differentiated epithelial cells, as well as ciliary defects, most of which are likely to be secondary to the chronic disease process. [12] These changes slow down mucociliary clearance and lead to a vicious cycle leading to chronicity. Thus restoration of correct mucosal apposition, continuity and sinus ventilation depend on the identification and correction of these factors.

Chronic sinusitis can occur after inappropriate or inadequate treatment of an acute infection. Infection due to atypical or anaerobic organisms can also lead to chronic sinusitis. If it fails to show response to treatment with routine antibiotics, a trial with metronidazole, clindamycin or coamoxyclav can be tried. As mentioned earlier prolonged treatment for 2 - 6 weeks may be required.

Thick, viscid, sticky secretions especially in the middle meatus form a sine qua non of chronic maxillary sinusitis. Clearance of these secretions alone can lead to better drainage of the affected sinus. Thus simple measures like increased water intake, steam inhalations must be stressed. Mucolytics give an added advantage. Saturated solution of potassium iodide (SSKI) has been traditionally used to promote mucolysis and help expectoration. However there is not enough documentation to recommend this mode of treatment.

Simple measures like improving nasal hygiene are very important. Nasal toilet is aimed at cleaning the nasal cavity and ridding it of thick and viscid secretions. Saline nasal sprays are commercially available but saline taken in a Higginson’s syringe is as effective. Steam inhalations to liquefy crusts and hot fomentation to the face to relieve pain are useful.

Topical steroids used after adequate nasal decongestion reduce oedema and inflammation. Instillation in the head down and forward position, they have been shown to affect the sinus ostia directly and achieve better drainage. They are to be used continuously for at least 2 weeks to have optimum effect. Thus they are not of much use for quick fire relief. Beclomethasone, 2 drops per nostril twice a day has been shown to be as effective as 1.15 mg of oral prednisolone.

Allergic Rhinitis

In these patients sinusitis occurs due to oedematous mucosa obstructing the sinus ostia causing retention and secondary infection of secretions.

The clinical features of allergic sinusitis include a low incidence and degree of postnasal discharge and a low rate of detection of bacteria. The sinus effusion is characterised by the presence of more activated eosinophils, and IL-5 than in those of chronic sinusitis. [13]

Nasal allergy is statistically related to inflammatory chronic sinusitis as a risk factor. Similarities in symptoms, eosinophils and mediators of inflammation in the mucosa have been found between allergic rhinitis and sinusitis. 1) Symptoms are common to both perennial nasal allergy and chronic ethmoidal sinusitis, 2) medical treatment failure in allergy must require a CT scan of the sinuses to assess a possible accompanying chronic sinusitis, 3) chronic ethmoidal sinusitis is probably the leading factor responsible for nasal symptoms such as rhinorrhoea and nasal obstruction when associated with perennial allergy. [14]

Antihistaminics compete and block histamine receptors. They prevent but do not reverse the action of histamine. Therefore they should be taken prior to anticipated exposure to offending agent. Tachyphylaxis is seen and changing the class of the antihistaminic can help to maintain effect. They also alleviate symptoms like sneezing, post nasal discharge, itching and rhinorrhoea due to their antimuscarinic effects. They need to be used cautiously in acute sinusitis as drying of secretions may lead to decreased drainage and worsening of symptoms.

Decongestants induce alpha receptors in nasal mucosa causing vasoconstriction and decrease in the swelling of mucosa. Used with antihistaminics they balance the sedative action of antihistaminics and hence a larger dose can be given. They are to be avoided in patients with benign enlargement of the prostate, glaucoma, hypertension and ischaemic heart disease. Excessive topical use can lead to rhinitis medicamentosa and hence they may be given systemically.

Cromolyn sodium prevents mast cell degranulation and has the best effect if given before exposure to the inciting allergen.

Sinusitis of Dental Origin

Acute or chronic sinusitis may be odontogenic. Bacteria involved in odontogenic sinusitis are specific organisms associated with the teeth (Streptococcus sanguis, Streptococcus salivarius, Streptococcus mutans, and anaerobic germs). They are often secondary to an intrasinus foreign body following periodontitis. The treatment is both naso-sinusal and dental. Cysts of the maxilla can also invade the sinus. In particular, radiculo-dental cysts (periapical) must be surgically excised, in some cases associated with a middle meatotomy. Finally, one should look for oro-antral fistulae. The surgical technique for its closure should take into account the reversibility of the sinus lesions. [15]

Paediatric Rhinosinusitis

In children, sinusitis is a common, generally uncomplicated disease that drops with age. The diagnosis is difficult because of relatively non-specific signs and symptoms that overlap with viral upper respiratory infection and allergy. Plain paranasal sinus radiographs are not adequate, in determining the extent of involvement in recurrent or chronic sinusitis, and so CT scan has become the standard. Viral illness appears to be the most common predisposing factor. Immune defects may exist in a significant percentage of children.

The role of allergy seems less important. With advances in the genetic field of cystic fibrosis, genetic factors are advocated in chronic or recurrent sinusitis.

The most common bacterial pathogens in paediatric sinusitis patients are streptococcus pneumoniae, haemophilus influenza and moraxella catarrhalis. Other less frequent bacterial species include group A streptococcus, group C streptococcus, streptococcus viridans, peptostreptococcus, moraxella species and eikenella corrodens. Respiratory anaerobes are not common. Antibiotics resistant to the action of the beta-lactamase, are the cornerstones in medical treatment. In recurrent acute sinusitis prophylactic antimicrobials may be helpful. The indication for surgery remains controversial. To date, we have no prospective studies comparing surgical to medical therapy in order to guide us in deciding surgical indication. It is therefore recommended to follow a conservative track and to limit surgical procedures in children with suppurative complications, nasal obstruction from polyposis or refractory sinusitis aggravating chronic pulmonary disease such as asthma16. A stepped treatment approach to refractory sinusitis can improve quality of life for children and caregivers. Additional antibiotic therapy and adenoidectomy should be considered before FESS.

REFERENCES

  1. Puhaka T, Makela M J et al. Sinusitis in the common cold. J Allergy Clin Immunol 1998 Sep; 102(3): 403-8
  2. Wilson R, Roberts D and Cole P J. Effect of bacterial products on human ciliary function in vitro. Thorax, 1985; 40, 125-131
  3. Mcnabb P. C. and Tomasi T. B. (1981). Host defence mechanisms at mucosal surfaces. Annual review of microbiology, 35, 477 - 496.
  4. Frederich J. and Braude A. Anaerobic infection of the paranasal sinusitis. New England Journal of medicine, 290, 1981;135-137.
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  6. Meikle D, Yarington C T and Winterbauer RH. Aspergillosis of the maxillary sinus in otherwise healthy patients. Laryngoscope, 1985; 95, 776-779
  7. Zinreich J. Imaging of inflammatory sinus disease. Otolaryngologic Clinics of North America, 1993; 26, 535-547.
  8. Jenson C and Sydow C. Radiography and ultrasonography in paranasal sinusitis. Acta Radiologica, 1987; 28, 31-34
  9. Gwaltney J M and Hayden F G, The nose and infection in The nose : upper airway physiology and the atmospheric environment, edited by D. F. Proctor and I. Andersen. Amsterdam : Elsevier Biomedical Press. 1982; Pp. 399-422.
  10. Messerklinger W. Endoscopy of the nose Baltimore : Urban and Schwartzenberg 1978.
  11. Cole P J. investigation of disordered respiratory defences. Clinics in Immunology and Allergy 1985; 5, 549 to 568
  12. Al-Rawi MM, Edelstein DR, Erlandson RA. Changes in Nasal epithelium in patients with severe chronic sinusitis: a clinicopathologic and electron microscopic study. Laryngoscope 1998 Dec; 108(12): 1816-23.
  13. Suzuki M Suko T, Sakamoto N, Mogi G. Clinical features and characteristics of paranasal sinus effusion in allergic sinusitis. Nippon Jibiinkoko Gakkai Kaiho 1998 Jun; 101(6): 821-8.
  14. Bertrand B, Eloy P, Rombeaux P. Allergy and sinusitis. Acta Otorhinolaryngol Belg 1997;51(4) : 227-37
  15. Bertrand B, Rombaux P, Eloy P, Reychler H. Sinusitis of dental origin. Acta Otorhinolaryngol Belg 1997;51(4) : 315-22
  16. Daele JJ. Chronic sinusitis in children. Acta Otorhinolaryngol Belg 1997;51(4) : 285-304

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