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INTRODUCTION CHRONIC rhinosinusitis has many forms. It constitutes one of the most common conditions encountered in medicine and may present to a wide range of clinicians.
Chronic rhinosinusitis (CRS) is an umbrella term and represents a group of disorders with different patho-physiologies, all producing a simi-lar constellation of clinical signs and symptoms. According to the European Position Statement on Rhinosinusi-tis and Nasal Polyps (EPOS) chronic rhinosinusitis in adults is defined as inflammation of the nose and para-nasal sinuses characterised by two or more symptoms, one of which must be “nasal obstruction, blockage or congestion” and the other, either ante-rior or posterior nasal discharge.1
Other ‘minor’ symptoms described include facial pain or pressure and loss of smell. The symptoms must be accompanied by either endoscopic findings, such as nasal polyps, mucopu-rulent discharge and mucosal oedema, or radiologic changes of mucosal swell-ing on computed tomography (CT).
Additionally, EPOS stipulates that these symptoms must last longer than
12 weeks without resolution, in con-trast to acute rhinosinusitis which lasts less than 12 weeks with complete symptomatic resolution.
Most of these symptoms are, how-ever, not specific to chronic rhinosi-nusitis, and are shared with other common sinonasal pathologies. Exam-ples include nasal obstruction and dis-charge commonly seen in rhinitis2; post-nasal drip (PND) that is a com-mon symptom of laryngopharyngeal reflux, and facial pain which is more likely a symptom of migraine or myo-fascial headache than a true sinus headache.3,4 It is therefore important to distinguish sinusitis from these other clinicopathological entities, as the management differs significantly.
The approach to diagnosis and management for CRS has changed substantially over the past decade. This How to Treat explores the recent advances in understanding of the pathophysiology of the disease, and the current paradigms for manage-ment. Additionally, it outlines the ini-tial medical management options that can reasonably be offered in the pri-mary care setting prior to referral to tertiary rhinology practice.
PATHOPHYSIOLOGYOUR understanding of the patho-physiology of chronic rhinosinusi-tis has changed significantly over the past few decades.
For many years, this condition was thought to be the result of sinus out-flow obstruction, particularly in the narrow channels of the osteomeatal complex. The latter is the common outflow tract from the frontal, ante-rior ethmoid and maxillary sinuses to the nasal cavity that mucociliary drainage follows. These obstructions cause inflammation and recurrent secondary bacterial infections.
However, more recently there has been increasing recognition that, in a similar manner to chronic lower airway diseases such as asthma, the major underlying driver of disease is a disordered chronic inflammatory reaction.
Rather than simple obstruction, several factors contribute to the development of chronic rhinosinus-itis.5 These include a genetic pre-disposition, inflammation, poor anatomy and secondary infections leading to biofilm formation. A pre-cipitating infection with either
Staphylococcus aureus or a virus such as RSV often sets the chain of events in motion.6 As the key issue is inflam-matory, all treatment options should be geared to managing inflamma-tion and not focused on the infective component.
The varying pathophysiological mechanisms manifest in a few clini-cally relevant phenotypes of chronic rhinosinusitis. These are defined by observable characteristics or traits identified on nasendoscopy.
The most obvious of these is the presence or absence of nasal polypo-sis. Therefore, this condition is com-monly categorised into cases with nasal polyps (CRSwNP) and those without (CRSsNP). However, these phenotypes provide only limited insight to the cellular and molecular pathophysiological mechanisms.
Therefore, contemporary views rely on the classification of chronic rhinosi-nusitis into various groups of biologi-cal subtypes, also known as endotypes. These are derived from histopathologi-cal biomarkers which better predict the patient response to different treat-ments. Recognition of such biomarkers has led to the development of routine
Chronic rhinosinusitis
NEED TO KNOW
Chronic rhinosinusitis, while common, is characterised by many non-specific symptoms which are also present in other common conditions.
Current treatment paradigms focus on treating ‘endotypes’ based upon mucosal histopa-thology, rather than phenotype.
Many patients with chronic rhi-nosinusitis can be adequately managed conservatively with courses of appropriate medi-cal therapy, consisting of saline douching, oral corticosteroid and antibiotic therapy.
Surgery is rarely curative. The purpose of surgery is to provide wide access for augmentation of mechanical irrigation and to facilitate transition from oral to topical corticosteroid delivery. Long-term compliance to treat-ment is key to avoid failure and revision surgery.
Dr Eugene Wong (left),ENT registrar currently working with NSW Health and completing his PhD under the supervision of Associate Professor Larry Kalish.
Associate Professor Larry Kalish (right),consultant ENT surgeon, tertiary rhinologist and Head of Department at Concord Repatriation General Hospital and active senior member of the Rhinology and Skull Base Research Group in Sydney, NSW.
This information was correct at the time of publication: 24 July 2020
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16 HOW TO TREAT: CHRONIC RHINOSINUSITIS 24 JULY 2020 ausdoc.com.au
histopathological profiling reports in practice.7
EPIDEMIOLOGY CHRONIC rhinosinusitis is widely believed to be a common disease with a reported prevalence of approxi-mately 10-15% in published studies.8,9
However, the true prevalence is diffi-cult to capture; significant differences can result from potential regional var-iations secondary to climate and pop-ulation profiles, sociodemographic and economic factors, health and life-style behaviours, access to health-care services, functional capacity and nutrition status.10-14
In addition, differences in the diag-nostic criteria used introduces selec-tion biases, particularly when relying purely on subjective symptoms which carry considerable overlap with many other common pathologies. Neverthe-less, large-scale accrual of objective endoscopic or radiologic evidence is often not feasible, leaving question-naire surveys as the usual population- level investigation for chronic rhinosinusitis.
The 2008 Global Allergy and Asthma European Network (GA2LEN) questionnaire-based survey, based upon the EPOS guidelines, found that 10.9% of 57,128 respondents met the subjective diagnosis for this condi-tion.15 Early unpublished literature on the Australian population reveals a similar trend.16 Based on 19,259 respondents of the National Health Survey 2014/15 conducted by the Australian Bureau of Statistics, prev-alence was estimated to be approx-imately 8.4%, affecting 1,940,000 Australians. This is a similar preva-lence to that of depression (8.9%) and more common than diabetes (5.1%) and ischaemic heart disease (3.3%). There was a preponderance towards older females, and those living in regional or remote areas.17
What is often poorly appreciated is the frequently debilitating bur-den of disease experienced by those with chronic rhinosinusitis. In addi-tion to the well-recognised sinona-sal symptoms, other wide-ranging consequences impact on quality of life. These ‘extra-rhinological’ symp-toms, including poor sleep, fatigue,
concentration loss, poor productiv-ity and psychological sequelae play a significant role in morbidity.18
With its relatively high prevalence and substantial impact on quality of life, chronic rhinosinusitis carries a substantial burden to society. The condition has been found to carry a mean utility value of 0.65 (on a scale where 1.0 represents perfect health and 0 represents death), a value lower than Parkinson’s disease, coronary artery disease, congestive heart failure and moderate chronic obstructive pulmonary disease.9,19-23
The direct economic burden is estimated to be high, at around $8.6 billion a year in the US, with further indirect costs secondary to reduced productivity estimated at $12.8 billion.24,25
Risk factors and associated conditions Despite ongoing active investigation, the risk factors for CRS remain con-troversial. However, in a manner sim-ilar to other aerodigestive diseases of disordered inflammation, the patho-genesis is thought to be multifacto-rial, involving genetic predisposition, presence of comorbid conditions and environmental exposures.
The peak incidence of CRS appears to present between the fourth and sixth decades of life, and
females appear to have a higher rate of CRSsNP phenotype while males appear to exhibit more CRSwNP.6
Many genes and their mutations have been associated with the devel-opment of CRS, including those involved with ion channels, type 2 inflammation, tissue remodelling and arachidonic acid metabolism.6 Several genes are proposed to be associated with specific phenotypes and endo-types of CRS. These findings have not changed current clinical practice and are outside the scope of this article.
Some monogenic disorders do carry significant clinical implications and cause particularly severe disease. These syndromes primarily cause an absence of normally functioning mucocilary clearance and include cystic fibrosis, primary ciliary dyski-nesia and Kartagener’s syndrome.
Environmental factors associated with an increased risk of CRS include smoking and air pollution.6 Aspirin- exacerbated respiratory disease, or Samter’s triad, refers to a subgroup of patients who have asthma and
CRSwNP, and experience severe exac-erbations of symptoms after expo-sure to aspirin or other non-steroidal anti-inflammatory drugs.26
Another condition to note, Churg-Strauss syndrome or eosinophilic granulomatosis with polyangiitis, is a small-vessel systemic vasculitis of unknown cause that presents as multi-organ eosinophilic infiltrative disease (including rhinosinusitis) and granulomatosis following an initial phase of allergic rhinitis and asthma.27
CRS in children A diagnosis of true chronic rhinosi-nusitis is rare in the paediatric pop-ulation. Most children who present with sinonasal complaints usually have allergic rhinitis, and any para-nasal sinus involvement is driven by underlying allergy. The small num-ber of true chronic sinusitis occurs in patients with comorbid conditions such as cystic fibrosis or primary ciliary dysfunction.
As true sinusitis is rare in a child, when present it should raise suspi-cion of an underlying genetic pre-disposition, such as cystic fibrosis, primary ciliary dyskinesia or Kartagener’s syndrome.
If true chronic rhinosinusi-tis is present, extensive sinus sur-gery is avoided because of concerns regarding impairment of midfacial growth. These children are therefore treated conservatively where possi-ble. Courses of appropriate medical treatment for symptomatic control are used during exacerbations until they reach adulthood, when surgery is no longer contraindicated. There is also a belief that bacterial superinfec-tion plays a larger role in paediatric CRS, and therefore several courses of broad-spectrum and culture-directed oral antibiotics are often prescribed in addition to appropriate medical treatment.28 Endoscopic sinus surgery (ESS) is typically reserved only for
cases when red-flag symptoms arise in the emergency setting.
CLINICAL PRESENTATION THERE is often considerable discord-ance between the patient and the ENT’s diagnosis of chronic rhinosinus-itis.29 Patients often present convinced that they are experiencing the condi-tion or ‘sinus’ even though their con-stellation of symptoms, examination findings and radiologic features do not support that diagnosis. It is often a dif-ficult task for the ENT to convince the patient that their diagnosis is some-thing other than chronic rhinosinusitis.
Chronic rhinosinusitis is a symptom-based diagnosis but always needs correlation with endoscopic and/or radiologic findings as well. As previously mentioned, many symp-toms are more commonly associated with other conditions (see box 1).
Red flags requiring immediate referral are discussed later.
Nasal obstruction This is present in several conditions but is most commonly secondary to an anatomical cause (such as a devi-ated nasal septum, see figures 1A and B) or rhinitis. In rhinitis, inflamma-tion is confined to the nasal cavity and is associated with reactive vascular changes, glandular hypertrophy and mucosal oedema.
In contrast, chronic rhinosinusitis is characterised by mucosal inflam-mation and polypoid changes within the paranasal sinuses, and the nasal airway tends to be less congested. Patients with rhinitis have more air-way oedema but, paradoxically, have a better sense of smell, while those with chronic rhinosinusitis can have almost normal nasal airway but have reduced smell (hyposmia). Similarly, patients with a patent airway but sinus con-gestion may feel ‘obstructed’. Studies have demonstrated that many patients who believe they have recurrent acute sinusitis have rhinitis, based on CT imaging during the acute event.30
Post-nasal drip This symptom is often attributed to chronic rhinosinusitis. The paranasal sinuses produce 1.5L of mucus daily
Box 1. Differential diagnoses and overlap syndromes
The features of chronic rhinosinusitis may overlap or coexist with the following:• Pain syndromes: Facial pain may be present in migraine headaches,
tension headaches, cluster headaches, dental pathology or other facial pain syndromes.
• Rhinitis without sinusitis: This may occur in rhinitis medicamentosa, seasonal or perennial allergic rhinitis, or idiopathic rhinitis. Patients do not fulfill the criteria for chronic rhinosinusitis and the nasal secretions are usually not mucopurulent. Rare causes include foreign body reaction, cerebrospinal fluid (CSF) leak and tumours.
• Laryngopharyngeal reflux: This variant of gastroesophageal reflux may be associated with post-nasal drip, hoarse voice, globus pharyngeus sensation and throat clearing.
• Olfactory disorders: Resulting from nasal or paranasal sinus disease, URTI or head trauma. Anosmia or hyposmia is a common finding in patients with CRS. Cachosmia and dysosmia (foul smell or distorted smell) is less suggestive of chronic rhinosinusitis and typically represents other sinonasal or neurological disease.
Figure 1A. Rhinoscopy using a Thudichum speculum demonstrating a nasal septum deviation to the left. Figure 1B. Coronal CT imaging confirming severe septal deviation to the left.
Prevalence was estimated to be approximately 8.4%, affecting 1,940,000 Australians — a similar prevalence to that of depression.
A B
HOW TO TREAT 17ausdoc.com.au 24 JULY 2020
as part of the humidification of the air we breathe through the nose. This mucous naturally runs down the back of the throat.
If the throat is inflamed, patients may become aware of what is normal physiological mucous. A significant proportion of patients who report PND have laryngopharyngeal reflux.31 Laryngopharyngeal reflux causes chemical irritation and inflamma-tion of the pharynx and larynx, often leading to discomfort and foreign- body sensation. Patients are often unable to differentiate these sensa-tions from PND, as visceral inner-vation to the pharynx and larynx is vague. PND as a standalone symptom is never enough to make the diagno-sis of chronic rhinosinusitis.
Facial pain or headaches Chronic rhinosinusitis rarely causes facial pain or headaches. Recent stud-ies have shown that most patients who believe they have ‘sinus head-aches’ have no sinus disease at all, and symptoms are usually attributable to muscle tension headaches (myofas-cial pain), migraines (with or without aura) or atypical facial pains.32 In fact, recent reviews have shown that in patients presenting with self-declared ‘sinus headaches’, only 3% can be attributed to rhinogenic headaches.32
Notable exceptions to this are dis-eases involving the sphenoid sinus, which may present as a ‘vertex’ head-ache located at the occiput and occa-sionally at other sites, and iatrogenic obstructions or post-sinus surgery failure.33 Iatrogenic obstructions or post-sinus surgery failure may lead to headaches isolated to the site of the obstructed sinus, for example frontal sinus headaches which are felt under the medial portion of the eyebrow.
These headaches are site-specific and usually unilateral with the history of previous surgery and are easily dif-ferentiated from a ‘sinus headache’, which is often described as band-like pain across forehead or ‘goggles-like’ distribution around both eyes.
Smell Hyposmia (reduced sense of smell), is much more specific to chronic rhinosinusitis. Olfactory neuroepi-thelium is located high in the nasal cavity, and is thought to include the superior nasal septum, cribriform plate, superior turbinate and superi-or-lateral nasal wall. Chronic rhinosi-nusitis causes polypoid change and mucosal inflammation often result-ing in obstruction of inhaled particles into the neuroepithelium, leading to olfactory dysfunction.34 Oedema and fluid in the sinuses also limit space for olfactants to circulate.
As loss of smell is more likely in patients with sinusitis than rhinitis, it is often a differentiating feature. A patient with allergic rhinitis who pre-sents with severe oedema and nasal polyps but has retained a good sense of smell is more likely to have cen-tral compartment atopic disease. A patient with minimal nasal oedema and reasonable airway, but marked hyposmia, is more likely to have underlying sinusitis.
ENT surgeons often use validated quality of life questionnaires to mon-itor the symptom changes. These include the Sinonasal Outcome Test (SNOT-22), a questionnaire assess-ing the severity of 22 sinonasal and ‘extra-rhinological’ symptoms on a five-point Likert scale.35,36
ASSESSMENT EXAMINATION of the patient begins with inspection of the external nose and anterior rhinoscopy aided by a headlight. This may reveal structural abnormalities such as septal devia-tions, enlarged inferior turbinates or valve collapse that can cause nasal obstruction. Obvious nasal polyps and mucopurulent discharge may be seen on anterior rhinoscopy.
In-office nasendoscopy is usu-ally required to examine the patency of the major outflow tracts of the sinuses. Assessment is also made regarding the presence of polyps (see figure 2), any mucopurulent dis-charge and the degree of mucosal inflammation. For complete assess-ment, the nasendoscope is often passed through the nose to view the pharynx and larynx. Changes associated with laryngopharyngeal reflux can often be identified here.
Investigation If chronic rhinosinusitis is suspected based on the patient’s history and examination, CT of the paranasal sinuses is used to confirm the diag-nosis (see figure 3.) Low-dose CT imaging is an option as bony
windows are satisfactory in deter-mining the bony anatomy and excluding most sinus pathologies. This reduces the radiation exposure for the patients and allows repeat scans to be performed if required.
Close inspection of bony anat-omy is required to appreciate if the mucosal inflammation is the primary problem or if there are structural anatomical reasons for obstruction, such as large infraor-bital cells blocking the maxillary outflow tract. Additionally, the paranasal sinuses demonstrate considerable variability between patients, and CT imaging is criti-cal in the planning of any surgical intervention.
In the context of an asymptomatic patient who presents with a report detailing incidental findings charac-teristic of CRS, the authors recom-mend referral to an otolaryngologist to rule out other conditions that require further intervention, such as an inverting papilloma or a fungal ball. However, if no other concern-ing features are present, there is lit-tle role in pursuing treatment for an asymptomatic patient.
The association between allergy and chronic rhinosinusitis is ill- defined in the literature and remains controversial.37 Recent evidence has suggested that a specific phenotype of chronic rhinosinusitis may occur secondary to inflammation of the nasal mucosa from inhalant allergy that causes sinus outflow tract
obstruction (central compartment atopic disease).38 Nevertheless, many surgeons will elect to investigate for inhalant allergy — through skin-prick tests or radioallergosorbent test-ing (RAST, serum specific IgE to aer-oallergens) to assess for concurrent inhalant allergy.
Red flags requiring immediate referral While emergency complications of CRS are rare, there are red-flag signs alerting the GP that urgent referral to hospital is required. Primarily, these complications occur secondary to invasive acute bacterial superinfec-tion of adjacent structures. These are typically grouped into intracranial, bony (osseous) and orbital structures.
Intracranial complications occur when infection breaches the skull base and enters the cranial vault, predisposing a patient to meningitis, encephalitis or an intracranial collec-tion. Consider this in patients with new-onset focal neurological signs, clinical examination findings sugges-tive of meningitis or reduced level of consciousness.
Orbital complications range from periorbital and orbital cellulitis, orbital abscess, and cavernous sinus throm-bosis, which may present as periorbi-tal erythema or oedema, reduced visual acuity, diplopia and ophthalmo-plegia or a displaced globe.39
Bony osteomyelitis most com-monly affects the frontal bone, and when associated with a subperiosteal
abscess is termed a Pott’s Puffy tumour, typically presenting as fluc-tuant frontal swelling and may lead to venous spread of infection into the cranial vault.40
MANAGEMENTTHE decision to pursue treatment remains predominantly driven by the patient. As chronic rhinosinusitis is a disease that affects a patient’s quality of life, even those with severe disease on radiology or endoscopy may find that their symptoms are manageable and do not elect to undergo any further treatment.
Symptomatic patients usually war-rant maximal medical therapy unless there are any specific contraindica-tions.41 This term has now been changed to appropriate medical treat-ment, and although all guidelines agree medical management must be trialled first, there is no consistency on what appropriate medical treat-ment entails.42
The appropriate medical treatment differs between chronic rhinosinusitis with polyps and chronic rhinosinusitis without polyps.
Patients with chronic rhinosinusi-tis with polyps benefit from saline irrigations (see figure 4), topical intra-nasal corticosteroids and oral corticosteroids.34
The role of oral antibiotics is more controversial and remains an option. As emphasised previously, this is an inflammatory condition and not an infective one. Secondary bacterial
infection can, and often does, compli-cate chronic inflammatory states. Cul-ture-directed oral antibiotics are preferred, while oral amoxicillin and clavulanic acid or azithromycin are options for empiric treatments.40
These courses are short and only given together with topical and oral corticosteroids so that the inflamma-tory component settles.
Patients with chronic rhinosinusi-tis without polyps benefit from saline irrigations and topical intranasal cor-ticosteroids. The role of oral corticos-teroids is more controversial and may be an option.
Again, short-course oral antibiotics may play a role if there is secondary bacterial infection. Longer-term mac-rolide antibiotics, effective because of their anti-inflammatory rather than bacteriostatic properties, are often indicated at low doses for six weeks to three months.43 They are most effec-tive in non-eosinophilic endotypes which make up the majority of, but not all, cases of CRS without polyps.
Evidence demonstrates that treatment courses should be longer than four weeks for more effective outcomes.5
Following appropriate medical treatment, surgeons typically elect to assess response by repeating the SNOT-22 questionnaire, endoscopic examination (see figure 5) and CT imaging. Many patients will experi-ence significant benefit with appro-priate medical treatment and can be managed conservatively with this
Figure 2. Anterior rhinoscopy, with blue arrow pointing to an inflammatory polyp.
Figure 3. Coronal slices of high-resolution CT of the paranasal sinuses in bone windows.
Figure 3A. Normal sinuses. Figure 3B. Evidence of mucosal inflammation and thickening. Figure 3C. Large grade 4 obstructive polyps.
A B C
18 HOW TO TREAT: CHRONIC RHINOSINUSITIS 24 JULY 2020 ausdoc.com.au
regimen when they experience a flare-up of their disease. However, sur-gical intervention may be considered if disease remains recalcitrant despite appropriate medical treatment, or if flare-ups are so frequent that side effects of long-term oral prednisone therapy become a concern.
The aim of functional endoscopic sinus surgery (FESS) is to provide good access to all inflamed sinus mucosa.44
This facilitates a total reduction in inflammatory load, adequate ventila-tion of the sinuses, augmentation of sinus mechanical irrigation and deliv-ery of topical medicines (specifically in the transition from oral to topical prednisone delivery). It can also allow for in-office treatments and post- surgical rescue.
There is mounting evidence that more aggressive primary surgery which ensures the achievement of the above goals results in better out-comes than traditional ‘step-up’ sur-geries. The development of a large single ‘neo-cavity’ is believed to max-imise postoperative access (see figure 6).34 This paradigm shift has resulted after recognising that the greatest predictor for surgical failure is previous surgery.
Early postoperative care is critical in ensuring a good outcome. FESS causes a significant insult to sinonasal mucosa. Therefore, patients are dis-charged home on regular saline douching to clear crust and clot build-up, as well as a short weaning course of oral prednisone. Regular and
frequent follow-up is required in the early postoperative period for in-office debridement of inflammatory debris.
Long-term follow-up is typi-cally defined by chronic rhinosinus-itis endotype, which is determined from histopathological analysis of a mucosal specimen taken at surgery. As this is predominantly a chronic disor-der of mucosal inflammation, surgery is not curative, but simply facilitates lifelong medical management to con-trol disease.
While many endotypes exist, one notable subtype that is particularly severe and difficult to control is eosin-ophilic disease.45 In patients with eosinophilic disease, regular topical steroid application and regular sur-veillance are required. To achieve this, steroid such as budesonide 1mg/2mls for nebulising is added to saline douching in favour of simple nasal sprays for their additional efficacy, or mometasone 2mg can also be added to the rinses.46,47
Our understanding of the uni-fied airway suggests that eosinophilic inflammation may also be present in other mucosal surfaces, causing several associated diseases such as eosinophilic asthma, atopic derma-titis and eosinophilic oesophagitis. Where a clinical history of these asso-ciated symptoms is suggested, con-sider further tertiary referral to the appropriate subspecialty, as well as an immunologist.
Long-term compliance with medi-cations is critical to ensure optimal
long-term outcomes. In a recent study published by the Sydney Rhi-nology and Skull Base Research Group, patients who had excellent compliance with corticosteroid irriga-tions were mostly managed well on topical therapies alone, while those who were less compliant experienced disease recurrence and require revision surgery.34
FUTURE DIRECTIONS THIS is an inflammatory process, and eosinophilic chronic rhinosinusitis is characterised by a TH-2 inflammation. Biologicals such as mepolizumab, a humanised monoclonal antibody that selectively blocks interleukin-5, can be used with great effect. It is currently being used under the PBS for severe refractory eosinophilic asthma.48 Mepolizumab has been found to reduce the risk of asthma exacerbations in this cohort.49
Dupilumab has also shown great benefit in patients with CRS. Dup-ilumab, also a human monoclonal antibody, inhibits the signalling of interleukin-4 (IL-4) and inter-leukin-13 (IL-13). These two key cytokines play a central role in type 2 inflammation that underlies specific types of asthma, CRS and several other allergic disorders.
Given the similar pathophysiology between eosinophilic chronic rhinosi-nusitis and nasal polyposis, studies are underway to examine the effect of mepolizumab on nasal polyposis.
Early results of mepolizumab in patients with recurrent nasal polypo-sis are promising.50
CASE STUDIES Case study one ANDREA, 66, presents to a respira-tory physician complaining of chronic cough and PND following a flu-like episode six months previously.
Her medical history includes well-controlled hypertension, a previ-ous DVT and a brain aneurysm which was successfully clipped. She is not on anticoagulants. She is diagnosed with adult-onset asthma and treated with fluticasone furoate/vilanterol and salbutamol inhalers. There is some improvement in her chest tightness and a reduction in cough, but the PND persists.
Andrea is prescribed a course of corticosteroid, topical nasal inhalant spray, oral antihistamine, and uses a variety of over-the-counter medica-tions for cough. There is a good, but short-lived, response to the corticos-teroid with a brief reduction in the PND and mild improvement in her sense of smell and taste.
After stopping the corticosteoid, Andrea is more aware of a sense of facial congestion, her decreased smell and taste, and increased discoloured nasal discharge especially when blowing her nose.
Andrea is prescribed a course of amoxicillin and clavulanic acid, and a CT scan of her paranasal sinuses is performed (see figure 7). This shows
widespread mucosal changes in all the sinuses. As the CT is performed after an appropriate medical course in a patient with ongoing symptoms beyond three months, this is, by definition, CRS.
She is referred to an ENT surgeon for review. Her SNOT-22 validated QOL form (see figure 8) shows signifi-cant sinonasal symptoms. Nasendos-copy reveals a severe septal deviation and gross turbinate congestion lim-iting access. There is oedema in the middle meati bilaterally, evidence of thick mucus discharge and mucus pooling in the post-nasal space. Skin-prick allergy tests are negative.
Based on the CT and clinical find-ings Andrea is diagnosed with CRS without polyps (the phenotype). Because Andrea has failed appro-priate medical treatment and has a limited airway preventing ongoing topical treatments, it is decided to proceed with surgery.
The management plan includes bilateral full-house endoscopic sinus surgery and septoplasty. As this is an inflammatory airway disease with adult-onset asthma, the role of sur-gery is discussed in detail, highlight-ing the need for ongoing medical management postoperatively.
Surgery is successful, with the septum reconstructed and all the sinuses widely opened for maximal access. At the time of surgery there is frank pus in both maxillary sinuses and oedematous mucosa throughout, with evidence of osteitic/
Figure 6. Above: Fine-slice CT images demonstrating evidence of severe chronic rhinosinusitis in A. Coronal. B. Axial. C. Mid-saggital views. Below: Improvement following extensive sinus surgery in the same patient in D. Coronal. E. Axial. F. Mid-saggital views.
A B C
D E F
Figure 7. CT scan of the paranasal sinuses, demonstrating widespread mucosal changes in all sinuses.
Figure 5. Endoscopic images at the middle meatus demonstrating:
A. Mucosal inflammation and sumping of mucopurulent secretions. B. Resolution following appropriate medical treatment.
A B
Figure 4. A standard nasal irrigation device being used.
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20 HOW TO TREAT: CHRONIC RHINOSINUSITIS 24 JULY 2020 ausdoc.com.au
thickened bone. Mucosal biopsies demonstrate non-eosino-philic chronic inflammation. Mucus samples do not show fungal elements but grow Haemophilus influenza sen-sitive to the antibiotics prescribed. Andrea receives another course of prednisone postoperatively.
Her recovery is unremarkable and at six weeks postoperatively she is enjoying a good nasal airway, no fur-ther facial congestion, full return of her sense of smell, resolution of the PND and cough, and improved asthma symptoms. She uses sinus rinses with budesonide 1mg/2mls added into the wash to deliver into her sinuses once daily.
At six months postoperatively Andrea presents with mild increase in PND and recurrence of the cough. Nasendoscopy shows mild oedema of the sinuses and thickened mucus dis-charge. She increases her sinus rinses with budesonide 1mg/2mls to twice a day and is treated with clarithromy-cin 250mg once a day for six weeks.
She responds well to the treat-ment plan and remains well one year postoperatively (see figure 9), with well-controlled asthma. Andrea will see her ENT surgeon for an annual check-up.
Patents with sinusitis often present to respiratory physicians, immunologists and dentists with manifestations of sinusitis such as asthma, cough or referred dental pain. These patients often respond well to systemic corticosteroids and realise only after treatment that symptoms they had thought were normal, such as facial pressure or congestion, post-nasal discharge and reduced smell, are problematic.
Sinusitis flare-ups in post- operative patients are usually less symptomatic. They can easily be diagnosed on endoscopy. Because the endotype is non-eosinophilic and there is an absence of any allergy, Andrea is an excellent candidate for macrolide therapy.
Case study twoLisa, 38, has a long history of asthma and nasal congestion. She presents to her GP with worsening asthma and complete nasal obstruction on the right. She also complains of long-standing poor smell and reduced taste, persistent clear rhinorrhoea, mild facial pressure which is worse on the right and exacerbated by ‘colds’.
She has had asthma since child-hood, but her symptoms and con-trol have deteriorated as an adult. Lisa has intermittent mild allergy symptoms characterised by allergic conjunctivitis and nasal and throat pruritis. She is aspirin-sensitive, as is her father, and Lisa avoids this drug. Lisa experienced a severe reaction, with wheezing, chest tightness and nasal congestion, to ibuprofen taken for analgesia.
She had nasal polyps diagnosed and has had two ‘polypectomies’, 17 and 20 years ago, with some relief of nasal congestion after each sur-gery. Lisa is otherwise in good health, works as a physical education teacher and has never smoked.
Her medications include terbu-taline turbuhaler and budesonide turbuhaler for her asthma. She has trialled various topical steroidal nasal sprays without success and gets mild temporary relief from oral corticosteroids.
Lisa fails a short corticosteroid (five days) and oral roxithromycin course and is referred to an ENT sur-geon. The ENT initiates a five-week course of oral weaning corticosteroid, topical intranasal steroid sprays and doxycyline 100mg daily for six weeks.
Lisa then undergoes a low- radiation CT of her sinuses (see figure 10). This shows extensive opacification of all her sinuses, with double densities seen in the maxillary sinuses, consistent with inspissated eosinophilic mucus.
Given the extent of her polyps and failure to respond to appropriate medical treatment, she is referred
to a specialist rhinologist for further treatment.
Lisa undergoes comprehensive sinus surgery including a modified endoscopic Lothrop procedure (fron-tal sinus drill-out), bilateral full-house functional endoscopic sinus surgery and bilateral inferior turbinoplasty. Her histology shows an eosinophilic chronic rhinosinusitis (see figure 11).
Lisa’s overall quality of life out-come improves significantly (see figures 12 and 13), and she feels there is an aesthetic improvement as the large polyps had made her nose appear broader.
Her asthma control is stable, and the polyps are not evident at one year after using daily budesonide 1mg/2mls in a sinus rinse.
Seventeen months postopera-tively she experiences an asthma flare-up after an URTI. There was sig-nificant eosinophilic mucus but no polyp recurrence.
She is treated with a two-week corticosteroid course and introduc-ing the monoclonal antibody anti-IL-5 mepoluzimab is discussed. She will be monitored to see if she meets the PBS eligibility criteria.
AERD (aspirin exacerbated respira-tory disease) is often associated with recalcitrant CRS and usually needs ongoing intensive management. Sim-ple polypectomies offer some relief of nasal obstruction but can cause scarring and complications, invaria-bly fail, and are no longer indicated except in patients who are poor candi-dates for surgery.
Doxycycline has some anti- inflammatory properties and good anti-staph cover, so it is useful in eosinophilic CRS.
Allergic fungal sinusitis can also present with double densities but tends to be unilateral and is not often associated with AERD.
AERD and eosinophilic CRS are chronic inflammatory diseases requir-ing lifelong care. Ongoing proactive planning to maintain good
Figure 11. Lisa’s histopathological report, confirming the diagnosis of eosinophilic chronic rhinosinusitis.
Figure 8. Andrea’s preoperative SNOT22 questionnaire, demonstrating significant sinonasal symptoms impacting on quality of life.
Figure 9. Andrea’s SNOT22 questionnaire one year postoperatively, demonstrating almost complete resolution of all sinonasal symptoms.
Figure 10. Coronal CT scan of the paranasal sinuses demonstrating extensive opacification and complete nasal obstruction; close observation of the maxillary sinus shows double density consistent with inspissated eosinophilic mucous.
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22 HOW TO TREAT: CHRONIC RHINOSINUSITIS 24 JULY 2020 ausdoc.com.au
outcomes and prevent relapses are important.
CONCLUSIONCHRONIC rhinosinusitis is an umbrella term describing a common condition that presents as a vari-ety of non-specific rhinological and extra-rhinological symptoms. How-ever, when these symptoms are pres-ent alone, the cause is rarely chronic rhinosinusitis, and more commonly another pathology such as allergic rhinitis or laryngopharyngeal reflux. Management paradigms for chronic rhinosinusitis have changed sub-stantially over the past few decades as our understanding of the under-lying pathology has improved, shift-ing from categorising the disease into observable characteristics (phe-notypes) toward biological groups defined by histopathological analysis (endotypes.)
Many patients with chronic rhi-nosinusitis can be managed effectively with systemic medicines, including antibiotics and corticosteroids. How-ever, when this fails, aggressive endo-scopic sinus surgery can be pursued to facilitate effective nasal irrigation, transition of medicines to a topical route of administration and effective in-office surveillance.
Conflict of interest statementDr Eugene H Wong has no conflicts of interest to declare. Associate Professor Larry Kalish is on the speaker’s bureau for Mylan and Care Pharmaceuticals.
How to Treat Quiz. GO ONLINE TO COMPLETE THE QUIZ ausdoc.com.au/howtotreat
CHRONIC RHINOSINUSITIS
1. Which THREE features are required to make a diagnosis of chronic rhinosinusitis?
a Symptoms must last longer than 12 weeks in duration without resolution.
b Patient report of nasal obstruction/discharge with associated facial pain.
c Inflammation of the nose and paranasal sinuses character-ised by two or more symptoms.
d Symptoms must be accompa-nied by either specific endo-scopic or radiologic changes.
2. Which TWO disorders have an absence of normally functioning mucociliary clearance?
a Cystic fibrosis. b Primary ciliary dyskinesia. c Samter’s triad. d Churg- Strauss syndrome.
3. Which THREE statements regarding chronic rhinosinusitis are correct?
a Chronic rhinosinusitis has a reported prevalence of around 10-15% in published studies, but the true prevalence is difficult to capture.
b Sinonasal symptoms and ‘extra-rhinological’ symptoms both contribute to morbidity and impact negatively on quality of life.
c The condition is more common in older females, and those living in regional or remote areas.
d The condition is less common than diabetes and ischaemic heart disease.
4. Which TWO statements regarding chronic rhinosinusitis in children are correct?
a Chronic rhinosinusitis is common in children as they have multiple URTIs in a single calendar year.
b Most children who present with sinonasal complaints usually have allergic rhinitis.
c True sinusitis in a child should raise suspicion of an underlying genetic predisposition.
d Endoscopic sinus surgery is indicated early to prevent long-term complications such as growth retardation.
5. Which THREE conditions may share symptoms with chronic rhinosinusitis?
a Migraine. b Glaucoma. c Laryngopharyngeal reflux. d Seasonal or perennial
allergic rhinitis.
6. Which TWO statements regarding the presentation of chronic rhinosinusitis are correct?
a Patients with rhinitis have anosmia more commonly than do those with chronic rhinosinusitis.
b Nasal obstruction is most commonly secondary to an anatomical cause.
c Post-nasal drip as a standalone symptom is never enough to make the diagnosis of chronic rhinosinusitis.
d Chronic rhinosinusitis commonly causes facial pain or headaches.
7. Which TWO are appropriate investigations in patients with suspected chronic rhinosinusitis?
a Anterior rhinoscopy and nasendoscopy.
b Microscopy, culture and sensitivity of nasal discharge.
c Low-dose CT imaging of the paranasal sinuses.
d Full allergy panel for inhaled and ingested allergens.
8. Which THREE are red flags requiring immediate referral?
a New-onset focal neurological signs.
b Diplopia. c Fluctuant frontal swelling. d Sudden change in the amount
and colour of the nasal discharge.
9. Which TWO statements regard-ing the treatment of chronic rhinosinusitis are correct?
a Treat chronic rhinosinusitis according to international consensus guidelines.
b Patients with chronic rhinosi-nusitis without polyps may benefit from saline irrigations, topical intranasal antibiotics and oral corticosteroids.
c Patients with chronic rhinosi-nusitis with polyps may benefit from saline irrigations, topical intranasal corticosteroids and oral corticosteroids.
d Short-course oral antibiotics may play a role in some endo-types of CRS.
10. Which THREE statements re-garding the treatment of chronic rhinosinusitis are correct?
a Surgery may be considered if disease is resistant to appropri-ate medical treatment, or if flare-ups are so frequent that side effects of long-term oral prednisone are a concern.
b The aim of functional endo-scopic sinus surgery is to pro-vide good access to all inflamed sinus mucosa.
c Surgery for CRS is often curative.
d Long-term compliance with medications is critical to ensure optimal long-term outcomes.
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Figure 12. Lisa’s preoperative SNOT-22 form. Her main concerns were smell and blocked nose typical of a patient with CRS with polyps. Her global scores were poor including the cosmetic appearance, as the polyps were widening her nasal dorsum and adding fullness to the lower one-third.
Figure 13. Lisa’s SNOT-22 one year post-operatively. As well as improvements in her airflow and discharge, her sense of smell returned completely. Her global cosmetic score also improved due to the reduced swollen appearance of the nose and narrower dorsum.
