Chronic upper airway inflammation can be divided into rhinitis or chronic rhinosinusitis, although there is a considerable overlap. Rhinitis is defined as a symptomatic inflammation with oedema of the nasal mucosa and engorgement of the turbinates resulting in at least two nasal symptoms being present for more than one hour per day.¹ It is classified as allergic, infectious or non-allergic, non-infectious.²

Chronic rhinosinusitis is divided into a group with and without endoscopic or radiologic evidence of nasal polyps CRSwNP or CRSsNP.²

Allergic rhinitis (AR)

Allergic rhinitis is an inflammatory condition caused by exposure to an allergen to which a patient is sensitised and this reaction triggers a series of symptoms.³ It is mediated by early-phase and late-phase hypersensitivity responses to environmental allergens.⁴ Typical stimulants are house dust mite, grass, tree and weed pollens, cat, dog, horse and moulds. We should remain mindful that many patients have mixed forms of AR. Diagnosis requires the demonstration of IgE-mediated hypersensitivity using appropriate cutaneous or systemic tests.⁵

Allergic rhinitis affects 10-30% of the population worldwide, estimated at approximately 400 million people.⁴ It is the fifth most common chronic illness in the US and is increasing in prevalence with a quadrupling of primary care attendances in the latter half of the 20th century.⁴ It is generally accepted that medical professionals are not identifying or addressing the condition as often as they should.

Sensitivity to inhaled allergens is rare before the age of two and tends to increase after that with approximately 60% of cases presenting by five years. It has been reported that 80% of eczema will present in the first year of life and food allergies such as milk or egg will also occur quite frequently before the first birthday.⁶ AR is more common in early age in boys, but this trend is reversed at puberty and is equal in adulthood.⁴

It is clear that genetic factors exist as an atopic family history will often be present. Higher socio-economic status, lack of siblings and environmental pollution have been demonstrated as important factors.⁴ There is strong support for the ‘hygiene hypothesis’ which includes a proven protection from AR and asthma by living on a farm and also by attending crèche facilities.⁶

It has been estimated that 45% of patients with AR are undiagnosed and that 60% diagnose their allergies themselves. Many do not present to their GP as they feel that the condition is not severe enough. If they do, they may have an inadequate preventative approach to the way they take their medications. About 60% of all AR patients are very interested in finding a new medication and 25% are constantly trying different medications to find one that works.

International guidelines

The international allergic rhinitis initiative, Allergic Rhinitis and its Impact on Asthma (ARIA), produces regular updates and revisions on clinical practice guidelines for the management of AR and asthma. This initiative was formulated during a World Health Organization workshop in 1999 (published in 2001). At the time it was becoming recognised that AR and asthma represent a global health problem for all age groups and frequently coexist in the same subjects. ARIA’s recommendations are universally acknowledged and the information produced by ARIA is disseminated and implemented in more than 50 countries.

There is a website available (www.whiar.org) with the current information on AR. This includes a free pocket reference booklet on the management of AR including various evidence-based algorithms on diagnosis, classification and treatment.⁷

Another useful organisation is GA2LEN – the Global Allergy & Asthma European Network. This is an EU-funded network of excellence involving epidemiological and clinical researchers to investigate allergy and asthma across the life stages.¹

Classification

ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patient needs and underlines the close relationship between rhinitis and asthma. More recently, controlled, partially controlled and uncontrolled has been added to the classification.⁵

How does one differentiate from mild to moderate/severe? Nasal symptoms in one patient may not have the same effect on another individual so whether or not sleep interference is present, is an appropriate leveller. Following on from that would be disturbance of normal daily functions or sports activities. There is no significant interference in the mild category. Most patients have the ‘moderate/severe’ form. In grass pollen allergy, sufferers have reported that an average symptom episode lasts 12.5 days whereas in mild patients an average episode lasts 9.8 days. Both groups experience several episodes every year

Four days and four weeks are the figures to remember. Intermittent disease is defined as symptoms for less than four days per week for less than four weeks per year and persistent is longer than four days and four weeks respectively. 

Defining controlled, part-controlled or uncontrolled is based on a combined evaluation of symptom severity, mucosal aspect and need for systemic medication.⁵

AR is often downplayed as a nuisance rather than a disease. However, it significantly impacts on sleep and reduces cognitive and emotional functioning affecting work and school productivity. It also creates a huge financial burden on the state in both direct and indirect costs. It has been estimated that the combined cost in Europe is as high as €3.5 billion per year.⁸

Clinical examination

On clinical examination one should look for transverse creases of the nasal skin or Dennie-Morgan lines. One should also look for or enquire about allergic shiners and/or salute. Swollen oedematous inferior turbinates are identified quite easily by looking into the nose, but can often be mistaken for nasal polyps. Simple decongestion will help and the use of an auriscope with a speculum will provide limited but often valuable information. The nose however, is never considered fully assessed unless a complete visualisation of both nasal cavities is performed with a telescope.

Differential diagnosis

Rhinitis or chronic rhinosinusitis? 

It can be difficult to ascertain the nature of the inflammatory causes as they can co-exist, but the defining markers are a positive skin prick or RAST test with or without a nasal allergen challenge. Occupational rhinitis may be obvious in the history, as might non-infective causes such as gustatory, hormonal, medication-related and laryngopharyngeal reflux.

Structural problems including nasal valve dysfunction, rhinitis sicca, septal perforation, deviated nasal septum, nasal polyps and adenoidal hypertrophy may also cause similar symptoms. Acute viral rhinosinusitis is usually of shorter duration. Cystic fibrosis or primary ciliary dyskinesia must be ruled out in children with nasal polyps or recalcitrant cases respectively. Systemic conditions like sarcoidosis, Churg Strauss syndrome, granulomatous polyangiitis (previously Wegener’s granulomatosis) are less common, but must be considered in severe cases, particularly with generalised complaints or persistent nasal crusting.

AR and acute or chronic rhinosinusitis can both lead to a blocked nose and rhinorrhoea. Associated sneezing and itchiness of eyes or nose are more likely AR whereas the opposite holds for headache and facial pressure.

The evidence from the literature is that standardised questionnaires are considered of great diagnostic value and are available through ARIA. 

Tests

Skin prick tests are the gold standard and if not readily available, serological IgE assessment with a radioallergo-sorbent test (RAST) can be used instead. Immediate hypersensitivity skin testing provides results within 15 minutes of doing the test. Serum testing can take a few days or weeks for results, although these are possibly more cost-effective.⁴ All IgE test results should be treated with a certain amount of caution as false-positive and false-negative results can occur.⁴ Nasal and/or conjunctival provocation tests may also help. 

Co-existing conditions

There are other conditions in the head and neck upon which AR can impact. It can synergise with viral inflammation and potentiate upper respiratory tract infections. Mucosal oedema can lead to obstruction of the sinus ostia and the subsequent reduction in ventilation of the sinuses leads to ciliary dysfunction and mucus stagnation promoting growth of bacterial pathogens.⁴

It is accepted but not proven that AR can potentiate Eustachian tube dysfunction, thereby increasing the frequency of otitis media with effusion. There may be a role in sleep disordered breathing with aggravation of snoring and sleep apnoea mainly due to an indirect effect from mouth breathing secondary to a blocked nose. It is often implicated in the aetiology of cough or laryngitis and the stimulation is distal from either a nasal neurogenic source or release of systemic inflammatory markers. A postnasal drip from the nose has not been demonstrated penetrating the laryngeal inlet in normal subjects.

Role for imaging?

CT scanning of all patients as an initial modality is not recommended as there is a substantial radiation exposure equivalent to multiple chest x-rays and a substantial financial cost incurred. Furthermore, there will be mucosal changes noted in an asymptomatic general population that are not considered significant using the Lund and Mackay grading system.⁹ These factors have led to the publication (EPOS) of evidence-based guidelines and indications by an expert group of European rhinologists with regular updates.⁹

CT scanning is recommended in failed medical treatment with severe symptoms, persistent or progressive unilateral symptoms, preoperative planning and complications of the disease process such as periorbital cellulitis. At present it should not be used as a first-line diagnostic tool, especially if an ENT assessment with nasendoscopy has not been performed. This approach is also recommended by a European respiratory expert panel.¹⁰

There is, however, an increasing trend for pulmonologists to include a CT scan of the paranasal sinuses in an initial battery of tests in respiratory patients. Our own, yet unpublished work, has demonstrated that these results are no more notable than if a cohort of asymptomatic members of the general population was scanned as a control group. 

The introduction of low-cost and much less dose-related radiation CT scans will probably change the indications in the future, particularly for primary care physicians. MRI is over-sensitive as an investigation of paranasal sinus inflammatory disease and is not recommended unless the disease process has extended beyond the confines of the sinuses or there is a need to differentiate retained secretions from tumour such an inverted papilloma.²

The ‘united airways’ concept 

The entire respiratory system, from the nasal aperture to the distal bronchioles, is linked structurally, epidemiologically and pathophysiologically and should be considered as a single functional unit.¹¹ Up to 80% of patients with asthma have chronic rhinosinusitis and 40% of patients with chronic nasal inflammation have asthma. Rhinitis is an independent risk factor for the development of asthma and allergen-directed immunotherapy in young children with allergic rhinitis has been shown to prevent the development of asthma in later life.¹¹ Inflammation is the driving force in both conditions and adequate treatment of AR allows for better asthma control.

In addressing the united airways patient, bronchial symptoms should be assessed in AR patients and managed accordingly if there is a clinical suspicion of asthma. Patients with persistent allergic rhinitis should be evaluated for asthma. A combined strategy should be used to treat the upper and lower airway diseases to optimise efficacy and safety. Asthma treatment is affected if patients fail to take AR medication when symptomatic, requiring 53.7% of asthmatic patients to increase their reliever and 19.5% the preventer.

The ‘allergic (atopic) march’ theory proposes that there is a progression of atopy mostly in early childhood, but which can occur at any age from eczema to asthma and allergic rhinitis, or the reverse of asthma to eczema or allergic rhinitis to asthma without eczema.⁶ In AR it also includes the development of multiple allergies commencing with a single hypersensitivity.

Treatment

Depending on the subdivision and severity, a stepwise therapeutic approach is proposed and an evidence-based treatment algorithm is available via ARIA.⁷ Treatment combines education, pharmacotherapy and immunotherapy. Treatment should be stepped up when control is poor and the initial response to therapy should be assessed after four weeks, unlike chronic rhinosinusitis where review is recommended after three months of medication.

Avoidance of allergens is still a guiding principle in prevention, but in real life can be very difficult to implement. Carpet removal, avoidance of soft toys in the bedroom, allergen-impermeable covers for pillows and mattress, vacuuming with a high-efficiency particulate (HEPA) air filter and washing bedclothes in hot water (60ºC) can help.⁸  There are extensive lists of avoidance measures recommended by various groups during the grass pollen season in recent years, including holidaying by the sea, staying inside early morning and early evening, wearing wraparound sunglasses and showering with change of clothes after being outside. 

The two most effective modalities are intranasal corticosteroids and also immunotherapy, with corticosteroids most likely not to cause harm.⁴ However, approximately 20% of patients with AR do not respond satisfactorily to appropriate treatment.

Despite the regular publication of management strategies, under-treatment is still commonplace.⁴ There are many medication classes available. However, no single rhinitis medication class targets all pathologic pathways of allergic rhinitis, and as a consequence no single medication class provides optimal relief from all symptoms. 

Oral and intranasal antihistamines, intranasal corticosteroids and chromones, oral anti-leukotrienes, intranasal or oral anticholinergics and decongestants are various single or multi-modality treatments traditionally used.  

Oral antihistamines are considered the cornerstone of first-line therapy in mild AR for both adults and children.  There are many intranasal steroid preparations of similar efficacy available for first-line treatment of the moderate to severe cases, and often the eventual choice is patient preference for cost and comfort. 

Intranasal corticosteroids have been shown to be more effective than either antihistamines and/or anti-leukotrienes. The most common reason for a poor response to intranasal steroids is poor compliance. The addition of an anti-leukotriene to an intranasal corticosteroid has not demonstrated much benefit.⁴

A more recent combination formulation of inhaled steroid and antihistamine for moderate to severe AR has been shown to have a statistically significant improved clinical efficacy as compared to other single or multiple combined available pharmacological medications.²

Depot steroid injections should not be used as they will predispose to osteoporosis, diabetes mellitus and local skin or muscle necrosis.⁴ First generation antihistamines are not recommended due to their sedating effects.

On the issue of intranasal corticosteroids and growth retardation in children, the lack of bioavailability in more recent preparations has made this worry highly unlikely. There is good long-term safety data available with the proviso that if maintenance therapy is advised in the paediatric population, a surveillance growth chart is recommended.⁴ In cases of a good response it is generally advised to wean down or off the spray gradually.

Blood-spotting and nasal dryness can occur with intranasal steroids. This is usually due to a drying effect on the midline septal mucosa and is more of a delivery problem than an actual side-effect. It can range from simple dryness to nasal crusting to a nasal vestibulitis with excoriation of the nasal aperture. Turning the nozzle of the spray laterally towards the inner canthus of the eye after gentle insertion should help. There are several nasal lubricant sprays on the market which can offset this drying impact. 

Nasal saline douches would also aggravate this rhinitis sicca, but nasal saline can help in the management of turbinate mucosal oedema which again should be applied laterally in the nose. 

A means of measuring treatment response is subjectively using the patient’s history and recording using a validated but simple visual analogue score (VAS). This has proven to be an excellent assessment tool with a quality of life questionnaire and a reflective total nasal symptoms score (RT4SS).¹²

Immunotherapy

Sublingual immunotherapy (SLIT) has become officially accepted as a viable and safer option to the subcutaneous (SCIT) method in recent years.¹² This is advocated when pharmacotherapy is not successful although more recent work is suggesting that it should be introduced earlier in the treatment algorithm and that it may help to stop the ‘allergic march’. 

The original sublingual medication for grass pollen allergy was prescribed on a daily basis for an optimum of four years and quality of life measurements were better during therapy and have persisted until now at over three years after stopping the medication.¹² Compliance and cost are an issue, but newer versions are due on the market for grass pollen allergy which are co-seasonal rather than perennial and not required to be taken all year round. Specific SLIT medication has also been introduced in some countries for housedust mite and pets with encouraging results. The identification of the patient who would benefit mostly from SLIT remains elusive.¹²

In relation to the safety profile there have been no fatalities, with 12 cases of anaphylaxis reported in the literature.¹¹ The incidence of local side-effects, including itching and swelling of the lips and floor of mouth, has been described in 35% of patients, but observed in clinical trials in up to 85% of patients. These usually appear within minutes or hours of intake and usually resolve within a fortnight.¹² Systemic reactions such as urticaria, angioedema and asthma are infrequent and seem to occur in cases requiring dose escalation.¹²

Can we prevent the ‘allergic march’? There is limited but promising data to suggest that probiotics, immunotherapy, breastfeeding and hydrolysed infant formulas may prevent the development of AR and asthma.⁷

Surgery

Surgery is rarely indicated for AR other than to improve the route for topical nasal treatment with either turbinate reduction or correction of septal deformities. Adenoidectomy may help in children with partial or uncontrolled symptoms. Endoscopic sinus surgery may also be necessary in recalcitrant chronic rhinosinusitis unresponsive to medical treatment and for complications of the chronic inflammatory disease process.  

The acronynm SCUAD represents a group of patients who persist with bothersome symptoms despite maximal medical therapy and termed severe (S) chronic (C) upper (U) airways (A) disease (D). In these cases the diagnosis should be reconsidered, and associated anatomic abnormalities, global airway dysfunction and systemic disorders  excluded.⁵

The future

Pharmacological and avoidance approaches involve symptom suppression. SLIT offers the promise of cure by altering the immune response and early results are promising in preventing the development of multiple allergens and asthma.⁴

References

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9. Fokkens WJ, Lund VJ, Mullol J, Bachert C, Alobid I, Baroody F et al. European Position Paper on Rhinosinusitis and nasal Polyps 2012.  Rhinol Suppl 2012; 23: 1-298
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12. Bousquet PJ, Bachert C, Canonica GW, Casale TB, Mullol J, Klosek JM et al.  Uncontrolled allergic rhinitis during treatment and its impact on quality-of-life: a cluster randomized control.  J Allergy Clin Immunol 2010; 126: 666-668: e661-665
13. Compalati E, Braido F, Canonica GW. Sublingual Immunotherapy: Recent Advances. Allergology International 2013; 62: 415-423