Consensus Document : South African Allergic Rhinitis Working Group

Reprinted from the S Afr Med J 1996; 86: 1315-1328.
Reproduced by kind permission of the editor of the South African Medical Journal.

INTRODUCTION
Allergic rhinitis must be regarded as a serious condition, because it can impact negatively on the quality of life of sufferers not only by producing severe symptoms but also by producing complications. School- and work-related dysfunction is common. Since allergic rhinitis occurs commonly and is still regarded by many as a trivial illness, it was considered that management guidelines should be formulated to elevate the status of rhinitis and thereby detrivialise it.

Following the example of the International Consensus Statement,1 the South African Allergic Rhinitis Working Group was convened from representatives of the ENT, paediatric, allergy and general practitioner communities to draw up these management guidelines. When initiating treatment for any disease, three important principles must be followed: Collating presenting symptoms and signs and results of any specific investigations to arrive at a diagnosis or short differential diagnosis. Planning a rational course of therapy – short-term or long-term, medical or surgical. Assessing whether the management plan is cost-effective. This does not mean compromising on patient care, but rather critically choosing a road forward which benefits not only the patient but also the community.
Definitions
Rhinitis is defined as inflammation of the lining of the nose, characterised by one or more of the following symptoms: itching, sneezing, rhinorrhoea and nasal congestion.1 Allergic rhinitis implies the existence of a hypersensitivity response to allergens mediated by IgE antibodies.

Classification
Allergic rhinitis is often classified into two types, viz.: Seasonal, Perennial.

Seasonal allergic rhinitis (‘hay fever’)
Symptoms are usually precipitated through contact with seasonal wind-borne pollens, e.g. grass and tree pollens or fungal spores. These symptoms usually occur in spring, early summer and with the change of seasons.

Perennial allergic rhinitis
Symptoms are due to sensitivity to and contact with allergens which are present in the environment throughout the year. These are usually indoor allergens such as house-dust mites, animal danders (cats and dogs), feathers, fungal spores and cockroaches.

Patients with pollen-sensitive seasonal allergic rhinitis living in the grasslands of South Africa (Fig. 1 (33 k ))2 can present with ‘perennial’ symptoms, because in these grasslands the pollen season is long-lasting with pollen levels of sufficiently high concentration to produce symptoms for about 10 months of the year. Since symptoms in these patients are perennial it would seen unnecessary to distinguish between ‘seasonal’ and ‘perennial’ allergic rhinitis. Patients living in the other regions with similar allergy are more likely to experience seasonal symptoms.

Differential diagnosis of allergic rhinitis
Allergic rhinitis can be distinguished from non-allergic rhinitis by a good clinical history and examination together with allergy testing.

Non-allergic rhinitis is inflammation of the nasal mucosa unrelated to allergy. The term is used to describe any disease of the nose presenting with the same symptoms of nasal blockage, increased nasal secretions and nasal hyperreactivity but without an allergic aetiology. This term is usually applied to chronic conditions only, thereby excluding acute infectious rhinitis. The non-allergic causes of chronic rhinitis are shown in Table I. Acute infectious rhinitis is included (in brackets) for completeness.

Table 1.
Classification of non-allergic chronic rhinitis

Infections

Acute viral or bacterial infections Chronic viral (HIV), bacterial or fungal infections secondary to
immunodeficiency, primary ciliary dyskinesia or cystic fibrosis

Non-allergic, non infectious

Idiopathic
Non-allergic rhinitis with eosinophilia (NARES)
Occupational
Hormonal – pregnancy, hypothyroidism
Drug-induced
Irritants
Food
Atrophic

Polyps

Mechanical Factors

Deviated septum
Hypertrophic turbinates
Adenoidal hypertrophy
Anatomical variants in the ostiomeatal complex
Foreign bodies
Choanal atresia

Tumours of the nose or paranasal sinuses

Benign
Malignant

Granulomas

Wegener’s granulomatosis
Sarcoid
Infectious
Tuberculosis
Leprosy

Cerebrospinal rhinorrhoea

Infectious rhinitis may be acute or chronic. Acute infectious rhinitis is usually due to a wide range of viruses (rhinovirus, respiratory syncytial virus, adenovirus, influenza virus), although secondary acute bacterial rhinitis with infective sinusitis can occur, with the commonest pathogens being Streptococcus pneumoniae and Haemophilus influenzae. Allergy, immunodeficiency and mucociliary disturbances such as primary ciliary dyskinesia and cystic fibrosis predispose individuals to the development of chronic infection. Chronic infectious rhinitis can also be caused by specific organisms such as HIV, Mycobacterium tuberculosis in tuberculosis and Treponema pallidum in syphilis. Fungal agents may also cause rhinosinusitis, the most common being Aspergillus genus.

Drug-induced rhinitis has been described for many medications, including:

Antihypertensive agents reserpine, guanethidine, phentolamine, methyldopa, a-adrenergic blockers (e.g. prazosin) and b-blockers.
Aspirin and other non-steroidal anti-inflammatory agents.
Topical ophthalmic b-blockers.
Chlorpromazine.
Oral contraceptives.

Nasal stuffiness or blockage may also result from drugs used to cause peripheral vasodilatation for the treatment of migraine and peripheral vascular disease. The term rhinitis medicamentosa is used to describe rebound nasal congestion and tolerance that the nasal vasculature develops to chronic use of topical decongestants (a-adrenergic agonists). Use of cocaine intranasally can cause severe irritation.

Physical and chemical factors that can act as triggers of rhinitis are:

Inhalation of cold dry air.
Ingestion of hot and spicy food.
Exposure to bright lights.
Many chemical and allergic stimuli have been implicated in rhinitis resulting from occupational exposure (see ‘Occupational allergic rhinitis’).

Factors producing mechanical obstruction may mimic rhinitis, in particular the symptoms of nasal blockage (Table I).

Factors producing mechanical obstruction may mimic rhinitis, in particular the symptoms of nasal blockage (Table I). If patients with non-allergic rhinitis cannot be categorised into one of the above conditions, one is left with a group of poorly defined conditions of unknown aetiology and pathophysiology which have been called idiopathic or vasomotor rhinitis. The name is unsatisfactory, firstly because the mechanism of all rhinitis, including allergic, is vasomotor, and secondly because there is no evidence to support the notion that the mechanism of this condition is indeed one of vascular dysfunction. Despite the uncertainty about this condition, these patients certainly exhibit increased nasal irritability to nonspecific triggers such as strong smells of perfumes, bleach and solvents, to irritants such as tobacco smoke, dusts and exhaust fumes, and to changes in environmental temperature and humidity. Within this group is a syndrome characterised by nasal eosinophilia, termed non-allergic rhinitis with eosinophilia syndrome (NARES). Classically patients are middle-aged and have perennial symptoms of sneezing paroxysms, nasal itching, rhinorrhoea and occasionally anosmia.

True food allergy producing respiratory symptoms is usually found together with skin (eczema) and gastro-intestinal allergy. Where a food substance is strongly suspected to cause symptoms, diagnosis should be confirmed using an elimination-challenge test. These tests should be conducted only in specialist clinics. Avoidance diets without adequate proof are not recommended. Certain foodstuffs (e.g. alcohol) may produce nasal symptoms, but these are not necessarily allergic in origin.

Epidemiology of allergic rhinitis (South African perspective)

The epidemiologies of allergic rhinitis and non-allergic rhinitis are different, as many patients with non-allergic rhinitis have no demonstrable allergy,3,4 and many individuals who are atopic do not present with rhinitic symptoms.5,6

Rhinitis occurs commonly, and its prevalence appears to be increasing.7 The reported prevalences of allergic rhinitis from various studies from different areas range from 4.5%8 to 38.3%.9 South African epidemiological data on this condition are lacking. Clinical experience suggests that the incidence of allergic rhinitis may be similar to that reported elsewhere.

There may be small sex, age and socio-economic variations in allergic rhinitis prevalence. It is slightly more common in boys, older children and young adults and in upper socio-economic groups, but these variations are small and therefore not useful in selecting patients for diagnosis.10,11 Note that allergic rhinitis can occur at any age from infancy, but in young children it is important to exclude the non-allergic causes of rhinitis.

Lastly, because of the geographical and climatic differences in South Africa, the distinction between seasonal and perennial allergic rhinitis varies from region to region. For example, in the grasslands around Gauteng, nasal symptoms due to grass allergy are almost perennial, while, by contrast, in the coastal regions of KwaZulu-Natal, Eastern Cape and Western Cape seasonal allergic rhinitis (spring) is well defined. Therefore, although allergic rhinitis in Gauteng is triggered by seasonal allergens it is less common for patients to have short-lived rhinitis. Some patients with grass-allergic rhinitis can have exacerbations and remissions during a single grass pollen season. Some international studies also report perennial allergic rhinitis to be more common than seasonal symptoms.12

Allergens in South Africa 13
ReturnThe correct identification and characterisation of the important aero-allergens and ingested allergens in southern Africa are essential in the diagnosis, prevention and treatment of allergic rhinitis in South Africa.

South Africa has a range of climates which include Mediterranean, subtropical, tropical, semi-desert and desert, as well as areas with summer rainfall (Fig. 1).2 There are humid coastal areas and dry inland areas, low-lying areas and elevated areas, and these have important bearings on the flora and allergens encountered in a given locality. The importance of a specific allergen for a given patient may therefore vary, depending on where the patient was born or where he/she currently lives or works.

In southern Africa there are 947 indigenous and 115 naturalised grass species. Grass pollens are important aero-allergens in South Africa. House-dust mites are also important, both at the coast and inland.14 The dominant house-dust mite species is Dermatophagoides pteronyssinus. Other allergens important in allergic rhinitis include pets (dogs, cats, rabbits, rats, horses), moulds (Aspergillus fumigatus, Alternaria alternata, Cladosporium herbarium and Epicoccum) and occupational allergens (see ‘Occupational allergic rhinitis’).

Grass pollen allergens
Grass pollens are conveniently divided into three sub-families: Pooideae – e.g. rye grass and wheat Panicoideae – e.g. maize and Kikuyu grass and Eragrostis species15 Chloridoideae sub-families, e.g. Bermuda and Buffalo grass. In South Africa allergy to all three sub-families occurs commonly. Not all grass pollens are allergenic, even though abundant pollen may be produced (e.g. Hypharrenia hirta or thatch grass). In the grassland regions (Fig. 1) seasons can be long (up to 10 months) and consequently many patients will have chronic symptoms.

Tree and weed allergens
Tree and weed allergens, in contrast to grasses, typically produce seasonal hay fever. Trees such as the plane, willow, cypress, oak, eucalyptus and syringa cause seasonal symptoms for short periods. Many of these have been introduced from Europe, Australia and America.

Indigenous trees such as acacia species may also account for symptoms in the savannah regions.

Many patients attribute symptoms to pine, jacaranda, mimosa and Port Jackson trees, which produce abundant pollen in the spring. Although specific IgE can be demonstrated in response to pine and Port Jackson tree pollen, the significance of these trees in producing symptoms is not conclusively established as yet, because most tree pollen-sensitive individuals have concurrent grass pollen allergy.

Birch pollen is not an important cause of allergic symptoms in South Africa.

South Africa fortunately does not have ragweed, but English plantain is commonly found. Flowers of the Compositae family may release pollen at different times of the year and may account for symptoms beyond springtime.16

The Phadiatop is a poor screening test for tree pollen allergy.

House-dust mite allergens
Allergens of the house-dust mites D. pteronyssinus (Der-p-1) and D. farinae are important causes of perennial rhinitis at the coast and also in certain inland areas where average relative humidity is high.17

Pet allergens
Allergens from cats (Fel-d-1), dogs (Can-f-1), horses and rodents (rats, hamsters, guinea-pigs and mice) cause perennial allergic rhinitis. In conclusion, note that:

Many allergens in South Africa are different from those encountered in Europe or America. This applies particularly to the grass pollens, weeds and tree allergens.

A knowledge of the geography and flora where the patient resides is important in assigning clinical relevance to the result of an allergen skin-prick or radio-allergosorbent (RAST) test (Table II).

House-dust mite allergy occurs both at the coast and inland and is an important cause of perennial rhinitis.

Food allergens are uncommon causes of allergic rhinitis. It is important to consider occupational allergens (e.g. latex) in patients who complain of predominantly work-related nasal symptoms which improve over weekends or when on vacation.

Patients with recurrent or chronic rhinitis require allergy testing (skin test or CAP RAST) to identify or confirm their allergy.

Clinical evaluation
History The diagnosis of allergic rhinitis is usually not difficult – in fact, it is often made by the patient or by the parents of the allergic child. In the first season in which patients experience seasonal rhinitis, the symptoms may be interpreted as the result of a prolonged cold. Eventually these patients recognise the seasonal nature of the condition. In assessing the relative importance of different allergens in patients with allergic rhinitis, it is essential first to take a detailed environmental history, which includes:

A clear definition of the geographical location of the patient.
Whether or not the patient has moved.
Place of birth.
Home environment, such as:
carpeting
pets
smoking
trees, plants, grass
hobbies.
Seasonality of symptoms.
Relationship of symptoms to:
working conditions
diet
indoors v. outdoors.

As allergic rhinitis commonly occurs in families, it is important to determine a family background of rhinitis or of the other allergic conditions (asthma, eczema, urticaria).

The dominant complaints of allergic rhinitis are itching, frequent explosive sneezing, profuse watery nasal discharge (runny nose or postnasal drip) and nasal blockage:

Sneezing, itching and rhinorrhoea are, not exclusively, the symptoms of the early phase in allergic rhinitis.
patients often mention that they ‘use a whole box of tissues every day!’
patients with a chronically blocked, full nose uncommonly sneeze – in fact, they may complain that as their more chronic symptoms improve they very often ‘regress’ through the sneezing, running nose ‘typical hay fever’ stages.
Itching can be intense, affecting the soft palate and the external auditory canals. The palatal itch often causes sufferers to make ‘clicking’ noises as they attempt to rub the palate with the tongue.
Nasal obstruction is often a factor of the later stages of allergic rhinitis, but is more commonly a result of other obstructing factors within the nose, e.g. adenoidal hypertrophy in association with allergic rhinitis.
Nasal blockage leads to a variety of other problems, including:
recurrent sinusitis
headaches
disturbed sleep patterns with tiredness and irritability
mouth breathing – children are often thirsty at night as a result of mouth breathing, which causes drying of the lips and buccal mucous membranes.
Allergic conjunctivitis with itchy, watery eyes and photophobia usually accompanies the nasal symptoms. In perennial allergic rhinitis, eye symptoms and itch do not usually occur.

Examination

Allergic facies
Patients with seasonal allergic rhinitis do not have the so-called ‘allergic facies’ – rather, they often have red, puffy faces with reddened, watery eyes. Their conjunctivae are hyperaemic and granular.
Patients with perennial allergic rhinitis commonly exhibit the ‘allergic facies’.
Features include:

Pallor – often appear remarkably pale.
‘Allergic shiners’ – bluish discoloration of the lower eyelids.
Dennie’s lines – slightly puffy lower eyelids and several skin creases.
Mouth breathing – many of these patients are constant mouth breathers, sometimes displaying the so-called ‘allergic gape’.
Patients can develop rather long, mournful faces. The palate is often high-arched and narrow in these patients and dental crowding is common, especially in young children. These features form the long-face syndrome.

Allergic mannerisms
Allergic mannerisms are common:
Patients often pull their faces in various ways, often like rabbits, in an attempt to open up their nasal passages.
The ‘allergic salute’ is seen – the patient pushes the tip of the nose up with the palm of the hand in an attempt to improve the patency of the nasal airway. In these patients a nasal crease may develop where the cartilaginous and bony portions of the nose meet.
The ‘allergic salute’ may also be characterised by a sidewards rubbing of the nose.
As, for obvious reasons, younger children cannot complain about their early symptoms, they frequently present with later sequelae such as otitis media with effusion. It is consequently important to recognise the presence of allergy at this age. Very young allergic children are often seen rubbing their noses on sheets and their mother’s shoulders, even before the hands can find their way to the nose.

ENT examination
Nose – often appears swollen, reddened and shiny from constant rubbing.
Nasal mucosa – examination of the nasal passages usually shows severe swelling of the nasal mucous membrane and lower turbinates with profuse secretions which range from clear to thick mucoid:
textbooks often describe the colour of the mucous membranes as grey or greyish-pink but this is extremely variable.
in many cases there is long-standing chronic inflammation of these mucous membranes, and the colour is often dark red.
it is not unusual for the swollen anterior turbinate to obstruct the nostril completely.
Throat – usually appears reddened with prominent lymphoid follicles on the posterior pharyngeal wall.
Ears – another common associated problem is otitis media with effusion, especially in infants and young children; it results from chronic oedema of the eustachian tube openings in the posterior nasopharynx.
Speech may have a nasal quality and there may be loss of taste and smell.

Investigations
Tests for allergy

Skin-prick test (SPT)21
The SPT is currently the optimal way to test for allergy.
It tests for immediate hypersensitivity and demonstrates an IgE-mediated allergic reaction.
Certain factors such as drugs (Table III), age and the season may influence the results.
In performing an SPT, the use of a large number of allergens is expensive, time-consuming and usually not necessary. SPTs should initially be limited to the common aero-allergens in the patient’s environment.

Table III.
Inhibition of histamine-induced skin reactions
Data from references 47, 48, 51, 56, 92-94.
Clinical Effect Terfenadine Astemizole* Loratadine Ceterizine
Onset of Action 0.5 – 1 h 1 – 2 h 1 – 2 h 20 m
Time of Maximum Effect 4 h 3 – 4 d 2 – 3 h 1 – 2 h
Duration of Action 2 d 6 – 8 wks 2 – 4 d 2 – 3 d

*Steady-state kinetics 3 – 4 weeks.
Total serum IgE
In normal subjects, levels of IgE increase from birth to adolescence and then decrease slowly to reach a plateau after the age of 20 – 30 years.
This test has a poor predictive value and should not be used as a screening test for allergy because:
raised values can result from a number of conditions other than allergy, e.g. worm infestations
approximately half of the IgE allergic patients will have a total IgE in the normal range.
Total IgE estimates have a place in children aged under 3 years, in whom the Phadiatop test is less reliable.
The full blood count, specifically the eosinophil count, is also a poor screening test for allergy and should therefore not be used.
Phadiatop test
The Phadiatop test is a screening test using several inhalant allergens on a single solid phase and therefore will detect specific IgE in a single assay.
It has an efficiency of over 95%, defining those individuals who need more detailed investigation.22
It is less useful in children under 3 years old, in whom the CAP RAST F x 5 (6-foods test) is generally more useful, particularly if combined with total serum IgE.
CAP RAST
This test is useful when SPTs are not available, e.g. in young children.
Table II lists suggested screening tests for the different regions of South Africa.
Doctors are advised not to send blood for this test without specifying which allergens they require and are appropriate for their region.
Laboratories offer an extremely wide range of CAP RAST tests, and failure to specify can make the cost to the patient unnecessarily high.
Nasal smears
Nasal smears may differentiate between allergic and infective rhinitis.
Eosinophils are characteristic of allergy or non-allergic rhinitis with eosinophilia (NARES), where neutrophils imply bacterial infection.
Specialist advice can be sought.
Other tests
Other tests such as the release of mediators from peripheral blood cells, mediators released during allergic reactions and nasal challenge are largely used as research tools.

Imaging in allergic rhinitis1,23,24
Radiology does not assist in the diagnosis of allergic rhinitis, but is used for the detection of complications arising from the disease and the exclusion of other conditions.
The changes present in the nasal mucosa are also reflected in the sinus mucosa.
Two methods of sinus imaging used today are plain X-rays and CT scanning.
Plain X-rays
Despite advances in imaging technology, plain films still have a limited role to play.
They are of most value in detecting the presence of acute infective
processes.
The main limitations of plain films lie in the poor visualisation of the ethmoid air cells, and the difficulty in distinguishing between infection, polyps and tumours in a completely opacified sinus.
The standard sub-mento vertical (Waters) view will clearly show an air/fluid level as well as a complicated septal deviation.
The frontal and ethmoid sinuses are more clearly shown in the postero-anterior (Caldwell) view.
The density of the orbital cavity correlates with the normal frontal and
ethmoid sinuses.
Problematic areas like the ostiomeatal complexes are not shown in any of these views.
They are also not of use in very young children as the sinuses are not fully aerated – 75% of children aged under 1 year will therefore have opaque maxillary sinuses.
The adenoidal fat pad is best visualised in the lateral view, but plain X-rays are not adequate to assess the posterior nasal space.
CT scanning25
CT scanning should be reserved for complicated sinusitis and as part of surgical planning.
It has become the imaging modality of choice for clearly viewing the anatomical and pathological changes present in the sinuses.
The key area, the ostiomeatal complex, is clearly shown, as are all the other changes in the sinuses if coronal views are requested.
Concern has been expressed about the radiation exposure during CT scanning. Although the radiation dose to the lens of the eye is higher than that for plain films, it is still well within safety limits.

Cost-effectiveness of investigations must always be considered. Unnecessary wastage of resources which will not alter the treatment outcome must be avoided. Radiology can be costly, and generally will not alter the treatment of patients with uncomplicated allergic rhinitis.
Endoscopy of the nose in allergic rhinitis26-28
Endoscopes can either be rigid or flexible. Most otolaryngology practices are fitted out with either a rigid scope or a flexible scope.
Endoscopy is relatively easy in adults but is difficult in children, in whom its use is therefore limited.
Endoscopy of the nose in allergic rhinitis not only helps to show the typical mucosal findings but also allows determination of additional pathology, e.g. polyps in the middle meatus or associated anatomical factors which may affect the treatment of allergic rhinitis, e.g. septal deviation.

Treatment
Environmental Control
House-dust mite
Pets
Irritants
Pharmacotherapy
Topical Steroids
Oral Antihistamines
Topical Antihistamines
Topical Nasal Decongestants
Sodium Cromoglycate
Anticholinergics
Systemic Steroids
Specific Immunotherapy (SIT)
Environmental control 29
The causal relationship (both in the aetiology and symptom response) between allergen exposure and allergic rhinitis is well established.
Environmental control measures can improve the patient’s symptoms and reduce the need for pharmacological treatment, and should therefore be seen as the primary treatment of allergic rhinitis.
However, note that when an allergen source such as a pet is removed from a patient’s environment, the benefits may take several weeks or months to be perceived.
Measures for the following allergen and irritant sources should be considered.

House-dust mite 30-32
House-dust mite levels should be measured before any attempts at mite reduction.
Where mites are shown to be prevalent and are producing problematic symptoms, the following measures should be considered:
regular damp dusting and regular vacuuming
mattress and pillow covers are beneficial and cost-effective (for further information contact the Allergy Society of South Africa, PO Box 88, Observatory, 7925)
expose mattresses to sunlight regularly
wash linen and mattress covers weekly in hot water (> 60C)
wooden or tiled floors are preferable to carpets in bedrooms.
Assessment of the efficacy of acaricides (e.g. benzyl benzoate) and allergen denaturing sprays (e.g. tannic acid) has not been encouraging. Their cost has also proved to be prohibitive, particularly since frequent retreatment is needed. Their toxicity to humans has also not been fully elucidated.
Pets
If possible, remove the offending pet.
Do not allow pets in the bedrooms at any time.
Bath pets regularly, including cats!
Irritants
The following irritants often produce symptoms:
Chlorine in swimming pools. Pool water is also a pollen trap. Swimming may increase symptoms, and nasal clips are therefore recommended.
Cigarette smoking. The patient’s environment MUST be smoke free – no smoking in the house, car or work place.
Aerosols – deodorants, perfumes, etc.
Pharmacotherapy
In selecting medication for individual patients, the doctor should consider the nature of the symptoms (e.g. primarily a runny nose or primarily a blocked nose) and whether the symptoms are seasonal or year-round. Table IV shows a comparison of the effects of the different drug classes on the predominant symptoms of allergic rhinitis.

Table IV.
Relative effects of drugs used in allergic rhinitis
Modified from reference 1.
Drug Itch/Sneezing Rhinorrhoea Blockage Impaired smell
Topical steroids +++ +++ ++ +
Oral antihistamines +++ ++ + – –
Topical antihistamines + + + – –
Topical decongestants – – +++ –
Sodium cromoglycate + + + – –
Anticholinergics – +++ + – –
Topical steroids
The introduction in 1973 of glucocorticosteroids (henceforth referred to as steroids) which could be given locally in the nose without significant risk of systemic adverse effects was a major therapeutic advance, and has strengthened the pharmacological approach to allergic rhinitis therapy.
Action of topical steroids:

Inhibition of the late nasal reaction by reduction:
of the numbers of basophils and eosinophils
in the sensitivity of irritant receptors
in the secretory response to stimulation of cholinergic receptors.33
Inhibition of allergen-induced early and late nasal responses by decreasing T-lymphocytes and/or mast cells and their products and a consequent reduction in tissue eosinophilia.34
Effect on IgE synthesis.35
Steroid molecules widely used for intranasal treatment are:

Beclomethasone dipropionate (Beconase, Clenil, Ventnaze, Viarox)
Budesonide (Rhinocort)
Flunisolide (Syntaris)
Fluticasone propionate (Flixonase)
Triamcinolone acetonide (Nasacor)
Betamethasone sodium phosphate (Betnesol).36
Topical steroid sprays are delivered as follows:
Beclomethasone dipropionate (Beconase), budesonide (Rhinocort) and fluticasone propionate (Flixonase) are available as aqueous suspensions delivered from mechanical pump sprays.37 These give better intranasal distribution, but there is usually some loss of fluid from the nostril.
Flunisolide is dissolved in polyethylene glycol and propylene glycol and therefore can be delivered from a metered-dose pump spray, but spraying of this solution causes some immediate stinging.
Betamethasone sodium phosphate (Betnesol) is administered as nasal drops and since some systemic absorption may occur its use should normally be restricted to a 10-day period and it should be used only where specifically required for intractable problems.38
Teaching the patient correct spray technique is important for successful outcome of the therapy.

The nozzle of the pressurised aerosol should not be pointed towards the septal wall and must be positioned in the sagittal plane.
One puff in the upper and one in the lower part of the nose will probably improve intranasal drug distribution (Fig 2.).
When the pump spray is used it is necessary to co-ordinate pumping the spray with a short sniff.
Patients must be told that immediate relief cannot be expected from steroid sprays, in contrast to a vasoconstrictor spray.
Initially a topical decongestant is often advantageous in very congested noses before instilling the intranasal steroid.
Emphasise that the spray must be used regularly.
Recommended frequency:

Beclomethasone dipropionate (Beconase, Clenil, Ventnaze, Viarox) and flunisolide (Syntaris) – twice daily.
Budesonide (Rhinocort), fluticasone propionate (Flixonase) and triamcinolone (Nasacor) – once daily.39
Clinical effects:

Topical steroids are effective in reducing nasal symptoms (especially nasal blockage, but also itching, sneezing and rhinorrhoea).
High-dose therapy cannot generally be recommended for allergic rhinitis, but a higher-than-normal dose may be beneficial for a short time in selected patients to control symptoms.
Once symptoms are controlled, the daily dosage may be reduced.40 To determine whether continued therapy is needed, patients can discontinue spraying once or twice a year; if disease is active, symptoms will recur. This can take weeks because of the long carry-over effect of the steroids.
Treatment of inflammation in the upper airways indirectly improves asthma symptoms and decreases bronchial hyperreactivity. Ignoring inflammation in the upper airway may lead to suboptimal results in asthma treatment.4l
Topical steroids have proved more effective in symptomatic control of allergic rhinitis (nasal secretion, nasal itching, sneezing and especially nasal blockage) than sodium cromoglycate.42
Steroids are significantly more effective for nasal blockage, against which antihistamines are ineffective.43,44
Side-effects:

Occasionally dryness in the nostril is followed by development of bloodstained crusts.
Epistaxis may be a temporary side-effect of intranasal steroids, but is more likely to be caused by acute rhinitis. This may be overcome by reducing the dosage or changing from a pressurised aerosol to an aqueous spray.45
In exceptional cases septal perforation has been reported with intranasal steroid preparations.46
Oral antihistamines
Histamine is one of the most important mediators released from mast cells and basophils. It exerts its effects by binding to histamine receptors in blood vessels and tissues. Histamine stimulation of blood vessels results in vasodilatation and increased permeability. Stimulation of sensory nerve endings in the nose results in itching, sneezing and secretion.

Action of oral antihistamines:

Antihistamines bind to histamine receptors, thereby blocking the effect of histamine (competitive antagonism).
They are effective in reducing established symptoms such as nasal itching, sneezing and watery rhinorrhoea but have little effect on nasal blockage.47,48
The older or first-generation antihistamines (e.g. chlorpheniramine, clemastine, dexchlorpheniramine, hydroxyzine, etc.) are effective in controlling symptoms of allergic rhinitis, but their use is limited because of varying sedative properties and the occurrence of tachyphylaxis with continued use of these drugs.
They tend to block the development of hyperresponsiveness, but not the influx of inflammatory cells into the mucosa following allergen exposure.
The newer or second-generation oral antihistamines (astemizole, cetirizine, loratadine and terfenadine) are non-sedating or less sedating, but more expensive.
They are highly effective in the treatment of allergic rhinitis. Apart from their H1-receptor antagonist effect, the new antihistamines may also have anti-inflammatory properties including inhibiting migration of eosinophils, neutrophils, lymphocytes and monocytes.49-52

There are marked differences in the pharmacokinetic properties of these drugs:

astemizole (Hismanal) has an extremely long half-life (10 days in serum), reducing skin prick reactions for 6 – 8 weeks; it can also cause weight gain in some individuals.53
cetirizine54 (Zyrtec), loratadine55 (Clarityne, Polarityne) and terfenadine56 (Triludan) are metabolised more rapidly, so the suppressive effect on skin reactions is present for 2 – 4 days after drug ingestion ().
Cetirizine (Zyrtec) differs from the others in that it is not metabolised in the liver and no active metabolites are generated; it is excreted largely unchanged in the urine.
The recommended dosages of the new antihistamines for children and adults are listed in Tables V and VI.

Side-effects:
Sedation is the main side-effect of antihistamines, especially the first-generation antihistamines.
Serious cardiotoxic effect of prolonged QT interval producing a potential for ventricular arrhythmia has been observed with terfenadine (Triludan) and astemizole 57 (Hismanal).
Cardiotoxicity is dose-related, occurring only with overdosage, but it may also occur in individuals in whom the hepatic metabolism of these drugs is impaired: e.g. with concurrent use of macrolide antibiotics (e.g. erythromycin) and certain antifungal agents (e.g. ketoconazole), or in the presence of severe liver disease. These drugs are generally safe if recommended doses are taken and if they are avoided in situations which may impair their metabolism.
Although the newer antihistamines are more expensive than the earlier preparations, the cost is substantially offset by their more favourable benefit/cost ratio, particularly lack of adverse effect on performance. They should be used preferentially in patients requiring long-term antihistamine therapy, but the continued use of oral antihistamines for chronic symptoms may require review of therapy.

Table V.
Recommended dosage of
new antihistamines in adults and children > 12 years

Drug Dosage
Terfenadine 60 mg twice daily
Astemizole 10 mg once daily
Cetirizine 10 mg once daily
Loratadine 10 mg once daily

Table VI.
Recommended dosages of
newer antihistamines in younger children

Drug Age Dosage
Terfenadine 3 – 6 yrs 15 mg twice daily
6 – 12 yrs 30 mg twice daily
Astemizole 6 – 12 yrs 5 mg daily
Cetirizine 6 – 12 yrs 5 mg daily
Loratadine 2 – 12 yrs (> 30 Kg) 10 mg daily
2 – 12 yrs (< 30 Kg) 5 mg daily
Topical antihistamines 58,59
Levocabastine (Livostin) and azelastine (Rhinolast) are effective for acute symptomatic relief from itching, sneezing and rhinorrhoea; as in seasonal allergic rhinitis.
nasalsprays.gif – 0.9 K Fig 2.
Method of intranasal spray application
modified from reference 95
(Click on image to see the 4 steps required)
Topical nasal decongestants
These agents are not considered first-line therapy for allergic rhinitis.
The only indication is as short-term therapy (7 – 10 days) to reduce inflammatory swelling, thereby facilitating the introduction of an anti-allergy preparation into the nose.60,61
Drugs used as topical decongestants are listed in Table VII:
imidazole derivatives are preferred because of their favourable safety profile
the phenylephrine group is banned in competitive sports.
Contraindications to topical nasal decongestants:
Other medication such as tricyclic antidepressants, MAO inhibitors and b-blockers.62
Concomitant diseases such as hyperthyroid disease, narrow-angle glaucoma and prostatic hypertrophy are also contraindications.
Rhinitis medicamentosa is thought to occur when the adrenergic receptors appear to become less sensitive to both endogenous and exogenous adrenergic stimulation. It is a rare condition.

Cessation of the drug, preferably gradually, possibly with the short-term use of a nasal (sometimes oral) steroid, is the preferred treatment. Follow-up to determine the cause is recommended.

s Table VII.
Topical decongestants available in South Africa.

Drug Imidazoline derivative Phenylephrine derivative
Advil + –
Arcana P + –
Drixine + –
ENT + +
Fenox + +
Iliadin + –
Nasdro + +
Nazene Z + –
Otrivin + –
Sinutab + –
Universal + –
Naphensyl – +
Nasomyxin – +
Vibrocil – +

Sodium cromoglycate Sodium cromoglycate (Rynacrom, Vividrin) nasal solution is effective for the prevention of the immediate and late nasal response associated with allergen challenge in patients with both seasonal and perennial allergic rhinitis.63,64

Clinically it appears that it is more useful for sneezing, rhinorrhoea and nasal itching than for nasal obstruction such as occurs in seasonal allergic rhinitis.
It can also be used for prevention of seasonal allergic rhinitis especially if administered before the onset of the season.
Proper contact with the nasal mucosa is essential for efficiency – in patients with nasal congestion and secretions, vasoconstrictors or saline lavages are indicated prior to use of sodium cromoglycate (Rynacrom, Vividrin).65
Sodium cromoglycate (Rynacrom, Vividrin) needs to be given 4 – 6 times a day. Owing to this frequency a potential disadvantage is poor compliance. Side-effects appear to be minimal with occasional sneezing, nasal stinging, burning, transient headache and an unpleasant aftertaste.
Tachyphylaxis has not been reported.
Several studies have been undertaken comparing the efficacy, convenience of use and side-effects of intranasal corticosteroids and antihistamines, with sodium cromoglycate (Rynacrom, Vividrin). Levocabastine (Livostin) was at least as effective as sodium cromoglycate (Rynacrom, Vividrin), with significant improvement in symptoms in the levocabastine group after 2 weeks.66-68 Topical steroids have been shown in many studies to have a greater efficacy than sodium cromoglycate (Rynacrom, Vividrin) in the treatment of seasonal allergic rhinitis in adults and children.42,69,70

Anticholinergics
The anticholinergic intranasal spray ipratropium bromide (Atronase) is effective against all forms of watery rhinorrhoea, irrespective of their cause, but has no anti- inflammatory properties and is therefore ineffective against all other symptoms of rhinitis.71 It has a rapid onset and side-effects are minimal.

Systemic steroids
Systemic steroids are not considered first-line treatment in allergic rhinitis.72 Short courses can be used with caution in adults with very severe allergic rhinitis provided there are no contraindications73 (i.e. pregnancy, diabetes mellitus, severe hypertension, herpes infection, peptic ulcer disease, osteoporosis and chronic infection). Other anti-rhinitis treatment should also be given concomitantly to reduce the dosage of the steroid and continue symptom control after the oral steroids are withdrawn.74 In children, because of the greater risk of side-effects, systemic steroids are not generally recommended.
If repeated courses of steroids are considered necessary specialist advice should be sought. Short-acting steroids (e.g. prednisone or prednisolone) are preferred and the longer-acting and injectable steroids and combination therapy (steroid/antihistamine) drugs are not recommended.

Specific immunotherapy (SIT) 75-77
SIT is considered by the working group to be a therapy that should be conducted by trained personnel in specialised clinics only. SIT is indicated in patients who are monosensitive to either grass pollen or house-dust mite as a treatment option for reducing the requirements for pharmacotherapy in such patients. In properly selected patients, immunotherapy may induce a total remission and cure of symptoms. Newer, more purified immunotherapy vaccines from Europe are expected on the South African market in the near future.
When SIT is indicated, a complete discussion with the patient to include the potential dangers as well as the optimal duration of therapy should be done before initiation of therapy.

The indications for SIT are as follows:
Patient has proven IgE-mediated allergy.
Patient must have a positive skin and/or CAP RAST test to an unavoidable single allergen.
Clinical history must correlate with the laboratory findings.
Recommended for allergic rhinitis caused by grass pollens, house-dust mites and animal dander (under certain conditions, e.g. veterinarians).
When pharmacotherapy, i.e. antihistamine and/or topical steroids, has failed to alleviate the symptoms, and there is progression of the severity of the disease. The patient should have prolonged symptoms for several months in a year.
Guidelines for immunotherapy should be strictly adhered to.
The contraindications to SIT are:
Patients aged under 5 and over 60 years of age.
Patients with coronary heart disease, hypothyroidism, auto-immune disease or active asthma and patients on b-blockers.
Patients with psychological and social problems are unlikely to comply with the long course of therapy.

Complications of allergic rhinitis
Return
Otitis media with effusion
If the paranasal sinuses and the middle ear cleft are regarded as extensions of the nasal cavity, lined by respiratory mucous membrane, it seems logical that both these areas would be influenced by conditions affecting the nose.
In allergic rhinitis the eustachian tube is effectively obstructed by both intrinsic venous engorgement and extrinsic mucus plugs (consequences of the inflammatory process). This in turn leads to a blocked middle ear cleft. Negative middle ear pressure and transudation of fluids into the middle ear space result in chronic inflammation, mucosal metaplasia and increased glandular activity, all of which are hallmarks of chronic otitis media with effusion. In various studies otitis media appears to be associated with allergy in 35 – 40% of cases.78 The incidence appears to be higher in young children.

Infective sinusitis
Infective sinusitis is a frequent complication of allergic rhinitis. Many of the symptoms of allergic rhinitis are called sinusitis or ‘chronic sinus’ by the patient. These include symptoms such as nasal obstruction with or without a runny nose, and facial discomfort.79
In cases where infective sinusitis is not responding to medical anti-infective treatment and surgical treatment is contemplated, it is important to treat the patient for underlying allergic problems to avoid the recurrence of obstruction and further sinusitis. This is particularly true for situations where nasal polyps have been the main cause of sinus obstruction.

In cases of asthma resistant to treatment, chronic sinusitis should be carefully sought as this has been shown to be a frequent association. Removal of tonsils and adenoids will not aggravate asthma.

Abnormal craniofacial growth and the ‘long-face syndrome’
There is still debate over whether reduced nasal breathing from nasal allergy or enlarged adenoidal masses may cause development of a specific facial type called the ‘long-face syndrome’. This manifests with vertical excess in the lower third facial height, lip incompetence, narrow maxillary arches with high palates, and a steep mandibular plane angle. Open and posterior cross-bite may also be present if the onset of nasal obstruction is early.
Nasal dysfunction could therefore cause facial development retardation, especially if it begins in the first year of life. Deformities occurring later would be less pronounced. It has been postulated that allergy produces oedematous nasal and paranasal membranes, venostasis around developing bony and dental areas, and dilatation of histamine-mediated capillaries in the dental areas. This influences local tissue metabolism, which may cause local tissue acidosis leading to dental and oral facial disorder.

Impaired quality of life
Sleep disturbance caused by allergic rhinitis includes obstructive sleep apnoea, periodic breathing and episodes of hypo-apnoea and hypoventilation, as well as significantly more than normal micro-arousals. These symptoms have been attributed to increased upper airway resistance.80,81
Disturbed sleep can result in the chronic fatigue syndrome, which impacts heavily on quality of life by resulting in limitation of activities, emotional problems, and impaired learning ability in children.82-84 Appropriate treatment of allergic rhinitis will improve sleep quality and thereby quality of life.

Special considerations in allergic rhinitis
Return
Children85-86
Allergic rhinitis is a common disorder in children, adolescents and young adults. However, it is frequently under-diagnosed and its importance as a cause of morbidity and an effect on school performance may be under-estimated. Noisy breathing, irritating sniffing, coughing and throat-clearing often lead to social isolation at school and discord at home. Children with severe nasal obstruction due to allergic rhinitis are often small for age. They may be unhappy, pale, and have the characteristic allergic facies.
Examination of the ears is essential in children with allergic rhinitis, as many will have otitis media with effusion. Hearing impairment is common and must be identified and corrected to avoid learning difficulties and speech defects.

The principles of treatment of rhinitis in children are generally the same as those in the adult with some special considerations. There is very little evidence that food is a particularly common cause of allergic rhinitis and exclusion diets are not usually indicated.
Elderly
Allergic rhinitis is not a common problem in individuals over 65 years of age. When rhinitis occurs it is usually due to a non-allergic mechanism, for example ‘old man’s drip’, which is a clear watery rhinorrhoea, the mechanism of which is not fully understood. Treatment with ipratropium bromide (Atronase) may afford some relief. It is important to exclude non-allergic conditions listed earlier when rhinitis is encountered in the elderly.
Treatment must be chosen with care, as specific risks are present in the elderly. The first-generation antihistamines can cause bladder disturbances, such as retention, and problems with visual accommodation.87 Second-generation antihistamines are probably safe, but astemizole (Hismanal) and terfenadine (Triludan) may be associated with QT prolongation and arrhythmias, which may be more likely in the elderly. Vasoconstrictors, especially when given orally, can give rise to cardiovascular and CNS side-effects.88

Intranasal topical steroids should be used with caution in the elderly. Greater attention should be paid to the complications, as these are more common in older patients.

Pregnancy
Allergic rhinitis is probably the most common cause of gestational nasal symptoms. Typically the symptoms predate the pregnancy. It is not sufficient to attribute symptoms to oestrogen. A proper search for the type of rhinitis is essential. A primary diagnosis of allergy in pregnancy is best conducted by CAP RAST testing, as skin prick testing may result in anaphylaxis.89
The diagnosis and treatment of these symptoms is complicated by the potential adverse effects on the fetus. Most mothers will tolerate nasal symptoms, especially during the first trimester when harm to the developing fetus from treatment is most likely. Severe symptoms warrant treatment, however, as does the need to prevent complications. Consideration must be given to safety information as well as comparative efficacy. The non-pharmacological approach of decreasing environmental allergens and irritants (such as cigarette smoke) is essential. Therapies (drugs and others) and their safety in pregnancy are listed in Table VIII.

Table VIII.
Suggested safe therapies for allergic rhinitis in pregnancy.

Environmental control
Normal saline lavage
Pharmacotherapy
Oxymetazoline topical
Pseudoephedrine orally
– do not use combination drugs
Sodium cromoglycate
Topical steroids
Occupational allergic rhinitis
Occupational allergic rhinitis may be more common and more severe than previously recognised, as highlighted by the reported increasing prevalence of latex allergy. Occupational allergic rhinitis occurs as a result of exposure to an allergen or a hapten at the work place. The distinction between allergic and non-allergic rhinitis may not be clear-cut, with a considerable degree of overlap occurring. A low concentration of a substance may act as an allergen resulting in the formation of specific IgE, whereas a higher concentration of the same substance may also act as an irritant.
The incidence of occupational allergic rhinitis may be higher than realised because:
Individuals might not complain about their symptoms for fear of jeopardising their job.
Allergic rhinitis is not a compensable illness, making it less likely to be reported, especially if symptoms are mild.
The incidence of allergic rhinitis is high in the general population, so it may be difficult to decide if symptoms are work-related.
Reports have appeared describing patients with allergic rhinitis, who have gone on to develop asthma after continued exposure to the allergen. This makes the need to prevent and treat allergic rhinitis more urgent. The symptoms and signs of occupational allergic rhinitis may differ slightly from those of non-occupational rhinitis.90 The incidence of crusting of the nasal mucosa was found to be higher, as were epistaxis and disturbances of olfaction.
Atopic individuals who are exposed to irritants and/or pollutants may become more prone to develop allergic rhinitis, e.g. exposure to sulphur dioxide may lead to a patient reacting to a lower concentration of the allergen which causes his or her allergic rhinitis. The diagnosis involves taking a careful history and confirming allergy through a positive skin test or CAP RAST. Nasal provocation may on rare occasions be required to confirm diagnosis.

Where the diagnosis is in doubt, a worker should be removed from exposure to a suspected allergen for I week and then re-introduced to the work area, where the patient’s symptoms and signs could be assessed. Rhinomanometry may assist in obtaining an objective measurement of nasal obstruction.

Causes of occupational allergic rhinitis include:
Allergic protein substances:
animal and insect proteins derived from cats, dogs, horses, cows, poultry, rats, mice, rabbits, fish, cockroaches, mites, enzymes (derived from the Bacillus subtilis etc.)
Plant and tree proteins (e.g. cereal grains, cotton seed, grasses, latex, wood dusts, papaine, colophony, etc.12)
Low-molecular-weight substances:
these usually act as haptens and include di-isocyanates, anhydrides and metallic salts (platinum, nickel, chromium and aluminium).91
Building-related illnesses.
Treatment includes the following:
Pre-employment assessment for atopy may allow appropriate placement.
Allergen reduction.
Effective ventilation may lower the concentration of the allergen to a level where symptoms are reduced and even eliminated.
If possible a sensitive worker may be moved to an area where allergen exposure is eliminated.
Medical treatment as has already been described.
The South African Allergic Rhinitis Working Group gratefully acknowledges sponsorship of the group by Glaxo Wellcome South Africa. The group would, in particular, like to thank Mr Bruno Adam and Mrs Marilyn du Plooy for liaison and organisation, and Mrs Dalene Goosen and Mrs Devi Nager for assistance in literature searches.

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