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BSACI Rhinitis Guideline Scadding et al. 2015
BSACI guideline for the diagnosis and management of allergic and
non-allergic rhinitis (Revised Edition 2014; First edition 2007)
Glenis. K. Scadding*, Harsha Kariyawasamǂ, Guy Scadding‡, Rita Mirakian*, Roger J.
Buckleyɸ, Tina Dixon¥, Stephen R. Durham‡, Sophie Farooqueǂ, Pia AJ Huber, Nicholas
Jones¶, Susan Leech, Shuaib M. Nasser#, Richard Powell, Graham Roberts||, Guiseppina
Rotiroti*, Angela Simpson≠, Helen Smith§, Andy T. Clark#
*The Royal National Throat Nose and Ear Hospital, Gray’s Inn Road, London UK#Cambridge University Hospital NHS Foundation Trust, Cambridge UK‡Department of Upper Respiratory Medicine, Imperial College NHLI, Guy Scadding Building Royal Brompton
Campus, London UK≠Academic Division of Medicine and Surgery, Manchester University, Manchester UKǂChest and Allergy Department, St Mary’s Hospital, Imperial College NHS Trust, London UK¥Royal Liverpool and Broadgreen University Hospital NHS Trust, Liverpool UK
¶The Park Hospital, Nottingham UK§Division of primary care and public health, University of Brighton, Brighton UK||Department of Child Health, University of Southampton Hospital, Southampton UKDepartment of Child Health, King’s College Hospital, London UKDepartment of Clinical Immunology and Allergy, Nottingham University, Nottingham UKɸVision and Eye Research Unit, Anglia Ruskin University, East Road, Cambridge, UKBritish Society for Allergy & Clinical Immunology, London, UK
Address for Correspondence:
Dr AT Clark
Cambridge University Hospitals NHS Foundation Trust
Box 40
Allergy Clinic
Cambridge CB2 0QQ
Email: atclark@doctors.org.uk
Tel: 01223 762603
Keywords: allergic, allergen, allergy, antihistamine, anti-leukotriene, aspirin, asthma, BSACI,
quality of life, cat allergen, child, corticosteroid, cromoglicate, decongestant, guideline,
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BSACI Rhinitis Guideline Scadding et al. 2015
house dust mite, idiopathic rhinitis, IgE, immunotherapy, ipratropium bromide, lactation,
nitric oxide, non-allergic, non-allergic, non- infectious rhinitis, NINAR, occupational,
pregnancy, rhinitis, rhinitis control, skin prick test, SOCC, subcutaneous immunotherapy,
sublingual immunotherapy, surgery
INTRODUCTION
Allergic rhinoconjunctivitis (AR) remains the most common immunological disease in man
and is still subject to under-recognition and poor management (1NEW). This matters
because AR significantly reduces quality of life (QOL) (Laforest and others 2005), interferes
with both attendance and performance at school and work (Blaiss 2004; Cockburn and
others 1999) and results in substantial societal costs (Blaiss 2000). In addition, since the
nose is the gateway to the respiratory tract, rhinitis is associated with symptoms arising
from the eyes (Hom and Bielory 2013), sinuses (Slavin 1998), middle ear (Doyle 2002), the
nasopharynx and lower airways (Passalacqua and others 2004). Both AR and non-allergic
rhinitis (NAR) are risk factors for the development of asthma (Barry 2000).
Recent advances in rhinitis include evidence for local allergic rhinitis, the demonstration of
the greater effectiveness of combination therapy, the concept of SCUAD, severe chronic
upper airways disease, and of rhinitis control.
All patients presenting with nasal symptoms require appropriate treatment based on an
accurate diagnosis. These guidelines for the management of patients with rhinitis are
intended to facilitate this. Evidence for the recommendations was obtained by using
electronic literature searches using the primary keyword – rhinitis. Further searches were
carried out by combining this search term with allergy, conjunctivitis, non-allergic,
epidemiology, occupational, concordance, adherence, compliance, comorbidities,
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vasomotor, idiopathic, neurogenic, asthma, immunotherapy, anti-IgE, sublingual
immunotherapy (SLIT), corticosteroid, antihistamine, anti-leukotriene, ipratropium bromide,
decongestant, cromoglicate, carbon dioxide, pharmacotherapy, complementary medicine,
alternative medicine, homeopathy, hypnotherapy, acupuncture, acupressure, herbal
medicine, allergen avoidance, cat, house dust mite(HDM), control, quality of life, anti-IgE,
child, pregnancy, lactation, surgery, turbinectomy, aspirin, economics.
Each article was reviewed for suitability for inclusion in the guideline. The recommendations
were evidence graded, see appendix A (British Thoracic Society 2003; Shekelle and others
1999). During guideline development a web-based system was used to allow consultation
with all BSACI members. The draft guidelines were amended by the Standards of Care
Committee (SOCC) after careful consideration of all comments and suggestions. Where
evidence was lacking, a consensus was reached among the experts on the committee.
Conflicts of interest were recorded by the SOCC; none jeopardized unbiased guideline
development.
Executive summary and recommendation
Allergic rhinitis
Is common and affects over 20% of the UK population
Affects quality of life, school and work attendance, and performance
Is diagnosed by history and examination backed up by specific allergy tests
Is a risk factor for the development of asthma
Topical nasal corticosteroids are the treatment of choice for moderate to severe disease
(Grade of recommendation=A)
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Combination therapy with intranasal corticosteroid plus intranasal antihistamine is more
effective than either alone and provides second line treatment for those rhinitis poorly
controlled on monotherapy (Grade B)
Treatment of rhinitis from retrospective studies is associated with benefits for asthma
(Grade of recommendation=A)
Immunotherapy is highly effective in selected cases (Grade of recommendation=A)
Non-allergic rhinitis
Is a risk factor for the development of asthma.
Has a variety of causes.
May be eosinophilic and steroid- responsive or neurogenic and non- inflammatory.
May be a presenting complaint for systemic disorders such as Wegener’s, Churg-Strauss and
sarcoidoisis.
Infective rhinitis
Can be caused by viruses, and less commonly by bacteria, fungi and protozoa.
Is often more severe in allergic patients especially if infection occurs at the time of allergen
exposure.
DEFINITIONS / CLASSIFICATION
Definitions
Rhinitis describes inflammation of the nasal mucosa but is clinically defined by symptoms of
nasal discharge, itching, sneezing and nasal blockage or congestion. When the conjunctivae
are also involved, the term rhinoconjunctivitis is more accurate. Involvement of the sinus
linings in more severe disease is known as rhinosinusitis.
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Rhinitis has multiple phenotypes, usually divided into allergic, non-allergic and infective.
Mixed forms exist. This document concerns itself predominantly with the evidence- rich
area of AR.
Classification of AR.
The WHO ARIA workshop ‘Allergic Rhinitis and its impact on Asthma’ (Bousquet and others
2001) classification of AR based on frequency and severity of symptoms (Fig. 1) has been
validated (Demoly and others 2003a). Additionally clinical classification into seasonal and
perennial rhinitis is useful in UK practice for diagnosis and allergen specific therapy. Triggers
for AR are shown in Table 1.
Infective rhinitis
Any cause of congestion of the nasal mucosa can lead to occlusion of the sinus ostia,
predisposing to rhinosinusitis, and/or eustachian tube dysfunction. The causes and disease
patterns of infective rhinitis are summarised in Table 2.
Non-allergic rhinitis
The numerous diagnoses in this category need to be borne in mind for patients with
negative skin prick tests (SPTs). Table 3 summarizes the causes and disease patterns of NAR.
EPIDEMIOLOGY
The prevalence of allergic rhinitis in the UK has been reported as 10.1% and 15.3% in 6-7
and 13-14 year olds, respectively (Asher and others 2006), and a study combining
questionnaire and clinical assessment, including analysis of allergen-sensitisation, estimated
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prevalence in UK adults at 26% (Bauchau and Durham 2004). Peak prevalence appears to
occur in the 3rd and 4th decades (Blomme and others 2013; Eriksson and others 2012), with
some evidence for remission in allergic sensitisation during adult life (Warm and others
2012).
The prevalence of allergic rhinitis in the UK and Western Europe has increased dramatically
over the past 4-5 decades (Braback and others 2004; Gupta and others 2007). Some studies
suggest a plateau may have been reached (Asher and others 2006; Bjorksten and others
2008; Braun-Fahrlander and others 2004; Gupta and others 2007), whilst others report
continued increases since the 1990s (Duggan and others 2012; Ghouri and others 2008;
McNeill and others 2009). There is a male preponderance before adolescence (Alm and
others 2011; Alm and others 1999; de Bot and others 2009; Duggan and others 2012),
reversing post-adolescence (Eriksson and others 2012; Kellberger and others 2012; Mai and
others 2014). Worldwide, there appears to be a correlation between economic and
industrial development and the prevalence of allergic rhinitis (Asher and others 2006;
Katelaris and others 2012); post-communist Eastern Europe has seen accelerating
occurrence (von Mutius E. and others 1998). Local allergic rhinitis, confirmable only by nasal
provocation, has been found to have a prevalence of over 25% in some centres (Rondon and
others 2012).
Rhinitis is strongly associated with asthma: 74-81% of asthmatics report symptoms of
rhinitis (Leynaert and others 2004); rhinitis, both allergic and non-allergic, is a strong risk
factor for new-onset asthma (Guerra and others 2002; Shaaban and others 2008). Most
epidemiological studies report on allergic rhinitis, fewer have investigated non-allergic
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rhinitis. A prevalence ratio of allergic to non-allergic rhinitis of 3:1 has been suggested
(Settipane 2009).
AETIOLOGY
An overview of aetiological factors and associations of rhinitis is given in table 4. Genetic
predisposition is probably the most important factor in its development, but identification
of specific susceptibility genes has proved difficult. The development of large scale, genome
wide association studies (GWAS) has allowed identification of several candidate loci and
genes for asthma and atopic dermatitis (Moffatt and others 2010; Moffatt and others 2007;
Paternoster and others 2012; Portelli and others 2014). To date, only one such GWAS has
been carried out for AR (Ramasamy and others 2011). Of note, classical genetic change (i.e.
change in DNA nucleotide sequence) is unable to account for the rapid increase in
prevalence of AR seen in recent years, suggesting environmental factors (and possible gene-
environment interactions) are important. Epidemiological evidence suggests various factors
are involved: smaller family size, urban environments, and reduced exposure to infectious
disease are some of the best supported candidates, and appear to have particular effect
during early life (Matricardi and others 2002; Riedler and others 2001; Strachan 1989a;
Strachan 1989b). Epigenetic modifications, such as DNA methylation, may be involved in the
mechanism of gene-environment interactions in allergic diseases (Kabesch 2014).
PATHOPHYSIOLOGY
The basic mechanisms of allergic rhinitis are illustrated in Figure 2. Sensitised patients with
allergic rhinitis have IgE antibodies for specific allergen(s) bound to receptors on the surface
of mast cells. On re-exposure to the specific allergen(s), cross-linking of adjacent IgE
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molecules occurs, and mast cell degranulation results. Pre-formed mediators such as
histamine stimulate sensory nerve endings within seconds, causing itch and sneezing, and
promote dilatation of local vasculature and glandular secretion, causing obstruction and
rhinorrhoea, respectively. Newly-synthesised mediators, including leukotrienes, as wells as
chemokines and cytokines contribute to a delayed eosinophil and Th2 T-cell predominant
inflammation, the late phase response, characterised by nasal obstruction and hyper-
reactivity (Hansen and others 2004).
Additional mechanisms are likely to be relevant. These include neuro-immune interactions,
such as release of neuropeptides (substance P, calcitonin gene-related peptide) and
neurokinins from sensory nerve endings in response to inflammatory mediators (Van
Gerven L. and others 2012). The role of the epithelium, particularly its interaction with
newly-defined type 2 innate lymphoid cells (ILC2), has been scrutinised in murine asthma
and allergy models (Licona-Limon and others 2013; Lloyd 2010) as well as in human asthma
(Saglani and others 2013; Ying and others 2008). Further research is needed to confirm the
relevance epithelial-derived cytokines such as TSLP, IL-33 and IL-25 as well as ILC2 cells in
allergic rhinitis (Scadding 2014).
Non- allergic rhinitis, NAR ( also called non-allergic, non- infectious rhinitis NINAR , or
idiopathic rhinitis)
This is a diagnosis of exclusion in patients negative for systemic IgE, when the many other
causes of rhinitis, have been ruled out (Table 3). The terminology of vasomotor rhinitis,
which is inaccurate, has been dropped in the UK. There remain many questions about the
nature of NAR (Bousquet and others 2008).
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Pathophysiology.
Unfortunately much of the evidence around NAR is of poor quality because of inadequate
patient selection. However reliable data suggests at least two subgroups: one with nasal
inflammation on histology (Powe and others 2001), the other without inflammation or local
IgE production (Kleinjan and others 2000). The former includes local allergic rhinitis and
non- allergic rhinitis with eosinophilia( NARES ); some of this group are aspirin / NSAID
sensitive (Szczeklik and others 2000).
The non-inflammatory rhinitis subjects are thought to suffer from a dysfunction of the
autonomic nerve supply to the nasal mucosa (an imbalance in favour of the
parasympathetic system, resulting in gland hypersecretion and loss of the normal
sympathetic vasomotor tone) and/or a dysfunction of non-adrenergic, non-cholinergic
unmyelinated sensory C-fibres, with an excess of neuropeptide-mediated responses
(Settipane and Kaliner 2013; Van Gerven L. and others 2012).
Triggers are non-allergic (Table 3) and symptoms continue despite a change of location.
Mixed forms of rhinitis, with inflammatory and neuronal elements are thought to occur in a
high proportion of sufferers (Bernstein 2010), with mediators such as histamine and
substance P irritating nerve endings in the mucosa. This combined with antidromic reflexes
may be the basis of rhinitis – induced conjunctival symptoms and bronchial hyper-
reactivity.
Co-morbid associations of rhinitis
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AR coexists with other organ-specific allergic disorders,such as asthma and atopic
dermatitis, especially in children. It also has other associated comorbid disorders which can
be subdivided into
a)other allergic diseases,e.g. asthma, atopic dermatitis ,food allergy,oral allergy syndrome,
anaphylaxis, eosinophilic oesophagitis;
b) problems related anatomically to the nose: conjunctivitis, rhinosinusitis, hyposmia,
middle ear problems, throat and laryngeal effects;
c) Sleep problems and secondary effects of symptoms on concentration, mood and
behaviour, such as depression, anxiety, sexual dysfunction, attention deficit hyperactivity
disorder, reduced driving ability.
d) Others- where cause and effect is uncertain: migraine, high arched palate, or where the
co- morbidity may cause rhinitis symptoms: e.g. gastro- oesophageal reflux, hypothyroidism.
Table 5 shows evidence for the major co-morbidities.
The most important co-morbidity is asthma: not only is rhinitis a risk factor for subsequent
asthma, but the majority of asthma sufferers have concomitant rhinitis, poor control of
which is a risk factor for asthma exacerbations (Clatworthy and others 2009; de Groot and
others 2012; Lasmar and others 2006; Price and others 2005; Thomas and others 2005).
Occupational rhinitis
Occupational rhinitis, which can be allergic or non-allergic, describes abnormalities of the
nasal mucosa mediated by airborne substances in the work environment. It is distinct from
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work-exacerbated rhinitis which refers to individuals with pre-existing rhinitis who
experience an exacerbation of symptoms due to workplace exposures.
There are over 300 agents that can give rise to occupational rhinitis and these are the same
as those that induce occupational asthma. These agents are classified as either high
molecular weight (HMW) (>5kDA) or low molecular weight (LMW) agents (<5kDA)(Table 6)
(Bernstein and others 2006). HMW agents are protein allergens derived from plants or
animals e.g. flour, latex, laboratory animals and elicit specific IgE (Raulf and others 2014).
Evidence of sensitisation to HMW agents will usually be seen on skin testing or serum
specific IgE. LMW agents can either cause mucosal inflammation either via airway immune
sensitisation, e.g. di-isocyanates and glutaraldehyde or via irritant exposures e.g. chlorine
and ammonia. An asymptomatic latency period of exposure lasting weeks to years often
precedes symptoms of occupational rhinitis to LMW agents (Hox and others 2014).
Occupational rhinitis is three times more frequent than occupational asthma but the two
conditions frequently occur together (Karjalainen and others 2003; Siracusa and others
2000). Occupational rhinitis generally precedes, and may be a risk factor for, occupational
asthma. The risk of occupational asthma is highest in the year after the development of
occupational rhinitis (Cortona and others 2001; Karjalainen and others 2003). (level of
evidence 2-). The early identification of a causative occupational agent and the avoidance of
exposure are important measures for the management of occupational rhinitis and
prevention of progression to occupational asthma (Colloff and others 1992; Filon and
Radman 2006; Kronqvist and others 1999; O'Meara and others 2005). (level of evidence = 2+
+; grade of recommendation=B)
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Diagnosis is based on a detailed history, symptomatic diary cards, improvement of nasal
symptoms during weekends and holidays, skin prick testing and measurement of specific IgE
when appropriate. Where available the gold-standard for diagnosis remains nasal
provocation testing.
Latex is a cause of both occupational rhinitis and asthma. Prevention of latex allergy by
removing powdered gloves or substituting non-latex ones is essential. All healthcare
environments should have a latex policy (Filon and Radman 2006; Hemery and others 2004).
(Level of evidence=2+ and 4; Grade of recommendation=D, C for adults and children with
perennial rhinitis or adults and children with latex allergy.)
DIAGNOSIS OF RHINITIS
History
A detailed history focusing on the severity of individual symptoms of rhinitis is required for
accurate diagnosis. The patient is asked to list their main symptoms in order of priority and
this usually produces a short list of differential diagnoses. Longstanding symptoms can also
result in systemic manifestations affecting quality of life such as difficulty sleeping, fatigue,
and impaired concentration leading to reduced productivity.
Symptoms
Nasal Symptoms
Sneezing, itchy nose, itchy palate
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Itching indicates a likely diagnosis of allergic rhinitis and asking whether the symptoms are
intermittent or persistent may provide a clue to the allergic cause. However, this is not a
substitute for specific allergen testing.
Seasonal at the same time each year? – pollens or mould spores
At home?- pets or house dust mite
At work? - occupational allergens
On holiday? – remission suggests an environmental or allergic cause
Rhinorrhoea
Rhinorrhoea is either anterior or leads to a post nasal drip:
Clear - infection unlikely
Unilateral - is uncommon and cerebrospinal fluid (CSF) leak should be excluded
(Marshall and others 2001)
Coloured
o yellow - allergy or infection
o green - usually infection
o blood tinged
unilateral – tumour, foreign body, nose picking or misapplication of nasal spray
bilateral – misapplication of nasal spray, granulomatous disorder, bleeding
diathesis, infection, nose picking.
Nasal obstruction
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Obstruction may be partial or complete with the severity often correlating with systemic
manifestations such as interrupted sleep.
Bilateral –most likely rhinitis or nasal polyps but maybe septal (sigmoid) deviation
Unilateral – usually septal deviation but also consider foreign body, antrochoanal polyp
and tumours
Alternating – generalised rhinitis exposing the nasal cycle (Flanagan and Eccles 1997)
Nasal crusting
Severe nasal crusting especially high inside the nose is an unusual symptom and requires
further investigation. Consider:
chronic rhinosinusitis (Jennings and others 1998)
nose picking
Wegener’s granulomatosis, sarcoidosis
other vasculitides
ozaena (wasting away of the bony ridges and mucous membranes inside the nose)
non-invasive ventilation
rarely, topical steroids may cause crusting
Cocaine abuse
Eye symptoms
Eye symptoms associated with allergic rhinitis and particularly with seasonal rhinitis include
intense itching, redness and swelling of the white of the eye (i.e. hyperaemia and oedema of
the conjunctival surfaces), and watering, which may momentarily blur the vision. Lid
swelling and (in severe cases) periorbital oedema are enhanced by eye rubbing.
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Lower respiratory tract symptoms
Cough, wheeze, shortness of breath- can occur with rhinitis alone since bronchial hyper-
reactivity can be induced by upper airway inflammation (Laitinen 1974; Laitinen and
Kokkola 1974; Townley and others 1965).
Disorders of the upper and lower respiratory tract often coexist:
Most asthmatics have rhinitis – see section on rhinitis and asthma
In asthma with aspirin sensitivity – 36-96% have upper airway disease, usually nasal
polyps with rhinosinusitis, a few have rhinitis (Settipane and Chafee 1977).
Other Symptoms
Other symptoms such as snoring, sleep problems, repeated sniffing or a nasal intonation of
the voice can be caused or exacerbated by nasal obstruction and rhinorrhoea from any
cause. In some patients with seasonal allergic rhinitis, oral allergy syndrome is triggered by
ingestion of cross-reacting antigens in some fruits, vegetables and nuts (Ortolani and others
1988).
Family history
A diagnosis of allergic rhinitis is more likely when rhinitis is seasonal, in the presence of
asthma or a family history of atopy (VAN ARSDEL PP and MOTULSKY 1959).
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Social history
In order to assess possible allergen and irritant exposure a full history of housing conditions,
presence of pets or other contact with animals, occupation or schooling and, in young
children, feeding details should be obtained.
Drugs
A number of drugs can cause or aggravate rhinitis symptoms and therefore a drug history
should include details of the use of alpha- and beta-blockers and other anti-hypertensives,
aspirin and other non-steroidal anti-inflammatory drugs, oral contraceptives as well as
topical sympathomimetics (see table 3). It is also important to enquire about the efficacy of
previous treatments for rhinitis and details of how they were used and for how long.
Occupation
When symptoms occur at work and improve when away from work or on holiday an
occupational irritant or allergen triggering rhinitis should be suspected.
Examination
Visual assessment
Allergic salute and/or horizontal nasal crease across dorsum of nose supports a diagnosis
of allergic rhinitis
Chronic mouth breathing
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An assessment of nasal airflow – (e.g. metal spatula misting in young children)
Depressed nasal bridge – post surgery, Wegener’s granulomatosis or cocaine misuse
Widened bridge; polyps (see also BSACI guideline on rhinosinusitis and nasal polyposis;
(Scadding and others 2008))
Purple nasal tip due to sarcoidosis
Anterior rhinoscopy
Hypertrophic, pale and boggy inferior or middle turbinates suggest inflammation, but
nasal appearance may be normal
Presence or absence of clear, coloured or purulent secretions
Presence or absence of nasal polyps, but it may not be possible to see small ones or if
they are confined to the sinuses. Larger polyps can be seen in the nasal vestibule
sometimes extending as low as the nares and can be distinguished from the inferior
turbinate by their lack of sensitivity, yellow/ grey colour and the ability to get between
them and the side wall of the nose.
Yellow sub-mucosal nodules with a cobblestone appearance suggest sarcoidosis (Fergie
and others 1999).
Crusting and granulations raise the possibility of vasculitis.
Septal perforation may occur after septal surgery or due to chronic vasoconstriction
(cocaine, alpha agonists), Wegener’s granulomatosis, nose picking and rarely due to
steroid nasal sprays.
INVESTIGATIONS
Objective measures of nasal airway
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Objective measurements of the nasal airway are not made in routine clinical practice but
can be useful when allergen or aspirin challenges are undertaken and may be helpful when
septal surgery or turbinate reduction are being contemplated.
Peak nasal inspiratory flow
Measurement of peak nasal inspiratory flow (PNIF) provides a simple and inexpensive
method for determining nasal airway patency using a nasal inspiratory flow meter. The
results are reproducible and correlate with rhinoscopic evidence of rhinitis but not with
symptom scores (Starling-Schwanz and others 2005). The technique is most useful for
comparing changes in airway patency within the same subject, although some normative
data is now available (Ottaviano and others 2006).
Acoustic Rhinometry
Acoustic rhinometry can be used to measure changes in mucosal congestion using reflected
sound. The technique is based on the physical principle that sound in the nasal cavity is
reflected by changes in acoustic impedance caused by changes in cavity dimensions. The
change in acoustic impedance between the incident wave and reflected sound waves is
proportional to the cross-sectional area. The method requires standardization and
considerable experience to interpret and obtain reproducible results. Guidelines for its use
are published (Hilberg and Pedersen 2000).
Rhinomanometry
Rhinomanometry allows an estimation of nasal resistance from pressure-flow relationships
and is difficult to perform reproducibly but still regarded by some as the most accurate
measure of nasal airway patency. With anterior rhinomanometry, the pressure sensor is
placed at the tip of each nostril and resistance measured in each nostril separately. With
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posterior rhinomanometry the pressure sensor is placed in the back of the nasal cavity and
total nasal airway resistance is determined. The technique requires expensive equipment
and considerable experience in interpretation (Clement 1984).
Nasal endoscopy
Used in specialist centres, this is more specific than rhinoscopy and alters the diagnosis in up
to a fifth of patients with nasal disease (Hughes and Jones 1998).
Allergen specific IgE can be detected with skin prick tests (SPTs) or by serum immunoassay.
Skin prick tests
Skin prick tests (SPT) should be carried out routinely in all cases in order to determine if the
rhinitis is allergic or non-allergic. Injectable adrenaline should be available, but is unlikely to
be needed.
Must be interpreted in the light of the clinical history. At least 15% of people with a
positive skin prick test do not develop symptoms on exposure to the relevant allergen
(Droste and others 1996).
Have a high negative predictive value.
Suppressed by antihistamines, tricyclic antidepressants and topical but not oral steroids
(Taborda-Barata and others 1996).
Are inadvisable outside specialist allergy clinics if the patient has a history of
anaphylaxis.
Serum total and specific IgE
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Serum specific IgE may be requested when skin tests are not possible or when the SPT
together with the clinical history give equivocal results.
Total IgE alone can be misleading but may aid interpretation of specific IgE.
Allergen specific IgE correlates with the results of skin prick tests and nasal challenges
although there are exceptions.
Currently available SPTs and immunoassays show similar sensitivity for house dust mite
(HDM), but SPTs are more sensitive to other inhalant allergens such as cat epithelium,
mould and grass pollen (Gleeson and others 1996).
Routine laboratory investigations
Other investigations to help with the initial management of patients with rhinitis are guided
by the findings from the history, examination and results of skin prick tests. Examples of
routine laboratory investigations include:
Full blood count (FBC) and differential white cell count
C-reactive protein (CRP)
Nasal smear/brushing for eosinophils
Microbiological examination of sputum and sinus swabs
Nasal secretions-CSF asialotransferrin for CSF rhinorrhoea
Urine toxicology when cocaine abuse is suspected
Olfactory tests
The University of Pennsylvania Smell Identification Test (UPSIT) is well validated, can identify
malingerers (Doty and others 1984) and is accepted for legal cases.
Cytology
The techniques for obtaining cells for cytology in secretions, lavage, scraping, cotton
pledgelets or brushings has not been standardised, nor have the criteria for evaluating cell
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counts (Romero and Scadding 1992). Nevertheless the presence of eosinophils implies
inflammation and may be helpful in predicting response to corticosteroids.
Exhaled nitric oxide (eNO)
Exhaled nitric oxide (FeNO = fractional exhaled nitric oxide) measurement can be useful
clinically in the diagnosis and monitoring of asthma. Normal levels are less than 20ppb, but
become elevated in eosinophilic lower respiratory tract inflammation (Prieto and others
1994).
Radiology
Radiology is not routinely recommended for rhinitis patients.
Nasal challenge
Is not routinely available outside specialist centres.
There is no standardised methodology.
Asthmatic reactions can occur.
May be useful to confirm aspirin sensitivity.
May be useful in patients with an unclear history and negative or equivocal tests for
allergen specific IgE or when the trigger is not IgE-mediated.
Has a role in occupational allergic rhinitis, where there is discrepancy between history
and when there are potentially important occupational implications.
Can be used to assess nasal hyper- reactivity to histamine or metacholine in a research
setting.
Tests for asthma
Measurements of lung function should be considered in all patients with persistent rhinitis
e.g. (peak expiratory flow rate (PEFR) or spirometry as detailed in the British Thoracic
Society guidelines on the management of asthma (British Thoracic Society 2003).
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ENT referral
Patients with unilateral symptoms, heavily blood stained discharge, pain, or orbital cellulitis
need ENT referral, urgently for orbital swelling, redness and pain. Those with structural
abnormalities, such as septal deviation, which render nasal therapy difficult, should also be
seen by a surgeon.
TREATMENT (see figure 3)
Allergen avoidance
Allergen avoidance clearly works in rhinitis - in the case of seasonal allergic rhino-
conjunctivitis patients are symptom-free outside the pollen season. For patients with
allergic rhinitis/ rhinoconjunctivitis who are sensitised to house dust mite, the situation is
complicated by the difficulties of reducing exposure to mites, and evidence from
randomised studies is summarised in Table 7. For occupational allergic rhinitis, complete
avoidance of exposure to the causal agent is recommended (Raulf and others 2014)).
Irritants such as smoke, traffic pollution, etc. can worsen rhinitis symptoms and should be
avoided, where possible.
House dust mite.
After pollen, HDM is the most common sensitisation found in patients with
rhinoconjunctivitis in the UK and sensitisation to mites is associated with perennial
symptoms. Many methods have been developed which aim to reduce exposure to mite
allergens in the home; those that have been tested in randomised trials of rhinitis include air
filtration (such as HEPA filters), chemicals to kill mites (acaricides) and barriers to keep mites
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BSACI Rhinitis Guideline Scadding et al. 2015
and allergen from reaching patients (such as mattress encasings) (Recer 2004; Terreehorst
and others 2003). A summary allergen avoidance measures with grades of evidence is
presented in Table 7 Acardust studies to be added to this table; studies published by 2009
were included in the updated Cochrane systematic review (Geller-Bernstein and others
1995; Nurmatov and others 2012).
Pollen avoidance in seasonal allergic rhinitis.
Nasal filters have been shown to reduce symptoms of AR and allergic conjunctivitis
significantly during the ragweed and grass pollen seasons (O'Meara and others 2005). A
number of other measures are often recommended to patients with pollen allergy to
minimize symptoms but these are based on expert consensus rather than clinical trial data
(Table 7). Haymax™ balm decreases levels of allergen entering the nose by a third; it is not
known whether other substances such as petroleum jelly have the same effect (Kennedy
and others 2012). In a DBRPC study the application of a cellulose powder (Nasaleze™)
resulted in significant reductions in severity scores for sneezing, runny nose, stuffy nose and
symptoms from eyes and lower airways and no clinically significant adverse effects were
reported (Aberg and others 2014). Ozturk and colleagues found in a randomised controlled
study that patients wearing sunglasses had significantly decreased ocular symptoms and
antihistamine use (Ozturk and others 2013).
Pet allergens
For patients with allergic rhino-conjunctivitis who are sensitized to and symptomatic on
contact with pets such as cats, dogs and horses, avoidance of the animal is clearly beneficial
and should be advised. For those who wish to keep pets to which they are sensitized, there
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BSACI Rhinitis Guideline Scadding et al. 2015
is limited information from randomized studies on which to base recommendations
(summarized in Table 7). Bjornsdottir (Bjornsdottir and others 2003) found in a randomised
controlled study that reducing cat allergen in the environment of cat allergic patients over
an 8 months period was leading to significant improvement in nasal inspiratory flow rate
and symptoms. However, trials of brief cat removal are ineffective (Colloff and others 1992).
A number of measures to minimize cat allergen levels at home are recommended (Table 7).
Laminar airflow used nocturnally improved quality of life, airway inflammation and systemic
allergy to Fel d1, the major cat allergen, in a double blind study in children with persistent
atopic asthma (Boyle and others 2012). Recently it has been shown to reduce allergen
exposure (Gore and others 2015).
Saline irrigation
Hypertonic saline irrigation has been shown to be effective in children for the short term
treatment of hay fever (Chen and others 2014; Marchisio and others 2012), and isotonic
saline is well tolerated in children as young as 2 years (Jeffe and others 2012). In a review in
2013 (Dunn and others 2013) the high volume, low pressure device was claimed to be the
most effective though it warned against microbial contamination and reported 2 cases of
primary amoebic meningoencephalitis. However, a meta -analysis (Hermelingmeier and
others 2012) determined that despite heterogeneity of type, amount, frequency and
solution, isotonic saline irrigation had a positive effect on all investigated outcome
parameters (nasal symptom scores, medicine consumption, mucociliary clearance time and
quality of life) in both adults and children with allergic rhinitis, and it is well tolerated,
inexpensive, easy to use and there was no evidence of adverse effect to health with regular
use.
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BSACI Rhinitis Guideline Scadding et al. 2015
Pharmacotherapy
Allergen and irritant avoidance is difficult and many rhinitis sufferers continue to have
persistent symptoms, the nature of which should determine the selection of medication.
Available treatments and their effects upon individual symptoms are detailed in Table 8. All
have Grade A level of recommendation. Following exact diagnosis and classification
according to disease severity, therapy using a stepwise pharmacotherapeutic approach
should be undertaken. A combination of treatments is often needed for more severe
disease and it is here that the option of immunotherapy should also be considered (figure
3).
Antihistamines
Antihistamines are available as oral, intranasal and ocular preparations.
All demonstrate clinical efficacy. It is important to use a drug that is considered safe for the
current situation (i.e. such as pregnancy) with the least prominent adverse effect profile.
Oral antihistamines are classified into first and second generation groups (Table 9).
First generation anti-histamines are contra- indicated due to sedation and cognitive
impairment which can worsen driving and examination results already impaired by rhinitis
(Walker and others 2007; Weiler and others 2000).
Second generation antihistamines are long acting, and more selective for peripheral over
central H1 receptors due to poor penetration of the blood-brain barrier. They are largely
non-sedating and have no clinically significant anti-cholinergic activity at therapeutic doses,
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BSACI Rhinitis Guideline Scadding et al. 2015
although there is variation in individual susceptibility to such effects (Shamsi and Hindmarch
2000)
Oral H1- antihistamines (Table 9)
Reduce mean daily rhinitis symptom scores (in absolute terms) by an estimated 7%
versus placebo (Wilson and others 2004a).
Act predominantly on neurally-mediated symptoms of itch, sneeze and rhinorrhoea.
Have modest effects on nasal congestion (Canonica and others 2007; Ciprandi and
others 2004; Ciprandi and others 2001; Hore and others 2005; Nayak and Schenkel
2001; Patou and others 2006; van Steekelenburg J. and others 2002).
Reduce histamine driven symptoms such as itch (Dhand and Aminoff 2014) at sites
other than just the nose such as conjunctiva, palate and skin (Nelson 2003; Portnoy
and Dinakar 2004; Schwarzer and others 2004).
Regular therapy is more effective than ‘as needed’ use in persistent rhinitis (Ciprandi
and others 1997a; Leurs and others 2002).
Can significantly improve quality of life (Bachert and others 2004; Pariente and
others 1997).
Acrivastine has the fastest onset of action, but needs to be used 8 hourly; fexofenadine is
the least sedating oral antihistamine with a wide therapeutic index.
Adverse Effects:
Second generation antihistamines
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BSACI Rhinitis Guideline Scadding et al. 2015
Terfenadine and astemizole were implicated in deaths from ventricular fibrillation via QT
interval prolongation. There are no significant effects on QT prolongation at therapeutic
doses for loratadine, desloratadine, cetirizine, levocetirizine, rupatadine or fexofenadine.
Ebastine and mizolastine are cautioned in those with cardiac risk factors (Davila and others
2006).
Interaction with other medications is rare other than for mizolastine with certain anti-
arrhythmics, antibiotics and beta-blockers leading to an increased risk of arrhythmia.
Rupatadine should not be co-prescribed with known CYP3A4 inhibitors (Picado 2006).
Place in therapy
• First line therapy for mild to moderate intermittent and mild persistent rhinitis
• Addition to intranasal steroids for moderate/severe persistent rhinitis uncontrolled
on topical intranasal corticosteroids alone, particularly when excess neurogenic symptoms
are present (Juniper and others 1989; Ratner and others 1998; Simpson 1994).
Topical H1- antihistamines
Nasal
Azelastine nasal spray is the only available intranasal antihistamine in the UK.
Superior to oral antihistamines in attenuating rhinitis symptoms (Lee and Pickard 2007),
and in decreasing nasal obstruction (Horak 2008; Lieberman and others 2005).
Do not improve symptoms due to histamine at other sites, such as skin.
Rapid onset of action (15 minutes), faster than oral antihistamines (Horak and others
2006) Thus the drug can be used on demand as rescue therapy for symptom
breakthrough. Continuous treatment is however more clinically effective than on-
demand use (Ciprandi and others 1997b).
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BSACI Rhinitis Guideline Scadding et al. 2015
Can be effective in patients who have previously failed oral anti-histamines (LaForce and
others 2004). Treatment with both an intranasal and oral antihistamine confers no
additional advantage in alleviating nasal symptoms (LaForce and others 2004).
Less effective than an intranasal steroid in relieving the symptoms of allergic rhinitis
(Yanez and Rodrigo 2002).
Adverse Events
Local tissue irritation
Taste disturbance with azelastine (dysguesia)
Place in therapy
First line therapy for mild to moderate intermittent and mild persistent rhinitis.
When oral antihistamines are ineffective and before intranasal steroid use in less severe
disease.
Addition to intranasal steroids for moderate/severe persistent rhinitis uncontrolled on
topical intranasal corticosteroids alone.
Corticosteroid therapy
Intranasal corticosteroids (INS)
Topical corticosteroids are the mainstay of anti-inflammatory and immunoregulatory intervention in
allergic rhinitis. All current preparations are clinically efficacious. Other factors which need
consideration are systemic drug bioavailability, overall safety and cost (Bielory and Bielory 2014).
Ease of device use and sensory attributes of the formulation may improve compliance.
INS reduce all symptoms of rhinitis by about 17% greater than placebo, with a variable effect on
associated allergic conjunctivitis (Hong and others 2011; Keith and Scadding 2009).
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BSACI Rhinitis Guideline Scadding et al. 2015
Meta-analysis shows that INS are superior to both oral antihistamines or leukotriene receptor
antagonist alone on all aspects of allergic rhinitis (Weiner and others 1998; Wilson and others
2004a) (Grade Ia).
INS reduce nasal congestion (Weiner and others 1998)
Onset of action is 6-8 hours after the first dose, clinical improvement may not be apparent for a few
days and maximal effect may not be apparent until after two weeks (Weiner and others 1998).
Starting treatment two weeks prior to a known allergen season improves efficacy (Graft and others
1996).
Similar clinical efficacy for all INS, but bioavailability varies considerably (see Figure 4).
Systemic absorption negligible with mometasone furoate, fluticasone furoate and
fluticasone propionate, modest for the remainder, and high for betamethasone and
dexamethasone – these should be used short term only (Derendorf and Meltzer 2008;
Homer and Gazis 1999)
Long term growth studies in children using fluticasone propionate, mometasone furoate and
have reassuring safety data, unlike beclomethasone (Sastre and Mosges 2012; Skoner and
others 2000)
Concomitant treatment with CYP3A inhibitors such as itraconazole or ritonivir may increase
systemic bioavailability of intranasal corticosteroids. (Johnson and others 2006; Skov and
others 2002).
Adverse events
Local nasal irritation, sore throat and epistaxis affect around 10% of users.
Benzalkonium chloride is used as a preservative in several topical corticosteroids, and may
irritate the nose, but does not adversely affect mucociliary clearance (McMahon and others
1997). In patients with nasal irritation symptoms such as burning for example, a trial with a
benzalkonium free preparation, e.g. Rhinocort, Flixonase nasules is suggested.
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BSACI Rhinitis Guideline Scadding et al. 2015
Reduction of local adverse effects such as nasal crusting, bleeding and pain can probably be
achieved by correct use of the intranasal device, see figure 4a; (Grade of
recommendation=D).
Nasal drops are useful for severe obstruction and should be used in the ‘head upside down’
position in order to reach the ostiomeatal complex (OMC), see figure 4b.
Hypothalamic-pituitary axis suppression may occur when multiple sites are treated with
topical corticosteroids in the same person (e.g. skin, nose and chest) (Allen 2000).
Raised intra-ocular pressure has been described with INS (Bui and others 2005) and patients
with a history of glaucoma should be monitored closely (in collaboration with an
ophthalmologist or optometrist).
Place in Therapy
First line therapy for moderate to severe persistent symptoms (Bousquet and others 2001).
First line of therapy if presenting with severe nasal obstruction (Weiner and others 1998),
possibly combined with a short term nasal decongestant. In severe nasal obstruction steroid
drops or oral steroids should be used initially.
Addition to topical antihistamines in uncontrolled rhinitis- see below.
Combination Therapy
INS and oral preparations
INS demonstrate similar or greater efficacy to an oral antihistamine plus a leukotriene receptor
antagonist (Pullerits and others 2002a; Wilson and others 2001b). INS combined with an oral
antihistamine and leukotriene receptor antagonist together does not confer better clinical outcomes
compared to an INS alone in SAR (Di Lorenzo G. and others 2004).
INS and topical H1-antihistamine combination
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BSACI Rhinitis Guideline Scadding et al. 2015
Currently available as a combination spray containing azelastine and fluticasone propionate (FP),
Dymista leads to greater symptom improvement than using either agent alone in SAR (Carr and
others 2012a) (Grade A ). All symptoms of allergic rhinitis were significantly improved with onset of
action by 30 minutes (Meltzer and others 2012).
The combination approach leads to clinical improvement of symptoms days earlier than seen with
azelastine or FP monotherapy (Carr and others 2012a). Ocular symptoms of allergy were better
treated with the azelastine-fluticasone propionate combination spray rather than fluticasone
propionate or azelastine alone (Meltzer and others 2012). Efficacy over FP is demonstrated in
perennial allergic rhinitis (Price and others 2013).
Place in therapy
Combination of topical AH with INS should be used in patients when symptoms remain uncontrolled
on AH or INS monotherapy or on a combination of oral AH plus INS.
Systemic glucocorticoids
There are no trials of oral steroid use and efficacy in AR, though there is grade A evidence in chronic
rhinosinusitis with nasal polyposis where inflammation is more severe. Use is rarely indicated in the
management of allergic rhinitis except for:
Severe nasal obstruction
Short term rescue medication for uncontrolled severe symptoms when first presenting or to obtain
control during severe exacerbation despite compliance on conventional pharmacotherapy. It is
important to ensure intranasal steroid therapy is co-administered alongside oral steroids with or
without a short term decongestant spray to allow intranasal drug penetration (see below). There is
no definite consensus on the dose and duration of systemic steroid therapy. A suggested regime for
adults is 0.5mg per kg for 5-10 days. Oral preparations of steroids as a short course are
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BSACI Rhinitis Guideline Scadding et al. 2015
recommended over depot injectable preparations. Frequent oral steroid rescue should prompt
immunotherapy as a treatment option
Injectable corticosteroids
Injected preparations are not recommended
Compared to other available treatments the risk-benefit profile for intramuscular
corticosteroids is poor (Aasbjerg and others 2013; Nasser and Ewan 2001).
Decongestants
Decrease nasal congestion via vasoconstriction.
A paradoxical increase in nasal congestion secondary to rebound vasodilatation (rhinitis
medicamentosa) can occur (Scadding 1995a). The risk of this is patient -dependent with some
individuals vulnerable after 3 days of use so short term use is advised (Morris and others 1997; Yoo
and others 1997).
Intranasal decongestants
Topical formulations allow relief of nasal congestion within minutes, faster and with greater impact
than intranasal steroids (Barnes and others 2005; Baroody and others 2011a). A decongestant spray
may allow delivery of intranasal drugs beyond the inferior turbinates. For example oxymetazoline
and fluticasone furoate when used together further improved nasal congestion more than either
alone (Baroody and others 2011b).
INS plus decongestant combination
There is no licensed preparation in the UK at present.
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BSACI Rhinitis Guideline Scadding et al. 2015
Adverse events
Only short term use (generally less than 10 days) is recommended as risk of developing rebound
treatment resistant nasal congestion termed rhinitis medicamentosa increases with duration
(Scadding 1995b)
Intranasal decongestants are less likely to lead to rhinitis medicamentosa when used with minimal
frequency and alongside an intranasal steroid (Baroody and others 2011b).
Nasal irritation
May increase rhinorrhoea
Place in Therapy
Eustachian tube dysfunction when flying (evidence level D)
Children with acute otitis media to relieve middle ear pain /pressure (Evidence level D)
During or after URTI to reduce nasal/sinus congestion (Evidence level D)
To increase nasal patency before douching or intranasal administration of nasal steroids (ask HK)
Oral decongestants (pseudoephedrine)
Weakly effective in reducing nasal obstruction (Malm 1994).
Do not cause rebound effect on withdrawal but are less effective than topical preparations for nasal
obstruction (Naclerio 1998).
Effect lasts 30min - 6hrs or longer with slow-release preparations.
Adverse events
Hypertension
Interact with antidepressants
Insomnia
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BSACI Rhinitis Guideline Scadding et al. 2015
Agitation
Tachycardia
Place in Therapy
Not recommended.
Anti-leukotrienes
Anti-leukotrienes are of two kinds i) receptor antagonists (LTRAs, e.g. montelukast
and zafirlukast) (Scadding and Scadding 2010) and ii) synthesis inhibitors, e.g.
zileuton (unavailable in the UK).
There is a spectrum of individual responsiveness to LTRAs which is currently not
predictable (Fowler and others 2002; Mastalerz and others 2002; Sampson and
others 2000).
Therapeutic profile similar to antihistamines, with efficacy comparable to loratadine
in seasonal allergic rhinitis (Philip and others 2002). However, the response is less
consistent than that observed with antihistamines. LTRAs reduce the mean daily
rhinitis symptom scores by 5% more than placebo (Wilson and others 2004b).
Anti-leukotrienes are less effective than topical nasal corticosteroids (Philip and
others 2002; Pullerits and others 1999; Ratner and others 2003; Wilson and others
2001a).
Anti-leukotriene plus antihistamine combinations do not improve efficacy to a
clinically relevant extent compared to either drug used alone (Meltzer and others
2000; Nayak and others 2002; Wilson and others 2002; Wilson and others 2001c).
Combination of antihistamine and anti-leukotriene is no more effective than topical
corticosteroid alone (Di Lorenzo G. and others 2004; Pullerits and others 2002b).
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BSACI Rhinitis Guideline Scadding et al. 2015
May have a place in asthma patients with seasonal allergic rhinitis (Philip and others
2004).
Adverse events
Usually well tolerated; occasional headache, gastrointestinal symptoms or rashes.
Possible causal link between LTRA use and Churg-Strauss syndrome (Hauser and
others 2008; Nathani and others 2008). The association may relate more to steroid
withdrawal rather than a direct effect of the drug, although further long term
evaluation is needed.
Long term use has been associated with depression ( needs ref)
Place in Therapy
Montelukast is licensed in the UK for those with seasonal allergic rhinitis who also
have concomitant asthma (UK license for age > 6 months; Zafirlukast UK license>12
years).
May be useful in patients with asthma and persistent rhinitis
Topical Anti-cholinergic: Ipratropium bromide
Decreases rhinorrhoea but has no effect on other nasal symptoms (Grossman and
others 1995a; Kaiser and others 1998; Meltzer and others 1992; Tan and Corren
1995).
Needs to be used 3 times daily.
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BSACI Rhinitis Guideline Scadding et al. 2015
Regular use may be effective, particularly as an ‘add on’ for allergic rhinitis when
watery rhinorrhoea persists despite topical steroids and antihistamines (Dockhorn
and others 1999; Grossman and others 1995b).
Adverse Events
Dry nose and epistaxis (Wood and others 1995)
Systemic anti-cholinergic effects are unusual (Bronsky and others 1995)
o Urinary retention (Pras and others 1991)
o Glaucoma (in relation to inhaled drug in asthma) (De Saint and others 2000;
Hall 1994)
Caution advised in the elderly
Place in therapy
Patients with rhinorrhoea despite compliance with an INS or INS plus antihistamine.
Chromones (Sodium cromoglicate (=cromolyn) and nedocromil sodium)
Sodium cromoglicate and nedocromil sodium inhibit the degranulation of sensitized mast
cells, inhibiting the release of inflammatory and allergic mediators (Ratner and others 2002).
Sodium cromoglicate is weakly effective in rhinitis with some effect on nasal obstruction
(James and others 2003; Meltzer 2002). The spray needs to be used several times (3-4x) per
day.
Side Effects
Generally very well tolerated (including in pregnancy)
Local irritation
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BSACI Rhinitis Guideline Scadding et al. 2015
Rarely transient bronchospasm
Occasional taste perversion
Headache
Place in therapy
Children and adults with mild symptoms only and sporadic problems in season or on
limited allergen exposure (Hadley 2003). Useful for young children (< 3 years
old),pregnant females and steroid phobics.
Cromoglicate and nedocromil eye drops are useful in conjunctivitis as topical therapy
(James and others 2003; Owen and others 2004).
Ocular therapy
As with rhinitis, allergen avoidance is difficult to achieve: sunglasses reduce eye
symptoms (Ozturk and others 2013), but since some occur secondary to nasal
inflammation complete protection is impossible . The ocular manifestations of
seasonal rhinoconjunctivitis can often be suppressed by oral antihistamines, usually
H1 receptor antagonists, and by intra-nasal agents, including corticosteroids,
antihistamines and combination products. However they are often better treated
selectively using topical therapy in eye drop form. Mast cell stabilisers such as
sodium cromoglicate, nedocromil sodium and lodoxamide are generally effective and
safe (Owen and others 2004). Antihistamines such as azelastine, emedastine and
epinastine may be preferred by some patients (Glacy.J and others 2013). A drug with
both mast cell stabilising and antihistaminic properties, olopatadine, is often
effective and well tolerated, and has the advantage of twice daily application, which
particularly suits contact lens wearers. The place of topical NSAIDs such as diclofenac
sodium is more difficult to define. Some patients find that tear supplement drops
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BSACI Rhinitis Guideline Scadding et al. 2015
(‘artificial tears’) provide a good measure of symptomatic relief. Topical steroids are
effective in suppressing inflammation but can have potentially sight-threatening
adverse effects including ocular hypertension / glaucoma, cataract, and the
enhancement of infection. If indicated, e.g. for vernal conjunctivitis, use should be
supervised by an ophthalmologist. Immunotherapy, where indicated, is effective for
ocular symptoms.
Immunotherapy
Allergen immunotherapy involves the repeated administration of allergen extracts in order
to improve symptoms, reduce medication requirements and improve quality of life of
allergy sufferers (Bousquet and others 1998; Canonica and others 2014; Passalacqua and
Durham 2007). It is indicated in patients with IgE-mediated allergic rhinoconjunctivitis in
whom allergen avoidance is not possible or undesirable and who fail to respond adequately
to anti-allergic drugs and/or develop unacceptable side effects on treatment (Walker and
others 2011).
Subcutaneous injection immunotherapy (SCIT) has been shown to be effective for both
seasonal rhinitis due to pollens (Cochrane meta-analysis (Calderon and others 2007)
evidence level 1++) and in patients with perennial allergy and sensitivity to house dust mite
((Eifan and others 2013), evidence level 1+). There are few randomised controlled trials of
immunotherapy for cat allergy ((Alvarez-Cuesta and others 1994; Varney and others 1997),
level 1+). SCIT requires weekly updosing regimens followed by 4-6 weekly maintenance
injections for 3-5 yr. In view of the risk of systemic allergic side effects that include
occasional anaphylaxis, SCIT should only be given in specialist clinics by trained personnel
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BSACI Rhinitis Guideline Scadding et al. 2015
and with immediate access to adrenaline and resuscitative measures (Alvarez-Cuesta and
others 2006).
Sublingual Immunotherapy
Sublingual immunotherapy (SLIT) has emerged as an effective and safe alternative to the
injection route in adults and children for the treatment of seasonal allergic rhinitis
with/without seasonal asthma (Canonica and others 2014). Cochrane meta-analysis
(Radulovic and others 2010) and several recent large randomised controlled trials in Europe
and in USA of sublingual tablet formulations have confirmed efficacy in patients with grass
pollen allergy (Bufe and others 2009; Cox and others 2012; Dahl and others 2008; Didier and
others 2007; Halken and others 2010; Maloney and others 2014) and in patients with
ragweed hay fever ((Creticos and others 2014; Creticos and others 2013), evidence level 1+
+). In contrast, the evidence for efficacy of SLIT in house dust mite-induced rhinitis,
particularly in children, is far less convincing, although several trials are in progress.
Sublingual immunotherapy is well-tolerated, with side effects largely confined to local
itching and swelling in the mouth such that after supervision of the first dose by the
prescribing physician with a one hour period of observation, SLIT may be self-administered
daily at home. There have been rare isolated case reports of systemic reactions after
sublingual immunotherapy (Makatsori and Calderon 2014) but these should be considered
in the light of an excellent safety record in many large controlled trials and extensive post-
registration experience with SLIT preparations. The subcutaneous and sublingual routes are
compared in general terms in table 10.
Long term benefits
In contrast to anti-allergic drugs, immunotherapy is the only treatment that has potential to
offer disease modification with longterm remission for several years after its
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BSACI Rhinitis Guideline Scadding et al. 2015
discontinuation. This has been demonstrated for subcutaneous immunotherapy (Durham
and others 1999) and recently confirmed for SLIT for seasonal grass allergy (Didier and
others 2013; Durham and others 2012). One randomised controlled trial of subcutaneous
immunotherapy in children with seasonal rhinitis showed a 2-3 fold reduction in progression
to physician-diagnosed asthma, an effect that persisted for 10 years (Jacobsen and others
2007). A large European double-blind randomised controlled trial is now investigating
whether 3 years grass tablet immunotherapy in 5-12 year olds with grass allergy can prevent
onset of asthma for up to 2 years after stopping treatment (Valovirta and others 2011).
Retrospective studies have suggested that immunotherapy may prevent development of
new sensitisations (Des and others 1997; Pajno and others 2001) although more robust
evidence is required in order to confirm this possibility.
Place in rhinitis therapy.
Allergen immunotherapy within United Kingdom is recommended in patients with a history
of symptoms on allergen exposure and objective confirmation of IgE sensitivity (skin prick
test positive and/or elevated allergen-specific IgE) in the following circumstances:
1. Seasonal pollen induced rhinoconjunctivitis in patients whose symptoms respond
inadequately to usual drug therapy (Evidence level 1++, category A). The choice of SCIT or
SLIT can be based largely on patient preference since the indications are the same and there
are no adequately powered head-to-head comparative trials.
2. Perennial allergic rhinoconjunctivitis in patients with an allergy to cat or house dust mite
who respond inadequately to anti-allergic drugs and where the allergen is not easily avoided
(for example veterinary surgeons and public sector workers). Here the evidence is stronger
for SCIT (Evidence Level 1+, Category A). At present SLIT for house dust mite allergy is not
recommended for routine use.
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BSACI Rhinitis Guideline Scadding et al. 2015
Recent advances
A European Academy of Allergy and Clinical Immunology position paper recommends an
equally weighted combined score of symptoms and use of rescue medication as the primary
outcome in immunotherapy trials (Pfaar and others 2014). A particular problem for
immunotherapy trials for seasonal allergy has been the high variation in pollen counts
within and between seasons. The environmental exposure chamber (Jacobs and others
2012) may provide an alternative solution for dose-finding and as an adjunct, although is
unlikely to replace phase III studies of natural exposure for regulatory approval. WAO has
published standardised reporting systems for systemic reactions to immunotherapy (Cox
and others 2010) and for local reactions (Passalacqua and others 2013a) following
sublingual treatment (‘speaking the same language’) that if implemented could enable more
effective cross-comparisons of adverse events among clinical trials of immunotherapy.
Novel immunotherapy approaches include better standardisation of vaccines by use of
recombinant allergens (Jutel and others 2005; Pauli and others 2008) and their hypo-
allergenic variants (Niederberger and others 2004). Strategies to improve ‘immunogenicity’
whilst reducing the risk of IgE-associated side effects include the development of T cell
peptide vaccines for cat (Couroux and others 2015; Patel and others 2013) and venom
allergy (Muller and others 1998), allergoids (Hoiby and others 2010) (chemically modified
allergens with disrupted tertiary structure) and the combination of allergen with adjuvants
to enhance ‘protective’ immune responses such as immune deviation in favour of Th1
responses (monophosphoryl lipid A (Creticos and others 2006)) or the induction of T
regulatory responses (Toll-like receptor 9 agonist, (DuBuske and others 2011)).
ECONOMIC CONSIDERATIONS WITH REGARDS TO DESENSITISATION
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BSACI Rhinitis Guideline Scadding et al. 2015
In 2013, a Health Technology Assessment of both subcutaneous (SCIT) and sublingual
immunotherapy (SLIT) in patients with seasonal allergic rhinitis undertook detailed cost
analyses recognizing the burden that Allergic Rhinitis places on individuals in the UK and on
the NHS (Meadows and others 2013). Compared to pharmacotherapy, immunotherapy was
cost effective at 6 years after the start of treatment (7 years from an NHS perspective only).
Staff costs and overall productivity losses were greater for SCIT compared to SLIT over the 3
years treatment period, but SCIT was shown to be more cost effective as early as 5 years
after the start of treatment (4 years from an NHS perspective). Pre-seasonal therapy with
SCIT (Pollinex) or SLIT (Oralair), should reduce respective costs further but there remains
uncertainty around their long-term effectiveness of these shorter treatment courses.
Treatment of NAR
Evidence quality from trials is reduced by inadequate patient selection which is often based
solely on negative skin prick tests with or without a history of non-specific triggers such as
smoke, perfume, weather changes. A database search to identify knowledge gaps and
research needs is being compiled by a working party of the American Academy of Asthma,
Allergy and Clinical Immunology and their full report is awaited. Present conclusions, based
on a search of literature from 1960-2010 and using 40% of 2000 articles, (Togias, personal
communication) suggests the following:
Intranasal ipratropium is effective for watery rhinorrhoea (level 1b). (Bonadonna and others
2001) …
Topical capsaicin desensitisation reduced symptoms for several months in NINAR (Blom and
others 1997b; Ciabatti and D'Ascanio 2009; van Rijswijk and others 2003).
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BSACI Rhinitis Guideline Scadding et al. 2015
Topical corticosteroids have an effect in skin prick test negative rhinitis patients (level 1b),
probably on those with underlying inflammation, since studies give variable results (Blom
and others 1997a; Jacobs and others 2009; Lofkvist and Svensson 1976; Lundblad and others
2001; Varricchio and others 2011), and relief was limited in subjects with low levels of nasal
eosinophils in a recent study (Philpot and others 2010).
Topical nasal antihistamines, azelastine and olopatadine (Banov and Lieberman 2001;
Lieberman and others 2011) (level 1b) and a combination of azelastine with fluticasone
(level 111) reduced symptoms in skin prick test negative patients over one year( Price D et
al.J Investig Allergol Clin Immunol 2013; Vol. 23(7): 495-503).
Decongestants and oral antihistamines are ineffective.
Montelukast has not been formally trialled in NAR but low quality studies (Wilson and
others 2001d). Effects of leukotriene receptor antagonist therapy in patients with chronic
rhinosinusitis in a real life rhinology clinic setting suggest a possible effect in SPT negative
patients.
TRPV1 was considered a prime target for neurogenic rhinitis therapy, but a recent study
proved negative when cold dry air challenges were used (Murdoch and others 2014), but did
reduce the response to capsaicin (Holland and others 2014).
Aspirin desensitization
This may be effective in those with aspirin – sensitive NAR, but should be preceded by nasal
or oral aspirin challenge to establish the diagnosis (Fruth and others 2013; Howe and others
2014; Miller and others 2013; Xu and others 2013).
A suggestion for NAR therapy is given in Figure 5.
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BSACI Rhinitis Guideline Scadding et al. 2015
Therapy in NAR depends upon the phenotype. Those with inflammation may respond to
anti-inflammatory therapy, though less well than in AR and higher INS doses and
combinations of therapy may be needed. If these fail a nasal aspirin challenge could be
undertaken, followed by desensitization if positive (Howe and others 2014; Miller and
others 2013). Non inflammatory NAR may respond to anti- cholinergic therapy or to
capsaicin. Some patients require both anti- inflammatory and anti-neurogenic treatments.
Surgery
Surgery is required in only a minority of cases. The indications for surgical intervention are:
1. Drug-resistant inferior turbinate hypertrophy [Poor objective evidence to support
this indication other than in the short term].
2. Anatomical variations of the septum with functional relevance (Passali and others
2003).
There are no well conducted (prospective and randomised) studies supporting the use of
coblation, laser or surgery to the inferior turbinates in patients with rhinitis which
demonstrate benefit, supported by objective measurements, other than in the short term.
Studies of this nature show that surgery to the inferior turbinate does not confer any lasting
benefit (Lavinsky-Wolff and others 2013).
If in future trials of surgery are to be done it would seem that, in the first instance, they
should be limited to patients who have failed to respond to medical treatment given the
evidence that is currently available for the benefit that compliant medical treatment
provides in the majority of patients.
Assessment of Rhinitis Control
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BSACI Rhinitis Guideline Scadding et al. 2015
Since 2001 the ARIA patient classification system for allergic rhinitis has been used in both
clinical and research settings. It focuses on patient symptoms, their time patterns (either
‘intermittent’ or ‘persistent’ and their severity (‘mild’ vs ‘moderate/severe’) and is simple
and quick to administer tool.
In response to a World Health Organisation endorsed trend, disease control rather than
severity is considered a preferable metric to measure and monitor. Three rigorously
developed and validated assessments are available (Control of Allergic Rhinitis and Asthma
Test (CARAT) (Nogueira-Silva and others 2009), Rhinitis Control Assessment Test (RCAT)
(Nathan and others 2010; Schatz and others 2010) and Allergic Rhinitis Control Test (ARCT)
(Demoly and others 2011). More recently the simple and quick MACVIA visual analogue
scale has been developed (reference from GS). To date there has been no head to head
comparison of these tools so it is not possible to rank their utility and validity.
Severe Chronic Upper Airways Disease (SCUAD)
SCUAD is a recently adopted term that defines those patients whose symptoms are
inadequately controlled despite adequate (i.e. effective, safe, and acceptable)
pharmacological treatment based on guidelines. Severe uncontrolled allergic rhinitis, of
whatever aetiology, can be classified as SCUAD which affects 18.5% of allergic rhinitis
patients (Bousquet and others 2009). It is important to differentiate between this situation
and those patients who are symptomatic because they are incorrectly treated or have poor
adherence. The pathophysiology, genotype-phenotype relationships and natural history of
SCUAD are currently poorly understood.
Improving patient adherence in rhinitis
45
BSACI Rhinitis Guideline Scadding et al. 2015
Poor adherence is a challenge in the management of allergic and non-allergic rhinitis, just as
it is in other chronic diseases where generic estimates of non-adherence range from 30-60%
and from 50 to 80% for preventive measures (Christensen 2004). There are very few ‘real
life’ studies of adherence in rhinitis to antihistamines and nasal corticosteroids and there
are no data available for adherence with intranasal anticholinergics and cromolyn
(Passalacqua and others 2013b).
Adherence to Specific Immunotherapy (SIT) has been documented in greater detail with
estimates for compliance with subcutaneous (SCIT) regimes ranging from 33-89%, and the
reasons for discontinuation being time taken and annoyance. Sublingual therapy adherence
rates range from 44-97% initially, but discontinuation rates are high with less than 20% of
patients progressing to the third year of therapy. The frequency of follow up visits,
perception of poor efficacy and cost contribute to these high rates of attrition (Passalacqua
and others 2013b).
Unlike some chronic disorders, there has been little effort expended to date in
understanding and improving adherence in rhinitis, however there is evidence to support
the importance of:
Frequent monitoring visits for SLIT. Paediatric patients who were reviewed at three monthly
intervals were significantly more adherent than those reviewed twice or once a year (Vita
and others 2010).
Enhanced patient education. A 3 hour educational program together with written
information achieved greater compliance than standard oral instruction (Incorvaia and
others 2010).
COMPLEMENTARY THERAPY IN ALLERGIC RHINITIS
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BSACI Rhinitis Guideline Scadding et al. 2015
Studies with complementary therapy have used several treatment approaches with view to
treating allergic rhinitis.
Acupuncture
Acupuncture as an intervention for AR has been evaluated in relation to placebo (sham
acupuncture) and medical treatment. Unfortunately robust meta-analysis has not been
possible given the limited number of studies that conform to the trial methodology required
by such reviews, and thus it is not possible to recommend acupuncture as a definite
intervention in AR. Blinding is impossible because of the physical nature of acupuncture.
Studies comparing acupuncture to medical treatment have also focussed on mild AR in that
the intervention has only been an oral antihistamine (Brinkhaus and others 2013; Cao and
others 2014; Hauswald and others 2014). Thus even if these studies show acupuncture
efficacy, the effect is shown in mild AR. The health economics of such intervention must be
considered if a generic second generation antihistamine is as effective. Ear acupressure
studies are limited and weakened further by single blinding, but may be a valuable add on
for patient controlled disease management (Xue and others 2011; Zhang and others 2014).
Recommendation-Grade C
Acupuncture may be considered in mild AR based on patient choice and funding availability.
Herbal therapy
The existing studies are limited and each study focuses on intervention with a specific
herb(s) and there is no available reproducibility of data in repeat studies. Small study
volunteer numbers and lack of robust methodology prevents meta-analysis of such existing
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BSACI Rhinitis Guideline Scadding et al. 2015
studies. It is therefore not possible to recommend a specific herbal product or an overall
herbal therapeutic approach until further studies are undertaken.
Recommendation-Grade D (Not recommended)
Photodynamic therapy
Different light wavelength used in studies have ranged from red light to ultraviolet. Mixed
treatment approaches, limited controlled studies, lack of meta-analysis and of long term
safety data makes it difficult to support such approaches at the current time.
Recommendation-Grade D (Not recommended)
RHINITIS IN PREGNANCY AND DURING BREASTFEEDING
Rhinitis affects at least 20% of pregnancies (Dzieciolowska-Baran and others 2013; Keles
2004) and can start during any gestational week (Dzieciolowska-Baran and others 2013;
Ellegard 2003). Although the pathogenesis is multifactorial, nasal vascular engorgement and
placental growth hormone are likely to be involved (Ellegard 2003; Incaudo 2004). Rhinitis
patients have higher levels of oestrogen and IGF1 during the third trimester. Rhinitis in
pregnancy may not be adequately treated during routine antenatal care, and patients
benefit from a multidisciplinary approach (Soares dos Reis and others 2009). Rhinitis in
pregnancy impacts negatively on quality of life, especially during the third trimester and
women with pre-existing allergic rhinitis are more severely affected (Gilbey and others
2012). Informing the patient that pregnancy-induced rhinitis is a self-limiting condition is
often reassuring.
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BSACI Rhinitis Guideline Scadding et al. 2015
Women developing rhinitis during pregnancy are more likely to deliver female babies
(Indirani and others 2013) and children of mothers developing rhinitis in early pregnancy are
more likely to develop rhinitis themselves (Shinohara and others 2007).
During pregnancy, most medications cross the placenta, and should only be prescribed
when the apparent benefit is greater than the risk to the foetus (Gani and others 2003).
Nasal lavage is safe and effective in pregnant women, reducing the need for antihistamines
(Garavello and others 2010). Chromones have not shown teratogenic effects in animals and
are the safest drug recommended in the first 3 months of pregnancy although they require
multiple daily administrations. The safety of nasal steroids in pregnancy has not been
established through clinical trials. Only minimal amounts of steroid pass into the
bloodstream after using a nasal spray and it is good practice to treat with ‘tried and tested’
drugs (Gani and others 2003). Beclomethasone, fluticasone and budesonide have good
safety records and are widely used in pregnant asthmatic women of these fluticasone has
least systemic bioavailability when used nasally (Demoly and others 2003b; Ellegard and
others 2001; Mazzotta and others 1999). There is considerable clinical experience with
chlorphenamine, loratadine and cetirizine in pregnancy, which may be used in addition, but
decongestants should be avoided (Diav-Citrin and others 2003; Moretti and others 2003).
Patients already on immunotherapy may continue if they have already reached the
maintenance phase but each case must be considered individually. The initiation of
immunotherapy and updosing is contraindicated (Keles 2004).
Similar recommendations can be made about the treatment of allergic rhinitis during
lactation. Nasal lavage is safe to use whilst breastfeeding. Nasal administration of sodium
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BSACI Rhinitis Guideline Scadding et al. 2015
cromoglicate is not known to have any harmful effects when used by breastfeeding
mothers. Antihistamines and nasal steroids should only be used when the clinical imperative
outweighs the potential harm to the child. Antihistamines are excreted in breast milk and,
although not known to be harmful, the manufacturers of most antihistamines advise
avoidance whilst breastfeeding. Chlorpheniramine may cause drowsiness and poor feeding
in the baby. Both loratidine (Hilbert and others 1988) and cetirizine appear safer with low
levels found in breast milk (Briggs and others 2001). The lowest dose should be used for the
shortest duration.
RHINITIS IN CHILDREN
Rhinitis is a common presentation in children and there are several underlying causes.
Acute infectious rhinitis is frequent, particularly in young children, and generally
does not require medical attention.
Chronic infectious rhinitis (rhinosinusitis), particularly if severe, can be a
manifestation of underlining pathologies such as Primary Ciliary Dyskinesia, Cystic
Fibrosis, and Immunodeficiency.
Retained foreign body, nasal septum deviation, unilateral choanal atresia, cerebro-
spinal fluid leak, and nasal polyposis can present with rhinitis.
Allergic rhinitis is the focus for allergy specialists and paediatricians:
o It has a significant impact on children’s quality of life and can have a
detrimental effect on sleep, behaviour, school performance and family
dynamics (Walker and others 2007)
o Its presentation in children can be atypical and it is influenced by the
associated co-morbidities in the different age groups, as summarised in the
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BSACI Rhinitis Guideline Scadding et al. 2015
recently published EAACI Paediatric Rhinitis Position Paper (Roberts and
others 2013) (figures x and z- reproduced with permission). The same
document gives guidance on how to recognize its comorbidities (Figure z –
reproduced with permission).
o It can present in association with other atopic disorders and it is often
associated with asthma, atopic dermatitis and food allergy.
o In children as in adults the link between rhinitis and asthma has been
demonstrated by several studies.
Otitis media with effusion and/or adenoidal hypertrophy have been reported as associated pathologies in younger patients; the mechanisms underlining this link have however yet to be fully elucidated. Some studies suggest benefit to these common paediatric conditions from rhinitis treatment (Scadding G1. Non-surgical treatment of adenoidal hypertrophy: the role of treating IgE-mediated inflammation. Pediatr Allergy Immunol. 2010 Dec;21(8):1095-106. doi: 10.1111/j.1399-3038.2010.01012.x.
Scadding and others 2014) (3,4,5). Ask Pina for these refs, include Scadding one on OME pub
2014= Glenis K. Scadding, Kaukau Rajput, Susan Hills, Yvonne Darby, Anna Jansz, David
Richards*, Helen Tate+ and Simon Gane
Double-blind, placebo controlled randomised trial of medical therapy in
otitis media with effusion.
o
o The approach to diagnosis in children is similar to that in adults: history, skin
prick test and anterior rhinoscopy. Component resolved diagnosis (CRD) may
be helpful in selected patients when allergen specific immunotherapy is being
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BSACI Rhinitis Guideline Scadding et al. 2015
considered and the seasonal symptoms are not clear (Stringari and others
2014).
o Entopy (local allergic rhinitis) is found in this age group ( level D) (Forester
and Calabria 2010; Payne and others 2011).
o Therapy of rhinitis in children is based on the same principles as in adults,
however it should take into account specific paediatric needs, such as
acceptability, practicality for both children and parents, and concern for
potential side effects.
o Nasal saline irrigation is effective in the treatment of AR in children (Chen and
others 2014; Garavello and others 2003).
o Brief concomitant use (3 days) of topical decongestants can be helpful in
children with significant nasal blockage to aid introduction of topical nasal
steroid therapy.
o Recommendation for continuous use of intranasal steroids can often create
anxiety in parents; Intranasal steroids with low bio-availability have a better
safety profile at recommended doses and should be used in preference
(Figure 4) (Allen and others 2002a; Schenkel and others 2000).
o It is advisable to monitor growth in children, especially if they are receiving
steroids by multiple routes (Allen and others 2002b) (see also table 7).
o A short course (3 to 7 days) of oral corticosteroids may be required in severe
cases. Intramuscular steroids have no role in the treatment of AR.
o Immunotherapy is recommended mostly for difficult to treat subjects who
have failed maximal pharmacotherapy; the potential added benefit in disease
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BSACI Rhinitis Guideline Scadding et al. 2015
prevention should be considered when treating children (Moller and others
2002; Niggemann and others 2006).
o Education on therapy plays an important role on treatment outcome and
both children and carers should be provided with the relevant information
and appropriate training (Indradat and others 2014).
Quality of Life Questionnaires for rhinitis
The burden of rhinitis for an individual patient can be estimated using Patient-Reported
Outcome Measures (PROMs). Generic PROMs such as the EQ-5D allow a comparison
between different diseases and are particularly useful when calculating the incremental
cost of new treatments. However, a disease-specific validated Quality of life (QoL)
questionnaire is more sensitive when assessing severity of disease and response to
treatment. In routine clinical practice the use of such tools allows greater focus on
symptoms important to the patient. Commonly used and validated quality of life disease
specific scoring systems include the RQLQ for allergic rhinitis and rhino-conjunctivitis,
the SNOT-22 or RSOM-31in chronic rhinosinusitis and a modified SNOT-16 in acute
rhinosinusitis.
FUTURE RESEARCH
AR
Prevention of AR development
Adoption of single scheme for assessing control
Prevention of progression from AR to asthma: confirmation of effect of immunotherapy,
investigation of AR well-controlled by pharmacotherapy.
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BSACI Rhinitis Guideline Scadding et al. 2015
Reduction of proportion of SCUAD sufferers
NAR
Prevalence- accurate figures needed.
Endotypes
Trials of therapy in well – selected endotypes
Acknowledgements
PATIENT INFORMATION LEAFLET
Rhinitis means inflammation of the lining of the nose. Rhinitis is defined clinically as
symptoms of runny nose itching, sneezing and nasal blockage (congestion). Common causes
of rhinitis are allergies which may be seasonal (‘hayfever’) or occur all-year-round (examples
include allergy to house dust mite, cats, dogs and moulds).Infections which may be acute or
chronic represent another common cause. Rhinitis (whether due to allergic or other causes)
is a risk factor for the development of asthma. Rhinitis is also implicated in otitis media with
effusion (glue ear) and in sinusitis which should rightly be termed rhinosinusitis since sinus
inflammation almost always involves the nasal passages as well.
Allergic rhinitis is very common, affecting one in four in the UK. As with other allergic
disorders (asthma, atopic dermatitis) rhinitis is much more common in westernized
societies; the prevalence of rhinitis continues to rise in many countries.
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BSACI Rhinitis Guideline Scadding et al. 2015
People with a family history of allergy are more likely to get allergic rhinitis. No method has
been found to prevent it developing. Allergic rhinitis may itself be the first manifestation of
allergic disease, e.g. as hay fever in teenagers or adults. Further allergies can occur- to things
like house dust mites, pet allergens. Rhinitis may progress to persistent symptoms with
resultant nasal congestion which impacts on adjacent structures such as the sinuses, throat,
middle ear and bronchial tubes.
It can be very mild, moderate or severe.Allergic rhinitis is frequently ignored or regarded as
trivial by family members, doctors and even sufferers themselves, probably because
recurrent colds are common, particularly in small children. This is a big mistake since not
only does rhinitis reduce quality of life, it can impair sleep and reduce school performance
and attendance at work. Allergic children have been shown to have more infections and
more problems with those infections.
Asthmatic children who get colds are 20 times more likely to be hospitalised due to their
asthma if they are allergic and if they are exposed to high levels of their provoking allergens.
Adequate treatment of underlying allergic disease helps to diminish these problems.
Diagnosis rests on taking an adequate detailed history and supplementing this by
examination and, if necessary, specific allergy tests. The timing of symptoms in relation to
possible allergen exposure is of primary relevance.
Treatment of Allergic Rhinitis
This falls into 4 categories:
1. Allergen and irritant avoidance. Rhinitis is usually caused by inhalant allergens and very
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BSACI Rhinitis Guideline Scadding et al. 2015
rarely by food. Some allergens such as pets can be avoided; others such as pollens are more
difficult- although a holiday abroad or by the sea at the height of the relevant season can
help. House dust mites are hard to avoid sufficiently reducing symptoms but some patients
do find benefit from allergen proof bed covers particularly if such measures are combined
with rigorous cleaning, avoidance where possible of soft furnishings and heavy curtains and
use of hard flooring. However, in controlled clinical trials, such mite avoidance measures are
not of proven value at the present time. Avoidance of irritants such as smoke also helps to
reduce symptoms. Simply washing out the nose with a salt water solution can be very
soothing. This can be achieved with half teaspoon of salt, half teaspoon of bicarbonate of
soda (baking powder) added to a pint of lukewarm water, with gentle sniffing of the solution
from the palm of the hand. Also salt sprays and custom-designed salt douches are
inexpensive and available from high street chemists.
2. Drug therapy. Mild-moderate hay fever responds to antihistamines but it is very
important to take advice from pharmacists and choose non-sedating antihistamines,
otherwise driving, work and school performance is very likely to be impaired even in people
who do not feel drowsy and who are not obviously sleepy. More problematic and persistent
rhinitis is better treated with a topical nasal corticosteroid administered by spray or, in the
case of associated sinusitis and/or nasal polyps by use of corticosteroid nasal drops. The
new nasal corticosteroid sprays are not absorbed and can be very safely be used in adults
and children.
Avoidance of directing the spray towards the nasal septum (the partition in the middle of
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BSACI Rhinitis Guideline Scadding et al. 2015
the nose) and use of the nasal device without fiercely sniffing the spray into the back of the
throat provides optimal benefit.(FIGURE X) Symptom relief is not immediate and treatment
may take several days or a week or two to be fully effective. Combinations of treatments
may be needed – intranasal antihistamine plus intranasal corticosteroid is better than either
alone in reducing all symptoms.Other potentially useful treatments include anti-leukotriene
tablets (Singulair), chromones (Intal, Nedocromil) and ipratropium (Rhinatec).
3. Immunotherapy (desensitization). Immunotherapy involves giving graded increases of
allergens to which the sufferer is sensitive in order to induce allergen tolerance, which may
last for years following discontinuation. Immunotherapy is reserved for patients with one or
two major problematic allergens and without chronic asthma who are not controlled by the
above measures. Injection (subcutaneous) or under the tongue (sublingual) immunotherapy
is usually given regularly over 3 years. This form of treatment must only be prescribed
initially by specialists in allergy.
Sublingual immunotherapy once the first dose has been given under expert supervision can
be administered each day in the home. Sublingual reactions are very mild- mostly involving
local itching and swelling in the mouth and throat- and short term lasting 1-2 weeks or less.
Local side effects are to be expected and usually apparent at the first dose which should be
given under supervision. Side effects from injection immunotherapy may occasionally be
more severe so injections must take place in the presence of a trained physician in a setting
where immediate resuscitation facilities are available. Pre-seasonal treatment is effective
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BSACI Rhinitis Guideline Scadding et al. 2015
for seasonal allergies, but it is not yet clear whether pre-seasonal use confers long term
benefit, as observed for the injection route when used regularly all year round for 3 years.
4. Surgery. Surgery is only very rarely needed for rhinitis. Occasionally surgery with/without
turbinate reduction is needed to allow access to the nose for more effective use of sprays or
to open the sinuses in patients insufficiently responsive to medical treatment because of
structural problems.
Progress of disease
Once present inhalant allergen sensitivity tends to remain in many, but not all, patients.
Some individuals lose their hay fever and their allergies do not progress.
It is worth making your friends and family aware of your allergies so that you do not suffer
from major exposure- such as a house with cats, or a very dusty bedroom.
Contact - ??Allergy UK
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LEGENDS TO TABLES and FIGURES
Table 1. Allergic triggers for rhinitis.Many inhalant allergens cause rhinitis symptoms- but occupational ( Table 6 ) and non- allergenic triggers( Table 3 ) should also be considered when taking the history.Table 2 Infectious causes of rhinitis.Table 3 Triggers for non – allergic rhinitisTable 4. Aetiology and Associations of Allergic Rhinitis
Table 5.Co- morbidities of Allergic Rhinitis.
Some co- morbidities appear as consequences of AR, e.g. concentration and sleep problems, others co- exist with it as a consequence of underlying allergy, eg atopic dermatitis .The mechanism of the association between asthma and rhinitis is uncertain, but the tendency for asthma to succeed rhinitis, the demonstration that nasal allergen challenge in AR gives lower respiratory tract inflammation and the prevention of progression of AR to asthma by allergen immunotherapy suggest that the asthma is consequential in individuals in whom rhinitis is the initial manifestation of atopic disease. Table 6.Occupational Rhinitis triggersTable 7.Allergen Avoidance measuresTable 8.Effects of medication upon individual rhinitis symptomsTable 9.Oral antihistamines.Table 10. Summary of SCIT and SLIT
Figure1. Modified ARIA Classification of Rhinitis NB THE FIGURE NEEDS THE PREVIOUS VERSION_ IN WHICH SEASONAL AND PERENNIAL IS ADDED AT THE BOTTOM
In the UK, where seasons are clear, an additional subdivision into seasonal and perennial is helpful, in diagnosis and in therapy, particularly allergen avoidance and immunotherapy.
Figure 2.Immunological mechanisms of Allergic Rhinitis Figure 3. AR Treatment algorithm.
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Additional therapies can be accomplished using two different medications, or a combination treatment in one device. There is , as yet , no comparative evidence on which to base this choice, however concordance appears more likely when the regime is simple. Figure 4. Bioavailability of intranasal corticosteroids. The more recent molecules have little systemic uptake and are suitable for use in children and for long term therapy(.Grade A evidence) Figure 5.Treatment of Non- Allergic Rhinitis.The division into those with and without nasal inflammation can be made on the basis of nasal smears, and possibly on nasal NO levels, though this latter is not certain .Patients who fail on therapy can be tried on a combination of BOTH ANTI- INFLAMMATORY PLUS ANTI – NEUROGENIC TREATMENT,( Grade D evidence)Figure 6. How to Use a Nasal Spray. Evidence grade D.Figure 7. Rhinitis in Children.With permission from EAACI.Figure 8.Recognition of Rhinitis in Children at different Ages.With permission from EAACI.
? add Figure 9.Treatment of Rhinitis in ChildrenWith permission from EAACI
Appendices
A1Levels of EvidenceA2.Grades of RecommendationA3.Combination therapy for Rhinitis.A4.Management of Non- Allergic Rhinitis.Trials of level 2+ , involving exclusion of patients with allergen specific IgE or a response to nasal corticosteroids , have been included
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Table 1. Allergic triggers for rhinitis
Trigger types Origin/specific example of trigger
Type of rhinitis caused
Mites House dust mite, storage mites, allergen in mite faecal pellets
Major causes of perennial rhinitis
Pollens Trees, grasses, shrubs, weeds Main causes of seasonal rhinitis; cross-reactivity among pollens
Animals Cats, dogs, horsesMice, rats
Allergen in sebaceous glands & salivaAllergen mainly in urine
Fungi (Moulds) Alternaria, Cladosporium, Aspergillus
Seasonal and/or perennial symptoms
Occupational-induced(see also table 2)
Occupation-Aggravated
Flour, latex, laboratory animals, wood dust, enzymes, other airborne proteins
Smoke, cold air, formaldehyde, sulphur dioxide, ammonia, glues, solvents, etc. (Drake-Lee and others 2002; Shusterman 2003)
Reversible with early diagnosis and avoidance but becomes chronic and irreversible if exposure is prolonged (Petrick and Slavin 2003).May progress to asthma. Diagnosis based on symptom diary cards and provocation tests (table 3).
Pre-existing rhinitis can be aggravated by work-place irritants
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Table 2 Infective causes of rhinitis
Infective agent type Examples of infective agent
Caused disease pattern
Viruses Common cold viruses, e.g. rhinovirus, coronaviruses, RSV, etc.
Sinus changes on CT scan remain for up to 6 weeks after the infection (Gwaltney 2002).0.5-2% become superinfected by bacteria (Gwaltney, Jr. 1999). “Colds” may exacerbate asthma and COPD (Hurst and others 2005; Johnston and others 1995).Children average 6-8 “colds” per year (Ramadan 2005).
Bacteria Streptococcus, Haemophilus, Moraxella, Staphylococcus, Mycobacteria
Acute infection causes nasal obstruction, facial pain, crusting, purulent discharge.Can progress to rhinosinusitis
Fungi and other opportunistic infections
Aspergillus Rarely cause symptoms; mainly affect immuno-suppressed individuals (Fokkens and others 2005).
Protozoa Leishmania Chronic indolent disease with granulomatous changes and destruction
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Table 3 Types and possible triggers of non-allergic rhinitis
Type Suggested triggers/cause Signs/symptomsEosinophilic or NARES (non allergic rhinitis with eosinophilia syndrome)
50% develop aspirin sensitive disease with asthma and nasal polyposis later in life (Leone and others 1997)
Skin tests negative but nasal smears show eosinophilia. Perennial symptoms with paroxysmal episodes. About 50% have bronchial hyper-reactivity (Leone and others 1997).
Autonomic (vasomotor)
Triggered by physical/chemical agents
More common in middle age with clear rhinorrhoea especially in the morning. Less favourable course than allergic. Possibly caused by parasympathetic hyperactivity (Garay 2004).
Drugs -adrenergic blockers, ACE inhibitors, chlorpromazineCocaine
Nasal decongestants (with prolonged use)Aspirin/NSAIDs
Nasal blockage
Rhinorrhoea, crusting, pain and nasal septum perforation reduced olfaction (Yewell and others 2002)Rhinitis medicamentosa with chronic nasal blockage (Tan and Corren 1995)Acute rhinitis symptoms +/- asthma
Hormonal Pregnancy (Canonica and Passalacqua 2003), puberty, HRT, contraceptive pill (Drake-Lee and others 2002; Shusterman 2003). Possibly hypothyroidism, acromegaly (Cullinan and others 1999; Petrick and Slavin 2003)
All can cause nasal blockage and/or rhinorrhoea
Food Alcohol, spicy foods, pepper, sulphites
Rhinorrhoea, facial flushingGustatory rhinorrhoea
Atrophic Klebsiella Ozonae (Gautrin and others 2001b) or secondary to trauma, surgery, radiation
Foul-smelling odour, crusting, hyposmia, nasal blockage (Gautrin and others 2001a)
Primary mucus defect Cystic fibrosis Children with polyps must be screened for cystic fibrosis (Cartier and others 1984)
Primary ciliary dyskinesias
Kartagener and Young syndromes
Rhinosinusitis, bronchiectasis and reduced fertility.
Systemic/Inflammatory Sjogren, SLE, rheumatoid arthritis,Churg-Strauss (Houba and others 1998)
Nasal blockagePolyps, sinusitis, asthma, eosinophilia
Immunodeficiency Antibody deficiency Chronic infective sinusitisMalignancy Lymphoma, melanoma,
squamous cell carcinomaBloody, purulent discharge, pain and nasal blockage – symptoms may be unilateral
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Granulomatous diseases
SarcoidosisWegener’s disease [274]
External nasal swelling or collapse, sinusitis, swelling, crusting, bleeding, septal perforation
Structural abnormalities
Nasal septal deviation Unilateral nasal obstruction unlikely to present unless additional cause, e.g. rhinitis
Idiopathic Unknown cause – Diagnosis of exclusion
May respond to topical capsaicin (Gwaltney 2002; Johnston and others 1995; Wernfors and others 1986)
Local AR Allergens as for AR (see table 1) Skin test negative, but positive response to nasal allergen challenge. The prevalence is up to 25% in Spain, there are only estimates in the UK.
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Table 4: Aetiology and associations of AR
Factor Comments Evidence level References
Non-modifiable factors
Genetics/family history of atopy
Hay fever: 60.3% concordance in MZ twins, 31.5% in DZ twins.
74-90% interindividual liability to AR accounted for by genetic factors.
Family history of atopy greatest risk factor for atopy and atopic disease in children.
1765 twin pairs, questionnaire only
8,633 5-year-old twin pairs, questionnaire only
Prospective birth cohort, 1,218 children followed up at age 4, cord blood IgE at birth
Rasanen, Allergy, 1998
van Beijsterveldt, ERJ, 2007
Tariq, JACI, 1998
FLG null mutations Presence of null mutations in the gene coding for the epithelial structural protein filaggrin are associated with AR, including in the absence of atopic eczema.
Systematic review and meta-analysis
Van den Oord, BMJ, 2009
Personal history of atopy
Positive skin tests to aeroallergens at baseline risk factor for incident AR in childhood and adolescence.
Eczema in 1st year of life risk factor for childhood AR.
Prospective, case-control, cohort, and birth cohort studies.
Codispoti, JACI, 2010; Ulrik, Allergy 2010; Westman, JACI, 2012; Alm, Paed All Imm, 2011; Kellberger, JACI, 2012; Schafer, Allergy, 2007.
Male sex pre-adolescence
Female sex post-adolescence
Greater risk of childhood AR
Greater risk of adult-onset AR
Prospective, longitudinal, cohort studies
Alm, Paed All Imm, 2011
Kellberger, JACI, 2012
Early life factors
Gestational age at birth Prematurity may be Cases (preterm, 166) Siltanen, JACI, 2011
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protective against adult atopy and AR (assessed by prescriptions for anti-histamines and intra-nasal corticosteroids
vs control (term, 172) study
Birth cohort study, 630,090, AR assessed by prescription rates.
Crump, JACI, 2011
Birth by caesarean section
Positive association with atopy and AR in school age in children with family history of atopy
‘At risk’ birth cohort (432, family history of atopy) followed to age 9
Pistiner, JACI, 2008
Family size and birth order
AR risk decreases with increasing number of siblings; effect more marked for presence of younger siblings
Finding repeated in several large cohorts
Strachan, BMJ, 1989; Braback, Clin Exp All, 1998; Colispoti, JACI, 2010
Early day care attendance
Children without siblings but attending day care have reduced risk of AR than those not attending day care; early day care attendance protective against atopy
Retrospective questionnaire data from European Community Respiratory
Health Survey; cross-sectional questionnaire and SPT/serum sIgE
Svanes, Thorax, 2002
Kramer, Lancet, 1999
Infectious disease markers
Serologic evidence of acquisition of Hepatitis A, T. gondii, HSV 1 associated with reduced frequency of AR; Hep A antibody positivity inversely correlated with SPT positivity
33, 994 individuals studied as part of US National Health and Nutrition Examination Survey; questionnaire, SPT and serological data.
Matricardi, JACI, 2002
Rural/farming environment
Growing up in rural environment, versus urban, appears to be protective, particularly farm animal exposure and exposure to unpasteurised milk before 1 year of age
Reproducible finding in several large observational studies
Braback, Clin Exp All, 2004; Eriksson, Allergy, 2010; Loss, JACI, 2011; Sozanska, Allergy, 2013; Riedler, Lancet, 2001
Breastfeeding Breastfeeding ever versus none not
ISAAC phase 3 Bjorksten, Allergol Immunopathol, 2011
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associated with altered risk of AR, but decreased risk of severe AR.
Absence of exclusive breastfeeding for 2 or more months associated with increased AR incidence in late adolescence
Breastfeeding retrospectively assessed at age 9-11, but effect on AR assessed prospectively at age 15-18
Kellberger, JACI, 2012
Weaning Greater food diversity at 6 and 12 months associated with less AR at age 5; early introduction of fish may be protective
Prospective, birth cohort, 3,142 children, HLA-limited; prospective, longitudinal cohort, 8,176 families
Nwaru, JACI, 2014; Nwaru, JACI, 2013; Alm, Paed All Imm, 2011
Anthroposophic lifestyle, paracetamol and antibiotic use
Use of paracetamol and antibiotics in early life associated with increased risk of AR at age 6-7.
ISAAC phase 3 studies Beasley, Lancet, 2008; Foliaki, JACI, 2009
Steiner school children have reduced incidence of AR ages 5-13
Cross-sectional, controlled study, questionnaire, SPT, sIgE, clinical examination
Alm, Lancet, 1999
Pet exposure Conflicting data: exposure to a cat or dog in the first year of life may be protective for AR at age 7-9 and for cat SPT positivity at 12-13.
Cross-sectional, questionnaire study at two time points, SPT in a subset
Hesselmar, Clin Exp All, 1999
Early exposure to cat a risk factor for AR in 6-7 year olds
ISAAC phase 3 study Brunekreef, Epidemiology, 2012
Other associations
Smoking Variable data: smoking not associated with increased risk of AR, but may increase risk of NAR; second hand smoke exposure may
Large cohort studies
Systematic review and meta-analysis
Eriksson, Clin Resp J, 2012; Eriksson, Allergy, 2013
Saulyte, PLOS medicine, 2014
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have modest association with AR, including in children; smoking may increase risk of house dust mite sensitisation, but reduce risk of pollen sensitisation
ECRHS analysis
Jarvis, JACI, 1999
Vitamin D Variable data: Low serum vit D associated with AR in men
Prospective study, vit D at baseline, incident AR at follow up
Mai, Allergy, 2014
Maternal vit D intake in pregnancy inversely associated with AR aged 5
Retrospective diet questionnaire after delivery, follow up of child at 5 years, HLA-limited
Erkkola, Clin Exp All, 2009
Serum vit D level positively correlated with AR in adults
18,224 individuals in NHANES 3
Wjst, Allergy, 2007
Traffic-related air pollution
No definitive demonstration of an association with AR or allergic sensitisation
Pooled analysis of 6 birth cohorts
Meta-analysis of European birth cohorts
Fuertes, JACI, 2013
Gruzieva, JACI, 2014
Housing High indoor humidity and poor ventilation risk factors
Visible damp (self-reported) associated with rhinitis; higher measured humidity associated with greater Der p 1 levels in mattresses
Retrospective questionnaire study, 2,481 7-9 year olds
ISAAC phase 2, 46,051 children
Aberg, Allergy, 1996
Weinmayr, Clin Exp All, 2013
Diet Consumption of fast food 3 or more times per week associated with AR in 6-7 year olds and adolescents; fruit consumption has opposite effect
ISAAC phase 3 study Ellwood, Thorax, 2013
Lifestyle/physical activity
Paradoxical data: Weak positive association with hours spent TV-viewing and
ISAAC phase 3 study Mitchell, Clin Exp All, 2013
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AR, but also between vigorous physical activity and AR in 13-14 year olds
Alcohol consumption Level of alcohol consumption positively correlates with development of AR in women
Prospective study, 5,870 Danish women, free from AR at baseline
Bendtsen, Clin Exp All, 2008
Climate change Warmer climate may lead to longer pollination seasons and greater geographical distribution of allergenic flora and fungal species
Retrospective analysis: correlation between minimum spring temperature, tree pollen counts, and number of patients visiting an outpatient clinic for AR
Kim, BMC Public Health, 2011
Occupation Occupations with highest risk of developing occupational asthma include bakers, furriers, veterinarians, livestock workers
Finnish Register of Occupational Diseases
Hytonen, Int Arch Occup Environ Health, 1997
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Table 5 Co-morbid associations with rhinitis
Conjunctivitis :PL ADD CANONICA GW paperAuthors Study No patients Age yrs Aim of the study ResultsBozkurt MK et al 2010
Prospective ENT examination in children with vernal keratoconjunctivitis (VKC)
26 males1 female
12+/-4.4 AR prevalence in children with VKC
37% of children with VKC suffer from AR.Median IgE in AR +ve was 262.5Ku/L vs 40.2 in non- ARPatients with VKC should see an ophthalmologistand an allergist
Ibanez MD et al 2010
Multicentre study
1275 recruited from271 centres
6-12 AR (60.7% seasonal and 39.3% perennial) conjunctivitis co-morbidities
Persistent/Severe AR has > co-morbidities .The most frequent is conjunctivitis (53%)
Bertelsen RJ et al 2010
Parental interviews of 1019 cohort
254 with rhinitis (=25%)
children Prevalence of rhinitis co-morbidities
87.4% had at least one rhinitis co-morbidity .Conjunctivitis was present in75.6% (11.8% of them also had asthma & eczema)
Kim Hy et al 2013
ISAACQuestionnaire(12 months evaluation)
615 3-6 Prevalence of rhinitis in children with conjunctivitisand conjunctivitis in children with rhinitis
Prevalence of rhinitis in children with conjunctivitis was 64.8%Prevalence of conjunctivitis in children with rhinitis was 23.6%
OME/Hearing abnormalities: suggest Rita adds add Umapathy D & Scadding GK A community based questionnaire study on the association between symptoms suggestive of otitis media with effusion, rhinitis and asthma in primary school children.Umapathy D, Alles R, Scadding GK.Int J Pediatr Otorhinolaryngol. 2007 May;71(5):705-12. Epub 2007 Mar 1.
Ibanez MD et al 2013
Multi centre prospective
1275271 centres
6-12 Evaluation of ear co-morbidities in AR
23.8% of AR had OME;17.3% of AR had adenoidal hypertrophy
Singh SJ et al 2011
Prospective 30patients 20controls
Adults Audiological and ontological status in AR
All patients had sensorineural hearing loss>high frequency& otoacustic emission abnormalities
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Bozkurt MK et al 2010
Prospective 26 males1 female
12.1+/-4.4 Prevalence of Eustachian tube dysfunction (ETD) in VKC and AR
Patients with AR and VKC are 3x> to have abnormal tympanograms and suffer from ETD than control
Depression/ADHD/ Altered sleeping patterns/anxiety in familiesChen MH et al 2013
NationwideProspective
1673 12-15 AssociationAR and depression after 10years FU
Severe depression 2.5%vs 1.2%Any other depression 4.9% vs 2.8%
Tsai MC et al 2011
Nationwide on Taiwan National Health Research Database
226550 <18 Prevalence & risk of ADH in AR children
Increased ADH rate P<0.001(eczema & asthma do not carry the same risk
Kalpakliogh AF 2009 et al
Observational study on sleeping symptoms
48 Adults Prevalence of OSA in AR vs NAR
OSA 36% in AR vs 83% in NAR (OSA OR in NAR 6.4).AR& NAR were snorers
Emin O 2009 et al
Prospective 82 vs 70 mothers of AR
7-15 Anxiety parameters scores in mothers of AR children vs controls
Anxiety scores significantly > in mothers with AR childrenP<0.02
Lavigne F 2011
Prospective for 12/weeks
34 AR21 NAR
Adults Effects of mometasone on sleep parameters & upper airway inflammation on biopsies
Significant improvement on sleeping parameters &reduction of eosin in AR only
Messias E et al 2010
National co-morbidity survey
5692 Adults Associationbetween seasonal allergies and suicide ideation
Significant association (OR 1.27);not with suicide attempts
Vuurman EFPM et al 2014
Double blind randomized cross-over following nasal provocation with pollen extract and during the season
19 (9 females/10men)
Adults Effect of untreated AR on driving performance compared with treated AR
Magnitude of impairment (evaluated on standard deviation of lateral position of performance) comparable to that seen driving with 0.03% alcohol. Rx with anti H1 or steroids reduces the effects on driving perfomance
Rhinosinusitis/anosmia
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Ibanez MD et al 2013
Multi centre prospective
1275271 centres
Children Co-morbidities in children with AR
26.1%of AR had rhinosinusitis
Guss J et al 2009
Prospective 51 (80% allergic)
Adults Investigate the olfactory function in AR (with Smell Identification Test and also CT scan)
50% of AR with normal CT scored in the 30th percentile on olfactory test . 50% of allergic patients had hyposmia
Asthma:Rita needs to add Shaaban, Lancet , ECHRS stud;Leynaert paper; Settipane papers and Magnan one.Ciprandi G et al 2011
Prospective 89 AR940 controls
Adults Follow up of patients with AR every 2 years for 8years to investigate spirometric abnormalities /BHR
34/89 AR patients develop BHR after 8years
Sensitization for mite, birch, parietaria as well as rhinitis duration are risk factors
Yiamaz o et al 2014
Prospective 57 Children with asthma ex’ion
Evaluate the risk factors for recovery of lung function tests after moderate/severe asthma exacerbation
AR is a significant factor affecting the recovery time of pulmonary function tests and impacts asthma management
Ibanez MD et al 2013
Prospective multicentre
1275 ChildrenFrom 271 centres
Evaluation of comorbidities for AR in a Spanish population
49.5% co-morbidity with asthma: allergy is a systemic disease
Navarro A et al2008
EpidemiologicprospectiveMulti centre
942with asthma
Mean age 35.563% female
Investigate the link between the upper and lower airways
89.5% had ARCorrelation between severity of rhinitis and asthma (P<0001) & inverse correlation with the age (P<0.0001) and severity of asthma (P<0.05)
De Andrade CR et al 2008
Cross sectional study using ISAAC questionnaire
3083 students(47.3% males)
13-14 Evaluation of Asthma and AR co-morbidity
comorbidity asthma and rhinitis symptoms was 8.4%Among asthmatic adolescents, AR symptomswere reported in 46.5%
Ko FW et al 2010
Cross sectionalon questionnaire
600 (with asthma)
267male333 female
Evaluation of prevalence of AR in asthma
77% of asthmatic had rhinitis in the past 12 months (of whom 96% were previously diagnosed with AR)Patients with asthma and rhinitis: nasal steroid usage (49%) had < ED visits 13vs25%) and <hospitalization for asthma (5%vs 13%)
Erikson J 2011 Postal Questionnaireon respiratory health
18087(62% responded)
Adults Evaluation between rhinitis phenotypes and symptoms presentation and risk factor patterns in asthma
Prevalence of asthma in AR was 19.8%Prevalence of AR in asthma was 63.9%Asthma with chronic rhinitis had>asthma symptoms and bronchitis (P<0.01)
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FH of allergy has a >OR for asthma and AR than for asthma and CRS
Bertelasan R Parental interviews
254 Childrenwith rhinitis
Evaluation of co morbidities of rhinitis
87.4% had at least one allergy related co-morbidityChildren with rhinitis and allergic sensitization (72.8%) had>BHR, severe BHR (7.5% vs 5.8%) and conjuntivitis
Valero A et al 2009
Cross sectional international population study based on questionnaire
3225 (one +ve skin test )
10-5053% Male
Evaluation on the link between AR, asthma and skin test sensitization
Asthma was present in 49% of ARAsthma severity was associated with longer time since the onset and allergic rhinitis severity.Patients with asthma have higher number of allergen sensitization and sensitization intensity than those without asthma (P<0.01)
Kin HY et al 2013
Cross sectionalStudy using ISAAC questionnaire
615 Children (306)
Evaluation of allergic co-morbidities in pre-school children
Prevalence of AR in children with asthma was 64.3%Prevalence of asthma in children with R was 21.6%
Oral allergy syndrome/food pollen syndrome/food allergyWestman M et al2012
Prospective 2024 Children IgE tested (inhalants) at 4 and 8years
Natural course of AR and co-morbidities in children
Increase AR from 5% to 14% from 4 to 8years; decrease of NAR from 8% to 6%.4yrs sensitized but not allergic had AR at 8years in 56% of cases
25% of 8yrs with AR has also OASCaliskanerZ et al 2010
Prospective 11178 men 33 women
Adults Clinical parameters comparison between AR with OAS and without
OAS > in women (P=0.01) (OR M/F3.80).OAS relates to nasal itching (P<0.05).OAS >IgE (ns)Regression analysis:association with asthma, age and severity of nasal symptom score
Sahin-Yilmaz A et al 2010
Retrospective 283 Peanut, shrimp and milk IgE and rhinitis
23.4% peanut IgE +ve and 22.2% IgE+ shrimp in inhalant +patientsPeanut and shrimp were the >common sensitivities in rhinitis patients
Laryngeal symptoms
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Vargut MM L 2011 et al
Observational prospective
6control6 AR adult singers
4 females2men
Effects of nasal provocation with pollen extracts and during the HF on Laryngeal parameters
Rapid induction of laryngeal irritation/ globus (no objective laryngeal changes on provocation and during the season)
Rhinitis/atopic disease and migraineMunoz-Jareno N et al et al 2011
Retrospective study FU for 6months
216 5-15 Prevalence of atopy in children with migraine
Prevalence of rhinoconjunctivitis, asthma and atopic dermatitis are statistically significant in children with migraine (OR 7.3; P<0.01for rhinoconjunctivitis;OR 4.69:P<0.01 for asthma; OR 7.1; P< 0.01 for atopic dermatitis
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Table 6 Common causes of occupational rhinitisAgents High MW Low MW Occupation/Industry
Animal proteins Mouse, rat, guinea pig, crabs, etc. urinary and epithelial proteins
Laboratory research, animal breeding [207-209], crab processing industry [210]
Vegetable proteins
Wheat and other cereal flours and grains, latex [51]
Baking [211], milling, food processing,hospital workers
Enzymes Protease, amylase, cellulase, lipase
Food processing, detergent manufacture, pharmaceuticals
Pharmaceuticals Antibiotics, morphine, cimetidine
Pharmaceutical manufacture and dispensing
Chemicals Diisocyanates, colophony fumes, (trimellitic) acid anhydrides (TMA) [212], cyanoacrylates, epoxy resins, alkyd/polyunsatu-rated polyester resins [213] Persulphate Salts, Plicatic Acid (Hox)
Spray painting, Electronic soldering, Plastics and paint manufacture, vinyl flooring, resin production. Cleaners. HairdressersCarpentry and Furniture Making
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Table 7 Recommendations on the use of single measures on HDM avoidance
Measures used individually
Grade of
recommendation
Encase mattress and pillows in plastic or special allergen proof fabric D*
Hot wash bedding at 55ºC and damp wipe mite proof covers every 1-2 weeks D
Remove carpets and replace with hard wood floor D
Use of acaricides on carpets and soft furnishing D B
Minimise objects that accumulate dust D
Remove soft toys from the bed as they harbour high levels of Der p1 D
Remove upholstered furniture and replace with leather, plastic or vinyl furniture D
Do not dry clothes on radiators and remove infrequently worn clothing from the bedroom D
Recommendations on the use of pollen avoidance measures
Nasal Filters (see: www.nasalairguard.co.uk), [47] B
Minimizing early morning activity when the greatest pollen is emitted - after the dew dries after sunrise to late morning D
Avoiding going out after thunderstorms or on windy days when dust and pollen are blown about. D
Wearing wraparound sun glasses. D
Not mowing the grass, and staying inside when it is being mown. If mowing is unavoidable, wear a mask. D
Planning holidays to avoid the pollen season. D
Keeping windows closed both at home and particularly when in the car. In particular keeping windows closed at night to prevent pollens or moulds from drifting into the home. Instead, if needed, use air conditioning, which cleans, cools and dries the air.
D
If the patient is sensitised to a particular plant or tree – consider removal. D
Shower and wash hair once home D
Bathing eyes and douche nose frequently D
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Staying indoors when the pollen count or humidity is reported to be high D
Bringing in washing before pollen levels increase in the evening D
Recommendations on cat allergen avoidance measures
Remove cat, followed by thorough cleaning of house, steam cleaning walls, shampooing carpets D
Keeping cat out of bedroom and other commonly used rooms D
Washing cat weekly D
Removing carpets and replacing with hardwood floors and cleaning regularly D
Laminar airflow over bed at night B
Increase ventilation with fans, air-conditioning OR by opening windows D
* The grade of recommendation against use is A. This measure may be useful if used as part of a range of measures to reduce HDM exposure.
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Table 8 Effect of therapies on rhinitis symptoms (adapted from (Van Cauwenberge and others 2000))
SUGGEST HARSHA ADDS THE DATA ON INS?DECONGESTANT COMBOs TO THIS TABLE. GS
Sneezing Rhinorrhoea
Nasal obstruction Nasal itch Eye symptoms
H1-antihistamines Oral ++ ++ + +++ ++ Intranasal ++ ++ + ++ 0 Eye drops 0 0 0 0 +++Corticosteroids Intranasal +++ +++ +++ ++ ++Chromones Intranasal + + + + 0Eye drops 0 0 0 0 ++Decongestants Intranasal 0 0 ++++ 0 0 Oral 0 0 + 0 0Anticholinergics 0 ++ 0 0 0Antileukotrienes 0 + ++ 0 ++Intranasal steroids and Intranasal anti-histamine 1
+++ +++ ++ +++ +++
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Table 9: Oral antihistamines licensed in the UK according to age
AgeNon-sedating Antihistamine Sedating Antihistamine
> 6 months Alimemazine (Trimeprazine)
> 1 year Desloratadine Hydroxyzine hydrochlorideClemastineChlorphenamine
> 2 years Cetirizine hydrochloride (SAR only)Rupatadine
Cyproheptadine hydrochloride
Loratadine Promethazine hydrochlorideKetotifen
> 6 years Fexofenadine hydrochloride (SAR only)Cetirizine hydrochlorideLevocetirizine hydrochloride
> 12 years AcrivastineMizolastineFexofenadine hydrochlorideBilastine
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Table 10 Summary of Subcutaneous and Sublingual Immunotherapy
SCIT SLIT
Clinical Effectiveness Effective at lowering symptoms, medication use and quality of life in a Cochrane review (ref 5)
Efficacy demonstrated up to 3 years post discontinuation (ref 20)
Effective at lowering symptoms, medication use and quality of life in a Cochrane review (ref 10)
Efficacy demonstrated up to 2 years post discontinuation (ref 21,22)
Major Contra-indications Asthma: BTS/SIGN step 2 or above
Beta-blockers
Not to be initiated in pregnancy
Asthma: BTS/SIGN step 2 or above
Beta-blockers
Not to be initiated in pregnancy
Convenience Typically 4-7 pre-seasonal injections for each of 3 years for allergoid.
For continuous SCIT approximately 25 injections in first year, 12 maintenance injections per year thereafter
Received in specialist clinic with resuscitation facilities
Grazax® is commenced 4 months before the pollen season, then taken daily for 3 years.
Some SLIT vaccines taken for only approx. 5 months per year (e.g. Oralair®)
Taken in the home setting, with first dose in specialist clinic with resuscitation facilities
SafetyLocal reactions Pruritus and swelling at injection site Oropharyngeal pruritus and swelling
Systemic reactions Small risk of anaphylaxis, 0 fatalities (Cochrane)*
Minimal risk of anaphylaxis, 0 fatalities (Cochrane)*
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Milder reactions may include: nausea, abdominal pain, rhinitis, conjunctivitis, headache, cough
* No fatalities reported in UK since CSM review 1986, since the exclusion of severe/uncontrolled asthmatics and SCIT administration in specialist clinics
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Appendix A1: Levels of evidence (British Thoracic Society 2003)
Level of evidence Definition
1++ High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias
1+ Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias1- Meta-analyses, systematic reviews, or RCTs with a high risk of bias2++ High quality systematic reviews of case control or cohort or studies
High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal
2+ Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate probability that the relationship is causal
2- Case control or cohort studies with a high risk of confounding or bias and a significant risk that the relationship is not causal
3 Non-analytic studies, e.g. case reports, case series4 Expert opinion
Table A2: Grades of recommendations (British Thoracic Society 2003; Shekelle and others 1999)
Grade of recommendation
Type of Evidence
A At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population;orA body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of results
B A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results;orExtrapolated evidence from studies rated as 1++ or 1+
C A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results;orExtrapolated evidence from studies rated as 2++
D Evidence level 3 or 4;orExtrapolated evidence from studies rated as 2+
E Recommended best practice based on the clinical experience of the guideline development group
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Appendix Evidence table – Recent combination therapy for rhinitis
Bibliogra-phic citation
Study type
Evidence level
No. patients
Patient characteristics
Interven-tion
Compa-rison
Length of follow-up
Outcome measures
Effect size
Source of funding
Has the study provided answers to the original question?
Weakness / limitations
Cited Y/N
Carr W 2012 JACI (Carr and others 2012b)
Meta-Analysis
1+(Grade A) 3398
12 or above. Mod-Sev SAR Dymista
Az/FP/Pl 14 days
Primary rTNSS change Time to response
minus 5.7 mean r TNSS MEDA
Yes-combination Az/FP better than individual drugs alone None Y
Carr W 2012 Allergy Asthma Proc (Carr and others 2012c)
Doub- blind placebo-control
2+(Grade C) 610
12 or above. Mod-Sev SAR Az vs FP vs Pl 14 days
primary rTNSS change. Secondary r T O S S
Az as good as FP overall in treating nose and eye. FP better for rhinorroea. At 14 days more volunteers eyes improved in Az group than FP
post-hoc analysis from previous study on Dymista vs AZ/FP/PL Y
Meltzer EO 2012 Allergy Asthma Proc (Carr and others 2012c)
Doub- blind placebo-control
2+(Grade C) 779
12 or above. Mod-Sev SAR Dymista
Az/FP/Pl 14 days
primary rTNSS change. Secondary r T O S S Time to onset of action and 12 hour r individual nasal symptom scores Eye QOL MEDA
Yes Time to onset action 30 minutes vs placebo. Dymista particulary decreaed nasal congestion compared to FP and Az used alone. Dymista overall better at treating eyes than FP alone and possibly just better than Az alone. None Y
Baroody F Am J Rhinol Allergy(Baroody and others
Doub- blind placebo-control 4 way X-over
2-(Grade C) 21
18-50 yrs NAC out of season in SAR
FF+OP vs FF/PL vs PL/OP vs PL/PL
4 way x over
Pre-Rx groups 1 week and then NACX2
Symptoms nose and eye and nasal histamine and tryptase GSK
FF/OL no better than FF/PL. Suggests treating the nose with an INS is best for treating the nasal
Small numbers NAC out of season is artificial Y
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2013)
ocular reflex. BUT if done in SAR will OL drops in eye act on effects of pollen in the conjunctiva
Bernstein D Ann Allergy Asthma Immunol 2012 (Bernstein and others 2012)
Pooled data from 4 DBPC studies
2+(Grade C) 962
12 or above. Mod-Sev SAR subgroup
MF-only looked at. Placebo 15 days
Ear and palate itch MSD
Yes. Decreases itch mouth and ears
post-hoc analy from previous studies. Confined only to MF Y
Baroody F JACI 2011 (Baroody and others 2011a)
Doub- blind placebo-control 4 group parallel
2+(Grade C) 60 PAR
Oxy vs Oxy/FF vs FF vs Pl
Parallel 4 groups
Rx 4 weeks + 2 weeks FU
TNSS and Acoustic Rhinometry GSK
FF/Oxy better than Oxy or FF alone or placebo in decreasing TNSS including congestion score.. AR shows FF/oxy better than oxy alone. Oxy adds to FF effects on nose.
Small numbers Y
Meltzer EO 2013 Am J Rhinol (Meltzer and others 2013)
Unblinded, single dummy for MF, placebo control for MF NOT Oxy
2-(Grade C) 705 SAR
MF + OXY different doses vs MF vs Oxy vs Placebo
vs baseline TNSS TNSS MSD
MF/OXY (both doses) same efficacy and better than Oxy or placebo alone. Faster onset of action than just MF alone (MF still as good fro relieving TNSS to same level as MF/OXY combinations
Blinding/Placebo/single dummy Y
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Intermittentsymptoms
< 4 days per weekor < 4 weeks at a time
Persistentsymptoms
> 4 days per weekand > 4 weeks at a time
Mild
Normal sleepNormal daily activities
Normal work and schoolNo troublesome symptoms
Moderate-severeOne or more items
Abnormal sleepImpairment of daily activities,
sport, leisureProblems caused at school or
workTroublesome symptoms
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Figure 1 Classification of allergic rhinitis. Each box may be further subclassified into seasonal or perennial.
Se
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Allergen
Mast cell
B cell
T cell(mast cell) Eosinophil
IL-4
IL-3, -5
GM-CSF
VCAM-1
IgE
IMMEDIATE RHINITISSYMPTOMS Itch, sneezing Watery discharge Nasal congestion
CHRONIC RHINITIS SYMPTOMS Nasal blockage Nasal hyper-reactivity
HistamineTryptaseLeukotrienesProstaglandinsBradykininPAF
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Figure 2 Mechanism of allergic rhinitis
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Figure 3 Treatment of allergic rhinitis (Rhinitis guideline 1st Edition)
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Check use, compliance, dose +/or OC
Rx failure
Key:IN=intranasalOC= oral corticosteroidsα-H1= antihistamineLTRA= leukotriene
receptor antagonist
*Spray or drops
Diagnosis by history ± SPT/Serum specific IgEAllergen / irritant avoidance ± douching
Oral/topical Non-sedatingα-H1
Topical nasal corticosteroid
* Rx failure
Rx failure
moderate/severe
Rx failure
Blockage
mild
?infection/structural problem
Surgicalreferral
CatarrhAdd LTRA if asthmatic
or IN azelastine
Itch/sneezeAdd
IN azelastine or non sedating oral anti-H1
Watery rhinorrhoeaAdd ipratropium or
IN azelastine
Add (briefly)-decongestant-or OC-or longer term:INS+ IN azelastine
Consider immunotherapyif Sx predominantly due to one allergen
Symptoms
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BSACI Rhinitis Guideline Scadding et al. 2015
Figure 4 Intranasal steroids bioavailability (proposed by Harsha Kariyawasam – to be decided)
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• Nasonex Summary of Product Characteristics. 2011 • Rhinocort: Summary of Product Characteristics. 2011 • Beconase Summary of Product Characteristic 2011• Daley-Yates P et al Br J Clin PharmPharmacol 2001
• Kariyawasam H and Scadding GK Journal of Asthma and Allergy 2011• Scadding GK Paediatric Drugs 2008• Homer JJ, Gazis TJ. BMJ 1999
(BetamethasoneNose Drops)
BSACI Rhinitis Guideline Scadding et al. 2015
Figure 5 Treatment of NAR ….
109
Anti-inflammatory:INS, IN antiH1,
both together
Eosinophilic
a) Ipratropium for rhinorrhoea
b) Capsaicin
No inflammation
BSACI Rhinitis Guideline Scadding et al. 2015
Figure 6 Correct procedure for the application of nasal sprays (Rhinitis guideline 1st Edition)
1. Shake bottle well
2. Look down
3. Using RIGHT hand for LEFT nostril put
nozzle just inside nose aiming towards
outside wall
4. Squirt once or twice (2 different
directions )
5. Change hands and repeat for other side
6. DO NOT SNIFF HARD
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BSACI Rhinitis Guideline Scadding et al. 2015
111
Figure 7 Classification of rhinitis causation in children - BSACI Rhinitis Guideline (subject to permission Roberts 2013)
Allergic rhinitis
Infectious rhinitis
Non-allergic, non-infectious rhinitis
Pre-school School Adolescent
Rhinitis symptoms that are associated with exposures to an allergen to which
the patient is sensitised.
Secondary to infection
Irritant exposure (e.g. exhaled tobacco smoke), gastroesophageal reflux and in older children, hormonal (hypothyroidism, pregnancy), drug-induced (e.g. beta-blockers, contraceptives, NSAID), neurogenic or vasomotor, idiopathic.
BSACI Rhinitis Guideline Scadding et al. 2015
112
Different pathophysiologies may co-exist, particularly allergic rhinitis and infectious rhinitis.
Figure 8 BSACI Rhinitis Guideline
Classic Symptoms and signs of
rhinitis
Potential atypical presentations
Rhinorrhea – clear or discoloured discharge, sniffingPruritus – nose rubbing, the allergic salute, allergic crease, sneeze, may be associated with complaints of an itchy mouth or throat in older childrenCongestion – mouth breathing, snoring, sleep apnoea, allergic shiners
Pre-school School Adolescent
Eustachian tube dysfunction – ear pain on pressure changes (e.g. flying), reduced hearing, chronic otitis media with effusion
Cough – often mislabelled as asthmaPoorly controlled asthma – may co-exist with asthmaSleep problems – tired, poor school performance, irritabilityProlonged and frequent respiratory tract infections
Rhinosinusitis – catarrh, headache, facial pain, halitosis, cough, hyposmiaPollen-food syndrome, particularly with pollen driven allergic rhinitis
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